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pubmed_904_3754
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INTRODUCTION
The giant muscular proteins titin and obscurin bind to each other at the Zdisk during muscle development. This binding event is mediated through two domains from each protein: ZIg9/10 from titin and Ig58/59 from obscurin. This interaction helps stabilize and organize the sarcomere; ablation of this binding leads to muscular dystrophy.
OBJECTIVE
Here we solve the high-resolution solution structure of titin ZIg10 and further delineate which sections of titin bind to obscurin.
MATERIALS AND METHODS
Solution NMR, Circular Dichroism, and SEC-MALS were used to biophysically characterize the titin domains involved in this titin-obscurin interaction.
RESULTS AND CONCLUSION
We present the high-resolution solution structure of titin ZIg10. Additionally, we show that titin ZIg9 drives the titin-obscurin interaction, while ZIg10 does not actively participate in the titin-obscurin interaction but instead acts to stabilize ZIg9.
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10.2174/0929866525666181004102031
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pubmed_734_20318
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Phytohormone indole-3-acetic acid (IAA) plays a vital role in regulating plant growth and development. Tryptophan-dependent IAA biosynthesis participates in IAA homeostasis by producing IAA via two sequential reactions, which involve a conversion of tryptophan to indole-3-pyruvic acid (IPyA) by tryptophan aminotransferase (TAA1) followed by the irreversible formation of IAA in the second reaction. Pad-1 from Solanaceae plants regulates IAA levels by catalyzing a reverse reaction of the first step of IAA biosynthesis. Pad-1 is a pyridoxal phosphate (PLP)-dependent aminotransferase, with IPyA as the amino acceptor and l-glutamine as the amino donor. Currently, the structural and functional basis for the substrate specificity of Pad-1 remains poorly understood. In this study, we carried out structural and kinetic analyses of Pad-1 from Solanum melongena. Pad-1 is a homodimeric enzyme, with coenzyme PLP present between a central large α/β domain and a protruding small domain. The active site of Pad-1 includes a vacancy near the phosphate group (P-side) and the 3'-O (O-side) of PLP. These features are distinct from those of TAA1, which is homologous in an overall structure with Pad-1 but includes only the P-side region in the active site. Kinetic analysis suggests that P-side residues constitute a binding pocket for l-glutamine, and O-side residues of Phe124 and Ile350 are involved in the binding of IPyA. These studies illuminate distinct differences in the active site between Pad-1 and TAA1, and provide structural and functional insights into the substrate specificity of Pad-1.
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10.1016/j.jsb.2022.107857
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pubmed_545_11683
|
AIMS
This study aimed to investigate the effect of previously synthesized 4,5-diazafluorene derivative (14c) on γδ T cell-mediated cytotoxicity against renal cell carcinoma (RCC).
MATERIALS AND METHODS
A real-time cell analyzer monitored cell proliferation, and Cell Counting Kit-8 determined cell viability. A reverse transcription-polymerase chain reaction analyzed gene expression, and protein expression was determined by cellular immunofluorescence analysis and Western blot.
KEY FINDINGS
The compound 14c induced the expression of immunomodulatory molecules, such as natural killer group 2, member D ligands (NKG2DLs), fibroblast-associated (Fas) death receptor, and tumor necrosis factor-related apoptosis-inducing ligand receptors (TRAILRs) in RCC. In addition, 14c induced DNA damage responses in RCC. Blocking DNA damage by KU-55933 reduced the effect of γδ T cells on 14c-treated RCC, suggesting that DNA damage responses were involved in the augmentation of γδ T cell-mediated cytotoxicity. Treating 786-O cells with a nitrogen-containing bisphosphonate prodrug further enhanced the anti-tumor effect of γδ T cell plus 14c combination treatment.
SIGNIFICANCE
The present evidence indicates that 14c induced DNA damage responses in RCC and augmented γδ T cell-mediated cytotoxicity primarily through NKG2D/NKG2DLs pathways, suggesting potential cancer immunotherapy for harnessing γδ T cells and small compounds that induce DNA damage responses.
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10.1016/j.lfs.2021.119066
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pubmed_412_6916
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Adenine phosphoribosyltransferase (APRT) is a purine metabolic enzyme and a homozygous deficiency in this enzyme causes 2,8-dihydroxyadenine urolithiasis. Various germline abnormalities have been described, but we report here a unique type of germline mutation in a homozygous individual (SY) who had excreted 2,8-dihydroxyadenine crystals. In SY, TCA was substituted for the physiological stop codon TGA. This base substitution generates a new HinfI restriction site, and, using the polymerase chain reaction and subsequent digestion by this enzyme, it was confirmed that SY is homozygous for the base substitution. This base change is unique in that it generates an open reading frame that extends to the poly(A) addition site. The amount of mRNA in transformed B cells from SY was approximately a quarter of that in control subjects and no APRT proteins were detected. In eukaryotes, unlike in prokaryotes, no rescue systems for defective polypeptide termination caused by a missing stop codon have been found. Therefore, the outcome of the defect of SY is unclear from present knowledge about termination of polypeptide synthesis. Investigations into the mechanisms of the absence of protein in the cells of SY may lead to a better understanding of the physiological and nonphysiological termination of polypeptide synthesis in eukaryotic cells.
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10.1007/s004390050677
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pubmed_830_19436
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In this work, blended nanofibrous membranes were prepared by an electrospinning technique with polyvinylpyrrolidone (PVP) K90 as the filament-forming polymer, and emodin, an extract of polygonum cuspidate known as a medicinal plant, as the treatment drug. Detailed analysis of the blended nanofibrous membrane by scanning electron microscopy, Differential scanning calorimetry and X-ray diffraction revealed that emodin was well distributed in the ultrafine fibers in the form of amorphous nanosolid dispersions. Results from attenuated total reflectance Fourier transform infrared spectra suggested that the main interactions between PVP and emodin might be mediated through hydrogen bonding. In vitro dissolution tests proved that the blended nanofibrous membrane produced more desired release kinetics of the entrapped drug (emodin) as compared to the pure drug. Furthermore, wound healing test and histological evaluation revealed that the emodin loaded nanofibrous membrane to be more effective as a healing accelerator thereby proving potential strategies to develop composite drug delivery system as well as promising materials for future therapeutic biomedical applications.
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10.1007/s10856-012-4728-x
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pubmed_1051_6467
|
Transmission electron microscopy (TEM) remains the gold standard for renal histopathological diagnoses, given its higher resolving power, compared with light microscopy. However, it imposes several limitations on pathologists, including longer sample preparation time and a small observation area. To overcome these, we introduced a scanning electron microscopy (SEM) technique for imaging resin-embedded semi-thin sections of renal tissue. We developed a rapid tissue preparation protocol for experimental models and human biopsies which, alongside SEM digital imaging acquisition of secondary electrons (SE-SEM), enables fast electron microscopy examination, with a resolution similar to that achieved by TEM. We used this unconventional SEM imaging approach to investigate the subpodocyte space (SPS) in BTBR ob/ob mice with type 2 diabetes. Analysis of semi-thin sections with secondary electrons revealed that the SPS had expanded in volume and covered large areas of the glomerular basement membrane, forming wide spaces between the podocyte body and the underlying filtering membrane. Our results show that SE-SEM is a valuable tool for imaging the kidney at the ultrastructural level, filling the magnification gap between light microscopy and TEM, and reveal that in diabetic mice, the SPS is larger than in normal controls, which is associated with podocyte damage and impaired kidney function.
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10.3390/ijms23031699
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pubmed_242_24818
|
AIMS
To assess the effects of peroxisome proliferator-activated receptor (PPAR) agonists on glucose tolerance and hepatic lipid metabolism in diet-induced obese mice.
MAIN METHODS
Male C57BL/6 mice received a standard chow diet (SC, 10% energy as lipids) or high-fat diet (HF, 50% energy as lipids) for 10 weeks, after which treatment was initiated, forming the groups: SC group, HF group, HF-BZ group (HF + bezafibrate, pan-PPAR agonist), HF-WY group (HF + WY-14643, PPARalpha agonist) and HF-GW group (HF + GW1929, PPARgamma agonist). Treatments lasted for four weeks. Insulin resistance and liver remodeling were evaluated by biochemical and molecular approaches.
KEY FINDINGS
The HF and HF-GW mice were overweight. Conversely, the HF-BZ and HF-WY mice presented with body masses equal to those of the SC mice. All treatments restored insulin sensitivity and blood lipid and adiponectin levels. Hepatic steatosis was prevented in the HF-WY and HF-BZ mice as shown by the elevated mRNA levels of PPARalpha and Carnitine palmitoyl transferase-1a in both groups, which favored enhanced beta-oxidation. Marked decreases in liver triacylglycerol levels confirmed these findings. In contrast, the HF-GW mice exhibited increased PPARgamma and fatty acid translocase/CD136 mRNA levels, contributing to enhanced hepatic lipogenesis.
SIGNIFICANCE
The WY14643 and bezafibrate treatments most effectively improved the adverse metabolic and hepatic effects caused by obesity and IR. The results reinforce the central role of PPARalpha, as well as its contrary relationship to PPARgamma in the regulation of metabolic homeostasis and lipolytic pathways in the liver.
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pubmed_242_24818
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pubmed_500_18739
|
Milk yield, feed intake, physiology, health, and reproduction of cows supplemented with somatotropin are like those of genetically superior cows. Lactation curves are shifted upward and are more persistent. Holsteins, Jerseys, Brown Swiss, and Ayrshires respond. In most cases, responses in primiparous and multiparous animals are similar. Milk composition, ration digestibility, maintenance requirements, and the partial efficiency of lactation are not affected by somatotropin. More nutrients are directed to milk synthesis. Initially, body stores of fat, protein, and glycogen provide these nutrients, but after a few weeks, feed intake increases. Cows supplemented with somatotropin should be fed like high producing cows. When ration energy density is increased by feeding grain, buffers such as sodium bicarbonate should be included to prevent alterations of hydrogen balance in the rumen and tissues. Ration energy density can also be increased with ruminally inert fat like calcium salts of fatty acids. Rations should be balanced for rumen degradable and undegradable protein. Rations for high milk yields are expensive, but income over feed costs are greater. Cows should be moved to rations with lower nutrient densities on the basis of body condition and milk yield. Current feeding recommendations can be used for cows supplemented with somatotropin.
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10.3168/jds.S0022-0302(89)79391-7
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pubmed_304_23608
|
TLRs sense components of microorganisms and are critical host mediators of inflammation during infection. Different TLR agonists can profoundly alter inflammatory effects of one another, and studies suggest that the sequence of exposure to TLR agonists may importantly impact on responses during infection. We tested the hypothesis that synergy, priming, and tolerance between TLR agonists follow a pattern that can be predicted based on differential engagement of the MyD88-dependent (D) and the MyD88-independent (I) intracellular signaling pathways. Inflammatory effects of combinations of D and I pathway agonists were quantified in vivo and in vitro. Experiments used several D-specific agonists, an I-specific agonist (poly(I:C)), and LPS, which acts through both the D and I pathways. D-specific agonists included: peptidoglycan-associated lipoprotein, Pam3Cys, flagellin, and CpG DNA, which act through TLR2 (peptidoglycan-associated lipoprotein and Pam3Cys), TLR5, and TLR9, respectively. D and I agonists were markedly synergistic in inducing cytokine production in vivo in mice. All of the D-specific agonists were synergistic with poly(I:C) in vitro in inducing TNF and IL-6 production by mouse bone marrow-derived macrophages. Pretreatment of bone marrow-derived macrophages with poly(I:C) led to a primed response to subsequent D-specific agonists and vice versa, as indicated by increased cytokine production, and increased NF-kappaB translocation. Pretreatment with a D-specific agonist augmented LPS-induced IFN-beta production. All D-specific agonists induced tolerance to one another. Thus, under the conditions studied here, simultaneous and sequential activation of both the D and I pathways causes synergy and priming, respectively, and tolerance is induced by agonists that act through the same pathway.
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10.4049/jimmunol.178.2.1164
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pubmed_434_17338
|
AIMS
To develop appropriate statistical approaches to plan and evaluate proficiency tests for the enumeration of Escherichia coli, addressing, in particular, a possible but frequently unavoidable lack of test sample homogeneity.
METHODS AND RESULTS
Each of 50 laboratories analysed two samples of a stabilized suspension of E. coli in duplicate, using various media, inoculation methods, and incubation times and conditions. In parallel, the E. coli suspension was tested by the organiser for homogeneity and stability. Escherichia coli counts followed a log-normal distribution. After eliminating, by Youden analysis, two data sets that were considered outliers and eight data sets for underperformance of the laboratories (substantial lack of repeatability), the standard deviation of the mean was about 0·06 log(10) units. There was no evidence of bimodality of the data. Lack of homogeneity of distribution of bacteria had a strong effect on measurement uncertainty, in addition to laboratory bias and method repeatability. The homogeneity decreases during storage of the individual test vials; this effect could be modelled by the known kinetics of inactivation of micro-organisms. The results were confirmed by Monte Carlo simulations.
CONCLUSIONS
By a tailored analysis of proficiency testing data, it is possible to distinguish the effect of lack of homogeneity, laboratory bias and method repeatability, on the measurement uncertainty.
SIGNIFICANCE AND IMPACT OF THE STUDY
A statistic tool is provided to solve problems related to lack of stability of microbiological test material and to separate the effects of sample inhomogeneity from the performance of the individual laboratory.
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10.1111/j.1365-2672.2010.04866.x
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pubmed_417_1545
|
We sought to prospectively identify the role of neurosonography in the evaluation of a consecutive group of small-for-gestational-age (SGA) neonates, and also to identify the association of neurosonographic findings with cocaine exposure and cytomegalovirus (CMV) infection. Neurosonographic imaging was performed in 180 SGA neonates within 72 hours of birth. Urine samples were screened for CMV and cocaine metabolites (CM) in all cases. Sixty-five neonates (37.5%) had an abnormal neurosonographic appearance. Nine neonates were positive for CMV and 31 neonates were positive for CM. Focal echolucencies (27), ventricular dilation (27), and subependymal hemorrhages (12) were the most common neurosonographic abnormalities. The first two were more common with CM (p < .05). An abnormal neurosonographic pattern was seen more often in SGA neonates with CM (54.8%, 17 of 31; p < .05) and CMV (67%, 6 of 9; p < .01) as compared with the rest (32.6%, 44 of 135; p < .01). Among those without CM or CMV, prematurity was associated with an increased risk for abnormality (p < .001 between groups), specifically subependymal hemorrhage, ventricular dilation, and porencephalic cysts. Five CMV-positive neonates showed periventricular, echogenic foci mainly in the area of the frontal horn. Two new findings with SGA were caudate nucleus echogenicity and a "moth-eaten" appearance of the thalamus, each found in three infants. Neurosonographic imaging is useful in the evaluation of SGA neonates. Focal echolucencies and caudate echogenicity suggest maternal cocaine use, and periventricular echogenic foci strongly suggest fetal CMV infection.
