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pubmed_159_16763 | OBJECTIVE
End-stage renal disease patients with vein diameter of ≤2.2 mm can undergo autogenous arteriovenous fistula (AVF) formation with the acceptable results.
METHODS
This observational retrospective study of prospectively collected data analyzed end-stage renal disease patients with a vein diameter of ≤ 2.2 mm, who underwent AVF formation at Shifa International Hospital Islamabad from January 2009 to December 2017. The fistulae were observed for immediate success and maturity at 3 months. The chi-square test was used to determine the effect of vein diameter on final maturity. All data were analyzed using SPSS.
RESULTS
The total number of patients with vein diameter of ≤2.2 mm was 38, with a mean age of 46.76 ± 12.790 years. Vein diameters ranged from 1.6 to 2.2 mm. Immediate success was observed in 35 (92.1%) cases. Veins of 31 (81.6%) patients showing maturity at 3 months and were used for hemodialysis. The overall success rate for the small caliber veins was 82%.
CONCLUSION
Although end-stage renal disease patients present late with very small diameter veins, these veins should still be accommodated for permanent vascular access, because their maturity rates are still acceptable, even though these are lower than those of patients with adequate sized veins. | 10.1007/s00268-020-05540-z |
pubmed_929_5797 | In this article, we report an integrated optical nanolens exhibiting a pseudo-graded index distribution in a guided configuration. This dielectric metalens relies on a permittivity distribution through dielectric strips of the core material, which is compatible with existing silicon photonic technology. We show in this paper that effective medium theory (EMT) inaccurately predicts the focal length of such devices, and we propose an efficient and accurate design approach based on 2D finite element method (FEM) mode calculations that are in good agreement with 3D FDTD simulations. The lens was fabricated on a 200 mm silicon on insulator pilot line, and fibre-to-fibre optical characterizations revealed an excellent transmission of 85% for TM polarization, in line with the simulated performance (90%). The proposed approach can be easily extended to width-variable strips, enabling the realization of all types of graded index devices, especially those derived from transformation optics. | 10.1038/s41598-020-58029-z |
pubmed_51_16285 | Chronic obstructive pulmonary disease is associated with altered cortical excitability. The relevance of this to the need for non-invasive ventilation is not known. We assessed the diaphragm response to transcranial magnetic stimulation in terms of motor threshold and latency as well as assessing intracortical excitability using paired stimulation in eight long-term users and six non-users of home ventilation with COPD. Overall, intracortical facilitation was strongly correlated with inspiratory muscle strength (r2 0.72, p<0.001) whereas intracortical inhibition was correlated with PaCO2 (r2 0.51, p=0.01). The two groups did not differ in motor evoked potential or latency, nor in the excitability of intracortical inhibitory or facilitatory circuits assessed using paired stimulation. The acute effect of isocapnic non-invasive ventilation was studied in six established ventilator users. Diaphragm motor evoked potential fell but there was no effect on intracortical facilitation or inhibition, implying an effect of neuromechanical feedback at brainstem or spinal level. | 10.1016/j.resp.2012.05.018 |
pubmed_158_12917 | Antiparallel complementary strands of DNA contribute symmetrically to the helical structure and its stability; rough conformational differences between complementary strands would interfere with this symmetric contribution and the stability. To detect conformational differences between complementary strands, we challenged the complementary strands to different "pore size" of acrylamide gels and measured differences in migration during electrophoretic mobility analysis. Changes in migration differences revealed a significant structural bias between the complementary strands of the dinucleotide repeat deoxy-(TG/AC)n. | 10.1002/elps.1150180104 |
pubmed_1004_1141 | In terms of the angular spectrum representation, general expressions are given to describe the free-space propagation of electromagnetic fields with radial or azimuthal polarization structure at a transverse plane. The transverse distributions of the radial, azimuthal and longitudinal components of these fields are also analysed. In particular, the on-axis behavior upon free propagation is studied. Furthermore, the special but important case of those fields that retain their polarization character (radial or azimuthal) under propagation is also considered. The analytical results are illustrated by application to some examples. | 10.1364/oe.16.009021 |
pubmed_757_718 | OBJECTIVES
Patients with severe spontaneous intracranial haemorrhages, managed in intensive care units, face ethical issues regarding the difficulty of anticipating their recovery. Prognostic tools help clinicians in counselling patients and relatives and guide therapeutic decisions. We aimed to methodologically assess prognostic tools for functional outcomes in severe spontaneous intracranial haemorrhages.
DATA SOURCES
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, we conducted a systematic review querying Medline, Embase, Web of Science, and the Cochrane in January 2020.
STUDY SELECTION
We included development or validation of multivariate prognostic models for severe intracerebral or subarachnoid haemorrhage.
DATA EXTRACTION
We evaluated the articles following the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies and Transparent Reporting of multivariable prediction model for Individual Prognosis Or Diagnosis statements to assess the tools' methodological reporting.
RESULTS
Of the 6149 references retrieved, we identified 85 articles eligible. We discarded 43 articles due to the absence of prognostic performance or predictor selection. Among the 42 articles included, 22 did not validate models, 6 developed and validated models and 14 only externally validated models. When adding 11 articles comparing developed models to existing ones, 25 articles externally validated models. We identified methodological pitfalls, notably the lack of adequate validations or insufficient performance levels. We finally retained three scores predicting mortality and unfavourable outcomes: the IntraCerebral Haemorrhages (ICH) score and the max-ICH score for intracerebral haemorrhages, the SubArachnoid Haemorrhage International Trialists score for subarachnoid haemorrhages.
CONCLUSIONS
Although prognostic studies on intracranial haemorrhages abound in the literature, they lack methodological robustness or show incomplete reporting. Rather than developing new scores, future authors should focus on externally validating and updating existing scores with large and recent cohorts. | 10.1136/bmjopen-2020-047279 |
pubmed_1000_11776 | The leishmanicidal property of piperine intercalated in liposomes and in mannose-coated liposomes was tested in experimental visceral leishmaniasis in hamsters. Mannose-coated liposomal piperine eliminated intracellular amastigotes of Leishmania donovani in splenic macrophages much more efficiently than did the liposomal piperine or free piperine. At a dose equivalent to 6 mg/kg body wt every 4th day for a total of 4 doses in 12 days, the mannose-coated liposomal piperine was found to reduce spleen parasite load to the extent of 90% in comparison to that achieved by liposomal piperine (77%) or free piperine (29%). Histological examination of spleen and liver function tests showed that the toxicity of piperine was reduced when mannosylated liposomal piperine was administered. | pubmed_1000_11776 |
pubmed_327_2916 | BACKGROUND
Adolescent smokers are often unsuccessful in quitting and difficult to retain in cessation programs. In health promotion, focusing on the right target groups is essential. Aim. The aim was to examine if adolescent occasional smokers differ from daily smokers, and if possible differences could be useful for targeted smoking cessation programs.
METHODS
Ninety-one percent of all teenagers attending junior high or high schools participated in a cross-sectional study, conducted in Nord-Trøndelag County, Norway, 1995-1997, including 8,460 students 13-18 years old. Information on smoking habits, education, after school activities, and parents was obtained by self-administered questionnaires.
RESULTS
Fifty-four percent of boys and 57% of girls had tried at least one cigarette. Of these, 36% of boys and 41% of girls were current smokers, half of whom reported occasional smoking. Students who had quit smoking had more often been occasional than daily smokers. Compared to daily smokers, occasional smokers participated in higher academic courses, were more engaged in organized activities and sports, had been drunk less often, and had better family role models.
CONCLUSION
Differences support potential utility of focusing on occasional smokers as a special target group in smoking cessation programs. | 10.1006/pmed.2000.0750 |
pubmed_881_2672 | Oxidatively modified LDLs are antigenic and elicit the generation of autoantibodies often detected in plasma and within plaques of atherosclerotic patients. Although Cu(2+)-oxidized LDL and malondialdehyde (MDA)-modified LDL are usually used as antigens in immunoassays, other, still unrecognized epitopes may be formed in vivo during LDL oxidation and may induce antibody production. Antibodies recognizing LDL oxidatively modified by Cu2+, 2,2'-azobis-(2-amidino propane) hydrochloride (AAPH), and the combination of horseradish peroxidase and H2O2 (HRP) were detected in serum of a group of 90 unselected patients. HRP-oxidized LDL was the antigen that revealed the highest IgG titers, although the extent of LDL oxidation (evaluated as conjugated diene formation, loss of tryptophan fluorescence, production of fluorescent aldehydic adducts, and change in electrophoretic mobility) was comparable to that obtained with Cu2+ and AAPH. There was a highly statistically significant correlation between the IgG titers detected using Cu(2+)- and AAPH-oxidized LDLs as antigens, but no correlation was found between the IgG titers revealed by HRP and Cu2+ or AAPH. In addition, the antibody titers against MDA-modified LDL exhibited a significant correlation with those against Cu(2+)- or AAPH-oxidized LDL but did not correlate with those against HRP-oxidized LDL. Finally, immunocompetition experiments revealed that IgG recognizing HRP-oxidized LDL did not cross-react with Cu(2+)-oxidized LDL and vice versa. The possibility that lipid peroxidation-independent modifications could play a role in HRP-induced formation of antigenic epitopes in LDL was supported by two lines of evidence. First, in probucol-enriched LDL, despite the complete inhibition of lipid peroxidation, HRP, but not Cu2+ and AAPH, was still able to generate epitopes that were recognized by the same sera reacting with HRP-oxidized native (not probucol-enriched) LDL. In addition, the presence of autoantibodies against Cu(2+)- and AAPH-oxidized LDLs was negatively correlated with serum alpha-tocopherol concentration, whereas the titers against HRP-oxidized LDL did not exhibit any statistically relevant correlation with alpha-tocopherol levels. Together, these findings indicate that peroxidase(s)-dependent mechanisms can trigger peculiar lipid peroxidation-independent modifications of LDL in vivo. | 10.1161/01.atv.17.1.134 |
pubmed_138_5789 | A family is described in which five members, three sibs in one branch and two sib cousins in another, died of acute myelogenous leukemia. C-Monosomy was found in the marrow of two of the sibs. C-deletion aneuploidy has been increasingly reported in conjunction with abnormal myelopoiesis. It is possible that this chromosomal aberration may serve as a useful clinical marker of the emergence of a leukemic state. | 10.1002/1097-0142(197608)38:2<841::aid-cncr2820380230>3.0.co;2-x |
pubmed_972_18509 | Selection of the cleavage plane during cytokinesis in dividing cells is linked to the position of the mitotic spindle. A major player in cleavage plane positioning is believed to be the anaphase central spindle and its associated signaling complex called centralspindlin, composed of MgcRacGap and MKLP1. Centralspindlin has the capacity to induce furrowing of the cell cortex by promoting the localized activation of RhoA, which in turn promotes assembly of the contractile ring. We have found a way to induce a cytokinesis-like process in unfertilized Drosophila eggs and very early embryos, when spindle structures are few and located far from invaginating egg cortex. The simple injection of a small molecule inhibitor of Cdk1/Cyclin B (either Roscovitin or RO3306) is sufficient to promote membrane invagination near the site of injection. The furrow generated is in many respects similar to a classical cleavage furrow. Actin, myosin, anillin and MKLP1 are all associated with the forming furrow, which in some cases can entirely circumscribe the unfertilized egg. A similar furrow can also be generated by the localized injection of constitutively active RhoA protein, suggesting that Cdk1 is normally an upstream inhibitor of RhoA activation. We show further that this process apparently is not associated with microtubules. Since simple localized inhibition of Cdk1 is sufficient to induce a furrow, we suggest that in real cytokinesis in normal cells, the localized downregulation of Cdk1 activity at the metaphase-anaphase transition may contribute, along with the spindle, to the positioning of the cleavage furrow. | 10.4161/cc.21190 |
pubmed_612_25558 | OBJECTIVE
To (a) determine the impact of Kentucky's (KY's) mandate requiring postmortem toxicology testing of coroner cases; (b) identify the influence of coroner experience and training, jurisdiction size, budget, and location on postmortem testing requests; (c) identify facilitators/barriers for postmortem toxicology testing requests and listing the specific drugs involved in drug-poisoning deaths on death certificates.
METHODS
A modified Dillman approach was used to deliver the survey to KY's elected coroners between April and May 2016. Responses stratified by identified influence factors were compared using χ2 tests and Fisher exact tests.
RESULTS
Fifty-eight percent of coroners reported that drug overdose investigations had changed since the mandate was enacted. Statistically significant differences in responses were found when stratified. Sixty-three percent of coroners reported always using testing results to complete death certificates.
CONCLUSIONS
Uptake of the mandate for postmortem toxicology testing of all decedents is not yet complete.
