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pubmed_572_1069
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The principal initial biological targets of free radicals formed under conditions of oxidative stress are the proteins. The most common products of the interaction are carbon-centered alkyl radicals which react rapidly with oxygen to form peroxyl radicals and hydroperoxides. All these species are reactive, capable of propagating the free radical damage to enzymes, nucleic acids, lipids, and endogenous antioxidants, leading finally to the pathologies associated with oxidative stress. The best chance of preventing this chain of damage is in early repair of the protein radicals by antioxidants. Estimate of the effectiveness of the physiologically significant antioxidants requires knowledge of the antioxidant tissue concentrations and rate constants of their reaction with protein radicals. Previous studies by pulse radiolysis have shown that only ascorbate can repair the Trp and Tyr protein radicals before they form peroxyl radicals under physiological concentrations of oxygen. We have now extended this work to other protein C-centered radicals generated by hydroxyl radicals because these and many other free radicals formed under oxidative stress can produce secondary radicals on virtually any amino acid residue. Pulse radiolysis identified two classes of rate constants for reactions of protein radicals with ascorbate, a faster one in the range (9-60) × 107 M-1 s-1 and a slow one with a range of (0.5-2) × 107 M-1 s-1. These results show that ascorbate can prevent further reactions of protein radicals only in the few human tissues where its concentration exceeds about 2.5 mM.
|
10.1021/acs.chemrestox.7b00160
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pubmed_405_9972
|
The authors present the case of a boy who was successfully managed through the spontaneous thrombosis of a cavernous internal carotid artery (ICA) aneurysm, the subsequent occlusion of the ICA, its recanalization, and ultimate endovascular sacrifice, using only two angiograms because of the diagnostic capability of CT angiography. Spontaneous recanalization of the ICA following occlusion in the setting of a giant aneurysm has not been previously reported.
|
10.3171/2014.10.PEDS13588
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pubmed_428_13108
|
The chemistry of hypervalent iodine(III) compounds has gained great interest over the past 30 years. Hypervalent iodine(III) compounds show valuable ionic reactivity due to their high electrophilicity but also express radical reactivity as single electron oxidants for carbon and heteroatom radical generation. Looking at ionic chemistry, these iodine(III) reagents can act as electrophiles to efficiently construct C-CF3, X-CF3 (X = heteroatom), C-Rf (Rf = perfluoroalkyl), X-Rf, C-N3, C-CN, S-CN, and C-X bonds. In some cases, a Lewis or a Bronsted acid is necessary to increase their electrophilicity. In these transformations, the iodine(III) compounds react as formal "CF3+", "Rf+", "N3+", "Ar+", "CN+", and "X+" equivalents. On the other hand, one electron reduction of the I(III) reagents opens the door to the radical world, which is the topic of this Account that focuses on radical reactivity of hypervalent iodine(III) compounds such as the Togni reagent, Zhdankin reagent, diaryliodonium salts, aryliodonium ylides, aryl(cyano)iodonium triflates, and aryl(perfluoroalkyl)iodonium triflates. Radical generation starting with I(III) reagents can also occur via thermal or light mediated homolysis of the weak hypervalent bond in such reagents. This reactivity can be used for alkane C-H functionalization. We will address important pioneering work in the area but will mainly focus on studies that have been conducted by our group over the last 5 years. We entered the field by investigating transition metal free single electron reduction of Togni type reagents using the readily available sodium 2,2,6,6-tetramethylpiperidine-1-oxyl salt (TEMPONa) as an organic one electron reductant for clean generation of the trifluoromethyl radical and perfluoroalkyl radicals. That valuable approach was later successfully also applied to the generation of azidyl and aryl radicals starting with the corresponding benziodoxole (Zhdankin reagent) and iodonium salts. In the presence of alkenes as radical acceptors, vicinal trifluoromethyl-, azido-, and arylaminoxylation products result via a sequence comprising radical addition to the alkene and subsequent TEMPO trapping. Electron-rich arenes also react with I(III) reagents via single electron transfer (SET) to give arene radical cations, which can then engage in arylation reactions. We also recognized that the isonitrile functionality in aryl isonitriles is a highly efficient perfluoroalkyl radical acceptor, and reaction of Rf-benziodoxoles (Togni type reagents) in the presence of a radical initiator provides various perfluoroalkylated N-heterocycles (indoles, phenanthridines, quinolines, etc.). We further found that aryliodonium ylides, previously used as carbene precursors in metal-mediated cyclopropanation reactions, react via SET reduction with TEMPONa to the corresponding aryl radicals. As a drawback of all these transformations, we realized that only one ligand of the iodine(III) reagent gets transferred to the substrate. To further increase atom-economy of such conversions, we identified cyano or perfluoroalkyl iodonium triflate salts as valuable reagents for stereoselective vicinal alkyne difunctionalization, where two ligands from the I(III) reagent are sequentially transferred to an alkyne acceptor. Finally, we will discuss alkynyl-benziodoxoles as radical acceptors for alkynylation reactions. Similar reactivity was found for the Zhdankin reagent that has been successfully applied to azidation of C-radicals, and also cyanation is possible with a cyano I(III) reagent. To summarize, this Account focuses on the design, development, mechanistic understanding, and synthetic application of hypervalent iodine(III) reagents in radical chemistry.
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10.1021/acs.accounts.7b00148
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pubmed_701_7176
|
BACKGROUND AND PURPOSE
Nitric oxide is an important regulator of vascular tone and may also be implicated in the modulation of vascular growth and structure. This study presents the effects of chronic nitric oxide inhibition, with or without antihypertensive treatment, on the structure and function of the basilar artery in rats.
METHODS
Rats were treated for 6 weeks with N omega-nitro-L-arginine methyl ester (50 mg/kg per day) alone or in combination with verapamil (100 mg/kg per day) or with trandolapril (1 mg/kg per day). Untreated rats served as controls. The structure and reactivity of perfused and pressurized basilar arteries were analyzed in vitro using a video dimension analyzer.
RESULTS
Systolic arterial pressure increased only in the nitro-arginine-treated group, as did the media-to-lumen ratio of the basilar artery. This structural alteration, which was prevented by verapamil and trandolapril, was mainly due to remodeling and not to growth. Chronic inhibition of the L-arginine pathway increased the response of the basilar artery to serotonin, while the opposite was found for endothelin. Verapamil and trandolapril prevented these functional alterations that seemed related to the changes in the vascular structure.
CONCLUSIONS
The remodeling and functional alterations of the basilar artery seem to depend mainly on the elevation of arterial pressure with little contribution of the L-arginine pathway. Furthermore, nitric oxide does not seem to be implicated in the modulation of normal cerebral vascular growth in vivo. However, hypertension-induced changes in vascular reactivity and structure could alter cerebral blood flow and eventually contribute to the development of stroke in this model of hypertension.
|
10.1161/01.str.26.10.1922
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pubmed_57_6394
|
[Purpose] This study implement ankle joint dorsiflexion training for ankle muscle the weakness that impairs stroke patients' gait performance, to examine the effect of the training on stroke patients' plantar pressure and gait ability. [Subjects and Methods] In this study, 36 stroke patients diagnosed with stroke due to cerebral infarction or cerebral hemorrhage performed the training. Static muscle stretching was performed four times a week for 20 minutes at a time for 6 weeks by the training group. Ankle dorsiflexor training was performed four times a week, two sets per time in the case of females and three sets per time in the case of males for 6 weeks, by another group. Center of pressure sway amplitude was measured using the F-scan system during gait. All subjects were assessed with the same measurements at a pre-study examination and reassessed at eight weeks. Data were analyzed statistically using the paired t-test and one-way ANOVA. [Results] Among the between ankle dorsiflexor training group, static muscle stretching group, and control group, the difference before and after the training were proven to be statistically significant. [Conclusion] Compared to other training groups, the ankle muscle strength training group showed statistically significant increases of forward thrust at stroke patients' toe-off which positively affected stroke patients' ability to perform gait.
|
10.1589/jpts.25.1613
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pubmed_500_8944
|
A 38-year-old Japanese man presented with a blue macule on the back. A spinal meningeal tumor at the C3-C5 levels was detected radiologically and excised. The histological findings in the biopsy specimen from the blue macule were consistent with an extensive Mongolian spot. The histological diagnosis of the meningeal tumor was benign melanocytoma. The case was thought to be a new variety of neurocutaneous melanosis.
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pubmed_500_8944
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pubmed_307_15291
|
The effect of two different CO(2) concentrations (400 and 800 μmol mol(-1)) on the photosynthesis rate, primary and secondary metabolite syntheses and the antioxidant activities of the leaves, stems and rhizomes of two Zingiber officinale varieties (Halia Bentong and Halia Bara) were assessed in an effort to compare and validate the medicinal potential of the subterranean part of the young ginger. High photosynthesis rate (10.05 μmol CO(2) m(-2)s(-1) in Halia Bara) and plant biomass (83.4 g in Halia Bentong) were observed at 800 μmol mol(-1) CO(2). Stomatal conductance decreased and water use efficiency increased with elevated CO(2) concentration. Total flavonoids (TF), total phenolics (TP), total soluble carbohydrates (TSC), starch and plant biomass increased significantly (P ≤ 0.05) in all parts of the ginger varieties under elevated CO(2) (800 μmol mol(-1)). The order of the TF and TP increment in the parts of the plant was rhizomes > stems > leaves. More specifically, Halia Bara had a greater increase of TF (2.05 mg/g dry weight) and TP (14.31 mg/g dry weight) compared to Halia Bentong (TF: 1.42 mg/g dry weight; TP: 9.11 mg/g dry weight) in average over the whole plant. Furthermore, plants with the highest rate of photosynthesis had the highest TSC and phenolics content. Significant differences between treatments and species were observed for TF and TP production. Correlation coefficient showed that TSC and TP content are positively correlated in both varieties. The antioxidant activity, as determined by the ferric reducing/antioxidant potential (FRAP) activity, increased in young ginger grown under elevated CO(2). The FRAP values for the leaves, rhizomes and stems extracts of both varieties grown under two different CO(2) concentrations (400 and 800 μmol mol(-1)) were significantly lower than those of vitamin C (3107.28 μmol Fe (II)/g) and α-tocopherol (953 μmol Fe (II)/g), but higher than that of BHT (74.31 μmol Fe (II)/g). These results indicate that the plant biomass, primary and secondary metabolite synthesis, and following that, antioxidant activities of Malaysian young ginger varieties can be enhanced through controlled environment (CE) and CO(2) enrichment.
|
10.3390/ijms12021101
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pubmed_689_8704
|
A two-year-old ball python with a submandibular mass was evaluated. Fine needle aspiration resulted in debris containing purulent materials and bacterial cells on cytology. Radiography demonstrated multi-focal radiopaque lesions in the mass, which were suspected to be mineralization; there was an absence of mandibular invasion or lung involvement. Gross examination of the surgically excised mass revealed a multi-nodular, well-circumscribed lesion with purulent material. The postoperative recovery was uneventful. The histopathological examination followed by immunohistochemistry analysis gave a diagnosis of leiomyosarcoma. As tumors containing purulent materials can be confused with an abscess, diagnostic confirmation with various diagnostical tools should be considered.
|
10.3390/vetsci8100224
|
pubmed_16_13264
|
NDP reductase activity can be inhibited either by treatment with hydroxyurea or by incubation of an nrdA (ts) mutant strain at the non-permissive temperature. Both methods inhibit replication, but experiments on these two types of inhibition yielded very different results. The chemical treatment immediately inhibited DNA synthesis but did not affect the cell and nucleoid appearance, while the incubation of an nrdA101 mutant strain at the non-permissive temperature inhibited DNA synthesis after more than 50 min, and resulted in aberrant chromosome segregation, long filaments, and a high frequency of anucleate cells. These phenotypes are not induced by SOS. In view of these results, we suggest there is an indirect relationship between NDP reductase and the chromosome segregation machinery through the maintenance of the proposed replication hyperstructure.
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10.2478/s11658-006-0060-0
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pubmed_417_4277
|
Islet cell antibodies (ICAs) in Chinese (23 IDDM, 13 NIDDM and 6 non-diabetic) were characterized for immunoglobulin isotypes and light chain specificity. All ICAs were IgG-type and none were IgM- or IgA-type (median titre: 20 JDF units; range 10-160). Light chain specificity showed that 25/36 (69.4%) of the diabetic patients had lambda and kappa chains. Half of the non-diabetic subjects had both lambda and kappa chains. The rest had only lambda chains. Isotyping for ICA-IgG subclass combination with IUIS/WHO reference monoclonal antibodies in the diabetic patients gave the following: IgG1 alone-9 (25%), IgG1+2+3-8 (22.2%), IgG1+2-11 (30.6%), IgG1+3-6 (16.7%), IgG2+3-2 (5.6%). No ICA-IgG4 was detected. The frequency of the subclasses would be: IgG1-94.4%, IgG2-58.3% and IgG3-44.4%. The distribution of ICA-IgG subclasses was not affected by diabetes type (IDDM or NIDDM) or duration of disease. Of the 6 non-diabetic subjects only one had a single ICA-IgG subclass (IgG1). Serum levels of IgG subclasses in a subgroup of the patients (n = 16) were not significantly different from normal individuals. Biochemical modification of pancreatic tissue prior to ICA testing showed that acetylneuraminic acid residues, lipid and protein components were associated with binding of ICAs. The co-existence of other autoantibodies was also tested in these 42 ICA-positive sera. Twelve individuals (1 non-diabetic) had thyroid autoantibodies. Antibodies to thyrotrophin receptor, gastric parietal cell and rheumatoid factor were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.3109/08916939309115753
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pubmed_975_4323
|
The active site of rubredoxins consists of a single iron tetrahedrally coordinated to four cysteinate sulfurs. One of the iron ligands, cysteine 42, has been mutated into serine in Clostridium pasteurianum rubredoxin. This mutation resulted in a shift to higher energy of the 320-800 nm region of the UV-visible absorption spectrum. Resonance Raman spectra showed that the nu 1 breathing mode of the iron chromophore was upshifted as a result of the C42S mutation. The spectral pattern, however, was not largely disturbed by the mutation. The EPR spectra of both the wild type and the C42S mutated protein displayed the characteristic features, at g = 4.3 and g = 9.5, of the "3/2" and "1/2" Kramers' doublets, respectively, of a S = 5/2 multiplet. These combined data afford strong evidence that in the C42S mutated rubredoxin serine has replaced cysteine 42 as a ligand of the iron, while maintaining the tetrahedral coordination of the metal. The most spectacular effect of the C42S mutation was a ca. 200 mV downshift of the redox potential of rubredoxin.
