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pubmed_842_19470
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Near-infrared spectroscopy (NIRS) for cerebral circulation monitoring has gained popularity in the neonatal intensive care setting, with studies showing the possibility of identifying preterm infants with intraventricular hemorrhage (IVH) by transfer function analysis of arterial blood pressure (BP) and NIRS measures. In this study, we examined a number of NIRS-derived measures in a cohort of preterm infants with IVH (n = 5) and without IVH (n = 12) within 1-3 hours after birth. The IVH infants were found to have significantly higher tissue oxygenation index (TOI), lower fractional tissue oxygen extraction (FTOE) and lower coherence between arterial BP and deoxygenated hemoglobin (HHb) in the very low frequency range (VLF, 0.02-0.04 Hz). Further studies with larger sample size are warranted for a more complete understanding of the clinical utility of these NIRS measures for early identification of IVH infants.
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10.1109/IEMBS.2011.6090547
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pubmed_169_11659
|
After extraction of 1% of the total collagen of rat skin by 150 mM NaCl, a 1% SDS solution extracts 80% of the total collagen, while the residue is extracted by a mixture of beta mercapto-ethanol and SDS. These extractions, which respect the peptide linkages, cleave the allysyl cross-links. They provide an insight on the composition of some insoluble collagen molecules of the skin and on the importance of disulfide bridges in their architecture.
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pubmed_169_11659
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pubmed_508_7174
|
BACKGROUND
While the role of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) in the diagnosis and management of choledocholithiasis is well established, this study evaluates the usefulness of ERCP and EST in patients with symptomatic cholecystolithiasis and suspected choledocholithiasis before undergoing laparoscopic cholecystectomy (LC), and the role of ERCP-EST in the management of complications resulting from LC.
MATERIALS AND METHODS
This paper reviews retrospectively our experience from 1992 to 1995. A total of 1221 LCs and 717 ERCPs were performed, out of which 257 ERCPs were performed on 225 patients who underwent LC (230 ERCPs before and 27 after). The age range was 10-85 years (mean 43.5). The study group comprised 148 females (66%) and 77 males (34%).
RESULTS
The overall success rate for ERCP was 92% (96% for diagnostic and 88% for therapeutic). Choledocholithiasis was found at preoperative ERCP in 45% of cases. Prediction of choledocholithiasis was accurate in 46%, based on abnormal liver chemistry, and 70% when based on a combination of abnormal liver tests and dilated main bile duct (>7 mm) by ultrasound. In 40 cases of acute biliary pancreatitis, choledocholithiasis was found at ERCP in eight cases (20%). In the post-LC group, all eight cases with residual stones and seven of eight cases with bile leaks were successfully treated endoscopically. There were four cases with major duct injuries that required surgical management. The complications related to ERCP-EST included two cases of bleeding post-EST (one was controlled with injection therapy and the second one was managed surgically), and three cases of mild pancreatitis.
CONCLUSION
ERCP and EST are effective and safe in the diagnosis and management of choledocholithiasis, and facilitate LC for symptomatic cholelithiasis. The procedures are also valuable in the diagnosis and management of most complications resulting from LC.
|
10.5144/0256-4947.1998.117
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pubmed_434_23970
|
Dopamine is an evolutionarily ancient neurotransmitter that plays an essential role in mediating behavior. In vertebrates, dopamine is central to the mesolimbic reward system, a neural network concerned with the valuation of stimulus salience, and to the nigrostriatal motor system and hypothalamic nuclei involved in the regulation of locomotion and social behavior. In amphibians, dopaminergic neurons have been mapped out in several species, yet the distribution of dopaminoreceptive cells is unknown. The túngara frog, Physalaemus pustulosus, is an excellent model system for the study of neural mechanisms by which valuations of stimuli salience and social decisions are made, especially in the context of mate choice. In order to better understand where dopamine acts to regulate social decisions in this species, we have determined the distribution of putative dopaminergic cells (using tyrosine hydroxylase immunohistochemistry) and cells receptive to dopaminergic signaling (using DARPP-32 immunohistochemistry) throughout the brain of P. pustulosus. The distribution of dopaminergic cells was comparable to other anurans. DARPP-32 immunoreactivity was identified in key brain regions known to modulate social behavior in other vertebrates including the proposed anuran homologues of the mammalian amygdalar complex, nucleus accumbens, hippocampus, striatum, preoptic area, anterior hypothalamus, ventromedial hypothalamus, and ventral tegmental area/substantia nigra pars compacta. Due to its widespread distribution, DARPP-32 likely also plays many roles in non-limbic brain regions that mediate non-social information processing. These results significantly extend our understanding of the distribution of the dopaminergic system in the anuran brain and beyond.
|
10.1159/000321715
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pubmed_918_24363
|
Rapid detection of drug resistance in Mycobacterium tuberculosis is important for the successful treatment of tuberculosis. Fluoroquinolone and aminoglycoside resistance detection by molecular methods becomes more complex due to cross resistance among them. Thus, we aimed to determine cross-resistance and mutations in resistance genes for these drugs. A total of 336 multidrug-resistant tuberculosis (MDR-TB) cases received in Mycobacteriology laboratory were screened for phenotypic drug sensitivity testing for second-line drugs, i.e., ofloxacin, amikacin, kanamycin, and capreomycin. Molecular characterization of resistance was done by DNA sequencing of gyrA gene for fluoroquinolones (FQ), and multiplex allele-specific polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (RFLP) of rrs gene for aminoglycosides. Of 336 MDR-TB isolates, 12 were extensively drug-resistant tuberculosis and 219 were sensitive to all the drugs tested. Ofloxacin, amikacin, kanamycin, and capreomycin resistance was detected in 101 (30.1%), 23 (6.8%), 27 (8.1%), and 19 (5.6%) cases, respectively. Eight different mutations were detected in gyrA gene in ofloxacin-resistant isolates and A1401G nucleotide change in rrs gene were seen in 55.6% (15/27), 65.2% (15/23), and 68.4% (13/29) for kanamycin-, amikacin-, and capreomycin-resistant isolates, respectively. Information on second-line drug resistance-associated mutations could potentially be used for development of newer rapid diagnostic tests.
|
10.2991/j.jegh.2018.02.100
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pubmed_576_3165
|
Interaction forces and topography of mixed phospholipid-glycolipid bilayers were investigated by atomic force microscopy (AFM) in aqueous conditions with probes functionalized with self-assembled monolayers terminating in hydroxy groups. Short-range repulsive forces were measured between the hydroxy-terminated probe and the surface of the two-dimensional (2-D) solid-like domains of distearoyl-phosphatidylethanolamine (DSPE) and digalactosyldiglyceride (DGDG). The form and range of the short-range repulsive force indicated that repulsive hydration/steric forces dominate the interaction at separation distances of 0.3-1.0 nm after which the probe makes mechanical contact with the bilayers. At loads < 5 nN the bilayer was elastically deformed by the probe, while at higher loads plastic deformation of the bilayer was observed. Surprisingly, a short-range repulsive force was not observed at the surface of the 2-D liquid-like dioleoylphosphatidylethanolamine (DOPE) film, despite the identical head groups of DOPE and DSPE. This provides direct evidence for the influence of the structure and mechanical properties of lipid bilayers on their interaction forces, an effect which may be a major importance in the control of biological processes such as cell adhesion and membrane fusion. The step height measured between lipid domains in the AFM topographic images was larger than could be accounted for by the thickness and mechanical properties of the molecules. A direct correlation was observed between the repulsive force range over the lipid domains and the topographic contrast, which provides direct insight into the fundamental mechanisms of AFM imaging in aqueous solutions. This study demonstrates that chemically modified AFM probes can be used in combination with patterned lipid bilayers as a novel and powerful approach to characterize the nanometer scale chemical and physical properties of heterogeneous biosurfaces such as cell membranes.
|
10.1039/a807637e
|
pubmed_1050_25046
|
Song and colleagues describe how N-glycans stabilize expression of checkpoint molecule B7-H4 that suppresses T-cell function. Inhibiting N-glycan stabilization of B7-H4 generates an immune hot cancer that is more responsive to combination therapies.See related article by Song et al., p. 1872.
|
10.1158/2159-8290.CD-20-1355
|
pubmed_1023_5666
|
Investigations regarding the chemical composition of the volatiles in male mouse urine have recently enabled the structural elucidation of a hitherto unreported urinary component, 7-exo-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]-3-octene. This compound's uniqueness to mouse urine and its dependence on testosterone levels in the male suggest its probable role as a mouse pheromone or pheromone adjuvant.
|
10.1007/BF01963608
|
pubmed_793_12533
|
A new variant of glucosephosphate isomerase (GPI) associated with hemolytic anemia, mental retardation, and muscular hypotonia is described. The defective enzyme showed increased affinity for fructose-6-phosphate (F-6-P), decreased affinity for glucose-6-phosphate (G-6-P) altered electrophoretic and isoelectrofocusing patterns, and shift to the left of the precipitin curve. The enzyme was stable under all the conditions tested (heat, urea, guanidine-HCl, and storage). Optimum pH, Ki for 6-phosphogluconic acid (6-PGA) and for erythrose-4-phosphate (E-4-P), molecular weight, GPI-related antigen concentration, immunodiffusion pattern, and immunoinactivation were in the normal range. This is the first example of the association of a stable mutant GPI with severe hemolytic anemia. Enzyme instability has been present in all previously reported cases.
|
10.1002/ajh.2830090102
|
pubmed_635_24843
|
BACKGROUND
Euthanasia remains a controversial topic in both public discourses and legislation. Although some determinants of acceptance of euthanasia and physician-assisted death have been identified in previous studies, there is still a shortage of information whether different forms of euthanasia are supported by the same or different sub-populations and whether authoritarian personality dispositions are linked to attitudes towards euthanasia.
METHODS
A large, representative face-to-face survey was conducted in Austria in 2014 (n = 1,971). Respondents faced three scenarios of euthanasia and one of physician assisted death differing regarding the level of specificity, voluntariness and subject, requiring either approval or rejection: (1) abstract description of euthanasia, (2) abstract description of physician-assisted suicide, (3) the case of euthanasia of a terminally-ill 79-year old cancer patient, and (4) the case of non-voluntary, physician assisted death of a severely disabled or ill neonate. A number of potential determinants for rejection ordered in three categories (socio-demographic, personal experience, orientations) including authoritarianism were tested via multiple logistic regression analyses.
RESULTS
Rejection was highest in the case of the neonate (69%) and lowest for the case of the older cancer patient (35%). A consistent negative impact of religiosity on the acceptance across all scenarios and differential effects for socio-economic status, area of residence, religious confession, liberalism, and authoritarianism were found. Individuals with a stronger authoritarian personality disposition were more likely to reject physician-assisted suicide for adults but at the same time also more likely to approve of physician-assisted death of a disabled neonate.
CONCLUSION
Euthanasia in adults was supported by a partially different sub-population than assisted death of disabled neonates.
|
10.1371/journal.pone.0124320
|
pubmed_1095_11742
|
We report the case of a 53-year-old woman with Ebstein's anomaly and intractable heart failure who had undergone only tricuspid valve replacement 30 years earlier. She was treated conservatively for 1 month; however, she was placed in the New York Heart Association functional class IV. Therefore, we operated on her with the objective of improving her quality of life and cardiac function. One-and-a-half repair and a second tricuspid valve replacement with right ventriculoplasty were quite effective in ameliorating her critical condition.
|
10.1016/j.athoracsur.2007.06.065
|
pubmed_639_14550
|
Within long-term symbioses, animals integrate their physiology and development with their symbiont. In a model nutritional mutualism, aphids harbor the endosymbiont, Buchnera, within specialized bacteriocyte cells. Buchnera synthesizes essential amino acids (EAAs) and vitamins for their host, which are lacking from the aphid's plant sap diet. It is unclear if the aphid host differentially expresses aphid EAA metabolism pathways and genes that collaborate with Buchnera for the production of EAA and vitamins throughout nymphal development when feeding on plants. It is also unclear if aphid bacteriocytes are differentially methylated throughout aphid development as DNA methylation may play a role in gene regulation. By analyzing aphid gene expression, we determined that the bacteriocyte is metabolically more active in metabolizing Buchnera's EAAs and vitamins early in nymphal development compared to intermediate or later immature and adult lifestages. The largest changes in aphid bacteriocyte gene expression, especially for aphid genes that collaborate with Buchnera, occurred during the 3rd to 4th instar transition. During this transition, there is a huge shift in the bacteriocyte from a high energy "nutrient-consuming state" to a "recovery and growth state" where patterning and signaling genes and pathways are upregulated and differentially methylated, and de novo methylation is reduced as evidenced by homogenous DNA methylation profiles after the 2nd instar. Moreover, bacteriocyte number increased and Buchnera's titer decreased throughout aphid nymphal development. These data suggest in combination that bacteriocytes of older nymphal and adult lifestages depend less on the nutritional symbiosis compared to early nymphal lifestages.
|
10.1093/g3journal/jkab115
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pubmed_1100_20402
|
The E. coli chromosome is known to carry at least five genes, each of which codes for a "D-E-A-D" box protein that is presumed to possess an ATP-dependent RNA helicase activity. Four of such genes (srmB, deaD, dbpA and rhlB) were already mapped on the E. coli chromosome and their DNA sequences determined. We here report the complete nucleotide sequence of the remaining rhlE gene located at about 17.8 min on the E. coli genetic map. RhlE protein possesses all of the motifs (I to VI) conserved among prokaryotic and eukaryotic "D-E-A-D" proteins and has an arginine-rich carboxyl-terminal region. A null mutant of the rhlE gene was constructed by a new method with a ColE1 plasmid mutant that replicates in RNAse HI-deficient bacterial strains, but not in the wild-type strains. The delta rhlE mutant can grow normally, implying that the rhlE gene product is nonessential for bacterial cell growth.
|
10.1266/jjg.69.1
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pubmed_512_7086
|
Promotion of cell adhesion on biomaterials is crucial for the long-term success of a titanium implant. Herein a novel concept is highlighted combining very stable and affine titanium surface adhesive properties with specific cell binding moieties in one molecule. A peptide containing L-3,4-dihydroxyphenylalanine was synthesized and affinity to titanium was investigated. Modification with a cyclic RGD peptide and a heparin binding peptide (HBP) was realized by an efficient on-resin combination of Diels-Alder reaction with inverse electron demand and Cu(I) catalyzed azide-alkyne cycloaddition. The peptide was fluorescently labeled by thiol Michael addition. Conjugating the cyclic RGD and HBP in one peptide gave improved spreading, proliferation, viability, and the formation of well-developed actin cytoskeleton and focal contacts of osteoblast-like cells.
|
10.1002/anie.201511781
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pubmed_582_10865
|
The role of social capital in promoting health is now widely debated within international public health. In relation to HIV, the results of previous observational and cross-sectional studies have been mixed. In some settings it has been suggested that high levels of social capital and community cohesion might be protective and facilitate more effective collective responses to the epidemic. In others, group membership has been a risk factor for HIV infection. There have been few attempts to strengthen social capital, particularly in developing countries, and examine its effect on vulnerability to HIV. Employing data from an intervention study, we examined associations between social capital and HIV risk among 1063 14 to 35-year-old male and female residents of 750 poor households from 8 villages in rural Limpopo province, South Africa. We assessed cognitive social capital (CSC) and structural social capital (SSC) separately, and examined associations with numerous aspects of HIV-related psycho-social attributes, risk behavior, prevalence and incidence. Among males, after adjusting for potential confounders, residing in households with greater levels of CSC was linked to lower HIV prevalence and higher levels of condom use. Among females, similar patterns of relationships with CSC were observed. However, while greater SSC was associated with protective psychosocial attributes and risk behavior, it was also associated with higher rates of HIV infection. This work underscores the complex and nuanced relationship between social capital and HIV risk in a rural African context. We suggest that not all social capital is protective or health promotive, and that getting the balance right is critical to informing HIV prevention efforts.
|
10.1016/j.socscimed.2008.01.023
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pubmed_330_22871
|
Animals and plants are exposed to myriads of potential microbial invaders. In case of animals, Toll-like receptors (TLRs) act as the primary defense against infection by pathogens. Arguably, less is known regarding the activation of TLRs that connect the innate and adaptive immune systems. Some TLR ligands have been used as adjuvants in various vaccines and have gained a great deal of attention due to their ability to elicit an effective immune response. Understanding the intricate relationships between various molecules involved in TLR signaling and their positive or negative regulation is a key focus for the development of effective therapeutics. In this review, recent developments in TLR signaling that will be very important in providing new drug target molecules and a better understanding of molecular regulation of innate immunity are discussed.
|
10.1007/s12272-009-2100-6
|
pubmed_349_15574
|
OBJECTIVE
The aim of this study was to determine oncological outcomes and incidence of lymph node (LN) metastases in women who underwent systematic pelvic and paraaortic lymphadenectomy for surgical staging of apparent stage I low-grade epithelial ovarian cancer (LGEOC).
