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pubmed_748_14661 | Evidence from epidemiologic and clinical secondary prevention trials suggest that the omega-3 polyunsaturated fatty acids (n-3 PUFAs) may have a significant role in the prevention of coronary heart disease. Dietary sources of n-3 PUFAs include fish oils, rich in eicosapentaenoic acid and docosahexaenoic acid, along with plants rich in a-linolenic acid. Randomized secondary prevention clinical trials with fish oils (eicosapentaenoic acid, docosahexaenoic acid) and a-linolenic acid have demonstrated reductions in risk that compare favorably to those seen in landmark secondary prevention trials with lipid-lowering drugs. Several mechanisms explaining the cardioprotective effect of the n-3 PUFA have been suggested including antiarrhythmic and antithrombotic roles. Although official US guidelines for the dietary intake of n-3 PUFA are not available, several international guidelines have been published. Fish is an important source of the n-3 PUFA in the US diet; however, vegetable sources including grains and oils offer an alternative source for those who are unable to regularly consume fish. | 10.1111/j.1520-037x.2003.1332.x |
pubmed_164_22124 | Gamete production in the hybridogenetic species hybrid Rana esculenta (Rana ridibunda X Rana lessonae) is preceded by a premeiotic elimination of the R. lessonae genome and subsequent duplication of the remaining R. ridibunda genome, so that only ridibunda chromosomes enter a quasi normal meiosis, and only ridibunda gametes are formed. This is demonstrated by differences in genome specific centromere fluorescence and electrophoretic patterns between somatic and gonadal tissue. | 10.1007/BF00273874 |
pubmed_556_17399 | INTRODUCTION
High exposure to heat and combustion byproducts is associated with health problems and an increased risk of cancer.
OBJECTIVE
To study the effects of heat and smoke derived from burning on the upper airway of firefighters.
METHODS
Thirteen firefighters underwent a 4-week training program in Compartment Fire Behavior Training simulators while working with live fire, heat, and smoke from pallets and oriented-strand board sheet burns. The firefighters were evaluated before exposure and at the end of the first and fourth weeks of training. The larynx was assessed by the Voice Handicap Index GRBASI scale, laryngoscopy, and peak expiratory flow.
RESULTS
There was no change in Voice Handicap Index and GRBASI (only one in three speech therapists judged tension as worse by one point). Laryngoscopy showed alterations in one-third of the firefighters, with the most frequent being increased viscous mucus. Peak expiratory flow decreased significantly from 685 to 552 and 550 L/min in the first and fourth weeks, respectively.
CONCLUSIONS
Although participants were protected from gases and smoke during the exercises, which proved to be very effective, the airway was slightly impacted by heat and combustion-derived byproducts. | 10.1016/j.jvoice.2020.08.020 |
pubmed_556_13278 | OBJECTIVES
Adderall (amphetamine-dextroamphetamine) is a controlled substance with harmful adverse effects if abused or misused. We assessed the availability of Adderall from common search engines, and evaluated the safety and marketing characteristics of online pharmacies selling Adderall.
DESIGN
Cross-sectional study.
SETTING AND PARTICIPANTS
From December 2019 to February 2020, the phrase "buy Adderall online" was queried in four search engines: Google (N = 100), Bing (N = 100), Yahoo (N = 50) and DuckDuckGo (N = 50). Online pharmacies that claimed to sell Adderall and had unique Uniform Resource Locators, were active, free-access, and in English language were included.
OUTCOME MEASURES
Online pharmacies were categorized as rogue, unclassified, or legitimate on the basis of LegitScript classifications. Safety and marketing characteristics, and costs were collected.
RESULTS
Of the 62 online pharmacies found to sell Adderall, 61 were rogue or unclassified. Across all rogue and unclassified online pharmacies, prescriptions were not required (100%), pharmacist services were not offered (100%), and quantity limits were not placed on the number of Adderall purchases (100%). Rogue and unclassified online pharmacies appealed to cost, offering price discounts (61%), bulk discounts (67%), and coupon codes (70%). Contrary to their claims, cheaper prices were available for all formulations and dosages of Adderall from GoodRx than from these online pharmacies. Rogue and unclassified online pharmacies promoted and enabled the illicit purchase of Adderall, appealing to privacy (74%), offering purchase through cryptocurrency (74%), and claiming registration or accreditation of their sites (33%).
CONCLUSION
Rogue online pharmacies are pervasive in search engine results, enabling the illicit purchase of Adderall without a prescription. Consumers are at risk of purchasing Adderall, a medication with high abuse potential, from unsafe sources. Law enforcement, regulatory agencies, and search engines should work to further protect consumers from unregistered and illegitimate online pharmacies selling Adderall. | 10.1016/j.japh.2020.07.022 |
pubmed_1014_19980 | The use of virtualization and cloud computing has changed the way we use computers. Virtualization is a method of placing software called a hypervisor on the hardware of a computer or a host operating system. It allows a guest operating system to run on top of the physical computer with a virtual machine (i.e., virtual computer). Virtualization allows multiple virtual computers to run on top of one physical computer and to share its hardware resources, such as printers, scanners, and modems. This increases the efficient use of the computer by decreasing costs (e.g., hardware, electricity administration, and management) since only one physical computer is needed and running. This virtualization platform is the basis for cloud computing. It has expanded into areas of server and storage virtualization. One of the commonly used dental storage systems is cloud storage. Patient information is encrypted as required by the Health Insurance Portability and Accountability Act (HIPAA) and stored on off-site private cloud services for a monthly service fee. As computer costs continue to increase, so too will the need for more storage and processing power. Virtual and cloud computing will be a method for dentists to minimize costs and maximize computer efficiency in the near future. This article will provide some useful information on current uses of cloud computing. | pubmed_1014_19980 |
pubmed_937_19545 | The auxin-inducible homeobox gene Oshox1 of rice (Oryza sativa) is a positive regulator of procambial cell fate commitment, and its overexpression reduces the sensitivity of polar auxin transport (PAT) to the PAT inhibitor 1-N-naphthylphthalamic acid (NPA). Here, we show that wild-type rice leaves formed under conditions of PAT inhibition display vein hypertrophy, reduced distance between longitudinal veins, and increased distance between transverse veins, providing experimental evidence for a role of PAT in vascular patterning in a monocot species. Furthermore, we show that Oshox1 overexpression confers insensitivity to these PAT inhibitor-induced vascular-patterning defects. Finally, we show that in the absence of any overt phenotypical change, Oshox1 overexpression specifically reduces the affinity of the NPA-binding protein toward NPA and enhances PAT and its sensitivity toward auxin. These results are consistent with the hypothesis that Oshox1 promotes fate commitment of procambial cells by increasing their auxin conductivity properties and stabilizing this state against modulations of PAT by an endogenous NPA-like molecule. | 10.1104/pp.009167 |
pubmed_949_2587 | Cystic formation in association with adrenal neuroblastoma may be related to hemorrhage and necrosis of the tumor. We present an unusual case of congenital cystic fetal neuroblastoma of the right adrenal gland detected at 37 weeks' gestation which evolved into a complex echogenic mass 6 weeks after birth. Surgical exploration revealed a 3.5 x 3 x 3 cm right complex adrenal tumor which was resected. The infant did well 10 weeks after tumor resection. Typically adrenal hemorrhage may appear sonographically to be entirely echogenic, of mixed echogenicity, or anechoic when first imaged. Gradually, the texture of the hematoma will evolve and become more cystic and echolucent on follow-up ultrasound examinations. In contrast, our case of congenital adrenal cystic neuroblastoma became more complex after resolution of the hemorrhagic cyst. This case suggests that adrenal hemorrhagic and adrenal cystic neuroblastoma with a hemorrhagic cyst have different sonographic appearances. We suggest that additional imaging and surgical intervention should be considered whenever a cystic suprarenal mass becomes more complex after resolution and demonstrates no significant decrease in size in postnatal examinations. | 10.1046/j.1469-0705.1997.10010068.x |
pubmed_496_13427 | Primary cell culture, techniques of gene transfection, gelatin zymography, and Western blot were used to investigate the effect of hypoxia on the secretion of MMP-2 and MMP-9 in pulmonary artery endothelial cells (PAEC) and smooth muscle cells (PASMC), and the role of HIF-1. Our results showed that (1) after exposure to hypoxia for 24 h, the protein content and activity of MMP-2 in the PAEC medium as well as these of MMP-2 and MMP-9 in PASMC medium (P < 0. 01) decreased significantly in contrast to those in normoxic group (P < 0.05); (2) after transfection of wild type EPO3'-enhancer, a HIF-1 decoy, the content and activity of MMP-2 and MMP-9 in hypoxic mediums became higher than those in normoxic group (P < 0.01), while transfection of mutant EPO3'-enhancer didn't affect the hypoxia-induced down-regulation. It is concluded that hypoxia could inhibit the secretion and activity of MMP-2 and MMP-9 in PAEC and PASMC, which could be mitigated by the transfection of EPO3'-enhancer and that HIF-1 pathway might contribute to hypoxia-induced down-regulation of MMP-2 and MMP-9. | 10.1007/BF02828202 |
pubmed_609_17830 | Extensive research into mechanisms of cytotoxic drug resistance and subsequent clinical trials of drug resistance modifiers have produced few encouraging results. In this report, we analyze 4,400+ ex vivo Differential Staining Cytotoxicity (DiSC) assay drug response results from patients with chronic lymphocytic leukemia (CLL) to investigate the development of drug resistance during treatment. Patients were untreated (n = 216) or previously treated with various cytotoxic agents (n = 188). Data was processed to identify ex vivo resistance (or sensitivity) induced by treating patients with prednisolone, chlorambucil, cyclophosphamide, anthracycline, or fludarabine. Induced resistance was apparently not associated with any one known mechanism. Treatment with chlorambucil induced a 10-fold sensitivity to steroids; cyclophosphamide induced greater resistance to anthracyclines than alkylating agents; anthracyclines induced greatest resistance to chlorambucil, cisplatin, carboplatin, and cladribine. Patients previously treated with at least two regimens were only 2.16-fold more resistant to CLL drugs than untreated patients, but had significantly reduced survival (median survival, 7.9 months compared with 61.1 months for untreated patients). These results suggest that chlorambucil and/or an antimetabolite should be administered before cyclophosphamide or anthracyclines to delay the onset of extensive pleiotropic drug resistance. Because individual differences in drug sensitivity are considerable, specific guidance could be obtained from ex vivo assay results. Furthermore, as a model for investigating drug resistance mechanisms, fresh CLL lymphocytes represent a useful alternative to drug-resistant cell lines. | pubmed_609_17830 |
pubmed_292_12912 | Viral nervous necrosis infections are causing severe problems on aquaculture industry due to ecological and economic impacts. Their causal agent is nervous necrosis virus or nodavirus, which has been classified into four genotypes. Different genotypes correlate with differences in viral pathogenicity. Therefore, rational development of effective vaccines and diagnostic reagents requires analysis of the genetic variation. The development and validation of a polymerase chain reaction amplification (PCR)-based methodology for nodavirus genotype assessment in a simple and robust format is described. Degenerate external primers and two genotype-specific internal primers were utilized for simultaneous amplification of nodavirus products in a single PCR. A first set of cycles produced a long PCR product, defined by the outer primers, and the internal primers amplified short DNA fragments specific for each genotype in lower annealing temperature. Detection was based on the size of the short products. Nodavirus infected and healthy samples were analyzed and none of the non-infected samples showed any bands, while all infected samples were positive. The proposed method can be performed within 4 h and consumes standard PCR and electrophoresis reagents, with costs lower than 2€ per sample. Tetra-primer PCR is a suitable alternative for virus sequencing in medium scale research laboratories and farming facilities. | 10.1007/s00284-015-0880-0 |
pubmed_120_19885 | BACKGROUND
To understand the gene networks that underlie plant stress and defense responses, it is necessary to identify and characterize the genes that respond both initially and as the physiological response to the stress or pathogen develops. We used PCR-based suppression subtractive hybridization to identify Arabidopsis genes that are differentially expressed in response to ozone, bacterial and oomycete pathogens and the signaling molecules salicylic acid (SA) and jasmonic acid.
RESULTS
We identified a total of 1,058 differentially expressed genes from eight stress cDNA libraries. Digital northern analysis revealed that 55% of the stress-inducible genes are rarely transcribed in unstressed plants and 17% of them were not previously represented in Arabidopsis expressed sequence tag databases. More than two-thirds of the genes in the stress cDNA collection have not been identified in previous studies as stress/defense response genes. Several stress-responsive cis-elements showed a statistically significant over-representation in the promoters of the genes in the stress cDNA collection. These include W- and G-boxes, the SA-inducible element, the abscisic acid response element and the TGA motif.
CONCLUSIONS
The stress cDNA collection comprises a broad repertoire of stress-responsive genes encoding proteins that are involved in both the initial and subsequent stages of the physiological response to abiotic stress and pathogens. This set of stress-, pathogen- and hormone-modulated genes is an important resource for understanding the genetic interactions underlying stress signaling and responses and may contribute to the characterization of the stress transcriptome through the construction of standardized specialized arrays. | 10.1186/gb-2003-4-3-r20 |
pubmed_229_7605 | Bothrojaracin (BJC) is a 27-kD snake venom protein from Bothrops jararaca that has been characterized as a potent thrombin inhibitor. BJC binds to exosites I and II, with a dissociation constant of 0.7 nM, and influences but does not block the proteinase catalytic site. BJC also binds prothrombin through an interaction that has not been characterized. In the present work we characterize the interaction of BJC with prothrombin quantitatively for the first time, and identify the BJC binding site on human prothrombin. Gel filtration chromatography demonstrated calcium-independent, 1:1 complex formation between fluorescein-labeled BJC ([5F]BJC) and prothrombin, whereas no interactions were observed with activation fragments 1 or 2 of prothrombin. Isothermal titration calorimetry showed that binding of BJC to prothrombin is endothermic, with a dissociation constant of 76 +/- 32 nM. The exosite I-specific ligand, hirudin(54-65) (Hir(54-65) (SO(3)(-)), displaced competitively [5F]BJC from prothrombin. Titration of the fluorescent hirudin(54-65) derivative, [5F]Hir(54-65)(SO(3)(-)), with human prothrombin showed a dissociation constant of 7.0 +/- 0.2 microM, indicating a approximately 100-fold lower binding affinity than that exhibited by BJC. Both ligands, however, displayed a similar, approximately 100-fold increase in affinity for exosite I when prothrombin was activated to thrombin. BJC efficiently displaced [5F]Hir(54-65)(SO(3)(-)) from complexes formed with thrombin or prothrombin with dissociation constants of 0.7 +/- 0.9 nM and 11 +/- 80 nM, respectively, indicating that BJC and Hir(54-65)(SO(3)(-)) compete for the same exosite on these molecules. The results indicate that BJC is a potent and specific probe of the partially exposed anion-binding exosite (proexosite I) of human prothrombin. | 10.1110/ps.09001 |
pubmed_167_21997 | BACKGROUND
HIV incidence is growing most rapidly in the United States among young men who have sex with men (YMSM). Overwhelming evidence demonstrates that routine testing and expanded use of pre-exposure prophylaxis (PrEP) would dramatically reduce the population burden of HIV; however, uptake of both interventions is suboptimal among young adults. The use of mobile phone apps by YMSM is ubiquitous and may offer unique opportunities for public health interventions. MyChoices is a theory-driven app to increase HIV testing and PrEP uptake. It was developed by an interdisciplinary team based on feedback from a diverse sample of YMSM.