POLICY IMPLICATION
Without uptake of the mandate, surveillance efforts may result in undercounting of drug overdose deaths and the involvement of specific drugs. Mandates for enhanced training and modification of funding structure for medico-legal death investigations could facilitate uptake. | 10.1177/1925362119851127 |
pubmed_1023_4134 | The effect of increased arterial pressure on aortic depressor nerve activity was studied in the conscious rabbit. Aortic baroreceptor resetting was observed following 15 min of sustained pressure elevation. At 15 min, there was a significant increase in the threshold arterial pressure for aortic nerve activity, but peak nerve activity did not change. This resulted in an increase in the slope of the pressure-nerve activity relationship. Therefore, except for peak nerve activity, aortic nerve activity was reduced at all pressures following 15 min of sustained pressure elevation. At 30 min, peak nerve activity also increased, resulting in a parallel shift in the pressure-activity curve. The early increase in slope of the pressure-activity relationship may be due to an early resetting of low threshold fibers with a high pressure differential between their threshold pressure and the sustained pressure elevation used to induce resetting. A late resetting of high threshold fibers with a low pressure differential between their threshold pressures and the pressure used to cause resetting of baroreceptors results in a parallel shift in the curve observed at 30 min. These data obtained from multiunit recordings provide unexpected evidence about baroreceptor resetting, which is not apparent from single-unit recordings. | 10.1152/ajpheart.1984.246.2.H302 |
pubmed_533_12194 | Gamma delta T (γδT) lymphocytes are primed for rapid function, including cytotoxicity toward cancer cells, and are a component of the immediate stress response. Following activation, they can function as professional antigen-presenting cells. Chimeric antigen receptors (CARs) work by focusing T cell function on defined cell surface tumor antigens and provide essential costimulation for robust activation. Given the natural tropism of γδT cells for the tumor microenvironment, we hypothesized that their transduction with CARs might enhance cytotoxicity while retaining their ability to migrate to tumor and act as antigen-presenting cells to prolong the intratumoral immune response. Using a GD2-targeting CAR as a model system, we showed that γδT cells of both Vδ1 and Vδ2 subsets could be expanded and transduced to sufficient numbers for clinical studies. The CAR added to the cells' innate cytotoxicity by enhancing GD2-specific killing of GD2-expressing cancer cell lines. Migration toward tumor cells in vitro was not impaired by the presence of the CAR. Expanded CAR-transduced Vδ2 cells retained the ability to take up tumor antigens and cross presented the processed peptide to responder alpha beta T (αβT) lymphocytes. γδ CAR-T cell products show promise for evaluation in clinical studies of solid tumors. | 10.1016/j.ymthe.2017.12.001 |
pubmed_754_4609 | In order to investigate the antidiuretic hormone (ADH) in essential hypertension and secondary hypertension, plasma ADH levels were measured in normal subjects, in patients with normal and low essential hypertension, and in other patients with various forms of secondary hypertension. Plasma ADH levels were significantly lower in low renin essential hypertension and higher in malignant hypertension than in normal subjects. The plasma ADH levels tended to be lower in renal hypertension and primary aldosteronism, and higher in renovascular hypertension, but these differences were not statistically significant. From these results, it appeared that ADH might play a role in malignant hypertension, but not in the other hypertensive diseases. | 10.1507/endocrj1954.30.567 |
pubmed_934_14374 | Effects of chemicals are, in most cases, caused by internal concentrations within organisms which rely on uptake and elimination kinetics. These processes might be key components for assessing the effects of time-variable exposure of chemicals which regularly occur in aquatic systems. However, the knowledge of toxicokinetic patterns caused by time-variable exposure is limited, and gaining such information is complex. In this work, a previously developed mechanistic growth model of Myriophyllum spicatum is coupled with a newly developed toxicokinetic part, providing a model that is able to predict uptake and elimination of chemicals, as well as distribution processes between plant compartments (leaves, stems, roots) of M. spicatum. It is shown, that toxicokinetic patterns, at least for most of the investigated chemicals, can be calculated in agreement with experimental observations, by only calibrating two chemical- specific parameters, the cuticular permeability and a plant/water partition coefficient. Through the model-based determination of the cuticular permeabilities of Isoproturon, Iofensulfuron, Fluridone, Imazamox and Penoxsulam, their toxicokinetic pattern can be described with the model approach. For the use of the model for predicting toxicokinetics of other chemicals, where experimental data is not available, equations are presented that are based on the log (P oct/wat) of a chemical and estimate parameters that are necessary to run the model. In general, a method is presented to analyze time-variable exposure of chemicals more in detail without conducting time and labour intensive experiments. | pubmed_934_14374 |
pubmed_726_13539 | Extrauterine endometrial stromal sarcoma (ESS) is rare and typified by delayed recurrence of primary ESS. Here, we report an unusual case of colonic ESS in a woman with a remote history of hysterectomy. An 80-year-old woman, with a history of hysterectomy and bilateral salpingo-oophorectomy for abnormal bleeding and endometriosis 37 years prior to presentation, was diagnosed with ESS in the colon. She was treated with laparoscopic low anterior resection, followed by megestrol acetate, and has been in remission for more than 4 years. This case highlights the rarity of extra-uterine ESS in the colon, especially in the absence of a known history of primary uterine ESS. The patient's history of endometriosis may have been a predisposing risk factor. ESS in the colon may be treated successfully with surgical resection and progestin therapy. Indefinite surveillance is recommended to monitor for late recurrences. | 10.1155/2013/202458 |
others_200_117 | Low-intensity fire is extensively used in Australian dry eucalypt forests to reduce fuel levels. The long-term impact of this management practice on terrestrial invertebrates is, however, unknown and is of concern given their contribution to ecosystem function and forest biodiversity. This study found that areas subjected to frequent low-intensity fire had significantly lower numbers of spiders, ticks and mites, pseudoscorpions, woodlice, springtails, bugs, beetles, ants and insect larvae in the leaf litter compared with adjacent unburnt areas. Taxa numbers were between 41 and 82% lower and these reductions in abundance have led to an overall decline in taxon richness. This decrease was attributed to a reduction in the amount of litter and associated moisture levels, and a simplification of habitat structure. The extent of local and regional extinctions will depend upon the scale of this disturbance, with future studies investigating the impact on individual species within these communities. A comparison of two sampling techniques, pitfall-trapping and litter extraction, highlighted important considerations for spatial components of invertebrate sampling designs | 10.1023/A:1009643627781 |
pubmed_609_6806 | A 34-yr-old Chinese woman presented with hypokalaemic periodic paralysis. She had a goitre and was biochemically thyrotoxic. However, she also had urinary potassium loss with a metabolic acidosis and reduced ability to acidify her urine. The co-existence of distal renal tubular acidosis (RTA) was confirmed. There was no evidence of xerostomia or xerophthalmia, although anti-Ro antibody and rheumatoid factor were positive. Paralytic attacks did not recur after the thyrotoxicosis was controlled with radioactive iodine. Possible pathogenic mechanisms for the association of these disorders are discussed. Female patients presenting with thyrotoxic periodic paralysis (TPP) should be thoroughly investigated for possible additional precipitating factors in view of the strong male predominance of TPP, particularly when there are atypical metabolic features. | 10.1093/rheumatology/35.3.289 |
pubmed_934_1478 | Extensive screening analyses of perfluorooctane sulfonate and related perfluorinated compounds (PFCs) in biota samples from all over the world have identified PFCs as global pollutants and have shown their bioaccumulation into higher trophic levels in the food chain. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are environmental contaminants belonging to a chemical group known as perfluorinated compounds. PFOS and PFOA are very persistent in the environment and bioaccumulate in humans. They are potential reproductive and developmental toxicants and are considered to be emerging endocrine disrupters. The United States Environmental Protection Agency (USEPA) considers both compounds to be carcinogenic and the European Food Safety Authority (EFSA) recently pointed out that they are associated with adverse health effects. Diet is considered the main source of exposure to PFCs, which have been found more frequently in fish and other seafood, compared to other food groups. In fact, aquatic ecosystems represent the final reservoir for PFCs due to their great affinity for sedimentary and living organic matter. In these systems, measured levels of persistent organic pollutants (POPs) could increase along the trophic web, ultimately affecting humans that consume aquatic species. In this study, PFOS and PFOA was detected by LC-MS/MS in muscle samples of Coregonus lavaretus (European whitefish) and Perca fluviatilis (European perch) collected from Lake Maggiore, a large lake located on the south side of the Italian Alps. PFOA was not found in any of the investigated samples above the limit of quantitation of 0.50 ng g(-1) fresh weight (fw), whereas PFOS was detected in all 90 samples with concentrations of up to 46.0 ng g(-1)fw. Mean concentrations were 22.2 ng g(-1)fw in P. fluviatilis and 20.0 ng g(-1)fw in C.lavaretus. Comparison of our results with literature data on PFOS intake suggested that fish from Lake Maggiore may be a significant source of dietary PFOS exposure, even if the reported values were lower than the Total Daily Intake (TDI) proposed by EFSA. | pubmed_934_1478 |
pubmed_642_21691 | Initially identified as a mammalian apoptosis suppressor, defender against apoptotic death 1 (DAD1) protein has conserved plant orthologs acting as negative regulators of cell death. The potential roles and action mechanisms of plant DADs in resistance against Phytophthora pathogens are still unknown. Here, we cloned GmDAD1 from soybean and performed functional dissection. GmDAD1 expression can be induced by Phytophthora sojae infection in both compatible and incompatible soybean varieties. By manipulating GmDAD1 expression in soybean hairy roots, we showed that GmDAD1 transcript accumulations are positively correlated with plant resistance levels against P. sojae. Heterologous expression of GmDAD1 in Nicotiana benthamiana enhanced its resistance to Phytophthora parasitica. NbDAD1 from N. benthamiana was shown to have similar role in conferring Phytophthora resistance. As an endoplasmic reticulum (ER)-localized protein, GmDAD1 was demonstrated to be involved in ER stress signaling and to affect the expression of multiple defense-related genes. Taken together, our findings reveal that GmDAD1 plays a critical role in defense against Phytophthora pathogens and might participate in the ER stress signaling pathway. The defense-associated characteristic of GmDAD1 makes it a valuable working target for breeding Phytophthora resistant soybean varieties. | 10.3389/fpls.2019.00107 |
pubmed_186_18321 | BACKGROUND
The present study aimed to identify factors affecting vaccination against influenza among health professionals.
METHODS
We used a multi-centre cross-sectional design to conduct an online self-administered questionnaire with physicians and nurses at state and foundation university hospitals in the south-east of Turkey, between 1 January 2015 and 1 February 2015. The five participating hospitals provided staff email address lists filtered for physicians and nurses. The questionnaire comprised multiple choice questions covering demographic data, knowledge sources, and Likert-type items on factors affecting vaccination against influenza. The target response rate was 20 %.
RESULTS
In total, 642 (22 %) of 2870 health professionals (1220 physicians and 1650 nurses) responded to the questionnaire. Participants' mean age was 29.6 ± 9.2 years (range 17-62 years); 177 (28.2 %) were physicians and 448 (71.3 %) were nurses. The rate of regular vaccination was 9.2 % (15.2 % for physicians and 8.2 % for nurses). Increasing age, longer work duration in health services, being male, being a physician, working in an internal medicine department, having a chronic disease, and living with a person over 65 years old significantly increased vaccination compliance (p < 0.05). We found differences between vaccine compliant and non-compliant groups for expected benefit from vaccination, social influences, and personal efficacy (p < 0.05). Univariate analysis showed differences between the groups in perceptions of personal risks, side effects, and efficacy of the vaccine (p < 0.05). Multivariate analysis found that important factors influencing vaccination behavior were work place, colleagues' opinions, having a chronic disease, belief that vaccination was effective, and belief that flu can be prevented by natural ways.
CONCLUSION
Numerous factors influence health professionals' decisions about influenza vaccination. Strategies to increase the ratio of vaccination among physicians and nurses should consider all of these factors to increase the likelihood of success. | 10.1186/s12879-016-1528-9 |
pubmed_603_17597 | Statins are widely used in the primary and secondary prevention of cardiovascular disease and prevent first and recurrent ischemic strokes mainly because of their lipid-lowering effect. However, they also have pleiotropic effects and might be neuroprotective in acute ischemic stroke. Improved functional outcome in patients with acute ischemic stroke treated with intravenous thrombolysis tissue plasminogen activator has been proposed, but not confirmed by other studies. Furthermore, some studies showed an increased risk of symptomatic intracranial hemorrhage in statin users. The article being evaluated presents a large observational cohort of acute ischemic stroke patients treated with intravenous tissue plasminogen activator and showed no association between statin use or lipid profiles and functional outcome or risk of symptomatic intracranial hemorrhage. The results of this article are discussed in the context of previous published studies. | 10.1586/ern.12.88 |
pubmed_652_19516 | N and S codoping of graphene is realized by a novel approach: covalent functionalization of graphene oxide using 2-aminothiophenol as a source of both N and S followed by thermal treatment. The resulting N- and S-codoped graphene has potential applications in high-performance lithium-ion batteries and as a metal-free catalyst for oxygen reduction reaction. | 10.1002/adma.201401427 |
others_117_13683 | Abstract: Glioblastoma multiforme is a highly malignant brain tumor with average survival time of 15 months. Less than 2% of the patients survive beyond 36 months. To understand the molecular mechanism responsible for poor prognosis, we analyzed GBM samples of TCGA microarray (n = 560) data. We identified 720 genes that have a significant impact upon survival based on univariate cox regression. We applied the Genome Enhancer pipeline to analyze potential mechanisms of regulation of activity of these genes and to build gene regulatory networks. We identified 12 transcription factors enriched in the promoters of these genes including the key molecule of GBM—STAT3. We found that STAT3 has significant differential expression across extreme survivor groups (short-term survivors– survival < 12 months and long-term survivors—survival > 36 months) and also has significant impact on survival. In the next step, we identified master regulators in the signal transduction network that regulate the activity of these transcription factors. Master regulators are filtered based on their differential expression across extreme survivor groups and impact on survival. This work validates our earlier report on master regulators IGFBP2, PDGFA, OSMR and AEBP1 driving short survival. Additionally, we propose CD14, CD44, DUSP6, GRB10, IL1RAP, FGFR3 and POSTN as master regulators driving poor survival. These master regulators are proposed as promising therapeutic targets to counter poor prognosis in GBM. Finally, the algorithm has prioritized several drugs for the further study as potential remedies to conquer the aggressive forms of GBM and to extend survival of the patients. © 2021, Pleiades Publishing, L | 10.1134/S1990750821040077 |
pubmed_235_3616 | The accurate computation of ground and excited states of many-fermion quantum systems is one of the most consequential, contemporary challenges in the physical and computational sciences whose solution stands to benefit significantly from the advent of quantum computing devices. Existing methodologies using phase estimation or variational algorithms have potential drawbacks such as deep circuits requiring substantial error correction or nontrivial high-dimensional classical optimization. Here, we introduce a quantum solver of contracted eigenvalue equations, the quantum analog of classical methods for the energies and reduced density matrices of ground and excited states. The solver does not require deep circuits or difficult classical optimization and achieves an exponential speed-up over its classical counterpart. We demonstrate the algorithm though computations on both a quantum simulator and two IBM quantum processing units. | 10.1103/PhysRevLett.126.070504 |
pubmed_137_11272 | OBJECTIVE
The purpose of this article is to establish a body of literature exploring the emergent topic of Indigenous doulas, in relation to Indigenous communities in remote locations, where women are routinely evacuated and no longer supported to give birth. In doing so the article will synthesise and critique key concepts in the literature and identify gaps for prioritisation in future research.