MATERIALS AND METHODS
A retrospective study was performed at nine institutions across Europe and the US, and patients who underwent surgical staging for presumed stage I LGEOC between 2000 and 2016 were included. To ensure surgical quality, a minimum number of ≥10 pelvic and ≥10 paraaortic LNs was required. Patients with preoperative radiologic or clinical evidence of extraovarian or LN disease, and those with nonepithelial histology, were excluded.
RESULTS
The overall incidence of LN metastases was 4.3% in the 163 evaluated patients, and the incidence of LN involvement in serous, endometrioid, and mucinous subtypes was 10.7, 1.5, and 0%, respectively. However, Upstaging due to LN involvement alone occurred in only 2.4% of the patients. Eighty-nine (54.6%) patients received adjuvant chemotherapy due to International Federation of Gynecology and Obstetrics stage IC or higher disease. The 5-year progression-free survival (PFS) and overall survival (OS) were 93.2% (95% confidence interval [CI] 89.4-97.1%) and 94.5% (95% CI 90.9-98.0%), respectively. There was no significant difference in PFS or OS between LN-negative and LN-positive patients. However, fewer patients received adjuvant chemotherapy in the LN-negative group. Multivariate analysis did not identify any independent prognostic factor of survival.
CONCLUSION
The risk of LN involvement in nonserous apparent stage I LGEOC appears low, with a rate of <1% in this retrospective analysis, raising questions about the value of lymphadenectomy in those patients. Larger-scale prospective studies are warranted to evaluate the oncologic safety of omitting systematic LN staging in apparent stage I nonserous LGEOC.
|
10.1245/s10434-017-5919-y
|
pubmed_617_1180
|
OBJECTIVES
This article explains how the issue of stakeholder involvement was addressed in the European network for Health Technology Assessment (EUnetHTA) Project and describes the structures of future stakeholder involvement in the EUnetHTA Collaboration.
METHODS
Initiatives led to a dialogue with stakeholders and exchanging views and expectations on health technology assessment (HTA) processes and the future development of EUnetHTA. The methods of involving different stakeholder groups in EUnetHTA included general information to stakeholders about EUnetHTA, targeted information on a Web site, analysis of stakeholder opinions on HTA and EUnetHTA, and development of a draft stakeholder policy.
RESULTS
First steps were taken to organize processes to consolidate the legitimacy of EUnetHTA and its products and encourage the representation of interests, thus contributing to promoting the utilization of HTA in national/regional policy making. A stakeholder Web site, analyses of stakeholder opinions on HTA and EUnetHTA in a discussion topic catalog, and a draft stakeholder policy resulted from the work.
CONCLUSIONS
Stakeholder involvement in EUnetHTA is necessary to ensure the legitimacy and prospects for utilization of EUnetHTA and its products. The described activities and results create the foundation for a continued dialogue with, and involvement of, stakeholders. The EUnetHTA stakeholder meeting can be considered as a successful experience of dialogue between EUnetHTA and stakeholders, which should be continued. Our experience shows the challenge of obtaining balanced stakeholder representation across the identified stakeholder groups. Continued attention should be given to achieving balanced stakeholder representation.
|
10.1017/S0266462309990729
|
pubmed_223_13722
|
Intraoperative frozen section plays an important role in surgical management of ovarian masses. Many hospitals in low- and middle-income countries lack this intraoperative pathologic guidance. In this retrospective analysis, we assessed the management of 62 patients who underwent surgical treatment for ovarian masses at Bhaktapur Cancer Hospital in Nepal in light of the final histopathology results. Final histopathology found that 64.5% of the ovarian masses were malignant, 1.0% were borderline, and 30.6% were benign. 55 of the 62 total cases were considered "clinically suspicious" and 52 of the 62 cases underwent hysterectomy and staging procedures in addition to oophorectomy. There was no significant difference in the surgical management or in the postoperative complications when comparing benign, borderline, and malignant masses. Without the support of intraoperative frozen section, benign and malignant masses were treated the same way. The majority of benign cases were overtreated and were exposed to additional risks of postoperative complications. Several malignant cases were undertreated and required additional surgery to appropriately treat and stage malignant ovarian masses. Improved pathology support in Bhaktapur Cancer Hospital would result in better patient outcomes, fewer complications, and avoidance of additional staging surgeries.
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10.1016/j.gore.2020.100589
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pubmed_720_22240
|
H13 die steel is characterized by its high hardness and need for special surface features that are obtained by nontraditional machining processes. Electrical discharge machining (EDM) is used to machine hard materials and to produce complicated shapes. In this work, different EDM process parameters are investigated on H13 die steel. Several experiments are conducted to study the effect of three process parameters: peak current (Ip), pulse on-time (Ton) and electrode material on the machining process of H13 die steel. The machining process is evaluated by material removal rate (MRR), electrode wear ratio (EWR%) and surface roughness (SR) as indicators of the process efficiency in terms of quality and cost. Taguchi method was used to investigate the significant effect of process parameters on the performance measurements and the optimal parameters of the EDM process. For analysis and explanations Minitab version 17 software was used. Different process parameters were experimentally investigated and statistically analyzed and the results showed that the copper electrode leads to the highest MRR and lowest EWR%; whereas the brass electrode leads to the lowest SR.
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10.1016/j.heliyon.2019.e01813
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pubmed_957_3515
|
In order to explore the diagnostic effect of the expert system in knee sports injury, a method of diagnostic value of expert system in sports knee sports injury is proposed. This paper mainly takes 200 professional football players in sports higher vocational colleges as the research object. There are 146 male athletes and 44 female athletes; we establish a football injury ontology knowledge base and use a reasoning engine to build an intelligent expert system diagnosis system, allowing users to quickly discover diseases, accurately diagnose injuries, and obtain the best means of rehabilitation. Through the investigation, it can be seen that the body parts caused by football injuries are more complex, and the types of injuries in each part are also different. Therefore, it is particularly important to establish an intelligent retrieval system with convenient query and clear diagnosis by the expert system. With the birth and development of computer and artificial intelligence technology, the development of artificial intelligence expert systems in the medical field has become a reality. The construction of this system will have theoretical and practical significance and application value.
|
10.1155/2022/1892877
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pubmed_576_22915
|
Allogeneic haematopoietic cell transplantation (HCT) is the only therapeutic modality capable of correcting the haematologic manifestations of Fanconi anaemia (FA). However, HCT from alternative donors has been associated with poor survival. Between June 1993 and July 1998, 29 FA patients (median age 12.1 years; range 3.7-48.5 years) were enrolled in a prospective phase I-II dose escalation study. All patients were treated with cyclophosphamide 40 mg/kg, total body irradiation (TBI) 450 cGy or 600 cGy and antithymocyte globulin (ATG), followed by HCT from an alternative donor. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A for 6 months, short course methylprednisolone (2 mg/kg/day) between days +5 and +19 and marrow T-cell depletion by counterflow elutriation. The probability of developing grade III-IV toxicity was 17% (95% CI 3-31%). For the 25 marrow recipients, the probability of neutrophil engraftment (ANC 0.5 x 109/l by day 45) was 63% (95% CI 42-82%). Probabilities of grade II-IV acute GVHD and chronic GVHD were 32% (95%CI 10-54%) and 0% respectively. With a median follow-up of 18 months, the probability of survival for the entire cohort at 1 year was 34% (95% CI 17-51%). The presence of lymphocyte somatic mosaicism [i.e. the presence of diepoxybutane (DEB)-insensitive cells] was associated with a significantly increased risk of graft failure. Disappointingly, the use of higher dose TBI and post-transplant ATG did not improve engraftment. More effective peritransplant immunosuppression, especially in FA patients with somatic mosaicism, was required to overcome the barrier of graft rejection. New conditioning regimens adapted to each individual's alkylator sensitivity are needed to improve the outcome of alternative donor HCT for FA.
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10.1046/j.1365-2141.2000.01955.x
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pubmed_524_19949
|
Composite films comprising modified corn starch and gelatin were developed using a solvent casting technique. The effect of varied content of citric acid and gelatin on the functional properties of the corn starch and composite films, respectively, was investigated. Modified corn starch films enriched with 5% citric acid presented excellent film properties like solubility, swelling index, water vapor permeability, and mechanical property as compared to other films. Similarly, composite films enriched with a ratio (4:1) also exhibited excellent film properties like mechanical and opacity than other composite films. FTIR results confirmed the cross linking among the modified corn starch chains, which is responsible for the enhancement in the film properties. From SEM results, it was noticed that the modified corn starch films exhibited slightly rougher, less shiny than the composite films. Efficacy of the composite solution as a coating formulation in terms of the quality and shelf life of the cucumber investigated. From the results, it was noted that the composite film forming solution as a coating formulation has the potential to extend the shelf-life of the cucumbers additionally up to 16 days.
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10.1007/s13197-020-04685-y
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pubmed_48_24886
|
Silver nanoparticles (AgNPs) are superior cluster of nanomaterials that are recently recognized for their different applications in various pharmaceutical and clinical settings. The objective of this work deals with novel method for biosynthesis of AgNPs using Azadirachta indica (neem) leaf extract as reducing agent. These bio and chemical synthesized nanoparticles were characterized with the help of UV-vis Spectroscopy, Nanotarc, Dynamic light scattering (DLS), Zeta Potential (ZP), Transmission Electron Microscopy and Fourier transform infrared spectroscopy (FTIR). The obtained results from Nanotrac and TEM revealed that the synthesized AgNPs possess spherical shape with a mean diameter at 94nm for green and 104nm for chemical method, the zeta potential values was -12.02mV for green AgNPs and -10.4mV for chemical AgNPs. In addition, FT-IR measurement analysis was conceded out to identify the Ag+ ions reduced from the specific functional groups on the AgNPs, which increased the stability of the particles. Further, we compared the toxicities of green and chemical AgNPs against human skin dermal fibroblast (HDFa) and brine shrimp followed by anticancer activity in NCI-H460 cells. We observed green AgNPs cause dose-dependent decrease in cell viability and increase in reactive oxygen species (ROS) generation. Further, we proved to exhibit excellent cytotoxic effect and induction of cellular apoptosis in NCI-H460 cells. Furthermore, green AgNPs had no significant changes in cell viability, ROS production and apoptotic changes in HDFa cells. In contrary, we observed that the chemical AgNPs possess significant toxicities in HDFa cells. Hence, the green AgNPs were able to induce selective toxicity in cancer cells than the chemical AgNPs. Furthermore, green AgNPs exhibit less toxic effects against human red blood cells and brine shrimp (Artemia salina) nauplii than the chemical AgNPs. It was concluded, that apart from being superior over chemical AgNPs, the green AgNPs are effective and safer to the milieu as they show less toxic effect to normal cells and can be extensively applied in biomedical sciences particularly in cancer field.
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10.1016/j.biopha.2016.09.003
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pubmed_482_17142
|
BACKGROUND
Anxiety disorders and depression (emotional disorders) are highly prevalent mental disorders. Extensive empirical evidence supports the efficacy of cognitive behavioral therapy (CBT) for the treatment of these disorders. However, there are still some barriers related to their dissemination and implementation, which make it difficult for patients to receive these treatments, especially in public health care settings where resources are limited. Recent advances in improving CBT dissemination encompass different perspectives. One is the transdiagnostic approach, which offers treatment protocols that can be used for a range of emotional disorders. Another approach is the use of the internet to reach a larger number of people who could benefit from CBT.
OBJECTIVE
This study aimed to analyze the effectiveness and acceptability of a transdiagnostic internet-delivered protocol (EmotionRegulation) with human and automated guidance in patients from public specialized mental health care settings.
METHODS
A 2-armed randomized controlled trial (RCT) was conducted to compare the effectiveness of EmotionRegulation with treatment as usual (TAU) in specialized mental health care. In all, 214 participants were randomly assigned to receive either EmotionRegulation (n=106) or TAU (n=108). Measurement assessments were conducted at pre- and postintervention and at a 3-month follow-up.
RESULTS
The results revealed the superiority of EmotionRegulation over TAU on measures of depression (d=0.41), anxiety (d=0.35), and health-related quality of life (d=-0.45) at posttreatment, and these gains were maintained at the 3-month follow-up. Furthermore, the results for expectations and opinions showed that EmotionRegulation was well accepted by participants.
CONCLUSIONS
EmotionRegulation was more effective than TAU for the treatment of emotional disorders in the Spanish public mental health system. The implications of this RCT, limitations, and suggestions for future research are discussed.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02345668; https://clinicaltrials.gov/ct2/show/NCT02345668.
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10.2196/18220
|
pubmed_121_4439
|
Ever greater technological advances and democratization of digital tools such as computers and smartphones offer researchers new possibilities to collect large amounts of health data in order to conduct clinical research. Such data, called real-world data, appears to be a perfect complement to traditional randomized clinical trials and has become more important in health decisions. Due to its longitudinal nature, real-world data is subject to specific and well-known methodological issues, namely issues with the analysis of cluster-correlated data, missing data and longitudinal data itself. These concepts have been widely discussed in the literature and many methods and solutions have been proposed to cope with these issues. As examples, mixed and trajectory models have been developed to explore longitudinal data sets, imputation methods can resolve missing data issues, and multilevel models facilitate the treatment of cluster-correlated data. Nevertheless, the analysis of real-world longitudinal occupational health data remains difficult, especially when the methodological challenges overlap. The purpose of this article is to present various solutions developed in the literature to deal with cluster-correlated data, missing data and longitudinal data, sometimes overlapped, in an occupational health context. The novelty and usefulness of our approach is supported by a step-by-step search strategy and an example from the Wittyfit database, which is an epidemiological database of occupational health data. Therefore, we hope that this article will facilitate the work of researchers in the field and improve the accuracy of future studies.
|
10.3390/ijerph19127023
|
pubmed_851_25977
|
BACKGROUND
Cervical magnetic resonance imaging (MRI) is the gold standard exam in the assessment of patients affected by cervical myelopathy and is very useful in planning the operation. Herein we present a series of patients affected by long tract symptoms who underwent dynamic MRI in addition to the static exam.
