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Follicular dendritic cell sarcoma (FDCS) is a rare and unusual cancer that arises from sustentacular cells of the lymph node that present antigen to B cells, rather than lymphocytes themselves. While surgery for primary disease is still paramount in primary management, for unresectable, recurrent and metastatic tumours, FDCS is frequently treated with anthracycline-based lymphoma chemotherapy regimens. In recent years, it is clear that Programmed Cell Death 1 (PD1)-directed immune checkpoint inhibitors (ICIs) are active in Hodgkin lymphoma, but significantly less active in non-Hodgkin's lymphoma. These data raised the question of whether FDCS respond to ICI therapy. We present two patients with FDCS who were treated with nivolumab and ipilimumab with evidence of tumour response. These cases also highlight the difficulty in arriving at a proper diagnosis, emphasising the need for expert review of pathology to optimise treatment for these and other patients with sarcoma." | Dendritic Cell Sarcoma, Follicular |
The naked core of bacteriophage T4 was isolated ex vivo after cross-linking with either glutaraldehyde or dithiobis(succinimidyl propionate). The isolated particles appeared to be morphologically identical to the cores found in thin sections, to those demonstrated in in situ lysis preparations, and to core structures assembled in vitro. Treatment with glutaraldehyde provided core particles which were morphologically well preserved, whereas dithiobis(succinimidyl propionate)-induced cross-linking was reversible and allowed analysis of the protein composition of the isolated particles. The identity of the reversibly cross-linked particles with those obtained after irreversible cross-linking was suggested by their morphology and their similar sedimentation behavior. Immunolabeling confirmed the structural presence of the main core protein in both structures. Gel electrophoresis of reversibly cross-linked cores revealed the essential head proteins gp22, gp67, and gp21, the three internal proteins IPI, IPII, and IPIII, and a 17K protein. | T-Phages |
Travertines, which precipitate from high temperature water saturated with calcium carbonate, are generally considered to be dominated by physico-chemical and microbial precipitates. Here, as an additional influence on organomineral formation, metagenomic data and microscopic analyses clearly demonstrate that highly diverse viral, bacterial and archaeal communities occur in the biofilms associated with several modern classic travertine sites in Europe and Asia, along with virus-like particles. Metagenomic analysis reveals that bacteriophages (bacterial viruses) containing icosahedral capsids and belonging to the Siphoviridae, Myoviridae and Podoviridae families are the most abundant of all viral strains, although the bacteriophage distribution does vary across the sampling sites. Icosahedral shapes of capsids are also the most frequently observed under the microscope, occurring as non-mineralized through to mineralized viruses and virus-like particles. Viruses are initially mineralized by Ca-Si amorphous precipitates with subordinate Mg and Al contents; these then alter to nanospheroids composed of Ca carbonate with minor silicate 80-300 nm in diameter. Understanding the roles of bacteriophages in modern carbonate-saturated settings and related organomineralization processes is critical for their broader inclusion in the geological record and ecosystem models. | Archaeal Viruses |
A 64-y-old female previously treated for lung fluke presented with shortness of breath and moderate left pleural effusion. Thoracentesis was performed and milky pleural effusion was obtained. Paragonimus ova and rhomboidal cholesterol crystals were found. Paragonimiasis was diagnosed, and the patient was treated with praziquantel 25 mg/kg/d. | Paragonimiasis |
Spontaneously hypertensive rats (SHR) were found to learn a visual discrimination paradigm better than Wistar normotensive rats (NT). The present analysis of choice strategies used by rats was performed to detect possible correlates between patterns of responding and duration of learning. The following strategies were included into the analysis: perseveration and alternation of choice (response-set hypotheses), win-stay lose-shift and win-shift lose-stay (prediction hypotheses). A computer programme called The Thinking Rat" was written to analyse rat strategies during the learning. The analysis was applied for two irrelevant dimensions of stimuli, i.e. position and orientation, and for colour as a relevant cue. SHR solved the task using different strategies than the NT rats. All subjects began by responding to position as a cue, but SHR gave up this strategy more quickly than NT rats did and responded earlier to colour. NT rats showed a strong preference to persevere in their choices with respect to stimulus position, whereas SHR used more frequently the prediction hypotheses with respect to colour. The analysis of performance and the analysis of choice strategies-could indicate that the discrepancy in learning between SHR and NT rats may be caused by differences in attention." | Rats, Inbred SHR |