DESIGN
The methodology is influenced by Indigenous, decolonising and feminist theoretical standpoints. A combined methodological approach of an integrative and scoping literature review was undertaken. Only published research, grey literature and grey data written in English and created between the years 2000 and 2018 was included. The search engines used were CINAHL plus, MEDLINE full text, Informat, Cochrane, Google Scholar and Google Search.
SETTING
Resources originating from only Canada and America identified and despite regional similarities, no literature from Australia or Greenland was sourced.
PARTICIPANTS
Of the entirety of identified resources two author's Indigenous identity was readily identifiable; and in the research articles there was a total of 191 research participants identified as Indigenous. Much of the grey literature and grey data included quotations from Indigenous women.
INTERVENTIONS (IF APPROPRIATE)
N/A.
MEASUREMENTS AND FINDINGS
Key concepts about the role and practice of Indigenous doulas were identified: reclaiming and supporting cultural practices; sovereignty over lands and bodies; strengthening families, training, work models and defiance of evacuation policies on the pathway to returning birth. Critique of these concepts suggests that Indigenous doulas have a unique role and practice scope in Western maternity care, which is readily distinguished from standard doula practice. Research gaps worthy of future research prioritisation include: Indigenous women's perspectives as recipients of Indigenous doula care, Indigenous doulas as a pathway into midwifery, escort policy and impacts on Indigenous doula provision; evaluation and alternative research settings.
KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE
The role and practice of Indigenous doulas offers a promising approach to redressing the colonisation of Indigenous childbirth while contributing to improving Indigenous maternal and infant outcomes. Indigenous doula practice shares many best-practice characteristics with Indigenous Healing Programs and as such is also likely to also promote inter-generational healing. Most of the resources located were descriptive, but this emergent topic is worthy of further applied research. | 10.1016/j.midw.2019.04.005 |
pubmed_947_13452 | Outbreaks of short beak dwarf syndrome caused by novel goose parvovirus (NGPV) have been prevalent in China since 2015, resulting in a high mortality rate of ducks. Herein we evaluated differences between two NGPV strains: Muscovy duck-origin (AH190917-RP: MD17) and Cherry Valley duck-origin (JS191021-RP: CVD21) NGPV. Both of them showed certain level of pathogenicity to primary duck embryo fibroblasts, Cherry Valley duck embryos and ducklings. CVD21 showed comparatively stronger pathogenicity than MD17. Only CVD21 caused obvious cytopathic effect (CPE), characterized by cell shedding; further, the virus titer of MD17 and CVD21 was 102.571 ELD50 (i.e. median embryo lethal dose)/0.2 ml and 106.156 ELD50 /0.2 ml, respectively, and the mortality rate of CVD21- and MD17-infected Cherry Valley ducklings was 100% and 80%, respectively. In addition, CVD21 had a greater influence on the growth and development of ducklings. Furthermore, we found that MD17 could infect Muscovy duck embryos and produce lesions similar to Cherry Valley duck embryos, but it could not infect Muscovy duck embryo fibroblasts (MDEFs,) and Muscovy ducklings. MDV21 had no infection to MDEFs, Muscovy duck embryo and Muscovy ducklings. We then sequenced the complete genome of the two isolates to enable genomic characterization. The complete genome of MD17 and CVD21 was 5046 and 5050 nucleotides in length, respectively. Nucleotide alignment, amino acid analysis and phylogenetic tree analysis revealed that MD17 showed higher homology to goose parvovirus (GPV), while CVD21 demonstrated stronger similarity with NGPV. Moreover, the two isolates shared 95.8% homology, with encoded proteins showing multiple amino acid variations. Our findings indicate that Muscovy ducks seem to have played a crucial role in the evolution of GPV to NGPV. We believe that our data should serve as a foundation for further studying the genetic evolution of waterfowl parvoviruses and their pathogenic mechanisms. | 10.1111/tbed.14453 |
pubmed_1055_15366 | The endocannabinoid system (ECS) is abundantly expressed in the brain. This system regulates a plethora of physiological functions and is composed of cannabinoid receptors, their endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of endocannabinoids. In this review, we highlight the new advances in cannabinoid signaling, focusing on a key component of the ECS, the type-1 cannabinoid receptor (CB 1). In recent years, the development of new imaging and molecular tools has demonstrated that this receptor can be distributed in many cell types (e.g., neuronal or glial cells) and intracellular compartments (e.g., mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB 1 receptors according to their specific localization (e.g., glutamatergic or GABAergic neurons). Moreover, this receptor is expressed in the periphery, where it can modulate periphery-brain connections. Finally, the better understanding of the CB 1 receptor structure led researchers to propose interesting and new allosteric modulators. Thus, the advances and the new directions of the CB 1 receptor field will provide new insights and better approaches to profit from its interesting therapeutic profile. | pubmed_1055_15366 |
pubmed_846_1124 | It has been suggested that large amounts of ketonic bile acids may be present in portal venous blood. We have therefore determined the approximate concentration of 3-oxo-, 7-oxo-, and 12-oxo-bile acids (monoketonic bile acids) in human peripheral and portal circulation. These compounds were converted into the corresponding 3alpha-, 7alpha-, and 12alpha-hydroxy bile acids by treatment with sodium borodeuteride, thus increasing the molecular weight of each bile acid formed by one mass unit. The ratio between deuterated and nondeuterated bile acid was determined by combined gas-liquid chromatography-mass spectrometry with use of selected ion monitoring. From the ratio obtained and from the concentration of unlabeled bile acid, determined by isotope dilution-mass spectrometry, the approximate concentration of the different ketonic bile acids could be calculated. This method underestimates 3-oxygenated bile acids by 4-8%, 7-oxygenated bile acids by 2-3%, and 12-oxygenated bile acids by about 25%. The approximate concentration of monoketonic 3,7-oxygenated bile acids was found to be 0.08 +/- 0.02 and 0.37 +/- 0.25 micro mol/l in the peripheral venous serum and the portal venous serum, respectively. The approximate concentration of monoketonic 3,12-oxygenated bile acids was found to be 0.07 +/- 0.02 and 0.32 +/- 0.12 micro mol/l in the peripheral venous serum and the portal venous serum, respectively. The approximate concentration of monoketonic 3,7,12-oxygenated bile acids was found to be 0.03 +/- 0.01 and 0.14 +/- 0.05 micro mol/l in the peripheral venous serum and in the portal venous serum, respectively. The total concentration of the ketonic bile acids constituted only 9 +/- 1% and 8 +/- 3% of the nonoxidized bile acids in the peripheral venous serum and in the portal venous serum, respectively. Thus it seems less likely that the portal inflow of ketonic bile acids is of significant physiological importance under normal conditions.-Björkhem, I., B. Angelin, K. Einarsson, and S. Ewerth. Fasting levels of monoketonic bile acids in human peripheral and portal circulation. | pubmed_846_1124 |
pubmed_385_4442 | Affective disorders often occur in combination with disrupted sleep-wake cycles and abnormal fluctuations in hypothalamic neurotransmitters. Hypocretin (orexin) is a hypothalamic neuropeptide linked to narcolepsy, a sleep-related disorder characterized by profound disturbances in the normal sleeping pattern and variable degrees of depression. Wistar-Kyoto (WKY) rats exhibit depressive characteristics and patterns of sleep disruption similar to that observed in depressed human patients. In this study we sought to determine whether the total number or the size of hypothalamic hypocretin neurons in WKY rats differ from their control, Wistar (WIS) rats. Immunocytochemical and stereological methods were applied to quantify hypocretin-1 containing neurons in the hypothalamus. The study revealed 18% fewer hypocretin-1 positive neurons as well as a 15% decrease in average neuronal soma size of hypocretin-1 producing cells in the hypothalamus of WKY rats compared to WIS rats. These findings support the view that reduced number or size of hypothalamic hypocretinergic neurons may underlie the disrupted sleep pattern associated with depressive characteristics in WKY rats. | 10.1016/j.npep.2004.06.004 |
pubmed_608_17302 | Children and adolescents with developmental language disorder (DLD) are, overall, vulnerable to difficulties in emotional adjustment and in peer relations. However, previous research has shown that different subgroups follow different trajectories in respect to the quality of peer relations. Less is known about the trajectories of emotional development. We consider here the possibility that development in these two domains is interrelated: that is, the trajectories of emotional and peer problems will proceed in parallel. We conducted longitudinal joint trajectories analyses of emotional and peer relations in a sample of young people identified as having DLD at the age of 7 years and seen at intervals up to 16 years. Potential influences on joint trajectory group membership were examined. Findings revealed five distinct joint trajectories. Emotional and peer difficulties do occur together from childhood to adolescence for just over half of the sample, but not all. The variables most clearly associated with group membership were pragmatic language ability, prosociality and parental mental health. This is the first study to examine joint longitudinal trajectories of emotional and peer difficulties in individuals with DLD. We demonstrate that development in individuals with DLD is heterogeneous and identify three key variables associated with personal and social adjustment from childhood to adolescence. Theoretical and clinical implications of these findings are discussed. | 10.1007/s00787-018-1261-6 |
pubmed_876_14748 | The characteristics of steroid nuclear and membrane receptors and their interactions with xenobiotic chemicals in two marine perciform species, Atlantic croaker (Micropogonias undulatus) and spotted seatrout (Cynoscion nebulosus) are briefly reviewed. Several organochlorines that bind to the nuclear progesterone receptor in mammals show negligible binding to the nuclear progestogen receptor in seatrout ovaries. Two distinct nuclear androgen receptors with different tissue distributions have been identified in croaker, but only one of them binds xenobiotic anti-androgens previously identified in mammals. Multiple forms of the nuclear estrogen receptor (ER) have been identified in fishes. The ER in croaker testis has a higher affinity than the croaker liver ER for estrogens and xenoestrogens and may be more susceptible to chemical interference. In addition, differences in the feedback effects of estrogens and xenoestrogens on gonadotropin secretion in croaker are observed, depending on the stage of the reproductive cycle. Finally, the first clear evidence in any vertebrate for xenobiotic chemical interference with the nongenomic actions of steroids by binding to steroid membrane receptors was obtained with the seatrout ovarian progestogen membrane receptor and since has been confirmed with progestogen and estrogen membrane receptors in croaker sperm and testes. These various factors that influence chemical/steroid receptor interactions are likely to significantly modify steroid hormone actions at target tissues and consequently the toxicological effects of chemical exposure. | 10.1016/s0141-1136(00)00114-8 |
pubmed_51_873 | Perceptual narrowing in the visual, auditory, and multisensory domains has its developmental origins during infancy. The current study shows that experimentally induced experience can reverse the effects of perceptual narrowing on infants' visual recognition memory of other-race faces. Caucasian 8- to 10-month-olds who could not discriminate between novel and familiarized Asian faces at the beginning of testing were given brief daily experience with Asian female faces in the experimental condition and Caucasian female faces in the control condition. At the end of 3 weeks, only infants who received daily experience with Asian females showed above-chance recognition of novel Asian female and male faces. Furthermore, infants in the experimental condition showed greater efficiency in learning novel Asian females compared with infants in the control condition. Thus, visual experience with a novel stimulus category can reverse the effects of perceptual narrowing during infancy via improved stimulus recognition and encoding. | 10.1016/j.jecp.2012.04.005 |
pubmed_324_10323 | Environmental constraints disturb plant metabolism and are often associated with photosynthetic impairments and yield reductions. Among them, low positive temperatures are of up most importance in tropical plant species, namely in Coffea spp. in which some acclimation ability has been reported. To further explain cold tolerance, the impacts on photosynthetic functioning and the expression of photosynthetic-related genes were analyzed. The experiments were carried out along a period of slow cold imposition (to allow acclimation), after chilling (4°C) exposure and in the following rewarming period, using 1.5-year-old coffee seedlings of 5 genotypes with different cold sensitivity: Coffea canephora cv. Apoatã, Coffea arabica cv. Catuaí, Coffea dewevrei and 2 hybrids, Icatu (C. arabica×C. canephora) and Piatã (C. dewevrei×C. arabica). All genotypes suffered a significant leaf area loss only after chilling exposure, with Icatu showing the lowest impact, a first indication of a higher cold tolerance, contrasting with Apoatã and C. dewevrei. During cold exposure, net photosynthesis and Chl a fluorescence parameters were strongly affected in all genotypes, but stomatal limitations were not detected. However, the extent of mesophyll limitation, reflecting regulatory mechanisms and/or damage, was genotype dependent. Overnight retention of zeaxanthin was common to Coffea genotypes, but the accumulation of photoprotective pigments was highest in Icatu. That down-regulated photochemical events but efficiently protected the photosynthetic structures, as shown, e.g., by the lowest impacts on A(max) and PSI activity and the strongest reinforcement of PSII activity, the latter possibly reflecting the presence of a photoprotective cycle around PSII in Icatu (and Catuaí). Concomitant to these protection mechanisms, Icatu was the sole genotype to present simultaneous upregulation of caCP22, caPI and caCytf, related to, respectively, PSII, PSI and to the complex Cytb(6)/f, which could promote better repair ability, contributing to the maintenance of efficient thylakoid functioning. We conclude that Icatu showed the best acclimation ability among the studied genotypes, mostly due to a better upregulation of photoprotection and repair mechanisms. We confirmed the presence of important variability in Coffea spp. that could be exploited in breeding programs, which should be assisted by useful markers of cold tolerance, namely the upregulation of antioxidative molecules, the expression of selected genes and PSI sensitivity. | 10.1016/j.jplph.2010.11.013 |
pubmed_453_13061 | A cross-over clinical trial was carried out to compare the efficacy and safety of granisetron alone (40 micrograms/kg) as a "single" group, with that of granisetron, methylprednisolone (250 mg/ body) and droperidol (0.5 ml/body) as a "cocktail" group for control of emesis and vomiting induced by CDDP-based chemotherapy in 68 courses of 34 patients with gynecologic malignancies. At the first course, "single" or "cocktail" drugs were administered at day 1, 2, and 3 of chemotherapy, and at the second course, "cocktail" or "single" drugs in as cross-over fashion. We examined the degree of nausea and frequency of vomiting during the first 7 days of chemotherapy. As for the severity of nausea, the "single" group showed prominent nausea immediately after CDDP and the most severe level at the 3rd or 4th day. The "cocktail" group showed mild symptoms from the next day and it lasted for several days. Vomiting started 12 hours later in the "single" group and the most frequent peak was the 2nd day, whereas the "cocktail" group showed less than one vomiting at the 2nd or 3rd day throughout the treatment. Clinical response (extremely good, good) in the current series of 68 courses of chemotherapy was also evaluated to be 45% and 35% in the "single" group, respectively, against 75% and 20% in the "cocktail" group, respectively. There was no clinical toxicity or side effects in either treatment group. We conclude that the cocktail treatment is very useful for not only acute, but also late emesis in CDDP-based chemotherapy in gynecologic malignancies. | pubmed_453_13061 |
pubmed_686_5 | To investigate the role of claudin-6 in adipogenesis, claudin-6 mRNA was examined in adipose tissues and adipocyte differentiation. Claudin-6 mRNA was found to be differentially expressed in four different adipose tissues, and up-regulated in each fat depot of mice fed a high-fat diet as compared to a normal-fat diet. Levels of claudin-6 transcripts were increased during differentiation of 3T3-L1 cells in vitro. Moreover, small interfering RNA (siRNA)-mediated reduction of claudin-6 mRNA inhibited differentiation of 3T3-L1 cells. These results suggest that claudin-6 is another important regulator in adipogenesis and fat deposition. | 10.1271/bbb.69.2117 |
pubmed_503_890 | The endoscope has been widely used in aesthetic surgery in recent years, but rarely has it been used in cases of facial trauma. From July of 1996 to December of 1996, the endoscope was used successfully to assist in the repair of mandibular subcondylar fractures in eight patients (five men and three women). Their ages ranged from 15 to 60 years with an average age of 31 years. Six of the patients had other associated mandibular fractures including angular, parasymphyseal, and contralateral subcondylar fractures. A 4.0-mm, 30-degree telescope was introduced to visualize the fracture site by means of an intraoral incision over the ascending ramus. A miniplate was used to stabilize the fracture site with the help of a percutaneous trocar. Intermaxillary fixation was applied for 3 to 6 days. Functionally, all patients returned to normal range of motion within 8 weeks. A slight deviation to the trauma site was noted on maximal opening in three patients, but this condition returned to normal 3 months after surgery. There was no facial palsy or lip numbness. The benefits of the endoscopic approach include not only the provision of better visualization and precise anatomic alignment of bony segments but also the avoidance of large facial scars and facial nerve injuries. | 10.1097/00006534-199901000-00011 |
pubmed_367_2912 | BACKGROUND
A projection-based method of intrinsic cardiac gating in small-animal computed tomography imaging is presented.