METHODS
In the period between March 2010 and March 2012, three-hundred-ten patients referred to our department since affected by neck/arm pain or symptoms related to cervical myelopathy. Thirty-eight patients complained "long-tract symptoms" related to cervical myelopathy. This series of patients was enrolled in the study. All patients underwent clinical and neurological exam. In all the cases, a static and dynamic cervical MRI was executed using a 3.0-T superconducting MR unit (Intera, Philips, Eindhoven, Netherlands). The dynamic exam was performed with as much neck flexion and extension the patient could achieve alone. On T2-weigthed MRI each level was assessed independently by two neuroradiologists and Muhle scale was applied.
RESULTS
According to Muhle's classification of spinal cord compressions, static MRI demonstrated 156 findings: 96 (61.54%) anterior and 60 (38.46%) posterior. Dynamic MRI showed 186 spinal cord compressions: 81 (43.5%) anterior and 105 (56.5%) posterior. The anterior compressions were: grade 1 in 23 cases (28.4%), grade 2 in 52 cases (64.2%), grade 3 in 6 cases (7.4%). The posterior compressions were: 32 (30.48%) of grade 1, 60 (57.14%) of grade 2, 13 (12.38%) of grade 3.
CONCLUSIONS
The dynamic MRI demonstrated a major number of findings and spinal cord compressions compared to the static exam. Finally, we consider the dynamic exam able to provide useful information in these patients, but we suggest a careful evaluation of the findings in the extension exam since they are probably over-expressed.
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10.21037/jss.2017.06.01
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pubmed_716_20074
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A health economic evaluation (HEE) is a comparative analysis of alternative courses of action in terms of both costs and consequences. A cost-effectiveness analysis is a type of HEE that compares an intervention to one or more alternatives by estimating how much it costs to gain an additional unit of health outcome. Cost-effectiveness analyses are commonly performed using Microsoft (MS) Excel. However, there is current interest in using other software that is better suited to more complex problems, methods, and data, as well as improved reproducibility and transparency. That is, it is increasingly important to be able to repeat an analysis of a particular data set and obtain the same results, and access the analysis and results in a clear and comprehensive openly available form. In this tutorial we provide a step-by-step guide on how to implement a mainstay model of HEE, namely a Markov model, in the statistical programming language R. The adoption of R for the purpose of cost-effectiveness analysis is highly dependent on the ability of the health economic modeller to understand, learn, and apply programming-type skills. R is likely to be less familiar than MS Excel for many modellers and so coding a cost-effectiveness model in R can be a large jump. We describe the technical details from the perspective of a MS Excel user to help bridge the gap between software and reduce the learning curve by providing for the first-time side-by-side comparisons of the Markov model example in MS Excel and R.
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10.1007/s40273-022-01199-7
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pubmed_809_10264
|
BACKGROUND
Stroke has emerged as an important complication of thoracic endovascular aortic repair (TEVAR). Identifying risk factors for stroke is important to define the risks of this procedure.
METHODS
All neurologic complications were analyzed in a prospective database of patients in thoracic aortic stent graft trials from 1999 to 2006. Serial neurological examination was performed. Stroke was defined as any new onset focal neurologic deficit.
RESULTS
The TEVAR was performed on 171 patients; 52 had lesions requiring coverage of the proximal descending thoracic aorta (extent A), 50 requiring coverage of the distal descending aorta (extent B), and 69 requiring coverage of the entire descending thoracic aorta (extent C). The incidence of stroke was 5.8%. Eighty-nine percent (8 of 9) of strokes occurred within 24 hours of operation. Stroke was associated with a 33% in-hospital mortality rate. Risk factors identified for stroke included prior stroke (odds ratio [OR] 9.4, confidence interval [CI] 2.3 to 38.1, p = 0.002) and extent A or C coverage (OR 5.5, CI 1.7-12.5, p = 0.001). The stroke rate in patients with both prior stroke and extent A or C coverage was 27.7%. Severe atheromatous disease involving the aortic arch by computed tomographic scan was strongly associated with perioperative stroke (OR = 14.8, CI 1.7 to 675.6, p = 0.0016). Transesophageal echocardiography demonstrated mobile atheroma in two patients with stroke.
CONCLUSIONS
Stroke after TEVAR was associated with a high mortality. The TEVAR of the proximal descending aorta (extent A or C) in patients with a history of stroke had the highest perioperative stroke rate. These risk factors, together with high grade aortic atheroma of the aortic arch, predicted a high probability for cerebral embolization and can be used to identify patients at high risk for stroke as a consequence of TEVAR.
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10.1016/j.athoracsur.2007.04.128
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pubmed_111_14673
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There have been several reports of paraplegia after intraaortic balloon counterpulsation in the surgical literature. In each instance, the paraplegia occurred during the period of counterpulsation support. We describe a patient in whom late paraplegia occurred three days after the removal of an intraaortic balloon catheter.
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10.1016/s0003-4975(10)60047-1
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pubmed_362_9283
|
Cyanobacteria, as one of the largest groups of phototrophic bacteria, have a high potential as an excellent source of fine chemicals and bioactive compounds, including lipid-like compounds, amino acid derivatives, proteins, and pigments. This study aimed to synthesize ZnO nanoparticles using the cell extract of the cyanobacterium Nostoc sp. EA03 (CEN-ZnO NPs) through a rapid and eco-friendly approach. The biosynthesized nanoparticles, CEN-ZnO NPs, were characterized by UV-Vis spectroscopy, X-ray diffraction (XRD), zeta potential measurement, differential scanning calorimetry (DSC)/thermogravimetric analysis (TGA), FTIR, SEM, TEM, and EDX spectroscopy. The UV-Vis spectrum showed an absorption peak at 370 nm. The star-shaped CEN-ZnO NPs, as observed in the TEM and SEM images, had an average diameter of 50-80 nm. MIC and MBC values for E. coli, P. aeruginosa and S. aureus, were determined to be, respectively, 2000, 2000, and 64 μg ml-1, and 2500, 2500 and 128 μg ml-1. Further analysis through confocal laser scanning microscopy (CLSM) provided the observable confirmation that the CEN-ZnO NPs stunted the bacterial growth, preventing the formation of exopolysaccharides. The AFM analysis of surface topography of bacterial biofilm samples treated with CEN-ZnO NPs showed a rugged topography in some parts of the biofilm surface, indicating the destruction of biofilms. In contrast, in the untreated control samples, the structured biofilms were flat and prominent. MTT assay indicated that CEN-ZnO NPs had less cytotoxicity on the MRC-5 lung fibroblast cells compared with the cancerous treated A549 cells. As the concentration of the CEN-ZnO NPs increased, the amount of ROS produced in the tested bacterial strains also increased. Analyzing the data obtained from flow cytometry showed that the higher concentrations of CEN-ZnO NPs lead to a reduction in the viability of P. aeruginosa PAO1, E. coli and S. aureus. The biosynthesized ZnO nanoparticles using Nostoc cell extracts exhibited different attributes, inspiring enough to be considered for further investigation.
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10.1039/c9ra03962g
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pubmed_424_24135
|
OBJECTIVE
To determine the characteristics of depressed older patients whose mental health status is detected by their general practitioner (GP).
METHOD
Cross-sectional analytical design of 218 patients scoring above the cut-off (> or = 16) of the Center for Epidemiological Studies-Depression Scale (CES-D), from a sample of 916 consecutive patients aged 60 years or over attending one of 54 randomly selected GPs in Western Australia. Prior to their medical consultation, patients completed a self-report questionnaire, which included questions about depressive symptomatology (CES-D). Following the consultation, general practitioners recorded the patient's presenting complaint(s), medication information, and mental health details on a patient summary sheet.
RESULTS
Among these 218 patients, 39.9% (87/218) were correctly classified as depressed by their GP. Detection of depressive symptomatology was associated with patients who acknowledged taking sleeping tablets (OR = 2.6, 95% CI = 1.3-5.4), had CES-D scores indicative of major depression (> or = 22) (OR = 2.8, 95% CI = 1.4-5.6) and were thought to be at risk for suicide (OR = 35.1, 95% CI = 4.5-274.2).
CONCLUSIONS
While GPs are most apt to detect depression among older patients with prominent mental health symptoms, many patients in this age group silently experience significant depressive symptomatology and miss the opportunity for effective treatment. The routine use of screening tools in primary care is recommended to enhance the detection rate of depression in older adults.
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10.1080/j.1440-1614.2005.01563.x
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pubmed_659_3432
|
The effector functions of the IgGs are modulated by the N-glycosylation of their Fc region. Particularly, the absence of core fucosylation is known to increase the affinity of IgG1s for the Fcγ receptor IIIa expressed by immune cells, in turn translating in an improvement in the antibody-dependent cellular cytotoxicity. However, the impact of galactosylation and sialylation is still debated in the literature. In this study, we have investigated the influence of high and low levels of core fucosylation, terminal galactosylation and terminal α2,6-sialylation of the Fc N-glycans of trastuzumab on its affinity for the FcγRIIIa. A large panel of antibody glycoforms (i.e., highly α2,6-sialylated or galactosylated IgG1s, with high or low levels of core fucosylation) were generated and characterized, while their interactions with the FcγRs were analysed by a robust surface plasmon resonance-based assay as well as in a cell-based reporter bioassay. Overall, IgG1 glycoforms with reduced fucosylation display a stronger affinity for the FcγRIIIa. In addition, fucosylation, and the presence of terminal galactose and sialic acids are shown to increase the affinity for the FcγRIIIa as compared to the agalactosylated forms. These observations perfectly translate in the response observed in our reporter bioassay.
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10.1016/j.crimmu.2020.06.001
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pubmed_1039_10915
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A proposal is described that justified adding one full-time equivalent (FTE) pharmacist in a 125-bed community hospital that already employed in its pharmacy department 2.5 FTE pharmacists and 5.2 FTE other personnel. The administrative steps taken included identifying the need for an additional staff member and documenting the cost effectiveness of various clinical activities. Literature references were used to justify the proposed ratio of pharmacists to technicians; to show the results of deficiencies in supervision, motivation, and scheduling; and to demonstrate the cost effectiveness of serum concentration monitoring, formulary review, and patient discharge-medication consultations. Results of formulary review, drug-use audits, dosing guidelines, and serum concentration monitoring performed by the pharmacy department were included in the proposal. Prospective drug-use reviews, computerized pharmacokinetic dose determinations, additional educational programs, and tighter purchasing policies were identified as other cost-saving activities that could be performed with an additional pharmacist. A 12-page proposal was submitted in July 1983 to the hospital administrator and the budget review committee, and the additional staff position was approved. The key to maintaining the new pharmacist position will be the continual documentation of cost-saving activities within the department.
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pubmed_1039_10915
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pubmed_87_9617
|
OBJECTIVES
To evaluate the prevalence of levothyroxine-treated hypothyroidism in rheumatoid arthritis (RA) patients at the time of RA diagnosis in comparison to age- and sex-specific general population. Other objectives were to determine whether the risk of hypothyroidism varies by age at the onset of RA, or by sex or rheumatoid factor (RF) status.
METHODS
We identified 7,209 incident RA patients diagnosed between January 2004 and December 2007 from a Finnish nationwide register of special reimbursements for medication costs. The presence of hypothyroidism at RA diagnosis was identified from the same register based on special reimbursement decisions for levothyroxine substitution. The prevalence of levothyroxine-treated hypothyroidism was compared to that of an age- and sex-specific Finnish population, and a standardised rate ratio (SRR) for hypothyroidism was calculated.
RESULTS
The SRR for levothyroxine-treated hypothyroidism preceding RA was 1.51 (95% CI 1.35 to 1.67). Neither RF status nor sex modified the risk, although the results did not reach statistical significance among men. The SRR was highest, almost 2.5 among younger female RA patients (20-49 years of age), the excess prevalence of hypothyroidism decreasing steadily and wearing off among patients who were older at the time of diagnosis. The absolute prevalence of hypothyroidism, however, increased with age as it does in the general population.
CONCLUSIONS
The risk of hypothyroidism is increased among RA patients already at the disease onset, especially among the young women, regardless of RF status. This calls for attention to screening for hypothyroidism in RA patients, preferably when RA has already been diagnosed.
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pubmed_87_9617
|
pubmed_664_10261
|
AIM
Increasing evidence suggests that overweight children are at increased risk of asthma. The association between weight gain and allergy is more complex. The aim was to evaluate the association between overweight or obesity and asthma, allergy, bronchial reactivity or atopic sensitization at school age in children with bronchiolitis in infancy.
SUBJECTS AND METHODS
Eighty-one children hospitalized for bronchiolitis at <24 months of age attended control visits at 7.2 and 12.3 years of ages. The visits consisted of medical examinations, weight and height measurements, body mass index (BMI) calculations, skin prick tests and exercise challenge tests. BMI >1.3 SD from age- and gender-specific references meant overweight and BMI >2.0 SD obesity.
RESULTS
Current or previous overweight or obesity did not increase the risk of asthma, allergy, bronchial reactivity or atopic sensitization at 7.2 or 12.3 years of age. Previous and current obesity decreased the risk of atopic dermatitis, and current overweight and obesity decreased the risk of sensitization to outdoor allergens at 12.3 years of age.
CONCLUSION
Previous or current overweight does not increase asthma or allergy risk but current obesity may decrease allergy risk at school age after bronchiolitis in infancy.
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10.1111/j.1651-2227.2011.02439.x
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pubmed_700_2084
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Fifty-one pediatric patients undergoing a first cadaveric kidney transplantation were followed for at least 2 years after grafting. They were divided into two groups: those treated with methylprednisolone plus azathioprine (AZA) and those treated with methylprednisolone plus low-dose cyclosporin A (CyA; median dose 109 mg/m2 per day = 3.4 mg/kg per day after 1 year). The steroid dosage given was significantly lower in the second group. The 4-year graft survival rate was 68% for the AZA group and 78% for the CyA group. Renal function did not differ significantly in the two groups; after 1, 2, and 3 years, the median 24-h creatinine clearance was 79, 69, and 51 ml/min/1.73 m2, respectively, for the AZA group and 78, 63, and 68 ml/min/1.73 m2, respectively, for the CyA group. Linear growth was similar in the two groups. We conclude that in pediatric patients the results of low-dose CyA immunosuppression do not differ significantly from those obtained with AZA in terms of graft survival, renal function, or growth.