The purpose of this study was to determine whether high intensity, long-term aerobic training causes the left ventricle to develop different mechanisms for increasing cardiac output during submaximal and maximal upright bicycle exercise. Fifteen competitive collegiate long distance runners and 14 healthy sedentary adults were studied with use of subcostal view four chamber two-dimensional echocardiography at rest and during and at peak maximal upright bicycle exercise. At rest, the athletes had a larger end-diastolic volume index (85 +/- 14 ml/m2) (mean +/- 1 SD) than that of the sedentary adults (62 +/- 14 ml/m2) and a larger end-systolic volume index (37 +/- 11 versus 21 +/- 6 ml/m2). During low and moderate intensity exercise, end-diastolic and stroke volume indexes increased in both groups, but at high intensity exercise and at peak exercise the end-diastolic volume index of both groups decreased significantly below rest value (athletes, 61 +/- 14; sedentary subjects, 46 +/- 10 ml/m2, both p less than 0.001 compared with rest). Reflecting the decreased end-diastolic volume index, at peak exercise, the stroke volume index had decreased from intermediate exercise values in both groups and was not different from rest values. Therefore, although long distance runners have a dilated left ventricle at rest, they utilize the same mechanisms as sedentary adults for increasing cardiac output during upright dynamic exercise. At low and moderate level exercise, the Frank-Starling mechanism is a dominant mechanism for increasing cardiac output, but at peak exercise, probably because of reduced diastolic left ventricular filling, enhanced contractility is the major mechanism for maintaining stroke volume. | Heart Function Tests |
A review has been made of the advances in knowledge on the treatment of tapeworm infections of man and animals from the time of the introduction to dichlorophen in 1956. This opened up the era of out-patient treatment for human tapeworm infections. The drugs studied have been compared, where possible, on the basis of estimates of the single dose ED90 or the number of treatments required to reach that efficacy at safe dose levels. During the period under review, niclosamide, introduced in 1960 has been regarded as the drug of choice for the treatment of human tapeworm infections with paromomycin as a possible alternative. The bunamidine salts, introduced in 1966 permitted the treatment of Echinococcus spp in dogs. Several treatments were required to achieve acceptable efficacy. In 1975 praziquantel was introduced and based on the ED90, a single dose at no more than 10mg/kg removed all tapeworms responsible for the cestode zoonoses and for which data are available with the exception of H. nana and D. latum; these require a higher dose rate. In the mid 1970s, several benzimidazoles and praziquantel were shown to have activity against metacestodes. This has opened up a new field of research promising a practical outcome. No progress has been made during the period under review in finding effective ovicides. | Antiplatyhelmintic Agents |
Definition of targets for vector control requires an understanding of the relationship between vector abundance and the intensity of arbovirus transmission. Using an extensive surveillance dataset with observations from sentinel chicken flocks and mosquito traps paired in time and space, hierarchical autoregressive logistic regression models were developed to predict the probability of seroconversion in chickens for western equine encephalomyelitis virus (WEEV) based on the relative abundance of the principal vector, Culex tarsalis. After adjustments for confounders, the abundance of Cx. tarsalis 29-42 d before the date of chicken sampling was credibly associated with the risk of WEEV transmission in both the Central and Coachella Valleys, and a doubling of relative Cx. tarsalis abundance was associated with a 58% increase in the odds of seroconversion. The critical time windows identified in our study highlight the need for surveillance of vector populations and forecasting models to guide proactive vector control measures before the detection of transmission to sentinel chickens." | Encephalomyelitis, Western Equine |
