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pubmed_298_3576 | Seeds are concentrated sources of protein and thus may be ideal 'bioreactors' for the production of heterologous proteins. For this application, strong seed-specific expression signals are required. A set of expression cassettes were designed using 5' and 3' regulatory sequences of the seed storage protein gene arcelin 5-I (arc5-I) from Phaseolus vulgaris, and evaluated for the production of heterologous proteins in dicotyledonous plant species. A murine single-chain variable fragment (scFv) was chosen as model protein because of the current industrial interest to produce antibodies and derived fragments in crops. Because the highest scFv accumulation in seed had previously been achieved in the endoplasmic reticulum (ER), the scFv-encoding sequence was provided with signal sequences for accumulation in the ER. Transgenic Arabidopsis seed stocks, expressing the scFv under control of the 35S promoter, contained scFv accumulation levels in the range of 1% of total soluble protein (TSP). However, the seed storage promoter constructs boosted the scFv to exceptionally high levels. Maximum scFv levels were obtained in homozygous seed stocks, being 12.5% of TSP under control of the arc5-I regulatory sequences and even up to 36.5% of TSP upon replacing the arc5-I promoter by the beta-phaseolin promoter of Phaseolus vulgaris. Even at such very high levels, the scFv proteins retain their full antigen-binding activity. Moreover, the presence of very high scFv levels has only minory effects on seed germination and no effect on seed production. These results demonstrate that the expression levels of arcelin 5-I and beta-phaseolin seed storage protein genes can be transferred to heterologous proteins, giving exceptionally high levels of heterologous proteins, which can be of great value for the molecular farming industry by raising production yield and lowering bio-mass production and purification costs. Finally, the feasibility of heterologous protein production using the arcelin 5-I construct was demonstrated in the legume Phaseolus acutifolius, an interesting and promising crop for large-scale production. | pubmed_298_3576 |
pubmed_531_19075 | The bone marrow is commonly present in the medullary cavity of long bones in most mammals at birth. In the present study, the persistence of the osseous tissue was examined in the medullary cavities of piglet bones at and after birth. Immediately after birth, medullary cavities of long bones were almost completely filled with the spongy bone. The persisted spongy bone, i.e., medullary bone was prominent in younger pigs but decreased with advance in age. By 90 days of age, the medullary bone almost disappeared to form the extended medullary cavity. During the disappearing process of the medullary bone, osteoclasts showed significant increase in size and number (p less than 0.05). In irregular and flat bones, osseous trabeculae of the medullary bone became slender with age. The extramedullary hematopoiesis in the liver and spleen was very active till 30 days of age. This may suggest that the persistence of the medullary bone narrows the medullary cavity to cause poor medullary hematopoiesis and is compensated by extramedullary hematopoiesis. The relationship among the medullary bone, extramedullary hematopoiesis and piglet anemia was discussed. | 10.1292/jvms.53.1009 |
pubmed_242_16020 | A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist GYKI 52466 on apoptosis of retinal ganglion cells following nerve injury. Hematoxylin-eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that retinal ganglion cells gradually decreased with increasing time of optic nerve injury, while GYKI 52466 could inhibit this process. The results demonstrate that following acute optic nerve injury, apoptosis of retinal ganglion cells is a programmed process, which can be inhibited by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. | 10.3969/j.issn.1673-5374.2012.10.002 |
pubmed_211_7610 | PURPOSE
Forty percent of cases of retinoblastoma, a childhood malignancy of the retina, are linked to the inheritance of a mutant allele of the retinoblastoma susceptibility gene Rb1. Tumor penetrance varies among carriers in different family pedigrees, indicating that other genetic factors may modify risk for occurrence of retinoblastoma. This study was undertaken to determine whether multiple genetic loci modify the risk for retinoblastoma in mice.
METHODS
A line of alphaAcry-HPV16E6/E7 transgenic mice expressing the human papillomavirus type 16 E6 and E7 oncogenes (HPV-16 E6 and E7) ectopically in the retina was characterized. E6 and E7 proteins bind to and inactivate the cellular tumor suppressor proteins p53 and Rb, respectively.
RESULTS
Retinoblastomas developed rarely when the alphaAcry-HPV16E6/E7 transgene was maintained on the FVB background, but tumors arose with high frequency on C57BL/6 X FVB and C3H x FVB F1 hybrid backgrounds. The incidence of retinoblastoma in the LHbeta-TAG transgenic mice, which express simian virus 40 large tumor antigen (SV40 T-ag), was also influenced by the FVB and C57BL/6 backgrounds. Resistance of the alphaAcry-HPV16E6/E7 FVB mice to retinoblastoma mapped in part to the retinal degeneration (rd) locus. However, multiple genetic experiments indicate that resistance to retinoblastoma depends on additional loci in FVB mice.
CONCLUSIONS
Multiple cellular genes can modify risk for retinoblastoma in mice. | pubmed_211_7610 |
pubmed_314_19206 | Experimental results have clearly demonstrated that the newly proposed optical contact screen pulse-width modulation image subtraction technique can be used for the evaluation both qualitative and quantitative of the subtle differences between two similar images. | 10.1364/AO.20.004234 |
pubmed_1053_17597 | The authors determined the effect of propofol on cerebral blood flow, intracranial pressure, and cerebral arteriovenous oxygen content difference in severely brain-injured patients during orthopedic treatment of fractures of the extremities. The Glasgow Coma Scale score was 6 or 7 at the time of the study. Data were collected in the operating room before and during (5 and 15 min) administration of propofol (2 mg/kg iv bolus immediately followed by a 150 micrograms.kg-1.min-1 infusion) before surgical stimulation. Propofol was infused during 41.4 +/- 7.3 min. After operation, the last set of measurements was made 15 min after propofol was stopped. The study was performed on 10 adults (age range, 15-40 yr) whose lungs were mechanically ventilated (air/O2) and who were sedated (phenoperidine, 1 mg/h), and was conducted using a radial artery cannula; a 7.5-Fr, thermodilution, flow-directed, pulmonary artery catheter; an intraventricular catheter; and a catheter in the jugular venous bulb. The 133xenon intra-internal carotid artery injection technique was used to determine regional cerebral blood flow (rCBF). Anesthetic blood concentration of propofol (3-5 micrograms/ml) was associated with decreases in cerebral perfusion pressure (CPP; from 82 +/- 14 to 59 +/- 7 mmHg; P less than 0.001), rCBF (from 35 +/- 6 to 26 +/- 5 ml.100 g-1.min-1; P less than 0.001), and intracranial pressure (ICP; from 11.3 +/- 2.6 to 9.2 +/- 2.5 mmHg; P less than 0.001). Cerebrovascular resistance and cerebral arteriovenous oxygen content difference were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1097/00000542-199009000-00007 |
pubmed_2_24595 | The term myofascia is referred to the skeleton of muscle fibres organized as an interconnected 3D network that surrounds and connects the musculoskeletal system. Extracellular matrix muscle is relevant in tissue structural support and transmission of mechanical signals between fibres and tendons. Acute and chronic musculoskeletal injuries (muscle strain) are one of the major problems faced by those who practice any type of sport, regardless of whether they are professionals or amateurs. Therapeutic boarding is of uncertain value in most cases because there are many contributing factors such as type, severity, functional implication of the damaged tissue, progression or risk of relapse. Different studies suggest that the musculoskeletal cell matrix is essential for the development, maintenance and regeneration of skeletal muscle. In this article, we highlight the action of "non-contractile" structures, in particular the myofascial system or muscle fascia, which can be responsible for the pathophysiology and healing process of muscular injuries. Manual therapy plays a predominant role in the treatment of these types of injuries and is key in the process of obtaining a scar capable of transmitting mechanical information. The scientific basis of this process is described in this article. Through real-time sonoelastography we have accurate information regarding the current stage of the repair process and, thus, guide our treatment at all times. Some new concepts are introduced, including local elasticity, the relationship between fascial pretension and the different stages of the physiological myofascia repair process, scar modelling technique, and sonoelastographic evolution control. | pubmed_2_24595 |
pubmed_588_8883 | Genomic DNAs of lambda phage (48.5 kbp) and E. coli (4.6 Mbp) were successfully cleaved at the target site by artificial restriction DNA cutter (ARCUT), which we recently developed by combining Ce(IV)/EDTA and PNA (peptide nucleic acid). PNA satisfactorily invaded the target site in such huge DNAs and activate there for Ce(IV)/EDTA-induced scission. | 10.1093/nass/nrl132 |
pubmed_223_15126 | Tubulin-based nanotubes (TNTs) to deliver microtubule-targeting agents (MTAs) for clinical oncology are reported. Three MTAs, docetaxel (DTX), laulimalide (LMD), and monomethyl auristatin E (MMAE), which attach to different binding sites in a tubulin, are loaded onto TNTs and cause structural changes in them, including shape anisotropy and tubulin layering. This drug-driven carrier transformation leads to changes in the drug-loading efficiency and stability characteristics of the carrier. TNTs coloaded with DTX and LMD efficiently deliver dual drug cargoes to cellular tubulins by the endolysosomal pathway, and results in synergistic anticancer and antiangiogenic action of the drugs in vitro. In in vivo tests, TNTs loaded with a microtubule-destabilizing agent MMAE suppress the growth of tumors with much higher efficacy than free MMAE did. This work suggests a new concept of using a drug's target protein as a carrier. The findings demonstrate that the TNTs developed here can be used universally as a delivery platform for many MTAs. | 10.1002/adma.202002902 |
pubmed_471_12746 | In this study, paraffin/red mud phase change energy storage composites were fabricated at 4 mix proportions with paraffin to red mud ratios of 0.4:0.6, 0.45:0.55, 0.5:0.5, and 0.55:0.45 by a mixed mill-heating method. Scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR) results reveal that paraffin flows well into red mud pores and has good compatibility. The differential scanning calorimetry (DSC) results reveal that the melting temperatures of the paraffin/red mud phase change energy storage composite vary from 75℃ to 85℃, and the latent heat value is approximately 25-40J/g. High thermal stability is observed by the thermogravimetric analysis (TG) method. The Brunauer Emmett Teller (BET) isotherms, laser particle sizer, X-ray diffraction analysis (XRD), and laser Raman spectrograph (LRS) show that the phase change energy storage composite does not produce a new material from the raw materials and that the material has a stable performance. Furthermore, the paraffin/red mud phase change energy storage composite was incorporated into the cement-based and gypsum-based materials at 10%, 20%, and 30% weight. The heat storage performance can be improved remarkably with an increase in the addition of phase change energy storage composite replacement. The compressive strength change is minimal with the addition of 10% and 20%, and the compressive strength decreases by nearly 40% with the addition of 30%. The paraffin/red mud phase change energy storage composite has a large influence on the flexural strength. | 10.1016/j.jhazmat.2018.10.061 |
pubmed_262_20155 | A bacterial collection (n=249) obtained in Hong Kong from 2002 to 2004 was used to investigate the molecular epidemiology of aminoglycoside resistance among Escherichia coli isolates from humans and food-producing animals. Of these, 89 isolates were gentamicin-sensitive (human n=60, animal n=29) and 160 isolates were gentamicin-resistant (human n=107, animal n=53). Overall, 84.1% (90/107) and 75.5% (40/53) of the gentamicin-resistant isolates from human and animal sources, respectively, were found to possess the aacC2 gene. The aacC2 gene for 20 isolates (10 each for human and animal isolates) was sequenced. Two alleles were found that were equally distributed in human and animal isolates. PFGE showed that the gentamicin-resistant isolates exhibited diverse patterns with little clonality. In some isolates, the aacC2 gene was encoded on large transferable plasmids of multiple incompatibility groups (IncF, IncI1 and IncN). An IncFII plasmid of 140 kb in size was shared by one human and three animal isolates. In summary, this study showed that human and animal isolates share the same pool of resistance genes. | 10.1099/jmm.0.015032-0 |
pubmed_587_4233 | Survivin is unique for its expression in human malignancies but not in normal adult cells. It has been implicated in sensitisation to chemotherapy and as a prognostic marker in several common cancers. Immunohistochemistry for Survivin, P53 and BCL-2 expression as well as cell proliferative index (Ki-67) and apoptosis index (TUNEL) was conducted on 52 pancreatic and 12 ampullary adenocarcinomas. Survivin was detected in the cytoplasm of carcinoma cells in 46 (88%) of pancreatic tumours. P53 and BCL-2 were detected in 54% and 12% of pancreatic tumours, respectively. Proliferative index was 26.2+/-10.5% and apoptosis index was 1.38+/-0.69%. Prevalence of Survivin expression was significantly higher in P53-positive than in P53-negative cases (P=0.05) but was not associated with BCL-2 expression. Incrementally higher weighted scores of Survivin expression were associated with increased proliferative index (P=0.001). Furthermore, there was linear correlation between increased proliferative index and higher apoptosis index (P<0.001). Surprisingly, higher scores of Survivin expression were associated with increased apoptosis index (P=0.007). Survival characteristics were not influenced by Survivin, P53 or BCL-2 expression, apoptosis index or proliferative index. Ampullary carcinoma showed Survivin expression in 83% of cases. However, unlike pancreatic carcinoma, there was no correlation between Survivin and P53 expression or proliferative index. In conclusion, Survivin is expressed in the majority of pancreatic adenocarcinomas and correlates with both cellular proliferation and apoptosis. Molecular manipulation of Survivin expression may enhance chemotherapy and radiation therapy for pancreatic cancer. | 10.1038/sj.bjc.6600133 |
pubmed_936_2847 | Network polymers of sulfur and poly(4-allyloxystyrene), PAOS (x = percent by mass sulfur, where x is varied from 10-99), were prepared by reaction between poly(4-allyloxystyrene) with thermal homolytic ring-opened S8 in a thiol-ene-type reaction. The extent to which sulfur content and crosslinking influence thermal/mechanical properties was assessed. Network materials having sulfur content below 50% were found to be thermosets, whereas those having >90% sulfur content are thermally healable and remeltable. DSC analysis revealed that low sulfur-content materials exhibited neither a T g nor a T m from -50 to 140 °C, whereas higher sulfur content materials featured T g or T m values that scale with the amount of sulfur. DSC data also revealed that sulfur-rich domains of PAOS90 are comprised of sulfur-crosslinked organic polymers and amorphous sulfur, whereas, sulfur-rich domains in PAOS99 are comprised largely of α-sulfur (orthorhombic sulfur). These conclusions are further corroborated by CS2-extraction and analysis of extractable/non-extractable fractions. Calculations based on TGA, FT-IR, H2S trapping experiments, CS2-extractable mass, and elemental combustion microanalysis data were used to assess the relative percentages of free and crosslinked sulfur and average number of S atoms per crosslink. Dynamic mechanical analyses indicate high storage moduli for PAOS90 and PAOS99 (on the order of 3 and 6 GPa at -37 °C, respectively), with a mechanical T g between -17 °C and 5 °C. A PAOS99 sample retains its full initial mechanical strength after at least 12 pulverization-thermal healing cycles, making it a candidate for facile repair and recyclability. | 10.1039/c8ra06847j |
others_79_3353 | Anopheles minimus Theobald 1901 and An. harrisoni Harbach & Manguin 2007 belong to the same species complex. They are morphologically similar and can exist in sympatry but have blood host preferences. The most accurate method for their identification is based on molecular techniques. Here, we measure the level of interspecific discrimination by geometric morphometry. Sixty-seven An. minimus and 22 An. harrisoni specimens were selected based on their morphological integrity and confirmed by identification polymerase chain reaction of internal transcribed spacer 2. These samples were used as reference data allowing for a morphometric identification based on geometric shape. Despite size overlap between the two species, there was a significant shape divergence allowing for differentiation of An. minimus and An. harrisoni with 90% accuracy. An intraspecific study of An. minimus showed a summer period associated to the reducing of wing size, which did not influence the shape-based differentiation of An. harrisoni. Wing venation geometry can be used to distinguish between these cryptic species mainly based on shaped divergence. This study suggests that geometric morphometrics represent a convenient low-cost method to complement morphological identification, especially concerning damaged specimens, i.e., insects having accidentally lost the anatomical features allowing a reliable morphological identification. © 2020 The Authors. Medical and Veterinary Entomology published by John Wiley & Sons Ltd on behalf of The Royal Entomological Society | 10.1111/mve.12493 |
pubmed_454_9457 | The determination of antigliadin antibodies from human serum samples is of vital importance for the diagnosis of an autoimmune disease such as celiac disease. An electrochemical immunosensor that mimics traditional ELISA type architecture has been constructed for the detection of antigliadin antibodies with control over the orientation and packing of gliadin antigen molecules on the surface of gold electrodes. The orientation of the antigen on the surface has been achieved using a carboxylic-ended bipodal alkanethiol that is covalently linked with amino groups of the antigen protein. The bipodal thiol presents a long poly(ethyleneglycol)-modified chain that acts as an excellent non-specific adsorption barrier. The bipodal nature of the thiol ensured a good spacing and hence good diffusion properties of electroactive species through the self-assembled monolayer, which is vital for the efficiency of the constructed electrochemical immunosensor. The electrochemical immunosensor was characterized using surface plasmon resonance as well as electrochemical impedance spectroscopy. Amperometric evaluation of the sensor with polyclonal antigliadin antibodies showed stable and reproducible low limits of detection (46 ng/mL; % RSD = 8.2, n = 5). The behaviour and performance of the electrochemical immunosensor with more complex matrixes such as reference serum solutions and real patient samples was evaluated and compared with commercial ELISA kits demonstrating an excellent degree of correlation in thirty minutes total assay time; the electrochemical immunosensor not only delivers a positive or negative result, it allows the estimation of semi-quantitative antibody contents based on the comparison against clinical reference solutions. | 10.1016/j.bios.2011.05.004 |
pubmed_617_5545 | BACKGROUND
The mammalian target of rapamycin (mTOR) pathway plays an important role in the regulation of cell growth and increasing evidence suggests its dysregulation in tumors. It also implements many other critical cellular functions, including protein degradation and angiogenesis. To date, a correlation between the mTOR pathway in human glioma and patients' prognosis has not been reported.