OBJECTIVE
The aim of this paper is to describe the protocol for the refinement, beta testing, and pilot randomized controlled trial (RCT) to examine the acceptability and feasibility of the MyChoices app.
METHODS
This 3-phase study includes 4 theater testing groups for app refinement with a total of approximately 30 YMSM; for beta testing, including quantitative assessments and exit interviews, with approximately 15 YMSM over a 2-month period; and for a pilot RCT with 60 YMSM. The pilot will assess feasibility, acceptability, and preliminary efficacy of the MyChoices app, compared with referrals only, in increasing HIV testing and PrEP uptake. All participants will be recruited at iTech clinical research sites in Boston, MA, and Bronx, NY.
RESULTS
App refinement is underway. Enrollment for the pilot RCT began in October 2018.
CONCLUSIONS
MyChoices is one of the first comprehensive, theory-driven HIV prevention apps designed specifically for YMSM. If MyChoices demonstrates acceptability and feasibility in this pilot RCT, a multicity, 3-arm randomized controlled efficacy trial of this app and another youth-optimized app (LYNX) versus standard of care is planned within iTech. If shown to be efficacious, the app will be scalable, with the ability to reach YMSM across the United States as well as be geographically individualized, with app content integrated with local prevention and testing activities.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/10694. | 10.2196/10694 |
pubmed_740_5140 | A scalable platform for on-chip optical quantum networks will rely on standard top-down nanofabrication techniques and solid-state emitters with long coherence times. We present a new hybrid platform that integrates amorphous silicon photonic waveguides and microresonators fabricated on top of a yttrium orthosilicate substrate doped with erbium ions. The quality factor of one such resonator was measured to exceed 100,000 and the ensemble cooperativity was measured to be 0.54. The resonator-coupled ions exhibited spontaneous emission rate enhancement and increased coupling to the input field, as required for further development of on-chip quantum light-matter interfaces. | 10.1364/OE.25.002863 |
pubmed_927_16457 | The nature of the oligosaccharide chains of the major envelope glycoprotein, gp85, from avian myeloblastosis-associated viruses has been examined for the subgroup A and subgroup B viruses replicated in fibroblasts from the same chicken embryos. Pronase-digested glycopeptides from [3H]mannose- or [3H]glucosamine-labeled viruses were analyzed by the combined techniques of gel filtration, endo-beta-N-acetylglucosaminidase digestion, and concanavalin A affinity chromatography. The gp85 protein from these two viruses, and also from another subgroup A avian leukosis virus replicated in the same cells, contained a diverse array of asparagine-linked oligosaccharides of the acidic type [(sialic acid +/- galactose-N-acetylglucosamine)2-4-(mannose)3-N-acetylglucosamine2(+/- fucose)-asparagine], hybrid type (sialic acid +/- galactose-N-acetylglucosamine-(mannose)5,4-N-acetylglucosamine2-asparagine), and neutral type [(mannose)5-9-N-acetylglucosamine2-asparagine], with the more highly branched (tri or tetraantennary or both) acidic-type structures representing the predominant class of oligosaccharide. Minor differences were observed between the gp85 of the subgroup B versus subgroup A viruses. | 10.1128/JVI.45.1.233-240.1983 |
pubmed_705_5369 | A Streptomyces sp. producing a high keratinolytic activity when cultured on feather meal medium was isolated from a naturally degraded feather. Maximal keratin degradation using supernatant fluid obtained from batch culture of this organism was observed at 70 degrees C and pH 10. Keratinolytic activity was only partially inhibited by EDTA or PMSF, suggesting that the overall keratinolytic activity was supported by different proteases. Comparisons between proteolytic activities derived from this new strain (S.K1-02) and commercial proteases indicated that S.K1-02 could be a useful biotechnological tool in valorization of keratin-containing wastes, or in the depilation process in the leather industry. | 10.1046/j.1472-765x.1998.00281.x |
pubmed_299_8715 | CTLA-4 and PD-1 are potential targets for tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint-modifying monoclonal antibodies oppose these effects, inducing T cell-mediated immune responses to various tumors including melanoma. Both anti-CTLA-4 and anti-PD-1 antibodies modify the interaction between tumor, antigen-presenting cells, and T lymphocytes. With respect to overall survival, clinical studies have shown a major benefit for the anti-CTLA-4 antibody ipilimumab as well as the two anti-PD-1 antibodies nivolumab and pembrolizumab. Following approval of ipilimumab in 2011, the latter two achieved market authorization in the summer of 2015. Immune responses thus induced and enhanced inevitably entail autoimmune phenomena, affecting various organs to varying degrees. Knowledge of these side effects is crucial with regard to prevention and management by treating physicians. Typically occurring early on and presenting with pronounced and persistent diarrhea, colitis represents a major and severe side effect. Other immune-mediated disorders include dermatitis, hypophysitis, thyroiditis, hepatitis, iridocyclitis as well as other less common autoimmune phenomena. Early recognition and initiation of treatment can reduce risks and sequelae for patients. This review describes the mechanisms of action of immune checkpoint blockade as well as its clinical effects in metastatic melanoma, with a detailed focus on the spectrum of adverse events and their therapeutic management. | 10.1111/ddg.13047 |
pubmed_398_19564 | The development of spinal cord circuitry in humans is poorly characterized, primarily because standard anatomical tracers must be actively transported, which requires living tissue. Intensely fluorescent lipid-soluble tracers have largely eliminated this problem, at least for circuits that can be traced over short distances. We have, therefore, used the carbocyanine dye DiI (1,1-dioctadecyl-3,3,3,3,-tetramethyl-indocarbocyanine perchlorate) to study the development of the dorsal root afferent projection to fetal human spinal cord between 8 and 19 weeks of gestation. We show here that the dorsal root afferents enter the gray matter of the spinal cord very early in gestation. By 8 weeks, a few axons have already reached the motor pools. These axons, presumably spindle afferents, traverse the length of the spinal gray matter in fascicles to reach different groups of motor neurons. As development progresses, these axons project to the ventral horn and branch in a restricted area in the intermediate zone as well as in the motor pools. Between 11 and 19 weeks of gestation, axons in the ventral horn elaborate boutons that appear to be in proximity to the motor neuron somata and their proximal dendrites. Other groups of axons penetrate the gray matter of the spinal cord all along the mediolateral extent of the dorsal horn. These axons descend to lamina IV, and then turn upward to terminate in laminae III and IV, arborizing primarily rostrocaudally. The time course of the development of these axons parallels that of the axons projecting to the ventral horn.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1002/cne.903540102 |
pubmed_880_2294 | Significant advances have been made in recent years in cancer research concerning the chemistry and biological action of the various mushroom hydrazines and related chemicals as well as two mushrooms, Agaricus bisporus and Gyromitra esculenta. In addition, there is limited information involving the teratogenic effects of some of these mycotoxins. It is apparent that a series of these chemicals, as well as the feeding of two raw mushrooms, induce many cancers in experimental animals. Even though recent findings in the chemistry field indicate that the baked mushroom might act similarly to the raw mushroom with regard to cancer induction, no such studies to date have been undertaken. Thus far cancer epidemiologists have not initiated any research in revealing the effect of mushroom consumption in humans. The practical, frequent question as to whether to cease the consumption of some of the baked mushrooms cannot be answered until additional critical information becomes available. At present, there is no reason for the public to panic. | pubmed_880_2294 |
pubmed_87_4288 | OBJECTIVE
We examined the interrelationships of pituitary thyrotropin (TSH) with circulating thyroid hormones to determine whether they were expressed either invariably or conditionally and distinctively related to influences such as levothyroxine (L-T4) treatment.
DESIGN AND METHODS
This prospective study employing 1912 consecutive patients analyses the interacting equilibria of TSH and free triiodothyronine (FT3) and free thyroxine (FT4) in the circulation.
RESULTS
The complex interrelations between FT3, FT4 and TSH were modulated by age, body mass, thyroid volume, antibody status and L-T4 treatment. By group comparison and confirmation by more individual TSH-related regression, FT3 levels were significantly lower in L-T4-treated vs untreated nonhypothyroid autoimmune thyroiditis (median 4·6 vs 4·9 pm, P < 0·001), despite lower TSH (1·49 vs 2·93 mU/l, P < 0·001) and higher FT4 levels (16·8 vs 13·8 pm, P < 0·001) in the treated group. Compared with disease-free controls, the FT3-TSH relationship was significantly displaced in treated patients with carcinoma, with median TSH of 0·21 vs 1·63 (P < 0·001) at a comparable FT3 of 5·0 pm in the groups. Disparities were reflected by calculated deiodinase activity and remained significant even after accounting for confounding influences in a multivariable model.
CONCLUSIONS
TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization. | 10.1111/cen.12527 |
pubmed_560_3829 | OBJECTIVE
To describe physiologic alterations in runners competing in a 160-km endurance event and to evaluate the utility of weight and blood pressure measurements in the assessment of runner performance.
DESIGN
Prospective cohort study.
SETTING
One hundred sixty-km ultramarathon.
PARTICIPANTS
Ninety-one of the 101 participants in the 2010 Tahoe Rim 100 Mile Endurance Run.
ASSESSMENT OF RISK FACTORS
Brachial blood pressure, heart rate, and weight were assessed before competition, at 80 km, and at 160 km.
MAIN OUTCOME MEASURES
Alterations in brachial blood pressure, heart rate, and weight were assessed in finishers. Weight loss, brachial blood pressure, pulse pressure, and heart rate at 80 km were assessed in all participants for their ability to predict failure to finish the race.
RESULTS
Participants who finished 160 km (57%) experienced their fastest heart rates (P < 0.05), lowest systolic pressures (P < 0.05), highest diastolic pressures (P < 0.05), narrowest pulse pressures (P < 0.05), and lowest weights (P < 0.05) at 80 km. High rates of finishing were seen in those who lost >5% of their prerace weight (87%). Categorical weight loss (<3%, 3%-5%, and >5%) was not associated with the ability to finish (P > 0.05) or finishing time (P > 0.05), whereas the presence of a narrow pulse pressure was associated with a high likelihood (likelihood ratio = 9.84; P = 0.002) of failure to finish.
CONCLUSIONS
Greater intracompetition weight loss is not associated with impaired performance but rather may be an aspect of superior performance. Narrow pulse pressure was associated with a high likelihood of failure to finish. | 10.1097/JSM.0b013e318243ffdc |
pubmed_286_5369 | The recent years witnessed a change in the perception of nutrition. Diet does not only provide nutrients to meet the metabolic requirements of the body, but it also constitutes an active way for the consumption of compounds beneficial for human health. Fruit and vegetables are an excellent source of such compounds, thus the growing interest in characterizing phytochemical sources, structures and activities. Given the interest for phytochemicals in food, the development of advanced and suitable analytical techniques for their identification is fundamental for the advancement of food research. In this review, the state of the art of phytochemical research in food plants is described, starting from sample preparation, throughout extract clean-up and compound separation techniques, to the final analysis, considering both qualitative and quantitative investigations. In this regard, from an analytical point of view, fruit and vegetable extracts are complex matrices, which greatly benefit from the use of modern hyphenated techniques, in particular from the combination of high performance liquid chromatography separation and high resolution mass spectrometry, powerful tools which are being increasingly used in the recent years. Therefore, selected applications to real samples are presented and discussed, in particular for the analysis of phenols, polyphenols and phenolic acids. Finally, some hot points are discussed, such as waste characterization for high value-compounds recovery and the untargeted metabolomics approach. | 10.1016/j.foodres.2017.07.080 |
pubmed_922_9729 | Four varieties of common vetch, including three improved varieties (Lanjian No. 1, Lanjian No. 2, and Lanjian No. 3) and one local variety (333A), were evaluated for varietal variations in grain yield, straw yield and straw quality attributes on the Qinghai-Tibetan Plateau. Crops were harvested at pod maturity to determine grain yield, straw yield, harvest index, and potential utility index (PUI). Straw quality was determined by measuring chemical composition, carbohydrate and protein fractions, in vitro gas production and in situ ruminal degradability. Results showed a significant effect (p < 0.01) of variety on the grain yield [875.2-1255 kg dry matter (DM)/ha], straw yield (3154-5556 kg DM/ha), harvest index (15.6-28.7%) and PUI (53.3-63.2%). Variety also had a significant effect on chemical composition, carbohydrate and protein fractions (p < 0.05) except non-structural carbohydrates and rapidly degradable sugars. Significant differences (p < 0.05) were observed among the varieties in potential gas production [188-234 mL/g DM], in vitro organic matter (OM) digestibility (43.7-54.2% of OM), and metabolizable energy (6.40-7.92 MJ/kg DM) of straw. Significant differences (p < 0.001) were also observed among the varieties in rapidly degradable DM fraction and effective DM degradability of straw; however, no difference was observed in other DM degradation parameters and neutral detergent fiber degradation parameters. In conclusion, based on straw yield and quality, Lanjian No. 1 has the greatest potential among the tested varieties as a crop for supplementing ruminant diets for smallholder farmers on the Qinghai-Tibetan plateau. | 10.3390/ani9080505 |
pubmed_379_14068 | Severe impaction of lower second molars often leads to their extraction to avoid potential damage to the first molar root. We present a case in which we used the clinical application of simple biomechanical principles to allow us to upright bilaterally impacted lower second molars into the desired location in a fairly short time. | 10.1016/s0889-5406(95)70137-0 |
pubmed_1135_5641 | In this article, we highlight the advantages of isolating human monoclonal antibodies from the human memory B cells and plasma cell repertoires by using high-throughput cellular screens. Memory B cells are immortalized with high efficiency using Epstein-Barr virus (EBV) in the presence of a toll-like receptor (TLR) agonist, while plasma cells are maintained in single-cell cultures by using interleukin 6 (IL-6) or stromal cells. In both cases, multiple parallel assays, including functional assays, can be used to identify rare cells that produce antibodies with unique properties. Using these methods, we have isolated potent and broadly neutralizing antibodies against a variety of viruses, in particular, a pan-influenza-A-neutralizing antibody and an antibody that neutralizes four different paramyxoviruses. Given the high throughput and the possibility of directly screening for function (rather than just binding), these methods are instrumental to implement a target-agnostic approach to identify the most effective antibodies and, consequently, the most promising targets for vaccine design. This approach is exemplified by the identification of unusually potent cytomegalovirus-neutralizing antibodies that led to the identification of the target, a pentameric complex that we are developing as a candidate vaccine. | 10.1128/microbiolspec.AID-0018-2014 |
pubmed_767_5995 | BACKGROUND
Evidence-based parenting programmes are recommended for the treatment of child mental health difficulties. Families with complex psychosocial needs show poorer retention and outcomes when participating in standard parenting programmes. The Helping Families Programme (HFP) is a 16-week community-based parenting intervention designed to meet the needs of these families, including families with parental personality disorder. This study aimed to explore the help seeking and participatory experiences of parents with a diagnosis of personality disorder. It further aimed to examine the acceptability of referral and intervention processes for the HFP from the perspectives of (i) clinicians referring into the programme; and (ii) referred parents.