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10.1002/jcu.1870220205
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pubmed_742_4891
|
MicroRNAs (miRNAs) are small, noncoding RNAs which regulate cell differentiation, proliferation, development, cell cycle, and apoptosis. Expression profiling of miRNAs has been performed and the data show that some miRNAs are upregulated or downregulated in cancer. Several studies suggest that the expression profiles of miRNAs are associated with clinical outcomes. However, the set of miRNAs with altered expressing differs depending on the type of cancer, suggesting that it is important to understand which miRNAs are related to which cancers. Therefore, this review aimed to discuss potentially crucial miRNAs in head and neck squamous cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC).
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10.3390/cancers2020653
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pubmed_367_2471
|
BACKGROUND
Because prostaglandins are involved in many (patho)physiological processes, SLCO2A1 was already characterized in several species in an attempt to unravel specific processes/deficiencies. Here, we describe the molecular cloning and characterization of the porcine ortholog in order to evaluate its possible involvement in F4 enterotoxigenic E. coli mediated neonatal diarrhoea, based on a positional candidate gene approach study.
RESULTS
Porcine SLCO2A1 is organized in 14 exons, containing an open reading frame of 1935 bp, encoding a 12-transmembrane organic anion cell surface transporter of 644 aa. The -388 to -5 upstream region comprises a (CpG)48 island containing a number of conserved promoter elements, including a TATA box. A potential alternative promoter region was found in the conserved -973 to -700 upstream region. No consensus polyadenylation signal was discovered in the 3' UTR. Repeat sequences were found in 15% of all the non coding sequences.As expected for a multifunctional protein, a wide tissue distribution was observed. mRNA expression was found in the adrenal gland, bladder, caecum, colon (centripetal coil/centrifugal coil), diaphragm, duodenum, gallbladder, heart, ileum, jejunum, kidney, liver, longissimus dorsi muscle, lung, lymph node, mesenterium, rectum, spleen, stomach, tongue and ureter, but not in the aorta, oesophagus and pancreas.The promoter region and the exons (including the splice sites) of SLCO2A1 were resequenced in 5 F4ab/ac receptor positive and 5 F4ab/ac receptor negative pigs. Two silent and 2 missense (both S --> L at position 360 and 633) mutations were found, but none was associated with the F4ab/ac receptor phenotype. In addition, no phenotype associated differential mRNA expression or alternative/abberant splicing/polyadenylation was found in the jejunum.
CONCLUSION
The molecular cloning and characterization of porcine SLCO2A1 not only contributes to the already existing knowledge about the transporter in general, but enables studies on porcine prostaglandin related processes/deficiencies as patient and/or model. Here we examined its possible involvement as receptor in F4 enterotoxigenic E. coli mediated neonatal diarrhoea. Because no phenotype associated differences could be found in the gene sequence nor in its jejunal transcription profile of F4ab/ac receptor positive/negative pigs, SLCO2A1 can most likely be excluded as receptor for F4 bacteria.
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10.1186/1471-2156-10-64
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pubmed_406_12012
|
There exist few reports concerning cancer presenting in forensic autopsies. This study of 1,300 consecutive forensic autopsies yielded 22 cases of single cancers (1.7%) of multiple primary sites and histologic types. The forensic autopsy affords unique opportunity to study not only diagnosed and treated trauma, disease, and cancer, but the natural evolution of untreated cancer as well. Clinically occult cancer is not uncommon and may eventually present clinically or at autopsy in unusual fashion. Advanced cancer may, sometimes on initial presentation, be responsible for sudden unexpected death. Persons with cancer, even in an advanced state, uncommonly commit suicide. Conversely, those committing suicide ostensibly because of known cancer infrequently prove to have cancer at autopsy. Through these autopsy studies, the forensic pathologist gains information invaluable for statistical, clinical, and medicolegal purposes, truly fulfilling his role of "community pathologist".
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pubmed_406_12012
|
pubmed_898_24662
|
Oxidative stress plays a crucial role in pathogenesis of various cardiovascular diseases. Recent studies reported that isosteviol sodium (STVNa) harbor cardioprotective properties. Here, we explore the potential cardioprotective effect of STVNa on H₂ O₂ -induced oxidative stress on heart embryonic H9c2 cardiomyocytes and the underlying mechanism. We have found that STVNa pretreatment improved cell viability, nuclear morphology and prevented LDH release induced by oxidative stress. STVNa pretreatment also reduced production of reactive oxygen species, preserved mitochondrial function, restored biological antioxidant defense systems and prevented cell death. Western blotting analysis revealed that STVNa regulated the mitochondrial related pro- and anti-apoptotic protein (Bax and Bcl-2 respectively) levels, increased phosphorylation of Akt (ser473) and GSK-3β (ser9) and promoted binding between HK-II and mitochondria under the normal or oxidative stress conditions. LY294002, a PI3K inhibitor, abolished cytoprotective effects of STVNa by inhibiting activation of Akt and GSK-3β. Based on these findings, we conclude that STVNa protects H9c2 cells against oxidative stress by activating Akt/GSK-3β signaling pathway, which, in turn, leads to recruitment of HK-II to mitochondria and regulating Bcl2/Bax levels.
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10.1691/ph.2020.9851
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pubmed_103_23336
|
OBJECTIVES
Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE). However, it remains unclear if all BE patients benefit from long-term surveillance. We investigated the risk of esophageal adenocarcinoma (EAC) in BE patients in relation to number of successive endoscopies, years of follow-up, and calendar year.
METHODS
We conducted a retrospective cohort study of male veterans with newly diagnosed BE during 2004-2009 with follow-up until 30 September 2011. EAC was verified using detailed structured electronic medical records reviews. We used Poisson regression to determine incidence rates, rate ratios (RR), and corresponding 95% confidence intervals (CI) for EAC according to number of successive endoscopies, years of follow-up independent of number of follow-up endoscopies, and calendar year of BE diagnosis.
RESULTS
Among 28,561 male patients with BE, 406 developed EAC during 140,499 person-years of follow-up (median 4.9 years). EAC incidence rates increased with each additional endoscopy following a previous negative endoscopy (RR per additional endoscopy, 1.43; 95% CI, 1.25-1.64). Compared to the EAC incidence rate at the 1st follow-up EGD, the EAC incidence rate at the 5th follow-up EGD was ninefold higher (adjusted RR, 8.82; 95% CI, 4.90-15.9). EAC incidence was highest at the first year of follow-up (5.34 per 1,000 person-years); however, EAC rates starting from the second follow-up year increased during successive years of follow up. Compared to the EAC incidence rate in the 2nd year of follow-up, the EAC incidence rate was 1.5-fold higher in EGDs conducted ≥5 years after the index BE date (adjusted RR, 1.49; 95% CI, 1.07-2.10). In contrast, we found no significant change in EAC incidence rates by calendar year.
CONCLUSIONS
Persistence of non-neoplastic BE on multiple consecutive endoscopies was not associated with lower EAC risk. These findings argue against discontinuation of endoscopic surveillance in patients with persistent nondysplastic BE after multiple negative endoscopies.
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10.1038/ajg.2017.18
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pubmed_662_6413
|
The HLA gene and haplotype frequencies in psoriatic population (N = 136) and families (N = 47) were estimated. The significant association with HLA-B17 and B13 was found. The relative risk for these antigens was 4.4 and 2.4, respectively. The most frequent haplotypes carrying the "psoriatic" antigens was HLA-A1, B17 and HLA-A10, B17, with significant relative risk, equalled 8.24 and 5.75. The distribution of HLA-B13 and B17 phenotypes according to the three groups of clinical activity and four groups of extent of skin lesions were considered. The strong association between HLA-B17 and psoriasis with large skin involvement (more than 50%) was observed. The possible role of antigen B17 in pathomechanism of psoriasis is discussed.
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10.1007/BF00409460
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pubmed_598_8943
|
Water-soluble ZnS:Mn quantum dots (QDs) were synthesized using a hydrothermal method with 3-mercaptopropionic acid as stabilizer. The optical properties of ZnS:Mn QDs were thoroughly investigated by tuning the doping concentration of Mn2+ and the Zn/S precursor ratio, to obtain an optimal parameter for QDs with excellent fluorescence characteristics. ZnS:Mn QDs excited at only one wavelength, however, which seriously limited their further application. Here, a trace Cd ion was doped into a ZnS host, resulting in QD excitation covering a wide adjustable waveband. Furthermore, when a ZnS shell was coated onto the surface of the ZnCdS:Mn QDs, photoluminescence intensity and stability were further enhanced. After coupling with an anti-CK 19 antibody, the ZnCdS:Mn/ZnS core/shell QDs were able to function by labeling cancer cells, indicating that they could be considered as a suitable bio-probe for cells and tissue imaging.
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10.1002/bio.3456
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pubmed_1085_6341
|
This paper is a reexamination of the Winter hypothesis, which holds that there was a marked difference in the development of civilian health during the First World War between the central powers and the Western allies. Ultimate success on the battlefield, according to Winter, required balancing the needs of the military with civilian demands; Germany lost because it failed to achieve such a balance. The resulting decline in health standards undermined the war effort and eventually led to defeat. This article proceeds in two steps. First, it demonstrates that Winter's data does not allow him to make a proper comparison between the two camps. Second, I argue that his hypothesis can be refuted once a truly comparable source is used--infant mortality rated. There is as yet no convincing evidence to suggest that the outcome of the First world War was determined by public health policy.
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10.3406/adh.1995.1903
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pubmed_177_15013
|
A 48-year-old man with lung squamous cell carcinoma was admitted to acute care with cognitive impairment after recent chemotherapy. He developed myoclonus, ataxia, agitation, and visual hallucinations. Morvan syndrome, a rare voltage-gated potassium channel antibody disorder characterized by neuromyotonia with central nervous system dysfunction, was eventually diagnosed. He received plasmapheresis and was admitted to inpatient rehabilitation, where he safely participated in therapies. By focusing on neuromuscular rehabilitation, balance training, fine motor skills, and cognitive retraining emphasizing skills relevant to the patient's premorbid cognitive activities, the patient demonstrated significant functional improvement, decreasing the burden of care of his caregivers.
LEVEL OF EVIDENCE
V.
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10.1016/j.pmrj.2017.10.014
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pubmed_969_10340
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Separation of the enzymes formate dehydrogenase, formaldehyde dehydrogenase and methanol oxidase from Candida boidinii crude extract has been explored using continuous flow zone electrophoresis in the VaP-22 and the scaled-up VaP-220 electrophoresis apparatus. Yields up to 95% and purification factors between 3 and 7 were obtained, together with separation of cell debris from the enzymes. Multiple injections of sample were used to obtain a protein throughput of 46.2 mg/h in the VaP-22. A tenfold higher throughput was achieved using the VaP-220. Correlation of the electrophoretic mobility in continuous flow zone electrophoresis with the elution behavior in ion-exchange chromatography confirmed the primary role of net surface charge in the separation of biological molecules. Proteins and enzymes with differences greater than 0.05 M elution molarities in ion-exchange chromatography can be separated. This corresponds to a preparative scale (mg/h or g/h) separation of proteins and enzymes whose difference in apparent electrophoretic mobility is greater than 0.70 x 10(-5) cm2/(V.s).
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10.1002/elps.1150111110
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pubmed_809_18230
|
Arterial thrombosis is the major reason for severe complications of coronary artery disease (CAD). Recently it has been suggested that the FXIII-A Val34Leu polymorphism, affecting clot stability, provides protection against thrombosis. Results published up to date implicate that there is a significant correlation between geographical area and the Leu34 allele prevalence and that its contribution to arterial thrombosis is different in different populations. The purpose of this study was to determine frequency of Leu34 allele in Croatian subjects as well as to estimate its association with a CAD. FXIII-A Val34Leu genotyping was carried out by real-time PCR method on the LightCycler using melting curve analysis with forward 5'-AACTTCCAGGACCGGCTTT-3' and reverse 5'-ACCCAGAGTGGTGGGGAA-3' primers. The Leu34 allele frequency in studied Croatian subjects was 24.3%. No significant differences were found in the prevalence of FXIII-A Val34Leu genotype or Leu34 allele distribution between studied subjects (P > 0.05). Carriage of the Leu34 allele was not significantly associated with CAD or MI risk reduction (P > 0.05). This is the first report that studies the prevalence of the Leu34 allele frequency in Croatian subjects and our results suggest that possession of the Leu 34 alele does not provide protection against MI.
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10.1007/s11033-007-9144-9
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pubmed_20_24844
|
AIM
To conduct an integrative review to examine evidence of pain and associated symptoms in adult (≥21 years of age), postcraniotomy, brain tumour patients hospitalized on intensive care units.
BACKGROUND
Healthcare providers believe craniotomies are less painful than other surgical procedures. Understanding how postcraniotomy pain unfolds over time will help inform patient care and aid in future research and policy development.
DESIGN
Systematic literature search to identify relevant literature. Information abstracted using the Theory of Unpleasant Symptoms' concepts of influencing factors, symptom clusters and patient performance. Inclusion criteria were indexed, peer-reviewed, full-length, English-language articles. Keywords were 'traumatic brain injury', 'pain, post-operative', 'brain injuries', 'postoperative pain', 'craniotomy', 'decompressive craniectomy' and 'trephining'.
DATA SOURCES
Medline, OVID, PubMed and CINAHL databases from 2000-2014.
REVIEW METHOD
Cooper's five-stage integrative review method was used to assess and synthesize literature.
RESULTS
The search yielded 115 manuscripts, with 26 meeting inclusion criteria. Most studies were randomized, controlled trials conducted outside of the United States. All tested pharmacological pain interventions. Postcraniotomy brain tumour pain was well-documented and associated with nausea, vomiting and changes in blood pressure, and it impacted the patient's length of hospital stay, but there was no consensus for how best to treat such pain.
CONCLUSION
The Theory of Unpleasant Symptoms provided structure to the search. Postcraniotomy pain is experienced by patients, but associated symptoms and impact on patient performance remain poorly understood. Further research is needed to improve understanding and management of postcraniotomy pain in this population.
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10.1111/jan.12890
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pubmed_1020_8529
|
For the CT iterative reconstruction, choosing the parameters of different regularization terms has been a difficult problem. Transforming the reconstruction problem into constrained optimization can solve this problem, but determining the constraint range and accurately solving it remains a challenge. This paper proposes a CT reconstruction method based on constrained data fidelity term, which estimates the distribution of the constraint function by Taylor expansion to determine the constraint range. We respectively use Douglas-Rachford splitting (DRS) and Projection-based primal-dual algorithm (PPD) to split the reconstruction problem and solve the data fidelity subproblem. This method can accurately estimate the constrained range of data fidelity terms to ensure reconstruction accuracy and use different regularization terms for reconstruction without parameter adjustment. Three regularization terms are used for reconstruction experiments, and simulation results show that the proposed method can converge stably, and its reconstruction quality is better than the filtered back-projection.