METHODS
To address this question, we carried out an immunohistochemical study of the mTOR upstream and downstream targets phosphorylated Akt (pAkt), phosphorylated S6 ribosomal protein (pS6), and p27, as well as phosphatase and tensin homologue (PTEN) using biopsies from 96 patients with primary glioma. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients.
RESULTS
Immunostaining revealed that the mTOR pathway was significantly associated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grade of patients with glioma. Especially, the positive expression rates of pAkt, cytoplasmic p27, and pS6 were significantly higher in patients with higher grade (P = 0.002, 0.001 and 0.002) and lower KPS score (P = 0.007, 0.005, and 0.008), which were opposite to the nuclear p27 and PENT expression. Statistical analysis showed that patients with glioma expressing pAkt, PTEN, cytoplasmic p27, nuclear p27, and pS6 have different overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.02), WHO grade (P = 0.005), pAkt (P = 0.009), PTEN (P = 0.006), cytoplasm p27 (P = 0.008), nuclear p27 (P = 0.01), and pS6 (P = 0.003) were independent prognosis factors for human glioma.
CONCLUSION
These results provide convincing evidence for the first time that the mTOR pathway correlated closely with overall survival of patients with glioma and might be a novel prognostic marker. | 10.1016/j.jss.2009.06.025 |
pubmed_686_18245 | STUDY DESIGN
Retrospective, case series.
DESIGN
A review of 10 surgical cases with symptoms of cervical angina.
OBJECTIVE
To stress the importance of symptoms of cervical angina in patients with cervical spine disorders.
SETTING
Fukui University Hospital, Japan.
RESULTS
A total of 10 patients complaining of symptoms of cervical angina were admitted with a tentative diagnosis of coronary artery disease. Pain relief was achieved by anterior surgical decompression in all patients.
CONCLUSION
We stress that physicians should be aware of the symptoms of cervical angina and that surgical intervention often leads to complete relief of symptoms. | 10.1038/sj.sc.3101888 |
pubmed_449_2039 | [3H]-spiperone binding on human lymphocytes did not reveal the occurrence of dopamine receptors. However, lower values were observed in Parkinsonism and the displaceable binding was increased after levodopa treatment although this was not specific only for levodopa and, furthermore, was not correlated with the clinical symptomatology. This non-specific binding in lymphocytes corresponds to trapping, presumably in lysosomes and thus does not reflect the dopaminergic receptors state in Parkinson's disease. | 10.1136/jnnp.46.12.1146 |
pubmed_282_7935 | We report electrochemical detection of single-catalase collisions at diamond ultramicroelectrodes and show the operative mechanism involves direct enzyme-mediated charge transfer between electrode and solution. Hydrogen peroxide increases the collision frequency, which fluorescence correlation spectroscopy diffusion measurements suggest stems from an increase in the diffusion rate as the underlying cause. | 10.1039/c7cc04085g |
pubmed_742_19711 | There are still some secrets left to this well-studied reaction. Previously unreported relationships discovered are as follows. The ordering of reactivities of C6H5X is the same as that of enthalpies of hydrogenation of the ring to the correspondingly substituted cyclohexane. The orientation of substitution (meta or ortho/para) is controlled by the dipole direction of the ipso-C-X bond, like an ON/OFF switch. The difference between the halogens and other deactivating groups is that the bond between the atom bonded to the ipso carbon has the positive end of the dipole on the ipso carbon for the halogens (C(δ+)-X(δ-)) but in the opposite direction (C(δ-)-X(δ+)) for other deactivating groups. This reverses the directing effect. For all X, including the halogens, ipso-C(δ+)-X(δ-) results in ortho/para substitution. p-(13)C NMR shifts of C6H5X greater than that of benzene predict meta substitution. A linear relationship exists between p-(13)C NMR shift and ΔHhyd, except for X = halogen. With halobenzenes, the ortho/para ratios of the products are linearly related to the ipso/ortho ratios of the (13)C shifts of C6H5X for chlorinations, brominations, nitrations, and protonations. The relative reactivities of the halobenzenes are linearly related to the p-(13)C NMR shifts. The electronegativities of X are linearly related to the (13)C NMR shifts of the ipso carbon. | 10.1021/jp409623j |
pubmed_804_16620 | Due to the development of dental materials and the esthetic requirements of patients, conservative restoration and esthetic dentistry is becoming more and more important.[...]. | 10.3390/dj6010005 |
pubmed_1048_745 | BACKGROUND
Quality of life (QOL) measures are effective in quantifying disease burden after stroke, more so than levels of debility. The objective of this study is to determine QOL and associated factors of stroke survivors in Lagos, Nigeria.
MATERIALS AND METHODS
Seventy stroke survivors (study sample) and seventy stable hypertensive patients (control sample) attending clinics at a Nigerian hospital were recruited for the study. Respondents were assessed using sociodemographic/clinical questionnaires, modified mini-mental state examination, modified Rankin Scale, schedule for clinical assessment in neuropsychiatry, and World Health Organization-QOL-BREF.
RESULTS
Mean ages of the study and control respondents were 57.43 (±9.67) years and 57.33 (±9.33) years, respectively. Each sample comprised 38 male and 32 female respondents. Stroke survivors were significantly more likely to: be unemployed (P = 0.001), pay more for healthcare (P = 0.001), consume alcohol (P = 0.02), and have physical impairments (P = 0.001) compared with control. The mean QOL scores of stroke survivors were significantly lower than controls across all spheres. Stroke survivors who were unemployed, younger, female, paying more for healthcare, more disabled, with right stroke lateralization, having comorbidities, and sexual dysfunction had significantly poorer QOL specific grades. Depression or anxiety poststroke was also associated with reduced QOL means scores.
CONCLUSION
Besides, clinical variables such as levels of disability and stroke lesion lateralization, other factors such as unemployment, health costs, age, gender, and emotional problems influenced QOL after stroke. | 10.4103/0300-1652.190602 |
pubmed_332_400 | Autologous stem cell transplantation (ASCT) is considered the standard therapy for younger patients with newly diagnosed symptomatic multiple myeloma (MM). The introduction into clinical practice of novel agents, such as the proteasome inhibitor bortezomib and the immunomodulatory derivatives (IMiDs) thalidomide and lenalidomide, has significantly contributed to major advances in MM therapy and prognosis. These novel agents are incorporated into induction regimens to enhance the depth of response before ASCT and further improve post-ASCT outcomes. Between January 2000 and November 2011, 65 patients with MM were transplanted in the Department of Biomedical Science and Clinical Oncology at the University of Bari. According to Durie-Salmon, 60 patients had stage III of disease and 5 stage II. Only 7 patients were in stage B (renal failure). Induction regimens that were administered in two or more cycles were VAD (vincristine, adriamycin, and dexamethasone), Thal-Dex (thalidomide, dexamethasone), Len-Dex (lenalidomide, dexamethasone), Vel-Dex (bortezomib, dexamethasone), VTD (bortezomib, thalidomide, and dexamethasone), and PAD (bortezomib, pegylated liposomal doxorubicin, and dexamethasone). In mobilization procedure, the patients received cyclophosphamide and granulocyte colony-stimulating factor (G-CSF). The number of cells collected through two or more leukapheresess, response after induction, and toxicity were evaluated to define the more adequate up-front induction regimen in transplantation-eligible MM patients. | 10.1155/2012/607260 |
pubmed_214_4290 | The purpose of the paper is to study how changes in neural network architecture and its hyperparameters affect the results of biometric identification based on keystroke dynamics. The publicly available dataset of keystrokes was used, and the models with different parameters were trained using this data. Various neural network layers-convolutional, recurrent, and dense-in different configurations were employed together with pooling and dropout layers. The results were compared with the state-of-the-art model using the same dataset. The results varied, with the best-achieved accuracy equal to 82% for the identification (1 of 20) task. | 10.3390/s22093158 |
pubmed_765_23702 | Natural sweeteners, such as agave syrup, might be a healthy alternative to sucrose used in sweet bakery products linked to obesity. We evaluated the effect of sucrose replacement by agave syrup on rheological and microstructural properties of muffin batter and on physical and sensorial properties of the baked product. Muffins were formulated by replacing 25%, 50%, 75%, and 100% of sucrose by agave syrup (AS) and partially hydrolyzed agave syrup (PHAS), and by adding xanthan gum and doubled quantities of leavening agents. Rheological and microstructural properties of batter during baking were analyzed over the range of 25-100 °C. In the muffins, the structure, texture, color, and sensory acceptance were studied. The combination of agave syrup with xanthan gum and doubled quantities of leavening agents affected (p < 0.05) rheological and microstructural properties of the batters and textural properties of the low-sucrose muffins compared to the controls. The increase in agave syrup levels resulted in a darker crumb and crust. Sensory evaluation showed that AS-75 and PHAS-75 were the best alternatives to the control samples. Our results suggest a plausible substitution of up to 75% of sucrose by agave syrup in preparation of muffins, with physical and sensorial characteristics similar to those of their sucrose-containing counterparts. | 10.3390/foods9070895 |
pubmed_781_13608 | Ku70-dependent canonical nonhomologous end-joining (c-NHEJ) DNA repair system is fundamental to the genome maintenance and B-cell lineage. c-NHEJ is upregulated and error-prone in incurable forms of chronic lymphocytic leukemia which also displays telomere dysfunction, multiple chromosomal aberrations and the resistance to DNA damage-induced apoptosis. We identify in these cells a novel DNA damage inducible form of phospho-Ku70. In vitro in different cancer cell lines, Ku70 phosphorylation occurs in a heterodimer Ku70/Ku80 complex within minutes of genotoxic stress, necessitating its interaction with DNA damage-induced kinase pS2056-DNA-PKcs and/or pS1981-ATM. The mutagenic effects of phospho-Ku70 are documented by a defective S/G2 checkpoint, accelerated disappearance of γ-H2AX foci and kinetics of DNA repair resulting in an increased level of genotoxic stress-induced chromosomal aberrations. Together, these data unveil an involvement of phospho-Ku70 in fast but inaccurate DNA repair; a new paradigm linked to both the deregulation of c-NHEJ and the resistance of malignant cells. | 10.18632/oncotarget.4735 |
pubmed_476_4680 | BACKGROUND
Prolonged field care is required when casualty evacuation to a surgical facility is delayed by distance, weather or tactical constraints. This situation can occur in both civilian and military environments. In these circumstances, there are no established treatment options for extremity compartment syndrome. Telementoring by a surgeon may enable the local clinician to perform a fasciotomy to decompress the affected compartments.
METHODS
Six military clinicians were asked to perform a two-incision leg fasciotomy in synthetic models under the guidance of an orthopaedic surgeon located 380 km away. Communication occurred through commercially available software and smartglasses, which also allowed the surgeon to send augmented-reality graphics to the operators. Two blinded surgeons evaluated the specimens according to objective criteria. Control specimens were added to ensure the integrity of the evaluation process.
RESULTS
The six study participants were military physician assistants who had extensive clinical experience but had never performed a fasciotomy. The average duration of the procedure was 53 min. All six procedures were completed without major errors: release of all four compartments was achieved through full-length incisions in the skin and fascia. The only surgical complication was a laceration of the saphenous vein. All three control specimens were correctly assessed by the evaluators. None of the participants experienced adverse effects from wearing the smartglasses. Four dropped calls occurred, but the connection was re-established in all cases.