METHOD
Semi-structured interviews were conducted with parents recruited to receive HFP (n = 5) as part of a research case series and the referring NHS child and adolescent mental health service (CAMHS) clinicians (n = 5). Transcripts were analysed using Interpretive Phenomenological Analysis.
RESULTS
Four themes were identified for parents: (i) the experience of parenthood, (ii) being a parent affected by personality disorder, (iii) experience of the intervention, and (iv) qualities of helping. Three themes emerged for clinicians: (i) challenges of addressing parental need, (ii) experience of engaging parents with personality disorders and (iii) limited involvement during HFP. Comparison of parent and clinician themes led to the identification of two key interlinked themes: (i) concerns prior to receiving the intervention, and (ii) the challenges of working together without a mutual understanding.
CONCLUSIONS
This pilot study identifies potentially significant challenges of working with parents affected by personality disorder and engaging them in HFP and other similar interventions. Results have important wider clinical implications by highlighting potential barriers to engagement and participation and providing insights on how these barriers might be overcome. Findings have been used to inform the referral and intervention processes of a pilot RCT and further intervention development. | 10.1186/s12888-018-1733-8 |
pubmed_543_10526 | It has been proposed that the depolarizing responses of chromaticity horizontal cells (C-HCs) to red light depend on a feedback signal from luminosity horizontal cells (L-HCs) to short-wavelength-sensitive cones in the retinas of lower vertebrates. In this regard we studied the C-HCs of the Xenopus retina. C-HCs and L-HCs were identified by physiological criteria and then injected with neurobiotin. The retina then was incubated with peanut agglutinin, which stains red-but not blue-sensitive cones. Electron microscopic examination revealed that L-HCs contact all cone classes, whereas C-HCs contact only blue-sensitive cones. Simultaneous recordings from C-HC/L-HC pairs established that when the L-HC was saturated by a steady bright red light, C-HCs alone responded to a superimposed blue stimulus. In response to red test flashes, the C-HC response was delayed by approximately 30 msec with respect to the L-HC response. Isolated HCs of both subtypes were examined by whole-cell patch clamp. Both responded to kainate with sustained inward currents and to quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) with desensitizing currents from a negative holding potential; i.e., both have AMPA-type glutamate receptors. gamma-Aminobutyric acid or glycine opened a chloride channel in the L-HC, whereas the C-HC was unresponsive to either inhibitory amino acid. Since glycine has been shown to abolish selectively the depolarizing response of the C-HC, this finding and other pharmacological data strongly implicate the L-HC in the underlying circuit. Moreover, because the C-HC does not respond to gamma-aminobutyric acid, the neurotransmitter of the L-HC, by elimination, a feedback synapse from L-HC to blue cone is the most plausible mechanism for the creation of depolarizing responses in C-HCs. | 10.1073/pnas.92.8.3556 |
pubmed_402_18678 | OBJECTIVE
To investigate the effects of retrovirus-based gene delivery of inhibitory cytokines and cytokine inhibitors into human synovial fibroblasts in the SCID mouse model of rheumatoid arthritis (RA).
METHODS
The MFG vector was used for gene delivery of tumor necrosis factor alpha receptor (TNFalphaR) p55, viral interleukin-10 (IL-10), and murine IL-10 into RA synovial fibroblasts. The effect on invasion of these cells into human articular cartilage and on perichondrocytic cartilage degradation was examined after 60 days of coimplantation into the SCID mouse.
RESULTS
TNFalphaR p55 gene transfer showed only a limited effect on inhibition of RA synovial fibroblast invasiveness and cartilage degradation. In contrast, invasion of the RA synovial fibroblasts into the coimplanted cartilage was strongly inhibited by both viral and murine IL-10. Perichondrocytic cartilage degradation was not affected by either form of IL-10.
CONCLUSION
The data show that cytokines can be successfully inserted into the genome of human RA synovial fibroblasts using a retroviral vector delivery system, and that the SCID mouse model of human RA is a valuable tool for examining the effects of gene transfer. In addition, inhibition of more than one cytokine pathway may be required to inhibit both synovial- and chondrocyte-mediated cartilage destruction in RA. | 10.1002/1529-0131(199904)42:3<490::AID-ANR14>3.0.CO;2-L |
pubmed_157_24300 | Brain vasogenic edema, involving disruption of the blood-brain barrier, is a common pathological condition in several neurological diseases, with a heterogeneous prognosis. It is sometimes reversible, as in posterior reversible encephalopathy syndrome, but often irreversible and our current clinical tools are insufficient to reveal its reversibility. Here, we show that increased fractional anisotropy in magnetic resonance imaging is associated with the reversibility of vasogenic edema. Spontaneously, hypertensive rats-stroke prone demonstrated posterior reversible encephalopathy syndrome-like acute encephalopathy in response to high-dose cyclosporine A treatment; the deteriorating neurological symptoms and worsening scores in behavioral tests, which were seen in acute phase, dissappered after recovery by cessation of cyclosporine A. In the acute phase of encephalopathy, the fractional anisotropy and apparent diffusion coefficient increased in areas with IgG leakage. This increase of fractional anisotropy occurred in the absence of demyelination: fluid leakage into the myelinated space increased the axial, but not the radial, diffusivity, resulting in the increased fractional anisotropy. This increased fractional anisotropy returned to pre-encephalopathy values in the recovery phase. Our results highlight the importance of the fractional anisotropy increase as a marker for the reversibility of brain edema, which can delineate the brain areas for which recovery is possible. | 10.1177/0271678X16630556 |
pubmed_755_14399 | The inevitable deterioration of the senses associated with ageing can significantly affect older people's quality of life. Adapting daily routines and the home environment to cope with these changes can restore temporarily lost independence. | pubmed_755_14399 |
pubmed_1069_2942 | Oncocytoma of the salivary gland is uncommon and its histogenesis and pattern of evolution are debated. The criteria for malignancy are not well established. We report a morphologically benign oncocytoma of the parotid gland that was studied using various cell proliferation and tumor markers. These markers may have prognostic value and correlate with the aggressiveness of the tumor. | pubmed_1069_2942 |
pubmed_117_24185 | Despite being introduced in clinical practice more than 20 years ago, selection criteria for deep brain stimulation (DBS) in Parkinson's disease (PD) rely on a document published in 1999 called 'Core Assessment Program for Surgical Interventional Therapies in Parkinson's Disease'. These criteria are useful in supporting the selection of candidates. However, they are both restrictive and out-of-date, because the knowledge on PD progression and phenotyping has massively evolved. Advances in understanding the heterogeneity of PD presentation, courses, phenotypes, and genotypes, render a better identification of good DBS outcome predictors a research priority. Additionally, DBS invasiveness, cost, and the possibility of serious adverse events make it mandatory to predict as accurately as possible the clinical outcome when informing the patients about their suitability for surgery. In this viewpoint, we analyzed the pre-surgical assessment according to the following topics: early versus delayed DBS; the evolution of the levodopa challenge test; and the relevance of axial symptoms; patient-centered outcome measures; non-motor symptoms; and genetics. Based on the literature, we encourage rethinking of the selection process for DBS in PD, which should move toward a broad clinical and instrumental assessment of non-motor symptoms, quantitative measurement of gait, posture, and balance, and in-depth genotypic and phenotypic characterization. | 10.3390/jcm9123931 |
pubmed_204_17710 | Objective: To investigate whether small conductance Ca2+ activatedK+ channels; Trigeminal ganglion; Trigeminal neuralgia. (SK3) exists in normal rats' trigeminal ganglions (TG) and its effect on their pain thresholds.Methods: In total, 110 healthy adult male Sprague-Dawley (SD) rats were involved in this study. Ten rats were dissected to collect their liver tissues, TG and DRG. The rest of the rats were randomly assigned to either the experimental group or the control group. The animal model of trigeminal neuralgia (TN) was established by infraorbital nerve ligation. The expression of SK3 channels in their livers, TG and dorsal root ganglions (DRG) were detected. And different doses of SK3 channel activator and inhibitor were administered to the rats in both groups 15 days after the operation; meanwhile, their pain thresholds were also measured.Results: The expression of SK3 channel was found in TG. In the experimental group, the pain threshold was significantly decreased and there was a decreased level of SK3 than that in the control group at 15 days after operation. The administration of SK3 channel agonist (CyPPA) could significantly improve the pain threshold, while, the pain threshold decreased after administration of SK3 channel antagonist (Apamin).Conclusion: The SK3 channel may play a pivotal role in the pathogenesis of trigeminal neuralgia, and it may be one of the potential targets for the treatment of trigeminal neuralgia. | 10.1080/01616412.2021.1948765 |
pubmed_188_24777 | Liver regeneration after two-thirds partial hepatectomy (PH) is a clinically significant repair process for restoring proper liver architecture. Although microRNA-155 (miR-155) has been found to serve as a crucial microRNA regulator that controls liver cell function and proliferation, little is known about its specific role in the regenerating liver. Using a mouse model with miR-155 overexpression or miR-155 knockout, we investigated the molecular mechanisms of miR-155 in liver regeneration. We found a marked induction of miR-155 in C57BL/6 mice after PH. Furthermore, RL-m155 mice showed enhanced liver regeneration as a result of accelerated progression of hepatocytes into the cell cycle, mainly through an increase in cyclin levels. However, proliferation of hepatocytes was delayed in miR-155-deficient livers. Expression of suppressor of cytokine signaling 1 (SOCS1) was dramatically downregulated in the process of liver regeneration, and enhancement of SOCS1 contributed to impaired proliferation of hepatocytes. Additionally, in vitro and in vivo experiments showed that adenovirus- or adeno-associated virus-mediated overexpression of SOCS1 attenuated improved liver regeneration induced by miR-155 overexpression. Our study shows that miR-155 is a pro-proliferative regulator in liver regeneration by facilitating the cell cycle and directly targeting SOCS1. NEW & NOTEWORTHY Our findings suggest a microRNA-155 (miR-155)-mediated positive regulation pattern in liver regeneration. A series of in vivo and in vitro studies showed that miR-155 upregulation enhanced partial hepatectomy-induced proliferation of hepatocytes by promoting the cell cycle without inducing DNA damage or apoptosis. Suppressor of cytokine signaling 1, a target gene of miR-155, antagonized the proliferation-promoting effect of miR-155. Therefore, pharmacological intervention targeting miR-155 may be therapeutically beneficial in various liver diseases. | 10.1152/ajpgi.00072.2018 |
pubmed_561_14140 | More precise prognostic models are needed for prediction of survival in patients with primary sclerosing cholangitis (PSC), particularly for the selection of candidates for liver transplantation. The aim of this study was to develop a time-dependent prognostic model for the calculation of updated short-term survival probability in PSC. Consecutive clinical and laboratory follow-up data from the time of diagnosis were collected from the files of 330 PSC patients from 5 European centers, followed for a median of 8.4 years since diagnosis. Time-fixed and time-dependent Cox regression analyses, as well as the additive regression model, were applied. The reliability of the models was tested by a cross-validation procedure. Bilirubin (on a logarithmic scale), albumin, and age at diagnosis of PSC were identified as independent prognostic factors in multivariate analysis of both the time-fixed and the time-dependent Cox regression models. The importance of bilirubin was more pronounced in the time-dependent model (hazard ratio [HR], 2.84) than in the time-fixed analysis (hazard ratio, 1.51). The additive regression model indicated that once the patients survive beyond the first 5 years, the impact on prognosis of albumin at diagnosis ceases. The time-dependent prognostic model was superior to the time-fixed variant in assigning low 1-year survival probabilities to patients that actually survived less than 1 year. In conclusion, a time-dependent Cox regression model has the potential to estimate a more precise short-term prognosis in PSC compared with the traditional time-fixed models. | 10.1053/jhep.2002.31872 |
pubmed_1019_8038 | BACKGROUND
Unprecedented efforts are underway to eliminate malaria. Mathematical modelling can help to determine the optimal strategies for malaria elimination in different epidemiological settings. This is necessary as there is limited scope for expensive and time-consuming field studies and failure of planned elimination strategies is likely to discourage ongoing investment by funders. However, there has been very little modelling of malaria elimination and little direct involvement of policymakers in its development. There is thus an urgent need for user-friendly and accessible models purpose-designed in collaboration with policymakers to answer pertinent questions arising from the field.
RESULTS
An internet site is presented with a simple mathematical modelling platform for population level models of malaria elimination. It is freely accessible to all and designed to be flexible so both the platform and models can be developed through interaction with users. The site is an accessible introduction to modelling for a non-mathematical audience, and lessons learned from the project will help inform future development of mathematical models and improve communication of modelling results. Currently it hosts a simple model of strategies for malaria elimination and this will be developed, and more models added, over time. The iterative process of feedback and development will result in an educational and planning tool for non-modellers to assist with malaria elimination efforts worldwide.