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10.1007/BF02414535
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pubmed_1018_21438
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The influence of sporulation temperature (20, 30 and 37 degrees C) on the heat resistance and initiation of germination and inactivation by high pressure on Bacillus cereus ATCC 14579 spores was investigated. Spores sporulated at 37 degrees C were the most heat-resistant. However, spores sporulated at 20 degrees C were more resistant to the initiation of germination and inactivation by high pressure. Spores were more sensitive to pressure at higher treatment temperatures. At 25 degrees C, there was an optimum pressure (250 MPa) for the initiation of germination for the three suspensions; at higher temperatures an increase of pressure up to 690 MPa caused progressively more germination. Resistance to the germinability and inactivation by high pressure of the spore population was distributed heterogeneously. Semilogarithmic curves of the ungerminated and survival fraction of B. cereus spores were concave. The resistant fraction of the spore population was lower at higher treatment temperatures. At 60 degrees C after 30 s of treatment at 690 MPa almost 5 log cycles of the population of B. cereus sporulated at 20 degrees C was germinated, and more than 7 log cycles of the population of B. cereus sporulated at 30 and 37 degrees C. The same treatment inactivated 4, 6 and 7 log cycles of the population of B. cereus sporulated at 20, 30 and 37 degrees C, respectively.
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10.1046/j.1365-2672.1998.00460.x
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pubmed_434_4957
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The performance of a demanding exercise can result in motor performance deterioration and depression of primary motor cortex excitability. In the present work we defined a motor task that requires measurable skilled performance to unveil motor performance changes during the execution of a demanding task and to investigate the dynamics of motor performance and cortical excitability changes in absence of overt peripheral fatigue. Twenty-one normal subjects, divided into three groups were asked to perform a sequence of finger opposition movements (SEQ) paced at 2 Hz for 5 min, quantitatively evaluated by means of a sensor-engineered glove able to perform a spatio-temporal analysis of motor performance. Maximal voluntary contraction (MVC) was evaluated before and after the motor task in group 1 while motor evoked potentials (MEP) were evaluated before and after the motor task in group 2 and 3. Group 1 and 2 performed the 5 min-SEQ while group 3 was asked to perform the 5 min-SEQ twice to assess the dynamics of motor performance and cortical excitability. As a result, we found that the execution of 5 min-SEQ induced motor performance deterioration associated with no change in MVC but a decrease in cortical excitability. We further found that the dynamics of cortical excitability and motor performance were different. In fact, a short rest period (i.e., period necessary to collect MEP) between the execution of two 5 min-SEQs was able to recover the motor performance but not the cortical excitability. Finally, no change in spinal excitability was observed. These findings suggest that although primary motor cortex seems to be mainly involved in motor performance deterioration during the execution of a demanding finger motor task, the recovery of motor performance does not follow cortical excitability dynamics.
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10.1016/j.neuroscience.2010.11.008
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pubmed_349_10428
|
In 2014, drug overdose surpassed automobile accidents as the number one cause of accidental death for the first time in the history of the United States. The overdose epidemic is largely driven by opioids, and genuine prescription opioid analgesics play the biggest role in this phenomenon. Despite advancements in abuse deterrent formulations, prescription drug monitoring programmes and clinical assessments for the detection of abuse potential, drug overdoses continue to escalate. The Center for Disease Control has recently issued new guidelines for opioid prescription, yet even these recommendations have their shortcomings. Furthermore, undertreated pain in patients with comorbid substance use disorder poses a major clinical challenge, particularly for patients on opioid replacement therapy. Despite the seemingly obvious interaction between the presence of pain and the abuse of pain-relieving opioids, there is surprisingly little mechanistic data to further our understanding of this vitally important topic. The need for novel pain interventions that minimize abuse liability is critical. Without a fundamental characterization of pain neurobiology and the interaction between chronic pain and the brain's reward system, we are unlikely to make progress in the alleviation of the opioid epidemic.
LINKED ARTICLES
This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.
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10.1111/bph.13873
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pubmed_387_7460
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Several specific inhibitors for plasminogen activators have been isolated from various organs and cell lines, those from human placenta and the human monocyte-like cell line U-937 being virtually identical. The reaction between this type of inhibitor, designated as type-2, and high-Mr and low-Mr urokinase-type plasminogen activators was followed by reversed-phase high-performance liquid chromatography and gel electrophoresis. The components, their stable complexes and their dissociation and cleavage products could be clearly identified in both systems. The amino acid sequence of the inhibitor at the cleavage site was determined to be -Met-Thr-Gly-Arg decreases Thr-Gly-His-Gly-. A 35-residue carboxy-terminal fragment was found to be released.
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10.1016/0014-5793(88)80640-9
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pubmed_1031_17907
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Circumstantial evidence based on anecdote, case reports, epidemiological data and studies in vitro and in situ implicate tooth brushing with toothpaste with tooth wear, gingival recession and dentine hypersensitivity. This review attempts to assess the clinical significance of the potential harm produced by this most common oral hygiene habit. The toothbrush alone appears to have no effect on enamel and very little on dentine. Most toothpaste also has very little effect on enamel and in normal use would not cause significant wear of dentine in a lifetime of use. Wear of enamel and dentine can be dramatically increased if tooth brushing follows an erosive challenge. Gingival recession has a multi-factorial aetiology and certain individuals and specific teeth may be predisposed to trauma from tooth brushing. Tooth brushing is known to cause gingival abrasions but how these relate to gingival recession is not known. The role of toothpaste in gingival abrasion and recession surprisingly has received little if any attention. Gingival recession most commonly exposes dentine and localises sites for dentine hypersensitivity. Some toothpaste products can expose dentinal tubules but erosion is probably the more dominant factor in dentine hypersensitivity. There is no evidence to indicate that electric and manual toothbrushes differ in effects on soft and hard tissues. It is only under, over or abusive use or when combined with erosion that significant harm may be thus caused. In normal use it must be concluded that the benefits of tooth brushing far out-way the potential harm.
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10.1111/j.1875-595x.2003.tb00768.x
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pubmed_418_17321
|
The development of point-of-care (POC) diagnostic systems has received well-deserved attention in recent years in the scientific literature, and many experimental systems show great promise in real settings. However, in the case of an epidemic emergency (or a natural disaster), the first line of response should be based on commercially available and validated resources. Here, we compare the performance and ease of use of the miniPCR, a recently commercially available compact and portable PCR device, and a conventional thermocycler for the diagnostics of viral nucleic acids. We used both thermocyclers to detect and amplify Ebola and Zika DNA sequences of different lengths (in the range of 91 to 300 nucleotides) at different concentrations (in the range of ~50 to 4.0 x 108 DNA copies). Our results suggest that the performance of both thermocyclers is quite similar. Moreover, the portability, ease of use, and reproducibility of the miniPCR makes it a reliable alternative for point-of-care nucleic acid detection and amplification.
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10.1371/journal.pone.0215642
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pubmed_132_3588
|
INTRODUCTION AND HYPOTHESIS
Vaginal tactile imaging (VTI) is based on principles similar to those of manual palpation. The objective of this study is to assess the clinical suitability of new approach for imaging and tissue elasticity quantification under normal and prolapse conditions.
METHODS
The study subjects included 31 women with normal and prolapse conditions. The tissue elasticity (Young's modulus) was calculated from spatial gradients in the resulting 3-D tactile images.
RESULTS
Average values for tissue elasticity for the anterior and posterior compartments for normal conditions were 7.4 ± 4.3 kPa and 6.2 ± 3.1 kPa respectively. For Stage III prolapse the average values for tissue elasticity for anterior and posterior compartments were 1.8 ± 0.7 kPa and 1.8 ± 0.5 kPa respectively.
CONCLUSIONS
VTI may serve as a means for 3-D imaging of the vagina and a quantitative assessment of vaginal tissue elasticity, providing important information for furthering our understanding of pelvic organ prolapse and surgical treatment.
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10.1007/s00192-011-1592-z
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pubmed_459_15815
|
A new NMR technique for nondestructive, noninvasive, nonradioactive concurrent measurements of blood flow and several energy-dependent metabolites were applied to in situ cat brain during high cerebral blood flow states (seizures) and low flow states (carotid occlusion plus hemorrhagic shock). An inductively coupled, quadruple-tuned surface coil with a 50-ohm match at all relevant frequencies was used for both excitation and receiving. A broadband spectometer was used to measure the 31P spectrum (PCr, ATP, Pi, and pH), a water-suppressed 1H spectrum (lactate), 23Na, and 19F (blood flow via CHF3 washout). Each nucleus was excited at an independently determined rate. Sodium, with a short T1, was excited more frequently than phosphorus. The results qualitatively agreed with other techniques. Blood flow greatly increased during seizures with a 10% decrease in the Na signal, minimal lactate accumulation, no pH shift, and a change in the PCr-to-Pi ratio from 3.4 to 1.7. During carotid occlusion plus hypotension blood flow, PCr and ATP decreased to less than 10% of baseline values. Changes in PCr and Pi preceded parallel changes in Na and ATP. These experiments demonstrated the feasibility of concurrent measurements of physiologically induced changes in high-energy phosphates, lactate, sodium, and blood flow from the same volume of brain, in a nondestructive manner using NMR spectroscopy.
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10.1002/mrm.1910070404
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pubmed_1050_19661
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A low-threshold miniaturized single-mode nanowire laser operating at telecommunication wavelengths was proposed and simulated. The device was constructed by combining a single InGaAs nanowire with a photonic crystal microcavity and asymmetric distributed-Bragg-reflector mirrors. The mode characteristics and threshold properties were calculated using the three-dimensional finite-different time-domain method. Due to the effective subwavelength confinement and strong optical feedback, provided by the photonic crystal microcavity, and distributed-Bragg-reflector mirrors, respectively, the confinement factor, end-facet reflectivity, and quality factor significantly improved. A lowest threshold of ~80 cm-1 and ultra-small cut-off radius of ~40 nm are obtained, reduced by 67%, and 70%, respectively, compared with a traditional nanowire laser. In addition, due to the photonic band gap effect, single-mode lasing is achieved with a high side-mode suppression ratio of >12 dB. By placing several identical nanowires in the photonic crystal with different lattice constants, an on-chip laser array is realized, which is promising in wavelength division multiplexing applications. This work may pave the way for the development of low-threshold miniaturized nanolasers and low-consumption high-density photonic integrated circuits.
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10.3390/nano10122344
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pubmed_895_18363
|
Shape is a key characteristic to determine the quality of outgoing flat-rolled products in the steel industry. It is greatly influenced by flatness, a feature to describe how the surface of a rolled product approaches a plane. Flatness is of the utmost importance in steelmaking, since it is used by most downstream processes and customers for the acceptance or rejection of rolled products. Flatness sensors compute flatness measurements based on comparing the length of several longitudinal fibers of the surface of the product under inspection. Two main different approaches are commonly used. On the one hand, most mechanical sensors measure the tensile stress across the width of the rolled product, while manufacturing and estimating the fiber lengths from this stress. On the other hand, optical sensors measure the length of the fibers by means of light patterns projected onto the product surface. In this paper, we review the techniques and the main sensors used in the steelmaking industry to measure and quantify flatness defects in steel plates, sheets and strips. Most of these techniques and sensors can be used in other industries involving rolling mills or continuous production lines, such as aluminum, copper and paper, to name a few. Encompassed in the special issue, State-of-the-Art Sensors Technology in Spain 2013, this paper also reviews the most important flatness sensors designed and developed for the steelmaking industry in Spain.
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10.3390/s130810245
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pubmed_1029_10255
|
A double-blind, placebo controlled, cross-over study was carried out in 10 normal healthy volunteers to investigate the effects of sertraline 25 mg, 50 mg, 75 mg and 100 mg on aspects of cognitive functioning. Changes with respect to placebo in objective tests of psychomotor function (critical flicker fusion and choice reaction time) showed that sertraline had an alerting effect. The changes were not consistent with subjective reports of drowsiness.
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10.1007/BF00609258
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pubmed_611_2130
|
Allylboration of representative vinylic epoxides with allyldiethylborane (1) and (2-cyclohexenyl)dicyclohexylborane (2) affords the corresponding 1,2- and 1,4-addition products. cis-1, 2-Addition is favored in the reaction of 1 with 3, 4-epoxycycloalkenes of six- to eight-membered rings. 3, 4-Epoxycyclopentene (3a) and 5,5-dimethyl-3,4-epoxycyclopentene (3b) undergo five-membered ring opening during allylboration with 1 and 2, producing the corresponding (Z)-trienols (4a and 4b) with high stereoselectivity. 1,4-Addition of 1 and 2 to monoepoxides of 1, 3-butadiene and isoprene is favored, producing predominantly the corresponding (E)-alcohols.
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10.1021/ol006641g
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pubmed_820_3517
|
Bcr/Abl-transformed cells strongly resist apoptosis induced by most chemotherapy agents. However, in Bcr/Abl-transformed cells the monocyclic monoterpene, perillyl alcohol (POH), induces G0/G1 arrest and apoptosis without affecting Bcr/Abl expression or activity. The primary effect of POH is to cause growth arrest while apoptosis is a consequence of this arrest. Since Bcr/Abl induces constitutive expression of c-Myc, which is necessary for cell cycle transit from G1 into the S phase, we tested whether POH causes growth arrest by inhibiting expression of c-Myc. However, in POH-arrested Bcr/Abl-transformed cells, expression of c-Myc RNA and protein was not affected. Because expression of c-Myc during growth arrest can lead to apoptosis, we examined the role of c-Myc in POH-induced apoptosis. c-Myc induces expression of the ornithine decarboxylase (ODC) gene, which synthesizes polyamines that are necessary for cell growth. Myc-induced apoptosis operates through ODC and can be prevented with the ODC inhibitor, alpha-difluoromethylornithine (DFMO). We report that DFMO strongly protects cells from POH-induced apoptosis. These results show that in Bcr/Abl-transformed cells, POH activates a Myc-ODC apoptotic pathway that is not protected by the Bcr/Abl antiapoptotic mechanism.
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10.1159/000091181
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pubmed_791_4093
|
Photocatalytic H2 evolution is a clean technology to alleviate energy and environmental issues. The limited light absorption and the separation efficiency of photogenerated charge carriers are the major hurdles constraining the application of numerous photocatalysts. Herein, we report a simple and effective strategy, a multistep heat-treatment method, to synthesise a defective g-C3N4/RGO/TiO2 composite to increase its rate of activity for H2 production. The defects, nitrogen and oxygen vacancies, are simultaneously introduced on the surface of the g-C3N4/RGO/TiO2 composite. The vacancy defects essentially endow g-C3N4/RGO/TiO2 with a boosted photocatalytic H2 evolution rate (4760 μmol h-1 g-1) under visible-light irradiation, which is higher than that of the most of g-C3N4/TiO2 composites. This is attributed to the improved visible-light absorption as well as the separation and transfer rate of photogenerated charge carriers arising from vacancy defects. This study may provide an avenue for preparing defective photocatalysts for efficient H2 evolution.
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10.1039/d0nr05141a
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pubmed_750_2841
|
Understanding the effects and limitations of solid/liquid interfaces on energy transport is crucial to applications ranging from nanoscale thermal engineering to chemical synthesis. Until now, the majority of experimental evidence regarding solid/liquid interactions has been limited to macroscale observations and experiments. The lack of experimental works exploring nanoscale solid/liquid interactions has been accentuated as the body of knowledge from theory and simulations at these scales has exploded in recent years. In this study, we expand on current nanoscale thermal measurement techniques in order to more fully understand solid/liquid interfacial energy transport. We use thermal ablation threshold measurements on thick Au films in various liquids as a metric to describe thermal transport at the Au/liquid interface. Furthermore, using ultrafast pump-probe experiments, we gain insight into this transport through picosecond ultrasonic coupling at solid/liquid interfaces with known macroscopic observations. We find significant variations in both the ablation threshold and the damping of the acoustic modes within the Au films depending on nanoscopic interactions at the solid/liquid interface rather than typical macroscale metrics such as acoustic mismatch, measured contact angle, and work of adhesion.