CONCLUSION
All six surgical procedures were completed successfully. We attribute the dropped calls to a mismatch between the size of the graphic files and the available bandwidth. A better technical understanding of the software by the mentoring surgeon would have avoided this problem. Important considerations for future research and practice include protocols for dropped communications, surgical skills training for the operators and communication training for the surgeons. | 10.1136/bmjmilitary-2021-001975 |
pubmed_398_15204 | The simple Badal Optometer consists of a movable target and a fixed positive power lens placed at its focal distance away from the eye. The perceived angular size of the target is independent of target position and the power scale is linear. Limitations of the simple Badal Optometer include restriction of negative (myopic) ocular vergence range, the need for targets to be small, and the problem of "proximal" accommodation. We describe two modifications to the Badal system in which these limitations may be overcome by the use of a movable auxiliary optical system. In one modification, the movable auxiliary system consists of a target and positive lens which together may provide a virtual "target" for the Badal lens and thus increase the negative range. In the second modification, the Badal lens is positioned as it would normally be, but the target is an image of a distant stimulus created by the auxiliary lens. The target position (and hence the ocular vergence) is changed by moving the auxiliary lens. The distant target eliminates the proximal accommodative stimulus and allows spatial detail near the resolution limit to be displayed. | 10.1097/00006324-199504000-00010 |
pubmed_680_6082 | Digital technology enhances predictability and reli-a-bility in restorative dentistry procedures, especially in cases where precision is crucial in the transfer of information. In this article, several procedures are described for the implementation of a restorative workflow, especially in direct composite anterior and posterior restorations, representing an evolution of the direct stratification techniques described thus far in the dental literature. The clinician's digital skills are important for accurately managing the workflows to avoid errors and distortions, so that not only the operat-ive phases but the patients themselves become 'digital entities.' A comprehensive digital 3D project requires a very -precise diagnosis and treatment plan. | pubmed_680_6082 |
pubmed_556_16441 | BACKGROUND
To report cases of extraspinal mimics of cauda equina syndrome (CES) to enable prompt diagnosis and treatment in the future. CES results from compression of spinal nerve roots. Current practice mandates lumbosacral magnetic resonance imaging (MRI) scanning to diagnose CES. However, it may not reveal compression or provide an explanation for the presentation. We present 3 cases of suspected CES who went on to have intracranial pathology.
METHODS
Retrospective review of all patients presenting with CES-type features who were subsequently found to have causative intracranial pathology over a 6-month period.
RESULTS
Three cases were found, and these are hereby presented.
CASE PRESENTATION
Case 1: A 57-year-old lady presented with urinary retention and bilateral leg weakness. She underwent an MRI spine which showed no evidence of CES. She was diagnosed with haemorrhagic intracranial metastases. Case 2: A 52-year-old lady presented with lower back and right buttock pain, with right-sided leg numbness, saddle hypoesthesia, and bowel and bladder incontinence. MRI spine showed no cauda equina compression. MRI neuraxis revealed a subdural haematoma. Case 3: A 69-year-old lady presented with a 6-day history of urinary incontinence, right foot drop, and leg weakness. MRI spine was negative for CES. She was diagnosed with an intraparenchymal haematoma of posterior left frontal lobe.
CONCLUSIONS
Negative lumbosacral MRI will not exclude extraspinal mimics of CES and, although rare, these cases should be considered. | 10.1016/j.wneu.2020.09.014 |
pubmed_1097_9265 | Three-dimensional structures of crack-tip dislocations in silicon crystals have been examined by combining scanning transmission electron microscopy and computed tomography. Cracks were introduced by a Vickers hardness tester at room temperature, and the sample was heated at 823 K for 1 h in order to introduce dislocations around the crack tips. Dislocation segments cut out from loops were observed around the crack tip, the three-dimensional structure of which was characterized by using by electron tomography. Their Burgers vectors including the sings were also determined by oscillating contrasts along dislocations. In order to investigate the effect of the dislocations on fracture behaviours, local stress intensity factor due to one dislocation was calculated, which indicates the dislocations observed were shielding type to increase fracture toughness. | 10.1093/jmicro/dfq031 |
pubmed_259_23578 | Haemodialysis in pregnancy is not common although, successful dialysis in pregnancy have been reported. It has also been found to improve survival of both mother and child especially, in patients with chronic renal failure, with pre-term labor being a common occurrence. Out of the 2,995 patients that were dialyzed at the University College Hospital, Ibadan in the last 10 years, only 2 of the patients were pregnant and both of them had acute renal failure. We present here the two cases, which represents our experience at the University College Hospital, Ibadan, Nigeria. | pubmed_259_23578 |
pubmed_171_5648 | Until recently, cortical Lewy body disease (CLB) was considered essentially the same as dementia with Lewy bodies (DLB). It is now known patients with Parkinson's disease (PD) with a later-onset dementia (PD-dementia) have the same pattern and extent of cortical Lewy body pathology. Inheritance patterns of CLB have not been evaluated previously. To identify genetic influence on CLB, all cases with this pathology need to be considered. We selected 180 cases meeting clinical and/or pathological criteria for DLB or PD (+/-dementia) from two patient groups: a PD and PD-dementia brain donor program, and a case-control study of Alzheimer's disease (AD). Cases meeting NINCDS-ADRDA criteria for probable AD were excluded and non-demented PD cases used as a comparison group. A detailed family history was taken analyzing onset and progression of dementia and PD phenotypes and a family tree constructed. The frequency of a positive family history of dementia and/or PD and risk of developing CLB in relatives was calculated. Fifty-five percent of dementia and 52% of PD cohorts did not have relatives with clinical disease. There was no increased frequency of familial disease in the CLB cohort compared with PD. However, in half the CLB families, rather than a dominant dementia, the clinical presentation varied (dementia and/or PD). Unlike PD, there was an increased risk of dementia if CLB was present in a parent ( approximately 20% risk) compared with another family member ( approximately 5% risk), suggesting CLB is more likely than PD to occur in a pattern consistent with autosomal dominant inheritance. | 10.1002/ajmg.b.30014 |
pubmed_204_12285 | Precautionary measures of physical isolation, social distancing, and masks have all aided in controlling the spread of COVID-19. However, detection of the virus is crucial to implement isolation of infected individuals. This paper presents the innovative repurposing of lab materials, workspace, and personnel in response to the COVID-19-induced shutdown and consequential shortage of commercially made virus transport media (VTM). This method for VTM production highlights the ability of standard research labs to fulfill the needs of those affected by the pandemic and potential recurrence of outbreaks. Further, the collaboration of the various entities at The Ohio State University Wexner Medical Center (OSUWMC) allowed for efficient production and distribution of VTM tubes to facilitate mass COVID-19 testing. We propose that implementation of this process by university research labs would enable quicker interventions, potentially better outcomes, and prevention of further spread of disease. | 10.1016/j.mex.2021.101433 |
pubmed_824_3901 | OBJECTIVE
To determine if early access to multidisciplinary surgical care affects outcomes in patients with skull base chordoma.
METHOD
A retrospective chart review of prospectively collected data was performed on 51 patients treated from 1993 to 2014. The cohort was divided into those presenting (1) for initial management (ID, n = 21) or (2) with persistent/progressive disease after prior biopsy/surgery (PD, n = 30) outside of a multidisciplinary setting. The impact of initial surgical management in a multidisciplinary center on progression-free survival (PFS) was assessed with Kaplan-Meier and log-rank analyses.
RESULTS
Mean follow-up, median PFS, median overall survival (OS), and 10-year OS for the entire cohort was 70 months, 47 months, 159 months, and 19%, respectively. Initial management in a multidisciplinary center resulted in a significant improvement in PFS versus initial surgery with or without radiotherapy (XRT) outside of this setting (64 vs 25 months, p = 0.035). Initial surgical resection outside of a multidisciplinary setting increased the risk of recurrence/progression on univariate (HR, 2.276; p = 0.022) and multivariate analysis (HR, 2.831; p = 0.006), respectively.
CONCLUSIONS
The results from this study emphasize the impact that coordinated multidisciplinary surgical care has on patient outcomes for chordomas of the clivus. Biopsy followed by attempted radical resection at a dedicated center does not affect PFS and, therefore, represents a reasonable first step in management for patients presenting outside of multidisciplinary setting. | 10.1007/s00701-017-3409-4 |
pubmed_529_3965 | OBJECTIVES
The authors' aim was to investigate whether serum neutrophil to lymphocyte ratio might be used as a predictive biomarker to help differentiate active from inactive chronic otitis media (COM).
METHODS
Two hundred fifty-nine patients having inactive COM received tympanoplasty without mastoidectomy and were identified as Group 1. On the other hand, 254 patients having active COM received tympanoplasty with mastoidectomy and were identified as Group 2. Routine hemogram tests were performed preoperatively for both the groups. By performing a chart review, white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet, and mean platelet volume values were compared between the groups in an age-matched and sex-matched manner.
RESULTS
A total of 513 COM patients with age range of 7 to 65 years were included in the study. Two hundred seventy-five patients (53.6%) were male, 238 were (46.4%) female. Preoperatively both serum neutrophil and lymphocyte counts were significantly higher in Group 2 (P = 0.015 and P = 0.004, respectively). However, the neutrophil-to-lymphocyte ratios between the groups were not significantly different (P = 0.511).
CONCLUSION
No statistically significant differences were identified from preoperative neutrophil-to-lymphocyte ratios between patients having active COM and inactive COM.
LEVEL OF EVIDENCE
Level NA. | 10.1097/SCS.0000000000003484 |
pubmed_628_10225 | Pharmacological uncoupling of mitochondrial oxidation from phosphorylation promotes preconditioning-like cardioprotection in the isolated rat heart. We hypothesized that modest mitochondrial uncoupling may be a critical cellular event in orchestrating preconditioning. Human-derived Girardi cells and murine C2C12 skeletal myotubes were preconditioned using simulated ischemia, adenosine, and diazoxide. Cell viability after 6 hours of simulated ischemia was measured using lactate dehydrogenase release and propidium iodide uptake. Mitochondrial inner membrane potential (DeltaPsim) was investigated by flow cytometry, cellular ATP by recombinant firefly-luciferase bioluminescence, and cellular oxygen consumption using oximetry. Preconditioning enhanced cell viability with attenuation of lactate dehydrogenase release (>/=30%, P<0.05 versus ischemic controls) and a reduction in propidium iodide uptake by >/=26% versus ischemic controls after simulated ischemia in both cell lines. In Girardi cells, preconditioning induced the following phenotype immediately before index ischemia: (1) decreased DeltaPsim (JC-1: simulated ischemia 90+/-3%, adenosine 82+/-7%, diazoxide 87+/-4%, versus control 100%, P<0.05); (2) attenuation in cellular ATP levels (CTL 0.21+/-0.03 nmol/L ATP/microg protein, simulated ischemia 0.12+/-0.02, adenosine 0.15+/-0.02, diazoxide 0.11+/-0.02, P<0.05); and (3) enhanced cellular oxygen consumption (control 2.3+/-0.1 nmol/L oxygen/min/1x10(6) cells, simulated ischemia 3.1+/-0.1, adenosine 3.1+/-0.3, diazoxide 2.6+/-0.2, P<0.05). Cytoprotection, mitochondrial depolarization, and enhanced oxygen consumption were attenuated by the putative mitochondrial K(ATP)-channel antagonist 5-hydroxydecanoate. The uncoupled phenotype in response to preconditioning was similarly observed in C2C12 myotubes. The present study suggests that modest mitochondrial uncoupling represents a unifying cellular response which may be important in directing preconditioning-mediated cytoprotection. | 10.1161/hh2101.098372 |
pubmed_171_16614 | OBJECTIVES
We investigated the prevalence and characteristics of HIV-positive women who do not report highly active antiretroviral therapy (HAART) use.
METHODS
We analyzed HAART use among 1165 HIV-positive participants in the Women's Interagency HIV Study.
RESULTS
Between October 1, 2000, and March 31, 2001, 254 women with clinical indications for HAART reported not using it, 635 reported HAART use, and 276 had no clinical indications. In multivariate analysis, using crack/cocaine/heroin and a history of abuse decreased the likelihood of using HAART, whereas being White increased it.
CONCLUSIONS
One of 4 women for whom HAART was indicated reported not using HAART. Childhood sexual abuse prevention, more intensive abuse treatment, and continuing drug treatment may enhance HIV disease treatment of women. | 10.2105/ajph.94.7.1147 |
pubmed_293_6786 | Brain areas that control gaze are also recruited for covert shifts of spatial attention1-9. In the external space of perception, there is a natural ecological link between the control of gaze and spatial attention, as information sampled at covertly attended locations can inform where to look next2,10,11. Attention can also be directed internally to representations held within the spatial layout of visual working memory12-16. In such cases, the incentive for using attention to direct gaze disappears, as there are no external targets to scan. Here we investigate whether the oculomotor system of the brain also participates in attention focusing within the internal space of memory. Paradoxically, we reveal this participation through gaze behaviour itself. We demonstrate that selecting an item from visual working memory biases gaze in the direction of the memorized location of that item, despite there being nothing to look at and location memory never explicitly being probed. This retrospective 'gaze bias' occurs only when an item is not already in the internal focus of attention, and it predicts the performance benefit associated with the focusing of internal attention. We conclude that the oculomotor system also participates in focusing attention within memorized space, leaving traces all the way to the eyes. | 10.1038/s41562-019-0549-y |
pubmed_738_23837 | Tip-enhanced Raman spectroscopy (TERS) has been recognized as a useful tool for nanoscale chemical analysis, and it can further reach down to the sub-nanometer scale in the gap-mode configuration. Using an atomic force microscopy (AFM) in gap-mode TERS for position control of a metallic tip, a unique and correlative analysis can be even realized at the single molecule level. However, one of crucial issues in AFM-based gap-mode TERS is the fabrication of reliable and reproducible cantilver metallic tips. Here, we propose a simple, cost-effective fabrication method of metal-coated tips for AFM-based gap-mode TERS by means of the physical vapor deposition technique in a reproducible way. Our plamonic tips have extremely smooth silver layers on one side of the pyramidal tip, which is totally different from the regular metallic tips that hold granular metallic structures randomly arranged on their bodies. Importantly, all fabricated tips exhibited a reasonably high enhancement factor of more than 104, which indicates that the reproducibility of our plasmonic tip is virtually 100% in the gap-mode configuration. The excellent reproducibility of gap-mode TERS measurement holds great promise for rendering AFM-based TERS as a powerful analytical technique in a broad range of fields. | 10.1088/1361-6528/ab90b6 |
pubmed_1133_2521 | OBJECTIVES
Even though polymethyl methacrylate (PMMA) resin is widely used as a dental material, it has poor microbial anti-adhesive properties, which accelerates oral infections. In this investigation, silver-sulfadiazine (AgSD)-loaded mesoporous silica nanoparticles (Ag-MSNs) were incorporated into PMMA to introduce long-term microbial anti-adhesive effects and to make PMMA a rechargeable resin.
METHODS
After characterization of the Ag-MSNs in terms of their mesoporous characteristics and drug loading capacity, the 3 point flexural test and hardness were evaluated in PMMA incorporating Ag-MSNs (0.5, 1, 2.5 and 5%). Anti-adhesive effects were observed for Candida albicans and Streptococcus oralis with experimental specimens for up to 28days and after recharging with AgSD.