The ascarids, Toxocara canis and Toxascaris leonina, are probably the most common gastrointestinal helminths encountered in dogs. In order to understand biological differences of 2 ascarids, we analyzed gene expression profiles of female adults of T. canis and T. leonina using CLC Genomics Workbench, and the results were compared with those of free-living nematode Caenorhabditis elegans. A total of 2,880 and 7,949 ESTs were collected from T. leonina and T. canis, respectively. The length of ESTs ranged from 106 to 4,637 bp with an average insert size of 820 bp. Overall, our results showed that most functional gene annotations of 2 ascarids were quite similar to each other in 3 major categories, i.e., cellular component, biological process, and molecular function. Although some different transcript expression categories were found, the distance was short and it was not enough to explain their different lifestyles. However, we found distinguished transcript differences between ascarid parasites and free-living nematodes. Understanding evolutionary genetic changes might be helpful for studies of the lifestyle and evolution of parasites. | Toxascariasis |
Although each case must be considered individually, there are several basic principles of management in cases of solitary pulmonary nodules: Every nodule must be regarded as potentially malignant until proven otherwise. Malignant nodules should be resected unless the procedure is contraindicated because of an unacceptably high surgical risk or evidence of metastasis. Resection of a benign nodule rarely benefits the patient and carries a small but significant mortality risk. Ruling out malignancy by less-invasive means than thoracotomy is desirable wherever possible. A management decision should be reached with reasonable promptness once a solitary pulmonary nodule has been detected. Under certain circumstances, a decision to observe the nodule for a period of time with serial chest films may be appropriate, but this must be a considered approach and not a default" position." | Solitary Pulmonary Nodule |
The aim of this study was to develop nanostructured lipid carriers (NLCs) for transdermal delivery of acid-labile lansoprazole (LPZ). The drug loading, particle size, zeta potential, thermal behavior and stability of NLCs were evaluated. The particle size of NLCs was in the range of 90-210nm and the zeta potential was -61.9 to +3.2mV dependent of the compositions. Stearylamine (SA) prevented lansoprazole degradation and maintained drug stable in NLCs. The anionic sodium dodecyl sulfate (SDS) adsorbed on the lipid surface and formed complex with cationic SA to prevent NLCs aggregation. The effects of type (e.g., isopropyl myristate (IPM), menthol) and concentration (e.g., 1.25, 2.50, 3.75%w/w) of enhancers on penetration of lansoprazole NLC hydrogels were investigated in vitro using Wistar rat skin. The steady-state flux of lansoprazole NLC hydrogel containing 3.75% IPM was the highest which was enhanced by 2.7 folds as compared to enhancer-free NLC hydrogel. In vivo pharmacokinetics of lansoprazole following transdermal delivery of NLC hydrogel showed that the elimination of drug was significantly reduced and the mean residence time of drug was prominently prolonged as compared to intravenous drug solution (p<0.005). The accumulation of drug in the skin and continuous penetration of drug through the skin accounted for the maintenance of drug concentration for at least 24h. | Lansoprazole |
BACKGROUND: Dental calculus (mineralised dental plaque) preserves many types of microfossils and biomolecules, including microbial and host DNA, and ancient calculus are thus an important source of information regarding our ancestral human oral microbiome. In this study, we taxonomically characterised the dental calculus microbiome from 20 ancient human skeletal remains originating from Trentino-South Tyrol, Italy, dating from the Neolithic (6000-3500 BCE) to the Early Middle Ages (400-1000 CE). RESULTS: We found a high abundance of the archaeal genus Methanobrevibacter in the calculus. However, only a fraction of the sequences showed high similarity to Methanobrevibacter oralis, the only described Methanobrevibacter species in the human oral microbiome so far. To further investigate the diversity of this genus, we used de novo metagenome assembly to reconstruct 11 Methanobrevibacter genomes from the ancient calculus samples. Besides the presence of M. oralis in one of the samples, our phylogenetic analysis revealed two hitherto uncharacterised and unnamed oral Methanobrevibacter species that are prevalent in ancient calculus samples sampled from a broad range of geographical locations and time periods. CONCLUSIONS: We have shown the potential of using de novo metagenomic assembly on ancient samples to explore microbial diversity and evolution. Our study suggests that there has been a possible shift in the human oral microbiome member Methanobrevibacter over the last millennia. Video abstract. | Methanobacteriales |