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10.1006/bbrc.1995.2043
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pubmed_523_511
|
In all cases of primary endocardial fibroelastosis investigated diffuse degenerative changes in the ganglion cells were detected. Thickened endocardium was formed by the proliferation of mesenchymal cells located under the endothelial endocardium and of the mesenchyme surrounding the necrobiotic muscle cells. In some cases ;axial' vacuolar degeneration, necrobiosis, and necrosis of muscle cells, interstitial oedema, and dilatation of capillaries and lymphatic spaces were found in the whole myocardium. In all cases these changes were in the subendocardial layer.In the cases discussed morphological changes in the endocardium were seen to be secondary to lesions in myocardial and possibly in neural structures.
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10.1136/jcp.24.3.263
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pubmed_646_7567
|
Using estimates for the anthelmintic efficacy of a single dose of ivermectin in the treatment of lymphatic filariasis patients, Anton Plaisier, Wilma Stolk, Gerrit van Oortmarssen and Dik Habbema here present and discuss model predictions of the impact of a five-year programme of annual community treatment on the intensity of infection. They show that the effectiveness of such programmes in terms of reductions in the microfilarial density depends critically on the treatment coverage and the pattern of attendance at repeated mass administrations. Improving these factors will possibly be more important than improving the efficacy of ivermectin by increasing its dosage or by adding other drugs.
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10.1016/s0169-4758(00)01691-4
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pubmed_965_21677
|
To estimate the pose of a C-Arm during interventions therapy we have developed a small sized X-Ray Target including a special set of beads with known locations in 3D space. Since the patient needs to remain in the X-Ray path for all feasible poses of the C-Arm during the intervention, we cannot construct a single marker which is entirely visible in all images. Therefore finding 2D-3D point correspondences is a non-trivial task. The marker pattern has to be chosen in a way such that its projection onto the image plane is unique in a minimal-sized window for all relevant poses of the C-Arm. We use a two dimensional adaption of a linear feedback shift register (LFSR) to generate a two-dimensional pattern with unique sub-patterns in a certain window range. Thereby uniqueness is not achieved by placing unique 2D sub patterns side by side but by the code property itself. The code is designed in a way that any sub window of a minimal size guarantees uniqueness and that even occlusions from medical instruments can be handled. Experiments showed that we were able to estimate the C-Arm's pose from a single image within one second with a precision below one millimeter and one degree.
|
10.1007/978-3-540-85990-1_78
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pubmed_938_3049
|
Tolerance to the hemodynamic and antianginal effects of the organic nitrates develops rapidly during therapy. This has been documented with a variety of nitrate preparations and with different routes of administration. Dosing strategies designed to provide therapeutic plasma nitrate concentrations throughout the 24 hours of the day are regularly associated with the development of tolerance. Recent information indicates that dosing schedules providing a nitrate-free period will permit continued efficacy of the organic nitrates without tolerance development. This can be accomplished in several ways. With oral preparations of isosorbide dinitrate, medication can be given 3 times daily, omitting the evening dose. Buccal nitroglycerin is usually given 3 times daily after meals, and this has been shown not to be associated with tolerance. Likewise, preliminary studies suggest that removal of the nitroglycerin patches for a period of several hours each day will prevent the development of tolerance. Much needs to be learned about the nitrate-free period. With oral isosorbide dinitrate, it appears that 12 hours is required, but this could be substantially less with nitroglycerin preparations. It is also possible that several short periods with low nitrate levels each day would suffice. Thus, simply increasing the interval between dosing of oral preparations may provide an adequate, low, nitrate-free period.
|
10.1007/BF00133214
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pubmed_546_11904
|
BACKGROUND
We previously demonstrated that alginate microencapsulation can prolong fish (tilapia) islet xenograft survival in diabetic animals. However, at present, microencapsulation does not provide complete immune protection to discordant islet xenografts, and long-term graft survival requires supplemental low-dose systemic immunosuppression. In the present study, fish islets were co-encapsulated with Sertoli enriched testicular cell fractions to find out whether this would further prolong fish islet graft survival in diabetic mice.
METHODS
Sertoli enriched testicular cell fractions were enzymatically harvested from adult Balb/c or Wistar-Furth rats. They were cultured and co-encapsulated with fragmented tilapia islets in alginate microcapsules. Encapsulated islets alone or islets co-encapsulated with Sertoli cells were then intraperitoneally transplanted into streptozotocin-diabetic Balb/c mice, and graft survival times were compared. Encapsulated and co-encapsulated islet function was also confirmed in streptozotocin-diabetic athymic nude mice.
RESULTS
Co-encapsulation with Sertoli enriched testicular cell fractions further prolonged mean fish islet graft survival time from 21+/-6.7 days (encapsulated islet cells alone) to >46+/-6.3 days (co-encapsulated with syngeneic murine Sertoli cells), without additional systemic immunosuppression. Testicular cells harvested from xenogeneic Wistar-Furth rats produced similar protective results (>46+/-10.9 days).
CONCLUSIONS
Our results support the theory that Sertoli cells produce local immunosuppressive factors. These factors supplement the immune protective feature of alginate microcapsules in our model. Testicular cell fractions may be an important naturally occurring facilitator in the development of new microencapsulation systems for islet xenotransplantation.
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10.1097/00007890-199903270-00006
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pubmed_499_7765
|
Smart monitoring and assisted living systems for cognitive health assessment play a central role in assessment of individuals' health conditions. Autistic children suffer from some difficulties including social skills, repetitive behaviors, speech and nonverbal communication, and accommodating to the environment around them. Thus, dealing with autistic children is a serious public health problem as it is hard to determine what they feel with a lack of emotional cognitive ability. Currently, no medical treatments have been shown to cure autistic children, with most of the social assistive research to date focusing on Autism Spectrum Disorder (ASD) without suggesting a real treatment. In this paper, we focus on improving cognitive ability and daily living skills and maximizing the ability of the autistic child to function and participate positively in the community. Through utilizing intelligent systems based Artificial Intelligence (AI) and Internet of Things (IoT) technologies, we facilitate the process of adaptation to the world around the autistic children. To this end, we propose an AI-enabled IoT system embodied in a sensor for measuring the heart rate to predict the state of the child and then sending the state to the guardian with feeling and expected behavior of the child via a mobile application. Further, the system can provide a new virtual environment to help the child to be capable of improving eye contact with other people. This way is represented in pictures of these persons in 3D models that break this child's fear barrier. The system follows strategies that have focused on social communication skill development particularly at young ages to be more interactive with others.
|
10.1155/2022/2247675
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pubmed_95_6324
|
Female genital schistosomiasis, FGS, was investigated in a gynaecological study as part of an overall community based morbidity survey, including parasitological and ultrasonographical examination, of a Schistosoma haematobium endemic area in Madagascar. Women (103), of childbearing age (15-49 years), were included for a gynaecological examination and visible lesions of vagina and cervix were biopsied in order to determine the origin of the lesion. Furthermore all women were screened for the presence of schistosome ova using PAP smears from the vagina and the endo/exo cervix. In total 15 women showed schistosome ova in the vagina and/or cervix (median age 24 years and range 15-36 years). Of 36 women with cervical abnormalities, 12 eggs were detected by cervical biopsy (33%). In addition, two of the 12 presented vaginal induration, which contained eggs. Six women had eggs in their PAP smears of which three were egg negative by cervical biopsy. The prevalence of positive S. haematobium egg excretion in the urine among the 103 women was 69% and the geometric mean egg count of positive individuals was 51 eggs/10 ml of urine. Five of the 15 women with confirmed FGS had < or = 1 egg/10 ml of urine. Bladder lesions and congestive changes in the kidneys were demonstrated by ultrasonographic examination in 33 and 9% of the 103 women, respectively. None of the 15 women with confirmed FGS had renal congestion. Our study demonstrates that FGS is a common manifestation of the infection with S. haematobium, even in lightly infected individuals.
|
10.1016/s0001-706x(97)00673-6
|
pubmed_1033_17016
|
An X-ray scanning method to nondestructively detect flaws that are hidden from direct observation is demonstrated. The method employs a rolling-window template-matching procedure that identifies statistically significant deviations between a response matrix characteristic of an unflawed sample and a response matrix obtained from a test sample. The methodology is illustrated with simulated data and implemented to measure the thickness of missing material hidden within engineered samples. The technology has application in detecting flaws in systems such as aircraft.
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10.1016/j.apradiso.2004.04.009
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pubmed_527_5420
|
The current study examined the extent to which seventy-five 5- to 13-year-old children and their mothers agreed about whether children had been exposed to intimate partner violence (IPV) and the association between parent-child agreement and children's psychological adjustment. One type of disagreement (i.e., parents failed to report IPV exposure that children reported) was associated with children's perceptions of less positive family relationships. Parents of these children, however, reported fewer child adjustment problems than did parents who agreed with their children about children's IPV exposure. The findings suggest the importance of obtaining children's reports of their own exposure to IPV in addition to parental reports. Moreover, parent-child concordance with respect to children's IPV exposure may be an important variable to examine in understanding variations in children's adjustment.
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10.1891/0886-6708.25.2.185
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pubmed_302_22054
|
Pulmonary surfactant is a lipid-protein complex which has the essential physiological role of stabilizing the respiratory surface of lungs against collapse. To achieve this function, surfactant forms films at the air-liquid interface that reduce dramatically the surface tension of the thin aqueous layer lining the alveoli. Natural surfactant has optimised two important properties. Once secreted to the alveolar spaces, surfactant adsorbs rapidly to the interface. There, surfactant films reduce surface tension close to 0 mN/m when compressed during expiration. The design and production of efficient artificial surfactants for respiratory therapeutics is critically dependent on the knowledge of the molecular mechanisms governing efficient interfacial adsorption and optimal surface activity, in the context of respiratory cycling. The present review summarizes the data available today on the behaviour of the different molecular components of pulmonary surfactant at air-liquid interfaces. A working model is proposed of how surfactant films could modulate the respiratory dynamics.
|
10.1159/000056765
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pubmed_982_19332
|
The aim of the study was to observe the changes in haematological parameters and blood lipid profile through copper (Cu) deficiency. Eighty broiler chicks were used in the study. The chicks were separated into two equal groups (n = 40), feed treatment according to the groups started on day 7. The animals in the control group were fed with normal feed. Those in the Cu-deficient group were fed with feed that did not contain supplemental Cu. Blood samples were taken from all the animals on days 7, 21 and 49. Fibrinogen and prothrombin time were assayed in plasma; total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDL-cholesterol), triglyceride and ceruloplasmin were assayed in sera; and haematocrit and thrombocyte levels were assayed in the blood samples. Total cholesterol, triglyceride and LDL-cholesterol levels were significantly higher in the Cu-deficient group than in the control group. Serum ceruloplasmin levels were lower in the Cu-deficient group than in the control group. Prothrombin time was higher in the Cu-deficient group than in the control group. Haematocrit levels were lower in the Cu-deficient group than in the control group. It was concluded that Cu deficiency created hypertriglyceridaemia, hypercholesterolaemia, insufficient growth and anaemia in broilers.
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10.1111/j.1439-0442.2006.00835.x
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pubmed_325_9984
|
Mutations in Wnt-signaling coreceptor LRP6 have been linked to coronary artery disease (CAD) by unknown mechanisms. Here, we show that reduced LRP6 activity in LRP6(R611C) mice promotes loss of vascular smooth muscle cell (VSMC) differentiation, leading to aortic medial hyperplasia. Carotid injury augmented these effects and led to partial to total vascular obstruction. LRP6(R611C) mice on high-fat diet displayed dramatic obstructive CAD and exhibited an accelerated atherosclerotic burden on LDLR knockout background. Mechanistically, impaired LRP6 activity leads to enhanced non-canonical Wnt signaling, culminating in diminished TCF7L2 and increased Sp1-dependent activation of PDGF signaling. Wnt3a administration to LRP6(R611C) mice improved LRP6 activity, led to TCF7L2-dependent VSMC differentiation, and rescued post-carotid-injury neointima formation. These findings demonstrate the critical role of intact Wnt signaling in the vessel wall, establish a causal link between impaired LRP6/TCF7L2 activities and arterial disease, and identify Wnt signaling as a therapeutic target against CAD.
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10.1016/j.celrep.2015.09.028
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pubmed_471_17519
|
Biological invasions have the potential to alter ecosystem processes profoundly, but invaders are rarely found alone. Interactions between different invasive alien species, and their cumulative impact on ecosystem functioning, have led to hypotheses of invasion meltdown whereby effects become additive leading to further ecosystem stress. Invasive riparian plants (e.g., Rhododendron ponticum) deposit leaf litter in freshwaters, which may be unconsumed by indigenous species, potentially affecting habitat heterogeneity and flow of energy to the food web. However, invasive alien decapod crustaceans are effective consumers of leaf litter, and it was hypothesized that they would also consume inputs of invasive riparian leaf litter. This study shows that invasive alien signal crayfish (Pacifastacus leniusculus) and Chinese mitten crab (Eriocheir sinensis) effectively break down different types of leaf litter, including invasive alien R. ponticum, at higher rates than indigenous white-clawed crayfish. Secondary products were more varied, with more fine particulate organic matter generated for the less palatable alien leaf litter species. Leaf species caused different changes in body mass of decapods but effects were heterogeneous by leaf and decapod: P. leniusculus showed lower mass loss when consuming R. ponticum while E. sinensis lost mass when consuming A. pseudoplatanus. Impacts of riparian invasions on detritus accumulation in freshwaters are thus potentially buffered by invasive alien decapods, illustrating a need for a more detailed consideration of both positive and negative interspecific feedbacks during biological invasions.
|
10.1002/ece3.4430
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pubmed_198_1128
|
Six young African patients are described with erosive pustular scalp lesions leading to extensive ulceration. No bacterial or fungal cause was found. Biopsies showed non-specific changes of atrophy with subacute or chronic inflammation. Four patients were malnourished and anaemic and three were infested with hookworm. The condition did not respond to antibiotics. Healing was obtained in one patient with systemic steroids. The relationship of this disorder to erosive pustular dermatosis of the scalp and to pyoderma gangrenosum of atypical distribution is discussed.