RESULTS
A typical spherical morphology and high mesoporosity were observed for the MSNs used for loading AgSD. Incorporation of Ag-MSNs into PMMA (0.5, 1, 2.5 and 5%) sustained its flexural strength but increased its surface hardness. Anti-adhesive effects were observed after 1h of exposure to both microbial species, and the effects accelerated with increasing Ag-MSN incorporation into PMMA. Long-term microbial anti-adhesive effects were observed for up to 14 days, and further long-term (7 days) anti-adhesive effects were observed after reloading the Ag-MSN-incorporated PMMA (aged for 28 days) with AgSD; these effects were largely caused by released silver ions and partially by changes in surface hydrophilicity. No cytotoxicity to keratinocytes was observed.
CONCLUSIONS
The improved mechanical properties and the prolonged microbial anti-adhesive effects, which lasted after reloading of the drug, suggest the potential usefulness of Ag-MSN-incorporated PMMA as a microbial anti-adhesive dental material.
SIGNIFICANCE
Ag-MSN-incorporated PMMA can be used as a microbial anti-adhesive dental material for dentures, orthodontic devices and provisional restorative materials. | 10.1016/j.dental.2017.07.009 |
pubmed_852_20040 | OBJECTIVES
Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety.
METHODS AND SUBJECTS
Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period.
RESULTS
A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml).
CONCLUSIONS
Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped. | 10.5414/CP201825 |
pubmed_854_6897 | The identification of variant Creutzfeldt-Jakob disease (vCJD) in human strongly reinforced the perception of risks associated with the infectious agent involved in Bovine Spongiform Encephalopathy (BSE). The development of rapid tests for the diagnosis of BSE by the detection of the abnormal prion protein allowed a huge increase in surveillance of the cattle disease. This first revealed a higher prevalence of the infection than previously believed. However, food safety measures, mainly based on the ban of the use of meat and bone meal in ruminants and the elimination of specified risk materials from the food chain, already allowed significant progress in the control of the cattle disease, especially in the United Kingdom. Nevertheless, the diagnosis can still not be obtained in the live animal, while the disease only appears following a several years incubation period. Another major issue is the identification of the BSE agent when it has been transmitted to another species. This question not only arises in veterinary medicine, with the major question of a possible infection of small ruminants by the BSE agent, but also in human in which the existence of other forms of the disease linked to the BSE agent but possibly differing from Creutzfeldt-Jakob disease cannot be excluded. | 10.1016/j.patbio.2004.09.009 |
pubmed_1055_20570 | While antipyretic analgesics are widely used to ameliorate vaccine adverse reactions, their use has been associated with blunted vaccine immune responses. Our objective was to review literature evaluating the effect of antipyretic analgesics on vaccine immune responses and to highlight potential underlying mechanisms. Observational studies reporting on antipyretic use around the time of immunization concluded that their use did not affect antibody responses. Only few randomized clinical trials demonstrated blunted antibody response of unknown clinical significance. This effect has only been noted following primary vaccination with novel antigens and disappears following booster immunization. The mechanism by which antipyretic analgesics reduce antibody response remains unclear and not fully explained by COX enzyme inhibition. Recent work has focused on the involvement of nuclear and subcellular signaling pathways. More detailed immunological investigations and a systems biology approach are needed to precisely define the impact and mechanism of antipyretic effects on vaccine immune responses. | 10.1080/21645515.2016.1183077 |
pubmed_784_15152 | Salmonella typhimurium has the capacity to enter into and multiply within epithelial cells. During the entire intracellular stage, bacteria are enclosed within a vacuole. To characterize the micro-environment of the bacteria-containing vacuoles, we have used a new method to measure the expression levels of several S. typhimurium genes in intracellular bacteria within Madin-Darby canine kidney (MDCK) epithelial cells. Our study was based on the determination of beta-galactosidase activity derived from lacZ transcriptional fusions using the highly sensitive substrate fluorescein-di-beta-D-galactoside (FDG). Expression of the iroA and mgtB genes (induced by Fe2+ and Mg2+ limitation respectively), and cadA (induced by pH 6.0 in the presence of lysine, with enhanced expression under anaerobiosis) were characterized at different post-infection times. High intracellular expression levels were detected for the iroA and mgtB genes, suggesting that the concentrations of free Fe2+ and Mg2+ in the vacuole may be low. cadA activity was detected only at early post-infection times (4 h), suggesting that the vacuole may have a mild-acidic pH, and oxygen and lysine present at this time. Globally, the results reported indicate that the use of a highly sensitive beta-galactosidase substrate can provide information about the micro-environment within which an intracellular pathogen, such as S. typhimurium, resides. | 10.1111/j.1365-2958.1992.tb02197.x |
pubmed_414_12447 | BACKGROUND
The cytochrome P450 (CYP) enzyme CYP26 (retinoic acid [RA] 4-hydroxylase) initiates the catabolism of all-trans RA (tRA) and limits the effects of tRA. The CYP26 enzyme acts specifically on tRA, but not 13-cis RA (isotretinoin), a retinoid used to treat severe acne. However, 13-cis RA can isomerize to tRA, which can then be metabolized by CYP26.
OBJECTIVE
In healthy individuals, we assessed the variability of CYP26 enzymatic activity. We then investigated whether response to oral 13-cis RA among patients with acne correlates with variability in CYP26 expression.
METHODS
In healthy individuals, we isolated microsomal fractions from the epidermis of keratome biopsy specimens and measured CYP26 enzymatic activity in untreated skin and skin treated with tRA. Enzymatic activity was determined based on rate of formation of 4-hydroxy RA (pg/min/mg microsomal protein). Using real-time polymerase chain reaction we quantified CYP26 messenger RNA induction after tRA application in patients with acne who responded or did not respond to one course of 13-cis RA.
RESULTS
In normal-appearing skin (N = 118), CYP26 enzymatic activity was widely variable (1-180 pg/min/mg microsomal fraction; mean 42.7 +/- 3.5). Furthermore, CYP26 enzymatic activity was inducible in a dose-dependent manner in normal-appearing skin after tRA application, but not correlated with age or sex (N = 29). In patients with acne, CYP26 messenger RNA induction after 0.1% tRA application did not differ (P > .05) between patients who responded (N = 8, 587 +/- 325-fold) or did not respond (N = 8, 657 +/- 227-fold) to one course of 13-cis RA.
LIMITATIONS
The small number of patients with acne treated with 13-cis RA was a major limitation.
CONCLUSION
Factors other than CYP26 activity may determine response to isotretinoin in acne. | 10.1016/j.jaad.2009.03.013 |
pubmed_505_11980 | The authors refer to congenic hypothyroidism, hypotyroxinemia in premature new-borns, thyroid dysfunction, congenic thyrotoxicosis, breastfeeding, composed anti-thyroid drugs and children nutrition based on iodine. Concerning to the fetus and new-born thyroid dysfunction, it's very important to make an early diagnosis in order to avoid later complications. Several studies revealed that the different types of composed anti-thyroid drugs can induce pregnant woman choice. | pubmed_505_11980 |
pubmed_882_24533 | We have previously demonstrated differences in eye-position spatial maps for anterior inferotemporal cortex (AIT) in the ventral stream and lateral intraparietal cortex (LIP) in the dorsal stream, based on population decoding of gaze angle modulations of neural visual responses (i.e., eye-position gain fields). Here we explore the basis of such spatial encoding differences through modeling of gain field characteristics. We created a population of model neurons, each having a different eye-position gain field. This population was used to reconstruct eye-position visual space using multidimensional scaling. As gain field shapes have never been well-established experimentally, we examined different functions, including planar, sigmoidal, elliptical, hyperbolic, and mixtures of those functions. All functions successfully recovered positions, indicating weak constraints on allowable gain field shapes. We then used a genetic algorithm to modify the characteristics of model gain field populations until the recovered spatial maps closely matched those derived from monkey neurophysiological data in AIT and LIP. The primary differences found between model AIT and LIP gain fields were that AIT gain fields were more foveally dominated. That is, gain fields in AIT operated on smaller spatial scales and smaller dispersions than in LIP. Thus, we show that the geometry of eye-position visual space depends on the population characteristics of gain fields, and that differences in gain field characteristics for different cortical areas may underlie differences in the representation of space. | 10.3389/fnint.2015.00072 |
pubmed_910_7985 | To explore the feasibility of chemical and biological method in evaluation of the in vitro dissolution rate of Liuwei Wuling tablet (LWT), this experiment investigated the inhibitory effect of LWT dissolving solutions on LX-2 hepatic stellate cells in 0.1% SDS dissolution medium in different dissolving periods. From these results, the cumulative dissolution rate of LWT was obtained based on the cell inhibitory rate. The dissolution rates of deoxyschizandrin, phillyrin, and Specnuezhenide were determined by HPLC method. A novel approach of self-defined weighting coefficient had been created to establish the integrated dissolution rate model. Then f2 similar factor method was used to evaluate the relevance of these two methods. The results showed that f2 values for deoxyschizandrin, phillyrin, Specnuezhenide, and the integrated dissolution were 61, 43, 61 and 75 respectively, indicating that the dissolution of multi-component integration could fully reflect the biological potency of the whole recipe. The dissolution evaluation method for multicomponent integration based on biological activity is expected to be one of the effective means for in vitro dissolution test of LWT. | pubmed_910_7985 |
pubmed_157_8807 | Rapidly growing tumours in vivo often outgrow their surrounding available blood supply, subjecting themselves to a severely hypoxic microenvironment. Understanding how tumour cells adapt themselves to survive hypoxia may help to develop new treatments of the tumours. Given the limited blood perfusion to the enlarging tumour, whatever factor(s) that allows the tumour cells to survive likely comes from the tumour cells themselves or its associated stromal cells. In this report, we show that HIF-1α-overexpressing breast cancer cells, MDA-MB-231, secrete heat shock protein-90alpha (Hsp90α) and use it to survive under hypoxia. Depletion of Hsp90α secretion from the tumour cells was permissive to cytotoxicity by hypoxia, whereas supplementation of Hsp90α-knockout tumour cells with recombinant Hsp90α, but not Hsp90β, protein prevented hypoxia-induced cell death via an autocrine mechanism through the LDL receptor-related protein-1 (LRP1) receptor. Finally, direct inhibition of the secreted Hsp90α with monoclonal antibody, 1G6-D7, enhanced tumour cell death under hypoxia. Therefore, secreted Hsp90α is a novel survival factor for certain tumours under hypoxia. | 10.1038/srep20605 |
pubmed_970_15284 | BACKGROUND
Neural tube defects (NTDs) occur in nervous tissue during embryogenesis when the neural tube fails to close. Approximately 70% of all human NTDs can be prevented by folic acid (FA). Altered expression and/or function of the tumor suppressor protein p53 can lead to NTDs in mouse models.
OBJECTIVES
The aim of this study was to determine if dietary FA could rescue p53-/--induced NTDs in mice, and to determine the effect loss of p53 has on pathways in folate 1-carbon metabolism.
METHODS
p53+/- female mice were randomly allocated and weaned onto either an FA-sufficient diet (2 mg/kg folic acid; +FA), or an FA-deficient diet (-FA). After 8 wk, the females were time-mated to p53-/- males. Embryos were examined at E12.5 for NTDs. Folate enzyme concentrations, nucleotide synthesis, uracil accumulation in DNA, and proliferation were measured in primary murine embryonic fibroblasts (MEFs). The "n - 1" chi-square test was used to compare NTD percentages, whereas all other data were analyzed by Student t test, except where noted a multilevel-fit model was used.
RESULTS
NTD rates of litters from dams consuming the +FA diet (20/46; 43%) did not differ from those of litters from dams consuming the -FA diet (14/35; 40%) (P > 0.05). p53-/- MEFs had 55% higher rates of folate-dependent de novo dTMP synthesis, a ∼2-fold higher accumulation of uracil in DNA, and a ∼30% higher rate of proliferation (P ≤ 0.05) than p53+/- MEFs independent of folate.
CONCLUSIONS
p53-related NTDs are not FA responsive. Increased dTMP synthesis in p53-/- MEFs might not have been sufficient to meet the demands for thymidine triphosphate (dTTP) synthesis as evidenced by the elevated amounts of uracil in DNA. This study provides additional evidence that elevated uracil in DNA is a risk factor for NTDs. | 10.1093/jn/nxaa090 |
pubmed_468_19634 | The present retrospective study was carried out to analyse clinical outcomes of 56 surgical interventions performed on renal arteries in a total of 48 patients suffering from atherosclerotic- aetiology vasorenal hypertension (VRH). Of these, 14 patients were subjected to stenting of renal vessels, 19 underwent aortorenal prosthetic repair, 11 patients endured transaortic endarterectomy (TEA), and four cases were treated by resection of the renal artery with reimplantation. The immediate postoperative outcomes turned out positive in 81% of the patients, to have remained so within an average follow-up period of up to 5 years in 72% of the patients. Most often good results were observed after renal artery prosthetic repair (in 85% of patients) and stenting (in 78% of patients). Good results were observed in 26% of patients with a history of VRH over 5 years, with its duration of less than that surgical renal revascularization being accompanied by positive outcomes in 58% of patients. | pubmed_468_19634 |
pubmed_165_12870 | We describe here the development of four sets of painting probes for mouse chromosomes 1 and 13, 2 and 8, 6 and 15, and X and Y by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) amplification of 10-20 copies of microdissected male meiotic chromosomes. The X,Y probe was obtained from the X-Y bivalent of diakinesis/metaphase I complements of mice with a normal karyotype, whereas the other probes were derived from tri- or quadrivalents in diakinesis/metaphase I of two reciprocal translocations, T(1;13)70H and T(2;8)2Wa, and one inversion heterozygote carrying a small deletion, In(6;15)Rb1Ald del6(15)1Wa. The specificity of these probes was established by fluorescence in situ hybridization (FISH) to meiotic and mitotic metaphase complements. The chromosomes painted by these probes could be identified by single or multicolor FISH. | 10.1159/000134458 |
pubmed_92_8850 | Perovskite oxide manganites with a general formula of R1-x AxMnO3 (where R is a trivalent rare-earth element such as La, Pr, Sm, and A is a divalent alkaline-earth element such as Ca, Sr, and Ba) have received much attention due to their unusual electron-transport and magnetic properties, which are indispensable for applications in microelectronic, magnetic, and spintronic devices. Recent advances in the science and technology have resulted in the feature sizes of microelectronic devices based on perovskite manganite oxides down-scaling into nanoscale dimensions. At the nanoscale, low-dimensional perovskite manganite oxide nanostructures display novel physical properties that are different from their bulk and film counterparts. Recently, there is strong experimental evidence to indicate that the low-dimensional perovskite manganite oxide nanostructures are electronically inhomogeneous, consisting of different spatial regions with different electronic orders, a phenomenon that is named as electronic phase separation (EPS). As the geometry sizes of the low-dimensional manganite nanostructures are reduced to the characteristic EPS length scale (typically several tens of nanometers in manganites), the EPS is expected to be strongly modulated, leading to quite dramatic changes in functionality and more emergent phenomena. Therefore, reduced dimensionality opens a door to the new functionalities in perovskite manganite oxides and offers a way to gain new insight into the nature of EPS. During the past few years, much progress has been made in understanding the physical nature of the EPS in low-dimensional perovskite manganite nanostructures both from experimentalists and theorists, which have a profound impact on the oxide nanoelectronics. This nanoreview covers the research progresses of the EPS in low-dimensional perovskite manganite nanostructures such as nanoparticles, nanowires/nanotubes, and nanostructured films and/or patterns. The possible physical origins of the EPS are also discussed from the signatures of electronic inhomogeneities as well as some theoretical scenarios, to shed light on understanding this phenomenon. Finally, the perspectives to the future researches in this area are also outlined. | 10.1186/1556-276X-9-325 |
pubmed_709_3661 | 1. Fractured porcelain bars repaired with Fusion/Concise displayed significantly greater repair strength (p less than .05) than bars repaired with Den-Mat and Cervident. 2. Comparing mean strengths of all samples before and after repair with Fusion/Concise indicated that only 18% of the original strength was regained following repair. 3. The low repair strengths of the tested materials indicate that their use is a temporary clinical procedure. | 10.1016/0022-3913(81)90240-7 |
pubmed_1052_22910 | OBJECTIVE
This study investigated the reliability of the Nepali version of the 21-item Depression Anxiety Stress Scale (DASS-21) among non-clinical sample. The purpose of this paper is to report the dimensionality and internal consistency of the DASS-21in a sample of non-clinical adults.