BACKGROUND: Gonadotropin injections for fertility treatment regimens are usually self-injected, typically over 8-12 days during the assisted reproductive technology cycle. Parenteral gonadotropins are available in different formulations and administered through various systems. A user experience study and risk assessment were performed to evaluate different product types for risks to the patient when preparing and administering injections. METHODS: Nine women of child-bearing age each prepared and administered injections of six products representing single- and multidose vials of menotropin for reconstitution (Merional(R) and Menopur(R)), follicle stimulating hormone (FSH) reusable pen injectors with (Puregon(R)), and without cartridges (Gonal-f(R)), and single-use FSH pre-filled pens (Bemfola(R)). Risk assessments based on user feedback were made with reference to EU regulations for implementing practices for safe use of injectable products. RESULTS: Products requiring reconstitution with diluent in glass ampoules were associated with medium risk for sharps injury and a lower level of user confidence. Pen injectors were considered easy-to-use, with a low risk of sharps injury. Single-use pens were associated with the lowest risk of dosing errors. CONCLUSIONS: The study identifies differences in the risks for both sharps injuries and dosing errors between FSH delivery options that practitioners should consider when making a treatment choice." | Follicle Stimulating Hormone, Human |
A replication of the levels effect" and reported correlation of "projection" and "pathology" was undertaken using a selected set of Thematic Apperception Test (Murray, 1943) cards varied for ambiguity and scored for pathology and projection. The levels effect was not found for pathology in either a normal or psychiatric group, but was found for projection in the normal group. The correlation between projection and pathology was again clearly confirmed. It was concluded that failure to take into consideration the stimulus properties of the cards and the context in which the test was administered may lead to false attribution of pathology to normal test-takers." | Thematic Apperception Test |
BACKGROUND: T cell activation is associated with increase in glycolysis and glutaminolysis. T cell immunoglobulin and mucin domain containing protein-3 (TIM-3), a T cell surface molecule, downregulates T cell activation and leads to insufficient immunity in cancer and chronic infection. TIM-3 regulates T cell activation possibly through alterations in metabolism; however, the relationship between TIM-3 expression and T cell metabolic changes has not been well studied. RESULTS: We investigated the association between TIM-3 expression and metabolic changes by analyzing glucose metabolism, glutamine metabolism, and mitochondrial function in TIM-3 overexpressing or knockout Jurkat T cell lines relative to their control cell lines. Glucose uptake and consumption, and lactate release were downregulated by TIM-3 expression but upregulated by TIM-3 knockout. Concomitantly, the expression of the glucose transporter, Glut1, but not Glut2, 3, or 4 was altered by TIM-3 expression. However, TIM-3 expression alone could not account for the change in glutamine consumption, glutamate release, and mitochondrial mass, ROS production or membrane potential in these cell lines. CONCLUSION: Our results show the association of TIM-3 expression with T cell glucose metabolism. These results are significant in chronic infections and cancers where it is necessary to control TIM-3 expressing T cells. | Glucose Transporter Type 1 |
The last known Tasmanian tiger (Thylacinus cynocephalus)-aka the thylacine-died in 1936. Because its natural behavior was never scientifically documented, we are left to infer aspects of its behavior from museum specimens and historical recollections of bushmen. Recent advances in brain imaging have made it possible to scan postmortem specimens of a wide range of animals, even more than a decade old. Any thylacine brain, however, would be more than 100 years old. Here, we show that it is possible to reconstruct white matter tracts in two thylacine brains. For functional interpretation, we compare to the white matter reconstructions of the brains of two Tasmanian devils (Sarcophilus harrisii). We reconstructed the cortical projection zones of the basal ganglia and major thalamic nuclei. The basal ganglia reconstruction showed a more modularized pattern in the cortex of the thylacine, while the devil cortex was dominated by the putamen. Similarly, the thalamic projections had a more orderly topography in the thylacine than the devil. These results are consistent with theories of brain evolution suggesting that larger brains are more modularized. Functionally, the thylacine's brain may have had relatively more cortex devoted to planning and decision-making, which would be consistent with a predatory ecological niche versus the scavenging niche of the devil. | Marsupialia |