METHODS AND RESULTS
In this method, which operates without external ECG monitoring, the gating reference signal is derived from the raw data of the computed tomography projections. After filtering, the derived gating reference signal is used to rearrange the projection images retrospectively into data sets representing different time points in the cardiac cycle during expiration. These time-stamped projection images are then used for tomographic reconstruction of different phases of the cardiac cycle. Intrinsic gating was evaluated in mice and rats and compared with extrinsic retrospective gating. An excellent agreement was achieved between ECG-derived gating signal and self-gating signal (coverage probability for a difference between the 2 measurements to be less than 5 ms was 89.2% in mice and 85.9% in rats). Functional parameters (ventricular volumes and ejection fraction) obtained from the intrinsic and the extrinsic data sets were not significantly different. The ease of use and reliability of intrinsic gating were demonstrated via a chemical stress test on 2 mice, in which the system performed flawlessly despite an increased heart rate. Because of intrinsic gating, the image quality was improved to the extent that even the coronary arteries of mice could be visualized in vivo despite a heart rate approaching 430 bpm. Feasibility of intrinsic gating for functional imaging and assessment of cardiac wall motion abnormalities was successfully tested in a mouse model of myocardial infarction.
CONCLUSIONS
Our results demonstrate that self-gating using advanced software postprocessing of projection data promises to be a valuable tool for rodent computed tomography imaging and renders ECG gating with external electrodes superfluous. | 10.1161/CIRCIMAGING.108.784702 |
pubmed_848_17982 | The pedigrees of 4 children with a severe phonological disorder demonstrating three generations of members with speech/language problems are presented. All 4 probands were female with two mothers, two fathers, and five out of six siblings affected. All pedigrees contained family members with dyslexia and learning disabilities as well as speech disorders. Family members varied in the type of speech problems that they demonstrated and the severity of their disorder, thus suggesting variable expressivity and incomplete penetrance. An autosomal dominant mode, a multifactorial-polygenic model, and a sex-specific threshold model for expression are discussed. | 10.1044/jshd.5501.160 |
pubmed_1111_12094 | OBJECTIVE
To discuss the individual operation standard and safety on the deep puncturing at Tianshu (ST 25).
METHODS
The deep insertion through the peritoneum about 1-2 millimeter was taken as individual standard depth at Tianshu (ST 25) for 39 patients. Using CT cross-section scanning and image surveying, the regression analysis was conducted on the impacts of abdominal circumference (AC,cm) to the peritoneum depth.
RESULTS
It was concluded the formula for calculating the satisfactory depth of individual insertion at Tianshu (ST 25), depth = -0.562 + 0.045 x AC.
CONCLUSION
The depth of insertion, 1-2 millimeter through peritoneum at Tianshu (ST 25) is safe and feasible in acupuncture treatment, which can be used significantly as the reference and guidance for the assessment of clinical operation and safety on the deep puncturing of the other acupoints on the abdominal region. | pubmed_1111_12094 |
others_314_96285 | Formalin fixed paraffin embedded (FFPE) tissues are an invaluable source of clinical specimens. Tyrosine phosphorylation (pTyr) plays a fundamental role in cellular processes and is commonly dysregulated in cancer but has not been studied to date in FFPE samples. We describe a method for quantitative analysis of pTyr signaling networks at an unprecedented sensitivity, with hundreds of sites quantified from 1-2 10-m sections of FFPE tissue specimens. Phosphotyrosine profiles of flash frozen and FFPE tissues derived from the same tumors suggest that FFPE tissues preserve pTyr signaling characteristics in PDX tumors and archived clinical specimens. Differential activation of oncogenic proteins was observed in triple negative breast cancer tumors as well as lung cancer tumors, highlighting patient specific oncogenic driving kinases and indicating potential targeted therapies for each patient. These data highlight the capability for direct translational insight from pTyr analysis of small amounts of FFPE tumor tissue specimens | 10.1101/2020.09.10.291922 |
pubmed_832_13079 | OBJECTIVE
To validate the Food Neophobia Scale (FNS) and determine factors associated with the presence of food neophobia (FN) in a sample of Lebanese children.
DESIGN
Cross-sectional study conducted between July and December 2019.
SETTING
All Lebanese governorates.
PARTICIPANTS
Parents of Lebanese children aged 2 to 10 years.
RESULTS
Out of 850 questionnaires, 194 were excluded. The mean age of children was 5·34 ± 2·20 years (50·8 % females); 238 (36·4 %) had low neophobia scores (≤37), whereas 219 (33·5 %) and 197 (30·1 %) had, respectively, moderate (between 38 and 41) and severe neophobia scores (≥42). All items of the FNS were extracted except item 8 and yielded a two-factor solution with Eigenvalues > 1 (variance explained = 51·64 %; Kaiser-Meyer-Olkin (KMO) test = 0·746; Bartlett's sphericity test P < 0·001; αCronbach = 0·739). Children who refused initially to eat vegetables (β = 5·51), fish (β = 4·57), fruits (β = 4·75) or eggs (β = 2·99) and higher parents' instrumental feeding scores (β = 0·3) were significantly associated with higher neophobia scores, whereas higher parents' encouragement scores (β = -0·21) were significantly associated with lower neophobia scores in children.
CONCLUSION
FN is common in children. Neophobic children tend to have lower variety in their diets. One of the ways to lower the levels of neophobia is the use of encouragement by the parents. In contrast, offering a reward to children for them to eat a certain food was associated with more signs of avoidance. More studies should be conducted to evaluate awareness levels concerning FN. | 10.1017/S1368980021000082 |
pubmed_186_22871 | Pyruvate kinase (PK) is the enzyme responsible for catalyzing the last step of glycolysis. Of the four PK isoforms expressed in mammalian cells, PKM2 has generated the most interest due to its impact on changes in cellular metabolism observed in cancer as well as in activated immune cells. As our understanding of dysregulated metabolism in cancer develops, and in light of the growing field of immunometabolism, intense efforts are in place to define the mechanism by which PKM2 regulates the metabolic profile of cancer as well as of immune cells. The enzymatic activity of PKM2 is heavily regulated by endogenous allosteric effectors as well as by intracellular signaling pathways, affecting both the enzymatic activity of PKM2 as a PK and the regulation of the recently described non-canonical nuclear functions of PKM2. We here review the current literature on PKM2 and its regulation, and discuss the potential for this protein as a therapeutic target in inflammatory disorders. | 10.3389/fimmu.2016.00145 |
pubmed_913_659 | Orthoptic therapy often entails the repetitive usage of detailed and complicated training procedures. Amblyopia and antisuppression therapy in particular may require weeks or months of trainning. A multipurpose training device has been constructed from commercially available components and promises to maintain a high level of patient interest and cooperation throughout the training procedure. | pubmed_913_659 |
pubmed_361_22812 | A DNA fragment encoding kanamycin resistance was inserted in vitro into a plasmid-borne prs gene encoding phosphoribosylpyrophosphate synthetase of Escherichia coli. The resulting plasmids were subsequently transferred to the chromosome by homologous recombination and the haploid strains prs-3::KanR and prs-4::KanR were obtained. These strains were fully viable, but required guanosine, uridine, histidine, tryptophan and nicotinamide mononucleotide. There was no phosphoribosylpyrophosphate synthetase activity or phosphoribosylpyrophosphate pool in the mutant strains. These results show that phosphoribosylpyrophosphate synthetase is dispensable for E. coli. | 10.1111/j.1365-2958.1989.tb00134.x |
pubmed_839_12517 | OBJECTIVE
To provide a preliminary comparison of traditional clinical neurosensory examination (CNE) and current perception threshold (CPT).
METHOD AND MATERIALS
This is a retrospective chart audit of patients with trigeminal nerve injuries related to dental treatment who were evaluated with both CNE and CPT assessments (electrical stimulus tests) after presenting with altered sensation involving either the inferior alveolar nerve (IAN) or lingual nerve (LN) distributions. The tests were performed on the anterior two-thirds of the tongue for LN injuries and the lower lip and chin for IAN injuries. Results were defined as hyper-, hypo-, or normal sensory response.
RESULTS
Twelve charts were reviewed; 10 of the 12 nerve injuries occurred secondary to mandibular third molar extraction affecting 7 LN and 5 IAN branches. Following LN injuries, the C, and A-delta fibers assessment demonstrated hyposensitivity in the affected nerve territory in CPT and the CNE tests with the exception of 1 normal nerve response in 5-Hz CPT. Within the LN injury group, good correlation was observed between the CNE and CPT tests with the exception of brush stroke and 250-Hz CPT stimuli. Following IAN injuries, sensory testing results were more varied. A-beta fiber evaluation demonstrated hyposensitivity to VF in all patients and in 4 of 5 for brush test. One patient was hypersensitive for the brush test. The response to 2,000-Hz electrical stimulus demonstrated hyposensitivity in 3 patients, hypersensitivity in 1 (the same patient that was hypersensitive for brush), and normal sensitivity in 1 patient. Good correlations were found only between the CPT 5-Hz and heat and cold tests. Only 1 patient (IAN injury) reported pain that was hypersensitive for heat, cold, pinprick, brush, and 250-Hz and 2,000-Hz stimuli.