METHOD
This study was conducted in Hong Kong among 212 Nepali adults, aged 18-60 years. Life satisfaction was assessed with the Life Satisfaction Scale. The dimensionality of the DASS-21 scale was investigated using exploratory factor analysis. Construct validity was evaluated using the life satisfaction scale.
RESULTS
The intercorrelation among depression, anxiety and stress subscales indicates that symptoms of psychological distress as measured by the DASS-21-N can distinguished between the three constructs in adult community sample. The results also showed inverse correlation among DASS-21-N and life satisfaction scale, supporting the assumption that the higher the life satisfaction, the lower the psychological distress.
CONCLUSION
The results of this study indicate that the Nepali version of the DASS-21 demonstrate adequate psychometric properties in relation to internal consistency and validity, lending support to prior studies and suggest that the DASS-21 can be utilized among diverse groups with confidence. It supports the reliability of the 3-factorial dimensionality of the DASS-21, and highlight that it is a valid and useful tool that can distinguish between depression and anxiety. | pubmed_1052_22910 |
others_7_12240 | Eleven Salmonella Choleraesuis and seven Salmonella Hadar strains isolated from various clinical human samples were investigated by plasmid profile analysis, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and pulsed-field gel electrophoresis (PFGE) in order to obtain information at a molecular level on the epidemiology of S. Choleraesuis and S. Hadar, which are significantly present in Turkey. Plasmid profile analysis showed that 10 (90.9%) of 11 S. Choleraesuis isolates harbored one to two plasmids with sizes of 2.0, 5.0 or 6.5 kb; and 5 (71.4%) of 7 S. Hadar isolates harbored one to three plasmids ranging from 2.5 to 70 kb. ERIC-PCR was performed using ERIC-2 primers; since isolates within each serotype showed similar band models, we concluded that ERIC-PCR is not suitable for differentiating isolates within the same serotype and for grouping into clusters. In PFGE using the AvrII enzyme, S. Choleraesuis isolates formed three clusters, and S. Hadar isolates formed three clusters; using the XbaI enzyme, S. Choleraesuis formed two clusters, and S. Hadar isolates formed four clusters. These results showed that plasmid profile analysis and PFGE are reliable and discriminative methods that would complement antibiograms, and could contribute to the investigation of outbreak epidemiology. This is the first report on S. Choleraesuis and S. Hadar isolates from Turkey investigated by plasmid profile analysis, ERIC-PCR and PFGE methods | others_7_12240 |
pubmed_1066_22005 | BACKGROUND
Evidence suggests that changes in dietary acid load may influence body weight, body composition, and insulin sensitivity.
METHODS
Participants (n = 244) were randomly assigned to an intervention (vegan) (n = 122) or control group (n = 122) for 16 weeks. Before and after the intervention period, body composition was measured by dual X-ray absorptiometry. Insulin resistance was assessed with the Homeostasis Model Assessment (HOMA-IR) index and predicted insulin sensitivity index (PREDIM). Repeated measure ANOVA was used for statistical analysis.
RESULTS
Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) decreased significantly in the vegan group with no change in the control group (treatment effect -24.7 mEq/day [95% CI -30.2 to -19.2]; p < 0.001; and -23.8 mEq/day [95% CI -29.6 to -18.0]; p < 0.001, respectively). Body weight decreased by 6.4 kg in the vegan group, compared with 0.5 kg in the control group (treatment effect -5.9 kg [95% CI -6.8 to -5.0]; Gxt, p < 0.001), largely due to a reduction in fat mass and visceral fat. HOMA-IR index decreased and PREDIM increased in the vegan group. After adjustment for energy intake, changes in PRAL and NEAP correlated positively with changes in body weight (r = +0.37; p < 0.001; and r = +0.37; p < 0.001, respectively), fat mass (r = +0.32; p < 0.001; and r = +0.32; p < 0.001, respectively), visceral fat (r = +0.19; p = 0.006; and r = +0.15; p = 0.03, respectively), and HOMA (r = +0.17; p = 0.02; and r = +0.20; p = 0.006, respectively), and negatively with changes in PREDIM (r = -0.22; p = 0.002; and r = -0.27; p < 0.001, respectively).
CONCLUSION
Dietary acid load as part of a plant-based diet was associated with changes in body weight, body composition, and insulin sensitivity, independent of energy intake. Mechanistic explanations suggest that the relationship may be causal.
TRIAL REGISTRATION
ClinicalTrials.gov number, NCT03698955. | 10.1016/j.clnesp.2021.05.015 |
pubmed_550_16879 | OBJECTIVE
The present study investigated whether lateralized ERP components triggered during covert manual response preparation (ADAN, LDAP) reflect effector selection, the selection of movement direction, or both.
METHODS
Event-related brain potentials were recorded during a response precueing paradigm where visual cues provided either partial (Experiment 1) or full (Experiment 2) information about the response hand and the direction for a subsequent reaching movement.
RESULTS
ADAN and LDAP components were elicited even when only partial response information was available, demonstrating that they do not require the presence of a fully specified motor program. The ADAN was elicited in a similar fashion regardless of whether effector or movement direction information was provided, suggesting that the underlying mechanisms are equally sensitive to both types of response-related information. In contrast, the LDAP was larger in response to cues providing effector information, but was also reliably present when movement direction was available.
CONCLUSIONS
ADAN and LDAP components reflect preparatory activity within anterior and posterior parts of the parieto-premotor sensorimotor network where different parameters for manual reaching movements are programmed independently.
SIGNIFICANCE
These results support the claim of the premotor theory of attention that shared sensorimotor control mechanisms are involved in attention and motor programming. | 10.1016/j.clinph.2007.06.003 |
others_64_17431 | Aims: Nitrogen (N) deposition has negative consequences for plant communities and ecosystem functioning. Nitrogen deposition is declining or is projected to decline in many regions due to the reduction of N-compound emissions. It remains unknown whether the cessation of N deposition will have legacy effects on plant nutrient stoichiometry. If there are stoichiometric legacy effects at the community-level from prior N enrichment, the contribution of changes in community composition relative to the stoichiometric responses of individual functional groups in driving these changes is unknown. Methods: We measured plant N:P ratio at both functional group level and community level in a temperate steppe in three consecutive years following cessation of a 7-year N addition experiment with a wide-range of total amount added N in which the total amount of N added ranged from 0 to 350 g m−2. Results: The total amount of N addition was positively correlated with tall rhizomatous grass productivity and negatively correlated with tall bunchgrass productivity. Plant N:P ratios at both functional group and community levels did not change across N addition gradient. Community composition shifts contributed less than intra-group variation to the total variation of community level nutrient status in response to historic N addition. Conclusions: Our results indicated that biological N:P imbalance in response to N deposition can be rapidly ameliorated after the cessation of N deposition. Such legacy effects of N deposition on plant nutrient status are largely driven by the changes of nutrient status of individual plants instead of N-induced shifts in community composition. © 2019, Springer Nature Switzerland AG | 10.1007/s11104-019-04357-7 |
pubmed_172_12348 | The repair of X-ray-induced DNA lesions in repair-deficient mutant strains was studied as a way of investigating the mechanism of the induction of genetic damage. Genetic effects on the recovery of X-ray-induced damage by the repair-deficient strains ebony (photoreactivation repair-deficient) and mus(1)101D1 (post-replication repair-deficient) were interpreted as impaired repair of single- and double-strand DNA breaks. We investigated the repair of X-ray-induced DNA breaks and alkaline-labile sites in primary cell cultures of ebony and mus(1)101D1 and in cultures of their control strains. No significant differences were found between the repair rates in the mutants and control strains. This indicates that the genetic effects of these mutants are not due to an impaired rate of repair of DNA breaks. | 10.1016/0027-5107(87)90025-x |
pubmed_1113_23276 | Myopic observers may not benefit to the same extent as emmetropes from adaptive optics (AO) correction in a visual acuity (VA) task. To investigate this, we measured AO-corrected VA in 10 low myopes and 9 emmetropes. Subjects were grouped by refractive error. Mean spherical equivalent refractive error was -2.73 D (SEM = 0.35) for the myopes and 0.04 D (SEM = 0.1) for the emmetropes. All subjects had best corrected VA of 20/20 or better. The AO scanning laser ophthalmoscope was used to project ultrasharp stimuli onto the retina of each observer. High-contrast photopic acuity was measured using a tumbling E test with and without AO correction. AO-corrected minimum angle of resolution was 0.61' (SEM = 0.02') for the myopes and 0.49' (SEM = 0.03') for the emmetropes. The difference between groups is significant (p = .0017). This effect is even greater (p = .00013) when accounting for spectacle magnification and axial length, with myopes and emmetropes able to resolve critical features on the retina with a mean size of 2.87 mum (SEM = 0.07) and 2.25 mum (SEM = 0.1), respectively. Emmetropes and low myopes will both benefit from AO correction in a VA task but not to the same extent. Optical aberrations do not limit VA in low myopia after AO correction. There is no difference in the high-order aberrations of emmetropes and low myopes. Retinal and/or cortical factors limit VA in low myopes after AO correction. | 10.1167/7.8.14 |
pubmed_947_2383 | BACKGROUND AND AIMS
Hepatocyte nuclear factor 4 alpha (HNF4α) is indispensable for hepatocyte differentiation and critical for maintaining liver health. Here, we demonstrate that loss of HNF4α activity is a crucial step in the pathogenesis of chronic liver diseases (CLDs) that lead to development of HCC.
APPROACH AND RESULTS
We developed an HNF4α target gene signature, which can accurately determine HNF4α activity, and performed an exhaustive in silico analysis using hierarchical and K-means clustering, survival, and rank-order analysis of 30 independent data sets containing over 3500 individual samples. The association of changes in HNF4α activity to CLD progression of various etiologies, including HCV- and HBV-induced liver cirrhosis (LC), NAFLD/NASH, and HCC, was determined. Results revealed a step-wise reduction in HNF4α activity with each progressive stage of pathogenesis. Cluster analysis of LC gene expression data sets using the HNF4α signature showed that loss of HNF4α activity was associated with progression of Child-Pugh class, faster decompensation, incidence of HCC, and lower survival with and without HCC. A moderate decrease in HNF4α activity was observed in NAFLD from normal liver, but a further significant decline was observed in patients from NAFLD to NASH. In HCC, loss of HNF4α activity was associated with advanced disease, increased inflammatory changes, portal vein thrombosis, and substantially lower survival.
CONCLUSIONS
In conclusion, these data indicate that loss of HNF4α function is a common event in the pathogenesis of CLDs leading to HCC and is important from both diagnostic and therapeutic standpoints. | 10.1002/hep.32326 |
pubmed_630_24132 | OBJECTIVES
This prospective research study was designed to analyze the surgical outcomes and the intensity of substance P (SP), neurokinin A (NA), and calcitonin gene-related peptide (CGRP) in contact and noncontact nasal mucosa of patients with headache.
METHODS
Twenty adults with secondary headache and correctible nasal obstruction were included in this study. The patients had nasal contact points between the nasal septum and the middle or inferior turbinates on nasal endoscopy and computed tomography scan. During surgical procedures, sample tissues were obtained from the nasal contact point and the noncontact area of the lateral nasal wall of these patients. Fluorescein staining intensity for antibodies against SP, NA, and CGRP was analyzed using image J software. Headaches were evaluated using a visual analog scale preoperatively and postoperatively.
RESULTS
The differences between the preoperative and the postoperative 3rd month (P < 0.001) and 12th month (P < 0.001) visual analog scale scores were statistically significant. However, fluorescein staining intensity for SP (P = 0.631), NA (P = 0.546), and CGRP (P = 0.683) did not show statistically significant differences between the contact mucosa and the noncontact mucosa groups.