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10.1111/j.1365-2133.1988.tb02441.x
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pubmed_851_18408
|
Indoleamine 2,3-dioxygenase-1 (IDO-1) catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine (Kyn). Apart from a normal physiological role, IDO-1 has also been identified to play a crucial role in immune suppression and tumour induced tolerance. Indeed, many primary tumours express high levels of IDO-1 compared to normal cells of the same stroma. IDO-1 is accepted as being an inducible negative regulator of T cell viability, proliferation and activation. As such, IDO-1 has become a target of intense interest for pharmacological inhibition, for the treatment of cancer. We have previously demonstrated that AA and the prostaglandin metabolite, PGD2, repressed the IFNγ mediated activity of IDO-1 in THP-1 cells and human monocytes. In this study, we characterise the structure-function relationship of fatty acids and eicosanoids towards inhibition of IDO-1 activity in THP-1 cells and human monocytes. Using a commercial library of fatty acids, 55% of fatty acids inhibited IDO-1 activity. The activity of individual FAs was affected by chain length, number of double bonds and bond configuration. Interrogation of an AA derived eicosanoid library identified 13 PGs with significant inhibitory activity. A structure-function analysis revealed that the γ position of the cyclopentenone ring, double bond in the α-β position of the cyclopentenone ring, the presence of multiple OH groups in the side arm and the addition of an ethanolamide group, significantly increased the inhibitory activity of the PGs. Based on this data we have identified the structure of two possible compounds that may be even more potent pharmacological repressors of IDO-1.
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10.1016/j.plefa.2017.06.010
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pubmed_125_4887
|
Background: Childhood overweight and obesity is a major public health issue. Responsive feeding has been identified as having a protective effect against child overweight and obesity, and is associated with healthy weight gain during infancy. Responsive feeding occurs when the caregiver recognises and responds in a timely and developmentally appropriate manner to infant hunger and satiety cues. Despite its benefits, responsive feeding is not ubiquitous. To better support caregivers to engage in responsive feeding behaviours, it is necessary to first systematically identify the barriers and enablers associated with this behaviour. This mixed-methods systematic review therefore aims to synthesise evidence on barriers and enablers to responsive feeding using the COM-B model of behavioural change. Methods: 7 electronic databases will be searched (Maternal and Infant Care, CINAHL, Cochrane, PubMed, Medline, PsycINFO, EMBASE). Studies examining factors associated with parental responsive and non-responsive feeding of infants and children (<2 years) will be included. Papers collecting primary data, or analysing primary data through secondary analysis will be included. All titles, abstracts and full texts will be screened by two reviewers. Quantitative and qualitative data from all eligible papers will be independently extracted by at least two reviewers using pre-determined standardised data extraction forms. Two reviewers will independently assess the methodological quality of the studies using the Mixed Methods Appraisal Tool (MMAT). This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta Analyses (PRISMA). Ethics and dissemination: Ethical approval is not required for this review as no primary data will be collected, and no identifying personal information will be present. The review will be disseminated in a peer reviewed journal. PROSPERO registration: CRD42019144570 (06/08/2019).
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10.12688/hrbopenres.12980.2
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pubmed_682_20549
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Primary mitochondrial diseases form one of the most common and severe groups of genetic disease, with a birth prevalence of at least 1 in 5000. These disorders are multi-genic and multi-phenotypic (even within the same gene defect) and span the entire age range from prenatal to late adult onset. Mitochondrial disease typically affects one or multiple high-energy demanding organs, and is frequently fatal in early life. Unfortunately, to date there are no known curative therapies, mostly owing to the rarity and heterogeneity of individual mitochondrial diseases, leading to diagnostic odysseys and difficulties in clinical trial design. This review aims to discuss recent advances and challenges of systems approaches for the study of primary mitochondrial diseases. Although there has been an explosion in the generation of omics data, few studies have progressed toward the integration of multiple levels of omics. It is evident that the integration of different types of data to create a more complete representation of biology remains challenging, perhaps due to the scarcity of available integrative tools and the complexity inherent in their use. In addition, "bottom-up" systems approaches have been adopted for use in the iterative cycle of systems biology: from data generation to model prediction and validation. Primary mitochondrial diseases, owing to their complex nature, will most likely benefit from a multidisciplinary approach encompassing clinical, molecular and computational studies integrated together by systems biology to elucidate underlying pathomechanisms for better diagnostics and therapeutic discovery. Just as next generation sequencing has rapidly increased diagnostic rates from approximately 5% up to 60% over two decades, more recent advancing technologies are encouraging; the generation of multi-omics, the integration of multiple types of data, and the ability to predict perturbations will, ultimately, be translated into improved patient care.
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10.3389/fgene.2019.00019
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pubmed_893_1088
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Serine proteases have significant functions over a broad range of relevant biological processes to the Leishmania spp lifecycle. Data gathered here present an update on the Leishmania spp serine proteases and the status of these enzymes as part of the parasite degradome. The serine protease genes (n = 26 to 28) in Leishmania spp, which encode proteins with a wide range of molecular masses (35 kDa-115 kDa), are described along with their degrees of chromosomal and allelic synteny. Amid 17 putative Leishmania spp serine proteases, only ∼18% were experimentally demonstrated, as: signal peptidases that remove the signal peptide from secretory pre-proteins, maturases of other proteins and with metacaspase-like activity. These enzymes include those of clans SB, SC and SF. Classical inhibitors of serine proteases are used as tools for the characterization and investigation of Leishmania spp. Endogenous serine protease inhibitors, which are ecotin-like, can act modulating host actions. However, crude or synthetic based-natural serine protease inhibitors, such as potato tuber extract, Stichodactyla helianthus protease inhibitor I, fukugetin and epoxy-α-lapachone act on parasitic serine proteases and are promising leishmanicidal agents. The functional interrelationship between serine proteases and other Leishmania spp proteins demonstrate essential functions of these enzymes in parasite physiology and therefore their value as targets for leishmaniasis treatment.
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10.1016/j.exppara.2017.11.008
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pubmed_590_4933
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The forces resulting from the presence of interfacial liquids have mechanical importance under ambient conditions. For holistic understanding of the liquid-mediated interactions, we combine the force-gradient sensitivity of an atomic force microscope (AFM) with the force measuring capability of a micro-electromechanical force sensor. Simultaneous measurement of the viscoelasticity of the water nanomeniscus and the absolute capillary force shows excellent agreement in its entire length, which justifies the validity of the widely used AFM results. We apply the hybrid system to measure the stress and strain, whose hysteretic response provides the intrinsic quantities of the liquid nanocluster.
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10.1039/c3nr06416f
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pubmed_582_19931
|
BACKGROUND
The use of a metal radial head prosthesis to help stabilize an elbow with traumatic instability is appealing because internal fixation of multifragment, displaced fractures of the radial head is susceptible to either early or late failure. The newer modular prostheses are easier to size and implant, but their effectiveness has not been investigated, to our knowledge.
METHODS
Twenty-seven patients in whom a radial head replacement with a modular metal spacer prosthesis had been performed to treat traumatic elbow instability were evaluated with use of the Mayo Elbow Performance Index (MEPI), the American Shoulder and Elbow Surgeons Elbow Evaluation Instrument (ASES), and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Radiographs were evaluated for arthrosis, periprosthetic radiolucency, and heterotopic ossification.
RESULTS
Seven patients underwent one or more subsequent operations to treat residual instability, heterotopic ossification and elbow contracture, ulnar neuropathy, or a misplaced screw. In two of these patients, the prosthesis was removed as part of an elbow contracture release or to treat infection. At an average of forty months postoperatively, elbow motion in the entire group of twenty-seven patients averaged 131 degrees of flexion with a 20 degrees flexion contracture, 73 degrees of pronation, and 57 degrees of supination. Stability was restored to all twenty-seven elbows, and twenty-two patients had a good or excellent result according to the MEPI. Seventeen patients had radiographic evidence of lucency around the neck of the prosthesis that was not associated with increased pain, thirteen patients had clinically inconsequential heterotopic ossification anterior to the radial neck, and nine patients had radiographic changes in the capitellum.
CONCLUSIONS
An intentionally loosely placed modular metal radial head prosthesis can help to restore stability in conjunction with repair of other fractures and reattachment of the lateral collateral ligament to the epicondyle in the setting of traumatic elbow instability with a comminuted fracture of the radial head. While a prosthesis that is too large can cause problems, lucencies around the stem of the intentionally loose prosthesis and most changes in the capitellum do not appear to cause problems, at least in the short term.
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10.2106/JBJS.G.01248
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pubmed_371_2421
|
Besides various clinical manifestations and made of spread of Salmonella infections, isolation of S. senftenberg a rare serotype from patients hospitalised for surgical procedures indicates nosocomial infection. A prolonged stay in hospital with surgical trauma facilitated the organism to cause infection in the compromised host.
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pubmed_371_2421
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pubmed_206_17324
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To prolong cell viability and facilitate replication, viruses have evolved multiple mechanisms to inhibit the host apoptotic response. Cellular proteases such as caspases and serine proteases are instrumental in promoting apoptosis. Thus, these enzymes are logical targets for virus-mediated modulation to suppress cell death. Four major classes of viral inhibitors antagonize caspase function: serpins, p35 family members, inhibitor of apoptosis proteins, and viral FLICE-inhibitory proteins. Viruses also subvert activity of the serine proteases, granzyme B and HtrA2/Omi, to avoid cell death. The combined efforts of viruses to suppress apoptosis suggest that this response should be avoided at all costs. However, some viruses utilize caspases during replication to aid virus protein maturation, progeny release, or both. Hence, a multifaceted relationship exists between viruses and the apoptotic response they induce. Examination of these interactions contributes to our understanding of both virus pathogenesis and the regulation of apoptotic enzymes in normal cellular functions.
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10.1146/annurev.micro.62.081307.163009
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pubmed_490_6359
|
OBJECTIVE
miR-329-3p has been reported to serve as a tumor suppressor in the progression of cervical cancer (CC). The aim of this study was to investigate the clinical significance of miR-329-3p in human CC.
PATIENTS AND METHODS
Quantitative RT-PCR (qRT-PCR) was used to detect miR-329-3p expression in CC tissue samples and matched normal cervical tissues. The x2 test was used to analyze the association between miR-329-3p expression and clinical features of CC patients. Moreover, we evaluated the prognostic value of miR-329-3p by Kaplan-Meier survival curve and Cox regression model.
RESULTS
We found that the mean expression level of miR-329-3p in CC tissues was significantly lower than the mean level in the adjacent normal tissues samples (p < 0.01). MiR-329-3p level was significantly associated with lymph node metastasis (p = 0.013), FIGO stage (p = 0.024) and distant metastasis (p = 0.001). Furthermore, a significant difference was found, that CC patients with low miR-329-3p expression level had distinctly shorter overall survival than patients with high miR-329-3p expression level (p = 0.001). Finally, multivariate analyses indicated that miR-329-3p represented an independent predictor for overall survival of CC (p = 0.04).
CONCLUSIONS
These results indicated, for the first time, that down-regulation of miR-329-3p was associated with poor prognosis in CC patients. MiR-329-3p can be used as an independent factor to predict survival of patients with CC.
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pubmed_490_6359
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pubmed_919_5381
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OBJECTIVE
The authors review and evaluate the literature and guidelines on care for individuals with a co-occurring affective or anxiety disorder and substance use disorder.
METHODS
MEDLINE and PsycINFO computerized searches of the English language literature were conducted for the period 1990-2002. These articles were supplemented with searches of the Cochrane Database of Systematic Reviews (1990 to 2002) and with articles that were sent to the authors by experts in the field to review. Bibliographies of selected papers were hand searched for additional articles. From these searches a total of 219 articles were found, of which 127 were selected for review.
RESULTS AND DISCUSSION
The literature shows that, over the past several decades, treatment for co-occurring disorders has undergone a broad shift in approach, from treating substance abuse before providing mental health care to providing simultaneous treatment for each disorder, regardless of the status of the comorbid condition. Many treatment recommendations are supported by a broad consensus. However, despite this broad agreement, recommendations are often not specific enough to guide clinical care. Most recommendations with specificity are for acute pharmacotherapy, but even specific recommendations lag behind current clinical practice. Although the use of psychotropic medication for mental illness is encouraged, experts disagree as to whether it is necessary to wait for abstinence before beginning pharmacotherapy. In addition, most diagnosis-specific guidelines are silent as to whether the specific treatment recommendation applies to co-occurring disorders. Finally, empirical evidence is lacking for most recommendations. The authors conclude that the mental health and substance abuse treatment fields need to consider its research priorities and how to address the multitude of potential combinations of disorders.
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10.1176/appi.ps.56.8.913
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pubmed_968_19723
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BACKGROUND
Delayed gastric emptying (DGE) following elective distal pancreatectomy (DP) is poorly known. This study aimed to report incidence of DGE following DP, to identify its predisposing factors, and to assess its impact on hospital stay.
METHODS
Patients who had elective DP without additional organ or vascular resection (2012-2017) in two academic hospitals were included. Factors predisposing to DGE, defined according to the International Study Group of Pancreatic Surgery, were identified by multivariate analysis. A systematic review was performed to evaluate DGE incidence following elective DP.