CONCLUSION
Following LN injuries, CNE and CPT tests provided similar findings. More disparity was observed between the CNE and CPT methods in the IAN injury evaluation. For LN injury assessments, CNE alone appears to be adequate for assessing nerve injuries. | pubmed_839_12517 |
pubmed_506_16613 | It has been suggested that hOGG1 Ser326Cys polymorphism may be a risk factor for colorectal cancer. Published data on its association with colorectal cancer generated contradictory results; thus, we performed an updated meta-analysis of eligible published studies to estimate the effect of hOGG1 Ser326Cys polymorphism on colorectal cancer susceptibility. We reviewed many abstracts and finally included 18 eligible case-control studies comprising 5235 cases and 8438 controls. We pooled data with a fixed or random-effect model. Subgroup analysis by ethnicity was also performed. The overall data indicated a significant association of hOGG1 Ser326Cys polymorphism on colorectal cancer risk (allele model OR = 1.14, 95 %CI 1.02-1.27; homozygote model OR = 1.32, 95 %CI 0.92-1.92; recessive model OR = 1.12, 95 %CI 1.00-1.26; dominant model OR = 1.15, 95 %CI 1.00-1.32). Furthermore, in the subgroup analysis by ethnicity, increased cancer risk was observed among Caucasians under the allele, heterogeneity, recessive, and dominant models (allele model OR = 1.23, 95 %CI = 1.05-1.44; homozygote model OR = 1.49, 95%CI 1.05-2.12; recessive model OR = 1.40, 95 %CI 1.16-1.69; dominant model OR = 1.21, 95 %CI = 1.12-1.45). In summary, the present meta-analysis suggested that hOGG1 Ser326Cys polymorphism might modify the susceptibility to colorectal cancer among the total population, especially among Caucasians. | 10.1007/s13277-014-2586-5 |
pubmed_666_19652 | Herein, we present a ruthenium-catalyzed new hydrogen evolution ortho-aminoalkylation of phenolic derivatives with cyclic amines as the coupling agents. The developed cross-coupling reaction offers a practical platform for direct access to a variety of functionalized phenols with the features of good substrate and functional group compatibility, readily available catalyst system and feedstocks, no need for additional sacrificial oxidants, and high atom efficiency. | 10.1021/acs.orglett.0c01580 |
pubmed_1053_20136 | The distribution of human carbonic anhydrase (HCA) isoenzymes I, II and VI in the human male reproductive tract was studied using specific antisera against affinity purified isoenzymes in conjunction with the peroxidase-antiperoxidase complex method. HCA VI-specific staining could not be demonstrated in any of the tissues studied, and HCA I was observed only in red blood cells. Immunostaining denoted HCA II in the epithelia of the seminal vesicle, ampulla of the ductus deferens and distal ductus deferens. Some cells in the epithelium of the corpus and cauda epididymidis also stained for HCA II. The staining for HCA II in the epithelium of the reproductive tract declined from the strongly positive seminal vesicle to the proximal part of the ductus deferens, which stained negatively. There were also HCA II-positive particles derived from the apical protrusions of the epithelium in the lumina of the seminal vesicle, ampulla of the ductus deferens and ductus deferens. The physiological role of HCA II is linked to the secretion of bicarbonate into the seminal plasma and thereby to the regulation of sperm motility and pH in the seminal plasma. | 10.1007/BF00266444 |
pubmed_1046_16298 | NGS-based multiple gene panel resequencing in combination with a high resolution CGH-array was used to identify genetic risk factors for hereditary breast and/or ovarian cancer in 237 high risk patients who were previously tested negative for pathogenic BRCA1/2 variants. All patients were screened for pathogenic variants in 94 different cancer predisposing genes. We identified 32 pathogenic variants in 14 different genes (ATM, BLM, BRCA1, CDH1, CHEK2, FANCG, FANCM, FH, HRAS, PALB2, PMS2, PTEN, RAD51C and NBN) in 30 patients (12.7%). Two pathogenic BRCA1 variants that were previously undetected due to less comprehensive and sensitive methods were found. Five pathogenic variants are novel, three of which occur in genes yet unrelated to hereditary breast and/or ovarian cancer (FANCG, FH and HRAS). In our cohort we discovered a remarkably high frequency of truncating variants in FANCM (2.1%), which has recently been suggested as a susceptibility gene for hereditary breast cancer. Two patients of our cohort carried two different pathogenic variants each and 10 other patients in whom a pathogenic variant was confirmed also harbored a variant of unknown significance in a breast and ovarian cancer susceptibility gene. We were able to identify pathogenic variants predisposing for tumor formation in 12.3% of BRCA1/2 negative breast and/or ovarian cancer patients. | 10.1002/ijc.31992 |
pubmed_0_18134 | Problem-based learning (PBL) is well established in health education. It is regarded as a constructionist approach to education that emphasizes students' active engagement with the learning process, self-direction, and learning in a meaningful context. This article details the experiences of nurse lecturers in one university in the Republic of Ireland during the introduction of a PBL module to students enrolled in a higher diploma in children's nursing program. All lecturers attended a three-day training program on the principles and processes of PBL. The lecturers, all experienced nurse educators, had no prior experience in implementing PBL. Data collection involved the use of reflective journals and group meetings. Thematic content analysis revealed key themes that chart the journey from transcending doubts to exceeding expectations of the PBL process. | pubmed_0_18134 |
pubmed_485_1063 | Previous studies of N,N'-dicyclohexylcarbodiimide (DCCD)-modified bacteriorhodopsin (Renthal, R. et al. (1985) Biochemistry 24, 4275-4279) used reaction conditions (detergent micelles) that are not optimal for subsequent physical studies. The present work describes new conditions for reaction of bacteriorhodopsin with DCCD in intact purple membrane sheets in the presence of 4.5% (v/v) diethylether and light. Like the detergent reaction system, the reaction is light induced, incorporates approximately 1 mol [14C]DCCD per mol bacteriorhodospin, and results in a bleached chromophore. Peptide mapping indicates that the likely site of modification in intact membranes is identical to the site in the detergent reaction system: Asp 115. The retinal chromophore of DCCD-modified purple membrane has an absorbance maximum at 390 nm and very little induced circular dichroism. The retinal is easily extracted in hexane, yielding a 3:1 ratio of all-trans to 13-cis retinal. Borohydride reduces the retinal onto the protein within the 1-71 region of the amino acid sequence. These results suggest that Asp-115 is near the retinal binding cavity of bacteriorhodopsin. When DCCD reacts with Asp 115, retinal is displaced from its binding site. | 10.1016/0005-2728(88)90207-1 |
pubmed_346_5467 | The phylogenetic diversity of the eukaryotic kingdom was assessed by comparing the structural and evolutionary diversity of 18-20S ribosomal RNA genes. The coding regions for cytoplasmic small subunit ribosomal RNA genes vary in length from 1753 to 2305 nucleotides, and they appear to be evolutionary mosaics in which highly and partially conserved sequences are interspersed among regions that display very high rates of genetic drift. Structural similarities between these gene sequences were used to establish a phylogenetic framework for the eukaryotes. The extent of sequence variation within the eukaryotes exceeds that displayed within the eubacterial or archaebacterial lines of descent. The kinetoplastids and euglenoids represent the earliest branchings among the eukaryotes. These branchings preceded the divergence of lineages leading to the slime molds and apicomplexans and far antedate a radiative period that gave rise to the plants, animals, fungi, and other protists. | 10.1111/j.1749-6632.1987.tb40603.x |
pubmed_481_18839 | The beta1D protein is a recently characterized isoform of the integrin beta1 subunit that is present in cardiac and skeletal muscles. In this study, we have examined the expression of beta1D in different types of skeletal muscle and in cardiac muscle and studied its distribution during mouse development, using new monoclonal antibodies specific for beta1D. Immunoprecipitation studies revealed that, while beta1A is strongly expressed in proliferating C2C12 myoblasts, beta1D is only expressed after their differentiation to myotubes. In these myotubes, beta1D is associated with different alpha subunits, namely alpha3A, alpha5, alpha7A, or alpha7B. Initially, during embryogenesis, the alpha1A subunit is the only beta1 variant expressed in skeletal and cardiac muscle. The beta1D subunit is first detected in skeletal muscle at E17.5, whereas in cardiac muscle its expression begins around the time of birth. Later the expression of beta1A in skeletal and cardiac muscle becomes restricted to capillary cells, whereas beta1D eventually becomes the only variant expressed in adult cardiac and skeletal muscle cells. The switch from the beta1A to the beta1D subunit in cardiac muscle cells coincides with the expression of alpha7. In adults there is a distinct concentration of beta1D at the myotendinous junctions of muscle fibers and at costameres in both cardiac and skeletal muscle. In addition, beta1D is present at intercalated discs in cardiac muscle and at neuromuscular junctions in skeletal muscle cells. The amount of beta1D in different types of skeletal muscle (fast, slow, and mixed-type) was similar, but cardiac muscle expressed almost five times as much of this protein. We suggest that beta1D plays a role in the maintenance of the cytoarchitecture of mature muscle and in the functional integrity of the muscle cells. | 10.1002/(SICI)1097-0177(199712)210:4<472::AID-AJA10>3.0.CO;2-9 |
pubmed_899_2048 | The 2015 Nobel Prize in Physiology or Medicine recognised the advances made in treating neglected tropical diseases, using drugs whose origins lie in natural products. | 10.1039/c5np90043c |
pubmed_926_21868 | BACKGROUND
Elevated hyaluronan-mediated motility receptor (RHAMM) has been reported to contribute to disease progression, aggressive phenotype and poor prognosis in multiple cancer types, however, RHAMM's role in ovarian cancer (OC) has not been elucidated. Therefore, we sought to evaluate the role for RHAMM in epithelial OC.
RESULTS
Despite little to no expression in normal ovarian surface epithelium, western immunoblotting, immunohistochemical staining and enzyme linked immunosorbent assay showed elevated RHAMM levels in clinical tissue sections, omental metastasis and urine specimens of serous OC patients, as well as in cell lysates. We also found that RHAMM levels increase with increasing grade and stage in serous OC tissues and that RHAMM localizes to the apical cell surface and inclusion cysts. Apical localization of RHAMM suggested protein secretion which was validated by detection of significantly elevated urinary RHAMM levels (p < 0.0001) in OC patients (116.66 pg/mL) compared with normal controls (8.16 pg/mL). Likewise, urinary RHAMM levels decreased following cytoreductive surgery in OC patients suggesting the source of urinary RHAMM from tumor tissue. Lastly, we validated RHAMM levels in OC cell lysate and found at least 12× greater levels compared to normal ovarian surface epithelial cells.
CONCLUSION
This pilot study shows, for the first time, that RHAMM may contribute to OC disease and could potentially be used as a prognostic marker. | 10.1186/s13048-017-0360-1 |
pubmed_132_18679 | The title compound, C(16)H(12)O(2), contains two prop-2-yn-1-yl-oxy groups attached to a naphthalene ring system at the 1- and 6-positions. The crystal packing includes an inter-molecular C-H⋯π inter-action between a terminal ethynyl H atom and an ethynyl group on a glide-related mol-ecule and another inter-action between an O-atom-linked methyl-ene H and an ethynyl group of a different glide-related mol-ecule. | 10.1107/S1600536811027310 |
pubmed_481_6034 | X-ray crystal structures of binary complexes of dUMP or dCMP with the Lactobacillus caseiTS mutant N229D, a dCMP methylase, revealed that there is a steric clash between the 4-NH2 of dCMP and His 199, a residue which normally H-bonds to the 4-O of dUMP but is not essential for activity. As a result, the cytosine moiety of dCMP is displaced from the active site and the catalytic thiol is moved from the C6 of the substrate about 0.5 A further than in the wild-type TS-dUMP complex. We reasoned that combining the N229D mutation with mutations at residue 199 which did not impinge on the 4-NH2 of dCMP should correct the displacements and further favor methylation of dCMP. We therefore prepared several TS N229D mutants and characterized their steady state kinetic parameters. TS H199A/N229D showed a 10(11) change in specificity for methylation of dCMP versus dUMP. The structures of TS H199A/N229D in complex with dCMP and dUMP confirmed that the position and orientation of bound dCMP closely approaches that of dUMP in wild-type TS, whereas dUMP was displaced from the optimal catalytic binding site. | 10.1021/bi971873h |
pubmed_92_10867 | BACKGROUND
In Ethiopia the average fertility rate in rural areas is about 6 children per woman, while it is 2.4 children per woman in urban areas. It is with this concept in mind that the investigators of this study wanted to correlate the promotion of after-child-birth-use of family planning and desire to limit childbearing in Ethiopia. Postpartum amenorrhea signifies the interval between childbirth and the return of menstruation.
OBJECTIVES
The specific objective is to examine the desire to limit family size, along with cases of sterilized, fecund, postpartum amenorrhoea, declared in-fecund and menopausal women within the study area.
METHODS
The study is based on the analysis of secondary data obtained from the 2011 Ethiopian Demographic and Health Survey (EDHS). This study is concentrated on couples because we need to know more about married people's desire to limit their family size. The bivariate, ANOVA, and multivariate analyses were used to analyse the association.
RESULTS
The total number of respondents was 6,745 (78.3% rural and 21.7% urban), with 93.6% of them being currently married and 6.4% of them living with a partner. The mean duration of amenorrhea among women who gave birth in the five years preceding the survey is 16 months. Women with equal numbers of sons and daughters were found to be 75.4% (OR=0.25) less likely to desire more children, compared to women with more sons than daughters.
CONCLUSION
Achievable resolutions include increasing females' ages at marriage, avoiding unwanted teenage pregnancies, completely eradicating home delivery, and inspiring young people to use modern methods of family planning to achieve Millennium Development Goals 4 & 5. | 10.1186/1742-4755-11-53 |
pubmed_374_2117 | Meningitis and meningoencephalitis are neurological inflammatory diseases, and although routine diagnostics include testing of a wide range of pathogens, still in many cases, no causative agent is detected. Human parvovirus B19 (B19V), human bocaviruses 1-4 (HBoV1-4), and human parvovirus 4 (hPARV4) are members of the Parvoviridae family and are associated with a wide range of clinical manifestations including neurological disorders. The main aim of this study was to determine whether human parvoviruses infection markers are present among patients with meningitis/meningoencephalitis in Latvia as well as to clarify the role of these viruses on the clinical course of the mentioned diseases. Our study revealed HBoV1-4 and B19V genomic sequences in 52.38% and 16.67% of patients, respectively. Furthermore, symptoms such as the presence of a headache and its severity, fatigue, disorientation, and difficulties to concentrate were significantly frequently present in patients with active parvovirus infection in comparison with parvoviruses negative patients, therefore we suggest that HBoV1-4 and B19V infection should be included in the diagnostics to reduce the number of meningitis/meningoencephalitis with unknown/unexplained etiology. | 10.3390/brainsci10060339 |
pubmed_1095_5409 | This paper describes the implementation of a human computer interface based on eye tracking. Current commercially available systems exist, but have limited use due mainly to their large cost. The system described in this paper was designed to be a low cost and unobtrusive. The technique was video-oculography assisted by corneal reflections. An off-the shelf CCD webcam was used to capture images. The images were analyzed in software to extract key features of the eye. The users gaze point was then calculated based on the relative position of these features. The system is capable of calculating eye-gaze in real-time to provide a responsive interaction. A throughput of eight gaze points per second was achieved. The accuracy of the fixations based on the calculated eye-gazes were within 1 cm of the on-screen gaze location. By developing a low-cost system, this technology is made accessible to a wider range of applications. | 10.1109/IEMBS.2006.260774 |
pubmed_468_14499 | After describing the role of sensations in the primary levels of mental organization, this part of the article suggests viewing somatic idioms as the language's way to connect with these levels. We seek to exemplify the qualities, meanings and functioning of idioms, since they serve as a basic key in investigating the different layers of the mind. Examples taken from clinical cases, as well as from universal literary products, such as fairy tales, provide useful contributions to this argument. | 10.1057/ajp.2010.33 |
pubmed_702_4172 | OBJECTIVE
To determine whether a cholera toxin-derived, novel immunomodulating fusion protein, CTA1R7K-COL-DD, carrying the class II major histocompatibility complex H-2q-restricted type II collagen peptide aa 259-274, can induce therapeutic tolerance and prevent collagen-induced arthritis (CIA) when administered intranasally in DBA/1 mice, and to assess whether ADP-ribosylation at the mucosal membranes exerts a regulatory function such that the outcome of tolerance or immune enhancement can be controlled.