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10.1021/acs.langmuir.8b03675
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pubmed_959_7887
|
This article examines knowledge production in the sociology of music. Focusing on the idea of cool music, we interrogate the nature of music researchers' relationship with their object of research. While the qualification and connotation of cool is widespread in popular music, sociology has largely neglected to engage with it as an object of research. Instead, the sociological investigation of music audiences is divided between two opposed but co-constructed paradigms that ultimately do not account for how cool emerges as a qualifier and connotation, how it performs as a discourse on music, and to what effect. Using the example of aging music researchers as a departure point, we examine how the cool connotations of music function as a mode of discourse that legitimates particular knowledge, practice, and taste, demarcating insider/outsider status. We explore how music acquires social connotations such as "cool" and whether that alters music researchers' approaches to it. We argue that apart from the disclosure of inclinations, social characteristics, and relationships to the object of research (music scenes, preferences, fandom, and so on), the tradition of reflexive empirical perspectives in music sociology should incorporate further deconstruction of the transformative dimensions in the relations between music and researcher. Music, as a complex and dynamic object, thus, requires sociology to produce accounts that both encompass people's enjoyment and experience as well as its boundary-defining capacity.
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10.1111/1468-4446.12829
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pubmed_744_11513
|
OBJECTIVE
Overweight has become a public health problem in most developing countries. Evidence suggests that adolescence is a critical period in determining adulthood obesity and its complications. The present study was carried out to assess the prevalence of overweight and obesity among secondary school students.
DESIGN AND SETTING
This descriptive study was conducted in Tehran city, 2000-2001. Body weight and height were measured and body mass index (BMI) values were calculated. Underweight, overweight and obesity were defined as <5th, > or = 85th and > or = 95th percentile, respectively, of age- and sex-specific BMI values from the National Center for Health Statistics/Centers for Disease Control and Prevention (2000).
SUBJECTS
Using a multistage sampling method, 2321 students (1068 males and 1253 females) aged 11-16 years were assessed in Tehran, the capital city of Iran.
RESULTS
The overall prevalences of overweight and obesity were 21.1 and 7.8%, respectively. The prevalence of overweight among girl students (i.e. 23.1%; 95% confidence interval (CI) 20.8-25.4) was significantly higher than that among boys (i.e. 18.8%; 95% CI 16.5-21.1, P=0.01) even after adjustment for age (odds ratio 1.26, 95% CI 1.03-1.55, P=0.02). No significant risk of obesity associated with age was found in girls or boys. In both sexes, median values of age-specific BMI in this study were statistically higher than corresponding values collected in Tehrani adolescents 10 years ago (P=0.03). Similarly, a significant difference was seen between girl students in this study and the reference population (P=0.03).
CONCLUSION
According to this study, overweight, especially in girls, should be considered an epidemic health problem among adolescent students in Tehran.
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10.1079/phn2003593
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pubmed_904_17709
|
Overactive bladder (OAB) syndrome is highly prevalent in both men and women and might have negative impact on quality of life. Clinical trials of OAB usually highly select participants that may not reflect the real-world practice of OAB patients. The spectrum of OAB includes patients with idiopathic, neuropathic, with bladder outlet obstruction, and patients in elderly and medical comorbidities. Patients might have poor response to OAB medication or have adverse events after treatment. Therefore, treatment of OAB should be individualized to obtain therapeutic efficacy and avoid unacceptable adverse events. This article reviews the recently published literature and provides a guide for physicians to choose the appropriate treatment for different OAB patients.
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10.4103/tcmj.tcmj_83_18
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pubmed_648_15956
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Chronic renal failure (CRF), also known as chronic kidney disease (CKD), is a common renal disorder characterized by gradual kidney dysfunction. Molecular dissection reveals that transforming growth factor beta (TGF-β) plays a central role in the pathogenesis of CRF. However, the mechanism underlying TGF-β upregulation has not been demonstrated. Here, we verified that the elevated level of TGF-β was associated with the severity of CRF stages and the activation of TGF-β-mediated signaling in 120 renal biopsies from CRF patients. By analyzing the promoter region of the TGFB1 gene, we identified one AP-1 (activator protein 1) and four NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) binding sites. Knockdown of two AP-1 subunits (c-Jun and c-FOS) or blockage of AP-1 signaling with two inhibitors T-5224 and SR11302 could cause the downregulation of TGFB1, whereas knockdown of two NF-κB subunits (p65 and p50) or blockage of NF-κB signaling with two inhibitors TPCA1 and BOT-64 could not change the expression of TGFB1. Using mass spectrometry and coimmunoprecipitation analyses, we found that both c-Jun and c-FOS formed a complex with CtBP2 (C-terminal binding protein 2) and histone acetyltransferase p300. Our in vitro data demonstrated that induction of CtBP2 by recombinant IL-1β (interleukin-1 beta) led to the upregulation of TGFB1 and the activation of TGF-β downstream signaling, while knockdown of CtBP2 resulted in the reversed effects. Using chromatin immunoprecipitation assays, we revealed that the CtBP2-p300-AP1 complex specifically bound to the promoter of TGFB and that knockdown or blockage of CtBP2 significantly decreased the occupancies of the p300 and AP-1 subunits. Our results support a model in which the CtBP2-p300-AP1 transcriptional complex activates the expression of TGFB1, increasing its production and extracellular secretion. The secreted TGF-β binds to its receptors and initiates downstream signaling.
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10.7150/ijbs.38841
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pubmed_704_18383
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EEG pattern recognition is an important part of motor imagery- (MI-) based brain computer interface (BCI) system. Traditional EEG pattern recognition algorithm usually includes two steps, namely, feature extraction and feature classification. In feature extraction, common spatial pattern (CSP) is one of the most frequently used algorithms. However, in order to extract the optimal CSP features, prior knowledge and complex parameter adjustment are often required. Convolutional neural network (CNN) is one of the most popular deep learning models at present. Within CNN, feature learning and pattern classification are carried out simultaneously during the procedure of iterative updating of network parameters; thus, it can remove the complicated manual feature engineering. In this paper, we propose a novel deep learning methodology which can be used for spatial-frequency feature learning and classification of motor imagery EEG. Specifically, a multilayer CNN model is designed according to the spatial-frequency characteristics of MI EEG signals. An experimental study is carried out on two MI EEG datasets (BCI competition III dataset IVa and a self-collected right index finger MI dataset) to validate the effectiveness of our algorithm in comparison with several closely related competing methods. Superior classification performance indicates that our proposed method is a promising pattern recognition algorithm for MI-based BCI system.
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10.1155/2020/1981728
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pubmed_1136_17709
|
Canada lynx face some unique breeding restrictions, which may have implications for population viability and captive management. The goal of this study was to improve our understanding of basic reproductive physiology in Canada lynx. Using fecal hormone metabolite analysis, we established normative patterns of fecal estrogen (fE) and progestagen (fP) expression in captive and wild female Canada lynx. Our results indicate that Canada lynx have persistent corpora lutea, which underlie their uncharacteristic fP profiles compared to other felids. Thus, fP are not useful for diagnosing pregnancy in Canada lynx. We also found that Canada lynx are capable of ovulating spontaneously. Captive females had higher concentrations of fE and fP than wild females. Both populations exhibit a seasonal increase in ovarian activity (as measured by fE) between February and April. Finally, there was evidence of ovarian suppression when females were housed together.
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10.1016/j.ygcen.2010.09.003
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pubmed_936_7225
|
One of the major obstacles in treating brain cancers, particularly glioblastoma multiforme, is the occurrence of secondary tumor lesions that arise in areas of the brain and are inoperable while obtaining resistance to current therapeutic agents. Thus, gaining a better understanding of the cellular factors that regulate glioblastoma multiforme cellular movement is imperative. In our study, we demonstrate that the 5'-3' exoribonuclease XRN2 is important to the invasive nature of glioblastoma. A loss of XRN2 decreases cellular speed, displacement, and movement through a matrix of established glioblastoma multiforme cell lines. Additionally, a loss of XRN2 abolishes tumor formation in orthotopic mouse xenograft implanted with G55 glioblastoma multiforme cells. One reason for these observations is that loss of XRN2 disrupts the expression profile of several cellular factors that are important for tumor invasion in glioblastoma multiforme cells. Importantly, XRN2 mRNA and protein levels are elevated in glioblastoma multiforme patient samples. Elevation in XRN2 mRNA also correlates with poor overall patient survival. These data demonstrate that XRN2 is an important cellular factor regulating one of the major obstacles in treating glioblastomas and is a potential molecular target that can greatly enhance patient survival.
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10.3390/cells11091481
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pubmed_748_5927
|
1. Electrical field stimulation (EFS) (0.5 ms in train of 2-32 Hz for 300 ms) in smooth muscle of pigeon oesophagus, in the presence of atropine (1 microm) and guanethidine (1 microm), elicited an inhibitory response consisting of a transient hyperpolarization (inhibitory junction potential, IJP) associated with muscle relaxation. 2. Sodium nitroprusside (SNP, 100 microm) induced hyperpolarization correlated to mechanical relaxation. 3. The nitric oxide (NO) synthase inhibitor N(omega)-nitro-l-arginine (from 0.1 to 100 microm) caused a concentration-dependent reduction of electromechanical response to EFS indicating a role for NO in this response. 4. Apamin (1 microm) reduced both IJP and relaxation to EFS but was without effect on the response to SNP indicating a role for purines, which are also blocked by apamin. 5. Adenosine, AMP, ADP and ATP (all from 1 microm to 1 mm) application caused transient hyperpolarization and muscular relaxation with the following order of potency: adenosine > AMP > ADP > ATP. 6. Inhibitory responses evoked by purines are TTX (1 microm) insensitive but they were inhibited by apamin. This indicates that a purine component for the non-adrenergic non-cholinergic (NANC) response exists but the purine receptor site is not located on the neurone. 7. Overall these results suggest that NANC inhibitory response elicited by EFS presents two different components apamin-sensitive, probably purines-mediated and apamin-insensitive probably NO-mediated as apamin only partially block the response to EFS.
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10.1111/j.1474-8673.2004.00304.x
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pubmed_1114_13898
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This paper presents the continuous-flowand single-step synthesis of a TiO2/MWCNT (multiwall carbon nanotubes) nanohybrid material. The synthesis method allows achieving high coverage and intimate interface between the TiO2particles and MWCNTs, together with a highly homogeneous distribution of nanotubes within the oxide. Such materials used as active layer in theporous photoelectrode of solid-state dye-sensitized solar cells leads to a substantial performance improvement (20%) as compared to reference devices.
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10.1021/am507179c
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pubmed_456_8282
|
BACKGROUND
LncRNA PVT1 has been reported to be involved in a variety of biological processes, including cell proliferation, cell differentiation and cancer progression. However, the mechanism by which LncRNA PVT1 contributes to chemoresistance of osteosarcoma cell, has not been fully elucidated.
METHODS
We first generatedLncRNA PVT1-overexpressed MG63 cells and LncRNA PVT1 knockdown MG63/DOX cells. Then, we examined the effect of LncRNA PVT1 on cell viability and colony formation ability by MTT assay and soft agar assay, respectively. In addition, we performed flow cytometry analysis to detect apoptosis induced by GEM. Dual luciferase reporter assay and RIP were used to confirmed the interaction between LncRNA PVT1 and miR-152. Finally, we determined protein level of c-MET, p-PI3K, and p-AKT by westernblot.
RESULTS
LncRNA PVT1 overexpression promoted cell proliferation and exhibited the anti-apoptotic property in LncRNA PVT1-overexpressing MG63 cells treated with gemcitabine. While, LncRNA PVT1-depleted MG63/DOX cells treated with gemcitabine exhibited significant lower survival rate and high percentage of apoptosis. Next, we found that LncRNA PVT1 could target and downregulated the level of miR-152. Interestingly, miR-152 greatly rescued the biological outcomes of LncRNA PVT1 not only in MG63 but also in MG63/DOX cells. We observed that LncRNA PVT1 markedly induced PI3K/AKT pathway activation, which was abolished by miR-152 mimics overexpression. Finally, c-MET inhibitor was used to confirm the essential role of c-MET in LncRNA PVT1 and miR-152-regulated PI3K/AKT signaling.
CONCLUSION
We showed thatlncRNA PVT1 played a contributory role in chemoresistance of osteosarcoma cells through c-MET/PI3K/AKT pathway activation, which was largely dependent on miR-152. Our findings advance our understanding of how lncRNA PVT1 promotes chemoresistance of osteosarcoma cells and facilitate development of novel strategies for treating osteosarcoma.
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10.1016/j.prp.2018.12.013
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pubmed_529_10687
|
Congenital isolated hypogonadotropic hypogonadism (IHH) is a clinically and genetically heterogenous disorder characterized by abnormal synthesis, secretion, or action of gonadotropin-releasing hormone, a key hypothalamic decapeptide that orchestrates the reproductive axis. Several modes of inheritance have been identified. A growing list of causative genes has been implicated in the molecular pathogenesis of syndromic and nonsyndromic IHH, largely contributing for better understanding the complex neuroendocrine control of reproduction. This article summarizes the great advances of molecular genetics of IHH and pointed up the heterogeneity and complexity of the genetic basis of this condition.
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10.1016/j.ecl.2017.01.010
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pubmed_112_2661
|
In a randomized, multicenter trial, nizatidine 150 mg or 300 mg, or placebo, was administered twice daily for six weeks to 515 patients with gastroesophageal reflux disease (GERD). Gelusil antacid tablets were taken as needed for pain. Significantly superior rates of endoscopically proven complete healing (normal-appearing mucosa) versus placebo occurred after three weeks with nizatidine 150 mg, and after six weeks with nizatidine 300 mg. Six-week healing rates were 38.5% for nizatidine 300 mg, 41.1% for nizatidine 150 mg, and 25.8% for placebo. The nizatidine 150 mg treatment group had significantly greater improvement in daytime and nighttime heartburn severity after one day of therapy versus placebo. Twice-daily administration of nizatidine 150 mg or 300 mg provides prompt relief from the major symptom of GERD, heartburn, and complete healing of esophagitis is seen in many patients.
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10.1007/BF01300384
|
pubmed_132_565
|
PURPOSE
We previously identified novel thiazole derivatives able to reduce histone acetylation and histone acetyltransferase (HAT) activity in yeast. Among these compounds, 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl]hydrazone (CPTH6) has been selected and used throughout this study.
EXPERIMENTAL DESIGN
The effect of CPTH6 on histone acetylation, cell viability and differentiation, cell-cycle distribution, and apoptosis in a panel of acute myeloid leukemia and solid tumor cell lines has been evaluated.
RESULTS
Here, we showed that CPTH6 leads to an inhibition of Gcn5 and pCAF HAT activity. Moreover, it inhibits H3/H4 histones and α-tubulin acetylation of a panel of leukemia cell lines. Concentration- and time-dependent inhibition of cell viability, paralleled by accumulation of cells in the G(0)/G(1) phase and depletion from the S/G(2)M phases, was observed. The role of mitochondrial pathway on CPTH6-induced apoptosis was shown, being a decrease of mitochondrial membrane potential and the release of cytochrome c, from mitochondria to cytosol, induced by CPTH6. Also the involvement of Bcl-2 and Bcl-xL on CPTH6-induced apoptosis was found after overexpression of the two proteins in leukemia cells. Solid tumor cell lines from several origins were shown to be differently sensitive to CPTH6 treatment in terms of cell viability, and a correlation between the inhibitory efficacy on H3/H4 histones acetylation and cytotoxicity was found. Differentiating effect on leukemia and neuroblastoma cell lines was also induced by CPTH6.