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10.1109/EMBC46164.2021.9631063
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pubmed_148_3086
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Various aspects of pulmonary function were measured in eight patients with chronic bronchial obstructive disease, after five-month oral administration of a sustained-release aminophylline preparation (BY 108: Euphyllin retard). In addition to a sustained bronchodilator effect there was an improvement in static pulmonary volumes and a marked increase in forced expiratory volumes. The reduction in residual volume and of midcapacity is felt to be of particular importance in the prevention of pulmonary emphysema.
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10.1055/s-0028-1106570
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pubmed_612_25350
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This study evaluated the antibacterial efficacy of methanolic extracts of isolated endophytic fungi from stem barks and leaves of Alstonia boonei De Wild and Greenwayodendron suaveolens (Engl. and Diels) Verdc. subsp. Suaveolens against Klebsiella pneumoniae ATCC 43816, Haemophilus influenzae ATCC 49247, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 35218, responsible for causing pneumonia. The endophytic fungi were isolated and characterized in the Potato Dextrose Agar (PDA), Sabouraud Dextrose Agar (SDA), and Czapek Dox Agar (CDA) media. The fungi and their methanolic extracts were tested for in vitro antibacterial potential by antagonistic assay for endophytic fungi against bacterial pathogens and microdilution method. The phytochemical screening of extracts was carried out according to the colorimetric and precipitation methods to reveal the presence of secondary metabolites. The results showed that 24 macroscopically and microscopically distinct endophytic fungi were isolated, identified, and stored. These endophytic fungi possessed antibacterial activity against the selected bacterial strains with inhibition zones ranging from 7.00 to 25.00 mm. The endophytic fungi GS15 and AB24 have presented the inhibitions zones of 20.33 mm and 25.00 mm, respectively, and these were better than the ones obtained for Levofloxacin®. The endophytes with inhibition zones greater than 10 mm were used for extraction of their secondary metabolites. The endophytic fungi extracts showed antibacterial activity with the minimum inhibitory concentrations (MICs) ranging from 6.25 × 10-4 to 2 × 10-2 g/L and the minimum bactericidal concentrations (MBCs) ranging from 2.5 × 10-3 to 2 × 10-2 g/L. The endophytic fungi GS15 extract was the most effective extract; it showed bactericidal effects on the tested bacterial strains. The phytochemical screening of the extracts revealed the presence of secondary metabolites classes, responsible for causing the obtained antibacterial activity. Thus, the endophytic fungi methanolic extracts from A. boonei and G. suaveolens have the potential to inhibit the growth of bacteria responsible for nosocomial pneumonia.
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10.1155/2021/9966323
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pubmed_959_21625
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Article-based theses and dissertations are increasingly being used in nursing and the health sciences as an alternate format to the traditional five-chapter monograph. A unique chapter in the article-based thesis is the integrated discussion, which differs in breadth and depth as compared to the discussion for a traditional thesis monograph or journal article. For many students and faculty, the integrated discussion is a challenging chapter to write, with minimal or no published guidance available. In this article, we offer a four-step approach with templates for planning and writing an integrated discussion. We also share several lessons learned with examples from published theses and dissertations. Writing an integrated discussion can be facilitated and written more efficiently by developing a clear and detailed outline of the chapter and broad discussion points prior to drafting the text, to achieve a higher-level synthesis, analysis, and interpretation of the overall significance of the thesis findings.
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10.1515/ijnes-2020-0057
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pubmed_482_2478
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In this study, the modification of the desorption behavior of LiAlH4 by the addition of K2NbF7 was explored for the first time. The addition of K2NbF7 causes a notable improvement in the desorption behavior of LiAlH4. Upon the addition of 10 wt.% of K2NbF7, the desorption temperature of LiAlH4 was significantly lowered. The desorption temperature of the LiAlH4 + 10 wt.% K2NbF7 sample was lowered to 90°C (first-stage reaction) and 149°C (second-stage reaction). Enhancement of the desorption kinetics performance with the LiAlH4 + 10 wt.% K2NbF7 sample was substantiated, with the composite sample being able to desorb hydrogen 30 times faster than did pure LiAlH4. Furthermore, with the presence of 10 wt.% K2NbF7, the calculated activation energy values for the first two desorption stages were significantly reduced to 80 and 86 kJ/mol; 24 and 26 kJ/mol lower than the as-milled LiAlH4. After analysis of the X-ray diffraction result, it is believed that the in situ formation of NbF4, LiF, and K or K-containing phases that appeared during the heating process promoted the amelioration of the desorption behavior of LiAlH4 with the addition of K2NbF7.
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10.3389/fchem.2020.00457
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pubmed_658_1924
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We describe a calcifying fibrous pseudotumour of pleura in a 46-year-old female, smoker. The patient presented with a well-delimited pleural mass, 3-cm across, located at the base of the right lung and attached to the lung with a short pedicle. Seven years after surgical excision of the mass, the patient is alive and well. Microscopically, the lesion was mostly composed of dense collagenous tissue, with sparse benign spindle cells, a rich inflammatory infiltrate and scattered calcifications, sometimes laminated. Immunohistochemically, spindle cells were positive for vimentin and negative for smooth muscle actin, desmin, S100 protein, CD34, CD99 and Bcl2. Calcifying fibrous pseudotumour is rare in the pleura. Pertinent data from the literature and problems in differential diagnosis are briefly discussed.
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10.1007/s102420200032
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pubmed_33_24082
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Serratia marcescens jn01 was employed as the host for the isolation of phages from environmental sewage. One strain of phage named SmPjn was purified by picking transparent plaque with 2mm diameter and clear edge on the double-layer agar repeatedly. Electron micrographs indicated that the phage head was icosahedral with head size and tail length of (58 +/- 2.16) x (55 +/- 0.47) nm and (7 +/- 1.25) nm, respectively. On the basis of the morphology, this phage belongs to the family Podoviridae. Host-range determination revealed that the phage was capable of infecting the other two isolates of S. marcescens, P25 and CMCC41002. The optimal multiplicity of infection was 1. A one-step growth curve of SmPjn indicated that the latent period and burst size were estimated at 50 min and 1,125 pfu/cell, respectively . Genomic DNA of SmPjn was above 27kb in size and could be digested by Hind Ill and EcoR I into 11 and 9 visible fragments after electrophoresis, respectively. A novel Podoviridae-phage infecting S. marcescens was firstly reported in China.
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pubmed_33_24082
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pubmed_248_3148
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Molecular modeling was used to analyze the phenomena involved in the sorption of hydrocarbons by the Pt/Al2O3 reforming catalyst. The interactions between the atoms of the catalyst structure and the molecules of the model reforming compounds were described in terms of the universal forcefield. Making use of the GCMC algorithms, the adsorption isotherms for the reagents in the catalytic system and the temperature dependence of the Henry constant were determined. The research has produced the following major findings: the amount of the hydrocarbon molecules adsorbed rises with increasing pressure and decreasing temperature, and the adsorption isotherm for toluene has a characteristic plot as compared to the isotherms of the other hydrocarbons studied. Mass cloud analysis has revealed a favorable effect of platinum on adsorption in the catalyst model.
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10.1016/j.jmgm.2005.11.009
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pubmed_495_782
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Propafenone is a sodium channel blocking agent with a mild beta- and calcium channel-blocking activity. Several controlled and noncomparative studies have documented its efficacy in a variety of supraventricular arrhythmias in both adults and children. Propafenone is comparable with other Vaughan-William class I antiarrhythmic drugs for acute conversion of atrial fibrillation. It is also comparable with other drugs for prevention of recurrences in paroxysmal atrial fibrillation and for maintenance of sinus rhythm following successful cardioversion of chronic atrial fibrillation. Although propafenone is effective in the acute management of junctional reentrant tachycardias, the availability of safer drugs precludes its routine use for these arrhythmias. It may, however, be preferred for the acute management of haemodynamically well tolerated pre-excited atrial fibrillation in patients with the Wolff-Parkinson-White (WPW) syndrome. It also has documented efficacy in the long term therapy of patients with junctional tachycardias, and is a useful first-line drug in the management of arrhythmias in patients with the WPW syndrome, particularly when there is a short anterograde refractory period of the accessory pathway. Noncomparative studies were confirmed good efficacy and tolerability of propafenone in the short and long term management of paediatric supraventricular arrhythmias. It seems to be particularly effective for the treatment of ectopic atrial and junctional tachycardias, which are generally difficult arrhythmias to manage. Propafenone appears to have an acceptable adverse effect profile during both short and long term therapy. As with most other antiarrhythmic agents, there is a proarrhythmic potential. This has also been observed in children. There is a theoretical possibility that the beta-blocking properties of propafenone may protect against its proarrhythmic potential. However, this has not been confirmed in clinical studies. In conclusion, propafenone appears to be effective in the management of a wide spectrum of supraventricular arrhythmias. It should be considered among the first line drugs for management of these arrhythmias in patients without structural heart disease.
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10.2165/00003495-199550020-00005
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pubmed_80_1128
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Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies.
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10.1016/S1470-2045(19)30318-3
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pubmed_445_9114
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A new DNA polymerase was partially purified from cell-free extracts of a continuous rat cell-line (XC). The XC cells had been transformed by the Prague strain of Rous sarcoma virus but did not produce infectious virus. The molecular weight of the DNA polymerase is 70,000, as estimated by glycerol gradient centrifugation and by Sephadex gel filtration. This enzyme can be distinguished from the other cellular DNA polymerases by its elution pattern on DNA-cellulose column chromatography, its molecular weight, and its primer-template specificity. The enzyme has some characteristics of the murine leukemia virus reverse transcriptase. It is partially inhibited by immunoglobulin G purified from rabbit antiserum prepared against Rauscher leukemia virus reverse transcriptase, but is not inhibited by IgG from rat antiserum prepared against avian myeloblastosis virus reverse transcriptase. However, the XC cell enzyme can be distinguished from the murine leukemia virus reverse transcriptase by its inefficiency in copying an oligo(dG)12-poly(rC)primer-template.
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10.1016/0005-2787(75)90019-2
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pubmed_72_7974
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Determining the mechanism of gene function is greatly enhanced using conditional mutagenesis. However, generating engineered conditional alleles is inefficient and has only been widely used in mice. Importantly, multiplex conditional mutagenesis requires extensive breeding. Here we demonstrate a system for one-generation multiplex conditional mutagenesis in zebrafish (Danio rerio) using transgenic expression of both cas9 and multiple single guide RNAs (sgRNAs). We describe five distinct zebrafish U6 promoters for sgRNA expression and demonstrate efficient multiplex biallelic inactivation of tyrosinase and insulin receptor a and b, resulting in defects in pigmentation and glucose homeostasis. Furthermore, we demonstrate temporal and tissue-specific mutagenesis using transgenic expression of Cas9. Heat-shock-inducible expression of cas9 allows temporal control of tyr mutagenesis. Liver-specific expression of cas9 disrupts insulin receptor a and b, causing fasting hypoglycemia and postprandial hyperglycemia. We also show that delivery of sgRNAs targeting ascl1a into the eye leads to impaired damage-induced photoreceptor regeneration. Our findings suggest that CRISPR/Cas9-based conditional mutagenesis in zebrafish is not only feasible but rapid and straightforward.
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10.1534/genetics.115.176917
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pubmed_87_24449
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We propose resilient quantum superposition states in closed-loop multilevel system which result in myriad quantum interference phenomena. An interplay of these superposition states results in a whole gamut of atomic phenomena including coherent population trapping (CPT), electromagnetically induced transparency (EIT), electromagnetically induced absorption (EIA), amplification without inversion (AWI) and enhancement of refractive index accompanied with negligible absorption. The polarization and the phases of the fields transform the underlying superposition of the excited states leading to all these effects, where, given the macroscopic nature of these phenomena the quantum superposition states as well as the synergy between them can be ascertained. Numerical simulations for D1 transition in room temperature Rb<sup>87</sup> atomic vapour system bear out these findings.
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10.1364/OE.22.015305
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pubmed_828_7573
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Transcription by all RNA polymerases (RNAPs) requires a series of large-scale conformational changes to form the transcriptionally competent open complex RP(o). At the lambdaP(R) promoter, Escherichia coli sigma(70) RNAP first forms a wrapped, closed 100 bp complex I(1). The subsequent step opens the entire DNA bubble, creating the relatively unstable (open) complex I(2). Additional conformational changes convert I(2) to the stable RP(o). Here we probe these events by dissecting the effects of Na(+) salts of Glu(-), F(-), and Cl(-) on each step in this critical process. Rapid mixing and nitrocellulose filter binding reveal that the binding constant for I(1) at 25 degrees C is approximately 30-fold larger in Glu(-) than in Cl(-) at the same Na(+) concentration, with the same log-log salt concentration dependence for both anions. In contrast, both the rate constant and equilibrium constant for DNA opening (I(1) to I(2)) are only weakly dependent on salt concentration, and the opening rate constant is insensitive to replacement of Cl(-) with Glu(-). These very small effects of salt concentration on a process (DNA opening) that is strongly dependent on salt concentration in solution may indicate that the backbones of both DNA strands interact with polymerase throughout the process and/or that compensation is present between ion uptake and release. Replacement of Cl(-) with Glu(-) or F(-) at 25 degrees C greatly increases the lifetime of RP(o) and greatly reduces its salt concentration dependence. By analogy to Hofmeister salt effects on protein folding, we propose that the excluded anions Glu(-) and F(-) drive the folding and assembly of the RNAP clamp/jaw domains in the conversion of I(2) to RP(o), while Cl(-) does not. Because the Hofmeister effect of Glu(-) or F(-) largely compensates for the destabilizing Coulombic effect of any salt on the binding of this assembly to downstream promoter DNA, RP(o) remains long-lived even at 0.5 M Na(+) in Glu(-) or F(-) salts. The observation that Esigma(70) RP(o) complexes are exceedingly long-lived at moderate to high Glu(-) concentrations argues that Esigma(70) RNAP does not dissociate from strong promoters in vivo when the cytoplasmic glutamate concentration increases during osmotic stress.
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10.1021/bi100092a
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pubmed_50_22470
|
BACKGROUND
Glutaric aciduria type 1, a deficiency of glutaryl-CoA dehydrogenase, causes an accumulation of neurotoxic metabolites glutaric acid and 3-hydroxyglutaric acid (3-HGA). Testing of these analytes is routinely done by GC-MS but seldom account for interference from isomers or compounds with similar ion transitions. We developed a liquid chromatography tandem mass spectrometry method that accurately measures 3-HGA in urine and plasma specimens, while utilizing similar reagents and instrumentation used for the routine performance of amino acid and acylcarnitine analysis in determining the diagnosis of several metabolic disorders.