METHODS
DBA/1 mice with CIA were treated intranasally with CTA1R7K-COL-DD. The therapeutic effect was monitored for 46 days after the onset of disease. Clinical scoring of disease, histologic examination of inflammation, and bone erosion were assessed, and cytokine levels were determined in the serum or supernatants from splenocytes stimulated with recall antigen.
RESULTS
The protective effect of CTA1R7K-COL-DD resulted in roughly 60% of the mice having no clinical signs or histologic evidence of disease after treatment, and those with CIA had significantly milder disease with less bone erosion. The protective status was associated with lower serum titers of IgG1, IgG2a, IgG2b, and IgG3 anticollagen and a substantial decrease in the production of interleukin-6 (IL-6), IL-17, and interferon-gamma, while levels of IL-10 were markedly up-regulated both in the serum and at the T cell level.
CONCLUSION
The enzymatically inactive mutant fusion protein CTA1R7K-COL-DD provided substantial therapeutic protection against CIA following intranasal administration. The mechanism behind the effect appears to be mediated by peptide-specific regulatory T cells induced by mucosal exposure to the peptide containing CTA1R7K-COL-DD vector. In addition, ADP-ribosylation at the mucosal membranes acts as a key regulator controlling mucosal tolerance or immunity. | 10.1002/art.24566 |
pubmed_169_7916 | In chronic experiments on cats, automatic regulation of polarizing current, monitored with the EEG changes, aided to study elements of the cerebral selfregulating system. The method proved effective for influencing the functional state of the structures to be regulated which revealed itself in long-lasting shifts of theta-rhythm, in changes of excitability and readjustment of EPs. Three types of connections between the temporal cortex and a number of cerebral modulating structures: rigid (positive and negative) and flexible those, were revealed. The active inhibition was accelerated with the bioregulated micropolarization of temporal cortex and hypothalamus on extinction of alerting response. | pubmed_169_7916 |
pubmed_1010_15787 | Spontaneous Raman micro-spectroscopy has been demonstrated great potential in delineating tumor margins; however, it is limited by slow acquisition speed. We describe a superpixel acquisition approach that can expedite acquisition between ~×100 and ×10 000, as compared to point-by-point scanning by trading off spatial resolution. We present the first demonstration of superpixel acquisition on rapid discrimination of basal cell carcinoma tumor from eight patients undergoing Mohs micrographic surgery. Results have been demonstrated high discriminant power for tumor vs normal skin based on the biochemical differences between nucleus, collagen, keratin and ceramide. We further perform raster-scanned superpixel Raman imaging on positive and negative margin samples. Our results indicate superpixel acquisition can facilitate the use of Raman microspectroscopy as a rapid and specific tool for tumor margin assessment. | 10.1002/jbio.201960109 |
pubmed_453_18915 | Measurement of the urinary albumin excretion rate (UAER) is essential for the early diagnosis and monitoring of diabetic nephropathy; immunonephelometry is a procedure used worldwide for routine screening of diabetic patients. Since we have met with occasional inconsistent values of UAER in serial urine collections, we searched for possible sources of analytic error. To assess the best working conditions of the instrument in use, the stability of urine samples during storage and the need for previous urine centrifugation, we assayed repeatedly the six automatically diluted points of the standard curve (55.6 to 1.7 mg/l), four control samples of human albumin in saline (100 to 1 mg/l) and 24-h urine collections from outpatient diabetic subjects. The last were also assayed with and without previous centrifugation, and both immediately after collection as well as after storage at -20 degrees C for 7, 42, 79, 97, 128 and 161 days. We concluded that: (1) pre-analytic centrifugation of urine samples in unnecessary; (2) the intra-assay coefficient of variation (CV) of the standard curve changed from 2.4% to 9.3% when moving from the highest to the lowest concentration; the inter-assay CV changed from 4.1% to 14.4%, respectively; (3) the intra-assay CV of the control samples (manually prepared) changed from 5.7% to 10.2% and the inter-assay CV from 7.7% to 22.9%; there was a constant and significant (P < 0.01) underestimation (from -9% to -30%) of the obtained values compared with the expected concentrations; (4) a progressive decrease in recovered albumin by multiple freezing and thawing of urine samples did occur, which became significant after 161 days of storage. In the BNA workbook (menu 7.1, assay protocols), a 7-day validity of the reference curve is reported. Moreover, to economize, pre-dilution cuvettes were often recycled in our hospital central laboratory. We observed that: the intra-assay CV for urine samples was 79.4% with recycled cuvettes and stored standard curve, 11.3% with new cuvettes and stored standard curve, 4.9% with both new cuvettes and newly performed standard curve; the inter-assay CV was 32.6%, 10.5% and 6.4%, respectively. These data emphasize, from the laboratory viewpoint, the need for both accurate calibration of BNA and use of native urines; in addition, they stress the importance of careful supervision of laboratory routine and interpreting analytic results in the clinical setting. | 10.1007/s005920050060 |
pubmed_719_23066 | PURPOSE
To evaluate the optimal dosing of preoperative intravitreal bevacizumab (IVB) in patients undergoing pars plana vitrectomy (PPV) for manifestations of proliferative diabetic retinopathy (PDR).
DESIGN
Randomized clinical trial.
PARTICIPANTS
Two hundred six patients with severe manifestations of PDR underwent PPV at a single university-based hospital.
METHODS
Patients were randomized into 1 of 3 treatment groups: group A received 0.625 mg IVB (0.025 ml) 1 to 10 days before PPV, group B received 1.25 mg IVB (0.05 ml) 1 to 10 days before PPV, and group C received 2.5 mg IVB (0.1 ml) 1 to 10 days before PPV.
MAIN OUTCOME MEASURES
The primary outcome was best-corrected visual acuity (BCVA) at 6 months. Secondary outcome measures were rates of perioperative tractional retinal detachment (TRD) development, intraoperative and postoperative complications, and incidence of unplanned PPV at 6 months.
RESULTS
One hundred sixty-seven patients underwent PPV and completed 6 months of follow-up. There were no significant differences between treatment groups regarding baseline characteristics, final BCVA, intraoperative complications, postoperative complications, or unplanned PPV rates. There were no patients in group A (0.0%), 3 patients in group B (7.0%), and 5 patients in group C (8.5%) who demonstrated perioperative TRD after IVB administration, but before PPV (P = 0.0283). This difference was significant between groups A and B (P = 0.0494) and between groups A and C (P = 0.0080).
CONCLUSIONS
This randomized clinical trial demonstrated that patients receiving the 0.625-mg dose of IVB before PPV for the treatment of PDR-related manifestations showed similar visual acuity, but a lower incidence of perioperative TRD development compared with patients receiving the 1.25-mg and 2.5-mg doses. Clinicians should consider adopting the lowest effective dose, 0.625 mg, into clinical practice. The current study is limited by the lack of a control group receiving no IVB before PPV. | 10.1016/j.oret.2018.04.014 |
pubmed_1051_6621 | Liver cancer has relatively few early symptoms and is usually diagnosed in the advanced stage. Sorafenib is the only first-line anticancer drug approved by the Food and Drug Administration (FDA) for advanced HCC; however, its use is limited due to resistance. Therefore, the development of new drugs is essential to achieving customized treatment. Many studies have suggested that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) is associated with metastasis and cancer formation and progression in various cancers. In the present study, YAP was overexpressed in various patient-derived hepatocarcinoma (HCC) tissues. In addition, this study examined whether evodiamine (which has anticancer effects) can inhibit YAP and, if so, modulate HCC. Evodiamine significantly reduced both the YAP level and cell growth of HCC in a dose-dependent manner. Biochemical analysis indicated mitochondria dysfunction-mediated apoptosis to be the cause of the reduction in HCC cell growth by evodiamine. YAP was overexpressed in metastatic HCC tissues as well when compared to primary HCC tissues. Migration and invasion analysis showed that evodiamine has anti-metastatic ability on Hep3B and Huh-7 cells and reduces the level of vimentin, an EMT marker. In conclusion, YAP is a critical target in HCC therapy, and evodiamine can be an effective HCC anticancer drug by reducing the YAP level. | 10.3390/ijms23031855 |
pubmed_370_6891 | Isolation, purification and characterization of inhibin from the testes of the Indian buffalo Bubalus bubalis is described. The biological activity of the final product, which produced a single band on disc gel electrophoresis, was affected by heat treatment, 6 m urea, pH alteration and pepsin digestion. Chemically, it appeared to be a glycoprotein. The protein and carbohydrate components together accounted for a total of 63% of the dry weight, whereas 37% of the constituents were unknown. | pubmed_370_6891 |
pubmed_509_9880 | PURPOSE OF REVIEW
This review summarizes herd immunity, focusing on conceptual developments with application to vaccination programs.
RECENT FINDINGS
The conventional idea of herd immunity is based on the relationship between the transmission dynamics of infectious agents and population immunity. However, there have been some recent conceptual developments in vaccine 'herd immunity' or 'herd protection' that address the complexities of imperfect immunity, heterogeneous populations, nonrandom vaccine uptake and 'freeloaders'. Some vaccines may provide better protection than others; for instance, meningococcal conjugate vaccines are superior to polysaccharide vaccines, as is true of pneumococcal and Haemophilus influenzae type b vaccines. Achieving a very high uptake rate should be the target for certain vaccines, for example, measles vaccine, in order to prevent the disease effectively. Emerging issues, for example, waning of immunity after pertussis vaccination, are fresh challenges.
SUMMARY
Herd immunity is a complex issue inherent to a vaccine and the population receiving the vaccine. We have more to learn and apply. | 10.1097/QCO.0b013e328352f727 |
pubmed_436_3951 | Steroids and free fatty acids (FFA) are noncompetitive antagonists of the nicotinic acetylcholine receptor (AChR). Their site of action is purportedly located at the lipid-AChR interface, but their exact mechanism of action is still unknown. Here we studied the effect of structurally different FFA and steroids on the conformational equilibrium of the AChR in Torpedo californica receptor-rich membranes. We took advantage of the higher affinity of the fluorescent AChR open channel blocker, crystal violet, for the desensitized state than for the resting state. Increasing concentrations of steroids and FFA decreased the K(D) of crystal violet in the absence of agonist; however, only cis-unsaturated FFA caused an increase in K(D) in the presence of agonist. This latter effect was also observed with treatments that caused the opposite effects on membrane polarity, such as phospholipase A(2) treatment or temperature increase (decreasing or increasing membrane polarity, respectively). Quenching by spin-labeled fatty acids of pyrene-labeled AChR reconstituted into model membranes, with the label located at the gammaM4 transmembrane segment, disclosed the occurrence of conformational changes induced by steroids and cis-unsaturated FFA. The present work is a step forward in understanding the mechanism of action of this type of molecules, suggesting that the direct contact between exogenous lipids and the AChR transmembrane segments removes the AChR from its resting state and that membrane polarity modulates the AChR activation equilibrium by an independent mechanism. | 10.1074/jbc.M800345200 |
pubmed_1105_16182 | Three experiments were conducted with a total of 1579 ewes to examine reproductive performance in response to synchronization of oestrus during the breeding season, using controlled internal drug releasing (CIDR-G) inserts in regimens designed to provide high concentrations of circulating progesterone. In experiment 1, treatment with two CIDR-G inserts for 12 days produced conception rate (79%) and prolificacy (1.9) to first service equivalent to breeding at natural oestrus (56% and 2.0, respectively). Pregnancy rates to two service periods were 90 and 79%, respectively. In experiments 2 and 3, progesterone was delivered by a single CIDR-G insert for 5 days in combination with prostaglandin F2alpha (PGF2alpha; 5 mg i.m., twice, 3 h apart) the day before (experiment 2), or at insert removal (experiment 3). The combined treatments improved rates of synchronization of oestrus (p<0.01) by 23 and 20% points, respectively, and pregnancy rates to the first service period by 19 (p<0.05) and 13 (p<0.01) percentage points, respectively, compared to treatment with PGF2alpha alone. It is concluded that the combination of treatment for 5 days with a CIDR-G insert and two injections of 5 mg PGF2alpha, the day before, or the day of insert removal, were effective treatments to obtain high fertility at synchronized oestrus in ewes during the breeding season. | 10.1111/j.1439-0531.2006.00656.x |
pubmed_1075_24264 | OBJECTIVE
To describe an unusual focal scleroderma-like skin changes in patient with dermatomyositis.
METHODS
Review of clinical records, laboratory investigations, and muscle and skin biopsies.
RESULTS
The patient developed unusual skin lesions characterized by symmetrical atrophy and hardening of focal skin and muscle over the lateral upper arms and posterior shoulders, and the left temporal and pectoral areas. Extensive blood work-up for scleroderma and other connective-tissue diseases was negative. A skin biopsy showed distinct pathologic features including increased interstitial mucin, hyperpigmentation, and perivascular lymphocytic inflammation without severe fibrosis. The scleroderma-like skin changes and muscle weakness improved with immunotherapy.
CONCLUSIONS
Dermatomyositis can manifest with focal scleroderma-like skin changes clinically and reticular erythematous mucinosis-like changes pathologically, and these distinct skin changes represent a new variant of skin lesions of dermatomyositis. | 10.1097/CND.0b013e3182461966 |
pubmed_271_24716 | Pistia stratiotes (Family: Araceae) is commonly used in Ayurvedic medicine. This review article is a compilation of all the updated information on its phytochemical and pharmacological activities, which were performed by different methods. Studies indicate that P. stratiotes possesses diuretic, antidiabetic, antidermatophytic, antifungal, and antimicrobial properties. These results are very encouraging and indicate that this plant should be studied more extensively to confirm the reproducibility of these results and also to reveal other potential therapeutic effects, along with some "leads" with possible isolation of active biomoieties and their mechanism of action. | 10.4103/0973-7847.70909 |
pubmed_875_791 | BACKGROUND
The Child Behavior Checklist (CBCL) has been widely utilized to estimate emotional and behavioral problems in children in the USA and Europe. Although the Indonesian version of the CBCL/6-18 was proven to have good validity and internal consistency in children with typical development (TD) in Indonesia, it has not been utilized for children with autism spectrum disorder (ASD). The purpose of this study was therefore to investigate the usefulness of CBCL/6-18 for detecting emotional and behavioral problems in Indonesian ASD children.