Exoskeleton robots are mechanical constructions attached to human body parts, containing actuators for influencing human motion. One important application area for exoskeletons is human motion support, for example, for disabled people, including rehabilitation training, and for force enhancement in healthy subjects. This paper surveys two exoskeleton systems developed in our laboratory. The first system is a lower-extremity exoskeleton with one actuated degree of freedom in the knee joint. This system was designed for motion support in disabled people. The second system is an exoskeleton for a human hand with 16 actuated joints, four for each finger. This hand exoskeleton will be used in rehabilitation training after hand surgeries. The application of EMG signals for motion control is presented. An overview of the design and control methods, and first experimental results for the leg exoskeleton are reported. | Bionics |
Beneficial interaction of members of the fungal genus Trichoderma with plant roots primes the plant immune system, promoting systemic resistance to pathogen infection. Some strains of Trichoderma virens produce gliotoxin, a fungal epidithiodioxopiperazine (ETP)-type secondary metabolite that is toxic to animal cells. It induces apoptosis, prevents NF-kappaB activation via the inhibition of the proteasome, and has immunosuppressive properties. Gliotoxin is known to be involved in the antagonism of rhizosphere microorganisms. To investigate whether this metabolite has a role in the interaction of Trichoderma with plant roots, we compared gliotoxin-producing and nonproducing T. virens strains. Both colonize the root surface and outer layers, but they have differential effects on root growth and architecture. The responses of tomato plants to a pathogen challenge were followed at several levels: lesion development, levels of ethylene, and reactive oxygen species. The transcriptomic signature of the shoot tissue in response to root interaction with producing and nonproducing T. virens strains was monitored. Gliotoxin producers provided stronger protection against foliar pathogens, compared to nonproducing strains. This was reflected in the transcriptomic signature, which showed the induction of defense-related genes. Two markers of plant defense response, PR1 and Pti-5, were differentially induced in response to pure gliotoxin. Gliotoxin thus acts as a microbial signal, which the plant immune system recognizes, directly or indirectly, to promote a defense response. IMPORTANCE A single fungal metabolite induces far-reaching transcriptomic reprogramming in the plant, priming immune responses and defense, in contrast to its immunosuppressive effect on animal cells. While the negative effects of gliotoxin-producing Trichoderma strains on growth may be observed only under a particular set of laboratory conditions, gliotoxin-linked molecular patterns, including the potential for limited cell death, could strongly prime plant defense, even in mature soil-grown plants in which the same Trichoderma strain promotes growth. | Gliotoxin |
OBJECTIVES: Many local communities in Kentucky, a state with one of the highest smoking prevalence rates in the United States, have enacted smoke-free ordinances that prohibit smoking in workplaces and enclosed buildings open to the public. Research has shown that such ordinances are clearly beneficial for public health, but their influence on smoking prevalence in the populations they cover remains unclear. This study explores the effect of local smoke-free ordinances on smoking prevalence in Kentucky. METHODS: We used a database of smoke-free ordinances maintained by the Kentucky Center for Smoke-Free Policy, Kentucky Behavioral Risk Factor Surveillance System survey data, and US Census data. We estimated the proportion of Kentucky adults living in counties with smoke-free ordinances of varying strength; examined bivariate associations between smoke-free ordinances and smoking prevalence; and fit regression models that adjusted for various county-level demographic, socioeconomic, and geographic factors. RESULTS: Smoking prevalence was