RESULTS
311 elective DPs were performed. Three perioperative mortalities (1.0%) were unrelated to DGE. DGE occurred in 31 (10.0%) patients (grade A = 21, grade B = 7, grade C = 3) with a median hospital stay of 16 (13-22) days versus 10 (7-14) without DGE (p < 0.001). In multivariate analysis, predisposing factors of DGE were age>75 years (OR = 4.32 [1.53-12.19]; p = 0.006), open approach (OR = 2.97 [1.1-8]; p = 0.031) and POPF grade B-C (OR = 2.54 [1.05-6.1]; p = 0.038). The systematic review identified 7 series including 876 patients with an overall 8.1% DGE incidence.
CONCLUSION
DGE complicates around 10% of elective DP. Laparoscopic approach and prevention of POPF should be encouraged to reduce DGE incidence.
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10.1016/j.hpb.2021.09.025
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pubmed_539_12037
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A 74-year-old woman was admitted with an asthma attack. She had a 40-year history of sinusitis, nasal polyp and analgesic-induced asthma; however, asthma had never occurred when she used a 0.3% ketoprofen adhesive patch (Mohrus) for stiff shoulder or lumbago. In the hospital, a life-threatening asthma attack suddenly occurred two and a half hours after application of a 2.0% ketoprofen adhesive tape (Mohrus tape) to her shoulder. She was treated with bronchodilator and glucocorticoid and extubated after 20 hours. A drug lymphocyte stimulating test (DLST) was strongly positive for ketoprofen. We suspected that drug-induced hypersensitivity coexisted in the present case, but it was not clear whether or not the hypersensitivity was related to the pathogenesis of analgesic-induced asthma.
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10.2169/internalmedicine.40.124
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pubmed_505_19783
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We previously performed a global analysis of the gene expression of gastric cancer cell lines established from metastases to the peritoneal cavity with the cDNA microarray method, which made it possible to analyse the expression of approximately 21168 genes for the identification of novel markers for the detection of micrometastases in the peritoneal cavity. One of the upregulated genes is dopa decarboxylase (DDC), which is responsible for the synthesis of the key neurotransmitters dopamine and serotonine. We have examined its potential as a novel marker for the detection of peritoneal micrometastases of gastric cancer.DDC mRNA in the peritoneal wash from 112 gastric cancer patients was quantified for comparison of carcinoembryonic antigen (CEA) mRNA by means of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) with a fluorescently labelled probe to predict peritoneal recurrence. The quantity of DDC and CEA correlated with wall penetration. Real-time RT-PCR could quantitate 10-10(6) DDC-expressing gastric cancer cells per 10(7) mesothelial cells. The cutoff value was set at the upper limit of the quantitative value for noncancer patients, and those above this cutoff value constituted the micrometastasis (MM+) group. Of 15 cases with peritoneal dissemination, 13 were MM+DDC (87% sensitivity), and one of 48 t1 cases was MM+ (98% specificity). DDC levels in peritoneal washes from patients with synchronous peritoneal metastases were more than 50 times higher than in those from patients without metastasis (P<0.01). For 15 cases of peritoneal dissemination (seven cases were cytologically positive), DDC was positive in 13 cases (87% sensitivity), but CEA failed to detect micrometastases in four cases (73% sensitivity), indicating that DDC is in some cases superior to CEA for the detection of peritoneal micrometastases of gastric cancer in terms of sensitivity as well as specificity, especially for poorly differentiated adenocarcinomas. A combination of CEA and DDC improved the accuracy of diagnosis up to 94%. These results suggest that DDC is potentially a novel marker for peritoneal dissemination of gastric cancer and that quantitative RT-PCR of DDC is reliable and efficient for the selection of patients for adjuvant intraperitoneal chemotherapy to prevent peritoneal recurrence.
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10.1038/sj.bjc.6601544
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pubmed_310_18076
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Type II mucopolysaccharidosis (Hunter's disease) is a hereditary condition due to a deficit of a lysosome specific hydrolase (iduronate sulfatase) inducing an accumulation of dermatane-sulphate and heparane-sulphate in certain organs. Cardiac involvement is constant in this disease and manifests itself essentially by aortic valve stenosis and insufficiency and/or mitral insufficiency which is progressive, irreversible and life-threatening. Two brothers of Portuguese nationality suffering from a so-called slight form of this disease had classical mucopolysaccharide infiltration of their aortic valves. The elder brother, aged 11, had severe aortic insufficiency associated with mild stenosis requiring treatment with vasodilator drugs. The younger, aged 8, had asymptomatic mild aortic regurgitation. Curiously, mitral valve prolapse with regurgitation was present in both children. The association of mitral valve prolapse and type II mucopolysaccharidosis, without other typical cardiac involvement, has only been reported once in the literature.
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pubmed_310_18076
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pubmed_1010_6109
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The inhibition of δ- and η-class carbonic anhydrases (CAs; EC 4.2.1.1) was poorly investigated so far. Only one δ-CA, TweCA from the diatom Thalassiosira weissflogii, and one η-CA, PfCA, from Plasmodium falciparum, have been cloned and characterised to date. To enrich δ- and η-CAs inhibition profiles, a panel of 22 phenols was investigated for TweCA and PfCA inhibition. Some derivatives showed effective, sub-micromolar inhibition of TweCA (KIs 0.81-65.4 µM) and PfCA (KIs 0.62-78.7 µM). A subset of compounds demonstrated a significant selectivity for the target CAs over the human physiologically relevant ones. This study promotes the identification of new potent and selective inhibitors of TweCA and PfCA, which could be considered as leads for finding molecular probes in the study of carbon fixation processes (in which TweCA and orthologue enzymes are involved) or drug candidates in the treatment of malaria.
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10.1080/14756366.2019.1706089
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pubmed_1089_12177
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The effect of two enzymatic hydrolyzed molasses (EHM)-feeding strategies including constant-(CFR) and exponential-(EFR) feeding rate on canthaxanthin (CTX) biosynthesis by Dietzia natronolimnaea HS-1 fed-batch fermentation was studied. The results showed that the CFR of 7 ml/h with an EHM content of 45 g/l led to the highest values of specific growth rate (0.127 h(-1)), biomass dry weight (17.66 g/l), total carotenoid (16.31 mg/l) and CTX (14.67 mg/l). A significant decrease in the kinetic growth and production parameters by the increasing EHM concentration from 30 to 60 g/l during EFR fed-batch bioprocess was observed (p<0.01). This study concluded that EHM alone can displace glucose-based medium towards improved CTX biosynthesis from D. natronolimnaea HS-1 using a CFR strategy during fed-batch culture.
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pubmed_1089_12177
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pubmed_1091_10763
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To enable the development of microbial agents and identify suitable candidate used for biodrying, the existence and function of Bacillus thermoamylovorans during sewage sludge biodrying merits investigation. This study isolated a strain of B. thermoamylovorans during sludge biodrying, submitted it for complete genome sequencing and analyzed its potential microbial functions. After biodrying, the moisture content of the biodrying material decreased from 66.33% to 50.18%, and B. thermoamylovorans was the ecologically dominant Bacillus, with the primary annotations associated with amino acid transport and metabolism (9.53%) and carbohydrate transport and metabolism (8.14%). It contains 96 carbohydrate-active- enzyme-encoding gene counts, mainly distributed in glycoside hydrolases (33.3%) and glycosyl transferases (27.1%). The virulence factors are mainly associated with biosynthesis of capsule and polysaccharide capsule. This work indicates that among the biodrying microorganisms, B. thermoamylovorans has good potential for degrading recalcitrant and readily degradable components, thus being a potential microbial agent used to improve biodrying.
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10.1016/j.biortech.2018.03.121
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pubmed_462_5362
|
To determine the effects of chronic nonocclusive coronary constriction on cardiac hemodynamics, structural integrity, and contractile protein enzyme activity, the left coronary artery was narrowed in rats, and measurements of ventricular performance, magnitude, and distribution of tissue damage and myofibrillar Mg2+ and Ca2+ myosin ATPase activities were evaluated 1 month later. In the presence of coronary artery stenosis averaging 58%, three levels of involvement of global cardiac performance were identified, and the rats were divided accordingly. In the first group, only left ventricular end-diastolic pressure (LVEDP) was increased; in the second group, LVEDP and left ventricular +dP/dt and/or -dP/dt were affected; and in the third group, LVEDP, left ventricular +dP/dt and -dP/dt, and right ventricular end-diastolic pressure were impaired. Thus, left ventricular moderate dysfunction, severe dysfunction, and failure occurred with coronary narrowing. On a structural basis, coronary constriction resulted in an ongoing process characterized by acute myocytolytic necrosis and foci of replacement fibrosis in different stages of healing. The number of these lesion profiles in the left ventricular myocardium increased 4.7-, 4.4-, and 8.3-fold in rats with moderate dysfunction, severe dysfunction, and failure, respectively. Biochemically, Mg(2+)-ATPase activity of myofibrils increased biventricularly when moderate dysfunction was present. However, this parameter decreased with the appearance of severe dysfunction, reaching control values in ventricular failure. Ca2+ myosin ATPase activity was reduced in the left ventricle of rats with severe dysfunction and failure, whereas it was elevated in the right ventricle of rats with severe dysfunction. In conclusion, a fixed lesion of the left main coronary artery with a modest reduction in vessel luminal diameter generates a conditioned state of the heart characterized by a continuous loss of myocytes and replacement scarring, which, in combination with alterations in contractile protein enzyme activity, may be responsible for a number of abnormalities in cardiac dynamics ranging from moderate dysfunction to pump failure.
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10.1161/01.res.70.1.148
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pubmed_226_11030
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Background: Emerging research suggests that long non-coding RNAs (lncRNAs) play an important role in a variety of developmental or physiological processes of hepatocellular carcinoma (HCC). Various differentially expressed lncRNAs have been identified in HCC. Thus, a deeper analysis of recent research concerning lncRNA and HCC development could provide scientists with a valuable reference for future studies. Methods: Related publications were retrieved from the Web of Science Core Collection database. CiteSpace version 5.6.R4 was employed to conduct bibliometric analysis. Several network maps were constructed to evaluate the collaborations between different countries, institutions, authors, journals, and keywords. Results: A total of 2,667 records were initially found from the year of 2010-2020. The annual related publications output had increased dramatically during these years. Although China was the most prolific country in terms of research publication, the United States played a leading role in collaborative network. The Nanjing Medical University was the most productive institute in the field of lncRNAs in HCC development. Gang Chen was the most prolific researcher, while Yang F was the most frequently co-cited author. Oncotarget, Cell, and Oncogene were the most highly co-cited journals. The most recent burst keywords were interaction, database, and pathway. Conclusion: This study provides a comprehensive overview for the field of lncRNAs in HCC development based on bibliometric and visualized methods. The results would provide a reference for scholars focusing on this field.
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10.3389/fgene.2021.771810
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pubmed_199_8149
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Over two years, the management regimes of: 1) opening a southeast Florida salt marsh impoundment to the adjacent estuary with culverts through the dike, then, 2) passively retaining water with flapgate risers was studied to determine the effects on marsh flooding and resultant mosquito production. Larval dipping demonstrated that all broods occurred at elevations of 0.25-0.90 ft (= 0.08-0.27 m) NGVD. Mosquito production differed significantly between some sampling quadrats and 65 (out of 75) broods were produced in the spring and summer from rainfall. Without artificial pumping, trapping of rainfall with flapgate risers aided in eliminating oviposition sites but still allowed mosquito production in some marsh locations. Even though tidal flooding permitted larvivorous fish access to mosquito larvae, they were not able to provide adequate control to eliminate larviciding.
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pubmed_199_8149
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pubmed_173_2023
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The thalamocingulate tract between the anterior thalamic nuclei and the cingulate gyrus is a part of the Papez circuit. Using diffusion tensor tractography, injury of the thalamocingulate tract was investigated in patients with mild traumatic brain injury. Two patients (patient 1: a 58-yr-old woman and patient 2: a 49-yr-old man) with head trauma resulting from a car accident were enrolled. They were classified as mild traumatic brain injury and no specific lesion was observed on brain magnetic resonance imaging. These patients complained of memory impairment after head trauma. The entire Papez circuits, including thalamocingulate tract, fornix, mammillothalamic tract, and cingulum, were reconstructed in both hemispheres except for the left thalamocingulate tract: patient 1, it was thinner and discontinued compared with the right thalamocingulate tract; and patient 2, it was not reconstructed. The injury of the left thalamocingulate tract appeared to be related to the memory impairment in these patients.
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10.1097/PHM.0000000000000413
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pubmed_33_24916
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The acaricidal activities of materials derived from Pyrus ussuriensis fruits were evaluated against Tyrophagus putrescentiae and compared with that of commercial acaricide (benzyl benzoate). On the basis of the 50 % lethal dose (LD(50)) values, the ethyl acetate fraction of the fractions obtained from an aqueous extract of P. ussuriensis fruits had the highest acaricidal activity (16.32 μg/cm(2)) against T. putrescentiae. The acaricidal constituent of P. ussuriensis fruits was isolated by chromatographic techniques and identified as 1,4-benzoquinone. On the basis of the LD(50) values, 1,4-benzoquinone (1.98 μg/cm(2)) was 5.9 times more toxic than benzyl benzoate (11.69 μg/cm(2)), followed by 2-isopropyl-5-methyl-1,4-benzoquinone (3.29 μg/cm(2)), and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (5.03 μg/cm(2)) against T. putrescentiae in the fumigant bioassay. In a filter paper bioassay, the acaricidal activity of 1,4-benzoquinone (0.07 μg/cm(2)) was 120.1 times more effective than that of benzyl benzoate (8.41 μg/cm(2)), followed by 2-isopropyl-5-methyl-1,4-benzoquinone (0.11 μg/cm(2)) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (0.30 μg/cm(2)) against T. putrescentiae. These results demonstrate that P. ussuriensis fruit-derived material and its derivatives have potential as new preventive agents for the control of stored food mites.
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10.4315/0362-028X.JFP-12-040
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pubmed_847_11319
|
OBJECTIVES
Good social functioning is important for people living with dementia and their families. The Social Functioning in Dementia Scale (SF-DEM) is a valid and reliable instrument measuring social functioning in dementia. However the minimum clinically important difference (MCID) has not yet been derived for SF-DEM. This study aims to define the MCID for the SF-DEM.