CONCLUSIONS
By collaboration with end users, iterative development of mathematical models of malaria elimination through this internet platform will maximize its potential as an educational and public health policy planning tool. It will also assist with preliminary optimisation of local malaria elimination strategies before commitment of valuable resources. | 10.1186/1475-2875-10-191 |
pubmed_638_1839 | Dendritic cells (DCs) have important functions as modulators of immune responses, and their ability to activate T cells is of great value in cancer immunotherapy. The isolation of DCs from the peripheral blood of rhesus and African green monkeys has been reported, but the immune system in the common marmoset remains poorly characterized, although it offers many potential advantages for preclinical studies. In the present study, we devised methods, based on techniques developed for mouse and human DC preparation, for isolating DCs from three major tissue sources in the common marmoset: bone marrow (BM), spleen and peripheral blood. Each set of separated cells was analysed using the cell surface DC-associated markers CD11c, CD80, CD83, CD86 and human leucocyte antigen (HLA)-DR, all of which are antibodies against human antigens, and the cells were further characterized both functionally and morphologically as antigen-presenting cells. BM proved to be an excellent cell source for the isolation of DCs intended for preclinical studies on cell therapy, for which large quantities of cells are required. In the BM-derived CD11c(+) cell population, cells exhibiting the characteristic features of DCs were enriched, with the typical DC morphology and the abilities to undergo endocytosis, to secrete interleukin (IL)-12, and to stimulate Xenogenic T cells. Moreover, BM-derived DCs produced the neurotrophic factor NT-3, which is also found in murine splenic DCs. These results suggest that BM-derived DCs from the common marmoset may be useful for biological analysis and for preclinical studies on cell therapy for central nervous system diseases and cancer. | 10.1111/j.1365-2567.2007.02727.x |
pubmed_1092_1196 | One of the most important challenges in modern quantum optical applications is the demonstration of efficient, scalable, on-chip single photon sources, which can operate at room temperature. In this paper we demonstrate a room-temperature single photon source based on a single colloidal nanocrystal quantum dot positioned inside a circular bulls-eye shaped hybrid metal-dielectric nanoantenna. Experimental results show that 20% of the photons are emitted into a very low numerical aperture (NA < 0.25), a 20-fold improvement over a free-standing quantum dot, and with a probability of more than 70% for a single photon emission. With an NA = 0.65 more than 35% of the single photon emission is collected. The single photon purity is limited only by emission from the metal, an obstacle that can be bypassed with careful design and fabrication. The concept presented here can be extended to many other types of quantum emitters. Such a device paves a promising route for a high purity, high efficiency, on-chip single photon source operating at room temperature. | 10.1021/acs.nanolett.6b00082 |
pubmed_345_14398 | BACKGROUND
Oral tacrolimus therapy is effective for refractory ulcerative colitis (UC), but dose adjustment according to the trough concentrations which varies largely among individuals, is required. This study aimed to identify factors to predict the tacrolimus dose required for achieving the target trough level for remission induction of UC.
METHODS
Forty-seven consecutive UC patients who were treated with tacrolimus were retrospectively analyzed. Tacrolimus doses were adjusted every 2 or 3 days to achieve trough concentrations of 10-15 ng/mL. The dose required for reaching the target trough level was analyzed based on disease characteristics, course of trough concentrations, and gene polymorphism related to tacrolimus metabolism.
RESULTS
Median daily dose of tacrolimus required for achieving the target trough level was 0.19 (0.07-0.42) mg/kg, and patients were divided into high or low dose group (< 0.2 mg/kg or > 0.2 mg/kg). The value of initial trough concentration/starting dose was higher in the low dose group than in the high dose group (1.35 ng/mL/mg vs. 0.78 ng/mL/mg, p < 0.0001). Although presence of CYP3A5 *1 was more frequently observed in the high dose group, initial trough concentration was the only significant factor for determining requirement of high dose of tacrolimus (OR = 28.0, 95% confidence interval 3.20 - 631).
CONCLUSIONS
The most practical predictor of the dose required for achieving the target trough concentration was the trough concentration measured 2 or 3 days after starting tacrolimus therapy. Our findings would make tarcolimus administration for UC safer, easier and more effective. | 10.1186/s12876-015-0285-3 |
pubmed_220_14767 | The use of Raman microspectroscopy to depth profile multi-layered polymer laminates is becoming increasingly popular. However, the results are generally degraded by aberrations introduced by the change in refractive index at the air/sample interface. Recent research has suggested that the use of an immersion oil and suitable objective can reduce this effect. This study evaluates this proposal by comparing depth profiling results on a multi-layer poly(styrene)/poly(methylmethacrylate) (PS/PMMA) laminate polymer from both dry metallurgical objectives and immersion objectives (used in combination with an oil of suitable refractive index). The immersion technique enabled successful depth profiling to the full working distance of the objective (100 microm), showing clear and distinct variations in 11 different layers within the laminate; a dry metallurgical objective used for comparison achieved poor resolution of only two layers. This is the first demonstration of depth profiling within a polymer laminate to this depth. The depth profiling results are compared to results obtained by sectioning the PS/PMMA sample after setting it in resin. | 10.1366/000370203322640099 |
pubmed_990_9719 | In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to 3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys mutation we described previously. Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low-HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group (4.8%) than in the high-HDL-C group (1.6%). In addition, we identified 1 carrier of the intron 14G-->A mutation of cholesterol ester transfer protein (CETP) in the high-HDL-C group and subsequently demonstrated cosegregation of the mutant allele with elevated HDL-C levels in the proband's family. In conclusion, we have identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with the LPL Asn291Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns. This article also reports occurrence of a CETP mutation in subjects having non-Japanese roots. | 10.1161/01.atv.18.4.591 |
pubmed_349_14569 | AIMS
While LAA closure has recently been incorporated into both European and US guidelines for stroke prevention, uncertainties regarding post-procedural drug therapy so far limit its adoption. The aim of this analysis is to compare real-world outcome data stratified for the post-procedural drug regimen employed.
METHODS AND RESULTS
One thousand and five patients were implanted with a WATCHMAN device in the prospective EWOLUTION study at 47 centres; 73.5% of the patients were deemed contraindicated for long-term OAC therapy. Here we report on three-month data including the first follow-up TOE exam for 94% of the study population. Following LAA closure, patients received DAPT, VKA, NOAC, single antiplatelet or no therapy (60.3%, 15.4%, 10.9%, 7% and 6.5%, respectively). Device thrombus (2.6%), stroke (0.4%) and major bleeding SAE (2.6%) rates were low overall and did not vary by post-implantation medication strategy. Patients on NOAC had the lowest bleeding rate, without an increase in device thrombus or stroke rates.
CONCLUSIONS
LAA closure with the WATCHMAN device is feasible in patients with a relative or absolute contraindication to oral anticoagulation. Neither DAPT nor NOAC therapy leads to a significant increase in device thrombus, stroke or bleeding compared to the standard VKA regimen. Numerically, NOAC therapy had the lowest event rate. | 10.4244/EIJ-D-17-00042 |
pubmed_890_24434 | In the present work, controlled experimental infection and transmission studies in domestic cattle (Bos taurus) and water buffaloes (Bubalus bubalis) were carried out to study the in vivo behaviour of bubaline herpesvirus 1 (BuHV1). Two bovine and two buffalo calves were infected with BuHV1 (20287N isolate) by intranasal aerosolisation. Two sentinel cattle did not receive the virus challenge, but were housed with infected buffaloes to evaluate horizontal transmission. All experimentally inoculated animals showed viral infection and respiratory clinical signs. BuHV1 experimentally infected calves showed intermittent viral excretion between 2 days and 18 days postinfection (dpi) with a maximum titre of excretion of 106 TCID50/ml and moderate rhinitis between 2 dpi and 20 dpi. BuHV1 experimentally inoculated buffaloes showed mild respiratory signs, which consisted mainly of serous nasal secretions during the infection period. Sentinel calves showed mucosal specific IgG1 antibodies at seven days postcontact. Viral DNA was detected by PCR and sequencing in both buffaloes and sentinel calves, which could be associated with latency. In conclusion, this study showed the susceptibility of cattle to BuHV1 after both experimental infection and contact with infected buffaloes. These data increase the scarce knowledge on the pathogenesis in natural host and the susceptibility of cattle to BuHV1 experimental infection. | 10.1136/vetreco-2015-000162 |
pubmed_385_7353 | OBJECTIVE
Enhanced DNA double-strand break (DSB) repair could be a primary cause for development of resistance in tumor cells to cisplatin, which induces crosslinks and DNA DSBs. A protein complex consisting of hMre11, hRad50, and Nbs1 (MRN) has been identified as a critical component in repair of DNA DSBs. The present study investigates whether the expression of a truncated form of Nbs1 interrupts the function of the MRN complex and therefore enhances cisplatin-induced DNA damage and cytotoxicity in human head and neck squamous cell carcinoma (HNSCC).
METHODS AND MEASURES
Two human HNSCC cell lines, JHU006 and JHU029, were used. A dominant negative recombinant adenovirus expressing domains of Nbs1 was constructed. Adenovirus-mediated mutant Nbs1 (Ad-Nbs1) gene transfer was performed with replication-defective virus (DL312) and no treatment as controls. Transgene expression and cell viability were evaluated in transfected cells. Neutral comet assay was performed and the "tail moment," the product of the amount of DNA in the tail and the distance of tail migration, was analyzed for evaluating DNA DSB damage at 24, 48, and 72 hours.
RESULTS
Transgene expression of mutant Nbs1 was confirmed by Western blotting. Ad-Nbs1 gene transfer significantly increased cisplatin-induced cytotoxicity as shown by stunting of 6-day growth curves. Neutral comet analysis revealed that the mean tail moment, indicative of DNA damage, was significantly elevated in cells treated with combined cisplatin and Ad-Nbs1 compared to cisplatin alone in both cell lines.
CONCLUSIONS
Expression of mutant Nbs1 significantly increases cisplatin-induced DNA DSBs and cytotoxicity. The increase in double-strand DNA damage corresponds to the level of cytotoxicity in the different treatment groups and suggests that tumor chemosensitization occurs through augmentation of DNA DSBs.
CLINICAL SIGNIFICANCE
Alteration of DNA repair may provide a novel approach to enhancing sensitivity of HNSCC to chemotherapy. Our study supports the potential application of Ad-Nbs1 in combination with cisplatin for treatment of advanced and metastatic HNSCC. | 10.1016/j.otohns.2004.04.019 |
pubmed_414_8386 | Necrotizing fasciitis due to methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon but life-threatening infection, and has mainly been reported as occurring in adults and the elderly. Recently, infant cases involving Panton-Valentine leukocidin (PVL)-positive community-acquired MRSA have been noted. Here, a case of fatal necrotizing fasciitis with sepsis and disseminated intravascular coagulation in an extremely low-birth-weight infant is described. The causative agent was the hospital-acquired MRSA New York/Japan clone carrying the spa variant gene and nine staphylococcal enterotoxin (SE) genes. These data suggest that a high-level combination of SEs and other virulence factors, but not PVL, could contribute to the pathogenesis of fatal necrotizing fasciitis. | 10.1111/j.1469-0691.2009.02806.x |
pubmed_719_12502 | During disease, cells experience various stresses that manifest as an accumulation of misfolded proteins and eventually lead to cell death. To combat this stress, cells activate a pathway called unfolded protein response that functions to maintain endoplasmic reticulum (ER) homeostasis and determines cell fate. We recently reported a hitherto unknown mechanism of regulating ER stress via a novel post-translational modification called Fic-mediatedadenylylation/AMPylation. Specifically, we showed that the human Fic (filamentation induced by cAMP) protein, HYPE/FicD, catalyzes the addition of an adenosine monophosphate (AMP) to the ER chaperone, BiP, to alter the cell's unfolded protein response-mediated response to misfolded proteins. Here, we report that we have now identified a second target for HYPE-alpha-synuclein (αSyn), a presynaptic protein involved in Parkinson's disease. Aggregated αSyn has been shown to induce ER stress and elicit neurotoxicity in Parkinson's disease models. We show that HYPE adenylylates αSyn and reduces phenotypes associated with αSyn aggregation invitro, suggesting a possible mechanism by which cells cope with αSyn toxicity. | 10.1016/j.jmb.2019.04.026 |
pubmed_1113_23814 | The long-term effects of sand extraction on macrozoobenthic communities were investigated in an offshore area in the Northern Adriatic Sea characterised by relict sands formed during the last Adriatic post-glacial transgression. Surveys were carried out before, during and 1, 6, 12, 18, 24 and 30 months after extraction at three impacted and seven reference stations. The operations did not influence the physical characteristics of the sediment, but they caused almost complete defaunation at dredged sites. Univariate and multivariate analyses highlighted that the macrozoobenthic community responses to the dredging operations were (1) a rapid initial recolonisation phase by the dominant taxa present before dredging, which took place 6-12 months after sand extraction; (2) a slower recovery phase, that ended 30 months after the operations, when the composition and structure of the communities were similar in the dredged and reference areas. This pattern of recolonisation-recovery fits well with the commonly encountered scenario where the substratum merely remains unchanged after marine aggregate extraction. | 10.1016/j.marenvres.2007.06.002 |
pubmed_732_2382 | Although it does offer some advantages, the one-staged exchange in periprosthetic joint infection (PJI) remains rare in the orthopedic world. Besides the reduced number of surgical interventions for the patients, it is usually associated with a decreased in-hospital stay and quicker mobilization. Furthermore, it might be the more cost-effective approach and allows for a reduced duration of postoperative systemic antibiotics, usually less than 14 days. Technically, the presence of a positive culture by preoperative aspiration or biopsy and respective antibiogram is mandatory. A cemented implant fixation using specified topic antibiotics, based on the antibiogram, is treatment of choice for one-staged procedures. The overall success is based on the well-defined and detailed intrahospital infrastructure, including a meticulous preoperative planning, joint aspiration regime, and aggressive intraoperative surgical approach. This article describes the one-staged exchange in infected PJI of the knee joint, which has been established 40 years ago in the HELIOS ENDO-Klinik Hamburg, Germany. | 10.1055/s-0034-1376882 |
pubmed_476_6265 | Eric Lander's resignation as President Biden's science adviser and director of the Office of Science Technology and Policy (OSTP), amid allegations that he bullied and demeaned subordinates, is the latest disappointment from an administration that has been struggling to guide the nation with sound science and science leadership. Lander's departure now leaves empty the first ever OSTP directorship to be added to the President's Cabinet. This vacancy joins the absence of permanent directors for the Food and Drug Administration (FDA) and the National Institutes of Health (NIH), not to mention a secretary of Health and Human Services (HHS) so disengaged as to appear absent. Let's hope the president appoints the best people-in brilliance and character-into these positions, stops undermining his own workplace policy of respect and dignity, and gets the country back on course to follow the science, as he pledged. | 10.1126/science.abo5170 |
pubmed_191_1652 | Structure-property relationships were obtained for 11 physical and chemical properties (boiling points (bp), melting points (mp), molar refractions (MR), molar volumes (MV), heats of combustion (HCKJ), molar heats of vaporization (HVMOL), flashpoints (FLASHK), second virial coefficients (VIRC2), critical temperatures (Tc), critical pressures (Pc), and viscosities (VISC)) for a data set consisting of 162 C4-C9 monoalkenes. Both molecular connectivity indices and ad hoc descriptors were tested as structural descriptors, and both produced high-quality regression equations for most of the properties. As was observed in an earlier study of alkanes [J. Am. Chem. Soc. 110 (1988) 4186], mp were not well described by either descriptor set. For most properties, the mass/bulk of the molecule was found to be the most important structural feature determining the property, suggesting that dispersion forces play a dominant role in determining those properties influenced by intermolecular interactions. The amount of branching in the molecule and the nature of the double bond environment were also found to be influential features. | 10.1016/s1093-3263(01)00099-7 |
pubmed_526_15431 | BACKGROUND
Given the demographic changes, the need for effective geriatric intervention is obvious. Geriatric care aims to maintain the highest possible level of independence and quality of life and to reduce the risk of need for care.