METHOD
Plasma and urine samples were added aliquots of the deuterated 3-HGA internal standard and acetonitrile. The protein-free supernatant was brought to dryness, and the residue derivatized using 3 M HCL in 1-butanol with heating. The dried derivative was then reconstituted in 50% methanol-water solution and aliquot transferred to an HPLC vial for analysis by LC-MS/MS. Separation was performed using a C8 HPLC column under flow gradient conditions of 0.2% formic acid in water and methanol, respectively. Ionization was by ESI and detection of selected precursor-product ion transitions by multiple reaction monitoring (MRM) in positive mode.
RESULTS
The butyl-ester derivative of 3-HGA eluted at 7.82 min while 2-hydroxyglutaric acid (2-HGA) eluted at 8.21 min. This was equivalent to a separation factor of 1.05 and a resolution of 1.03, respectively. The 3-HGA calibration curve was linear over the range 6.20-319 ng mL-1 (r2 = 0.9996), and the reportable range determined by the linearity was found to be 1.54-384 ng mL-1. The calculated limits of detection and quantitation were 0.348 and 1.56 ng mL-1, respectively. Intra- and Inter-assay %CVs for quality control plasma and urine samples ranged from 2 to 18%, with recoveries of 66-115%. The method correlated to the gold standard GC-MS method for both serum (r2 ≥ 0.996) and urine analysis (r2 ≥ 0.949). The concentration of 3-HGA in normal, non-GA1 individuals was ≤25.2 ng mL-1 (in plasma) and ≤ 35.0 μmol mmol-1 of creatinine (in urine).
CONCLUSIONS
This LC-MS/MS method accurately quantified plasma and urine 3-HGA concentration after successful resolution from 2-HGA and other compounds with similar ion transitions. This method is suitable for confirmatory testing of 3-HGA, as a follow-up to an abnormal newborn screen test result, with concern for GA type 1.
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10.1016/j.jchromb.2018.09.007
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pubmed_804_2381
|
Background
Many patients with common cancers are late diagnosed.
Objectives
Identify consultation profiles and clinical features in patients with the seven most common cancers, who had consulted a general practitioner (GP) frequently before their cancer diagnosis.
Methods
A case-control study was conducted in Region Västra Götaland, Sweden. A total of 2570 patients, diagnosed in 2011 with prostate, breast, colorectal, lung, gynaecological and skin cancers including malignant melanoma, and 9424 controls were selected from the Swedish Cancer Register and a regional health care database. Diagnostic codes [International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10)] from primary care for patients with ≥4 GP consultations registered in the year before cancer diagnosis were collected. Likelihood ratios (LRs) were calculated for variables associated with the different cancers.
Results
Fifty-six percent of the patients had consulted a GP four or more times in the year before cancer diagnosis. Alarm symptoms or signs represented 60% of the codes with the highest LR, but only 40% of the 10 most prevalent codes. Breast lump had the highest LR, 11.9 [95% confidence interval (CI) 8.0-17.8]; abnormalities of plasma proteins had an LR of 5.0 (95% CI 3.0-8.2) and abnormal serum enzyme levels had an LR of 4.6 (95% CI 3.6-5.9). Early clinical features associated with cancer had been registered already at the first two GP consultations.
Conclusion
One out of six clinical features associated with cancer were presented by cancer patients with four or more pre-referral consultations already at the two first consultations. These early clinical features that were focal and had benign characteristics might have been missed diagnostic opportunities.
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10.1093/fampra/cmy012
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pubmed_596_19092
|
In this study two time scales were looked at: a yearlong study was completed, and a 180-day decay experiment was done. Juncus maritimus and Scirpus maritimus have different life cycles, and this seems to have implications in the Hg-contaminated salt marsh sediment chemical environment, namely Eh and pH. In addition, the belowground biomass decomposition rates were faster for J. maritimus, as well as the biomass turnover rates. Results show that all these species-specific factors have implications in the mercury dynamics and sequestration. Meaning that J. maritimus belowground biomass has a sequestration capacity for mercury per square metre approximately 4-5 times higher than S. maritimus, i.e., in S. maritimus colonized areas Hg is more extensively exchange between belowground biomass and the rhizosediment. In conclusion, J. maritimus seems to provide a comparatively higher ecosystem service through phytostabilization (Hg complexation in the rhizosediment) and through phytoaccumulation (Hg sequestration in the belowground biomass).
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10.1016/j.envpol.2011.03.036
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pubmed_896_21084
|
BACKGROUND
Patients with Substance use disorder have distinct personality traits, they were high score in novelty seeking (NS) and sensation seeking and lower in Self-directedness and higher in Self-transcendence, so we aim to investigate the relationships of temperament and characteristics with related some variables such as substance of choice.
DESIGN AND SETTING
A case-control study enrolling 70 Substance use disorder patients and 70 controls was conducted at Mashhad University of medical sciences.
METHODS
Using a case-control design, a group of 70 Substance use disorder patients and 70 controls was conducted at Mashhad university of medical sciences. All participation completed the 240 questions of Temperament and Character Inventory-Revised (TCI-R). Multivariate analysis of covariance (MANCOVA) was employed to compare the relationship between temperament and character traits and patterns of substance use.
RESULTS
The scores of reward dependence, persistence, self-directedness, cooperativeness, and self-transcendence were significantly lower in the case group compared to healthy individuals (P < 0.05). In contrast, the score of novel seeking was significantly higher in the case group (P < 0.05). On the other hand, harm avoidance was not significantly different between the two studied groups (P = 0.637).
CONCLUSIONS
Higher NS in patients with substance use disorder is common and different traits, and temperaments would choose different substance combinations.
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10.1186/s40359-021-00647-x
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pubmed_327_6190
|
A laboratory-scale continuously mixed anaerobic digester was inoculated with a mix of anaerobic sludge and fed with glucose. The start-up strategy was progressive and chemical analyses were done to evaluate digester performance from day 1 to day 107. In parallel, Archaeal community dynamics were monitored by SSCP analysis of the V3 region of 16S rDNA genes and further characterized by partial sequencing of 16S rDNA genes. At day 1 the inoculum contained at least five distinct Archaeal peaks close to known methanogenic species. The dominant peak was very close to Methanosaeta concilli, the remaining species being members of the Methanobacteriales and Methanomicrobiales. A rapid shift of the Archaeal population was observed during the experiment. At day 21 Methanobacterium formicicum, which was not detected at day 1, became the dominant methanogenic species in the bioreactor and remained so until the end of the experiment.
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10.1111/j.1574-6941.2001.tb00772.x
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pubmed_175_23839
|
The high presence of microplastics (MPs) in different sizes, materials and concentrations in the aquatic environment is a global concern due to their potential physically and chemically harm to aquatic organisms including mammals. Furthermore, the bioaccumulation of these compounds is leading to their ingestion by humans through the consumption of sea food and even through the terrestrial food chain. Even though conventional wastewater treatment plants are capable of eliminating more than 90% of the influent MPs, these systems are still the main source of MPs introduction in the environment due to the high volumes of effluents generated and returned to the environment. The amount of MPs dumped by WWTP is influenced by the configuration of the WWTP, population served and influent flow. Thus, the average of MP/L disposed vary widely depending on the region. In addition to MPs disposed in water bodies, more than 80% of these emerging contaminants, which enter the WWTP, are retained in biosolids that can be applied as fertilizers, representing a potential source of soil contamination. Due to the continuous disposal of MPs in the environment by effluent treatment systems and their polluting potential, separation and identification techniques have been assessed by several researchers, but unfortunately, there are no standard protocols for them. Aiming to provide insight about the relevance of studying the WWTP as source of MPs, this review summarizes the currently methodologies used to classify and identify them.
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10.1016/j.jenvman.2019.109739
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pubmed_60_6241
|
Many proteins act as molecular machines that are fuelled by a nonthermal energy source. Examples include transmembrane pumps and stator-rotor complexes. These systems undergo cyclic motions (CMs) that are being driven along a well-defined conformational trajectory. Superimposed on these CMs are thermal fluctuations (TFs) that are coupled to stochastic motions of the solvent. Here we explore whether the TFs of a molecular machine are affected by the occurrence of CMs. Bacteriorhodopsin (BR) is a light-driven proton pump that serves as a model system in this study. The function of BR is based on a photocycle that involves trans/cis isomerization of a retinal chromophore, as well as motions of transmembrane helices. Hydrogen/deuterium exchange (HDX) mass spectrometry was used to monitor the TFs of BR, focusing on the monomeric form of the protein. Comparative HDX studies were conducted under illumination and in the dark. The HDX kinetics of BR are dramatically accelerated in the presence of light. The isotope exchange rates and the number of backbone amides involved in EX2 opening transitions increase roughly 2-fold upon illumination. In contrast, light/dark control experiments on retinal-free protein produced no discernible differences. It can be concluded that the extent of TFs in BR strongly depends on photon-driven CMs. The light-induced differences in HDX behavior are ascribed to protein destabilization. Specifically, the thermodynamic stability of the dark-adapted protein is estimated to be 5.5 kJ mol(-1) under the conditions of our work. This value represents the free energy difference between the folded state F and a significantly unfolded conformer U. Illumination reduces the stability of F by 2.2 kJ mol(-1). Mechanical agitation caused by isomerization of the chromophore is transferred to the surrounding protein scaffold, and subsequently, the energy dissipates into the solvent. Light-induced retinal motions therefore act analogously to an internal heat source that promotes the occurrence of TFs. Overall, our data highlight the potential of HDX methods for probing the structural dynamics of molecular machines under "engine on" and "engine off" conditions.
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10.1021/ja206197h
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pubmed_346_5008
|
In view of published results of epidemiologic studies which suggested an association between nitrate in drinking water and human malformations, an assessment of the toxicology of nitrates and nitrites in relation to possible adverse effects on reproduction and development was performed. The current water standard for nitrate is based on protection from methemoglobinemia. A review of the animal data failed to provide evidence for teratogenic effects attributable to nitrate or nitrite ingestion. Adverse reproductive effects reported occurred at doses that were about one thousand times and higher than the estimated human intake. Neither nitrate nor nitrite in experimental animals concentrated in the mammary gland or milk. The present assessment concludes that the maximum contaminant level of 45 ppm nitrate ion, or 10 ppm nitrate-nitrogen, adequately protects the very young from nitrate-induced toxicity, both pre- and postnatally.
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10.1016/0273-2300(87)90024-9
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pubmed_27_11886
|
A group of 30 patients clinically described as having the Prader-Willi Syndrome (PWS) were studied using microsatellites from 15q11-13 and methylation analysis with probe PW71B (D15S63). The patients were categorized according to clinical symptoms. 80% of all patients were informative using molecular and cytogenetic methods. Among 8 patients with an atypical PWS phenotype, 2 showed uniparental disomy, and 2 had a mosaic deletion for 15q. The last 4 atypical and 2 typical patients had neither molecular defects confirmed by microsatellite analysis nor a parent-of-origin-specific methylation pattern for PWS. Our results confirm that methylation pattern analysis provides an additional and alternative microsatellite analysis to diagnose PWS.
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10.1017/s0001566000001446
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pubmed_635_21550
|
International Journal of Radiation Biology, November 2014; 90(11): 948–952© 2014 Informa UK, Ltd.ISSN 0955-3002 print / ISSN 1362-3095 online. DOI: 10.3109/09553002.2014.950714 .French contribution to develop Prussian blue: Isabelle Besse Bardot, Sebastien Bardot, Florence Menetrier, Alexandra Leiterer & Annick Pech. The publishers would like to apologise on behalf of the authors. Following the publication of an article in the International Journal of Radiation Biology, Volume 90, Issue (11) 948– 952, we have been informed by the author of an error. On page 952 the wrong table was submitted and subsequently included in the article. The correct Table II follows.
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10.3109/09553002.2015.1039247
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pubmed_1031_19370
|
This research quantitatively evaluated the marginal adaptation of pit and fissure sealants. The occlusal surfaces of 48 intact, caries-free human molars were cleaned with an air-abrasion unit. The teeth were then randomly divided into eight groups of six teeth each according to the type of enamel conditioning, sealant material applied and curing unit used. After applying either 40% phosphoric acid gel (K-etch, Kuraray Co) or a self-etching primer adhesive system (Clearfil SE Bond, Kuraray Co), sealant materials of two viscosities were applied (Teethmate F-1 and Protect-Liner-F, Kuraray Co) and cured with halogen (Optilux 500, Demetron) or plasma arc (Apollo-95E, Dental & Medical Diagnostic Systems, Ltd) curing units. The marginal adaptation of the pit and fissure sealant restorations was evaluated by using a computer-assisted quantitative margin analysis in a scanning electron microscope (SEM) on epoxy replicas before and after thermal and mechanical stressing of the teeth. The results were statistically analyzed with one-way analysis of variance (ANOVA) at a confidence level of 95% (p=0.05). A post-hoc Tukey HSD-test was used for multiple pairwise comparisons between groups. The null hypothesis was that there was no statistically significant difference between the groups that were tested in this study. The statistically significant differences between groups were more pronounced after loading. In most cases, the self-etching adhesive system (SE Bond) proved as effective as phosphoric acid etching (K-etch). The low viscosity sealant material (Teethmate F-1), in most cases, exhibited better marginal adaptation than the high viscosity material (Protect-Liner F). The high viscosity material performed equally well only when used in combination with the self-etching primer adhesive system as an intermediate layer. The halogen curing unit (Optilux 500) led to better marginal adaptation than the plasma arc curing unit (Apollo 95E), especially after thermal and mechanical stressing.
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pubmed_1031_19370
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pubmed_732_25106
|
OBJECTIVE
This research aims to investigate magnetic resonance imaging (MRI) in the tibial epiphyseal growth plate development of Wistar rat.
METHODS
Fifty weanling Wistar rats were divided by a computerized blocking procedure into five groups. The rats received standard commercial feed with or without T-2 toxin additive, low-protein feed with or without T-2 toxin additive, and Kashin-Beck disease (KBD)-affected feed.
RESULTS
Compared with the control group rat, MRI showed localized epiphyseal plate swelling, rough appearance, and uneven signal on the tibia of rats fed with KBD-affected feed. Histology confirmed the epiphyseal plate degeneration seen by MRI, and the degenerative changes were characterized by abnormal distribution of chondrocytes with loss and clustering, cartilage fragmentation, and erosion in group E.
CONCLUSIONS
The MR image of the rat epiphyseal plate is altered in the KBD model rats, and epiphyseal plate MRI appearance has been reproduced by using T-2 toxin and KBD-affected feed of epidemic district.