METHODS
One hundred and eight mothers of children with ASD and with TD were enrolled in this study. The diagnosis of ASD in Indonesia was made by expert child neurologists based on DSM-IV-TR. Mothers of children aged 6-18 years completed the Indonesian version of the CBCL.
RESULTS
The scores of total problems, internalizing, and externalizing were significantly higher in the ASD group than the TD group. Children with ASD scored significantly higher in seven of the eight CBCL subscales (except somatic complaints) compared with TD children.
CONCLUSIONS
The CBCL/6-18 Indonesian version could be considered as a useful tool for detecting emotional and behavioral problems in children with ASD in Indonesia in Muslim populations. | 10.1111/ped.13085 |
pubmed_247_6321 | Acute-phase protein (APR) synthesis was studied under conditions in which the acute-phase response to a sublethal scald was interrupted at the onset of APR synthesis by the infliction of a second scald that overwhelmed the defense mechanisms. The rate of APR synthesis increased shortly after the second scald and then declined rapidly to the control level. At this time point, APR messenger RNA (mRNA) concentrations exceeded severalfold the control values, whereas the APR gene transcription rates fell to the control level. These mRNAs were active in APR synthesis in a cell-free system, as well as in hepatocytes grown in a standard culture medium. These results and those demonstrating a drop in the free amino acid pool level in the liver after the second scald suggested that the lethal outcome was preceded by an impaired supply of liver cells with amino acids and resulting inhibition of APR mRNA translation. Changes in amino acid transport were considered to occur secondarily to those causing hypovolemia and circulatory shock. | pubmed_247_6321 |
pubmed_137_11282 | Chitosan (Ch) is used in different biomedical applications to promote tissue repair. However, tissue injury caused by biomaterial implantation lead to the release of danger signals that engage different inflammatory pathways on the host. Different implanted materials activate the inflammasome leading to the modulation of the immune response. Here we have studied how macroscopic biomaterials, Ch scaffolds with different chemical composition: 4% or 15% degree of acetylation (DA) modulate the activation of the NLRP3 inflammasome in vitro. For that, we assessed the NLRP3 inflammasome in bone marrow derived mouse macrophages (BMDM) and human macrophages cultured within 3D Ch scaffolds. We found that both Ch scaffolds did not trigger the NLRP3 inflammasome activation in macrophages. Furthermore, BMDMs and human macrophages cultured in both Ch scaffolds presented a reduction in the number of apoptosis-associated speck-like protein containing a caspase activating recruitment domain (ASC) specks and in IL-1β release upon classical NLRP3 inflammasome stimulation. We also found a decrease in proIL-1β in BMDMs after priming with LPS when cultured in Ch scaffolds with DA 4% DA after priming with LPS when compared to Ch scaffolds with 15% DA or to macrophages cultured in cell-culture plates. Our results shows that 3D Ch scaffolds with different DA impair NLRP3 inflammasome priming and activation. STATEMENT OF SIGNIFICANCE: In this research work we have assessed the role of the NLRP3 inflammasome in the macrophage response to 3D chitosan scaffolds with different degrees of acetylation (DA). To our knowledge this is the first work that demonstrates the modulatory capacity of 3D porous chitosan scaffolds in the NLRP3 inflammasome activation, because our results show that Ch scaffolds impair NLRP3 inflammasome assembly in macrophages. Interestingly, our results are in contrast with studies reported in the literature that indicate that chitosan is a powerful activator of the NLRP3 inflammasome in nanoscale chitosan products. Our studies that were performed in large scale chitosan scaffolds, stress out that the process of phagocytosis is pivotal in inflammasome assembly and activation, are rather important since they clearly illustrate the different role of the inflammasome in the biological response to large scale and nanoscale biomaterials. | 10.1016/j.actbio.2019.04.035 |
pubmed_474_1881 | Of 45 diabetic pregnancies, 80% were Class C, D, or R. The perinatal mortality rate was 4.4% (corrected 2.2%); however, neonatal morbidity was high. Of the infants, 28% developed respiratory distress syndrome (RDS); 18%, asphyxia; and 42%, hypoglycemia. Thus, the woman with overt diabetes needs delivery in an institution where neonatal expertise and modern neonatal facilities exist. Of the mother 28% had a family history that was negative for diabetes mellitus. Four neonates developed RDS despite mature lecithin/sphingomyelin ratios. | 10.1016/0002-9378(79)90678-1 |
pubmed_651_11310 | The last hours of intrafollicular maturation are important to preserve the potential of oocytes for fertilization and development. To collect mature oocytes it is consequently essential to predict accurately the time of ovulation. Therefore we have modified a regular and specific plasma LH radioimmunoassay to a convenient assay providing reliable results within four to five hours. Using this technique we have been able to detect the LH peak with a delay small enough to predict the moment of ovulation; then we have been able to observe and photograph ovulation. The antigen-antibody reaction takes place during a two hour incubation at 37 degrees C. The immune complex is precipitated by addition of a rabbit anti-gamma-globulin and incubation at 22 degrees C for 30 minutes. The variation between fast and regular assays is lower than 15%. From a study of 25 cycles in 12 animals we suggest intervals of approximately 27 hours between the beginning of the LH peak and ovulation and of about 17 hours between the end of the peak and ovulation. Intervals between the beginning of heat and ovulation appear irregular and cannot be used with certainty as a reference point to predict ovulation. Five ovulations were observed closely and in the five cases, the formation of an apex was noted Our results clearly show that with the technique mentioned above we can predict rapidly and precisely bovine ovulation. | pubmed_651_11310 |
pubmed_872_20984 | The methanolic extracts and the fractions (petrol, dichloromethane, ethyl acetate, butanol) obtained from the leaves, seeds, stem and root barks of Sarcocephalus coadunatus exhibited a high level of broad spectrum antibacterial activity. The activity was more pronounced in the dichloromethane, ethyl acetate and butanol fractions of the leaves; ethyl acetate and butanol fractions of the seeds; dichloromethane fractions of the stem bark and the ethyl acetate fractions of the root bark. None of the fractions showed any antifungal activity. | 10.1016/s0367-326x(03)00157-6 |
pubmed_693_1724 | Seventeen 4-[3-(N-cyclohexylamino)propyl]-1-substituted-3-thiosemicarbazones were synthesized and evaluated for their ability to inhibit rat brain monoamine oxidase (MAO) and pyruvate oxidase in vitro. Anticonvulsant activity exhibited by these thiosemicarbazones (100 mg/kg,i.p.) against pentylenetetrazol-induced seizures ranged from 10-50%. | pubmed_693_1724 |
pubmed_683_15322 | Prothymosin alpha (ProT alpha) is a highly acidic nuclear protein, once believed to have an extracellular immunoregulatory role but more recently implicated in cell proliferation and/or differentiation. Several recent studies have revealed that ProT alpha mRNA is present during embryogenesis. However, these studies did not investigate the spatial distribution of ProT alpha mRNA in the embryo. Here we present a detailed study of the spatial distribution of ProT alpha mRNA during the early stages of postimplantation development (6.5-12.5 dpc) of the mouse. Three findings are of particular interest. First, ProT alpha mRNA levels increase during the early postimplantation stages (6.5-8.5 dpc) of mouse embryogenesis. Second, ProT alpha mRNA is not uniformly distributed in the mouse embryo, but is present in a spatially specific manner. Third, we have observed that the mouse ProT alpha gene is expressed almost exclusively in ectodermal and mesoderm-derived structures, and not in cells which give rise to the definitive endoderm. | 10.1016/0014-5793(94)01427-3 |
others_115_1210 | Gerbera represents a valuable commodity in the global cut flower industry. However, commercial production is hampered by low propagation rates using conventional methods. Hence, the current contribution investigated the application of silver nanoparticles (AgNPs: Argovit™) in temporary immersion bioreactors to promote plant growth. The results showed that AgNPs at the tested concentrations displayed minimal promotive effects in terms of biomass accumulation (with the highest biomass recorded in control plants and those exposed to 25.0 mg L−1 AgNP) and resulted in a reduction in the levels of iron and molybdenum in treated plants. Interesting results testing 50.0 mg L−1 AgNPs yielded plants with elevated levels of chlorophylls a and b and total chlorophyll compared with control plants. This effect was similarly observed in the levels of free and cell wall bound phenolics which were present at more than a two-fold higher concentration in AgNP-treated plants (329.00 to 482.10 Trolox equivalents (TE) g−1 DW) than in control plants (154.02 TE g−1 DW). The trends observed indicated a hormetic response in terms of the biochemical indicators assessed where elicitation occurred between 50 and 75 mg L−1 AgNP and inhibition at 100.0 mg L−1. This hormetic effect of AgNPs was also observed in the antioxidant capacity of phenolics. It is proposed that the accumulation of the abovementioned biochemical compounds is indicative of a stress response elicited by the AgNPs that is mediated through the secondary metabolite biosynthetic pathway. It was further shown that this response displayed a classic hormetic effect. Future work will further investigate this interesting outcome which will be valuable in the context of biotic and abiotic stress research. © 2023, The Society for In Vitro Biology | 10.1007/s11627-023-10365-1 |
pubmed_472_13142 | Negative cooperativity in enzyme reactions, in which the first event makes subsequent events less favorable, is sometimes well understood at the molecular level, but its physiological role has often been obscure. Negative cooperativity occurs in human glutathione transferase (GST) GSTP1-1 when it binds and neutralizes a toxic nitric oxide adduct, the dinitrosyl-diglutathionyl iron complex (DNDGIC). However, the generality of this behavior across the divergent GST family and its evolutionary significance were unclear. To investigate, we studied 16 different GSTs, revealing that negative cooperativity is present only in more recently evolved GSTs, indicating evolutionary drift in this direction. In some variants, Hill coefficients were close to 0.5, the highest degree of negative cooperativity commonly observed (although smaller values of nH are theoretically possible). As DNDGIC is also a strong inhibitor of GSTs, we suggest negative cooperativity might have evolved to maintain a residual conjugating activity of GST against toxins even in the presence of high DNDGIC concentrations. Interestingly, two human isoenzymes that play a special protective role, safeguarding DNA from DNDGIC, display a classical half-of-the-sites interaction. Analysis of GST structures identified elements that could play a role in negative cooperativity in GSTs. Beside the well known lock-and-key and clasp motifs, other alternative structural interactions between subunits may be proposed for a few GSTs. Taken together, our findings suggest the evolution of self-preservation of enzyme function as a novel facility emerging from negative cooperativity. | 10.1074/jbc.M116.749507 |
pubmed_290_22064 | Cellular genes that are functionally related to each other are usually confined in specialized subcellular compartments for efficient biochemical reactions. Construction of spatially controlled biosynthetic systems will facilitate the study of biological design principles. Herein, we fabricated a gene circuit compartment by coanchoring two function-related genes on surface of gold nanoparticles and investigated the compartment effect on cascade gene expression in a cell-free system. The gene circuit consisted of a T7 RNA polymerase (T7 RNAP) expression cassette as regulatory gene and a fluorescent protein expression cassette as regulated reporter gene. Both the expression cassettes were attached on a Y-shaped DNA nanostructure whose other two branches were mercapto-modified in order to steadily anchor the gene expression cassettes on the surface of gold nanoparticles. Experimental results demonstrated that both the yield and initial expression rate of the fluorescent reporter protein in the gene circuit compartment system were enhanced compared with those in free gene circuit system. Mechanism investigation revealed that the gene circuit compartment on nanoparticle made the regulatory gene and regulated reporter gene spatially proximal at nanoscale, thus effectively improving the transfer efficiency of the regulatory proteins (T7 RNAP) from regulatory genes to the regulated reporter genes in the compartments, and consequently, the biochemical reaction efficiency was significantly increased. This work not only provided a simplified model for rational molecular programming of genes circuit compartments on nanointerface but also presented implications for the cellular structure-function relationship. | 10.1021/jacs.9b11407 |
pubmed_460_250 | The full-dimensional time-dependent Schrödinger equation for the electronic dynamics of single-electron systems in intense external fields is solved directly using a discrete method. Our approach combines the finite-difference and Lagrange mesh methods. The method is applied to calculate the quasienergies and ionization probabilities of atomic and molecular systems in intense static and dynamic electric fields. The gauge invariance and accuracy of the method is established. Applications to multiphoton ionization of positronium, the hydrogen atom and the hydrogen molecular ion are presented. At very high laser intensity, above the saturation threshold, we extend the method using a scaling technique to estimate the quasienergies of metastable states of the hydrogen molecular ion. The results are in good agreement with recent experiments. | 10.1063/1.1735662 |
pubmed_36_7464 | We present the enantioselective synthesis of P-stereogenic phosphinamides through Pd-catalyzed desymmetric ortho C-H arylation of diarylphosphinamides with boronic esters. The method represents the first example of the synthesis of P-stereogenic phosphorus compounds via the desymmetric C-H functionalization strategy. The reaction proceeded efficiently with a wide array of reaction partners to afford the P-stereogenic phosphinamides in up to 74% yield and 98% ee. The efficiency was further demonstrated by gram scale syntheses. Moreover, the flexible conversion of the P-stereogenic phosphinamides into various types of P-stereogenic phosphorus derivatives was also elaborated. Thus, the protocol provides a novel tool for the efficient and versatile synthesis of P-stereogenic compounds. | 10.1021/ja512029x |
pubmed_213_20551 | 1. Membrane preparations obtained from RSMT-A5, an established rat submandibular cell line, possess alpha 1-adrenergic receptors as judged by [3H]prazosin binding studies. Scatchard analysis reveals a single class of binding sites with an equilibrium dissociation constant (Kd) of 0.052 nM and a receptor density (Bmax) of 104 fmol/mg protein. 2. These receptors are functional since stimulation by epinephrine results in an increased rate of phosphatidylinositol turnover which is blocked by both phentolamine and phenoxybenzamine. 3. Phenoxybenzamine (10(-5) M) irreversibly blocks 95% of the receptors within 2 min. A kinetic analysis shows that the receptors subsequently reappear at a rate of 6 fmol/mg protein/h. The calculated rate constant for receptor clearance (Kc) is 0.027 hr-1, and the half life (t 1/2) of the receptor is 26 hr. 4. These results are comparable to those reported for alpha 1-adrenergic receptors in the BC3H-1 smooth muscle cell line and suggest that alpha 1-adrenergic receptors in cultured cells, from diverse tissues, display similar characteristics. | 10.1016/0306-3623(89)90011-6 |
pubmed_596_9233 | Our objective was to directly compare the accuracy of the high-risk human papillomavirus (HPV) assays, Hybrid Capture 2 (hc2; Qiagen, Gaithersburg, MD) and Cervista (Hologic, Bedford, MA), in diagnosing cervical intraepithelial neoplasia (CIN) 3 or worse (cancer). A population-based, cross-sectional study (The Shenzhen Cervical Cancer Screening Trial II) was conducted in Guangdong Province in China. Three high-risk HPV assays, self and direct cervical sampling and cytology, were studied. Abnormal results on any of 6 study tests (33%) resulted in referral to colposcopy. At colposcopy, every patient had at least 5 cervical biopsy specimens obtained. For 8,556 women between the ages of 25 and 59 years (mean, 38.9 years), the rate for CIN 3 or worse was 1.6% (141/8,556). The sensitivity (confidence interval) values for CIN 3 or worse were 97.9% (94.0%-99.6%) and 95.1% (90.0%-98.0%) for hc2 and Cervista, respectively (P > .05). The specificity (confidence interval) values were 87.8% (87.1%-88.5%) and 90.3% (89.6%-90.9%), respectively (P < .05). Differences in accuracy in diagnosing CIN 3 or worse with the hc2 and Cervista tests are minor and result from the decisions made in selecting the cut points. | 10.1309/AJCPKA6ATAPBZ6JQ |
pubmed_254_19237 | BACKGROUND
Spinal cord injury (SCI) presents a significant challenge for the field of neurotherapeutics. Stem cells have shown promise in replenishing the cells lost to the injury process, but the release of axon growth-inhibitory molecules such as chondroitin sulfate proteoglycans (CSPGs) by activated cells within the injury site hinders the integration of transplanted cells. We hypothesised that simultaneous application of enteric neural stem cells (ENSCs) isolated from the gastrointestinal tract, with a lentivirus (LV) containing the enzyme chondroitinase ABC (ChABC), would enhance the regenerative potential of ENSCs after transplantation into the injured spinal cord.