OBJECTIVES
This study investigated the benefits of geriatric care on functional performance, mobility and cognition.
MATERIAL AND METHODS
This study involved a retrospective analysis of clinical data from 646 patients. At hospital admission and discharge functional status was assessed using the Barthel index. Mobility was evaluated by means of the Tinetti test and cognition by the mini-mental state examination (MMSE). A follow-up was conducted on 112 patients 2-5 months after hospital discharge. Statistical analysis included t-tests including Cohen's d for effect size and multivariate regression analysis.
RESULTS
The mean age of the study population was 81.1 ± 7.1 years including 439 women (68%) and 207 men (32%). There were significant average improvements for activities of daily living (ADL), mobility and cognition comparing discharge and admission scores. For functional and mobility status, effect sizes were medium to high. Regression analyses showed that ADL improvement was predicted by functional, mobile and cognitive status at admission. Follow-up analyses revealed a high percentage of former patients still living at home and an overall maintenance of ADL levels.
CONCLUSION
Geriatric patients seem to experience long-term improvements during geriatric treatment, which appears to fulfill its aim of recovering independence. For a better understanding of relevant factors for the recreation of geriatric patients, further research is needed, e.g. with respect to the impact of the nutritional status. | 10.1007/s00391-015-0870-7 |
pubmed_453_11483 | The mRNA expression and localization of the aquaporin (AQP) family in rat kidney were examined by ribonuclease protection assay and immunohistochemistry. AQP1, AQP2, AQP3, and AQP4 mRNA were hardly detectable in 16-day gestation fetuses. AQP1 mRNA was explosively expressed at 1 wk, keeping the level throughout life. AQP2 mRNA expression was apparently noticed in 18-day fetuses and was enhanced gradually with age to reach a plateau at 4 wk. AQP3 and AQP4 mRNA expression was significantly found at birth but was not changed remarkably thereafter. AQP2 protein appeared first at the apical side of collecting duct cells in 18-day fetuses. The staining intensity at the site increased with age, and basolateral staining was added in adult rats. AQP3 was distinctly demonstrated at the basolateral side of collecting duct cells after birth, and the staining intensity was almost stable throughout life. The progressive induction of AQP2 expression in the first 4 wk after birth is presumed to contribute to the maturation of urinary concentrating capacity during the kidney development. | 10.1152/ajprenal.1997.272.2.F198 |
pubmed_845_23380 | BACKGROUND
The specific underlying pathogenesis of prolactinoma has not been clarified yet, to the best of our knowledge. p38 mitogen-activated protein kinase (MAPK) signaling including p38α MAPK (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is associated with the development and progression of several types of cancer.
METHODS
Immunofluorescence analysis was performed on the prolactin (PRL) and MAPK14 expressions of pituitary gland in C57BL/6 mice and human prolactinoma specimen. In the present study, the role of MAPK14 in prolactinoma was determined using estradiol-induced mice and dopamine D2 receptor knockout (DRD2-/-) mice models in C57BL/6 wild-type (WT), MAPK14-/- and DRD2-/-MAPK14+/- mice. GH3 cells were transfected with different sets of MAPK14 small interfering RNA, which to study MAPK14 and PRL expression in GH3 cells.
RESULTS
Immunofluorescence analysis showed that PRL and MAPK14 expression were colocalized and increased in the pituitary gland of mice and human prolactinoma specimen compared with the control specimen. It was shown that PRL and MAPK14 expression was colocalized and increased significantly in the pituitary gland of estradiol-injected prolactinoma mice compared with the control mice. Knockout of MAPK14 significantly inhibited tumor overgrowth, and PRL expression was decreased in estradiol-induced mice. Furthermore, MAPK14 knockout of DRD2-/-MAPK14+/- mice significantly reduced the overgrowth of pituitary gland and PRL production and secretion compared with DRD2-/- mice. MAPK14 knockout using siRNA inhibited PRL production in GH3 cells.
CONCLUSION
These results suggest that MAPK14 serves a promoting role in the formation of prolactinoma, and highlights the potential of MAPK14 as a potential therapeutic target in the treatment of prolactinoma. | 10.1186/s12902-020-00619-z |
pubmed_85_9741 | BACKGROUND
Thumb collateral ligament injuries occur frequently in the National Football League (NFL). In the general population or in recreational athletes, pure metacarpophalangeal (MCP) abduction or adduction mechanisms yield isolated ulnar collateral ligament (UCL) and radial collateral ligament (RCL) tears, respectively, while NFL athletes may sustain combined mechanism injury patterns.
PURPOSE
To evaluate the incidence of simultaneous combined thumb UCL and RCL tears among all thumb MCP collateral ligament injuries in NFL athletes on a single team.
STUDY DESIGN
Case series; Level of evidence, 4.
METHODS
A retrospective review of all thumb injuries on a single NFL team from 1991 to 2014 was performed. All players with a thumb MCP collateral ligament injury were included. Collateral ligament injuries were confirmed by review of both physical examination findings and magnetic resonance imaging. Player demographics, surgical details, and return-to-play data were obtained from the team electronic medical record and surgeons' records.
RESULTS
A total of 36 thumbs in 32 NFL players were included in the study, yielding an incidence of 1.6 thumb MCP collateral ligament injuries per year on a single NFL team. Of these, 9 thumbs (25%) had a simultaneous combined UCL and RCL tear injury pattern confirmed on both physical examination and MRI. The remaining 27 thumbs (75%) were isolated UCL injuries. All combined UCL/RCL injuries required surgery due to dysfunction from instability; 63.0% of isolated UCL injuries required surgical repair ( P = .032) due to continued pain and dysfunction from instability. Repair, when required, was delayed until the end of the season. All players with combined UCL/RCL injuries and isolated UCL injuries returned to play professional football the following season.
CONCLUSION
Simultaneous combined thumb UCL and RCL tear is a previously undescribed injury pattern that occurred in 25% of thumb MCP collateral ligament injuries on a single NFL team over a 23-year period. All players with combined thumb UCL/RCL injuries required surgical repair, which was significantly higher compared with players with isolated UCL injuries. Team physicians and hand surgeons treating elite football players with suspected thumb collateral ligament injuries should examine for RCL and UCL instability and consider MRI if any concern exists for a combined ligament injury pattern, as this injury is likely frequently missed. | 10.1177/0363546516660979 |
pubmed_695_20667 | The sodium pump (Na+, K+-ATPase, NKA) is vital for animal cells, as it actively maintains Na+ and K+ electrochemical gradients across the cell membrane. It is a target of cardiotonic steroids (CTSs) such as ouabain and digoxin. As CTSs are almost unique strong inhibitors specific to NKA, a wide range of derivatives has been developed for potential therapeutic use. Several crystal structures have been published for NKA-CTS complexes, but they fail to explain the largely different inhibitory properties of the various CTSs. For instance, although CTSs are thought to inhibit ATPase activity by binding to NKA in the E2P state, we do not know if large conformational changes accompany binding, as no crystal structure is available for the E2P state free of CTS. Here, we describe crystal structures of the BeF3- complex of NKA representing the E2P ground state and then eight crystal structures of seven CTSs, including rostafuroxin and istaroxime, two new members under clinical trials, in complex with NKA in the E2P state. The conformations of NKA are virtually identical in all complexes with and without CTSs, showing that CTSs bind to a preformed cavity in NKA. By comparing the inhibitory potency of the CTSs measured under four different conditions, we elucidate how different structural features of the CTSs result in different inhibitory properties. The crystal structures also explain K+-antagonism and suggest a route to isoform specific CTSs. | 10.1073/pnas.2020438118 |
pubmed_889_24674 | Middle school is a risky period, marked by increased peer victimization, and the onset of several mental disorders, including suicidal thoughts and behaviors (STBs). Parental involvement is critical to students' well-being; however, few studies have examined the role of parental involvement among middle school students or its effect on their mental health. This study examined the effects of perceived parental involvement and victimization on adolescents' mental health difficulties (MHDs) and STBs. We also investigated whether these effects varied across demographic groups, and whether perceived parental involvement buffers the relationship between victimization and students' mental health outcomes. The sample consisted of 301,628 students (50.7% female) from 615 middle schools (Grades 6 to 8) in Georgia (United States). Hierarchical linear modeling showed that higher student-level perceived parental involvement was related to fewer MHDs (b = -0.20) and STBs (b = -0.10), and higher school-level perceived parental involvement was related to fewer STBs (b = -0.11). However, higher student-level (b = 0.25, 0.08) and school-level (b = 0.37, 0.10) traditional victimization were associated with more MHDs and STBs. Student-level perceived parental involvement was also more positively related to MHDs and STBs for 6th (b = 0.06, 0.04) and 7th graders (b = 0.03, 0.02) than for 8th graders, and it was more negatively related to MHDs (b = -0.24) and STBs (b = -0.13) for girls than for boys. Perceived parental involvement also moderated the relationships among traditional victimization, cyber victimization MHDs, and STBs. Implications are discussed relating to how schools can promote parental involvement and student mental health. (PsycINFO Database Record (c) 2019 APA, all rights reserved). | 10.1037/spq0000300 |
pubmed_433_13726 | Posterior lumbar interbody fusion (PLIF) with a spacer and posterior instrument (PI) via minimally invasive surgery (MIS) restores intervertebral height in degenerated disks. To align with MIS, the spacer has to be shaped with a slim geometry. However, the thin spacer increases the subsidence and migration after PLIF. This study aimed to propose a new lumbar fusion approach using bone cement to achieve a larger supporting area than that achieved by the currently used poly aryl-ether-ether-ketone (PEEK) spacer and assess the feasibility of this approach using a sawbone model. Furthermore, the mechanical responses, including the range of motion (ROM) and bone stress with the bone cement spacer were compared to those noted with the PEEK spacer by finite element (FE) simulation. An FE lumbar L3-L4 model with PEEK and bone cement spacers and PI was developed. Four fixing conditions were considered: intact lumbar L3-L4 segment, lumbar L3-L4 segment with PI, PEEK spacer plus PI, and bone cement spacer plus PI. Four kinds of 10-NM moments (flexion, extension, lateral bending, and rotation) and two different bone qualities (normal and osteoporotic) were considered. The bone cement spacer yielded smaller ROMs in extension and rotation than the PEEK spacer, while the ROMs of the bone cement spacer in flexion and lateral bending were slightly greater than with the PEEK spacer. Compared with the PEEK spacer, peak contact pressure on the superior surface of L4 with the bone cement spacer in rotation decreased by 74% (from 8.68 to 2.25 MPa) and 69.1% (from 9.1 to 2.82 MPa), respectively, in the normal and osteoporotic bone. Use of bone cement as a spacer with PI is a potential approach to decrease the bone stress in lumbar fusion and warrants further research. | 10.1007/s13246-019-00832-8 |
pubmed_867_12314 | The heat beam dolorimeter (HBD) was developed to evaluate cutaneous pain thresholds in humans. In the present study, the hypothesis that a patient's underlying pain status affects his pain tolerance to an incident HBD stimulus was tested. Twenty-seven chronic pain patients with a variety of clinical problems unresponsive to conventional algological therapy were scheduled for neurosurgical procedures. These patients were evaluated pre- and postoperatively by the HBD procedure. On initial testing, drug-free pain patients showed significantly higher pain tolerance thresholds than normal volunteers (P less than 0.02, Mann-Whitney U test). Postoperatively, incident pain tolerance thresholds in the HBD test were reduced from pre-surgical levels in these patients and were indistinguishable from the second evaluation latencies of volunteers (P greater than 0.05). Twenty-four of the 27 patients reported significant pain relief following surgery. Our results show that, in chronic pain patients, endogenous pain significantly affected incident pain perception in the HBD test when compared with the responses of normal pain-free volunteers. Consequently, HBD may be useful in objectively assessing chronic pain and its relief by neurosurgical procedures. | 10.1016/0304-3959(87)90083-2 |
pubmed_290_17139 | A second species of Acherontides from Brazil is described. Acherontides serrasapoensis sp. nov. has two ocular area chaetae, tenaculum with 3+3, two clavate tenent hairs, and anal spines about 1/3 the length of unguis III. A comparative table is presented and an identification key for the species of Acherontides. | 10.11646/zootaxa.4623.1.9 |
pubmed_330_23469 | The objective of this study was to investigate variants of localization of cranial chordomas. We examined 220 patients treated in Burdenko Neurosurgical Institute (Moscow, Russia) since 1985 till 2007. In the vast majority of cases (93%) tumors were localized in sellar region (34%), clivus (32%) and craniovertebral junction (27%). As addition to previously suggested classifications we distinguish special group of craniofacial chordomas (5%). Although chordomas are theoretically midline tumors, according to our data in many cases (40%) they may be lateralized. | pubmed_330_23469 |
pubmed_988_12746 | In order to investigate the single dose oral toxicity of BMY-28100 in juvenile animals, the drug was administered in single doses to 4-day-old and 14-day-old Crj: CD (SD) rats of both sexes at a dose of 2,000 mg/kg, and to 4-week-old beagle dogs of both sexes at doses of 500, 1,000 and 2,000 mg/kg by oral route. The results obtained are summarized as follows: 1. In rats, decreases of the body weight gain were observed for male and female rats treated with the drug on postnatal day 4 through 5 days and 3 days after dosing, respectively. There were no apparent drug-related toxic signs. No deaths occurred during the observation period. Enlargement of the cecum was found in a few rats of both sexes administered the drug on postnatal day 4 or 14. 2. In dogs, watery-mucous diarrhea observed at 2 to 3 hours after dosing in all dose groups was not dose-related. This finding lasted in some dogs till 4 days after dosing. An increased incidence of emesis was induced in all males at 2,000 mg/kg and all females of all dose groups except one female at 2,000 mg/kg. Body weights increased normally for all dogs, but one male at 1,000 mg/kg showed a transient decrease in food consumption. No drug-related histopathological changes were found. Based upon these results, BMY-28100 at 2,000 mg/kg induced no apparent toxic changes in the present experimental conditions. Therefore, the single dose oral toxicity of the drug in juvenile animals appeared to be very slight and generally similar to that in adults.(ABSTRACT TRUNCATED AT 250 WORDS) | pubmed_988_12746 |
pubmed_149_8126 | A 35-year-old male patient reached the emergency department after an episode of massive haemoptysis a few hours ago. Fever and dyspnea were mentioned to be present the last 5 days. His medical history included only malaria, successfully treated 2 years ago. Clinical examination revealed high fever, jaundice, cyanosis, tachypnea and bilateral rales on pulmonary auscultation. Laboratory investigation showed high erythrocyte sedimentation rate and C reactive protein, leucocytosis, anaemia, mild thrombocytopaenia, renal impairment, hyperbilirubinaemia and abnormal liver function tests; arterial blood gas analysis showed respiratory alkalosis with severe hypoxia. Thoracic X-ray revealed bilateral pulmonary infiltrates, whereas abdominal and heart ultrasound detected hepatomegaly and small pericardial infusion, respectively. The diagnosis of leptospirosis along with acute respiratory distress syndrome was confirmed by positive IgM Leptospira antibodies. Empirical treatment with triple antibiotic therapy and corticosteroids was applied. The patient was discharged after 1 week, without any symptoms and with almost normal laboratory tests. | 10.1136/bcr-2019-229350 |
pubmed_65_2251 | Poliovirus live virus vectors are a candidate recombinant vaccine system. Previous studies using this system showed that a live poliovirus vector expressing a foreign antigen between the structural and nonstructural proteins generates both antibody and cytotoxic T-lymphocyte responses in mice. Here we describe a novel in vitro method of cloning recombinant polioviruses involving a hybrid-PCR approach. We report the construction of recombinant vectors of two different serotypes of poliovirus-expressing simian immunodeficiency virus (SIV) antigens and the intranasal and intravenous inoculations of four adult cynomolgus macaques with these poliovirus vectors expressing the SIV proteins p17(gag) and gp41(env). All macaques generated a mucosal anti-SIV immunoglobulin A (IgA) response in rectal secretions. Two of the four macaques generated mucosal antibody responses detectable in vaginal lavages. Strong serum IgG responses lasting for at least 1 year were detected in two of the four monkeys. SIV-specific T-cell lymphoproliferative responses were detected in three of the four monkeys. SIV-specific cytotoxic T lymphocytes were detected in two of the four monkeys. This is the first report of poliovirus-elicited vaginal IgA or cytotoxic T lymphocytes in any naturally infectable primate, including humans. These findings support the concept that a live poliovirus vector is a potentially useful delivery system that elicits humoral, mucosal, and cellular immune responses against exogenous antigens. | 10.1128/JVI.73.11.9485-9495.1999 |
pubmed_868_14653 | BACKGROUND
Critically ill intensive care unit (ICU) patients often experience pain, anxiety, panic, fear, dyspnea, and distress related to mechanical ventilation. Patients' recollections vary from having little or no memory of actual events to having total recall. Few studies have examined family members' memories and congruence with patients' symptom report and nurse observation.