CONCLUSIONS
Although in selected patients significant relief of headache can be obtained by surgery, there is no evidence from this study that SP, NA, and CGRP are responsible for the initiation of headache. | 10.1097/SCS.0000000000002553 |
pubmed_656_13107 | ConspectusExcitons and polarons play a central role in the electronic and optical properties of organic semiconducting polymers and molecular aggregates and are of fundamental importance in understanding the operation of organic optoelectronic devices such as solar cells and light-emitting diodes. For many conjugated organic molecules and polymers, the creation of neutral electronic excitations or ionic radicals is associated with significant nuclear relaxation, the bulk of which occurs along the vinyl-stretching mode or the aromatic-quinoidal stretching mode when conjugated rings are present. Within a polymer chain or molecular aggregate, nuclear relaxation competes with energy- and charge-transfer, mediated by electronic interactions between the constituent units (repeat units for polymers and individual chromophores for a molecular aggregate); for neutral electronic excitations, such inter-unit interactions lead to extended excited states or excitons, while for positive (or negative) charges, interactions lead to delocalized hole (or electron) polarons. The electronic coupling as well as the local coupling between electronic and nuclear degrees of freedom in both excitons and polarons can be described with a Holstein Hamiltonian. However, although excitons and polarons derive from similarly structured Hamiltonians, their optical signatures are quite distinct, largely due to differing ground states and optical selection rules.In this Account, we explore the similarities and differences in the spectral response of excitons and polarons in organic polymers and molecular aggregates. We limit our analysis to the subspace of excitons and hole polarons containing at most one excitation; hence we omit the influence of bipolarons, biexcitons, and higher multiparticle excitations. Using a generic linear array of coupled units as a model host for both excitons and polarons, we compare and contrast the optical responses of both quasiparticles, with a particular emphasis on the spatial coherence length, the length over which an exciton or polaron possesses wave-like properties important for more efficient transport. For excitons, the UV-vis absorption spectrum is generally represented by a distorted vibronic progression with H-like or J-like signatures depending on the sign of the electronic coupling, Jex. The spectrum broadens with increasing site disorder, with the spectral area preserved due to an oscillator strength sum rule. For (hole) polarons, the generally stronger electronic coupling results in a mid-IR spectrum consisting of a narrow, low-energy peak (A) with energy near a vibrational quantum of the vinyl stretching mode, and a broader, higher-energy feature (B). In contrast to the UV-vis spectrum, the mid-IR spectrum is invariant to the sign of the electronic coupling, th, and completely resistant to long-range disorder, where it remains entirely homogeneously broadened. Even in the presence of short-range disorder, the width of peak A remains surprisingly narrow as long as |th| remains sufficiently large, a property that can be understood in terms of Herzberg-Teller coupling. Unlike for excitons, for polarons, the absorption spectral area decreases with increasing short-range disorder σ (i.e., there is no oscillator sum rule) reflective of a decreasing polaron coherence length. The intensity of the low-energy peak A in relation to B is an important signature of polaron coherence. By contrast, for excitons, the absorption spectrum contains no unambiguous signs of exciton coherence. One must instead resort to the shape of the steady-state photoluminescence spectrum. The Holstein-based model has been highly successful in accounting for the spectral properties of molecular aggregates as well as conjugated polymers like poly(3-hexylthiophene) (P3HT) in the mid-IR and UV-vis spectral regions. | 10.1021/acs.accounts.0c00349 |
pubmed_813_23336 | OBJECTIVE
To attempt to reduce the incidence of hepatic and cardiac failure after radical surgery for the Budd-Chiari syndrome.
DESIGN
Retrospective case study.
SETTING
University hospital, Japan
SUBJECTS
Three patients with obstruction of the vena cava (Budd-Chiari syndrome) by a thick membrane, thrombus, and a long stenosis, respectively.
INTERVENTION
Direct excision and repair by patch dilatation under hepatic vascular exclusion using a Biomedicus centrifugal pump.
RESULTS
Hepatic vascular exclusion provides good visibility and enables accurate assessment of the obstruction, proper treatment, and relatively little blood loss. There were no complications, particularly liver failure or heart failure, and the inferior vena cava stayed patent in all cases. Liver function was improved in all three patients.
CONCLUSION
This technique is safe and reliable for removal of obstruction of the inferior vena cava (Budd-Chiari syndrome). | 10.1080/11024159950189672 |
pubmed_630_1638 | In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant and anti-tumor activities. In the present study, the viability inhibition effects of SFN in U251MG glioblastoma cells were analyzed by MTS. Morphology changes were observed by microscope. Apoptotic effects of SFN were evaluated by annexin V binding capacity with flow cytometric analysis. Invasion inhibition effects of SFN were tested by the invasion assay. The molecular mechanisms of apoptotic effects and invasion inhibition effects of SFN were detected by western blot and gelatin zymography. The results indicated that SFN has potent apoptotic effects and invasion inhibition effects against U251MG glioblastoma cells. These effects are both dose dependent. Taken together, SFN possessed apoptotic activity on U251MG cells indicated by increased annexin V-binding capacity, Bad, Bax, cytochrome C expression, and decreased Bcl-2 and survivin expressions. SFN inhibited invasion in U251MG cells via upregulation of E-cadherin and downregulation of MMP-2, MMP-9 and Galectin-3. | 10.1186/s40064-016-1910-5 |
pubmed_624_15302 | Thirty-nine newborn infants with severe persistent pulmonary hypertension and respiratory failure who met criteria for 85% likelihood of dying were enrolled in a randomized trial in which extracorporeal membrane oxygenation (ECMO) therapy was compared with conventional medical therapy (CMT). In phase I, 4 of 10 babies in the CMT group died and 9 of 9 babies in the ECMO group survived. Randomization was halted after the fourth CMT death, as planned before initiating the study, and the next 20 babies were treated with ECMO (phase II). Of the 20, 19 survived. All three treatment groups (CMT and ECMO in phase I and ECMO, phase II) were comparable in severity of illness and mechanical ventilator support. The overall survival of ECMO-treated infants was 97% (28 of 29) compared with 60% (6 of 10) in the CMT group (P less than .05). | pubmed_624_15302 |
pubmed_568_11688 | B10 cells play negative roles in inflammatory disorders by producing IL-10. However, their effects on fibrosis have not been elucidated. Therefore, this study was conducted to examine the dynamic changes of B10 cell frequency and their potential role in cardiac fibrosis. We found that the frequency of B10 cells was significantly increased, and they participated in the regression of fibrosis via IL-10, particularly by accelerating hyaluronan secretion and inhibiting collagen deposition. In vivo, hyaluronan ablation or treatment significantly restricted cardiac fibrosis development. hyaluronan-induced conversion of M1/M2 Mc was dependent on the size of hyaluronan. Low molecular weight hyaluronan promoted the conversion to M1 Mϕ, whereas medium and high molecular weight hyaluronan accelerated Mϕ transdifferentiation into the M2 phenotype. Adoptive transfer of B10 cells significantly attenuated collagen deposition whereas CD19-/- mice with reduced B10 cells exacerbated fibrosis following cardiac injury. Our results provide new evidence suggesting that B10 cells exert antifibrotic effects by regulating the extracellular matrix composition during cardiac injury, and also highlight that B10 cells may serve as a promising therapeutic candidate for managing cardiac fibrosis-associated disorders. | 10.1002/JLB.3A0121-003RR |
pubmed_438_6124 | PURPOSE
We designed an investigational study and placebo controlled trial to evaluate the efficacy of magnetic stimulation of the sacral roots for treating urinary frequency and urge incontinence.
MATERIALS AND METHODS
A total of 48 women 43 to 75 years old (mean age 61) with the complaint of urinary frequency and/or urge incontinence were studied. We applied 15 Hz. repetitive magnetic stimulation of the sacral roots with 50% intensity output for 5 seconds per minute for 30 minutes. Urodynamic investigations during magnetic stimulation were performed in 11 cases to evaluate acute effects for lowering urinary tract function. Another 37 women were enrolled in a placebo controlled study to investigate short-term effects. The mean number of voids daily, mean urine volume per void, number of leaks for 3 days and quality of life score were evaluated before and 1 week after stimulation.
RESULTS
Urodynamic investigations revealed apparent elevation in mean maximum urethral closure pressure plus or minus standard deviation during stimulation in all 11 cases (8.4 +/- 3.6 cm. water, p = 0.00001) and a significant increase in mean bladder capacity after stimulation (58.2 +/- 50.2 ml., p = 0.003). In the placebo controlled study all parameters significantly improved in the active stimulation group. Intergroup comparison showed that mean urine volume per void, mean number of leaks and mean quality of life score improved more significantly in the active than in the sham stimulation group (23.5 +/- 25.6 ml. versus 6.2 +/- 22.5, p = 0.04, 3.6 +/- 4.1 versus 0.4 +/- 1.4, p = 0.04 and 1.4 +/- 1.3 versus 0.4 +/- 0.8, p = 0.01, respectively). No adverse effects were noted in any patients.
CONCLUSIONS
These results suggest that magnetic stimulation of the sacral roots may be useful for treating urinary frequency and urge incontinence. | 10.1097/01.ju.0000025868.08859.9e |
pubmed_917_3462 | Fifty-eight grafts have been assessed using duplex scanning and ankle brachial pressure indices. This assessment is compared with the findings by angiography. Eighteen grafts were occluded and 40 patent. Duplex scanning defined graft status with a greater accuracy than pressure indices. Pressure indices alone would not differentiate "satisfactory" grafts from those with localised, haemodynamically significant disease. Only 55% of those grafts with localised stenoses demonstrated a fall of greater than 0.2 in ankle brachial pressure index after exercise. When the information obtained using pressure indices and duplex scanning was combined non-invasive assessment had a sensitivity of 86% and specificity of 94% for detection of localised, haemodynamically significant disease in patent grafts. Haemodynamically significant disease, as defined by angiography, can be detected and localised with duplex scanning complementing the use of pressure indices in graft assessment. | 10.1016/s0950-821x(87)80035-x |
pubmed_354_25937 | Cancer metabolic reprogramming promotes tumorigenesis and metastasis; however, the underlying molecular mechanisms are still being uncovered. In this study, we show that the glycolytic enzyme aldolase A (ALDOA) is a key enzyme involved in lung cancer metabolic reprogramming and metastasis. Overexpression of ALDOA increased migration and invasion of lung cancer cell lines in vitro and formation of metastatic lung cancer foci in vivo. ALDOA promoted metastasis independent of its enzymatic activity. Immunoprecipitation and proteomic analyses revealed γ-actin binds to ALDOA; blocking this interaction using specific peptides decreased metastasis both in vitro and in vivo. Screening of clinically available drugs based on the crystal structure of ALDOA identified raltegravir, an antiretroviral agent that targets HIV integrase, as a pharmacologic inhibitor of ALDOA-γ-actin binding that produced antimetastatic and survival benefits in a xenograft model with no significant toxicity. In summary, ALDOA promotes lung cancer metastasis by interacting with γ-actin. Targeting this interaction provides a new therapeutic strategy to treat lung cancer metastasis. SIGNIFICANCE: This study demonstrates the role of aldolase A and its interaction with γ-actin in the metastasis of non-small lung cancer and that blocking this interaction could be an effective cancer treatment. | 10.1158/0008-5472.CAN-18-4080 |
pubmed_812_16259 | MAD2 is localized to kinetochores of unaligned chromosomes, where it inactivates the anaphase-promoting complex/cyclosome, thus contributing to the production of a diffusible anaphase inhibitory signal. Disruption of MAD2 expression leads to defects in the mitotic checkpoint, chromosome missegregation, and tumorigenesis. However, the mechanism by which deregulation and/or abnormality of hsMAD2 expression remains to be elucidated. Here, we clone and analyze a approximately 0.5 kb fragment upstream of hsMAD2 and show that this fragment acts as a strong promoter. Transcriptional dysfunction of hsMAD2 is frequently observed in hepatocellular carcinoma cells, and down-regulation of hsMAD2 protein expression is correlated with transcriptional silencing of the hsMAD2 promoter by hypermethylation. These results imply a relationship between transcriptional abnormality of this mitotic checkpoint gene and mitotic abnormality in human cancers. | 10.1158/0008-5472.CAN-03-3455 |
pubmed_137_3511 | BACKGROUND
This study explored the way families support self-determination in young adults with intellectual and developmental disabilities (IDD) during life transitions.
METHOD
Qualitative case studies were conducted with two Canadian families who participated in semi-structured interviews and ethnographic observations every quarter for one year. Analyses were informed by family systems theory and self-determination theory.
FINDINGS
Families considered the needs and preferences of the young adults with IDD, suggesting individualized approaches for balancing independence and protection. Families set short-term and long-term goals for increased independence, scaffolded the learning of new skills and collaborated on important choices. Collaboration occurred to the extent that all family members perceived agency in planning and implementing transitions.
CONCLUSIONS
Families supported the young adults with IDD in their psychological needs for competence, relatedness and autonomy, which allowed them to experience self-determination. Findings have implications for supporting self-determination and transition planning in the family system. | 10.1111/jar.12601 |
pubmed_1129_11367 | BACKGROUND
Arsenic trioxide (As2O3), a drug that has been used in China for approximately two thousand years, induces cell death in a variety of cancer cell types, including neuroblastoma (NB). The tyrosine kinase receptor (Trk) family comprises three members, namely TrkA, TrkB and TrkC. Various studies have confirmed that TrkA and TrkC expression is associated with a good prognosis in NB, while TrkB overexpression can lead to tumor cell growth and invasive metastasis. Previous studies have shown that As2O3 can inhibit the growth and proliferation of a human NB cell line and can also affect the N-Myc mRNA expression. It remains unclear whether As2O3 regulates Trks for the purposes of treating NB.
METHODS
The aim of the present study was to investigate the effect of As2O3 on Trk expression in NB cell lines and its potential therapeutic efficacy. SK-N-SH cells were grown with increasing doses of As2O3 at different time points. We cultured SK-N-SH cells, which were treated with increasing doses of As2O3 at different time points. Trk expression in the NB samples was quantified by immunohistochemistry, and the cell cycle was analyzed by flow cytometry. TrkA, TrkB and TrkC mRNA expression was evaluated by real-time PCR analysis.
RESULTS
Immunohistochemical and real-time PCR analyses indicated that TrkA and TrkC were over-expressed in NB, and specifically during stages 1, 2 and 4S of the disease progression. TrkB expression was increased in stage 3 and 4 NB. As2O3 significantly arrested SK-N-SH cells in the G2/M phase. In addition, TrkA, TrkB and TrkC expression levels were significantly upregulated by higher concentrations of As2O3 treatment, notably in the 48-h treatment period. Our findings suggested that to achieve the maximum effect and appropriate regulation of Trk expression in NB stages 1, 2 and 4S, As2O3 treatment should be at relatively higher concentrations for longer delivery times;however, for NB stages 3 and 4, an appropriate concentration and infusion time for As2O3 must be carefully determined.