approximately 5% lower in counties with smoke-free ordinances, even after adjusting for other relevant factors, including a trend in decreasing prevalence throughout the study region. There was a slight dose-response effect related to the strength of smoke-free ordinances after adjustment for these covariates. Smoke-free ordinances appear to have a modest effect on smoking prevalence across the span of several years. CONCLUSIONS: Findings demonstrate that although smoking prevalence fell throughout the state during the study period, counties with smoke-free ordinances experienced a greater decline. Future research should examine the strength of smoke-free ordinances in greater detail to better understand their influence on smoking prevalence. | Smoke-Free Policy |
PURPOSE OF REVIEW: To systematically review the current literature to assess the role of radiomics in the detection and evaluation of prostate cancer (PCa). RECENT FINDINGS: Radiomics involves the high-throughput extraction of radiologic features from clinical imaging, using a panel of sophisticated data-characterization algorithms to make an objective and quantitative determination of diagnoses and clinical characteristics. Radiomics evaluation of existing clinical images would increase their clinical value in many cancer management pathways, including PCa. However, a consensus on the implementation of radiomics has not been established across different sites, delaying its implementation in clinical practice. There are many potential advantages to radiomics. The ability to extract features from existing clinical imaging is one such advantage. A second is the empiric nature of the analysis. The third lies in the application of new technologies, such as machine learning, to be able to evaluate large quantities of data to make clinical conclusions. In this systematic review, we identify publications regarding the role of radiomics in PCa detection and evaluation. Many of these studies noted that radiomics, when incorporated into predictive models, had an advantageous impact on detection of PCa, clinically significant PCa, and extracapsular extension. This may assist in individualized decision making not only for diagnosis of PCa, but also for surveillance and surgical planning. With additional validation in large sample sizes, and randomized, multicenter studies using a consensus driven methodology, radiomics has the potential to alter the landscape of PCa detection and management, necessitating further prospective randomized investigation. SUMMARY: Radiomics is a promising new field, allowing for high-throughput analysis of imaging features for PCa detection and evaluation. These features can be extracted from existing data; therefore, the potential for future study is immense. | Phenomics |
During mammalian cell division, DNA methylation patterns are transferred accurately to the newly synthesized DNA strand. This depends on maintenance DNA methyltransferase activity. DNA methylation can affect chromatin organization and gene expression by recruitment of histone deacetylases (HDACs). Here we show that the methyl-CpG binding protein, MeCP2, interacts directly with the maintenance DNA methyltransferase, Dnmt1. The region of MeCP2 that interacts with Dnmt1 corresponds to the transcription repressor domain which can also recruit HDACs via a corepressor, mSin3A. Dnmt1 can form complexes with HDACs as well as MeCP2. Surprisingly, the MeCP2-Dnmt1 complex does not contain the histone deacetylase, HDAC1. Thus, Dnmt1 takes the place of the mSin3A-HDAC1 complex, indicating that the MeCP2-interacting Dnmt1 does not bind to HDAC1. Further, we demonstrate that MeCP2 can form a complex with hemimethylated as well as fully methylated DNA. Immunoprecipitated MeCP2 complexes show DNA methyltransferase activity to hemimethylated DNA. These results suggest that Dnmt1 associates with MeCP2 in order to perform maintenance methylation in vivo. We propose that genome-wide and/or -specific local DNA methylation may be maintained by the Dnmt1-MeCP2 complexes, bound to hemimethylated DNA. Dnmt1 may be recruited to targeted regions via multiple steps that may or may not involve histone deacetylases. | DNA-Cytosine Methylases |
Blood loss and the incidence of emetic sequelae were assessed in 148 patients undergoing midcavity forceps delivery under continuous lumbar extradural analgesia. Five units of oxytocin i.v. was found to be as effective as ergometrine 0.5 mg i.v. in reducing blood loss at delivery. Nausea, retching or vomiting occurred in 35 (46%) of the mothers who received ergometrine and in none of those who received i.v. oxytocin. The cardiovascular side-effects of ergometrine and oxytocin are reviewed and compared with special reference to patients with hypertension and heart disease. It is suggested that 5 units of oxytocin i.v. should be preferred in these high-risk patients. Because of the absence of an emetic action, i.v. oxytocin is preferable to i.v. ergometrine for patients receiving extradural analgesia. | Ergonovine |