OBJECTIVES
To describe the experience of the mechanically ventilated ICU patient.
AIMS
(1) to explore patient and family memories of pain, anxiety, distress, and dyspnea following mechanical ventilation; (2) to determine if there is a correlation among nurse-documented pain assessment and patient- and family-reported pain intensity; and (3) to determine the level of patient and family satisfaction with care while on the ventilator.
METHODS
This was a descriptive study design. A convenience sample of ICU patients (n = 84) and family members (n = 77) was interviewed. Medical record data abstraction included patient demographics, medication administration, and nurse assessment of pain and sedation.
RESULTS
Most patient and family members reported memories of pain, anxiety/panic, nightmares or distress, and trouble breathing. Patients' perception of anxiety, nightmares, and dyspnea were moderately correlated with their pain perception (P = .000). Family members' memories of pain were correlated with nurse pain assessment behavioral scale ratings, but patients' memories of pain were not. Patients and family reported high satisfaction scores.
CONCLUSION
Further inquiry of the patient's experience with mechanical ventilation, the use of a ventilation sedation management protocol, and the evaluation of effective communication tools such as the use of bedside reporting or patient communication boards is warranted. | 10.1097/DCC.0000000000000128 |
pubmed_1104_9488 | Domain I of the Cry1Ab insecticidal toxic protein has seven alpha-helices and is considered to be involved in the ion channel activity. While other alpha-helices, particularly alpha-4 and alpha-5, have been extensively explored, the remaining alpha-helices have been slightly studied. Site-directed mutagenesis was used to generate mutations throughout sequences encoding the alpha-helix 7 to test its role in ion channel function. Every amino acid residue in alpha-helix 7 was mutated to alanine. Most resultant proteins, e.g., D225A, W226A, Y229A, N230A, R233A, R234A, D242A, and F247A yielded no protoxin or were sensitive to degradation by trypsin or Manduca sexta midgut juice. Other mutant proteins, R224A, R228A, and E235A, were resistant to degradation to the above proteases but were 8, 30, and 12 times less toxic to M. sexta, respectively, than the wild-type Cry1Ab. Circular dichroism spectroscopy indicated a very small change in the R228A spectrum, while R224A and E235A display the same spectrum as the wild-type protein. These three mutant proteins showed little differences from Cry1Ab when analyzed by saturation binding and competition binding kinetics with (125)I-labeled toxin or by surface plasmon resonance to M. sexta brush border membrane vesicles. More conservative amino acid substitutions were introduced into alpha-helix 7 residues: R228K, F232Y, E235Q, and F247Y. In comparison with wild-type Cry1Ab, mutant proteins R228K, F232Y, E235A, and E235Q selectively discriminate between K+ and Rb+, while R224A and R228A had reduced inhibition of short-circuit current for both ions, when analyzed by voltage clamping of M. sexta midguts. | 10.1021/bi0022240 |
pubmed_622_10228 | We studied the utility of ABPM in patients with elevated clinic BP on 1-2 antihypertensive medications (group B, N=117), compared with those on no medications (group A, N=76) and on > or =3 medications (group C, N=110). 35% of patients in group B had adequately controlled 24-h BP based on ABPM, compared with 22.4% in group A (P=0.06) and 19.1% in group C (P=0.007). Antihypertensive treatment was not escalated in patients with adequately controlled BP. This suggests that ABPM has an important role in therapeutic decision-making for patients on 1-2 antihypertensive medications. | 10.1016/j.ijcard.2007.01.014 |
pubmed_881_15254 | OBJECTIVES
To determine whether changes in injecting drug use and sexual behavior over a 12-month follow-up are associated with HIV counseling and testing (C and T) of injecting drug users in methadone maintenance treatment programs (MMTP) in Massachusetts and Connecticut.
METHODS
Clients were invited to participate in a longitudinal study involving five interviews. Data were also obtained by ethnographers and from clinical records. Behavioral outcomes of interest were number of drug injections, sharing of unclean 'works' (injecting equipment), number of unprotected sex partners, and number of unprotected sexual episodes. Data analyses included multiple regression, odds ratios, and quantitative analysis of text-based data.
RESULTS
Subjects reported reductions in both injecting drug use and sexual behavior Primary associations with reduced injecting drug use were remaining in the MMTP and attending HIV-positive support groups. A reduction in high-risk sexual behavior was associated with an HIV-positive test result and duration of HIV counseling in the MMTP. Increase in drug injecting use was associated with an HIV-positive test result. Inconsistent condom use was associated with enrollment in the MMTP where condoms were available only upon request and abstinence and monogamy between uninfected partners were promoted.
CONCLUSIONS
Injecting drug users who self-select to participate in MMTP and HIV C and T, two public health HIV-prevention interventions, reduce their HIV-risk behaviors. Clients should be encouraged to remain in MMTP and HIV-infected clients should attend support groups for HIV-positive persons. MMTP staff should promote a variety of safer sex behaviors and provide condoms without request. | 10.1097/00002030-199702000-00014 |
pubmed_570_21155 | BACKGROUND
During inflammation, the serum concentrations of granulocyte colony stimulating factor (G-CSF), plasma interleukin-6 (IL-6), and C-reactive protein (CRP) increase. A positive correlation between CRP and the percentages of neutrophils exhibiting toxic granulation during inflammation has been demonstrated, and that the fluctuations of CRP and toxic granulation of neutrophils were similar.
OBJECTIVES
We studied whether grading of toxic granulated neutrophils can be used as a surrogate marker for infection or inflammation, and also be an easier method than previously described methods.
MATERIALS AND METHODS
We graded 357 consecutive peripheral blood slides from patients on whom a full blood count with differential count and CRP level was performed, according to intensity of toxic granulation in the neutrophil population, according to a newly proposed grading system.
RESULTS
The CRP range was between 1 and 530.3 mg/l. The results confirm the association between a rise in CRP and progressive intensity of toxic granulation in neutrophils in peripheral blood. Kruskal-Wallis equality of populations rank test showed a statistically significant difference between the graded categories (p=0.0001). The Trend test was also statistically significant (p=0.000).
CONCLUSION
The proposed system can be applied to patients with inflammatory or infectious conditions, where grading of toxic granulation of neutrophils can possibly be used as a surrogate marker to assess infection or inflammation and their response to treatment. It may be of particular use in cases where traditional infectious or inflammatory markers cannot be used, owing to inherent problems associated with the respective conditions. | 10.7196/samj.3912 |
pubmed_196_10343 | PURPOSE
Although pharmacokinetic (PK) interaction effects of methotrexate (MTX) on adalimumab have been found, the mechanism of these effects is still unclear. In this work, effects of MTX on the concentration of neonatal Fc receptor (FcRn) and the role of FcRn in the interaction between MTX and adalimumab were investigated.
METHODS
The experiment was performed in rats whose FcRn had normal physiological function and also in rats whose FcRn was blocked with FcRn antibody. Rats were randomly assigned to receive placebo or 0.2 mg/kg MTX orally every week while taking one abdominal subcutaneous injection of 0.5 mg/kg adalimumab. The FcRn concentration in tissues and the PK parameters of adalimumab were compared between MTX-treated and placebo groups.
RESULTS
In rats with normally functioning FcRn, the concentrations of FcRn were significantly increased in the liver (F=105.5, p=0.000) and kidney (F=996.312, p=0.000) after treatment with MTX, and the clearance (CL/F) of adalimumab was decreased accordingly (F=4.423, p=0.048). However, in rats injected with FcRn antibody, the concentrations of FcRn in MTX-treated rats were close to that of the placebo rats in the tissues of the liver (F=1.279, p=0.268) and kidney (F=0.661, p=0.424). The CL/F of adalimumab in rats was also not affected by MTX (F=0.002, p=0.961).
CONCLUSIONS
FcRn may play a vital role in the interaction between adalimumab and MTX. | 10.1007/s11095-019-2696-2 |
pubmed_896_8759 | Conflict of interest (COI) is a conflict between related parties, such as researchers, research institutions, academic societies, and third parties (commercial companies and patients). COI sometimes twists research and clinical practice, resulting in the profit instruction of related individuals or organizations. In medical research, high ethical standards are demanded to protect human rights, life, and safety of study participants, and COI must be properly enforced to maintain study fairness and ensure transparency. In Japan, the Japanese Association of Medical Science issued COI guideline in 2017, which formed the basis of many societies in making their common COI guidelines. The Japanese Society of Hematology issued COI management guideline in 2018 and is strictly managing COI of its members, organization, and clinical guideline committee members. As industry-academia collaboration activities become more active, the concept of COI is deepening; therefore, appropriate COI disclosure should be conducted based on recent trends to promote sound research and business activities. | 10.11406/rinketsu.62.1349 |
pubmed_866_25652 | Statin-associated muscle symptoms (SAMS) are the most frequent clinically relevant adverse effects of statins causing discontinuation of statin treatment, and subsequent increase in cardiovascular events. The incidence of SAMS in clinical practice is 5-10%. Clinical manifestations of SAMS are highly heterogeneous and range from mild weakness, cramps, and muscle pains to the very rare and severe rhabdomyolysis. The most common type of SAMS (>80%) is muscle pains without or with mild increase in creatine kinase. The management of patients with SAMS is a clinical challenge. A strategic approach involving clinical assessment, patients' reassurance regarding statin safety, and reintroduction of low statin dose (daily or alternate scheme) combined with nonstatins (ezetimibe first and if required, the addition of alirocumab or evolocumab) will allow the majority of them to achieve meaningful low-density lipoprotein-cholesterol reductions. | 10.1016/j.hjc.2019.09.001 |
pubmed_254_6805 | Reaction of the tri(μ-sulfido)triiron(iii) tris(β-diketiminate) cyclophane complex, Fe3S3LEt/Me (1), or of the di(μ-sulfido)diiron(iii) complex Fe2S2HLEt/Me (5), with the related tri(bromide)triiron(ii) complex Fe3Br3LEt/Me (2) results in electron and ligand redistribution to yield the mixed-ligand multiiron complexes, including Fe3Br2SLEt/Me (3) and Fe2Br2SHLEt/Me (4). The cleavage and redistribution observed in these complexes is reminiscent of necessary Fe-S bond cleavage for substrate activation in nitrogenase enzymes, and provides a new perspective on the lability of Fe-S bonds in FeS clusters. | 10.1039/d0dt03805a |
pubmed_752_23197 | PDZ domains are common 80- to 90-amino-acid regions named after the first three proteins discovered to share these domains: postsynaptic density 95, discs large, and zonula occludens. PDZ domain-containing proteins typically interact with the C-terminus of membrane receptors. Glutamate receptor interacting protein 1 (GRIP1), a seven-PDZ domain protein scaffold, regulates glutamate receptor surface expression and trafficking in neurons. We have found that human and mouse T cells also express GRIP1. T cell-specific GRIP1(-/-) mice >11 weeks old had prolonged cardiac allograft survival. Compared with wild-type T cells, in vitro stimulated GRIP1(-/-) T cells had decreased expression of activation markers and increased apoptotic surface marker expression. Surface expression of the strong T cell inhibitory molecule cytotoxic T lymphocyte antigen-4 (CTLA-4) was increased on GRIP1(-/-) T cells from mice >11 weeks old. CTLA-4 increases with T cell stimulation and its surface expression on GRIP1(-/-) T cells remained high after stimulation was removed, indicating a possible internalization defect in GRIP1-deficient T cells. CTLA-4-blocking antibody treatment following heart transplantation led to complete rejection in T cell GRIP1(-/-) mice, indicating that increased CTLA-4 surface expression contributed to the extended graft survival. Our data indicate that GRIP1 regulates T cell activation by regulating CTLA-4 surface expression. | 10.1111/ajt.13623 |
pubmed_633_6484 | In the contemporary world, "race" narratives are so multifaceted that at times, different views of the concept appear mutually incompatible. In recent decades biologists, especially geneticists, have repeatedly stated that the notion of race does not apply to the human species. On the other hand, social scientists claim that race is highly significant in cultural, historical, and socioeconomic terms because it molds everyday social relations and because it is a powerful motivator for social and political movements based on race differences. In this paper we present the results of an interdisciplinary research project incorporating approaches from genetics and anthropology. Our objective is to explore the interface between information about biology/genetics and perceptions about color/ race in Rio de Janeiro, Brazil. We argue that the data and interpretation of our research resonate far beyond the local level, stimulating discussion about methodological, theoretical, and political issues of wider national and international relevance. Topics addressed include the complex terminology of color/race classification in Brazil, perceptions about ancestry in the context of ideologies of Brazilian national identity, and the relationship between genetic information about the Brazilian population and a sociopolitical agenda that turns on questions of race and racism. | 10.1086/644532 |
pubmed_871_16044 | We have studied the equilibrium unfolding and the kinetics of folding and unfolding of an antibody scFv fragment devoid of cis-prolines. An anti-GCN4 scFv fragment carrying a VL lambda domain, obtained by ribosome display, served as the model system together with an engineered destabilized mutant in VH carrying the R66K exchange. Kinetic and equilibrium unfolding experiments indicate that the VH mutation also affects VL unfolding, possibly by partially destabilizing the interface provided by VH, even though the mutation is distant from the interface. Upon folding of the scFv fragment, a kinetic trap is populated whose escape rate is much faster with the more stable VH domain. The formation of the trap can be avoided if refolding is carried out stepwise, with VH folding first. These results show that antibody scFv fragments do not fold by the much faster independent domain folding, but instead form a kinetically trapped off-pathway intermediate, which slows down folding under native conditions. This intermediate is characterized by premature interaction of the unfolded domains, and particularly involving unfolded VH, independent of proline cis-trans isomerization in VL. This work also implies that VH should be a prime target in engineering well behaving antibody fragments. | 10.1016/s0301-4622(02)00022-4 |
pubmed_106_20597 | Surgical clipping has been considered for years a "golden standard" in the treatment of middle cerebral artery (MCA) aneurysms. The recent development of materials and endovascular techniques has permitted the use of embolization for the treatment of intracranial aneurysms regardless of their locations and size. In 30 patients with 32 MCA aneurysms (group I) the endovascular approach with GDC-10 coils was used, while in other 30 patients with 31 aneurysms (group II) surgical clipping was performed. On completion of the diagnostic process the patients were randomly assigned either to the endovascular or microsurgical treatment. Group I: 21 (70%) embolization procedures were carried out, while in 9 (30%) cases with 10 aneurysms embolisation was impossible or regarded as too risky due to various causes. The total occlusion of aneurysm SAC was achieved in 17 (77%) aneurysms, subtotal in 5 (23%). The morbidity rate was 8%, mortality-0%. Group II: Microsurgical clipping was performed in 27 (90%) cases, 3 (10%) patients were disqualified from treatment due to their poor clinical status. An excellent technical result was achieved in 24 (86%) patients, in 4 (14%) cases the neck remnant was observed in control angiography. The morbidity rate was 14%, mortality-0%. | pubmed_106_20597 |
pubmed_46_20401 | BACKGROUND
There are few clinical studies on late follow-up of the Omnicarbon monoleaflet valve. We report our 10-year experience with this valve in the aortic position and also compare late hemodynamic performance of this valve with that of the CarboMedics valve in the aortic position.