DESIGN
We used triangulation, incorporating data from a cross-sectional study to calculate the MCID using distribution-based and anchor-based methods, and a Delphi survey.
SETTING AND PARTICIPANTS
The cross-sectional survey comprised 299 family carers of people with dementia. Twenty dementia experts (researchers, clinicians, family carers) rated whether changes on clinical vignettes represented a meaningful change in the Delphi survey.
PRIMARY OUTCOME MEASURES
We calculated the distribution-based MCID as 0.5 of an SD for each of the three SF-DEM domains (1-spending time with others, 2-communicating with others, 3-sensitivity to others). We used the carers' rating of social functioning to calculate the anchor-based MCID. For the Delphi survey, we defined consensus as ≥75% agreement. Where there was lack of consensus, experts were asked to complete a further survey round.
RESULTS
We found that 0.5 SD of SF-DEM was 1.9 points, 2.2 and 1.4 points in domains 1, 2 and 3, respectively. Using the anchoring analysis, the MCIDs were 1.7 points, 1.7 points, and 0.9 points in domains 1, 2 and 3, respectively. The Delphi method required two rounds. In the second round, a consensus was reached that a 2-point change was considered significant in all three domains, but no consensus was reached on a 1-point change.
CONCLUSIONS
By triangulating all three methods, the SF-DEM's MCIDs were 1.9, 2.0 and 1.4 points for domains 1, 2 and 3, respectively. For individuals, these values should be rounded to a 2-point change for each domain.
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10.1136/bmjopen-2021-058252
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pubmed_584_15920
|
A study of blood circulation in the pancreas of 42 patients with the metabolic syndrome by the method of intracavitary rheography revealed a drop in the intensity of terminal blood circulation and presence of venous congestion with the activation of venous-arterial shunting. Hemodynamic disorders directly depended on the adiposity degree and patients' age, being evident as signs of a more obvious disorder of terminal blood circulation in patients with HLP of the II and III type.
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pubmed_584_15920
|
pubmed_880_24613
|
In crystal of the the title compound, C(10)H(9)F(3)O(2), inversion dimers linked by pairs of O-H⋯O hydrogen bonds occur.
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10.1107/S1600536809010125
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pubmed_659_10241
|
INTRODUCTION
In 2020, during the first wave of the COVID-19 pandemic in Melbourne, visitor access to acute hospitals including intensive care units (ICUs) was initially barred, followed by a limit of one person per patient for one hour per day. This study explores the care and communication experienced by family members of ICU patients during this time.
METHODS
This qualitative descriptive study was conducted at an Australian quaternary hospital. Semistructured phone interviews were conducted using an aide-memoire designed to understand participants' experiences as family of a patient during this time. Interviews were recorded, transcribed, and thematically analysed.
FINDINGS
Twenty family members of patients in the ICU participated. Three major themes were identified: 'impact of restricting visiting procedures', 'family experiences of communication', and 'care and support'. Inflexible visiting restrictions had a momentous impact on families. Participants objected to having to nominate only two people to visit during the admission and the short visiting time limit. Some family members suffered extreme stress and anxiety during their absence from the bedside. Additional challenges were experienced by rural families, visitors with disabilities, and the young children of patients who were excluded. Communication with clinicians varied. Telehealth was valued by some but not universally embraced. The relationship between staff members and families and involvement in decision-making were unaffected.
CONCLUSION
Families experienced significant psychological distress from being separated from their critically ill relatives. Patient care and involvement in decision-making appeared to be unchanged, but communication with staff felt to be lacking. Better alternatives to face-to-face communication must be sought to limit the impact of family separation on mental health. Families are a key link between the patient and clinicians and often play a major role in patient support and recovery after discharge. There is an urgent need to support them and facilitate meaningful engagement despite the obstacles.
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10.1016/j.aucc.2022.03.003
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pubmed_960_1237
|
As the main risk factor for cardiovascular disease, hypercholesterolemia is one of the most studied age-related metabolic alterations. In the liver, cholesterol homeostasis is strictly regulated through the modulation of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the key enzyme of cholesterol biosynthesis. With ageing, hepatic HMG-CoA reductase becomes completely activated and cholesterol content increases in the blood. The research reported in this paper uses the regulatory enzymes of reductase (i.e., the AMP-dependent kinase (AMPK) and the protein phosphatase 2A (PP2A)), the HMG-CoA reductase thermodependent activity and the "in vitro" enzyme degradation to elucidate the role played by the HMG-CoA reductase regulation and its membrane interaction. Related experiments were performed on 3 and 24 months "ad libitum" (AL) fed rats and 24 months caloric-restricted rats. The results show no changes in the PP2A level and the activation state of AMP dependent kinase in aged "ad libitum" fed rats. By contrast, the activation state of the kinase is enhanced in the aged caloric-restricted animals. With respect to the adult, the thermodependent activity of reductase remains unchanged, while the degradation rate of the HMG-CoA reductase is slower and independent on proteasome. These findings support the hypothesis that a different arrangement of the HMG-CoA reductase membrane domain in aged rats is a cause of reductase deregulation.
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10.1016/j.mad.2004.08.001
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pubmed_746_9564
|
Language comprehension studies have identified the N400, an event-related potential (ERP) correlate of the processing of meaning, modulation of which is typically assumed to reflect the activation of semantic information. However, N400 studies of conscious language processing have not clearly distinguished between meaning derived from a semantic relationship and meaning extracted through association. We independently manipulated the presence of associative and semantic relationships while examining the N400 effect. Participants were asked to read and remember visually presented word pairs that shared an association (traffic-jam), an association+semantic relationship (lemon-orange), a semantic relationship alone (cereal-bread), or were unrelated (beard-tower). Modulation of the N400 (relative to unrelated word pairs) was observed for association and association+semantic word pairs but not for those that only shared a semantic relationship.
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10.1111/j.1469-8986.2007.00598.x
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pubmed_123_5307
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We have examined the interaction between NusA and the nascent RNA in Escherichia coli transcription complexes on four different templates. Photocrosslinking CTP and UTP analogs were incorporated internally and at the 3' end of the RNA. Identical templates with and without boxA sequences were compared. We found that NusA did not contact the ten nucleotides nearest to the 3' end of the RNA in complexes containing RNA up to 20 nucleotides long. Longer RNA did crosslink to NusA with all four templates examined, however. We reported that RNA 80 nucleotides long from the bacteriophage T7 A1 promoter substituted in two RNA stem-loops with photocrosslinking UMP analogs did not crosslink to NusA, even though interaction between NusA and the transcription complex were demonstrated. Here, we report that when this same RNA is substituted at CMP residues, it does crosslink to NusA. Templates containing the E. coli ribosomal RNA promoter rrnG P2, with and without a boxA sequence downstream, were compared. Long RNAs from both crosslinked to NusA, and thus boxA RNA sequences are not required for interaction with NusA. NusA did not interact with the free RNA containing boxA once released from the transcription complex, nor did it interact with RNA in a binary complex containing only RNA polymerase and RNA, without the DNA template.
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10.1006/jmbi.1994.0161
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pubmed_364_24201
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Foetus sterility until parturition is under debate due to reports of microorganisms in the foetal environment and meconium. Sufficient controls to overcome sample contamination and provide direct evidence of microorganism viability in the pre-rectal gastrointestinal tract (GIT) have been lacking. We conducted molecular and culture-based analyses to investigate the presence of a microbiome in the foetal GIT of calves at 5, 6 and 7 months gestation, while controlling for contamination. The 5 components of the GIT (ruminal fluid, ruminal tissue, caecal fluid, caecal tissue and meconium) and amniotic fluid were found to contain a pioneer microbiome of distinct bacterial and archaeal communities. Bacterial and archaeal richness varied between GIT components. The dominant bacterial phyla in amniotic fluid differed to those in ruminal and caecal fluids and meconium. The lowest bacterial and archaeal abundances were associated with ruminal tissues. Viable bacteria unique to the ruminal fluids, which were not found in the controls from 5, 6 and 7 months gestation, were cultured, subcultured, sequenced and identified. We report that the foetal GIT is not sterile but is spatially colonised before birth by a pioneer microbiome.
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10.1038/s41598-020-74677-7
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pubmed_687_3469
|
Root apical meristem histological organization in Zea mays has been carefully studied previously. Classical histology describes its system as having a "closed organization" and a development of xylem that conforms to predictable rules. Among the first cell types to begin differentiation are late-maturing metaxylem (LMX) vessels. As part of a larger study comparing domestic maize root development to a wild subspecies of Z. mays (teosinte), we encountered a metaxylem development abnormality in a small percentage of our specimens that begged further study, as it interrupted normal maturation of LMX. Primary root tips of young seedlings of Zea mays ssp. mexicana were fixed, embedded in appropriate resins, and sectioned for light and transmission electron microscopy. Longitudinal and serial transverse sections were analyzed using computer imaging to determine the position and timing of key xylem developmental events. We observed a severe abnormality of LMX development among 3.5% of the 227 mexicana seedlings we screened. All LMX vessel elements in these abnormal roots collapsed and probably became non-functional shortly after differentiation began. Cytoplasm and nucleoplasm in the abnormal LMX elements became condensed and subdivided into irregularly-shaped "macrovesicles" as their cell walls collapsed inward. We propose that these seedlings possibly suffered from a mutation that affected the timing of the programmed cell death (PCD) that is required to produce functional xylem vessels, such that autolysis of the cytoplasm was prematurely executed, i.e., prior to the development and lignification of secondary walls.
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10.3390/plants9030374
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pubmed_804_1657
|
Arabidopsis heterotrimeric G proteins regulate diverse processes by coupling to single-transmembrane receptors. One such receptor is the FLS2 receptor kinase, which perceives bacterial flagellin epitope flg22 to activate immunity through a class of cytoplasmic kinases called BIK1/PBLs. Unlike animal and fungal heterotrimeric G proteins that are activated by a ligand-induced guanine nucleotide exchange activity of seven-transmembrane G protein-coupled receptors (GPCRs), plant heterotrimeric G proteins are self-activating. How plant receptors regulate heterotrimeric G proteins in response to external ligands remains unknown. Here we show that RGS1, a GTPase accelerating protein, maintains Arabidopsis G proteins in an inactive state in complex with FLS2. Activation of FLS2 by flg22 induces a BIK1/PBL-mediated phosphorylation of RGS1 at Ser428 and Ser431 and that promotes RGS1 dissociation from the FLS2-G protein complex. This relieves G proteins from the RGS1-mediated repression and enables positive regulation of immune signaling. We additionally show that RGS1 is similarly regulated by multiple immune receptors. Our results uncover ligand-induced de-repression as a mechanism for G protein signaling in plants that is distinct from previously reported mechanism underlying the activation of heterotrimeric G proteins in other systems.
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10.1038/s41422-018-0027-5
|
pubmed_857_13164
|
We have previously shown that a pig kidney cell line (LLC-PK1/Cl4) responds to chronic exposure to 0.25 mM extracellular K+ by increasing the beta-, not alpha-, subunit mRNA levels and both alpha- and beta-abundance twofold over control. Our objective in the present study was to determine how the LLC-PK1/Cl4 cells respond when returned to control (5.5 mM) medium. A 1.8-fold increase in ouabain binding established that the induced pumps were expressed at the cell surface following 24-h incubation in low K+. On restoration to 5.5 mM K+, intracellular Na+ and K+ concentrations ([Na+]i and [K+]i, respectively) rapidly returned to control levels within 15 min. The doubled pool size of pumps in the chronic low K+ cells had no significant influence on the rate of ion restoration when compared with the rate in cells acutely exposed to low K+. Despite the rapid return of ions to control values, beta-mRNA levels remained elevated for 2 h, then sharply declined to control levels by 6 h of K+ restoration. From these data, we estimate that the half-life of beta-mRNA is 2-3 h during restoration. alpha-Subunit mRNA remained essentially unchanged from control after return of K+ to the medium and restoration of intracellular ions.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1152/ajpcell.1993.265.4.C887
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pubmed_602_11780
|
Although rare, blast injury to the intestine can result from penetrating thoraco-abdominal extra-peritoneal gunshot (and shotgun) wounds despite the absence of injury to the diaphragm or to the peritoneum. Injuries of the spleen, small intestine and the mesentery by this mechanism have been previously reported in the world literature. This paper reports the first two cases of non-penetrating ballistic trauma to the colon.
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10.1016/s0020-1383(03)00102-5
|
pubmed_849_11090
|
INTRODUCTION
Illegal alcohol production remains as a common issue worldwide. Methanol poisoning mostly occurs because of the methanol used in production of counterfeit alcohol instead of ethyl alcohol due to its low price or by drinking the liquids containing methyl alcohol. Pectolytic enzymes results in an increase of methanol levels in many fermentation products such as ciders or wines. Methanol poisonings are infrequently encountered in forensic medicine practice. However, sporadic cases due to methanol intoxication as well as epidemic cases have been reported. In this study, we aimed to identify existence of methanol and its metabolites in illegally produced alcoholic beverages used in Antakya region.
MATERIAL AND METHODS
Twelve legally produced alcohol samples and Fifty-six different illegally produced alcohol samples were collected from the markets and local producers. Existence of methanol, formic acid, methyl amine, methyl formate and trioxan were determined using GC-MS method in these samples.
RESULTS
Fifty-six different illegal alcohol samples were analyzed in this study and methanol was detected in 39 (75%) of samples. Formic acid was detected in 3, formamide in 1, methyl amine in 6, methyl formate in 10 and trioxan in 2 samples.
CONCLUSION
Overwhelming majority of illegal alcoholic beverages was detected to contain methanol. Interestingly this study also revealed the presence of trioxane, which has not previously reported among toxic agents in illegal alcohol samples.
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pubmed_849_11090
|
pubmed_530_15597
|
Dissociative identity disorder (DID), once considered rare, was frequently diagnosed during the 1980s and 1990s, after which interest declined. This is the trajectory of a medical fad. DID was based on poorly conceived theories and used potentially damaging treatment methods. The problem continues, given that the DSM-5 includes DID and accords dissociative disorders a separate chapter in its manual.