Understanding the hearing of marine mammals has been a priority to quantify and mitigate the impact of anthropogenic sound on these apex predators. Yet our knowledge of cetacean hearing is still limited to a few dozen species, therefore compromising any attempt to design adaptive management strategies. The use of auditory evoked potentials allows scientists to rapidly and noninvasively obtain the hearing data of species rarely available in captivity. Unfortunately, many practical and ethical reasons still limit the availability of large whales, thus restricting the possibility to effectively ensure that anthropogenic sounds have minimum effects on these species. The example of a recent Blainville's beaked whale (Mesoplodon densirostris) audiogram collected after a stranding indicated, for instance, very specialized hearing between 40 and 50 kHz, which corresponded to the frequency-modulated upsweep signals used by this species during echolocation. The methods used during a stranding event are presented along with the major difficulties that have slowed down the scientific community in measuring the audition of large whales and the potential value in obtaining such results when successful. | Whales |
Microbial communities' taxonomic and functional diversity has been broadly studied since sequencing technologies enabled faster and cheaper data obtainment. Nevertheless, the programming skills needed and the amount of software available may be overwhelming to someone trying to analyze these data. Here, we present a comprehensive and straightforward pipeline that takes shotgun metagenomics data through the needed steps to obtain valuable results. The raw data goes through a quality control process, metagenomic assembly, binning (the obtention of single genomes from a metagenome), taxonomic assignment, and taxonomic diversity analysis and visualization. | Metagenomics |
The equine-virulent Venezuelan encephalitis virus, Trinidad donkey (TRD), was compared to its vaccine derivative, TC-83 virus, by examining the glycosylation of the two structural envelope glycoproteins (E1 and E2). The number of size classes of glycopeptides on the glycoproteins was determined by P-6 column chromatography following Pronase digestion. The E1 glycoprotein had three glycopeptide size species and the E2 glycoprotein contained four size species ranging in mol. wt. from 1900 to 2700. Both viruses contained similar glycopeptide size species, although the relative amounts on the E2 glycoproteins appeared to be somewhat different. All of the glycopeptide species appeared to be complex, since all were labelled with glucosamine, mannose, galactose and fucose. No mannose-rich species could be detected. The different glycopeptide species appeared to be sialylation isomers of a smaller core glycopeptide with an apparent mol. wt. of 1800 which was the sole product following desialylation of the larger glycopeptides. The number of oligosaccharide attachment sites present on both E1 and E2 of each virus was determined using reverse-phase high pressure liquid chromatography. This analysis indicated that the E1 glycoprotein of both viruses had six or seven similar sugar-labelled peptide fragments following trypsin digestion. However, the E2 glycoprotein of TRD virus contained three oligosaccharide attachment sites, whereas TC-83 E2 glycoprotein had only two." | Encephalitis Virus, Venezuelan Equine |
INTRODUCTION: In Brazil, the Unified Health System (Sistema Unico de Saude, or SUS) provides health care, and an aging population overwhelms the system due to the greater vulnerability of the elderly. In the Federal District, two models of primary care coexist-the traditional primary care and the family health strategy. The present study aimed to analyze the factors associated with mortality of the elderly due to conditions sensitive to ambulatory care in the Federal District, Brazil. MATERIALS AND METHODS: This cross-sectional study investigated all deaths that occurred in people over 60 years old between 2008 and 2018. The variables studied were age at death, sex, marital status, education, race/color, death by condition sensitive to ambulatory care, and population coverage of primary care services. The Urban Well-Being Index (UWBI) was used, which includes the dimensions: mobility, environmental and housing conditions, infrastructure, and collective services, to analyze issues