METHODS
From January 1985 to June 1995, 117 consecutive patients underwent aortic valve replacement (AVR) with the Omnicarbon valve. There were 66 men and 51 women aged 13 to 69 years (mean age, 50 +/- 12 years). They were divided into three groups: group 1 (43 patients) had isolated AVR, group 2 (36) had AVR and concomitant operations, and group 3 (38) had combined AVR and mitral valve replacement. Follow-up was 96.6% complete and consisted of 882.7 patient-years (range, 2.5 to 10.6 years; mean follow-up, 7.5 +/- 2.7 years).
RESULTS
There were three early deaths (2.6%) and 18 late deaths (2.0%/patient-year) ten of which were due to valve-related causes and eight, non-valve-related causes. Survival rates at 10 years in groups 1, 2, and 3 were 77.6%, 82.4%, and 78.6%, respectively. The overall rates of freedom from valve-related complications in groups 1, 2, and 3 at 10 years were 77.4%, 100%, and 80.9%, respectively. The rates of freedom from the following complications in groups 1, 2, and 3 at 10 years were as follows: thromboembolism--94.8%, 100%, and 89.4%, respectively; valvar thrombosis--95.0%, 100%, and 100%; anticoagulant-related hemorrhage--93.6%, 100%, and 93.4%; prosthetic valve endocarditis--93.0%, 100%, and 97.2%; and reoperation--90.6%, 100%, and 97.2%. There were no significant differences between groups. All survivors showed marked improvement in New York Heart Association functional class, from 86% in classes III and IV preoperatively to 96% in classes I and II postoperatively. The Omnicarbon valve exhibited no significant difference in hemodynamic performance after isolated AVR compared with the CarboMedics bileaflet valve at the same follow-up periods.
CONCLUSIONS
This 10-year study confirms that the Omnicarbon valve is a durable prosthesis and provides excellent functional improvement with low rates of thromboembolism and valvar thrombosis in the aortic position. | 10.1016/0003-4975(96)00007-0 |
pubmed_305_21343 | Nanofibers with the cationic fluorescent molecules, 1-pyrenemethylamine hydrochloride (PyrMA) and α,β,γ,δ-tetrakis(1-methylpyridinium-4-yl)porphyrin p-toluenesulfonate (TMPyP), in the presence of complementary anionic chiral polysaccharide, hyaluronic acid (HA) and transparent polymer, polyethylene oxide (PEO) were successfully prepared using an electrospinning technique. The results showed that the fluorescence spectra of electrospun nanofibers (ENFs) of PEO-HA-PyrMA exhibit a higher amount of pyrene excimer emission when the [PyrMA]/[HA] ratio was increased from 0.5 to 1, while the concentration of TMPyP had no remarkable effect on the fluorescence of the PEO-HA-TMPyP ENFs. From circular dichroism (CD) characterization, the ENFs of both dyes exhibit stronger intensities in the apparent CD spectra upon increasing the dye ratio. Moreover, they also showed higher CD intensities when compared with those of solutions and thin films prepared using other methods. The apparent CD in this work was proved to mainly originate from linear dichroism (LD) and linear birefringence (LB) obtained by macroscopic alignment along the electrospinning process. These results suggest the advantages of molecular orientation via electrospinning, together with chirality induction by incorporation of a chiral HA polymer. The enhancement of these polarization properties provides great possibilities for improving fluorescent-chiral nanofibers for further optoelectronic applications. | 10.1039/c7pp00413c |
pubmed_447_3859 | Thirteen- and 52-week oral toxicity studies of Z-103 (catena-(S)-[mu- [N alpha-(3-aminopropionyl) histidinato (2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) were carried out in rats. In a 13-week repeated dose toxicity study (37.5, 75, 150, 300, 600 or 1200 mg/kg/d), deterioration of the general condition was observed at 300 mg/kg/d or more, a decrease in body weight gain at 600 mg/kg/d or more. Approximately 40% of the animals were found dead or sacrificed in a moribund state at 1200 mg/kg/d. Furthermore, in the 600 mg/kg group changes in urine volume, blood urea nitrogen and weight of kidneys were observed, suggesting that Z-103 may have had adverse effects on the kidney. No sex difference was noted. From these results the no-effect dose level was estimated to be 150 mg/kg/d under the conditions of this experiment. In a 52-week repeated dose toxicity study (18.75, 37.5, 75 or 150 mg/kg/d), proliferation of small duct and atrophy of acinar cells in the pancreas were observed in both sexes of the 150 mg/kg/d group. No other dose-related changes were observed throughout the administration period. Therefore, the no-effect dose level was estimated to be 75 mg/kg/d under this condition. | pubmed_447_3859 |
pubmed_225_10538 | HPLC analysis of guanidinium hydrochloride extracts of neonatal and adult rat brain revealed a polypeptide that is present in high concentration in the immature nervous system, but whose levels decline dramatically in the adult. This polypeptide has been isolated and its complete amino acid sequence determined by gas-phase Edman degradation following specific chemical and enzymatic cleavages. The molecule is identified as thymosin beta 10, a member of a multigene family that encodes a structurally conserved series of small acidic polypeptides of uncertain function. Thymosin beta 10 is present in the developing nervous system as early as embryonic day 9. Levels subsequently increase to peak values between embryonic day 15 and postpartum day 3, before falling to adult values (about a 20-fold reduction) by postpartum day 14. The elevated levels of thymosin beta 10 in fetal and neonatal brain correlate with high levels of thymosin beta 10 mRNA, whereas the low values of the polypeptide in the adult and juvenile are mirrored by an approximate 15-fold reduction in specific mRNA. In comparison, the levels of thymosin beta 4 polypeptide, a homologue of thymosin beta 10, only decline by about 20% during the same developmental period. However, the mRNA encoding thymosin beta 4 is elevated in fetal brain, and its levels decrease approximately four-fold to a stable value around the time of birth. The reason for this discrepancy between thymosin beta 4 protein and mRNA levels is unknown. Thymosin beta 10 can also be detected by HPLC in fetal liver, where levels are approximately 5% of those in brain. In liver, thymosin beta 10 also declines following birth. It is concluded that beta-thymosin expression (as measured by steady-state mRNA and polypeptide levels) is both up- and down-regulated during different phases of maturation of the mammalian nervous system. | 10.1111/j.1471-4159.1991.tb08172.x |
pubmed_307_16027 | In the last 10 years, rising rates of obesity in the United States have drawn significant and increasing public attention from various quarters, which has led to commensurately increased news coverage of the issue. A handful of scholars to date have examined how obesity has been "framed" in the news, given that news framing of issues has proven effects on cultural and political attitudes, practices, and policies as regards the subject of coverage. Consistent with these studies, this qualitative framing analysis assesses how obesity is framed in more recent mainstream news coverage. Framing patterns identified in this analysis represent a notable departure from those identified in earlier studies, specifically as relevant to troubling the individual/environmental attribution binary that historically has characterized public discourse around obesity, in particular, and health more broadly. These findings signal important shifts for contemporary cultural attitudes toward obesity and, accordingly, public health policies designed to redress the issue. Further, the findings suggest a reconsideration and elaboration of established tenets of framing theory. | 10.1080/10410236.2011.561833 |
pubmed_585_6463 | PURPOSE
Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays.
METHODS AND MATERIALS
Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays.
RESULTS
Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO(2)-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ß-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function.
CONCLUSIONS
The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation. | 10.1016/j.ijrobp.2011.12.003 |
pubmed_234_1321 | In order to determine the frequency of neck vessel injuries, Doppler investigations were performed in 60 patients following either severe head injury (n = 29), cervical spine injury (n = 26), or combined head and cervical spine injury (n = 5). The majority of patients were referred to our hospital for early rehabilitation; before admission Doppler investigations had been performed in only 2 patients. Clinically, 3 patients sustained severe cerebral ischemia due to neck vessel trauma: 1 patient with left-sided ICA dissection after head trauma revealed Doppler abnormalities only in the early phase of the disease; the second patient demonstrated persistent Doppler abnormalities due to traumatic right-sided ICA and VA occlusion. The third patient sustained a fatal vertebral and basilar artery thrombosis following cervical spine injury. In 57 patients without clinical signs suspicious of neck vessel trauma, sonography revealed abnormalities in 3 patients (11%) with severe head injury and in 6 patients (20%) with cervical spine or combined head and spine injury, in both groups mainly related to the vertebrobasilar system. Neck vessel injury is probably an underdiagnosed complication of severe head or cervical spine trauma. Although interpretation of Doppler findings may be difficult, particularly in the vertebrobasilar system, Doppler investigations can be recommended as a screening method to exclude neck vessel injuries. | 10.1159/000015956 |
pubmed_2_24992 | BACKGROUND
Fetal exposure to maternal diabetes mellitus (DM) is associated with high birth weight, congenital heart malformations, childhood adiposity, DM, hypertension and dyslipidemia. The long term cardiovascular consequences of fetal exposure to maternal DM during pregnancy and high birth weight are not known.
METHOD
All individuals born in Sweden 1973-1988 (n = 1,551,603) were included in the study. The Swedish Medical Birth Register was merged with the Swedish Prescribed Drug Register. The association between offspring's adult consumption of cardiovascular medication and i) maternal DM during pregnancy and ii) birth weight were analyzed. Follow up time ranged between 17 and 36 years.
RESULTS
Offspring exposed to maternal DM in utero had an increased risk of non-malformation cardiovascular disease (NMCVD), odds ratio (OR) 1.46 (95% confidence interval (CI) 1.16-1.83). After also excluding offspring with insulin dependent DM, no increased risk of NMCVD was found, OR 1.19 (95% CI 0.92-1.55). No increased risk of NMCVD was found in offspring born large for gestational age, OR 1.02 (95% CI 0.96-1.08). An increased risk of NMCVD was found in offspring born small for gestational age, OR 1.29 (95% CI 1.24-1.35).