CONCLUSION
The present findings suggested that As2O3 induced Trk expression in SK-N-SH cells to varying degrees and may be a promising adjuvant to current treatments for NB due to its apoptotic effects. | 10.1186/s40659-018-0167-6 |
pubmed_678_16244 | Hemolysis is the red blood cell abnormality most often associated with adverse effect of drug therapy. Drug-induced or drug-associated hyperglycemia could decrease the activity of hexokinase. The aim of this study was to investigate the inhibitory effects of some commonly used drugs that have hyperglycemic side effect on the human erythrocyte hexokinase enzyme in vitro. Hexokinase was purified from human erythrocytes using sequential chromatography, with a specific activity of 0.96 ± 0.18 U/g hemoglobin, and assayed in the presence of selected drugs that have hyperglycemic side effect. The IC50 were determined from the regression analysis graph. Correlation analysis showed that there was positive correlation between the hyperglycemic side effect of some of the tested drugs and decrease of hexokinase activity. This suggests that, at least in part, these drugs exert their hyperglycemic effect by inhibiting glucose phosphorylation by the hexokinase, which consequently causes the glucose accumulation. | 10.1002/jbt.21910 |
pubmed_837_15492 | One hundred patients with cirrhosis underwent abdominal computed tomography (CT) using a delayed contrast technique to determine liver and spleen volume. These scans were reviewed to screen this "at risk" population for hepatocellular carcinoma (HCC). Fifteen of the 100 screened patients had focal abnormalities suspicious for HCC. On biopsy, only 1 patient was shown to have HCC. The other 14 patients had either fatty infiltration or focal regeneration. In the same time interval, a total of 10 patients had histologically proven HCC. All presented with symptoms and died within 4 months of diagnosis. The results show that focal hepatic lesions can be detected by CT but in this population the lesions may not be due to HCC. The incidence of HCC was approximately 1%, probably reflecting a truly low incidence in this population. | 10.1007/BF01889041 |
pubmed_429_4665 | This work compares various conventional venoarterial closed-chest circuits where satisfactory oxygenation of myocardium and brain in total apnea with extracorporeal circulation is concerned. Eleven dogs were studied during 3 hours of curare-induced apnea. We used single and double vena caval drainages connected to an oxygenator. A single-vein drainage yielded approximately 50 per cent and a double-vein drainage 75 per cent bypass. Two separate roller pumps fed arterialized blood variously into carotid and femoral arteries. In single-vein drainage, the oxygen partial pressure in the coronary artery was consistently poor and carotid oxygen partial pressure was poor for 100 per cent femoral infusion while more and more arterialized blood reached the carotid arteries in the other single-vein drainage circuits. In double-vein drainage, the coronary oxygen partial pressure for 100 per cent femoral infusion remained poor while, for the other circuit types, the coronary arteries received arterialized blood except where 100 per cent carotid infusion was concerned. The carotid oxygen partial pressure was sound for all groups in the double-vein drainage except for some obtained in 100 per cent femoral infusion. Consequently, where the bypass was large and the carotid and femoral arteries received a share of arterialized blood, both heart and brain received sound oxygenation. | pubmed_429_4665 |
pubmed_367_3924 | Growing evidence indicates that inflammatory reactions play an important role in the pathogenesis of alcoholic liver disease (ALD). The implication of immunity in fueling chronic inflammation in ALD has emerged from clinical and experimental evidence showing the recruitment and the activation of lymphocytes in the inflammatory infiltrates of ALD and has received further support by the recent demonstration of a role of Th17 lymphocytes in alcoholic hepatitis. Nonetheless, the mechanisms by which alcohol triggers adaptive immune responses are still incompletely characterized. Patients with advanced ALD show a high prevalence of circulating IgG and T-lymphocytes towards epitopes derived from protein modification by hydroxyethyl free radicals (HER) and end-products of lipid peroxidation. In both chronic alcohol-fed rats and heavy drinkers the elevation of IgG against lipid peroxidation-derived antigens is associated with an increased production of pro-inflammatory cytokines/chemokines and with the severity of histological signs of liver inflammation. Moreover, CYP2E1-alkylation by HER favors the development of anti-CYP2E1 auto-antibodies in a sub-set of ALD patients. Altogether, these results suggest that allo- and auto-immune reactions triggered by oxidative stress might contribute to fuel chronic hepatic inflammation during the progression of ALD. | 10.1007/s12263-009-0151-4 |
pubmed_406_8452 | In soybean root nodules, leghaemoglobin (Lb) accounts for 25--30% of the total soluble protein but is not detected in other tissues. In order to determine whether the Lb genes are plant or bacterial in origin a cDNA probe for Lb was prepared from 9S poly (A) containing mRNA of root nodules. Although this 9S mRNA directed synthesis of predominantly three forms of Lb in vitro, the kinetics of hybridisation of cDNA and the 9S mRNA showed a transition at about 30% hybridisation which suggested that the 9S-cDNA was not pure Lb-cDNA. The abundant, Lb-cDNA was prepared by two cycles of hybridising 9S mRNA and cDNA to a Rot of 3 X 10(-3) and isolation of the hybridised cDNA on hydroxyapatite. The Lb-cDNA was homogeneous in hybridisation analysis with 9S mRNA and electrophoresis in 98% formamide gels. This cDNA hybridised with soybean DNA and not with Rhizobium DNA, thus directly demonstrating that Lb genes are of plant origin. Titration of Lb-cDNA with soybean DNA showed that Lb genes are reiterated about forty-fold per haploid genome. | 10.1093/nar/5.11.4141 |
pubmed_892_17698 | Established NMR methods are increasingly being applied to the non-native states of proteins. For small denatured proteins, full assignment of proton, 15N and 13C resonances is often straightforward. Sensitive methods exist for detecting fractionally populated alpha helices and beta strands, but defining transient interactions among side chains is proving more problematic. The non-native states of several small proteins are being intensively investigated to address a number of questions about protein folding. | 10.1016/s0959-440x(96)80091-1 |
pubmed_847_4017 | Efflux transporters such as MexAB-OprM contribute to bacterial resistance to diverse antimicrobial compounds. Here, we show that MexB contributes to epiphytic and late-stage apoplastic growth of Pseudomonas syringae strain B728a, as well as lesion formation in common bean (Phaseolus vulgaris). Although a ∆mexB mutant formed fewer lesions after topical application to common bean, these lesions contain the same number of cells (105 to 107 cells) as those caused by the wild-type strain. The internalized population size of both the wild-type and the ∆mexB mutant within small samples of surface-sterilized asymptomatic portions of leaves varied from undetectably low to as high as 105 cells/cm2. Localized bacterial populations within individual lesions consistently exceeded 105 cells/cm2. Strain B728a was capable of moderate to extensive apoplastic growth in diverse host plants, including lima bean (P. lunatus), fava bean (Vicia faba), pepper (Capsicum annuum), Nicotiana benthamiana, sunflower (Helianthus annuus), and tomato (Solanum lycopersicum), but MexB was not required for growth in a subset of these plant species. A model is proposed that MexB provides resistance to as-yet-unidentified antimicrobials that differ between plant species. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license. | 10.1094/MPMI-04-21-0099-R |
pubmed_100_9725 | OBJECTIVE
Double prophylaxis for deep venous thrombosis (DVT) with thromboprophylaxis plus sequential compression devices (SCDs) is recommended for high-risk surgical patients with gynecologic oncology. Despite the use of preoperative thromboprophylaxis in clinical trials, the schedule of perioperative low molecular-weight heparin varies widely. We sought to determine the effectiveness and adverse effects of a preoperative dose of anticoagulation in patients with gynecologic oncology.
METHODS
A multi-institutional chart review from January 2006 to July 2008 was performed. Patients with gynecologic oncology who received double prophylaxis for laparotomy were eligible. The patients were grouped according to whether they received preoperative anticoagulation (YES PREOP vs NO PREOP). All patients received postoperative low molecular-weight heparin for thromboprophylaxis and SCDs until discharge. Demographic, surgicopathologic, and complication data were collected.
RESULTS
A total of 239 patients were identified: YES PREOP (n = 101) and NO PREOP (n = 138). Groups were similar with respect to demographics, diagnosis, and length of hospital stay. There were 2 DVTs in the YES PREOP group compared with 11 in the NO PREOP group (P = 0.04; relative risk, 0.77). There were also fewer DVT-attributable deaths in the YES PREOP group (0 vs 2; P < 0.001). Postoperative hematocrit (30.2% vs 31.4%; P = 0.42) and number of transfusions (26 vs 14; P = 0.31) were similar.
CONCLUSION
The use of preoperative anticoagulation seems to significantly decrease the risk of DVT in this patient population, and complication rates are not increased. Patients receiving double prophylaxis should receive a preoperative dose of anticoagulation for maximum benefit. | 10.1097/IGC.0b013e31821dc9f0 |
pubmed_398_9111 | The A/WySn mouse strain has a high frequency (20%) of the craniofacial defect, cleft lip with or without cleft palate, CL(P), in fetuses or newborns. Previous genetic studies have indicated that the genetic control of the risk of CL(P) is complex, but the cause of the liability of the embryo involves only one or two loci. The genes that cause the liability to CL(P) in A/WySn have been transferred by 12 generations of selective breeding to a normal strain background, AEJ/RkBc, to form a congenic strain pair. The new strain, AEJ.A/Jur, has been used to map a major CL(P) locus, clf1. Analysis of the genetic data from the process of constructing the AEJ.A/Jur strain indicates that the cause of CL(P) in A/WySn mice is the joint action of two recessive loci, clf1 and clf2 with unequal duplicate epistasis. That is, the normal allele at clf1 is a dominant suppressor of the recessive phenotype at clf2, and the normal allele at clf2 is a semidominant suppressor of the recessive phenotype at the clf1 locus. To be at risk for CL(P), embryos must be homozygous for clf1 mutations and at least heterozygous for clf2 mutations, and the risk is higher if they are homozygous for mutations at both loci. The delineation of this epistatic model involving a locus, clf1, that has linkage homology with a region implicated in human CL(P), and that has three paralogous regions in both species, supports the following arguments: and that has three paralogous regions in both species, supports the following arguments: that the CL(P) of the A/WySn mouse strain is a homologue of human CL(P); that the genetic complexity of CL(P) in both species originates in epistasis, not in polygenic modifiers; that human linkage analyses should specify epistatic models for CL(P); that the paralogous linkage groups should be considered candidate regions for other CL(P) loci. | pubmed_398_9111 |
pubmed_302_1897 | Loose anagen syndrome (LAS) is an autosomal dominant, age-related disorder characterized by the ability to easily and painlessly extract unsheathed anagen hairs from the scalp with a gentle hair pull. The phenotype is heterogeneous with three distinct clinical presentations. To further characterize the phenotype of loose anagen syndrome and its fluctuations over time, a prospective study of eight cases from three families was conducted over a period of 18 months. Patients were examined using standardized hair-pull and hair-pluck protocols. Each of the three different phenotypes of LAS were found to be present in one family. This implies that these phenotypes are variants of a single genotype, modified by environmental or age-related factors. The hair-pluck trichogram from LAS cases consistently showed a high proportion of loose anagen (LA) hairs. In contrast the hair-pull test was found to vary over time with regards to the number of LA hairs that could be extracted. Periods where no hairs could be obtained on hair pull were found. These findings have important implications in the diagnosis of LAS. A single negative hair-pull test does not exclude the diagnosis. If LAS is suspected on clinical grounds, then either a hair-pluck trichogram or serial re-examination by hair pull would be required to exclude the diagnosis. | 10.1046/j.1440-0960.2002.00572.x |
pubmed_1038_2559 | Acute ingestion of a low dose of alcohol (0.3 g/Kg) in a group of 18 healthy volunteers does not alter RR mean nor RR variance, producing only a slight decrease in the heart rate variability (HRV) measured by the mean momentary arrhythmia. However, power spectral of the HRV signal shows appreciable changes in the magnitude of the short-term RR fluctuations. Low frequency RR oscillations (0.02-0.06 Hz) increase in power during the 20-45 min. period after alcohol intake, while middle (0.08-0.15 Hz) frequency oscillations decrease in power during the 20-60 min. period and higher (0.20-0.35 Hz) frequency oscillations decrease in power during the 5-60 min. period after intake. The most drastic changes were observed in the middle frequency oscillations during the 20-30 min. period after intake while higher frequency oscillations seem to be less affected by the alcohol ingestion. | 10.15288/jsa.1992.53.86 |
pubmed_393_2049 | The effects of procaine and pentobarbital on lens placodes, otic placodes and non-placodal head ectoderm of the chick embryo in vitro have been examined by scanning and transmission electron microscopy. Both types of placode cells were less sensitive to both drugs than non-placodal cells. Cellular responses to pentobarbital were microvilli formation, reduction in cetylpyridinium chloride-stainable surface coat and epithelial dissociation with thinning of the basement membrane. Procaine treatment induced the formation of large cytoplasmic blebs and cytoskeletal condensations but did not affect the surface coat. Examination of head ectoderm appears to be of value in the evaluation and comparison of drug effects on differentiating tissues. Anaesthetics also form useful probes for structural and functional changes in the cells of such developing systems. | pubmed_393_2049 |
others_389_9439 | An orthogonal L16(45) design of combined effects of the five factors, nitrogen (N) fertilizer, phosphorus (P) fertilizer, potassium (K) fertilizer, organic manure, and water on the spring wheat (Triticum aestivum L.) yield, has been conducted for three years on Orthic Anthrosols at Shapotou in the southeast margin of the Tengger Desert. The results show that N and P fertilizers have significantly influenced spring wheat yield, that characterized by increase of the yields by increasing applies of N and P fertilizers. If the application rates of N and P fertilizers reach 200 kg ha-1 and 35.6 kg ha-1, the spring wheat yield was the highest. Potassium fertilizer has a less influence on spring wheat yield, suggesting that it is unsuitable to use it in the fertile Anthrosols in the loess region. Irrigation intensity is also a key factor affecting crop production in this and region. The irrigation intensity in the experimental range is directly proportional to the wheat yield, but lower irrigation intensity has larger yield-increasing efficiency than that of higher irrigation intensity. In addition, the influences of NPK fertilizers on the nutrient contents in soil and spring wheat straw, and the interactions between various fertilizers and water are analyzed. The optimal water-fertilizer combination and maximum production potential were determined by establishing a water-fertilizer-yield model | 10.1081/CSS-120027641 |
pubmed_556_25759 | PURPOSE
To characterize newly diagnosed primary open-angle glaucoma (OAG) patients and to describe their treatment journey in United States clinical practice according to the use of topical therapy, laser trabeculoplasty, and surgical procedures.
DESIGN
Retrospective claims database study.
PARTICIPANTS
Patients with at least 2 diagnoses of OAG 7 days or more apart and within 1 year, with the first (index) diagnosis in 2010, at least 30 months of continuous enrollment before index diagnosis with no OAG diagnosis or medication (exception for ocular hypertension diagnosis), and 48 months of continuous enrollment.
METHODS
Analysis of United States healthcare insurance claims database (July 2007-December 2014).
MAIN OUTCOME MEASURES
Treatment patterns and ophthalmology visits were evaluated over 48 months in 4 cohorts based on initial therapy after the index diagnosis: (1) drug monotherapy, (2) combination drug therapy, (3) glaucoma procedure, or (4) no claims for treatment. Treatment modification was defined as an addition to or change in drug therapy or procedure.
RESULTS
In total, 83.0% of patients (5120/6172) began a drug therapy (69.5%) or underwent a procedure initially (13.5%); topical prostaglandin analogs (n = 2887/5120 [56.4%]) and laser trabeculoplasty (n = 705/5120 [13.8%]) were the most common. During the 4-year follow-up, 58.3% of patients (2109/3620) who began drug monotherapy experienced no further treatment modification. Over this period, 43.8% of patients who began treatment (2242/5120) experienced a treatment modification to the first treatment. Two thirds (1505/2242 [67.1%]) of these patients subsequently underwent a third treatment modification. Ophthalmology visits declined over time regardless of initial therapy, with the greatest decrease among the untreated and first-treatment procedure cohorts.