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10.1186/1749-799X-9-39
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pubmed_808_9941
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One of the most serious complications of diabetes mellitus, which could lead to end-stage renal disease across all demographics, is 'diabetic kidney disease'. However, how diabetic kidney disease develops remains unclear. Studies conducted thus far suggest that a major factor in the origination and development of the disease occurs through histone acetylation modifications. This study aims to examine the probable relationship in Chinese patients suffering from type 2 diabetes. A case-control study was conducted in the Chongqing region of China on the Chinese Han population. Patients suffering from type 2 diabetes mellitus were selected between March 2014 and Dec 2014 from the Department of Endocrinology, which is the First Affiliated Hospital of Chongqing Medical University. TaqMan probes were employed to perform an allelic discrimination assay for genotyping p300 and the SIRT1 (Silent Information Regulator 1) polymorphism. The risk factors diabetic kidney disease were determined by statistical analysis. The dispersion of the p300 genotype frequencies and SIRT1 gene polymorphism adheres to the Hardy-Weinberg equilibrium. The DKD group had a greater allele G frequency distribution, and allele G patients have a higher probability of diabetic kidney disease. Female patients, patients younger than 65 years of age, and those with the AG or GG genotype are more likely to develop diabetic kidney disease than patients with the AA phenotype. Patients with the AG or GG genotype are more likely to suffer from a severe diabetic kidney disease than patients with the AA genotype, particularly if the patients are older than 65 years of age. The SIRT1 rs4746720 allele C is a risk factor for urinary Alb/Cr. Allele G and the TC genotype patients are more likely to develop diabetic kidney disease, while allele G and TT genotype patients are more likely develop a severe diabetic kidney disease. Transcriptional coactivator p300 gene polymorphism correlates with the development and advancement of diabetic kidney disease. Additionally, the SIRT1 gene collaborates with the p300 gene and participates in promoting albuminuria in type 2 diabetes mellitus patients.
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10.1055/s-0043-103966
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pubmed_115_15358
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The reductive transformation of pentachloronitrobenzene (PCNB), an organochlorine fungicide, was investigated with a mixed, methanogenic culture developed from a contaminated estuarine sediment. Batch assays performed with this enrichment culture resulted in the biotransformation of PCNB to pentachloroaniline (PCA), which was then sequentially dechlorinated as follows: PCA --> 2,3,4,5- and 2,3,5,6-tetrachloroaniline (TeCA) --> 2,4,5- and 2,3,5-trichloroaniline (TrCA) --> 2,4-, 2,5-, and 3,5-dichloroaniline (DCA) --> 3- and 4-chloroaniline (CA) (low levels). Glucose fermentation, methanogenesis, and dechlorination were not inhibited at an initial PCNB concentration up to 40 microM, which is 27 times higher than its aqueous solubility. The addition of 25 mM 2-bromoethanesulfonate (BES) to the PCNB-amended culture resulted in the complete inhibition of methanogenesis, but the biotransformation of PCNB to PCA and its sequential dechlorination pathway were not affected. The addition of sodium azide (200 mg/L) to the PCNB-amended culture resulted in complete inhibition of methanogenesis, but did not inhibit the transformation of PCNB to PCA; however, PCA dechlorination was not observed. PCNB was also abiotically transformed to PCA in autoclaved culture media but at much lower rates as compared to the biotic assays. In contrast, the rate of PCNB to PCA transformation in autoclaved culture controls was similar to the rates observed in the azide-amended culture and the active enrichment culture, indicating that biotically derived reductants facilitated the observed transformation of PCNB to PCA. Dechlorination of PCA was not observed in any of the abiotic controls. These findings have significant environmental implications in terms of the fate and transport of PCNB, PCA, and its dechlorination products in subsurface systems.
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10.1021/es050407+
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pubmed_1112_25294
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Proper N- and O-glycosylation of recombinant proteins is important for their biological function. Although the N-glycan processing pathway of different expression hosts has been successfully modified in the past, comparatively little attention has been paid to the generation of customized O-linked glycans. Plants are attractive hosts for engineering of O-glycosylation steps, as they contain no endogenous glycosyltransferases that perform mammalian-type Ser/Thr glycosylation and could interfere with the production of defined O-glycans. Here, we produced mucin-type O-GalNAc and core 1 O-linked glycan structures on recombinant human erythropoietin fused to an IgG heavy chain fragment (EPO-Fc) by transient expression in Nicotiana benthamiana plants. Furthermore, for the generation of sialylated core 1 structures constructs encoding human polypeptide:N-acetylgalactosaminyltransferase 2, Drosophila melanogaster core 1 β1,3-galactosyltransferase, human α2,3-sialyltransferase, and Mus musculus α2,6-sialyltransferase were transiently co-expressed in N. benthamiana together with EPO-Fc and the machinery for sialylation of N-glycans. The formation of significant amounts of mono- and disialylated O-linked glycans was confirmed by liquid chromatography-electrospray ionization-mass spectrometry. Analysis of the three EPO glycopeptides carrying N-glycans revealed the presence of biantennary structures with terminal sialic acid residues. Our data demonstrate that N. benthamiana plants are amenable to engineering of the O-glycosylation pathway and can produce well defined human-type O- and N-linked glycans on recombinant therapeutics.
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10.1074/jbc.M112.402685
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pubmed_205_15478
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Factors affecting in-line near infrared (NIR) moisture measurement with a four-wavelength sensor were evaluated (choice of binder used in granulation liquid and the increase in particle size). An entire NIR spectrum is not necessary for the measurement of water, and often the use of only a few NIR wavelengths around the water band enables reliable and high-speed detection of moisture. Glass ballotini and microcrystalline cellulose (MCC) were used as model test materials. The binders studied were poly[1-(2-oxo-1-pyrrolidinyl)ethylene] (PVP) and gelatin. Full off-line NIR spectra of test materials at different levels of binder solutions were measured. The major spectral features for both the binders were bands around 1700 nm (first overtones CH related stretches) and 2200 nm (combination bands). Gelatin also had an NH band around 1500 nm (first overtones of NH stretches) and combination bands at about 2050 nm. Particle size effects were observed as an increase in spectra baseline. All these factors should be considered when choosing NIR wavelengths used for detection of water with a fixed wavelength set-up. A robust calibration model enables the development of in-process control of wet granulation processes.
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10.1016/s0939-6411(00)00096-5
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pubmed_879_12437
|
BACKGROUND
Endovascular access is usually achieved through the common femoral artery due to its large size and accessibility. Access through the upper extremity can however be necessary due to anatomic reasons, obesity, or peripheral arterial disease. The 2 main methods of access are surgical cutdown and percutaneous puncture. In this single-centre retrospective cohort study we compared complication risks for both surgical cutdown and percutaneous puncture of an upper arm approach.
MATERIALS AND METHODS
Data was obtained from patients receiving endovascular access through the brachial or axillary artery between 2005 and 2018. A total of 109 patients were included. Patient demographics including age, sex, medical history, smoking status, and actual medication were registered, as well as postoperative complications including hematoma, thrombosis, dissection, infection, pseudoaneurysm, nerve injury, reoperation, and readmission.
RESULTS
Access was achieved through surgical cutdown in 53% (n = 58) and through percutaneous puncture in 47% (n = 51) of patients. Fifty-eight percent (n = 63) received access via the brachial artery (BA) and 42% (n = 46) via the axillary artery. Complication rate was 25.0% (3 of 12) for surgical cutdown via the BA, 29.4% (15 of 51) for percutaneous puncture via the BA, and 10.9% (5 of 46) for surgical cutdown via the axillary artery. Major complication rate was 8.3% (1 of 12) for surgical cutdown via the BA, 13.7% (7 of 51) for percutaneous puncture via the BA, and 4.3% (2 of 46) for surgical cutdown via the axillary artery. There was no association between baseline patient characteristics and complication rate.
CONCLUSIONS
In this nonrandomized retrospective study, surgical cutdown via the axillary artery was the safest option with fewest complications, but selection of patients may have blurred the results. Surgical cutdown and percutaneous puncture seem equally safe in terms of complication rate in the BA.
|
10.1016/j.avsg.2021.09.052
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pubmed_825_15279
|
This paper presents the results of treatment of 81 children, aged 5 to 14 years, suffering from exudation ethmoid sinusitis; isolated ethmoid sinusitis was diagnosed in 17.8% and ethmoid sinusitis combined with maxillary sinusitis was detected in 61.7% cases. Most sinusitis cases (82.7%) were diagnosed in 5 to 10 year-old children. The ethmoidal labyrinth and maxillary sinus were treated by the puncture method, infection of other paranasal sinuses being excluded by the application of antibacterial, enzymic, corticosteroid drugs, immune agents, and adenotomy. Antibiotic therapy of 2 weeks in duration applied to the ethmoid labyrinth and maxillary sinus was more efficient when compared to the sinus treatment alone. The stable clinical effect was seen in 86.4% cases. This therapeutic approach can find application in practical otolaryngology.
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pubmed_825_15279
|
pubmed_743_26833
|
Black patients have a higher incidence of heart failure (HF) and worse outcomes than white patients. Guidelines recommend palliative care for patients with advanced HF, but no studies have examined outcomes in a black patient cohort. This is a post hoc analysis of the Palliative Care in Heart Failure trial, which randomized patients to usual care plus a palliative care intervention (UC+PAL) or usual care (UC). Quality of life (QoL) was measured using Kansas City Cardiomyopathy Questionnaire (KCCQ) and Functional Assessment of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal). Black patients represented 41% of the 148 patients. At six months, QoL improved more in UC+PAL than UC for both racial subgroups. The difference was greater for black than white patients (difference: KCCQ 10.8 vs. 2.5; FACIT-Pal: 14.8 vs. 3.9). However, the findings were not statistically significant. Larger studies are needed to assess the benefits of palliative care for black patients with HF. ClinicalTrials.gov Identifier: NCT01589601.
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10.1089/jpm.2021.0220
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pubmed_540_15562
|
Background
Fingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood.
Objective
Investigate fingolimod's temporal effects on immune cell subsets, and safety outcomes.
Methods
In FLUENT, a 12-month, prospective, non-randomized, open-label, phase IV study, adult participants received fingolimod 0.5 mg/day. Changes in immune cell subsets, anti-John Cunningham virus (JCV) antibody index, and serum neurofilament levels were assessed.
Results
165 fingolimod-naive and 217 participants treated for 2-12 years in routine clinical practice were enrolled. Levels of all monitored peripheral lymphocyte subsets were reduced from month 3 in fingolimod-naive participants. Greatest reductions occurred in naive and central memory CD4+ and CD8+ T cells, and in naive and memory B cells. Most lymphocyte subset levels remained stable in the continuous fingolimod group. Components of the innate immune system remained within reference ranges. No increase in JCV seropositivity was observed. No single cellular subset correlated with anti-JCV antibody index at any time point. Neurofilament levels remained within healthy adult reference limits throughout. No opportunistic infections were reported; no new or unexpected safety signals were observed.
Conclusion
FLUENT provides insights into the utility of immunological profiling to evaluate therapy response and potential infection risk.
|
10.1177/20552173221115023
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pubmed_214_3613
|
BACKGROUND
A conventional treatment outcome is suboptimal for sensory impairments in stroke patients. Novel approaches based on electrical stimulation or robotics are proposed as an adjuvant for rehabilitation, though their efficacy for motor, sensory, and body representation recovery have not been tested.
METHODS
Sixty chronic stroke patients with unilateral motor deficits were included in a pseudo-randomized open-label multi-arm control trial (ClinicalTrials.gov: NCT03349138). We tested the effects of a robotic glove (GloReha [GR]) and a new neuromuscular electrical stimulation system (Helping Hand [HH]) and compared them with conventional treatment (CT) in restoring motor and sensory functions and the affected limb perception. HH was designed to concurrently deliver peripheral motor activation and enhanced cutaneous sensation. Patients were split in four dose-matched groups: CT, GR, HH, and GRHH (receiving 50% GR and 50% HH). Assessments were performed at inclusion, halfway, end of treatment (week 9), and follow-up (week 13).
FINDINGS
HH provided an earlier benefit, quantified by the Motricity Index (MI), than GR. At the end of the treatment, the amelioration was higher in groups GRHH and HH and extended to somatosensory functions. These benefits persisted at the follow-up. GRHH and HH also improved the perceived dimensions and altered feeling toward the affected limb. Interestingly, the reduction of altered feelings correlated with MI improvements and depended on the amount of HH.
CONCLUSIONS
We suggest that HH concurrently stimulates sensory and motor systems by generating an enhanced cutaneous sensation, coherent in location with the elicited motor recruitment, leading to ameliorated sensorimotor functions and bodily perceptions in stroke patients.
FUNDING
This work was supported by a Foundation advised by CARIGEST, by Fondazione CARIPLO, by the SNSF NCCR Robotics, and by the Bertarelli Foundation.
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10.1016/j.medj.2021.12.001
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pubmed_91_9728
|
1. Captopril was shown to be as effective as hydrochlorothiazide in lowering the blood pressure in patients with moderately severe essential hypertension. 2. With the combination of captopril and hydrochlorothiazide satisfactory control of blood pressure was maintained over 8 months. 3. Inhibition of angiotensin converting enzyme by captopril in man was associated with falls in plasma angiotensin II and urinary aldosterone and rises in angiotensin I and plasma renin. 4. No change in venous concentrations of bradykinin could be demonstrated during therapy. 5. Captopril attenuated the hyperaldosteronism and hypokalaemia associated with diuretic therapy.
|
10.1042/cs057135s
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pubmed_686_1801
|
OBJECTIVE
To search for an effective method for treatment of ankylosing spondylitis (AS).
METHODS
The treatment group (n = 32) were treated by acupuncture combined with cupping therapy and the control group (n = 30) by simple acupuncture for 40 days.
RESULTS
The clinical remission rate was 62.5% in the treatment group and 33.3% in the control group with a significant difference between the two groups (P<0.01); the total effective rate in the treatment group was 93.8% which was better than 83.3% in the control group (P<0.01); the recurrence rate after one year was 3.3% in the treatment group and 24.0% in the control group with significant difference between the two groups (P<0.01).
CONCLUSION
Acupuncture combined with cupping therapy in the therapeutic effect on ankylosing spondylitis is better than simple acupuncture, with shorter therapeutic course and lower recurrence rate.
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pubmed_686_1801
|
pubmed_78_8862
|
During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
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10.1161/CIRCULATIONAHA.105.537878
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pubmed_888_2654
|
BACKGROUND
We have recently demonstrated that peroxisome proliferator activated receptor (PPAR) gamma activation by its selective ligand, troglitazone, potently inhibited cell proliferation in human pancreatic cancer cells. The present study was performed to clarify the role of PPARgamma in cell invasion/motility in human pancreatic cancer cells.
METHODS
Cell invasive activity was assessed by an in vitro invasion assay, using a Transwell chamber, and by a wound-healing assay, in the human pancreatic cancer cell lines, PK-1 and PK-9. Cell morphology and actin structure were evaluated by phase-contrast and fluorescence microscopy.