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10.1097/NMD.0b013e318275d285
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pubmed_212_1826
|
Antibody-dependent cell-mediated cytotoxicity (ADCC) by peripheral blood mononuclear cells in patients with Sjögren's syndrome (SjS) was estimated with special reference to differentiation from phagocytic activity caused by phagocytes. There was no significant difference in ADCC activity of peripheral blood lymphocytes (phagocyte-depleted lymphocyte fraction) between patients with SjS and normal persons. Higher ADCC activity of the crude lymphocyte fraction (CLF), however, was demonstrated in patients with SjS than in normal persons. It was proved that increased ADCC activity of CLF in patients with SjS resulted from reduced erythro-phagocytic activity of contaminating monocytes in this fraction.
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pubmed_212_1826
|
pubmed_898_9238
|
High levels of ultrafine particles (UFPs; diameter of less than 50 nm) are frequently produced from new particle formation under urban conditions, with profound implications on human health, weather, and climate. However, the fundamental mechanisms of new particle formation remain elusive, and few experimental studies have realistically replicated the relevant atmospheric conditions. Previous experimental studies simulated oxidation of one compound or a mixture of a few compounds, and extrapolation of the laboratory results to chemically complex air was uncertain. Here, we show striking formation of UFPs in urban air from combining ambient and chamber measurements. By capturing the ambient conditions (i.e., temperature, relative humidity, sunlight, and the types and abundances of chemical species), we elucidate the roles of existing particles, photochemistry, and synergy of multipollutants in new particle formation. Aerosol nucleation in urban air is limited by existing particles but negligibly by nitrogen oxides. Photooxidation of vehicular exhaust yields abundant precursors, and organics, rather than sulfuric acid or base species, dominate formation of UFPs under urban conditions. Recognition of this source of UFPs is essential to assessing their impacts and developing mitigation policies. Our results imply that reduction of primary particles or removal of existing particles without simultaneously limiting organics from automobile emissions is ineffective and can even exacerbate this problem.
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10.1073/pnas.1916366117
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pubmed_866_25143
|
Importance
The Hospital Readmissions Reduction Program (HRRP) is a Centers for Medicare and Medicaid Services policy that levies hospital reimbursement penalties based on excess readmissions of patients with 4 medical conditions and 3 surgical procedures. A greater understanding of factors associated with the 3 surgical reimbursement penalties is needed for clinicians in surgical practice.
Objective
To investigate the first year of HRRP readmission penalties applied to 2 surgical procedures-elective total hip arthroplasty (THA) and total knee arthroplasty (TKA)-in the context of hospital and patient characteristics.
Design, Setting, and Participants
Fiscal year 2015 HRRP penalization data from Hospital Compare were linked with the American Hospital Association Annual Survey and with the Healthcare Cost and Utilization Project State Inpatient Database for hospitals in the state of Florida. By using a case-control framework, those hospitals were separated based on HRRP penalty severity, as measured with the HRRP THA and TKA excess readmission ratio, and compared according to orthopedic volume as well as hospital-level and patient-level characteristics. The first year of HRRP readmission penalties applied to surgery in Florida Medicare subsection (d) hospitals was examined, identifying 60 663 Medicare patients who underwent elective THA or TKA in 143 Florida hospitals. The data analysis was conducted from February 2016 to January 2017.
Exposures
Annual hospital THA and TKA volume, other hospital-level characteristics, and patient factors used in HRRP risk adjustment.
Main Outcomes and Measures
The HRRP penalties with HRRP excess readmission ratios were measured, and their association with annual THA and TKA volume, a common measure of surgical quality, was evaluated. The HRRP penalties for surgical care according to hospital and readmitted patient characteristics were then examined.
Results
Among 143 Florida hospitals, 2991 of 60 663 Medicare patients (4.9%) who underwent THA or TKA were readmitted within 30 days. Annual hospital arthroplasty volume seemed to follow an inverse association with both unadjusted readmission rates (r = -0.16, P = .06) and HRRP risk-adjusted readmission penalties (r = -0.12, P = .14), but these associations were not statistically significant. Other hospital characteristics and readmitted patient characteristics were similar across HRRP orthopedic penalty severity.
Conclusions and Relevance
This study's findings suggest that higher-volume hospitals had less severe, but not significantly different, rates of readmission and HRRP penalties, without systematic differences across readmitted patients.
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10.1001/jamanetworkopen.2019.16008
|
pubmed_400_1022
|
PURPOSE
The aim of the study was to assess the place of cardiac Magnetic Resonance Imaging (MRI) in patients with sarcoidosis with or without cardiac involvement.
MATERIALS AND METHODS
Fifty patients with histologically-proven sarcoidosis underwent initial cardiac evaluation including MRI, ECG, holter ECG, echocardiography. Seven of them had cardiac involvement (cardiac insufficiency, auriculo-ventricular block, bundle-branch block). Fiveteen patients had a second evaluation at 10-month follow-up. MRI was classified in three stages, on the base of literature data (stage 1 "granulomatous", stage 2 "exsudative", stage 3 "fibrotic").
RESULTS
A good correlation between the type of the sarcoidosis and MRI was observed: patients with cardiac involvement had all stage 2 MRI; patients with quiescent sarcoidosis had normal or stage 3 MRI; patients without cardiac involvement had all stages on MRI. A good correlation was observed between cardiac MRI abnormalities and evolution of sarcoidosis. Patients under corticoid, with or without cardiac involvement all had regression of MRI lesions and sarcoidosis. In 2 cases, MRI was predictive of clinical cardiac involvement.
CONCLUSION
Cardiac MRI is a useful non-invasive method for the early diagnosis and follow-up of cardiac sarcoidosis.
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10.1016/s0248-8663(02)00808-1
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pubmed_180_20359
|
The intestine of marine fish plays a crucial role in ion homeostasis by selective processing of ingested fluid. Although arginine vasotocin (AVT) is suggested to play a role in ion regulation in fish, its action in the intestine has not been demonstrated. Thus, the present study investigated in vitro the putative role of AVT in intestinal ion transport in the sea bream (Sparus aurata). A cDNA encoding part of an AVT receptor was isolated and phylogenetic analysis revealed it clustered with the V1a2-type receptor clade. V1a2 transcripts were expressed throughout the gastrointestinal tract, from esophagus to rectum, and were most abundant in the rectum regardless of long-term exposure to external salinities of 12, 35 or 55p.p.t. Basolateral addition of AVT (10(-6)M) to the anterior intestine and rectum of sea bream adapted to 12, 35 or 55p.p.t. mounted in Ussing chambers produced rapid salinity and region dependent responses in short circuit current (Isc), always in the absorptive direction. In addition, AVT stimulation of absorptive Isc conformed to a dose-response curve, with significant effects achieved at 10(-8)M, which corresponds to physiological values of plasma AVT for this species. The effect of AVT on intestinal Isc was insensitive to the CFTR selective inhibitor NPPB (200μM) applied apically, but was completely abolished in the presence of apical bumetanide (200μM). We propose a role for AVT in the regulation of ion absorption in the intestine of the sea bream mediated by an absorptive bumetanide-sensitive mechanism, likely NKCC2.
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pubmed_180_20359
|
pubmed_992_2037
|
Variations in clinical practice are commonly viewed as a sign of uneven quality of care and attributed to provider self-interest. However, patient preferences, physician practice patterns, and diagnostic and therapeutic uncertainty also cause variations. Greater attention to both doctor-patient interactions and limits to the available evidence might enable more effective assessment and improvement of health-care quality.
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10.1038/nrurol.2017.102
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pubmed_882_19108
|
Highly inbred mice of fast and slow conditioning strains (N = 228) were trained in avoidance conditioning and 180 were continued to extinction. The principal goal was to determine optimal stimulus conditions for fast learning, small variances, and maximal strain differences. Conclusions are: a) the major effect of change in CS-US and intertrial intervals occurs, respectively, for intervals less than 3 sec. and 60 sec.; b) change in amperage (150-400 pa) or voltage (250-400 v.) caused no significant differences; c) strain differences in extinction occurred after nearly optimal conditioning, and d) strain differences were altered considerably as stimulus conditions became optimal. Optimal levels of parameters are: 3 sec. CS-US interval, 120-sec. intertrial interval, and 400 v. (220 K ohm impedance circuit).
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10.1207/s15327906mbr0102_7
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pubmed_873_16898
|
Membranes are recognized as a key component in many environment and energy-related applications, but conventional membranes are challenged to satisfy the growing demand for ever more energy-efficient processes. Janus membranes, a novel class with asymmetric properties on each side, have recently emerged and represent enticing opportunities to address this challenge. With an inner driving force arising from their asymmetric configuration, Janus membranes are appealing for enhancing energy efficiency in a variety of membrane processes by promoting the desired transport. Here, the fundamental principles to prepare Janus membranes with asymmetric surface wettability and charges are summarized, and how they work in conventional and unconventional membrane processes is demonstrated.
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10.1002/adma.201801495
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pubmed_364_24125
|
Honey has been valued as a powerful antimicrobial since ancient times. However, the understanding of the underlying antibacterial mechanism is incomplete. The complexity and variability of honey composition represent a challenge to this scope. In this study, a simple model system was used to investigate the antibacterial effect of, and possible synergies between, the three main stressors present in honey: sugars, gluconic acid, and hydrogen peroxide (H2O2), which result from the enzymatic conversion of glucose on honey dilution. Our results demonstrated that the synergy of H2O2 and gluconic acid is essential for the antibacterial activity of honey. This synergy caused membrane depolarization, destruction of the cell wall, and eventually growth inhibition of E. coli K-12. The presence of H2O2 stimulated the generation of other long-lived ROS in a dose-dependent manner. Sugars caused osmosis-related morphological changes, however, decreased the toxicity of the H2O2/gluconic acid. The susceptibility of catalase and general stress response sigma factor mutants confirmed the synergy of the three stressors, which is enhanced at higher H2O2 concentrations. By monitoring cellular phenotypic changes caused by model honey, we explained how this can be bactericidal even though the antimicrobial compounds which it contains are at non-inhibitory concentrations.
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10.1038/s41598-020-74937-6
|
pubmed_74_12167
|
Aperiodicity in the voice source is caused by changes in the vocal fold vibrations, other than the normal quasi-periodicity and the turbulence at the glottis. The aperiodicity appears to be one of the main properties that is responsible for conveying the emotion in artistic voices. In this paper, the feasibility of representing the excitation source characteristics in artistic (Noh) singing voice by an impulse-like sequence in the time domain is examined. The impulses at the glottal closure instants contribute to the major excitation of the vocal tract system. The sequence of such impulses produces harmonics of the fundamental frequency in the spectrum. The amplitude variation or amplitude modulation (AM) of these impulses in the sequence contributes to the aperiodicity in the excitation, and can result in appearance of subharmonics in the spectrum. The variation in the impulse intervals or frequency modulation (FM) can also contribute to the aperiodicity in the excitation. The aperiodic component of the excitation in the Noh voice is examined in the impulse-like sequence derived from the signal using the single frequency filtering analysis. The effects of aperiodicity are explained for synthetic AM and FM sequences of impulses using spectrograms and saliency plots.
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10.1121/1.5139225
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pubmed_1025_5015
|
With improvements in both early detection and treatments for breast cancer, the number of survivors has increased dramatically in recent decades. One of the most common lingering symptoms posttreatment for cancer survivors is chronic fatigue. Based on family stress theory and Rolland's typology of illness, this qualitative study extends our understanding of the impact of persistent posttreatment fatigue on families and how breast cancer survivors manage the family issues that arise because of this chronic stressor. Participants included 35 female survivors of breast cancer (mean age = 54 years) who experienced fatigue after the completion of active cancer treatment, with the exception of long-term hormonal therapy. Data were generated from (a) observations of group sessions from a randomized controlled fatigue intervention designed to reduce fatigue in breast cancer survivors, (b) individual in-depth interviews, and (c) family sessions. Qualitative analysis revealed two broad themes that illustrate how the survivors manage the impact of fatigue on their families: Interpreting the meaning of the fatigue and Dealing with the inability to perform family roles. Study findings describe the difficulties in family adaptation when the family is not able to assign a clear meaning to a chronic symptom posttreatment and build upon family stress theory by highlighting interrelationships among communication patterns and role shifts in the family system.
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10.1037/a0023947
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pubmed_1054_6564
|
Spinal cord stimulation, which has been shown to be beneficial in multiple sclerosis as well as in sustained spinal cord injury, works through modification of specific motor mechanisms. This modification occurs through regional recruitment of spinal cord activity in posterior aspects of the spinal cord. Substantial involvement of the placebo effect can be ruled out by noting the persistence of beneficial effects observed in spinal cord injury patients and by the fact that the effects are related only to depolarization of posterior structures of the spinal cord, rather than to perception of a 'tingling' sensation caused by spinal cord stimulation. Such a sensation can also occur when electrodes are over anterior or lateral structures of the spinal cord, when the stimulation is not effective in alleviating motor symptoms.
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10.1159/000102191
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pubmed_750_4594
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An 83-year-old man with main pancreatic duct (MPD) stenosis in the pancreatic body had undergone surveillance with semiannual imaging studies for 3 years. During surveillance, magnetic resonance cholangiopancreatography revealed gradual enlargement of a small cyst near the MPD stenosis and contrast-enhanced computed tomography revealed locally progressive atrophic parenchyma in the pancreatic body. On endoscopic retrograde pancreatography, the MPD stenosis was more severe than it had been at diagnosis 3 years earlier. Endoscopic ultrasonography (EUS) showed a 10-mm hypoechoic mass adjacent to the MPD stenosis. The mass was pathologically diagnosed as an adenocarcinoma using EUS-guided fine needle aspiration, and distal pancreatectomy was performed. On histopathological examination, the resected specimen was found to be a moderately differentiated 9-mm invasive ductal carcinoma. Additionally, multiple high-grade pancreatic intraepithelial neoplasms (i.e., carcinoma in situ) were detected in the MPD and branch ducts near the invasive carcinoma.