METHODS
ENSCs were harvested from the GI tract of p7 rats, expanded in vitro and characterised. Adult rats bearing a contusion injury were randomly assigned to one of four groups: no treatment, LV-ChABC injection only, ENSC transplantation only or ENSC transplantation+LV-ChABC injection. After 16 weeks, rats were sacrificed and the harvested spinal cords examined for evidence of repair.
RESULTS
ENSC cultures contained a variety of neuronal subtypes suitable for replenishing cells lost through SCI. Following injury, transplanted ENSC-derived cells survived and ChABC successfully degraded CSPGs. We observed significant reductions in the injured tissue and cavity area, with the greatest improvements seen in the combined treatment group. ENSC-derived cells extended projections across the injury site into both the rostral and caudal host spinal cord, and ENSC transplantation significantly increased the number of cells extending axons across the injury site. Furthermore, the combined treatment resulted in a modest, but significant functional improvement by week 16, and we found no evidence of the spread of transplanted cells to ectopic locations or formation of tumours.
CONCLUSIONS
Regenerative effects of a combined treatment with ENSCs and ChABC surpassed either treatment alone, highlighting the importance of further research into combinatorial therapies for SCI. Our work provides evidence that stem cells taken from the adult gastrointestinal tract, an easily accessible source for autologous transplantation, could be strongly considered for the repair of central nervous system disorders. | 10.1186/s13287-020-02031-9 |
pubmed_605_19371 | BACKGROUND
Previous studies have shown a decrease in cervical cancer associated with intrauterine device use. It has been hypothesized that intrauterine device use may alter the natural history of human papillomavirus infections, preempting development of precancerous lesions of the cervix and cervical cancer, but the effect of intrauterine devices on the natural history of human papillomavirus infection and subsequent development of cervical cancer is poorly understood.
OBJECTIVE
The purpose of this study was to evaluate the association between intrauterine device use and cervical high-risk human papillomavirus acquisition and clearance.
STUDY DESIGN
This is a prospective cohort study conducted from October 2000 through June 2014 among 676 sexually active young women and girls enrolled from family planning clinics in San Francisco, CA. Data were analyzed using a Cox proportional hazards model, including time-varying indicators of intrauterine device use, and adjusting for fixed and time-dependent predictor variables.
RESULTS
A total of 85 women used an intrauterine device at some time during follow-up. Among 14,513 study visits, women reported intrauterine device use at 505 visits. After adjusting for potential behavioral confounders, there was no association between intrauterine device use and human papillomavirus acquisition (hazard ratio, 0.50; 95% confidence interval, 0.20-1.23; P = .13) or clearance of human papillomavirus infection (hazard ratio, 1.44; 95% confidence interval, 0.76-2.72; P = .26).
CONCLUSION
Current intrauterine device use is not associated with acquisition or persistence of human papillomavirus infection. Intrauterine device use is safe among women and girls with human papillomavirus infections and at risk for human papillomavirus acquisition. Intrauterine device use may play a role further downstream in the natural history of cervical cancer by inhibiting the development of precancerous lesions of the cervix in human papillomavirus-infected women, or enhancing clearance of established precancerous lesions. | 10.1016/j.ajog.2016.11.1053 |
pubmed_313_17334 | BACKGROUND
The adipokine hormone, leptin, is a major component of body weight homeostasis. Numerous studies have been performed administering recombinant mouse leptin as an experimental reagent; however, the half-life of circulating leptin following exogenous administration of recombinant mouse leptin has not been carefully evaluated.
METHODS
Exogenous leptin was administered (3 mg leptin per kg body weight) to 10-week-old fasted non-obese male mice and plasma was serially collected at seven time points; plasma leptin concentration was measured by enzyme-linked immunosorbent assay at each time point to estimate the circulating half-life of mouse leptin.
RESULTS
Under the physiological circumstances tested, the half-life of mouse leptin was 40.2 (±2.2) min. Circulating leptin concentrations up to 1 h following exogenous leptin administration were 170-fold higher than endogenous levels at fasting.
CONCLUSIONS
The half-life of mouse leptin was determined to be 40.2 min. These results should be useful in planning and interpreting experiments employing exogenous leptin. The unphysiological elevations in circulating leptin resulting from widely used dosing regimens for exogenous leptin are likely to confound inferences regarding some aspects of the hormone's clinical biology. | 10.1038/ijo.2016.238 |
pubmed_744_14393 | A combination of laser flash photolysis and competitive kinetic methods has been used to measure the absolute bimolecular rate constants for hydrogen atom abstraction in water from a series of fluorinated alkoxides and aldehyde hydrates by the perfluoroalkyl radical, *CF2CF2OCF2CF2SO3- Na+. The bimolecular rate constants observed for the beta-fluorinated alkoxides were in the 10(5) M(-1) s(-1) range, such rates representing enhancements (relative to the respective alcohols) of between 100 and almost 1000-fold, depending on the reactivity of the alkoxide. Likewise, the monobasic sodium salts of chloral and fluoral hydrate exhibit similar rate enhancements, relative to their respective hydrates. | 10.1039/b405074f |
pubmed_646_18794 | The tumor suppressor protein p53 is a multifunctional transcription factor involved in the control of cell cycle progression, DNA integrity, and cell survival. p53 is mutated in half of all tumors and has a wide spectrum of mutation types. p53 mutants show different degrees of dominance over coexpressed wild-type p53, and loss of the wild-type p53 allele has been observed frequently. Several p53 mutants can exert oncogenic functions beyond their negative domination over the wild-type p53 tumor suppressor functions. These so-called gain-of-function effects, such as enhancement of tumorigenicity and therapy resistance, were investigated in p53-null cells. The possible mechanisms by which p53 mutants exert their gain-of-function effects are reviewed. The existence of functional gains of certain p53 mutants has important ramifications for tumor prognosis and cancer therapies. | pubmed_646_18794 |
pubmed_674_1602 | The temperatures at which chlorophyll fluorescence yield is substantially increased and the temperatures at which the quantum yield for CO2 uptake is irreversibly inhibited were measured for three shortgrass prairie species. The experimental taxa include, a cool season species (Agropyron smithii), a warm season species (Bouteloua gracilis), and a species which grows throughout the cool and warm seasons (Carex stenophylla). Agropyron smithii exhibited lower high temperature damage thresholds (43°C in cool grown plants, 46°C in warm grown plants), relative to the other two species. Bouteloua gracilis exhibited the highest tolerance to high temperature, with threshold values being 44-49°C for cool grown plants and 53-55°C for warm grown plants. Carex stenophylla exhibited threshold values which were intermediate to the other two species (43-47°C for cool grown plants, and 51-53°C for warm grown plants). Seasonal patterns in the fluorescence rise temperatures of field grown plants indicated acclimation to increased temperatures in all three species. The results demonstrate a correlation between the high temperature thresholds for damage to the photosynthetic apparatus, and in situ seasonal phenology patterns for the three species. | 10.1007/BF00541108 |
pubmed_1018_11954 | Kaposi's sarcoma and non-Hodgkin's lymphoma were among the earliest recognized manifestations of the acquired immunodeficiency syndrome (AIDS) epidemic. Excluding these two tumors, the overall risk of all other cancers in human immunodeficiency virus (HIV)-infected individuals is similar to that of the general population. However, varying levels of evidence link several additional neoplasms to HIV infection. The evidence is strongest for an association with Hodgkin's disease, with lower relative and absolute risks than for non-Hodgkin's lymphoma. Anogenital intraepithelial neoplasia also appears to be HIV associated, but increases of invasive disease are still uncertain for both cervical and anal cancers. Various studies have suggested associations with testicular seminoma, multiple myeloma, oral cancer, and melanoma, but the data are inconsistent. Leiomyosarcoma and benign leiomyomas have increased in incidence in HIV-infected children but are unusual in HIV-infected adults. Conjunctival carcinoma is seen in HIV-infected individuals in sub-Saharan Africa but it is uncommon in Western countries. Most other cancers do not seem to have increased incidences in HIV infection. The etiologic mechanisms of HIV-related cancer likely differ among these diverse cancers and do not globally increase cancer risk. | 10.1093/oxfordjournals.jncimonographs.a024168 |
pubmed_915_1731 | Ovarian cancer (OVAC) remains the most lethal gynecological malignancy; it is ranked fifth among the most common types of cancer that affect women worldwide. Several aspects of the disease, including molecular pathogenesis, epidemiology, histological subtypes, poor prognosis at early stages due to the absence of specific signs and symptoms, and curative treatments in the advanced stages are all responsible for the poor survival rate, which is evaluated to be at 5 years once the cancer is diagnosed and treatment begins. A better understanding of the pathogenesis of ovarian cancer is therefore crucial, even though unexplored pathways, in order to improve the prognosis of patients with OVAC and to develop novel therapeutic approaches. Accordingly, the tumor microenvironment, defined as the combination of proteins produced by all tumor cells and by non-cancerous cells or the stroma, and composed of several cells, including those from the immune, inflammatory and adipose systems, as well as the mesenchymal stem, endothelial and fibroblasts cells, has recently attracted attention. Of particular interest are fibroblasts, which can be activated into cancer-associated fibroblast (CAFs) to become a potent supporter of carcinogenesis, promoting the initiation of epithelial tumor formation, tumor growth, angiogenesis and metastasis, as well as therapeutic resistance and immunosuppression. Thus, the targeting of CAFs for early diagnosis and effective therapy warrants our attention. In this review, we discuss the mechanisms through which CAFs may affect the structure, composition and microenvironment of the ovarian tumor. We also aim to highlight important aspects of OVAC pathobiology involving CAFs, in an attempt to provide insight into novel diagnostic windows and provide new therapeutic perspectives. | 10.3892/ol.2019.10587 |
pubmed_897_14712 | Cerebral ischemic injury is a significant portion of the burden of disease in developed countries; rates of mortality are high and the costs associated with morbidity are enormous. Recent therapeutic approaches have aimed at mitigating the extent of damage and/or promoting repair once injury has occurred. Often, patients at high risk of ischemic injury can be identified in advance and targeted for antecedent neuroprotective therapy. Agents that stimulate the innate pattern recognition receptor, Toll-like receptor 9, have been shown to induce tolerance (precondition) to ischemic brain injury in a mouse model of stroke. Here, we demonstrate for the first time that pharmacological preconditioning against cerebrovascular ischemic injury is also possible in a nonhuman primate model of stroke in the rhesus macaque. The model of stroke used is a minimally invasive transient vascular occlusion, resulting in brain damage that is primarily localized to the cortex and as such, represents a model with substantial clinical relevance. Finally, K-type (also referred to as B-type) cytosine-guanine-rich DNA oligonucleotides, the class of agents employed in this study, are currently in use in human clinical trials, underscoring the feasibility of this treatment in patients at risk of cerebral ischemia. | 10.1038/jcbfm.2011.6 |
pubmed_582_12704 | We report the efficient operation of a continuous-wave, single-frequency, diode-pumped Nd:FAP laser at 1.126 mum. When frequency quadrupled, such a laser might be used as a local oscillator for an optical frequency standard based on the single-photon (2)S(1/2)-(2)D(5/2) electric quadrupole transition of a trapped and laser-cooled (199)Hg(+) ion. Since the frequencies of the atomic transition and the laser are harmonically related, this scheme helps to simplify the measurement of the S-D clock transition frequency by a phase-coherent chain to the cesium primary frequency standard. | 10.1364/ao.37.007801 |
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