CONCLUSIONS
The high rates of 2 or 3 treatment modifications over the 4-year period suggest an unmet need for glaucoma therapies with durable and predictable actions. | 10.1016/j.ogla.2020.09.002 |
others_375_2982 | Juvenile Atlantic salmon Salmo salar and lake trout Salvelinus namaycush of different sizes were exposed for 96 h to water supersaturated with air. Underyearlings (Atlantic salmon shorter than 66 ± 8 mm [mean total length ± SD] and lake trout shorter than 96 mm) were resistant to high dissolved-gas pressures. The level of supersaturation causing 50% mortality was lower for yearling Atlantic salmon (148 ± 17 mm long) than for underyearling Atlantic salmon, and sensitivity to supersaturation was greater in lake trout 96 ± 1 to 153 ± 17 mm long than in those 23 ± 1 to 46 ± 4 mm long. Incidence of cutaneous emphysema and other signs of gas bubble disease increased as supersaturation increased. The number of bubbles and number of sites with bubbles were higher in the older fish. Among fish 150 ± 17 mm long, Atlantic salmon seemed to be less resistant to gas supersaturation than did lake trout. © by the American Fisheries Society 1991 | 10.1577/1548-8667(1991)003<0248:ROUAYA>2.3.CO;2 |
pubmed_910_16895 | A 64-year-old patient developed sudden hypoglycemia leading to unconsciousness. Hypoglycemic episodes recurred on several occasions but were not accompanied by unconsciousness. Magnetic resonance imaging revealed a liver tumor in the right lobe sized 20.0 × 14.6 × 19.0 cm. No other masses were detected. Right hemihepatectomy was indicated but could not be performed due to heavy bleeding near the tumor. Histological examination showed a relatively cellular tumor made of elongated bland cells. The mitotic index was fewer than 4 mitoses per 10 HPF. The tumor was without necrosis or hemorrhage. The excised tumor was not encapsulated and showed no signs of invasive growth. On immunohistological examination, the tumor expressed NSE, CD34, CD99, Bcl2 and STAT6; Ki-67 was positive in approximately 20% of the cells. Both the histological pattern and immunophenotype were suggestive of solitary fibrous tumor of the liver. Given its size, cellularity and relatively high expression of the proliferation marker Ki-67, the tumor was classified as potentially malignant. The patient underwent embolization of arteries supplying the tumor with blood. The effect of the procedure on the tumor will only be assessed later. Hypoglycemia has resolved and the patient feels well. | pubmed_910_16895 |
pubmed_643_14617 | The incorporation of magnetic impurities into semiconductor nanocrystals with size confinement promotes enhanced spin exchange interaction between photogenerated carriers and the guest spins. This interaction stimulates new magneto-optical properties with significant advantages for emerging spin-based technologies. Here we observe and elaborate on carrier-guest interactions in magnetically doped colloidal nanoplatelets with the chemical formula CdSe/Cd1-MnS, explored by optically detected magnetic resonance and magneto-photoluminescence spectroscopy. The host matrix, with a quasi-type II electronic configuration, introduces a dominant interaction between a photogenerated electron and a magnetic dopant. Furthermore, the data convincingly presents the interaction between an electron and nuclear spins of the doped ions located at neighboring surroundings, with consequent influence on the carrier's spin relaxation time. The nuclear spin contribution by the magnetic dopants in colloidal nanoplatelets is considered here for the first time. | 10.1021/acs.jpclett.9b01999 |
pubmed_500_9011 | We studied the frequency of ST-T changes and ischemic heart disease (IHD) in prednisolone (PSL)-treated systemic lupus erythematosus (SLE) patients and compared them with the age-matched control of rheumatoid arthritis patients not receiving PSL. Twenty-five (38%) of the 65 SLE patients revealed ST-T changes as ST elevation (4%), ST depression (36%) and T wave flattening or inversion (60%). Among the control patients 4 (10%) had T wave flattening or inversion. The frequencies of ST-T changes in patients receiving total PSL dose of up to 5g and greater than 5g were 23% and 48%, respectively. Four patients developed IHD at an unusually young age during remission of SLE while receiving low dose of PSL and 2 of them later died of myocardial infarction (MI). The latter 2 patients had received PSL pulse therapy prior to MI. Regular ECG check up for SLE patients while they are on low dose PSL or pulse therapy may help reveal early ECG abnormalities and thus detect and treat one of the major risks of long-term effects of corticosteroid therapy. | 10.2169/internalmedicine1962.28.599 |
pubmed_515_13486 | OBJECTIVES
Our objective was to examine the extent to which serious psychological distress (SPD) is associated with behavioral and social correlates among US adults with self-reported disabilities.
METHODS
Self-reported data on disability, SPD, and behavioral and social correlates were collected from 202,383 participants (aged > or = 18 years) of the 2007 Behavioral Risk Factor Surveillance System. Adults with self-reported disabilities were identified using two standardized questions--one relating to activity limitation, the other to special equipment.
RESULTS
The age-adjusted prevalence of SPD among adults with disabilities was nearly seven times higher than among adults without disabilities (14.1 % vs. 1.8 %, respectively). Adults with disabilities who have both activity limitations and who use assistive technology, and those with activity limitations only consistently experienced a higher prevalence of SPD than those who used assistive technology only (age-adjusted prevalence: 21.0 % and 12.7 % vs. 4.9 %). After adjusting for age, sex, race/ethnicity, educational attainment, marital status, and employment status, in the past 30 days SPD was more common among Hispanic persons, and was significantly associated with younger age, lower educational attainment, marital history, and employment status. Adults with SPD and disabilities experienced increased levels of risk behaviors, life dissatisfaction, and inadequate social support. Most importantly, just over half of adults with disabilities and SPD (51.6 % [95 % CI = 48.6-54.6]) were receiving medical care for a mental health condition compared to 20.6 % (95 % CI = 19.9-21.3) without SPD.
CONCLUSIONS
Given that SPD is strongly associated with both the behavioral and psychosocial determinants of health, this work underscores the need for evidence-based interventions that may reduce its prevalence among people living with disabilities. | 10.1007/s00038-009-0077-z |
pubmed_529_637 | OBJECTIVE
Until now, it has been unclear if the three subsyndromes of adolescent-onset generalized genetic epilepsy (GGE) differ in long-term prognosis. Therefore, this study aimed to compare long-term seizure outcome in juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic-clonic seizures alone (EGTCS).
METHODS
This retrospective study is based on the archive of an institutional tertiary care outpatient clinic for adult patients with epilepsy. Charts of 870 epilepsy outpatients were reviewed among whom 176 had adolescent-onset GGE (53 JAE, 66 JME, 57 EGTCS). Median patient age at investigation was 60 years; median follow-up time was 42.5 years. If possible, GGE patients were additionally interviewed on psychosocial and clinical variables.
RESULTS
Age at first seizure was significantly higher in EGTCS patients (median 18 years) than in patients with JAE or JME (14 years each; p ≤ 0.001). Long-term seizure outcome hardly differed between the three subsyndromes. At the end of follow-up, 60% of all patients were in 5-year terminal seizure remission, and in 14%, epilepsy even had resolved (>10 years without seizures, >5 years without pharmacotherapy). Twenty percent of patients had persistent seizures during the last year of follow-up. Across all patients, 23% reported a psychiatric comorbidity, 87% had married, and 57% had achieved university entrance qualification.
SIGNIFICANCE
Long-term outcome was shown to be highly similar across all subsyndromes of adolescent-onset GGE. Even in a selection of difficult-to-treat epilepsy patients still attending an adult epilepsy clinic, most become seizure-free. To confirm these findings, prospective studies are needed. | 10.1111/epi.13761 |
pubmed_635_2138 | BACKGROUND
Allogeneic skin grafts onto C57BL/6 mice are rejected, and the rejected skin is replaced by surrounding skin with black hair. In contrast, syngeneic skin grafts are tolerated, and gray hair grows on the grafts.
METHODS
To explore the mechanism of gray hair growing on the tolerated skin grafts, we prepared full-thickness skin (2-cm square) autografts, 2 (2 cm + 2 cm) horizontal or vertical parallel incisions, and U-shaped (2 cm × 2 cm × 2 cm) flaps with or without pedicle vessels. The grafts, incisions, and flaps were fixed by suturing with string and protected by a transparent bandage. On day 14 after the operation, the bandages were removed to observe the color of the hair growing on the skin.
RESULTS
Skin autografts from wild-type or hepatocyte growth factor-transgenic (Tg) C57BL/6 mice survived with gray hair, whereas those from steel factor (Kitl)-Tg C57BL/6 mice survived with black hair. In addition, U-shaped flaps lacking both of the 2 main feeding vessels of wild-type mice had gray hair at the tip of the flaps. Light microscopy after staining with hematoxylin and eosin or dihydroxyphenylalanine showed that the formation of melanin pigment in the follicles, but not in the interadnexal skin, was susceptible to the blood supply.
CONCLUSIONS
Melanin pigment formation in the hair bulb melanocytes appeared to be susceptible to the blood supply, and melanocytosis was promoted in the follicles and in the epidermis of Kitl-Tg C57BL/6 mice. | 10.1097/GOX.0000000000000284 |
pubmed_95_7353 | Emerging evidence indicates the importance of nucleosides and nucleotides in the maintenance of functions of the bone marrow hematopoietic cells, intestinal mucosa, and the brain, which have limited de novo synthesis of purine and pyrimidine bases. We have found that nucleosides and nucleotides stimulate hemopoieses and increase peripheral neutrophil counts in mice treated with cyclophosphoamide. Intraperitoneal administration of nucleosides and nucleotides decreased bacterial translocation, the number of colony-forming units, and increased survival against methicillin-resistant Staphylococcus aureus. In vitro immune studies in mice showed that nucleosides and nucleotides increase the delayed-type cutaneous hypersensitivity and the popliteal lymph node blastogenic response to antigens, allogens, and mitogens. Both intraperitoneal and oral administration of nucleosides and nucleotides reduced endotoxin-induced bacterial translocation and improved injury to the gut in protein-deficient mice. However, oral administration of nucleosides and nucleotides in experimental colitis resulted in a worsening of colitic conditions and increased interleukin-8 and tumor necrosis factor-alpha concentrations in inflamed colonic portions, indicating the pro-inflammatory activities of nucleosides and nucleotides. Memory-deficient senescence-accelerated mice and mice with dementia showed improved memory with dietary nucleosides and nucleotides supplementation. These results indicate that supplementation with nucleosides and nucleotides is beneficial to the functions of the system and the brain. However, beneficial effects to the gut appear to depend on the type of damage sustained by the gut. | 10.1016/s0899-9007(96)00376-0 |
pubmed_573_14480 | BACKGROUND
The etiology of pediatric trigger thumb is unknown, although ultrasound in adults has shown thickening of the A1 pulley leading to constriction of the flexor pollicis longus (FPL) tendon. The purpose of this study is to characterize the underlying cause of the pediatric trigger thumb and factors responsible for resolution utilizing sonography.
METHODS
A prospective analysis of children with trigger thumbs was conducted from May 2008 through June 2010. All children were initially treated with splinting. Surgical release of the A1 pulley was performed at the family's request. Bilateral dynamic ultrasonography was performed at presentation and follow-up until resolution of triggering. Ultrasound images were evaluated for tendon gliding, echotexture, cross-sectional area, and anatomic variations.
RESULTS
There were 35 trigger thumbs in 28 patients. Ten thumbs resolved spontaneously. Eight patients (9 thumbs) underwent surgical release of the A1 pulley. One child who underwent bilateral release achieved only unilateral resolution. Ultrasound imaging of all 56 thumbs demonstrated normal echotexture of the FPL without evidence of inflammation or trauma. Triggering always occurred at the A1 pulley, and there was focal enlargement of the FPL but no definite ultrasound abnormality of the A1 pulley. Surgical release allowed the thickened tendon to pass smoothly, which coincided with resolution of triggering. Two of 3 patients with unilateral triggering presenting with a trigger ratio (cross-sectional area of involved maxFPL to uninvolved FPL) <1.5 converted to bilateral trigger thumbs. An FPL size for age graph was created for nontriggering thumbs in unilateral patients.
CONCLUSIONS
The pediatric trigger thumb is a developmental condition with normal echotexture noted in all FPL tendons without inflammation or trauma. Triggering occurs when the cross-sectional area of the FPL exceeds the cross-sectional area at the A1 pulley, and it resolves when this size disparity is eliminated. Patients with unilateral triggering and a trigger ratio <1.5 on the uninvolved thumb are at risk for developing triggering bilaterally.
LEVEL OF EVIDENCE
Level 2 diagnostic study. | 10.1097/BPO.0b013e318287f728 |
pubmed_1084_10972 | INTRODUCTION
Dog bites present a complex problem. Extensive facial trauma is a challenging problem to treat with priority for functional outcome. This paper describes the conservative treatment in a very difficult case of facial trauma with unusual infections due to the bites.
CASE REPORT
A 45 year-old woman was admitted in hypovolaemic shock with amputation of nose, upper and lower lips, left cheek and chin caused by dog bites. After vital parameters and volaemy were stabilized, wound toilet was performed, followed by skin and mucosal rotation flaps and anterior nasal tamponade; the lesion has then been covered with a collagen/oxidized regenerated cellulose dressing and sterile gauzes. Culture test highlighted coagulase-negative Staphylococcus and Candida albicans. However after few days, the patient developed septic-undulant hyperpyrexia, retinitis, renal candidiasis, folliculitis. Systemic Candida infection resistant to fluconazole was diagnosed. Amphotericin B was given to the patient and the facial wound was managed conservatively with an active medication because of inoperability conditions. The outcome of the use of active medications was an immediate response with excessive granulation tissue followed by a rapid re-epithelization.
CONCLUSION
As our case has shown, conservative treatment can be a valid alternative therapy in the treatment of large wounds with invasive candidosis and candidaemia or other major contraindications to surgery. In fact, in cases where surgical reconstruction is not a feasible option, conservative treatment can allow a rapid repair of the skin barrier. | pubmed_1084_10972 |
pubmed_455_18562 | CONTEXT
Since 1996, 414 laparoscopic live donor nephrectomy procedures have been completed at our institution. Although this procedure has gained acceptance within the past 5 years, little is known about its nursing implications.
OBJECTIVE
The purpose of this performance improvement project was to identify pain management practices, satisfaction levels, and clinical outcomes among patients undergoing laparoscopic live donor nephrectomy.
PATIENTS
Data were collected for a convenience sample of 70 patients for 18 months.
INTERVENTION
Several pain management methods were used, including patient-controlled analgesia and intramuscular and oral medications.
RESULTS
Pain ratings ranged from 3.2 to 3.8 for the first 36 hours postoperatively. The mean pain level did not differ significantly between pain regimes. At discharge, patients perceived a mean overall pain level of 5.0 but anticipated a pain level of 6.1. A significant negative correlation between satisfaction and pain rating also was noted.
CONCLUSIONS
Opportunities exist to standardize current regimens of pain medications and address pain level and treatment 24 hours postoperatively. | 10.1177/152692480301300208 |
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