CONCLUSIONS
Exposure to maternal DM during pregnancy was not associated with NMCVD in offspring at a maximum of 36 years of follow up. Low birth weight was confirmed to be a risk factor for NMCVD while high birth weight was not. | pubmed_2_24992 |
pubmed_1029_14848 | Since 1984, a new method for intra-arterial administration of anti-cancer drug and radiosensitizer, named 'superselective continuous intra-arterial infusion therapy' has been used in combination with simultaneous irradiation, for the treatment of 67 patients with the head and neck tumors. Under fluoroscopy, a preshaped catheter was introduced retrogradely from the superficial temporal artery and inserted superselectively into the main feeding artery of the tumor. Through this catheter, continuous intra-arterial infusion chemotherapy was done. The primary therapeutic effects were appreciated as complete or partial response in all cases. It was considered that this method was more effective and with less adverse reactions for the treatment of the head and neck tumors compared with the conventional method. | pubmed_1029_14848 |
pubmed_49_11821 | The regulation of glucose transport in normal and insulin-resistant obese rat hearts have been studied by measuring glucose transport via the efflux of labelled 3-0-methyl-D-glucose. Glucose transporters in obese rat hearts were also investigated using the labelled cytochalasin B-binding assay. Basal, and insulin- or increasing workload-induced stimulation of glucose transport was decreased in obese rat hearts compared to those of normal ones. Total number of glucose transporters (plasma membrane plus microsomal ones) was about half that previously reported for normal rat hearts. Insulin or workload favoured the translocation of glucose transporters from an intercellular pool (microsomes) to the plasma membrane, as they do in normal rats. Due to the measured decrease in total number of transporters of obese rat hearts, those present in the plasma membrane (under basal conditions, or following stimulation by insulin or workload) were less than those previously found in normal rat hearts tested under identical conditions. In obese rat hearts, regulation of plasma membrane transporters was perturbed. The Hill coefficient (an index of positive cooperativity amongst glucose transporters) was paradoxically decreased by insulin while leaving affinity values unaltered. The Hill coefficient was unaltered by workload, although the affinity values were increased compared to respective controls. To sum up, obese rat hearts have decreased total transporter number, and although the two stimuli studied favour the translocation of available transporters, they fail to "activate" them adequately once present in the plasma membrane. | 10.1007/BF00265405 |
pubmed_173_12809 | Non-Hodgkin lymphomas encompass a heterogeneous group of cancers, with 85-90% arising from B lymphocytes and the remainder deriving from T lymphocytes or NK lymphocytes. These tumors are molecularly and clinically heterogeneous, showing dramatically different responses and outcomes with standard therapies. Deregulated PI3K signaling is linked to oncogenesis and disease progression in hematologic malignancies and in a variety of solid tumors and apparently enhances resistance to antineoplastic therapy, resulting in a poor prognosis. Here, we have evaluated and compared the effects of the pan-PI3K inhibitor BKM120 and the dual PI3K/mTOR inhibitor BEZ235 on mantle, follicular, and T-cell lymphomas. Our results suggest that BKM120 and BEZ235 can effectively inhibit lymphoma cell proliferation by causing cell cycle arrest and can lead to cell death by inducing apoptosis and autophagy mediated by ROS accumulation. Despite great advances in lymphoma therapy after the introduction of monoclonal antibodies, many patients still die from disease progression. Therefore, novel treatment approaches are needed. BKM120 and BEZ235 alone and in combination are very effective against lymphoma cells in vitro. If further studies confirm their effectiveness in animal models, they may be promising candidates for development as new drugs. | 10.1155/2015/870918 |
pubmed_580_18248 | Polymerized ionic liquid (PIL) nanoparticles are for the first time applied as sole stabilizers in aqueous emulsion polymerization and reveal an astonishing and unexpected behavior. In a well-dispersed state, the PIL nanoparticles serve as an unexpectedly effective stabilizer for polystyrene dispersions, enabling solids content of greater than 40%. However, the same PIL as dry powder is hydrophobic and, in accordance with Bancroft's rule, unable to stabilize aqueous dispersions. This ambivalent behavior of PIL is extremely beneficial for the application of aqueous dispersions because, as desired for decades, the hydrophilic dispersed state during synthesis turns hydrophobic in the dried state during application of the polymer. | 10.1002/marc.201200827 |
pubmed_750_15752 | The association between cystatin C and depressive symptoms in the general population has not been thoroughly elucidated to date. We investigated the association of cystatin C with new-onset depressive symptoms among individuals with normal creatinine-based estimated glomerular filtration rates (eGFR). In the China Health and Retirement Longitudinal Study, 5111 participants without depressive symptoms or renal dysfunction (eGFR < 60 ml/min/1.73 m2) were included. The outcome was new-onset depressive symptoms over 4 years, defined as a score of ≥12 on the 10-item Center for Epidemiologic Studies Depressive Symptoms Scale. The incidence risk ratio (IRR) and 95% confidence interval (CI) were calculated using modified Poisson regression models. During a 4-year follow-up period, 1746 (34.16%) incidents of depressive symptoms occurred. In a multivariable-adjusted model, the risk of incident depressive symptoms was 1.07 (95% CI 1.02-1.11) per-SD change in cystatin C. A greater cystatin C level was associated with a higher risk of new-onset depressive symptoms among subjects with relatively normal renal function. | 10.1016/j.psychres.2019.01.009 |
pubmed_740_20998 | We investigated the discrepancy between competence and real-world performance in major depressive disorder (MDD) for adaptive and interpersonal behaviors, determining whether self-efficacy significantly predicts this discrepancy, after considering depressive symptoms. Forty-two participants (Mage = 37.64, 66.67% female) with MDD were recruited from mental health clinics. Competence, self-efficacy, and real-world functioning were evaluated in adaptive and interpersonal domains; depressive symptoms were assessed with the Beck Depression Inventory II. Hierarchical regression analysis identified predictors of functional disability and the discrepancy between competence and real-world functioning. Self-efficacy significantly predicted functioning in the adaptive and interpersonal domains over and above depressive symptoms. Interpersonal self-efficacy accounted for significant variance in the discrepancy between interpersonal competence and functioning beyond symptoms. Using a multilevel, multidimensional approach, we provide the first data regarding relationships among competence, functioning, and self-efficacy in MDD. Self-efficacy plays an important role in deployment of functional skills in everyday life for individuals with MDD. | 10.1097/NMD.0000000000000804 |
pubmed_559_13088 | Mathematical models for the population dynamics of de novo resistant Mycobacterium tuberculosis within individuals are studied. The models address the use of one or two antimicrobial drugs for treating latent tuberculosis (TB). They consider the effect of varying individual immune response strength on the dynamics for the appearance of resistant bacteria. From the analysis of the models, equilibria and local stabilities are determined. For assessing temporal dynamics and global stability for sensitive and drug-resistant bacteria, numerical simulations are used. Results indicate that for a low bacteria load that is characteristic of latent TB and for small reduction in an immune response, the use of a single drug is capable of curing the infection before the appearance of drug resistance. However, for severe immune deficiency, the use of two drugs will provide a larger time period before the emergence of resistance. Therefore, in this case, two-drugs treatment will be more efficient in controlling the infection. | 10.1093/imammb/dql026 |
pubmed_1072_4152 | BACKGROUND
Berry juices are a rich source of phenolic compounds exhibiting antioxidant activity. Unfortu- nately, polyphenols and especially anthocyanins are degraded during storage.
METHODS
The levels of total phenolic compounds, phenolic acids, flavonoids, and antho- cyanins as well as antioxidant activity (radical scavenging ability against DPPH and ABTS+• and chelating power Fe2+) were determined in raspberry juices (obtained after enzymatic treatment with three commercial pectinolytic enzyme preparations) and syrups (obtained by the addition of sucrose at concentrations of 30% and 70%) during storage.
RESULTS
During the five-month storage of juices and syrups at room temperature, there was significant re- duction in the level of phenolic compounds, in particular anthocyanins (up to 95% in relation to the initial content). Storage of raspberry juices and syrups also resulted in a reduction in antioxidant activity.
CONCLUSIONS
The enzymatic treatment of the raspberry mash generally increased the losses of anthocyanins. The addition of sugar to fruit juices only slightly reduced these losses. | 10.17306/J.AFS.0491 |
pubmed_178_16379 | The cellular tumor antigen p53 was isolated from mouse neuroblastoma cells and was found in a form not complexed to another protein. The p53 in these cells was stable, turning over about every 10 h. Its methionine-labelled tryptic peptides were very similar to those of the p53 isolated from SV40-transformed mouse cells. The labelled protein was purified from neuroblastoma cells by immunoaffinity using specific monoclonal antibodies and was about 80% radiochemically pure. Furthermore, the purified p53 sedimented in sucrose gradients with a sedimentation coefficient of approximately 8S. This correlated with the sedimentation coefficient of p53 prior to purification, showing that the purified protein retained its native size. | 10.1002/ijc.2910320513 |
pubmed_97_9088 | Surfactant is a lipoprotein complex which reduces alveolar surface tension, thus reducing the work of respiration. Defective secretion of surfactant in the premature newborn infant gives rise to the respiratory distress syndrome (RDS). Several surfactant preparations, natural (purified) and synthetic, have been evolved. They have been used for prophylaxis and also therapy. Several controlled studies have shown decreased mortality, while the effect on neonatal complications and late results are still uncertain. | pubmed_97_9088 |
pubmed_680_19554 | Decades of political turmoil and stifling war, among other issues, has turned Afghanistan into the world's largest humanitarian crisis. Just 4 months after the Taliban seized control, the majority of the Afghan population face starvation, with >3.3 million children unable to afford basic food resources, leading to dozens of deaths every week. Restrictions on humanitarian assistance, withholding of vital food supplies and inadequate medical care play a major role in exacerbating the rates of malnutrition in the vulnerable paediatric population. Global interference is warranted to avoid unfathomable consequences in mitigating this public health catastrophe. | 10.1093/inthealth/ihac055 |
pubmed_71_5165 | Recently, a rigorous mathematical theory has been developed for spatial games with weak selection, i.e., when the payoff differences between strategies are small. The key to the analysis is that when space and time are suitably rescaled, the spatial model converges to the solution of a partial differential equation (PDE). This approach can be used to analyze all [Formula: see text] games, but there are a number of [Formula: see text] games for which the behavior of the limiting PDE is not known. In this paper, we give rules for determining the behavior of a large class of [Formula: see text] games and check their validity using simulation. In words, the effect of space is equivalent to making changes in the payoff matrix, and once this is done, the behavior of the spatial game can be predicted from the behavior of the replicator equation for the modified game. We say predicted here because in some cases the behavior of the spatial game is different from that of the replicator equation for the modified game. For example, if a rock-paper-scissors game has a replicator equation that spirals out to the boundary, space stabilizes the system and produces an equilibrium. | 10.1073/pnas.1620852114 |
pubmed_367_8316 | A highly methylated genome, like a somatic donor cell, is observed in somatic cell nuclear transfer (SCNT) embryos. The aberrant DNA methylation status causes global gene expression failure, resulting in low developmental competence of SCNT embryos. In addition, recent studies have uncovered the relationship between DNA methylation status and reprogramming efficiency. Because DNA methylation is performed by DNA methyltransferases (DNMTs), developing a technique which specifically inhibits DNMTs is necessary for further SCNT studies. In the present study, we examined the potential use of RNA interference for knockdown of DNMT mRNA in bovine fibroblast cells that were commonly used as karyoplast donors in SCNT studies. We designed three siRNAs corresponding to DNMT1, DNMT2 and DNMT3a mRNA. In Experiment 1, to optimize transfection conditions, fluorescence and cell viability after transfection were evaluated at different concentrations of transfection reagent using a FITC-labeled nonsilencing control siRNA. Although fluorescence was observed in all groups transfected except for the negative control group, transfection with a higher concentration of transfection reagent significantly decreased in cell viability (P<0.05). In Experiment 2, the amount of DNMT mRNA was measured by real-time PCR at 0, 48 and 96 h after siRNA transfection into the cells. The levels of each DNMT mRNA were significantly decreased at 48 and 96 h after transfection (P<0.01). Furthermore, decreased expression of DNMT1 protein was confirmed by western blotting. In Experiment 3, the DNA methylation statuses were analyzed in each of the siRNA-transfected groups. The DNMT1 siRNA-transfected group had a significantly decreased level of DNA methylation (P<0.05), but the other groups did not. Our data demonstrate that RNA interference with siRNA can be analyzed the function and expression of DNMT genes in bovine fibroblast cells. The present study provides useful information for further SCNT studies. | 10.1262/jrd.09-105a |
pubmed_798_10513 | In this study, a molecularly imprinted functionalized polymer for the selective separation of ractopamine (RAC) was prepared by combining a surface molecular imprinting technique with a sol-gel method process. The polymer was evaluated by static, kinetic adsorption, and selective experiments. Results indicated that the molecularly imprinted polymer had high adsorption capacity, selective ability, and fast mass transfer rate. The polymer was applied for the determination of trace RAC through online SPE-HPLC. With a sample loading flow rate of 2 mL/min, the enhancement factor of 516.26 and the LOD (S/N = 3) of 4.6 ng/L were achieved, respectively, and the linear range of the calibration curve was 0.04-18 microg/L with r(2) >0.99. The RAC in pork was determined at three spiked levels (0.5, 1, and 2 ng/g) with recoveries ranging from 55.86 to 67.28%. | 10.1002/jssc.200800565 |
pubmed_159_20439 | Electrowinning is a technique that can be used to obtain high-purity elements through electrolysis. The degradation of accelerated life testing for Pd-based electrodes is discussed in this study. The lifetime of the electrodes was examined by multiplying the acceleration rate with the current to measure the voltage of the electrodes. The acceleration rate was set to 10, 20, and 30 times. Four components were deposited on the TiO2 plate. The ratio of Ir to Sn was fixed at 1:1, while Ta was deposited at 10 wt.%. Pd was deposited at 2, 4, 8 and 10 wt.% to create Pd-Ir/Sn-Ta. The initial voltage decreased as the Pd deposition amount increased irrespective of the acceleration rate. The lower the acceleration rate, the lower the voltage. An increase in the Pd content caused the initial voltage to be low. The multiple of the acceleration rate slightly increased for all cases of life testing for one year. When the test was conducted by increasing the current density by 20 times, the increase in voltage was proportional to the Pd deposition amount. However, for the 30 times acceleration rate, the lifetime of the electrodes was shortened as the Pd content increased. It can be inferred that the content of Pd and the ratio of Ir to Sn can influence the lifetime of the electrodes. According to these results, if the multiple of the acceleration rate is too extreme, the lifetime of the electrodes cannot be evaluated because they are damaged in an extreme situation. | 10.3390/ma13081969 |
pubmed_251_2998 | BACKGROUND
The light-harvesting complexes II (LH-2s) are integral membrane proteins that form ring-like structures, oligomers of alpha beta-heterodimers, in the photosynthetic membranes of purple bacteria. They contain a large number of chromophores organized optimally for light absorption and rapid light energy migration. Recently, the structure of the nonameric LH-2 of Rhodopseudomonas acidophila has been determined; we report here the crystal structure of the octameric LH-2 from Rhodospirillum molischianum. The unveiling of similarities and differences in the architecture of these proteins may provide valuable insight into the efficient energy transfer mechanisms of bacterial photosynthesis.
RESULTS
The crystal structure of LH-2 from Rs. molischianum has been determined by molecular replacement at 2.4 A resolution using X-ray diffraction. The crystal structure displays two concentric cylinders of sixteen membrane-spanning helical subunits, containing two rings of bacteriochlorophyll-a (BChl-a) molecules. One ring comprises sixteen B850 BChl-as perpendicular to the membrane plane and the other eight B800 BChl-as that are nearly parallel to the membrane plane; eight membrane-spanning lycopenes (the major carotenoid in this complex) stretch out between the B800 and B850 BChl-as. The B800 BChl-as exhibit a different ligation from that of Rps. acidophila (aspartate is the Mg ligand as opposed to formyl-methionine in Rps. acidophila).
CONCLUSIONS
The light-harvesting complexes from different bacteria assume various ring sizes. In LH-2 of Rs. molischianum, the Qy transition dipole moments of neighbouring B850 and B800 BChl-as are nearly parallel to each other, that is, they are optimally aligned for Föster exciton transfer. Dexter energy transfer between these chlorophylls is also possible through interactions mediated by lycopenes and B850 BChl-a phytyl tails; the B800 BChl-a and one of the two B850 BChl-as associated with each heterodimeric unit are in van der Waals distance to a lycopene, such that singlet and triplet energy transfer between lycopene and the BChl-as can occur by the Dexter mechanism. The ring structure of the B850 BChl-as is optimal for light energy transfer in that it samples all spatial absorption and emission characteristics and places all oscillator strength into energetically low lying, thermally accessible exciton states. | 10.1016/s0969-2126(96)00063-9 |
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