RESULTS
PPARgamma activation by troglitazone inhibited cell invasion and cell migration in PK-1 and PK-9 cells. We also examined the effect of troglitazone on cell morphology and actin structure because of its effect on cell motility. The size of PK-1 and PK-9 cells that had been incubated with troglitazone became smaller, and the in shape changed from flat to spindle, followed by round. The troglitazone-induced cell rounding was reversible by replacement with troglitazone-free medium. Rhodamine-phalloidin staining revealed a decreased number of actin filaments in PK-1 cells treated with troglitazone. In cells treated with mycalolide B, an actin depolymerizing agent, troglitazone failed to induce cell rounding.
CONCLUSIONS
These results suggest that PPARgamma activation by troglitazone inhibited cell motility and changed cell morphology through modulating actin organization.
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10.1007/s00535-003-1324-3
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pubmed_273_6843
|
African trypanosomiasis (AT), also known as sleeping sickness in humans and Nagana in animals, is a disease caused by the protozoan parasite Trypanosoma brucei. AT is an extremely debilitating disease in human, cattle, and wild animals, and the treatment is difficult with frequent relapses. This work shows that BALB-c mice immunized intramuscularly with a single dose (100 microg) of a plasmid DNA encoding the 5'-terminal region of the trans-sialidase (nTSA) gene of T. brucei brucei are able to produce IgG antibodies that bind to the bloodstream form of T. brucei-protein extract and recognize the recombinant nTSA protein, expressed in Escherichia coli. Furthermore, this DNA vaccination process was able to protect 60% of mice submitted to a challenge assay with the infective form of T. brucei brucei parasites. These results demonstrate that a DNA vaccine coding for trans-sialidase from T. brucei is potentially useful in the prophylaxis of AT.
|
10.1007/s00436-009-1542-6
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pubmed_180_16966
|
Pertuzumab is a novel antihuman epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody. Combined with trastuzumab plus docetaxel, pertuzumab improved progression-free and overall survival versus trastuzumab plus docetaxel in the phase III CLEOPATRA trial (NCT00567190) in first-line HER2-positive metastatic breast cancer. Thirty-seven patients participated in a pharmacokinetic (PK)/corrected QT interval substudy of CLEOPATRA, which evaluated potential PK drug-drug interaction (DDI). PK parameters were calculated using noncompartmental methods, and DDI analyses were carried out. In the presence of trastuzumab and docetaxel, the mean pertuzumab Cmin and Cmax in cycle 3 were 63.6 and 183 µg/ml, respectively. The pertuzumab concentrations observed were consistent with simulations from a validated population PK model, indicating that trastuzumab and docetaxel did not alter pertuzumab PK. Comparison of geometric least-squares mean PK parameters between arms showed no impact of pertuzumab on the PK of trastuzumab or docetaxel. In conclusion, no PK DDI was observed when pertuzumab, trastuzumab, and docetaxel were combined for the treatment of HER2-positive metastatic breast cancer.
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10.1097/CAD.0000000000000016
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pubmed_204_23405
|
BACKGROUND
Studies generally use cognitive assessment done at one timepoint to define cognitive impairment in order to examine conversion to dementia. Our objective was to examine the predictive accuracy and conversion rate of seven alternate definitions of cognitive impairment for dementia.
METHODS
In this prospective study, we included participants from the Whitehall II cohort study who were assessed for cognitive impairment in 2007-09 and were followed up for clinically diagnosed dementia. Algorithms based on poor cognitive performance (defined using age-specific and sex-specific thresholds, and subsequently thresholds by education or occupation levels) and objective cognitive decline (using data from cognitive assessments in 1997-99, 2002-04, and 2007-09) were used to generate seven alternate definitions of cognitive impairment. We compared predictive accuracy using Royston's R 2, the Akaike information criterion (AIC), sensitivity, specificity, and Harrell's C-statistic.
FINDINGS
5687 participants, with a mean age of 65·7 years (SD 5·9) in 2007-09, were included and followed up for a median of 10·5 years (IQR 10·1-10·9). Over follow-up, 270 (4·7%) participants were clinically diagnosed with dementia. Cognitive impairment defined using both cognitive performance and decline had higher hazard ratios (from 5·08 [95% CI 3·82-6·76] to 5·48 [4·13-7·26]) for dementia than did definitions based on cognitive performance alone (from 3·25 [2·52-4·17] to 3·39 [2·64-4·36]) and cognitive decline alone (3·01 [2·37-3·82]). However, all definitions had poor predictive performance (C-statistic ranged from 0·591 [0·565-0·616] to 0·631 [0·601-0·660]), primarily due to low sensitivity (21·6-48·4%). A predictive model containing age, sex, and education without measures of cognitive impairment had better predictive performance (C-statistic 0·783 [0·758-0·809], sensitivity 74·2%, specificity 72·2%) than all seven definitions of cognitive impairment (all p<0·0001).
INTERPRETATION
These findings suggest that cognitive impairment in early old age might not be useful for dementia prediction, even when it is defined using longitudinal data on cognitive decline and thresholds of poor cognitive performance additionally defined by education or occupation.
FUNDING
National Institutes of Health, UK Medical Research Council.
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10.1016/S2666-7568(21)00117-3
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pubmed_476_8795
|
In recent years, environmental factors, particularly humidity, have been used to inform influenza prediction models. This study aims to quantify the relationship between humidity and influenza incidence at the state-level in the contiguous United States. Piecewise segmented regressions were performed on specific humidity data from NASA's Atmospheric Infrared Sounder (AIRS) and incident influenza estimates from Google Flu Trends to identify threshold values of humidity that signal the onset of an influenza outbreak. Our results suggest that influenza incidence increases after reaching a humidity threshold that is state-specific. A linear regression showed that the state-specific thresholds were associated with annual average humidity conditions (R 2 = 0.9). Threshold values statistically significantly varied by region (F-statistic = 8.274, p < 0.001) and of their 36 pairwise combinations, 13 pairs had at least marginally statistically significant differences in their means. All of the significant comparisons included either the South or Southeast region, which had higher humidity threshold values. Results from this study improve our understanding of the significance of humidity in the transmission of influenza and reinforce the need for local and regional conditions to be considered in this relationship. Ultimately this could help researchers to produce more accurate forecasts of seasonal influenza onset and provide health officials with better information prior to outbreaks.
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10.1029/2021GH000469
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pubmed_10_11132
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The proprotein convertase subtilisin / kexin type 9 (PCSK9) plays an important role in LDL cholesterol (LDL-C) metabolism. Subjects harboring loss-of-function mutations in the gene encoding for PCSK9 display markedly reduced LDL-C plasma levels. PCSK9 is secreted by the liver, binds to the LDL receptor and, following endocytosis, induces lysosomal degradation of the receptor together with the bound LDL-C. Current PCSK9 inhibitors are monoclonal antibodies that specifically absorb PCSK9. Subsequently, instead of being degraded the receptor can dissociate from LDL-C and recycle, consecutively resulting in an increased hepatocyte LDL receptor density and higher LDL-C clearance. In clinical trials, the PCSK9 inhibitors alirocumab and evolocumab induced reductions in LDL-C of up to 70 % in statin-treated as well as statin-naïve patients. So far, serious side effects (requiring cessation of drug treatment) occurred only in rare cases. Since this new class of lipid lowering drugs promises a high potential benefit, they have been approved by the EMA even before completion of the studies addressing clinically relevant endpoints like cardiovascular events and mortality. Therefore, the expected publication of these study results in 2017 may allow a better assessment of the efficacy and safety of PCSK9 inhibitors.
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10.1055/s-0042-102801
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pubmed_927_11217
|
Binding of 125I-labelled epidermal growth factor (EGF) to C3H/2K cells and the effect of a tumor promotor, 12-O-tetradecanoyl phorbol-13-acetate (TPA) and of a tumor promotor antagonist, retinoic acid, on the binding was studied. Scatchard plot analysis of the binding showed the presence of two types of binding sites with different affinity to EGF. Treatment of the cells with retinoic acid for 1 h resulted in elevation of the affinity of both sites without changing their number per cell. Prolonged exposure to retinoic acid abrogated this elevation of the affinity and caused cycloheximide-sensitive increase of the number of the binding sites of both types. TPA inhibited binding of EGF to the cells by abolishing the binding to the high affinity sites, whereas retinoic acid, in the presence of TPA, enhanced it by increasing the number of the low affinity sites.
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10.1016/0304-4165(82)90183-0
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pubmed_986_2351
|
The effects of varying concentrations of nutrients present in Bold's basal medium on the extent of colony formation from vegetative fragments, sporulation and spore germination of the green alga Stigeoclonium pascheri were studied. A decrease of colony formation was observed in media deficient in MgSO4, NaNO3, phosphates, and containing a 10-fold increase of H3BO3. Sporulation decreased in the same media. However, sporulation was greater in an increasing order in media containing 2- to 10-fold increase in MgSO4. There was a decrease in spore germination in media deficient in phosphates, MgSO4, containing 5- or 10-fold MgSO4, or containing 2- to 10-fold of CaCl2, H3BO3 or microelements. Spore germination increased in media containing 2-fold MgSO4, deficient in H3BO3 or microelements or containing none of the three micronutrient solutions.
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10.1007/BF02879772
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pubmed_414_17402
|
For jets, large eddy resolving simulations are compared for a range of numerical schemes with no subgrid scale (SGS) model and for a range of SGS models with the same scheme. There is little variation in results for the different SGS models, and it is shown that, for schemes which tend towards having dissipative elements, the SGS model can be abandoned, giving what can be termed numerical large eddy simulation (NLES). More complex geometries are investigated, including coaxial and chevron nozzle jets. A near-wall Reynolds-averaged Navier-Stokes (RANS) model is used to cover over streak-like structures that cannot be resolved. Compressor and turbine flows are also successfully computed using a similar NLES-RANS strategy. Upstream of the compressor leading edge, the RANS layer is helpful in preventing premature separation. Capturing the correct flow over the turbine is particularly challenging, but nonetheless the RANS layer is helpful. In relation to the SGS model, for the flows considered, evidence suggests issues such as inflow conditions, problem definition and transition are more influential.
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10.1098/rsta.2008.0281
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pubmed_774_2871
|
Neonatal inflammation is common and has lasting consequences for adult health. We investigated the lasting effects of a single bout of neonatal inflammation on adult respiratory control in the form of respiratory motor plasticity induced by acute intermittent hypoxia, which likely compensates and stabilizes breathing during injury or disease and has significant therapeutic potential. Lipopolysaccharide-induced inflammation at postnatal day four induced lasting impairments in two distinct pathways to adult respiratory plasticity in male and female rats. Despite a lack of adult pro-inflammatory gene expression or alterations in glial morphology, one mechanistic pathway to plasticity was restored by acute, adult anti-inflammatory treatment, suggesting ongoing inflammatory signaling after neonatal inflammation. An alternative pathway to plasticity was not restored by anti-inflammatory treatment, but was evoked by exogenous adenosine receptor agonism, suggesting upstream impairment, likely astrocytic-dependent. Thus, the respiratory control network is vulnerable to early-life inflammation, limiting respiratory compensation to adult disease or injury.
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pubmed_774_2871
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pubmed_639_11815
|
The phosphorylation status of oncoproteins is regulated by both kinases and phosphatases. Kinase inhibitors are rarely sufficient for successful cancer treatment, and phosphatases have been considered undruggable targets for cancer drug development. However, innovative pharmacological approaches for targeting phosphatases have recently emerged. Here, we review progress in the therapeutic targeting of oncogenic Src homology region 2 domain-containing phosphatase-2 (SHP2) and tumor suppressor protein phosphatase 2A (PP2A) and select other druggable oncogenic and tumor suppressor phosphatases. We describe the modes of action for currently available small molecules that target phosphatases, their use in drug combinations, and advances in clinical development toward future cancer therapies.
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10.1126/scitranslmed.abe2967
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pubmed_364_24868
|
Marine microalga Isochrysis sp. contains omega-3 fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Environmental factors play a major role in PUFA biosynthesis. Hence, the study focused to optimize factors such as temperature, pH, and photoperiod by response surface methodology (RSM). RSM results showed that the model is significant (p ≤ 0.05) with a high correlation coefficient (R2 = 0.908). The optimum conditions showed that maximum biomass (327 mg/L) at the temperature of 30 °C, pH of 7.5 and 16:8 (Light: Dark cycle), whereas the higher amount of DHA (13.3%) and EPA (9.0%) was observed in the conditions of 18 °C, pH of 7.5 and 16:8 (Light: Dark cycle). The biomass content was directly proportional to the temperature whereas DHA content was inversely proportional. It was revealed that the mRNA expression of EPA and DHA specific desaturases (5Des & 4Des) were significantly elevated in low temperature (20 °C) conditions. The results were highly correlated with the fatty acid profile of Isochrysis sp. grown under low temperature (20 °C) conditions which enhanced the EPA and DHA levels. This study suggests that the temperature is the most influencing factor which can be exploited in the industrial application of DHA and EPA production from Isochrysis sp.
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10.1080/10826068.2020.1833345
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pubmed_553_13506
|
Patients with hypertension have a impaired baroreflex sensitivity, the reduction being proportional to the blood pressure elevation. Coarctation of the aorta is characterized by hypertension in the upper part of the body. In eight young men, operated upon for coarctation of the aorta during childhood, baroreflex sensitivity was estimated from the prolongation of the R-R interval during the transient rise of arterial blood pressure induced by intravenous injections of small doses of angiotensin. The patients were compared with normotensive and hypertensive reference groups, of the same age and sex, who were examined in the same way. The resting mean blood pressure in the coarctation group was slightly elevated, and the baroreflex sensitivity was reduced proportionally. The fact that the baroreceptors were more sensitive than would be expected from the patients pre-operative high blood pressure suggests that the baroreceptor-resetting in high blood pressure is to a considerable degree reversible when the blood pressure is reduced.
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10.1111/j.1475-097x.1981.tb00917.x
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pubmed_257_9052
|
Changing the temperature from 10-40 degrees C modifies the transmission at an established monosynaptic connection between the fast extensor tibiae (FETi) and flexor tibiae motor neurons in the metathoracic ganglion of the locust Schistocerca gregaria (Forskål). Striking changes occur to the shape of the spikes, to membrane resistance, to the synaptic delay, and to the evoked synaptic potentials. In the presynaptic FETi motor neuron, raising the temperature reduces the amplitude of an antidromic spike recorded in the soma by a factor of 10 (40 mV to 4 mV), reduces the time taken to reach peak amplitude by 5 (3.5 to 0.7 ms) and decreases the duration at half maximum amplitude by 0.5. The conduction velocity of the spike in the axon is increased by 50% from 10 degrees C to 40 degrees C. Orthodromic spikes are affected by temperature in a similar way to the antidromic spikes. The membrane resistance of both pre- and postsynaptic motor neurons falls as the temperature is raised. The membrane resistance of FETi falls by a factor of 4 (about 4 M omega at 10 degrees C to 1 M omega at 40 degrees C). A contributory component to this fall could be the increase in the frequency of synaptic potentials generated as a result of inputs from other neurons. No temperature dependence could be demonstrated on the voltage threshold relative to resting potential for evoking orthodromic spikes, but because the resistance changes, the current needed to achieve this voltage must be increased at higher temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)
|
10.1007/BF00611000
|
pubmed_392_20460
|
BACKGROUND
The prevalence and outcomes of allergic bronchopulmonary aspergillosis (ABPA) in the elderly remain unknown.