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10.11405/nisshoshi.116.99
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pubmed_204_11643
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The hypothalamic neuropeptide oxytocin (OT) is critically involved in the modulation of socio-emotional behavior, sexual competence, and pain perception and anticipation. While intracellular signaling of OT and its receptor (OTR), as well as the functional connectivity of hypothalamic and extra-hypothalamic OT projections, have been recently explored, it remains elusive how one single molecule has pleotropic effects from cell proliferation all the way to modulation of complex cognitive processes. Moreover, there are astonishing species-dependent differences in the way OT regulates various sensory modalities such as touch, olfaction, and vision, which can be explained by differences in OTR expression in brain regions processing sensory information. Recent research highlights a small subpopulation of OT-synthesizing cells, namely, parvocellular cells, which merely constitute 1% of the total number of OT cells but act as "master cells' that regulate the activity of the entire OT system. In this chapter, we summarize the latest advances in the field of OT research with a particular focus on differences between rodents, monkeys and humans and highlight the main differences between OT and its "sister" peptide arginine-vasopressin, which often exerts opposite effects on physiology and behavior.
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10.1016/B978-0-12-820107-7.00003-3
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pubmed_457_7098
|
This article reviews 100 years of research on individual differences and their measurement, with a focus on research published in the Journal of Applied Psychology. We focus on 3 major individual differences domains: (a) knowledge, skill, and ability, including both the cognitive and physical domains; (b) personality, including integrity, emotional intelligence, stable motivational attributes (e.g., achievement motivation, core self-evaluations), and creativity; and (c) vocational interests. For each domain, we describe the evolution of the domain across the years and highlight major theoretical, empirical, and methodological developments, including relationships between individual differences and variables such as job performance, job satisfaction, and career development. We conclude by discussing future directions for individual differences research. Trends in the literature include a growing focus on substantive issues rather than on the measurement of individual differences, a differentiation between constructs and measurement methods, and the use of innovative ways of assessing individual differences, such as simulations, other-reports, and implicit measures. (PsycINFO Database Record
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10.1037/apl0000151
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pubmed_1_15843
|
Correction for 'Emerging approaches for the synthesis of triazoles: beyond metal-catalyzed and strain-promoted azide-alkyne cycloaddition' by Carolina G. S. Lima et al., Chem. Commun., 2015, 51, 10784-10796.
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10.1039/c5cc90314a
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pubmed_240_1050
|
ATR-X syndrome is a severe intellectual disability disorder caused by mutations in the ATRX gene. Many ancillary clinical features are attributed to CNS deficiencies, yet most patients have muscle hypotonia, delayed ambulation, or kyphosis, pointing to an underlying skeletal muscle defect. Here, we identified a cell-intrinsic requirement for Atrx in postnatal muscle growth and regeneration in mice. Mice with skeletal muscle-specific Atrx conditional knockout (Atrx cKO mice) were viable, but by 3 weeks of age presented hallmarks of underdeveloped musculature, including kyphosis, 20% reduction in body mass, and 34% reduction in muscle fiber caliber. Atrx cKO mice also demonstrated a marked regeneration deficit that was not due to fewer resident satellite cells or their inability to terminally differentiate. However, activation of Atrx-null satellite cells from isolated muscle fibers resulted in a 9-fold reduction in myoblast expansion, caused by delayed progression through mid to late S phase. While in S phase, Atrx colocalized specifically to late-replicating chromatin, and its loss resulted in rampant signs of genomic instability. These observations support a model in which Atrx maintains chromatin integrity during the rapid developmental growth of a tissue.
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pubmed_240_1050
|
pubmed_880_1065
|
This study is the first to investigate the antiproliferative effect of eupatilin in human endometrial cancer cells. Eupatilin, a naturally occurring flavonoid isolated from Artemisia princeps, has anti-inflammatory, anti-oxidative, and anti-tumor activities. In the present study, we investigated the potential effect of eupatilin on cell growth and its molecular mechanism of action in human endometrial cancer cells. Eupatilin was more potent than cisplatin in inhibiting cell viability in the human endometrial cancer cell lines Hec1A and KLE. Eupatilin showed relatively low cytotoxicity in normal human endometrial cells HES and HESC cells when compared to cisplatin. Eupatilin induced G2/M phase cell cycle arrest in a time- and dose-dependent manner, as indicated by flow cytometry analysis. In addition, treatment of Hec1A cells with eupatilin resulted in a significant increase in the expression of p21(WAF1/CIP1) and in the phosphorylation of Cdc25C and Cdc2. Knockdown of p21 using specific siRNAs significantly compromised eupatilin-induced cell growth inhibition. Interestingly, levels of mutant p53 in Hec1A cells decreased markedly upon treatment with eupatilin, and p53 siRNA significantly increased p21 expression. Moreover, eupatilin modulated the phosphorylation of protein kinases ERK1/2, Akt, ATM, and Chk2. These results suggest that eupatilin inhibits the growth of human endometrial cancer cells via G2/M phase cell cycle arrest through the up-regulation of p21 by the inhibition of mutant p53 and the activation of the ATM/Chk2/Cdc25C/Cdc2 checkpoint pathway.
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10.1016/j.fct.2011.04.019
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pubmed_389_7949
|
OBJECTIVE
Numerous studies have shown that stereotype threat (ST) reduces older people's cognitive performance, but few have studied its impact on clinical cognitive outcomes. Our study was designed to further examine the impact of ST on the clinical assessment of older subjects' cognitive functioning, as well as the moderating role of fear of Alzheimer's Disease (AD) (or 'dementia worry').
METHOD
Seventy-two neurologically normal (MMSE > 26) participants aged between 59 and 70 completed a set of neuropsychological tasks in either an ST or a positive condition (condition in which negative stereotypes were invalidated).
RESULTS
Regression-based path analyses showed that only participants who expressed moderate or high fear of AD underperformed on executive tasks in the ST condition compared to their counterparts in the positive condition. Moreover, in the ST condition, participants' performance on executive tasks was more impaired (relative to normative data) than in the positive condition. However, ST had no effect on memory and attention performance.
DISCUSSION
Our results showed that ST can cause older people to perform at pathological levels on executive tasks. Results highlight the need for clinicians to be cautious when conducting neuropsychological assessments of older people who express high levels of dementia worry.
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10.1080/13854046.2017.1307456
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pubmed_448_24163
|
BACKGROUND
Since the emergence of coronavirus disease 2019 (COVID-19), various clinical manifestations ranging from asymptomatic to severe, life-threatening courses have been presented. It is well known that COVID-19 patients are at an increased risk of pulmonary thromboembolism (PTE) development; however, the associated demographic, medical, and clinical factors for developing PTE remain unknown. The current study aimed to assess the characteristics of patients with PTE.
METHODS
This case-control study was derived from an ongoing population-based investigation of hospitalized patients with COVID-19 pneumonia. The case group included 99 patients with PTE confirmed by computed tomography pulmonary angiography (CTPA), and the controls (N=132) were age-matched patients selected from the PTE-suspected patients with a negative CTPA. The demographic, medical, and clinical characteristics of the study population were entered into the study checklist and compared. A logistic regression test was used to determine the factors associated with PTE development.
RESULTS
Among the 13,099 admitted patients, 690 (5.26%) were suspected of having PTE according to their clinical manifestations. CTPA was performed for suspected cases, and PTE was confirmed in 132 patients (19.13%). Logistic regression assessments revealed that male gender (OR, 2.39; 95%CI, 1.38‒4.13), decreased oxygen saturation (OR, 2.33; 95%CI, 1.27‒4.26), and lower hemoglobin (OR, 0.83, 0.95), and albumin (OR, 0.31; 95%CI, 0.18‒0.53) levels were associated with PTE development.
CONCLUSION
PTE was confirmed in one-fifth of suspected patients who underwent CTPA imaging. Male sex, decreased oxygen saturation, and lower levels of hemoglobin and albumin were independent predictors of PTE in patients with COVID-19 pneumonia.
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10.5045/br.2021.2021131
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pubmed_1098_23571
|
This paper presents the results of an eyetracking study that uses the Visual World Paradigm to determine whether heritage speakers of Polish can use grammatical gender cues to facilitate lexical retrieval of the subsequent noun during real time processing. Previous work has investigated this question for heritage speakers of Spanish with gender cues located on definite articles, which are highly frequent in Spanish; the results are therefore consistent both with a grammatical account, wherein heritage speakers access abstract syntactic gender features during processing, and a probabilistic account, wherein facilitation is due to transition probabilities between frequently co-occurring elements. In Polish, gender cues appear on adjectives, which are optional and infrequent. Results of the present study show that heritage speakers of Polish can use gender on inflected adjectives to fixate on the target noun faster in trials where that gender cue uniquely identifies the target noun. This finding supports a grammatical rather than probabilistic account of the facilitative use of grammatical gender in this population: heritage speakers are able to access abstract syntactic information in real time to aid word recognition in a target-like manner.
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10.3389/fpsyg.2022.960376
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pubmed_528_2044
|
Peritoneal carcinomatosis (PC) is commonly seen in colorectal cancer and is uniformly fatal. Cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIIC) is a new treatment in strictly selected patients with PC. CS includes peritonectomy procedures and resection of infiltrated viscera leaving no macroscopic tumor thicker than 2.5 mm behind. Peritoneal perfusion with mitomycin C at a temperature of 40 degrees -41 degrees C is performed at the end of surgery. The postoperative morbidity and mortality rates are 20%-30% and 4%-8% respectively. Median survival is 1-2 years and the 5-year survival is 19%.
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pubmed_528_2044
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pubmed_924_7832
|
Despite its high coding capacity, murine CMV (mCMV) does not encode functional enzymes for nucleotide biosynthesis. It thus depends on cellular enzymes, such as ribonucleotide reductase (RNR) and thymidylate synthase (TS), to be supplied with deoxynucleoside triphosphates (dNTPs) for its DNA replication. Viral transactivation of these cellular genes in quiescent cells of host tissues is therefore a parameter of viral fitness relevant to pathogenicity. Previous work has shown that the IE1, but not the IE3, protein of mCMV transactivates RNR and TS gene promoters and has revealed an in vivo attenuation of the mutant virus mCMV-DeltaIE1. It was attractive to propose the hypothesis that lack of transactivation by IE1 and a resulting deficiency in the supply of dNTPs are the reasons for growth attenuation. Here, we have tested this hypothesis with the mutant virus mCMV-IE1-Y165C expressing an IE1 protein that selectively fails to transactivate RNR and TS in quiescent cells upon transfection while maintaining the capacity to disperse repressive nuclear domains (ND10). Our results confirm in vivo attenuation of mCMV-DeltaIE1, as indicated by a longer doubling time in host organs, whereas mCMV-IE1-Y165C replicated like mCMV-WT and the revertant virus mCMV-IE1-C165Y. Notably, the mutant virus transactivated RNR and TS upon infection of quiescent cells, thus indicating that IE1 is not the only viral transactivator involved. We conclude that transactivation of cellular genes of dNTP biosynthesis is ensured by redundancy and that attenuation of mCMV-DeltaIE1 results from the loss of other critical functions of IE1, with its function in the dispersal of ND10 being a promising candidate.
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10.1128/JVI.00928-08
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pubmed_491_22217
|
Correction for 'Is there an intramolecular hydrogen bond in 2-halophenols? A theoretical and spectroscopic investigation' by Michael H. Abraham et al., Phys. Chem. Chem. Phys., 2015, DOI: 10.1039/c5cp04061b.
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10.1039/c5cp90167g
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pubmed_938_14132
|
We have investigated the functional ability of a choriocarcinoma-cell-derived factor to block human T cell responses and the factor's immunoregulatory site of action on the T cell signal transduction pathway. The factor completely suppressed human T cell responses activated by phorbol ester and calcium ionophore, reagents which strongly stimulate IL-2-mediated T cell responses. It failed to inhibit CD 25 expression and IL-2 production by T cell blasts in the T cell activation phase, but completely blocked recombinant IL-2-induced proliferation of T cell blasts in the T cell proliferation phase. Absorption experiments with the factor and Con A-induced T cell blasts as well as [125I]IL-2 binding experiments with T cell blasts revealed that the factor acted on the physiological events occurring after IL-2-mediated stimulation of IL-2 receptor complexes, demonstrating no interaction of the factor with either IL-2 molecules or IL-2 receptor complexes. Moreover, it suppressed murine IL-2 dependent T cell line proliferation, suggesting the presence of common pathways in human and murine T cell proliferation. The biological and immunological significance of the factor during pregnancy and in the immunosuppressed tumor-bearing hosts are discussed.
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10.1016/0165-0378(89)90010-7
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pubmed_828_11896
|
Asian rhinoplasty differs from traditional rhinoplasty approaches in preoperative analysis, patient expectations, nasal anatomy, and surgical techniques used. Platyrrhine nasal characteristics are common, with low dorsum, weak lower lateral cartilages, columellar retraction, and thick sebaceous skin often noted. Typically, patients seek augmentation of these existing structures rather than reductive procedures. Autologous cartilage, in particular use of costal cartilage, has been shown to be a reliable technique, which, when executed properly, produces excellent long-term results. An understanding of cultural perspectives, knowledge of the nasal anatomy unique to Asian patients, and proficiency with augmentation techniques are prerequisites in attaining the desired results for patient and surgeon.
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10.1016/j.cps.2009.12.008
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pubmed_541_16001
|
Epstein-Barr virus (EBV)-encoded oncogene latent membrane protein (LMP) 1, which is consistently expressed in multiple EBV-associated malignancies, has been proposed as a potential target antigen for any future vaccine designed to control these malignancies. However, the high degree of genetic variation in the LMP1 sequence has been considered a major impediment for its use as a potential immunotherapeutic target for the treatment of EBV-associated malignancies. In the present study, we have employed a highly efficient strategy, based on ex vivo functional assays, to conduct an extensive sequence-wide analysis of LMP1-specific T-cell responses in a large panel of healthy virus carriers of diverse ethnic origin and nasopharyngeal carcinoma patients. By comparing the frequencies of T cells specific for overlapping peptides spanning LMP1, we mapped a number of novel HLA class I- and class II-restricted LMP1 T-cell epitopes, including an epitope with dual HLA class I restriction. More importantly, extensive sequence analysis of LMP1 revealed that the majority of the T-cell epitopes were highly conserved in EBV isolates from Caucasian, Papua New Guinean, African, and Southeast Asian populations, while unique geographically constrained genetic variation was observed within one HLA A2 supertype-restricted epitope. These findings indicate that conserved LMP1 epitopes should be considered in designing epitope-based immunotherapeutic strategies against EBV-associated malignancies in different ethnic populations.