CONCLUSIONS
These results make CPTH6 a suitable tool for discovery of molecular targets of HAT and, potentially, for the development of new anticancer therapies, which warrants further investigations.
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10.1158/1078-0432.CCR-11-0579
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pubmed_983_17508
|
It is well known that post menopausal women are more prone to cardiovascular diseases, osteoporosis and cancer. This study was done to detect the effect of early onset of menopause on the cardiac performance in postmenopausal women. The cardiac functions were evaluated by the noninvasive technique of measuring systolic time intervals (STI) in the form of total electromechanical systolic time (OS2), left ventricular ejection time (LVET), pre-ejection period (PEP) and PEP/LVET ratio. The study included 50 postmenopausal women with age at the onset of menopause ranging from 29 years to 55 years, divided into three groups I, II and III with mean age at onset of menopause being 36.80 +/- 2.97, 43.97 +/- 2.97 and 52.05 +/- 1.61 years, respectively. In group I, there was a highly significant increase in QS2, PEP and PEP/LVET ratio and in group II, there is a significant decrease in LVET with a highly significant increase in PEP and PEP/LVET ratio. This signifies asymptomatic and subclinical cardiac systolic dysfunction in groups I and II as compared to group III. Early onset of menopause could thus be considered as a risk factor for increased cardiovascular morbidity; hence efforts should be made to timely detect and prevent these diseases in the postmenopausal stage.
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pubmed_983_17508
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pubmed_740_13009
|
Algae are considered water pollutants because they form algal blooms in stagnant water. Algae harvesting technology, however, can help convert them into a useful industrial material like biomass. The core technique (flocculation) separates microalgae from other flocculants, allowing for the harvest of clean and pure algal biomass. This study aims to estimate and evaluate algal separation (removal or harvesting) efficiency (X) to concurrently obtain the objectives of algal bloom management and algal particle collection. To simulate algal separation by auto-flocculation (no flocculants) related flotation, the population balance in turbulence (PBT) model is used. Model simulations are conducted under optimal conditions provided by previous studies about the biological impact factors of algae, operating parameters of the flotation process, and so on. This modeling study determines the efficiency (X) of separating algae from the water body in the separation zone after forming auto-flocculated bubble-floc agglomerates by making them collide and attach to each other in the contact zone of the flotation tank. The X is examined as a function of size distribution of agglomerates and bubbles and of the number of initially injected bubbles. Optimal conditions for forming and harvesting the agglomerates may be found through further modeling studies.
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10.2166/wst.2017.491
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pubmed_199_13252
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Multiple congenital anomalies were identified at 16 weeks gestation in one fetus of an unsuspected twin pregnancy while ultrasound examination was performed before routine genetic amniocentesis. Further sonographic studies documented the amniotic band sequence (ABS) and transient oligohydramnios in the affected fetus. The latter finding supports the theory of amnion rupture followed by amniotic fluid leakage through an ineffective chorion barrier as the pathogenesis of compression related anomalies in this syndrome. Extensive craniofacial involvement including hydrocephalus, encephalocele, and multiple facial clefts in the affected fetus, combined with an erroneous ultrasound diagnosis of ABS in the unaffected twin, created an extremely difficult management and counseling situation. A review of ABS, the embryology of placental membrane development, and a discussion of selective termination procedures are presented.
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10.1002/ajmg.1320200414
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pubmed_754_14915
|
Improved early detection of neoplasia by screening of urothelial cells requires an understanding of the features distinguishing normal and neoplastic cell populations. We have begun a program of study based upon a rat model system for the controlled observation of early-stage lesions produced by the carcinogen N-butyl-N-(4-hydroxybutyl)- nitrosamine. Cells dissociated directly from normal and malignant urothelium were characterized by conventional cytopathology techniques and by quantitative microscopy (for nuclear texture and nuclear and cytoplasmic size, shape, and stain content) to derive a comprehensive picture of bladder tumor development. By following the changes that occur in the dissociated urothelial cells we have found that the nuclear area, total nuclear stain, nuclear shape, and the nuclear chromatin change significantly over a 48-wk interval as the lesions progress toward malignancy.
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10.1002/cyto.990050504
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pubmed_845_12279
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Breast cancer is the second most commonly diagnosed malignancy among women globally. Past MRI studies have linked a high animal fat diet (HAFD) to increased mammary cancer risk in the SV40Tag mouse model of triple-negative breast cancer. Here, serial MRI examines tumor progression and measures the arterial blood volume feeding mammary glands in low fat diet (LFD) or HAFD fed mice. Virgin female C3(1)SV40Tag mice (n = 8), weaned at 3 weeks old, were assigned to an LFD (n = 4, 3.7 kcal/g, 17.2% kcal from vegetable oil) or an HAFD (n = 4, 5.3 kcal/g, 60% kcal from lard) group. From ages 8 to 12 weeks, weekly fast spin echo MR images and time-of-flight (TOF) MR angiography of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed. Inguinal mammary glands were excised and fixed for ex vivo MRI and histology. Tumor, blood, and mammary gland volumes for each time point were measured from manually traced regions of interest; tumors were classified as invasive by histopathology-blinded observers. Our analysis confirmed a strong correlation between total tumor volume and blood volume in the mammary gland. Tumor growth rates from weeks 8-12 were twice as high in HAFD-fed mice (0.42 ± 0.14/week) as in LFD-fed mice (0.21 ± 0.03/week), p < 0.004. Mammary gland blood volume growth rate was 2.2 times higher in HAFD mice (0.29 ± 0.11/week) compared with LFD mice (0.13 ± 0.06/week), p < 0.02. The mammary gland growth rate of HAFD-fed mice (0.071 ± 0.011/week) was 2.7 times larger than that of LFD-fed mice (0.026 ± 0.009/week), p < 0.01. This is the first non-invasive, in vivo MRI study to demonstrate a strong correlation between an HAFD and increased cancer burden and blood volume in mammary cancer without using contrast agents, strengthening the evidence supporting the adverse effects of an HAFD on mammary cancer. These results support the potential future use of TOF angiography to evaluate vasculature of suspicious lesions.
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10.1002/nbm.4363
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pubmed_458_17861
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This study examined the relationship between three midlife transitions and depressive symptoms among 952 women 50 to 59 years of age. Using longitudinal data from women interviewed for the 1992 and 2000 Health and Retirement Study, the study described changes in marital status, change to a parental caregiving role, and changes in perceived health across the eight years. Further, it examined the impact of these changes on mental health. The findings indicate that becoming widowed, becoming a caregiver, and perceiving health declines significantly increased depressive symptoms in the year 2000, even when controlling for pre-transition levels of depressive symptoms. The findings are consistent with the lifecourse perspective that individual development occurs in context and across the lifespan. The findings confirm and add to current midlife research literature.
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10.2190/4CUU-KDKC-2XAD-HY0W
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pubmed_805_7840
|
In this study we have utilized human elastin cDNAs in molecular hybridizations to establish the chromosomal location of the human elastin gene. First, in situ hybridizations were performed with metaphase chromosomes from phytohemagglutinin-stimulated human peripheral blood lymphocytes. In three separate experiments using two different regions of human elastin cDNAs, the distribution of grains was found to be concentrated on the long arm of chromosome 7 within the [q11.1-21.1] region, and the peak number of grains coincided with the locus 7q11.2. Second, hybridizations with a panel of human-rodent cell hybrids showed concordance with human chromosome 7. Third, PCR analyses with elastin-specific primers of DNA from a hybrid cell line containing chromosome 7 as the only human chromosome yielded a product of the expected size, while DNA containing human chromosome 2, but not chromosome 7, did not result in a product. The results indicate that the human elastin gene is located in the proximal region of the long arm of chromosome 7. The precise localization of the elastin gene in the human genome is useful in establishing genetic linkage between inheritance of an allele with a mutated elastin gene and a heritable disorder.
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pubmed_805_7840
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pubmed_374_2211
|
Carotenoids are bioactive compounds with widely accepted health benefits. Their quantification in human faeces can be a useful non-invasive approach to assess their bioavailability. Identification and quantification of major dietary carotenoids in human faeces was the aim of the present study. Faeces and dietary intake were obtained from 101 healthy adults (45-65 years). Carotenoid concentrations were determined by HPLC in faeces and by 3-day food records in dietary intake. Carotenoids quantified in faeces (µg/g dry weight, median) were: β-carotene (39.5), lycopene (20), lutein (17.5), phytoene (11.4), zeaxanthin (6.3), β-cryptoxanthin (4.5), phytofluene (2.9). α-carotene (5.3) and violaxanthin were found 75.5% and 7.1% of the faeces. The carotenoids found in the highest concentrations corresponded to the ones consumed in the greatest amounts (µg/d): lycopene (13,146), phytoene (2697), β-carotene (1812), lutein+zeaxanthin (1148). Carotenoid concentration in faeces and in dietary intake showed correlation for the total non-provitamin A carotenoids (r = 0.302; p = 0.003), phytoene (r = 0.339; p = 0.001), phytofluene (r = 0.279; p = 0.005), lycopene (0.223; p = 0.027), lutein+zeaxanthin (r = 0.291; p = 0.04) and β-cryptoxanthin (r = 0.323; p = 0.001). A high proportion of dietary carotenoids, especially those with provitamin A activity and some of their isomers, reach the large intestine, suggesting a low bioavailability of their intact forms.
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10.3390/antiox9060484
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pubmed_1104_4673
|
Chemotherapy doses are sometimes reduced because of obesity in patients. This study examines the effect of parameters reflecting the body size, body weight and height, body mass index (BMI), and body surface area (BSA) on the depth of the blood leukocyte nadir in breast cancer patients receiving adjuvant chemotherapy, when drug dosing was based on the BSA. Three hundred and forty patients with node positive breast cancer without distant metastases were treated with 6 cycles of adjuvant postoperative CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 i.v. every 3 weeks). Patients within the highest BMI had the highest leukocyte nadir values (Spearman correlation coefficient 0.3, p < 0.001). A high body weight and a large BSA were also associated with high leukocyte nadirs. We conclude that when the blood leukocyte nadir is used as a surrogate marker for the drug effect, obese patients receiving intravenous CMF have higher leukocyte nadirs than the lean ones. Therefore, the drug doses should not be reduced because of obesity, and even when obese patients are treated according to the scheduled doses they may remain slightly underdosed.
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10.1080/028418601750071082
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pubmed_279_11253
|
BACKGROUND
The abnormal transmembrane action potentials of subendocardial Purkinje fibers that survive 24 to 48 hours after coronary artery occlusion can be a source of the multiform ventricular tachycardias that occur during this time. A change in the density or function of either or both the T-type and L-type cardiac Ca2+ channels may contribute to the altered electrical activity of these Purkinje myocytes.
METHODS AND RESULTS
The purpose of this study was to determine the function of the T- and L-type Ca2+ currents (iCat and iCaL, respectively) in Purkinje myocytes dispersed from the subendocardium of the left ventricle 24 and 48 hours after coronary artery occlusion (IZPC24 and IZPC48, respectively). To do this we compared whole-cell Ca2+ currents from Purkinje myocytes enzymatically dispersed from free-running fiber bundles (SPCs), from the subendocardium of the noninfarcted canine heart (NZPCs), and from IZPC24 and IZPC48. ICaL and iCat were recorded with Cs(+)- and EGTA-rich pipettes and in Na(+)-K(+)-free external solutions to eliminate overlapping currents. ICaL density was significantly reduced in IZPC48 compared with NZPC or IZPC24. This was not accompanied by a shift in the current-voltage relation or by a change in the time course of decay of iCaL. Replacement of Ca2+ with equimolar Ba2+ increased iCaL density in all cell types, but peak iBaL of IZPC48 remained reduced compared with control iBaL values. T-type Ca2+ currents were recorded in all SPCs and NZPCs. In IZPC24 and IZPC48 there was a reduction in peak iCat amplitudes and densities. This was not accompanied by a shift in the current-voltage relation or by a change in the time course of decay of peak iCat. However, there was a hyperpolarizing shift in the steady-state availability relations in both IZPC24 and IZPC48. In addition, the maximally available iCat in IZPC24 was not different from control, whereas it was significantly reduced in IZPC48.
CONCLUSIONS
The L-type ICa density in subendocardial Purkinje myocytes that survive in the infarcted heart is significantly decreased by 48 hours after the time of coronary artery occlusion. The peak T-type ICa density is decreased in subendocardial Purkinje myocytes that survive in the infarcted heart at 24 hours, but further reduction occurs in these myocytes by 48 hours. This loss in Ca2+ channel function could contribute to the abnormal transmembrane potentials of these myocytes surviving in the infarcted heart.
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10.1161/01.cir.89.6.2747
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pubmed_987_12445
|
The medial habenula (mHb), a subregion of the habenula, is involved in diverse brain functions, such as nicotine addiction, anxiety, and anhedonia. We recently reported that TMEM16A deficiency, a calcium-activated chloride channel, decreased the activity of mHb cholinergic neurons. Since downregulated activity in cholinergic neurons of the mHb is involved in anhedonia-like behavior, we here investigated whether conditional deletion of TMEM16A in mHb cholinergic neurons also displays anhedonia-like behavior. The conditional deletion of TMEM16A in the mHb cholinergic neurons of mice (TMEM16A cKO mice) was generated by crossing ChaT-Cre (+) with floxed TMEM16A f/f mice. TMEM16A cKO mice displayed significantly reduced social interaction, sucrose preference, female urine sniffing, and increased marble burying. These behavioral data suggest the potential role of TMEM16A in anhedonic-like behavior in mice. Taken together, the presented data suggest that TMEM16A-mediated mHb activity might be a therapeutic target for anhedonia-related symptoms.
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10.1016/j.bbr.2022.113841
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pubmed_886_11393
|
We describe the prevalence of doctor-diagnosed arthritis and its impact on activities, work, and joint pain for 6 racial/ethnic groups: non-Hispanic whites, non-Hispanic blacks, Hispanics, American Indians/Alaska Natives, Asians and Pacific Islanders, and multiracial or "other" respondents. We combined data from the 2002, 2003, and 2006 National Health Interview Survey (n = 85,784) and, after adjusting for age, sex, and body mass index, compared racial/ethnic differences. Arthritis-attributable activity limitation, arthritis-attributable work limitation, and severe joint pain were higher for non-Hispanic blacks, Hispanics, and multiracial or other respondents with arthritis compared with non-Hispanic whites with arthritis. Our finding that arthritis disproportionately affects certain racial/ethnic minorities may be useful for planning interventions.