METHODS
We reviewed our database to identify the proportion of subjects diagnosed with ABPA at ≥60 years of age (ABPA-elderly). We compared the clinical features, treatment and outcomes of ABPA-elderly versus the non-elderly (ABPA diagnosed at <60 years of age).
RESULTS
Between 2007 and 2019, we encountered 810 ABPA subjects with a mean age of 34.9 years (49.4% women). Of these, 43 (5.3%) were aged ≥60 years (ABPA-elderly). There was a trend towards lower median (interquartile range [IQR]) serum total IgE (4900 [2659-10000] vs. 7156 [23360-11963] IU/mL; P = .06) and Aspergillus fumigatus-specific IgE (12.3 [4.8-29.6] vs. 22.4 [7.7-41.5] kUA/L; P = .06) in the elderly than the non-elderly. Eosinophil counts were similar in the two groups. The median [IQR] number of segments involved by bronchiectasis (5 [2-9] vs. 7 [4-11]) was significantly lower in the ABPA-elderly (P = .001). The proportion of subjects experiencing ABPA exacerbations was significantly (P = .047) lower in the elderly (25.6%) vs. the non-elderly (40.8%). There was also a tendency towards a lower mean number of exacerbations in the elderly (155 vs. 208 exacerbation per 1000 person-years) than the non-elderly (P = .09). There was also a trend towards longer mean time to first exacerbation in the ABPA-elderly than the non-elderly (1612 vs. 1159 days).
CONCLUSION
ABPA was uncommon in the elderly. The bronchiectasis is less extensive with a trend towards lower immunological severity and fewer exacerbations in the elderly than the non-elderly subjects with ABPA.
|
10.1111/myc.13388
|
pubmed_368_8522
|
Cutaneous squamous cell carcinoma (cSCC) constitutes the most common cancer capable of metastasis. While the latest version of the American Joint Committee on Cancer guidelines represents a significant step forward in accurate staging of cSCC, several proven independent risk factors remain excluded. We review the current literature on the incidence and proven independent risk factors of metastasis for cSCC and proposes their full inclusion in the staging system for primary lesions.
|
10.1002/jso.23731
|
pubmed_1136_2563
|
The irrigation or agricultural land with wastewater is increasingly practiced in many parts of the world as a consequence of growing populations and urbanization. The risks emerging from pharmaceuticals that are contained in wastewater for soils and groundwater have hardly been investigated. We studied leaching and effects of naproxen, ibuprofen, bezafibrate, diclofenac, gemfibrocil, clarithromycin, trimethoprim, clindamycin, erythromycin, and metoprolol in a soil column experiment simulating an irrigation event with 8.6 cm of wastewater containing 20 microg L(-1) or 2000 microg L(-1) of each compound or of erythromycin alone. The leached fraction of applied pharmaceuticals ranged from 0.1 +/- 0.1% (clarithromycin, 2000 microg L(-1)) to 130 +/- 41% (naproxen, 20 microg L(-1)) and tended to increase with decreasing K(d) or K(oc). Naproxen transport was similar to that of the tracer chloride. Ibuprofen was also hardly retarded (R = 1.20 +/- 0.18), but showed a higher degradation rate of 0.02 +/- 0.004 h(-1) (2000 microg L(-1)) than naproxen. The transport of a pulse of 2000 microg L(-1) of bezafibrate could be described with a retardation factor of 1.5 and a degradation rate of 0.033 h(-1). The application of erythromycin alone or of a cocktail of all pharmaceuticals significantly increased soil CO2 emissions by 50% 1 d after the application. There is a considerable risk that pharmaceuticals are leached to groundwater during wastewater irrigation.
|
10.2134/jeq2009.0105
|
pubmed_470_9131
|
OBJECTIVE
Prior to the use of pcDNA3/pacA and pcDNA3/pacP in vivo, the transcription and expression products of these two eukaryotic expression plasmids in mammalian cells were detected.
METHODS
The eukaryotic expression plasmids pcDNA3/pacA and pcDNA3/pacP were transfected into COS-7 cells respectively with liposome according to the manufacturer's protocol. In order to generate stable transfectants, after a 48 h incubation period in regular Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% heat inactivated fetal bovine serum, cells were treated with neomycin (1 mg.ml-1 of G418) and maintained under continuous selective pressure. G418-resistant colonies, which became visible after 2 weeks, were isolated and screened for expression of the vector-encoded protein. The control transfections were performed with the pcDNA3 vector and without recombinant as well as vector plasmid DNA. The mRNA transcriptions of the two insertional genes were detected by RT-PCR assay and their expression products were analysed by labelled-avidin-biotin enzymed-linked immunosorbent assay, flow cytometry and Western blotting. The cells transfected by pcDNA3 were used as the negative control.
RESULTS
1. The two eukaryotic expression plasmids could be correctly transcripted and translated under the control of the CMV immediate early promoter in mammalian cells. 2. The protein products could be detected in cell plasma, cell membrane and the culture supernatant.
CONCLUSION
The two eukaryotic expression plasmids pcDNA3/pacA and pcDNA3/pacP can express protein products which were encoded by insertional gene pac-A and pac-P in mammalian cells.
|
pubmed_470_9131
|
pubmed_1089_18964
|
AIMS AND OBJECTIVES
The aim of this study was to identify the organisms responsible and to determine the antibiotic susceptibility pattern of the bacterial isolates from conjunctiva and nasal mucosa in cases of chronic dacryocystitis and comparing with lacrimal sac specimen.
DESIGN
Prospective longitudinal study.
METHODS
A prospective analysis of 44 lacrimal sac contents of patients with chronic dacryocystitis conducted during the period from April 2012 to March 2013. Material was obtained directly from the lacrimal sac while making sac flap during external dacryocystorhinostomy for chronic dacryocystitis. Samples were also collected from ipsilateral conjunctiva and inferior meatus of nose. The specimens were cultured and results analyzed.
STATISTICAL ANALYSIS
The results were analyzed by using Chi-square (χ(2)) test.
RESULTS
All the patients were in age group of 30 and above. Gram positive bacteria i.e., Coagulase negative staphylococci and Staphylococcus aureus were the most common isolates (71% and 14% respectively). Vancomycin, amikacin, 3(rd) generation cephalosporins and amoxyclav were most sensitive antibiotics (100%, 89%, 83%, and 78% respectively). Comparison between lacrimal and nasal/conjunctival isolates showed high degree of identicalness between the isolates of two sites (p< 0.05).
CONCLUSION
Majority of the chronic dacryocystitis cases are caused by Coagulase negative Staphylococci and Staphylococcus aureus. Amoxyclav and 3(rd) generation cephalosporins can be used to treat chronic dacryocystitis. Commensal flora of nose and conjunctiva have a direct role in pathogenesis of chronic dacryocystitis.
|
10.7860/JCDR/2013/6636.3590
|
pubmed_570_10035
|
OBJECTIVE
The purpose of this study was to evaluate the ultrasonographic features of benign adenomyoepithelioma of the breast.
MATERIALS AND METHODS
Between 2005 and 2009, five patients had histologically confirmed adenomyoepithelioma of the breast. We retrospectively evaluated the ultrasonographic findings of the tumors in correlation with the pathology, and reviewed medical records.
RESULTS
The clinical manifestations included a palpable mass in three patients, while mammographic screening helped detect abnormalities in two patients. Ultrasonograms showed masses with an oval (n = 3) or irregular (n = 2) shape, with uncircumscribed (n = 4) or relatively well-circumscribed (n = 1) margins, as well as with a hypoechoic (n = 3) or a complex echoic (n = 2) internal echo texture. Three patients had focal ductectasia adjacent to the mass. The ultrasonographic assessments were classified as Breast Imaging Reporting and Data System (BI-RADS) category 4A, with low suspicion of malignancy in two cases, and as category 4B, with intermediate suspicion of malignancy in three cases. The pathology revealed benign adenomyoepithelioma in all patients.
CONCLUSION
Benign adenomyoepitheliomas appear as solid or complex echoic masses with suspicious malignant ultrasonographic features, which may be associated with adjacent ductectasia. Although adenomyoepithelioma is a rare breast tumor, awareness of its sonographic features will be helpful for the differential diagnosis from other tumors.
|
10.3348/kjr.2010.11.5.522
|
pubmed_382_8478
|
Sympathetic activation has been considered as a link between insulin resistance, hyperinsulinemia, and hypertension. However, little is known about the association between insulin sensitivity and autonomic regulation or about the effect of acute hyperinsulinemia on cardiac sympathovagal balance. The aim of this study was to investigate heart rate variability (HRV) during the euglycemic-hyperinsulinemic clamp in nondiabetic offspring of patients with type 2 diabetes. We studied 35 nondiabetic offspring of patients with type 2 diabetes and 19 control subjects. Probands were chosen from a 10-year follow-up study of patients with well-characterized type 2 diabetes according to their fasting C-peptide level (selected from both ends of the distribution) and from control subjects to form three groups: 1) a group including subjects who were offspring of type 2 diabetic patients with low C-peptide levels (deficient insulin secretion group [IS group], n = 17), 2) a group including subjects who were offspring of type 2 diabetic patients with high C-peptide levels (insulin-resistant group [IR group], n = 18), and 3) a control group without a history of type 2 diabetes in first-degree relatives (n = 19). HRV was assessed at baseline and at the steady state during the euglycemic-hyperinsulinemic clamp. Rates of whole-body glucose uptake (M value) were lower in the IR group than in the IS group and the control group (41+/-3 vs. 54+/-2 vs. 60+/-4 micromol x kg(-1) x min(-1), P < 0.01 and P < 0.01, respectively). In all groups, heart rate increased significantly during hyperinsulinemia. In the IR group, insulin infusion increased total power of HRV [from 7.70+/-0.15 to 8.05+/-0.15 ln(ms2), P < 0.01] and the low frequency-to-high frequency ratio (from 0.62+/-0.14 to 1.14+/-0.18, P < 0.01) and decreased power of the high frequency spectral component (from 5.73+/-0.17 to 5.43+/-0.16 ln(ms2), P < 0.05), whereas in other groups, changes in HRV were not significant. We conclude that the HRV response to acute hyperinsulinemia in the offspring of type 2 diabetic probands was likely to be modulated by the type 2 diabetic phenotype of the parent. In insulin-resistant subjects, autonomic dysfunction may be an earlier defect than hitherto acknowledged.
|
10.2337/diabetes.48.6.1295
|
pubmed_130_4554
|
BACKGROUND
As part of infection control measures during the COVID-19 pandemic, labour companionship was suspended intermittently at public hospitals across Hong Kong.
AIMS
The aim was to assess the impact of restricting labour companionship on intrapartum care and maternal and neonatal outcomes.
MATERIALS AND METHODS
This is a retrospective cohort study comparing patients admitted for vaginal delivery with and without a labour companion. Deliveries during 1 February to 20 May and 17 July to 11 September 2020 ('alone group') were compared to deliveries during the same periods one year earlier when companionship was unrestricted ('accompanied group'). Outcomes were controlled for age, parity, body mass index, birth weight, education level and induction of labour.
RESULTS
There were 651 and 491 deliveries in the accompanied and alone groups, respectively. Overall, physiological maternal and neonatal outcomes were not significantly different. Neonates in the alone group were more likely to have skin-to-skin contact delayed beyond 60 min after delivery (odds ratio 1.48, 95% confidence interval 1.45-1.51). None of these infants were exclusively breastfed at the time of discharge.
CONCLUSIONS
The presence of a labour companion may encourage earlier initiation of skin-to-skin contact, which has been shown to improve bonding experience. However, families that have already been affected by previous restrictions can be provided some reassurance that physiological outcomes do not appear to be significantly different. In addition, interventions that encourage companion involvement, such as breathing exercises and massages, were not hindered, as midwives took on a greater role in supporting the parturient.
|
10.1111/ajo.13490
|
pubmed_196_21287
|
Celiac disease (CD) is an autoimmune enteropathy that primarily affects the small intestine and is characterized by atrophy of intestinal villi. The manifestations of the disease improve following a gluten-free diet (GFD). CD is associated with various extra-intestinal diseases. Several skin manifestations are described in CD patients. The present paper reviews all CD-associated skin diseases reported in the literature and tries to analyze the pathogenic mechanisms possibly involved in these associations. Different hypotheses have been proposed to explain the possible mechanisms involved in every association between CD and cutaneous manifestations. An abnormal small intestinal permeability seems to be implicated in various dermatological manifestations. However, most of the associations between CD and cutaneous diseases is based on case reports and case series and a few controlled studies. To better assess the real involvement of the cutaneous district in CD patients, large multicentric controlled clinical trials are required.
|
10.3390/medicina55090578
|
pubmed_99_8668
|
The authors have studied 43 patients operated on for medullary thyroïd carcinoma. Plasma calcitonin was measured regularly in all patients, while carcinoembryonic antigen assay was performed in only 30 patients. Calcitonin assay was found to be useful for preoperative diagnosis of medullary carcinoma, and the level of plasma calcitonin appeared to be roughly correlated with tumor extension. After surgery, simultaneous assay of calcitonin and carcinoembryonic antigen was performed, in order to obtain more accurate information concerning the evolution and prognosis of the disease. In most cases in which no metastatic lymph nodes had been discovered at operation, the level of the two markers rapidly fell to undetectable values. It was observed that in patients with lymph node involvement, cervico-mediastinal radiation treatment did not change the slow and progressive evolution of the disease. However, a rapid increase in titre of carcinoembryonic antigen occurred simultaneously with the discovery of metastases, even when calcitonin levels did not dramatically change.
|
pubmed_99_8668
|
pubmed_192_6999
|
Silicon (Si) attracts extensive attention as the advanced anode material for lithium (Li)-ion batteries (LIBs) because of its ultrahigh Li storage capacity and suitable voltage plateau. Hollow porous structure and dopant-induced lattice expansion can enhance the cycling stability and transporting kinetics of Li ions. However, it is still difficult to synthesize the Si anode possessing these structures simultaneously by a facile method. Herein, the lightly boron (B)-doped spherical hollow-porous Si (B-HPSi) anode material for LIBs is synthesized by a facile magnesiothermic reduction from B-doped silica. B-HPSi exhibits local lattice expansion located on boundaries of refined subgrains. B atoms in Si contribute to the increase of the conductivity and the expansion of lattices. On the basis of the first-principles calculations, the B dopants induce the conductivity increase and local lattice expansion. As a result, B-HPSi electrodes exhibit a high specific capacity of ∼1500 mAh g-1 at 0.84 A g-1 and maintains 93% after 150 cycles. The reversible capacities of ∼1250, ∼1000, and ∼800 mAh g-1 can be delivered at 2.1, 4.2, and 8.4 A g-1, respectively.