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10.1128/jvi.77.13.7401-7410.2003
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pubmed_538_8572
|
BACKGROUND
The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions.
DESCRIPTION
CoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria.
CONCLUSION
CoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation.
|
10.1186/1471-2164-7-24
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pubmed_783_1284
|
Candida guilliermondii is an ascomycetous yeast widely studied due to its clinical importance, biotechnological interest, and biological control potential. During a series of preliminary experiments aiming at optimizing the electroporation procedure of C. guilliermondii cells, we observed that the efficiency of transformation of an ura5 recipient strain with the corresponding dominant marker URA5 was more than a thousand fold higher as compared with the transformation of an ura3 strain with the URA3 wild type allele. This result allowed the identification of an autonomously replicating sequence (ARS) within an A/T rich region located upstream of the URA5 open reading frame (ORF). Interestingly, linear double strand DNAs (dsDNAs) containing this putative ARS are circularized and then autonomously replicated in C. guilliermondii transformed cells. We demonstrated that the C. guilliermondii Lig4p ligase, involved in the canonical non-homologous end-joining (NHEJ) pathway, was responsible for this phenomenon since a lig4 mutant was unable to circularize and to autonomously maintain transforming dsDNAs containing the putative ARS. Finally, a functional dissection of the C. guilliermondii A/T rich region located upstream of the URA5 ORF revealed the presence of a 60 bp-length sequence essential and sufficient to confer ARS properties to shuttle plasmid and linear dsDNAs.
|
pubmed_783_1284
|
pubmed_804_5859
|
Reported findings on reactivity to stress of the sympathetic-adreno-medullar (SAM) and hypothalamic-pituitary-adrenal (HPA) systems in panic disorder (PD) are very variable. This inconsistency may be explained by differences in treatment exposure, illness duration and emotion regulation strategies. The present study examined the reactivity to mental stress of the SAM and HPA axes in a sample of first episode, drug naïve patients with PD which avoids confounds of medications exposure and illness chronicity. Activation of the SAM axis was evaluated by dosage of salivary alpha-amylase (sAA) and heart rate. Activation of the HPA axis was tested by dosage of salivary cortisol. Psychological assessments were done by the Self-Rating Depression Scale, the Self-Rating Anxiety Scale, the State-Trait Anxiety Inventory, the Cope Orientation to Problems Experienced (COPE) Inventory and the 16 Personality Factor Questionnaire (16PF). Patients showed reduced sAA stress reactivity, higher baseline cortisol levels and a more rapid decrease in stress cortisol levels as compared with controls. A significant correlation was found between active coping strategies and cortisol levels (response to stress). The findings suggest that blunted SAM stress reactivity and a rapid decrease in stress cortisol levels reflect traits that may enhance vulnerability to psychopathology in patients with PD.
|
10.1016/j.neures.2018.03.003
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pubmed_1133_15743
|
Iron hollow sphere filled aluminum matrix syntactic foams (AMSFs) were produced by low pressure, inert gas assisted infiltration. The microstructure of the produced AMSFs was investigated by light and electron microscopy, extended by energy dispersive X-ray spectroscopy and electron back-scattered diffraction. The investigations revealed almost perfect infiltration and a slight gradient in the grain size of the matrix. A very thin interface layer that ensures good bonding between the hollow spheres and the matrix was also observed. Compression tests were performed on cylindrical specimens to explore the characteristic mechanical properties of the AMSFs. Compared to other (conventional) metallic foams, the investigated AMSFs proved to have outstanding mechanical properties (yield strength, plateau strength, etc.) and energy absorbing capability.
|
10.3390/ma8115432
|
pubmed_1066_22867
|
BACKGROUND
Sedation for lumbar punctures (LPs) in pediatric acute lymphoblastic leukemia (ALL) patients has been the standard for decades to reduce pain and anxiety. Recent studies on the potential long-term neurocognitive effects of cumulative propofol exposure have raised concerns about this practice. The recent pandemic introduced additional burdens to patients, with the requirement of a negative COVID-19 test prior to each sedated procedure.
PROCEDURE
These factors prompted a quality improvement intervention at our institution where we aimed to reduce postinduction sedated LPs by 50%. Our intervention included patient and family education, followed by a simulation of the procedure for selected patients. Those converted to unsedated LPs were queried for their preference. Comparative cost, clinical time, and LP success rates were collected for sedated and unsedated LPs.
RESULTS
Following the intervention, the percentage of LPs performed with sedation dropped from 100% to 48%. All LPs were successful using both techniques. Most patients who experienced the unsedated LP technique, and their guardians, strongly preferred this approach. Unsedated LPs significantly reduced clinical time (169 vs. 83 minutes) for families, decreased expenditures ($5736 reduction per procedure), and improved institutional opportunity cost due to a decrease in last-minute cancelations.
CONCLUSION
We have shown that it is feasible to significantly reduce the use of sedation for LPs in patients with ALL, which has the potential to improve health and patient experience at a lower cost.
|
10.1002/pbc.29272
|
pubmed_1034_5962
|
Lipids are highly diverse metabolites of pronounced importance in health and disease. While metabolomics is a broad field under the omics umbrella that may also relate to lipids, lipidomics is an emerging field which specializes in the identification, quantification and functional interpretation of complex lipidomes. Today, it is possible to identify and distinguish lipids in a high-resolution, high-throughput manner and simultaneously with a lot of structural detail. However, doing so may produce thousands of mass spectra in a single experiment which has created a high demand for specialized computational support to analyze these spectral libraries. The computational biology and bioinformatics community has so far established methodology in genomics, transcriptomics and proteomics but there are many (combinatorial) challenges when it comes to structural diversity of lipids and their identification, quantification and interpretation. This review gives an overview and outlook on lipidomics research and illustrates ongoing computational and bioinformatics efforts. These efforts are important and necessary steps to advance the lipidomics field alongside analytic, biochemistry, biomedical and biology communities and to close the gap in available computational methodology between lipidomics and other omics sub-branches.
|
10.2390/biecoll-jib-2016-299
|
pubmed_262_17678
|
This article presents the third in a series of three interviews that P&T conducted with several members of the American Society of Health-System Pharmacists (ASHP) Expert Panel on Formulary Management.In 2008, ASHP convened this panel of experts to develop revised guidelines for P&T committee and formulary management to replace the previous guidance issued in 1991.1 These revised guidelines include recommendations concerning the review and evaluation of drugs for formulary inclusion, pharmacoeconomic assessments, therapeutic interchange, medication-use evaluations (MUEs), management of drug shortages, and many other important topics.In this series, ASHP experts discuss P&T committee and formulary management guidelines in their respective institutions as well as other observations and insights. In Part 3, the author interviews Sabrina Cole, PharmD, Clinical Specialist, Drug Information, at the Grady Health System in Atlanta, Georgia.
|
pubmed_262_17678
|
pubmed_132_15385
|
Retooling RNA: RNA aptamers are high-affinity ligands that can be assembled with other structures to yield multivalent molecules. These properties have been addressed in two recent studies: One describes a GFP-like RNA reporter used to study the dynamics of endogenous RNA; the other study reports on an aptamer-templated assembly of multi-enzyme complexes in bacteria for the controlled production of secondary molecules (see picture).
|
10.1002/anie.201106636
|
pubmed_1088_3932
|
Although paracrine effects of mesenchymal stem cells (MSCs) have been suggested previously, cardioprotection by human MSC secretions has never been demonstrated. Human MSC-conditioned medium (CM) was collected by following a clinically compliant protocol. In a porcine model of ischemia and reperfusion injury, intravenous and intracoronary MSC-CM treatment significantly reduced myocardial nuclear oxidative stress as determined by immunostaining for 8-hydroxy-2'-deoxyguanosine. In addition, expression levels of phospho-SMAD2 and active caspase 3 were diminished following CM treatment, suggesting that TGF-beta signaling and apoptosis were reduced. This was associated with a 60% reduction in infarct size and marked improvement of systolic and diastolic cardiac performance as assessed with echocardiography and pressure volume loops. Fractionation studies revealed that only the fraction of the CM containing products >1000 kDa (100-220 nm) provided cardioprotection in a mouse model of ischemia and reperfusion injury. This indicates that the responsible paracrine factor of human MSCs is likely a large complex rather than a single small molecule. These data identify human MSC-CM as a promising therapeutic option to reduce myocardial infarct size in patients with acute MI and suggest that the use of stem cell secretions could extend the applicability of stem cells for therapeutic purposes.
|
10.1016/j.scr.2008.02.002
|
pubmed_334_4137
|
OBJECTIVE
Reduced tensile strength of the human fetal membranes overlying the cervix has previously been identified. We used transcervical application of Bonney's blue dye, before the onset of term labor to identify the supracervical membranes for analysis after elective cesarean section delivery. We hypothesized that pro- and antiapoptotic proteins, which are representative of both the extrinsic and intrinsic pathways, would be expressed differentially in the supracervical membranes compared with membranes taken from distal sites. Membrane apoptosis would provide a mechanism for the reduced tensile strength that presumably precedes spontaneous intrapartum rupture of the membranes.
STUDY DESIGN
Bonney's blue dye was applied transcervically to the chorion-facing fetal membrane before elective cesarean delivery at term. After delivery, samples of fetal membranes were obtained from the supracervical site, where the membrane was marked by the dye (approximately 8-cm diameter) and compared with samples from a distal site (2-cm from the placental edge). Samples from the supracervical and distal sites were fixed and paraffin embedded for immunohistochemical analyses and histologic review and stored at -80 degrees C for Western blotting analysis.
RESULTS
The supracervical area of fetal membranes exhibited increased markers of apoptosis that included M30 immunohistochemical staining, cleaved-caspase-3, cleaved-caspase-9, and decreased immunoreactive Bcl-2. Histologic sections that were stained with hematoxylin and eosin demonstrated features of degenerative changes and apoptosis that occurred predominantly at the supracervical site.
CONCLUSION
There is evidence of increased cellular apoptosis at the supracervical site in fetal membranes at term. Both morphologic and biochemical changes that were observed at the supracervical site suggest that the intrinsic apoptotic pathway plays an important role in spontaneous membrane rupture at term.
|
10.1016/j.ajog.2007.01.021
|
pubmed_623_9706
|
BACKGROUND
Periodontitis is one of the most common oral diseases associated with the host's immune response against periodontopathogenic infection. Failure to accurately diagnose the stage of periodontitis has limited the ability to predict disease status. Therefore, we aimed to look for reliable diagnostic markers for detection or differentiation of early stage periodontitis using the immunoprotemic approach.
METHOD
In the present study, patient serum samples from four distinct stages of periodontitis (i.e., mild chronic, moderate chronic, severe chronic, and aggressive) and healthy controls were subjected to two-dimensional gel electrophoresis (2-DE), followed by silver staining. Notably, we consistently identified 14 protein clusters in the sera of patients and normal controls.
RESULTS
Overall, we found that protein levels were comparable between patients and controls, with the exception of the clusters corresponding to A1AT, HP, IGKC and KNG1 (p < 0.05). In addition, the immunogenicity of these proteins was analysed via immunoblotting, which revealed differential profiles for periodontal disease and controls. For this reason, IgM obtained from severe chronic periodontitis (CP) sera could be employed as a suitable autoantibody for the detection of periodontitis.
DISCUSSION
Taken together, the present study suggests that differentially expressed host immune response proteins could be used as potential biomarkers for screening periodontitis. Future studies exploring the diagnostic potential of such factors are warranted.
|
10.7717/peerj.2327
|
pubmed_821_13404
|
Mutations in the beta-cell genes encoding the glycolytic enzyme glucokinase (GCK) and the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the most common causes of maturity-onset diabetes of the young (MODY). Studying patients with mutations in these genes gives insights into the functions of these two critical beta-cell genes in humans. We studied 178 U.K. and French MODY family members, including 45 GCK mutation carriers and 40 HNF-1alpha mutation carriers. Homeostasis model assessment of fasting insulin and glucose showed reduced beta-cell function in both GCK (48% controls, P<0.0001) and HNF-1alpha (42% controls, P<0.0001). Insulin sensitivity was similar to that of control subjects in the GCK subjects (93% controls, P = 0.78) but increased in the HNF-1alpha subjects (134.5% controls, P = 0.005). The GCK patients showed a similar phenotype between and within families with mild lifelong fasting hyperglycemia (fasting plasma glucose [FPG] 5.5-9.2 mmol/l, interquartile [IQ] range 6.6-7.4), which declined slightly with age (0.017 mmol/l per year) and rarely required pharmacological treatment (17% oral hypoglycemic agents, 4% insulin). HNF-1alpha patients showed far greater variation in fasting glucose both between and within families (FPG 4.1-18.5 mmol/l, IQ range 5.45-10.4), with a marked deterioration with age (0.06 mmol/l per year), and 59% of patients required treatment with tablets or insulin. Proinsulin-to-insulin ratios are increased in HNF-1alpha subjects (29.5%) but not in GCK (18.5%) subjects. In an oral glucose tolerance test, the 0- to 120-min glucose increment was small in GCK patients (2.4+/-1.8 mmol/l) but large in HNF-1alpha patients (8.5+/-3.0 mmol/l, P< 0.0001). This comparison shows that the clear clinical differences in these two genetic subgroups of diabetes reflect the quantitative and qualitative differences in beta-cell dysfunction. The defect in GCK is a stable defect of glucose sensing, whereas the HNF-1alpha mutation causes a progressive defect that alters beta-cell insulin secretion directly rather than the sensing of glucose.
|
10.2337/diabetes.50.2007.s101
|
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