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pubmed_886_11393
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pubmed_204_12223
|
With increasing numbers of GPS-equipped mobile devices, we are witnessing a deluge of spatial information that needs to be effectively and efficiently managed. Even though there are several distributed spatial data processing systems such as GeoSpark (Apache Sedona), the effects of underlying storage engines have not been well studied for spatial data processing. In this paper, we evaluate the performance of various distributed storage engines for processing large-scale spatial data using GeoSpark, a state-of-the-art distributed spatial data processing system running on top of Apache Spark. For our performance evaluation, we choose three distributed storage engines having different characteristics: (1) HDFS, (2) MongoDB, and (3) Amazon S3. To conduct our experimental study on a real cloud computing environment, we utilize Amazon EMR instances (up to 6 instances) for distributed spatial data processing. For the evaluation of big spatial data processing, we generate data sets considering four kinds of various data distributions and various data sizes up to one billion point records (38.5GB raw size). Through the extensive experiments, we measure the processing time of storage engines with the following variations: (1) sharding strategies in MongoDB, (2) caching effects, (3) data distributions, (4) data set sizes, (5) the number of running executors and storage nodes, and (6) the selectivity of queries. The major points observed from the experiments are summarized as follows. (1) The overall performance of MongoDB-based GeoSpark is degraded compared to HDFS- and S3-based GeoSpark in our experimental settings. (2) The performance of MongoDB-based GeoSpark is relatively improved in large-scale data sets compared to the others. (3) HDFS- and S3-based GeoSpark are more scalable to running executors and storage nodes compared to MongoDB-based GeoSpark. (4) The sharding strategy based on the spatial proximity significantly improves the performance of MongoDB-based GeoSpark. (5) S3- and HDFS-based GeoSpark show similar performances in all the environmental settings. (6) Caching in distributed environments improves the overall performance of spatial data processing. These results can be usefully utilized in decision-making of choosing the most adequate storage engine for big spatial data processing in a target distributed environment.
|
10.1007/s11227-021-03946-7
|
pubmed_436_14626
|
We have demonstrated up-regulation of the immunomodulatory genes decay accelerating factor (DAF), interleukin 15 (IL-15) and osteopontin (OPN) during the window of implantation (WOI). Here, we characterized gene expression and determined the localization of their protein products and respective ligands at the opening and closure of the WOI. In addition, we used laser capture microdissection (LCM) to analyze the cell type-specific gene expression. Human endometrial biopsies from cycle Days 16, 21 and 24 were evaluated by real-time RT-PCR. Purified epithelial and stromal cells were obtained by LCM. Localization of the proteins and their ligands was assessed by immunohistochemistry. mRNA expression of DAF, IL-15 and OPN was significantly increased throughout the WOI. DAF, OPN and alpha(v)beta(3) integrin were strongly immunolocalized to the glandular compartment by Days 21 and 24, whereas C3, IL-15 and IL-15Ralpha were highly stained in both glandular and stromal compartments. After LCM, gene expression of DAF was 4.8-fold increased in epithelium versus stroma, whereas for OPN there was a 2-fold increase. For IL-15, the expression in stroma was 8.7-fold higher than in epithelial cells. The progressive increase of the expression of these immunomodulatory genes, proteins and ligands during the WOI, support a critical role at the time of endometrial receptiveness.
|
10.1093/molehr/gan029
|
pubmed_373_13537
|
It has recently been found that many buildings in Taiwan were constructed with radioactively contaminated rebar, which raised great concern among the residents as well as governmental officials. In order to investigate the possible cytogenetic damage to the residents of contaminated buildings, a G-banding method was carried out on the lymphocytes of 30 radiation-exposed individuals from four families and one office building, as well as 15 control individuals from laboratory personnel. The estimated cumulative radiation doses for the exposed people range from 19.63 to 280.50 mSv. Altogether, 13 females and 17 males belonging to the radiation-exposed group, and 7 females and 8 males in the control group, were included in this study. With the exception of one sample, at least 500 metaphase spreads were scored and analyzed for each individual. All the recognizable structural aberrations of chromosomes or chromatids were recorded and statistically analyzed. Comparison of either percentage of cells with chromosome aberrations or number of aberrated chromosomes per 100 cells between the radiation-exposed and the control groups manifested insignificant differences (p = 0.1145 and 0.0766, respectively). In addition, the chromosomal regions close to the centromere were found to break more frequently than elsewhere in the genome.
|
10.1016/s0027-5107(97)00081-x
|
pubmed_335_8060
|
A triazene-based synthetic strategy for the construction of the complex biaryl ethers and a Suzuki coupling reaction were the key steps in the synthesis of precursor 1 of the aglycon of vancomycin, which already contains the complete skeleton of the target compound. The cleavage of the triazene unit from the D ring and the removal of the other protecting groups led to the aglycon of vancomycin. These strategies should be particularly valuable for the synthesis of other naturally occurring glycopeptide antibiotics and offer opportunities for the synthesis of combinatorial libraries of compounds of the vancomycin family for chemical biology studies.
|
10.1002/(SICI)1521-3773(19981016)37:19<2717::AID-ANIE2717>3.0.CO;2-I
|
pubmed_845_11212
|
STUDY OBJECTIVE
To validate the Vibe actigraph in assessing sleep-wake patterns compared to polysomnography (PSG) in patients with COPD.
METHODS
Nine stable COPD patients wore actigraphs while undergoing PSG. The correlation between total sleep time (TST), total sleep period (TSP), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency was determined for corresponding measurements from the actigraph and PSG. Sensitivity, specificity, and positive and negative predictive values were calculated for the actigraph, considering PSG the gold standard. Levels of agreement between the variables of PSG and the actigraph were estimated using Bland-Altman plots.
RESULTS
A strong and statistically significant correlation was noted between PSG and the actigraph in detecting movement during sleep [mean activity score (counts)], TST and TSP (all rs = 0.83; p = 0.005). The median agreement of sleep and wake counts between PSG and the actigraph was 73% and the Cohen's Kappa value was 0.66. The medians of sensitivity and specificity of the actigraph for detecting sleep versus PSG were 84 and 66%, respectively. The median positive and negative predictive values of the actigraph were 74 and 72%, respectively.
CONCLUSIONS
This study demonstrated that, under controlled laboratory conditions, the Vibe actigraph in its default settings is a promising tool for the detection of sleep-wake parameters in a small number of ambulatory patients with COPD. Clinical Impact: The actigraph used in this pilot study suggests that these devices could provide clinically relevant information in COPD to better understand the relationship between sleep and health in this population.
|
10.1109/JTEHM.2020.3018399
|
pubmed_20_25420
|
Arsenic is well established as a human carcinogen, but the molecular mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It is also not known if lncRNAs are involved in arsenic-induced liver carcinogenesis. We have found that MALAT1, a non-coding RNA, is over-expressed in the sera of people exposed to arsenite and in hepatocellular carcinomas (HCCs), and MALAT1 has a close relation with the clinicopathological characteristics of HCC. In addition, hypoxia-inducible factor (HIF)-2α is up-regulated in HCCs, and MALAT1 and HIF-2α have a positive correlation in HCC tissues. During the malignant transformation of human hepatic epithelial (L-02) cells induced by a low concentration (2.0 μM) of arsenite, MALAT1 and HIF-2α are increased. In addition, arsenite-induced MALAT1 causes disassociation of the von Hippel-Lindau (VHL) protein from HIF-2α, therefore, alleviating VHL-mediated HIF-2α ubiquitination, which causes HIF-2α accumulation. In turn, HIF-2α transcriptionally regulates MALAT1, thus forming a positive feedback loop to ensure expression of arsenite-induced MALAT1 and HIF-2α, which are involved in malignant transformation. Moreover, MALAT1 and HIF-2α promote the invasive and metastatic capacities of arsenite-induced transformed L-02 cells and in HCC-LM3 cells. The capacities of MALAT1 and HIF-2α to promote tumor growth are validated in mouse xenograft models. In mice, arsenite induces an inflammatory response, and MALAT1 and HIF-2α are over-expressed. Together, these findings suggest that the MALAT1/HIF-2α feedback loop is involved in regulation of arsenite-induced malignant transformation. Our results not only confirm a novel mechanism involving reciprocal regulation between MALAT1 and HIF-2α, but also expand the understanding of the carcinogenic potential of arsenite.
|
10.18632/oncotarget.6806
|
pubmed_153_19094
|
'Normal' genomic DNA contains hundreds of mismatches that are generated daily by the spontaneous deamination of C (U/G) and methyl-C (T/G). Thus, a mutagenic effect of their repair could constitute a serious genetic burden. We show here that while mismatches introduced into human cells on an SV40-based episome were invariably repaired, this process induced mutations in flanking DNA at a significantly higher rate than no mismatch controls. Most mutations involved the C of TpC, the substrate of some single strand-specific APOBEC cytidine deaminases, similar to the mutations that can typify the 'mutator phenotype' of numerous tumors. siRNA knockdowns and chromatin immunoprecipitation showed that TpC preferring APOBECs mediate the mutagenesis, and siRNA knockdowns showed that both the base excision and mismatch repair pathways are involved. That naturally occurring mispairs can be converted to mutators, represents an heretofore unsuspected source of genetic changes that could underlie disease, aging, and evolutionary change.DOI: http://dx.doi.org/10.7554/eLife.02001.001.
|
10.7554/eLife.02001
|
pubmed_60_6645
|
CASE DESCRIPTION
A 2-year-old spayed female Border Collie was treated with IV lipid emulsion (ILE) after ingesting 6 mg/kg (2.73 mg/lb) of an equine ivermectin anthelmintic paste 8 hours prior to examination.
CLINICAL FINDINGS
On initial examination, the dog had stable cardiovascular signs but had diffuse muscle tremors and was hyperthermic. Neurologic evaluation revealed that the dog was ataxic and had mydriasis with bilaterally absent menace responses and pupillary light reflexes. The remaining physical examination findings were unremarkable. Results of CBC, serum biochemical analysis, venous blood gas analysis, and measurement of plasma lactate concentration were also within reference limits.
TREATMENT AND OUTCOME
The dog was treated with ILE in addition to supportive care with IV fluid therapy and cardiovascular, respiratory, and neurologic monitoring. The use of ILE treatment was initiated in this patient on the basis of previous clinical and experimental evidence supporting its use for toxicosis resulting from lipid-soluble agents. An initial bolus of 1.5 mL/kg (0.68 mL/lb) of a 20% sterile lipid solution was administered IV over 10 minutes, followed by a constant rate infusion of 0.25 mL/kg/min (0.11 mL/lb/min) over 60 minutes that was administered twice to treat clinical signs of ivermectin toxicosis. The dog was discharged from the hospital 48 hours after admission and was clinically normal within 4 days after ivermectin ingestion. Further diagnostic evaluation subsequently revealed that this dog was unaffected by the multidrug resistance gene (MDR-1) deletion, known as the ATP-binding cassette polymorphism.
CLINICAL RELEVANCE
Ivermectin toxicosis in veterinary patients can result in death without aggressive treatment, and severe toxicosis often requires mechanical ventilation and intensive supportive care. This is particularly true in dogs affected by the ATP-binding cassette polymorphism. Novel ILE treatment has been shown to be effective in human patients with lipid-soluble drug toxicoses, although the exact mechanism is unknown. In the patient in the present report, ILE was used successfully to treat ivermectin toxicosis, and results of serial measurement of serum ivermectin concentration supported the proposed lipid sink mechanism of action.
|
10.2460/javma.239.10.1328
|
pubmed_760_11849
|
During the last 20 years pigs have become increasingly popular in large animal translational neuroscience research as an economical and ethical feasible substitute to non-human primates. The anatomy of the pig telencephalon is, however, not well known. We present, accordingly, a detailed description of the surface anatomy and cytoarchitecture of the Göttingen minipig telencephalon based on macrophotos and consecutive high-power microphotographs of 15 μm thick paraffin embedded Nissl-stained coronal sections. In 1-year-old specimens the formalin perfused brain measures approximately 55 × 47 × 36 mm (length, width, height) and weighs around 69 g. The telencephalic part of the Göttingen minipig cerebrum covers a large surface area, which can be divided into a neocortical gyrencephalic part located dorsal to the rhinal fissure, and a ventral subrhinal part dominated by olfactory, amygdaloid, septal, and hippocampal structures. This part of the telencephalon is named the subrhinal lobe, and based on cytoarchitectural and sulcal anatomy, can be discerned from the remaining dorsally located neocortical perirhinal/insular, pericallosal, frontal, parietal, temporal, and occipital lobes. The inner subcortical structure of the minipig telencephalon is dominated by a prominent ventricular system and large basal ganglia, wherein the putamen and the caudate nucleus posterior and dorsally are separated into two entities by the internal capsule, whereas both structures ventrally fuse into a large accumbens nucleus. The presented anatomical data is accompanied by surface renderings and high-power macrophotographs illustrating the telencephalic sulcal pattern, and the localization of the identified lobes and cytoarchitectonic areas. Additionally, 24 representative Nissl-stained telencephalic coronal sections are presented as supplementary material in atlas form on http://www.cense.dk/minipig_atlas/index.html and referred to as S1-S24 throughout the manuscript.
|
10.1007/s00429-016-1327-5
|
pubmed_1075_16575
|
AIMS
The current study includes all consecutive patients with advanced heart failure and cardiac resynchronization therapy (CRT) with an implantable cardioverter defibrillator (ICD) over a 10-year period in a tertiary referral centre. It aims at identifying independent risk factors for mortality during CRT-defibrillator (CRT-D) treatment.
METHODS AND RESULTS
This study includes 239 consecutive patients who had undergone implantation of a CRT-D system (ejection fraction 25.9 ± 8%; 139 patients with ischaemic, 100 patients with non-ischaemic cardiomyopathy). Enrolment took place between 2001 and 2010, resulting in a median follow-up of 43 ± 30 months. During follow-up, 59 patients (25%) died. An impaired baseline kidney function [hazard ratio (HR) 1.98; 95% confidence interval (CI) 1.7-3; P< 0.0001], appropriate ICD therapy during follow-up (HR 2.1; CI 1.1-3.4; P= 0.001), lack of beta-blocker therapy (HR 2.3; CI 1.6-3.8; P= 0.004), and intake of amiodarone (HR 2; CI 1.8-4.1; P< 0.0001) were identified as predictors of overall mortality.
CONCLUSION
This study demonstrates the benefit of beta-blocker therapy also in patients on long-term CRT-D treatment. It confirms the prognostic significance of impaired renal function and the occurrence of appropriate ICD therapies also in CRT-D patients. It argues for an intensified follow-up regimen and adjustment of heart failure treatment whenever these prognostic markers are identified in a patient treated with CRT-D.
|
10.1093/europace/eus152
|
pubmed_285_9172
|
INTRODUCTION
There are few reports of in vivo muscle strength measurements in animal models of ICU-acquired weakness (ICU-AW). In this study we investigated whether the Escherichia coli (E. coli) septic peritonitis mouse model may serve as an ICU-AW model using in vivo strength measurements and myosin/actin assays, and whether development of ICU-AW is age-dependent in this model.
METHODS
Young and old mice were injected intraperitoneally with E. coli and treated with ceftriaxone. Forelimb grip strength was measured at multiple time points, and the myosin/actin ratio in muscle was determined.
RESULTS
E. coli administration was not associated with grip strength decrease, neither in young nor in old mice. In old mice, the myosin/actin ratio was lower in E. coli mice at t = 48 h and higher at t = 72 h compared with controls.