|
10.1021/acs.inorgchem.9b00158
|
pubmed_158_10619
|
A colloidal dispersion of calcium thiophosphate in hydrocarbon medium was synthesized by reacting calcium oxide with tetraphosphorus decasulfide and water in the presence of a surfactant under specific conditions. The resulting product can be defined as a distribution of inorganic cores surrounded by a surfactant layer in a reverse-micelle-type association. The chemical composition was determined by 31P NMR, dialysis, and thermogravimetric analysis. The core particles were found to be a mixture of calcium thiophosphates, consisting mainly of mono- and dithiophosphates, with a small amount of phosphate. Shape, size distribution, and average core radius were investigated using transmission electron microscopy and small angle X-ray scattering. According to these techniques, the colloidal species can be defined as polydisperse spherical micelles with the radius of the mineral cores ranging from 10 to 80 A.
|
10.1006/jcis.1996.4636
|
pubmed_845_12448
|
On March 11, 2020, the World Health Organization declared its assessment of coronavirus disease 2019 (COVID-19) as a global pandemic. However, specific anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) drugs are still under development, and patients are managed by multiple complementary treatments. We performed a retrospective analysis to compare and evaluate the effect of low molecular weight heparin (LMWH) treatment on disease progression. For this purpose, the clinical records and laboratory indicators were extracted from electronic medical records of 42 patients with COVID-19 (21 of whom were treated with LMWH, and 21 without LMWH) hospitalized (Union Hospital of Huazhong University of Science and Technology) from February 1 to March 15, 2020. Changes in the percentage of lymphocytes before and after LMWH treatment were significantly different from those in the control group (P = 0.011). Likewise, changes in the levels of D-dimer and fibrinogen degradation products in the LMWH group before and after treatment were significantly different from those in the control group (P = 0.035). Remarkably, IL-6 levels were significantly reduced after LMWH treatment (P = 0.006), indicating that, besides other beneficial properties, LMWH may exert an anti-inflammatory effect and attenuate in part the "cytokine storm" induced by the virus. Our results support the use of LMWH as a potential therapeutic drug for the treatment of COVID-19, paving the way for a subsequent well-controlled clinical study.
|
10.1111/cts.12880
|
pubmed_549_4786
|
OBJECTIVES/HYPOTHESIS
The morphologic features of upper and lower lateral cartilage and septal cartilage of the cadaveric nose were analyzed to provide practical anatomical knowledge for Asian rhinoplasty.
STUDY DESIGN
Cadaveric dissection.
METHODS
A total of 21 Korean adult cadavers were dissected. External nasal morphology was observed, measured, photographed, and analyzed. Histologic features were observed with a light microscope in coronally-transected specimens stained with hematoxylin and eosin.
RESULTS
The lengths of the upper and lower lateral cartilage of Korean cadaveric noses were similar to those of white noses. The widths of the upper and lower lateral cartilage were substantially smaller in Korean cadaveric noses than in those of whites. Upper lateral cartilage include substantial transverse portions near the keystone area that should be preserved in component reduction rhinoplasty. The relationships between the upper lateral cartilage and the lower lateral cartilage were divided into four types. Type I, in which the upper lateral cartilage and lower lateral cartilage are interlocked to form a Z-shape, is the most common. The posterior portion of the septal cartilage, which is connected to the perpendicular plate of the ethmoid and vomer, is thickest.
CONCLUSIONS
Cartilaginous structures of Asian noses were substantially different from those of whites in terms of their shape, size, thickness, and relationship with other structures. The data from surgical anatomical observations of the cartilaginous framework of Korean cadaveric noses provided in this report will provide valuable information for performing rhinoplasty on Asian patients.
|
10.1002/lary.20895
|
pubmed_348_25046
|
BACKGROUND
In the United States, folic acid fortification of cereal- grain foods has significantly increased folate status. However, blood folate concentrations have decreased from their postfortification high as a result, in part, of decreasing food fortification concentrations and the popularity of low-carbohydrate weight-loss diets.
OBJECTIVES
The objectives of the study were to quantify changes in folate intake after folic acid fortification and to estimate the effect on neural tube defect (NTD) occurrence.
DESIGN
Expanding on an earlier model, we used data from 11 intervention studies to determine the relation between chronic folate intervention and changes in steady state serum folate concentrations. With serum folate data from the National Health and Nutrition Examination Survey (NHANES), we used reverse prediction to calculate postfortification changes in daily folate equivalents (DFEs). With the use of NHANES red blood cell folate data and a published equation that related NTD risk to maternal red cell folate concentrations, we calculated NTD risk.
RESULTS
Folate intake decreased by approximately 130 microg DFE/d from its postfortification high, primarily as a result of changes seen in women with the highest folate status. This decrease in folate intake was predicted to increase the incidence of NTD by 4-7%, relative to a predicted 43% postfortification decrease. In addition, the number of women consuming >1 mg bioavailable folate/d decreased.
CONCLUSIONS
Folate consumption by women of childbearing age in the United States has decreased. However, the decrease in those women with the lowest folate status was disproportionately small. Consequently, the effect on NTD risk should be less than would be seen if a uniform decrease in folate concentrations had occurred. These results reinforce the need to maintain monitoring of the way fortification is implemented.
|
10.1093/ajcn/86.5.1773
|
pubmed_490_25206
|
The excretion route and dynamics of the glutathione (GSH) conjugate of microcystin-RR (MCRR), MCRR-GSH, were quantitatively studied in Sprague Dawley rat exposed with MCRR-GSH via liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). In the MCRR-GSH-treated rat, the average MCRR-Cysteine (MCRR-Cys)/MCRR-GSH ratio reached as high as 105.3, which indicated that the intermediate conjugate MCRR-GSH was rapidly converted to the product compound MCRR-Cys. Besides, MCRR was consistently detected in MCRR-GSH-treated rat, which suggested that MCRR can be dissociated from the MCRR-GSH conjugate and the reversibility of the MC-GSH conjugate. Results of total MC contents analysis in excrement showed that the total MC contents in urine were significantly higher than those in feces. The ratio of the total MC content in urine to feces was as high as 129.3, which demonstrates that the urine is the main route of excretion after MCRR-GSH-treatment. In urine, the MCRR-Cys concentration was 27.8-fold, 19.4-fold higher than MCRR-GSH and MCRR, respectively. Our results, for the first time, quantitatively found that MCRR-GSH was rapidly converted to MCRR-Cys after exposed to rat, and was excreted mainly through urine in the form of the MCRR-Cys conjugate. This study suggests that the GSH detoxification pathway of MCs could help to explain the greater sensitivity of mammals to MCs.
|
10.1016/j.chemosphere.2017.09.083
|
pubmed_559_1639
|
The products formed in reactions of the square-planar platinum(II) anticancer complexes, [Pt(en)Cl(2)] and [Pt(R,R-dach)Cl(2)] where en=ethylenediamine and dach=diaminocyclohexane, with trypanothione, a glutathione analogue found in some parasites, and octreotide, a synthetic analogue of the hormone somatostatin, have been investigated. Mononuclear and binuclear platinum adducts were formed in reactions of the cyclic disulfides in their oxidised and reduced forms, and were analysed by UV-visible spectroscopy and liquid chromatography-mass spectrometry (LC-MS). NMR and molecular modelling studies were carried out on the mononuclear adducts.
|
10.1016/j.jinorgbio.2006.08.011
|
pubmed_768_9404
|
Copper-catalyzed cyclization of an oxime ester toward divergent heterocycle synthesis is reported. Oxime ester serves as an enamine precursor to cyclize with malononitrile and aldehydes for access to 2-aminonicotinonitriles in a one-pot reaction, while cyclizing with N-sulfonylimines leads to synthesis of pyrazolines.
|
10.1021/ol500094w
|
pubmed_771_3742
|
The characteristically flat structure of Arabidopsis thaliana vegetative leaves requires coordinating the growth of the epidermal, palisade mesophyll, spongy mesophyll and vascular tissues. Mutations disrupting such coordination or the specific growth properties of any of these tissues can cause hyponasty, epinasty, waviness or other deviations from flatness. Here, we show that the incurvata6 (icu6) semi-dominant allele of the AUXIN RESISTANT3 (AXR3) gene causes leaf hyponasty. Cotyledons and leaves of icu6/AXR3 plants exhibited reduced size of adaxial pavement cells, and abnormal expansion of palisade mesophyll cells. Enhanced auxin responses in the adaxial domain of icu6/AXR3 developing cotyledons and leaves correlated with increased cell divisions in the adaxial epidermis. Leaf incurvature in icu6/AXR3 leaves was alleviated by loss-of-function alleles of the ASYMMETRIC LEAVES1 (AS1) and AS2 genes, which restrict the expression of class I KNOX genes to the shoot apical meristem and regulate cell proliferation in leaf primordia. Taken together, our results suggest that an interaction between auxin responses and the AS1-AS2 pathway coordinates tissue growth during Arabidopsis thaliana leaf expansion.
|
10.1093/pcp/pcq123
|
pubmed_675_12484
|
We develop a new generalization of Koopman operator theory that incorporates the e ects of inputs and control. Koopman spectral analysis is a theoretical tool for the analysis of nonlinear dynamical systems. Moreover, Koopman is intimately connected to dynamic mode decomposition (DMD), a method that discovers coherent, spatio-temporal modes from data, connects local-linear analysis to nonlinear operator theory, and importantly creates an equation-free architecture for the study of complex systems. For actuated systems, standard Koopman analysis and DMD are incapable of producing input-output models; moreover, the dynamics and the modes will be corrupted by external forcing. Our new theoretical developments extend Koopman operator theory to allow for systems with nonlinear input-output characteristics. We show how this generalization is rigorously connected to a recent development called dynamic mode decomposition with control. We demonstrate this new theory on nonlinear dynamical systems, including a standard susceptible-infectious-recovered model with relevance to the analysis of infectious disease data with mass vaccination (actuation).
|
10.1137/16M1062296
|
pubmed_177_1101
|
A series of novel CoFe-based catalysts are successfully fabricated by hydrogen reduction of CoFeAl layered-double-hydroxide (LDH) nanosheets at 300-700 °C. The chemical composition and morphology of the reaction products (denoted herein as CoFe-x) are highly dependent on the reduction temperature (x). CO2 hydrogenation experiments are conducted on the CoFe-x catalysts under UV-vis excitation. With increasing LDH-nanosheet reduction temperature, the CoFe-x catalysts show a progressive selectivity shift from CO to CH4 , and eventually to high-value hydrocarbons (C2+ ). CoFe-650 shows remarkable selectivity toward hydrocarbons (60% CH4 , 35% C2+ ). X-ray absorption fine structure, high-resolution transmission electron microscopy, Mössbauer spectroscopy, and density functional theory calculations demonstrate that alumina-supported CoFe-alloy nanoparticles are responsible for the high selectivity of CoFe-650 for C2+ hydrocarbons, also allowing exploitation of photothermal effects. This study demonstrates a vibrant new catalyst platform for harnessing clean, abundant solar-energy to produce valuable chemicals and fuels from CO2 .
|
10.1002/adma.201704663
|
pubmed_281_16063
|
The goal of this study was to determine the metabolism of multiparous female yaks during the late perinatal period and identify its effects on reproductive recovery in order to explain the low reproduction rate of yaks. Eight multiparous female yaks were randomly selected as the sample, and serum was collected from the yaks every 7 days from the day of delivery until 28 days after the delivery (five time points). The presence of serum metabolic profiles and reproductive hormones was identified using ELISA. The key metabolites were identified using liquid chromatography-mass spectrometry, and a dynamic metabolic network representation was created using bioinformatics analysis. A total of 117 different metabolites were identified by calculating the fold change of the metabolite expression at each time point. The dynamic metabolic network was created to represent the activities of the key metabolites, metabolic indexes and reproductive hormones. The initial efficiency of the glucose metabolism in the late perinatal period was found to be low, but it increased during the final period. The initial efficiencies of the lipid and amino acid metabolisms were high but decreased during the final period. We inferred that there was a postpartum negative energy balance in female yaks and that the synthesis and secretion of estrogen were blocked due to an excessive fatty acid mobilization. As a result, the reproductive hormone synthesis and secretion were maintained at a low level in the late perinatal period, and this was the main reason for the delayed recovery of the reproductive function postpartum. However, the specific mechanism needs to be further verified.
|
10.3390/metabo12111113
|
pubmed_803_2665
|
Pyruvate dehydrogenase activity was present and comparable (giving a colour change of 202-673 od units/min/g protein in our assay system) in two clinical strains of Bacteroides fragilis exhibiting reduced sensitivity to metronidazole (MIC 2-8 mg/l at 48 h) in a resistant strain (Ingham's) of Bact. fragilis (MIC 64/mg/l) and in two sensitive strains of Bact. fragilis (MIC 0.5 mg/l). Pyruvate dehydrogenase activity was not detected in a capnocytophaga strain (sensitive to 50 micrograms disc of metronidazole), in Escherichia coli or in 'Bact. fragilis' strain (Britz) AM24s (MIC greater than 64 mg/l). Further testing of AM24s strain indicated that it was not Bact. fragilis but a facultatively anaerobic Gram-negative rod. Pyruvate dehydrogenase activity therefore, is similar in sensitive and resistant strains of Bact. fragilis and is unlikely to be related to the mechanism of resistance to metronidazole.
|
10.1093/jac/11.5.393
|
pubmed_561_8776
|
The case-control study design, a common staple of epidemiology, is increasingly used to test for genetic association. The simplicity of the design accounts for both its appeal and its limitations. Too often, however, apparent controversy arises for lack of appreciation of basic tenets underlying statistical testing. Power and replication are two concepts most commonly ignored in evaluating such studies. We review the basic principles of statistical testing, recall simple means to calculate power, and provide numerical examples pertaining to the association between angiotensinogen and essential hypertension.
|
10.1016/s0895-7061(01)02285-3
|
pubmed_649_9584
|
Eight rats were trained to use their left paw to rapidly press the right lever of an operant chamber once and the left lever twice to obtain a food reward. Between-levers interresponse times and same lever interresponse times were measured daily for several weeks before and after bilateral removal of frontal motor/sensory cortex. This surgery resulted in a permanent deficit in most rats' ability to rapidly alternate between levers, but resulted in only a temporary deficit in their ability to rapidly press the same lever. Sham surgery and removal of hindlimb motor cortex had little immediate effect on interresponse times. The data demonstrate that sequential motor behavior tested in the between-levers tasks is chronically affected by cortical lesions, but the speed of the same repetitive movement tested in the same lever task is not. Measuring the time to rapidly alternate between two different levers, therefore, provides a quantitative method for measuring acute and chronic forelimb motor deficits due to motor cortex injury in rats which could be applied to any mammal.
|
10.1016/0166-4328(86)90082-3
|
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