CONCLUSIONS
This E. coli septic peritonitis mouse model did not induce decreased grip strength. In its current form, it seems unsuitable as a model for ICU-AW.
|
10.1002/mus.24711
|
pubmed_567_11913
|
OBJECTIVE
To determine the efficacy, tolerability and safety of oral rifaximin given at three dose levels in patients with cirrhosis and mild to moderate hepatic encephalopathy (HE).
DESIGN
Prospective, double-blind, randomized, parallel-group study.
SETTING
Multi-centre trial in four university teaching hospitals.
PARTICIPANTS
Fifty-four patients with cirrhosis and mild to moderate HE.
INTERVENTION
Seven days treatment with rifaximin, 600, 1200 or 2400 mg/day in three divided doses.
MAIN OUTCOME MEASURE
Change in the portal-systemic encephalopathy (PSE) index between baseline and day 7, calculated on the basis of mental state, asterixis, number connection test time, EEG mean cycle frequency and blood ammonia concentrations.
RESULTS
Treatment with rifaximin was associated with an improvement in the PSE index. There was a trend towards a greater treatment effect of rifaximin with the highest dose of 2400 mg/day. Rifaximin was well tolerated; the few treatment-related adverse events showed no consistent pattern or dose relationship.
CONCLUSION
Rifaximin may be useful as alternative or adjuvant therapy for grade I-III hepatic encephalopathy in patients with cirrhosis at a dose of 1200 mg/day.
|
10.1097/00042737-200012020-00012
|
pubmed_76_13399
|
To investigate the alterations in insulin secretion induced by aging, 2-month-old, 12-month-old, and 12-month old lean rats (submitted to a caloric restriction during the last month that causes a weight loss of approximately 20%) were studied. As expected, glucose intolerance and increased insulin response were observed during IV-GTT in 12-month-old rats. These effects were, however, reversed by weight loss. Insulin secretion was investigated in isolated islets both during static incubation and perifusion. In 12-month-old rats insulin secretion and 45Ca2+ efflux were lower only in the second phase of the hormonal secretion, suggesting an involvement of voltage-sensitive calcium channels in these phenomena. Considering that in vivo and in vitro alterations were reversed after weight loss, it is possible to conclude that obesity is probably a major cause of impaired insulin secretion in 12-month-old albino rats. Since 14C-glucose metabolism was not changed in islets from aged rats, the effect of obesity on insulin secretion is not due to altered glucose metabolism in pancreatic B-cells.
|
10.1016/0031-9384(92)90403-o
|
pubmed_825_9687
|
The many invasive arterial procedures that require cannulation of an artery with a large or traumatic catheter can be expected to produce iatrogenic injuries in a certain number of patients. While almost all arterial cannulation procedures are performed by physicians, nurses play a major role in performing baseline assessment of arterial blood flow, monitoring indwelling catheters, and detecting evidence of arterial injury. Clinical manifestations may appear during a procedure, while an indwelling arterial catheter is in place or after the catheter has been removed. Vigilant attention is essential to prevent serious injury or death due to a complication of an iatrogenic arterial injury.
|
pubmed_825_9687
|
pubmed_160_24466
|
The Queen Mary conference on “Integrating Genetic and Cultural Evolutionary Approaches to Language,” and the papers in this special issue, clearly illustrate the excitement and potential of trans-disciplinary approaches to language as an evolved biological capacity (phylogeny) and an evolving cultural entity (glossogeny). Excepting the present author, the presenters/authors are mostly young rising stars in their respective fields, and include scientists with backgrounds in linguistics, animal communication, neuroscience, evolutionary biology, anthropology, and computer science. On display was a clear willingness to engage with different approaches and terminology and a commitment to shared standards of scientific rigor, empirically driven theory, and logical argument. Because the papers assembled here, together with the introduction, speak for themselves, I will focus in this “extro-duction” on some of the terminological and conceptual difficulties which threaten to block this exciting wave of scientific progress in understanding language evolution, in both senses of that term. In particular I will first argue against the regrettably widespread practice of opposing cultural and genetic explanations of human cognition as if they were dichotomous. Second, I will unpack the debate concerning “general-purpose” and “domain-specific” mechanisms, which masquerades as a debate about nativism but is nothing of the sort. I believe that framing discussions of language in these terms has generated more heat than light, and that a modern molecular understanding of genes, development, behavior, and evolution renders many of the assumptions underlying this debate invalid.
|
10.3378/027.083.0210
|
pubmed_285_6173
|
OBJECTIVES
Progranulin has been reported to have neuroprotective actions in cultured neurons. This study investigated the effect of recombinant rat progranulin on early brain injury after subarachnoid hemorrhage.
DESIGN
Controlled in vivo laboratory study.
SETTING
Animal research laboratory.
SUBJECTS
Two hundred thirty adult male Sprague-Dawley rats weighing 280-320 g.
INTERVENTIONS
Subarachnoid hemorrhage was induced in rats by endovascular perforation. Rat recombinant progranulin (1 and 3 ng) was administrated intracerebroventricularly at 1.5 hours after subarachnoid hemorrhage. Progranulin small interfering RNA was administrated by intracerebroventricularly at 1 day before subarachnoid hemorrhage induction. Subarachnoid hemorrhage grade, neurologic score, and brain water content were measured at 24 and 72 hours after subarachnoid hemorrhage. Neural apoptosis was evaluated by double immunofluorescence staining using terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick-end labeling and neuronal nuclei. For mechanistic study, the expression of progranulin, phosphorylated Akt, Akt, p-Erk, Erk, Bcl-2, and cleaved caspase-3 were analyzed by Western blot at 24 hours after subarachnoid hemorrhage. siRNA for sortilin 1 (a progranulin receptor) was used to intervene the downstream pathway.
MEASUREMENTS AND MAIN RESULTS
The expression of progranulin decreased and reached the lowest point at 24 hours after subarachnoid hemorrhage. Administration of rat recombinant progranulin decreased brain water content and improved neurologic functions at both 24 and 72 hours after subarachnoid hemorrhage, while knockdown of endogenous progranulin aggravated neurologic deficits after subarachnoid hemorrhage. Rat recombinant progranulin treatment reduced neuronal apoptosis, while progranulin deficiency promoted neuronal apoptosis at 24 hours after subarachnoid hemorrhage. Rat recombinant progranulin promoted Akt activation, increased Bcl-2 level, but reduced caspase-3 level. Knockdown of progranulin binding factor sortilin 1 abolished the beneficial effects of rat recombinant progranulin at 24 hours after subarachnoid hemorrhage.
CONCLUSION
Rat recombinant progranulin alleviated neuronal death via sortilin 1-mediated and Akt-related antiapoptosis pathway. Rat recombinant progranulin may have potentials to ameliorate early brain injury for subarachnoid hemorrhage patients.
|
10.1097/CCM.0000000000001096
|
pubmed_803_7632
|
Microelectrode recordings have been made of the activity of neurons in the left dorsal horn of the lumbar enlargement of cats in which the left sciatic and saphenous nerves had been crushed 9 months earlier. In normal animals the receptive fields of neurons in this part of the spinal cord excited by gentle mechanical stimulation of the leg are somatotopically organized in such a way that they provide a map of the hind-leg skin. Previous experiments have shown that 9 months after cutting the nerves supplying the lower half of the hind-leg this somatotopic map is lost. The present experiments show that 9 months after nerve crush the somatotopic map is restored and indistinguishable from that seen in normal animals.
|
10.1016/0006-8993(83)91379-3
|
pubmed_1135_13430
|
INTRODUCTION
Strategies to transfer international health research training programs to sub-Saharan African institutions focus on developing cadres of local investigators who will lead such programs. Using a critical leadership theory framework, we conducted a qualitative study of one program to understand how collaborative training and research can support early career investigators in Kenya toward the program transfer goal.
METHODS
We used purposive sampling methods and a semi-structured protocol to conduct in-depth interviews with US (N = 5) and Kenyan (N = 5) independent investigators. Transcripts were coded using a two-step process, and then compared with each other to identify major themes.
RESULTS
A limited local research environment, funding needs and research career mentorship were identified as major influences on early career researchers. Institutional demands on Kenyan faculty to teach rather than complete research restricted investigators' ability to develop research careers. This was coupled with lack of local funding to support research. Sustainable collaborations between Kenyan, US and other international investigators were perceived to mitigate these challenges and support early career investigators who would help build a robust local research environment for training.
CONCLUSION
Mutually beneficial collaborations between Kenyan and US investigators developed during training mitigate these challenges and build a supportive research environment for training. In these collaborations, early career investigators learn how to navigate the complex international research environment to build local HIV research capacity. Shared and mutually beneficial resources within international research collaborations are required to support early career investigators and plans to transfer health research training to African institutions.
|
10.11604/pamj.2015.20.192.5964
|
pubmed_955_18272
|
The aim of these studies was to investigate the mechanism underlying the haemodynamic changes associated with brain death. The initial series of studies were to assess whether these changes involved some blood-borne factor. When control rats (n = 6) were exsanguinated whilst being simultaneously transfused with blood from rats that had been brain-dead for 60 min, their haemodynamic function did not deteriorate. Likewise, when brain-dead rats (n = 6) were exsanguinated and transfused with blood from control rats there was no improvement of haemodynamic function. The absence of any blood-borne factor was further confirmed in studies in which isolated hearts from control rats were perfused with blood from a support rat which had been brain-dead for 15 min (n = 6/group). The brain-death-induced haemodynamic changes in the support rat (mean arterial pressure increased from 98 +/- 6 to 176 +/- 9 mm Hg after 30 s and then fell to 44 +/- 5 mm Hg after 5 min) were not associated with changes in cardiac function of the perfused heart (left ventricular developed pressure was 146 +/- 4 mmHg before the induction of brain death and 147 +/- 4 and 151 +/- 7 mm Hg at 30 s and 5 min, respectively, after the induction). In further in vivo studies, we assessed the involvement of the autonomic nervous system in brain-death-induced haemodynamic instability. We achieved this by employing beta-adrenoreceptor blockade or bilateral vagotomy (n = 6/group); propranolol (1 mg/kg given as a bolus 6 min before brain death followed by 0.5 mg/kg/h continuous infusion) abolished the early transient tachycardia and positive inotropic response to brain death but did not alter the subsequent deterioration of function (mean arterial pressure fell from 75 +/- 7 mmHg before brain death to 49 +/- 5 mmHg after 30 min). Bilateral vagotomy had no effect on the functional changes induced by brain death. The effect of catecholamine depletion was then investigated; 6-hydroxydopamine (given over 15 days) depleted myocardial norepinephrine content by approximately 90% (from 2.3 +/- 0.1 to 0.3 +/- 0.1 nmol/g wet wt; P < 0.05). Depletion of cardiac catecholamines reduced brain-death-induced mortality to zero but did not affect cardiac dysfunction. Finally, we used L-NAME and naloxone in an attempt to identify roles for nitric oxide and endogenous opioid peptides but were again unable to influence the cardiac events. In conclusion, the initial transient hyperdynamic response induced by brain death appears to be mediated through cardiac innervation and can be inhibited by beta-adrenoreceptor blockade. However, the autonomic nervous system, nitric oxide, endogenous opioid peptides and blood-borne factors do not appear to be involved in the subsequent deterioration of cardiac function.
|
10.1006/jmcc.1994.1059
|
pubmed_215_4988
|
The Lyon-Marseille-Curie-Est (LMCE) of France cooperative group has previously reported successive series of unselected stage four children older than 1 year at diagnosis with metastatic neuroblastoma (LMCE 1 and 3). The goal of LMCE 5 study was to increase progression free survival rate as compared to LMCE 1 and 3. Based on improvements reported with post induction chemotherapy, the LMCE 5 used post induction for all children, but omitted total body irradiation and immunomagnetic purging in megatherapy regimen for all children. Twenty-five sequentially diagnosed children received an induction regimen which compared with previous induction included an increased dose of etoposide and cyclophosphamide, delivered similar dose of cisplatinum, and deleted doxorubicin and vincristin. After surgery treatment was stratified based on response and eligible children received etoposide carboplatin (LMCE 5A : n=10)+/-doxorubicin (LMCE 5B-C n=13) followed by megatherapy (melphalan without total body irradiation and unpurged peripheral blood stem cell rescue). The increase in drug doses during induction did not improve remission rate. The progression free survival at 6 years is 8%. It is significantly worse than LMCE 3, and equivalent to LMCE 1 study though toxic death rate has decreased with increasing experience. Failure to improve the response rate during induction and reducing the megatherapy regimen may be the main factors in this disappointing result. Modified strategies for induction, non toxic alternative to total body irradiation, and post megatherapy regimen should be developed.
|
10.1038/sj.bjc.6600627
|
pubmed_74_9941
|
BACKGROUND
Successful dissemination of the new classification of periodontitis is facilitated by emphasis on the basic ground rules, clarification of ambiguities, and identification of "gray zones" where thoughtful application of the guidelines by an informed, experienced clinician is paramount to arrive at a correct Stage and Grade.
METHODS
Highlighted ground rules are (1) Stage is a patient-based, not a tooth-based concept, therefore, a single Stage is assigned per patient; (2) Stage can shift upward over time, if the periodontal status deteriorates, but the initially assigned Stage is retained even after improvement post-therapy; (3) the complexity factors that determine Stage must be evaluated collectively, not in isolation, to arrive at a clinically meaningful assessment; (4) a single Grade is assigned to a patient based on a deliberate evaluation of the "biological fabric" of the case, in terms of history of/risk for further progression, interplay of risk factors, and the two-way effects of periodontitis or its treatment on general health; (v) shift of Grade over time is possible towards either direction, after thorough, collective, evaluation of changes in the above parameters. Exemplified gray zones include a radiographically intact patient with minimal attachment loss in older age; presence of "frank" periodontitis affecting a single tooth; and assessment of factors that do/do not lead to increased complexity of therapy.
CONCLUSION
Differentiating between Stage I/II versus Stage III/IV periodontitis is relatively uncomplicated; further distinction between Stages and correct assignment of Grade requires nuanced, thorough interpretation of a broad array of findings by a knowledgeable clinician.
|
10.1002/JPER.19-0557
|
pubmed_687_16717
|
In the wake of North America's opioid crisis, access to evidence-based treatment for opioid use disorder (OUD) is of critical importance. While buprenorphine/naloxone and methadone are currently indicated as first-line medications for the treatment of OUD, there are a proportion of individuals who do not benefit from these therapies. Recent Canadian guidelines suggest the use of alternate therapies, including slow-release oral morphine or injectable opioid agonist therapy (iOAT) for individuals unsuccessful with either methadone or buprenorphine/naloxone. While the guidelines highlight the need to intensify OUD treatment as disease severity increases, equally important is the consideration for deintensification of treatment (eg, from iOAT to an oral opioid agonist treatment (OAT) option) following successful stabilisation. Literature addressing how best to accomplish this, however, is currently lacking. Accordingly, the case presented here describes a patient that successfully transitions from iOAT to oral buprenorphine/naloxone using a novel induction approach termed microdosing.
|
10.1136/bcr-2019-233715
|
pubmed_755_20145
|
Neonatal alloimmune thrombocytopenia is caused by the transplacental passage of maternal antibodies directed against platelet-specific antigens. Because complications from bleeding may result, prompt institution of therapy may be necessary. Accurate diagnosis by serologic techniques permits appropriate therapy to be administered both prenatally and postnatally.
|
pubmed_755_20145
|
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