related to the place where the senior citizen resides. RESULTS: The deaths 70,503 senior citizens were recorded during the study period. The factors associated with mortality in the elderly due to ambulatory care sensitive conditions were male, lower income, and less education. Residing in a place with poor UWBI presented a response gradient with higher mortality. Increased ambulatory care coverage was also associated with lower mortality. CONCLUSIONS: The study evidenced an association between male gender, age, income, and education, and UWBI with lower mortality due to ambulatory care sensitive conditions, and these associations presented a response gradient. The study also found that increased coverage of the elderly population was associated with lower mortality from sensitive conditions." | Ambulatory Care Sensitive Conditions |
The Dombrock blood group system (Do) consists of two antithetical antigens (Do(a) and Do(b)) and five antigens of high prevalence (Gy(a), Hy, Jo(a), DOYA, and DOMR). Do antigens are carried on the Dombrock glycoprotein, which is attached to the RBC membrane via glycosylphosphatidylinositol linkage. The gene (DO, ART4) encoding the Do glycoprotein, located on the short arm of chromosome 12, has been cloned and sequenced, allowing the molecular basis of the various Do phenotypes to be determined. Do(a) and Do(b) have a prevalence that makes them useful as genetic markers; however, the paucity of reliable anti-Do(a) and anti-Do(b) has prevented this potential from being realized. The ease with which these antigens can be predicted by analysis of DNA opens the door for such studies to be carried out. Anti-Do(a) and anti-Do(b) are rarely found as a single specificity, but they have been implicated in causing hemolytic transfusion reactions. This review is a synthesis of our current knowledge of he Dombrock blood group system. | Chromosomes, Human, Pair 12 |
Regulatory divergence is likely a major driving force in evolution. Comparative transcriptomics provides a new glimpse into the evolution of gene regulation. Ascomycota fungi are uniquely suited among eukaryotes for studies of regulatory evolution, because of broad phylogenetic scope, many sequenced genomes, and facility of genomic analysis. Here we review the substantial divergence in gene expression in Ascomycota and how this is reconciled with the modular organization of transcriptional networks. We show that flexibility and redundancy in both cis-regulation and trans-regulation can lead to changes from altered expression of single genes to wholesale rewiring of regulatory modules. Redundancy thus emerges as a major driving force facilitating expression divergence while preserving the coherent functional organization of a transcriptional response. | Base Sequence |
We have discovered a new 4 h ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of individual mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the histories of the dry mass of thousands of single live cells simultaneously, each at a resolution of five minutes. It was vital that the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias. The rhythm is independent of circadian rhythm, and is temperature-compensated. We show that the amplitude of the fundamental frequency provides a way to quantify the effects of, chemical reagents on cells, thus shedding light on its mechanism. The rhythm is suppressed by proteostasis disruptors and is detected only in proliferating cells, suggesting that it represents a massive degradation and re-synthesis of protein every 4 h in growing cells. | Ultradian Rhythm |
Increasing interest in root caries has resulted in several reports during the year. Problems with diagnosis, epidemiology, structural histopathology, and treatments have clarified some problems concerning root caries. Only active lesions should be registered, but it is important to search for lesions in the periodontal pocket. In several countries, root caries have been found in 30% to 50% of elderly people. In structural investigations, remineralization may occur as irregular precipitation of crystals clearly distinguishable from those of normal sound dentin. Presence of plaque with gram-positive bacteria is closely associated with root caries. Treatment with varnish containing chlorhexidine and thymol may have a reducing effect. Little has been written about the operative treatment of root caries. | Tooth Demineralization |
A new benzophenanthridine alkaloid, 6-[2'-ethoxy-2'-(2'',4'',5''-trimethoxyphenyl)] ethyl-7,8-dimethoxy-5-methyl-2,3-methylenedioxy-5,6-dihydrobenzo[c]phenanthridine named buesgeniine (1), as well as the known decarine, were isolated from the extract of the stem bark of Zanthoxylum buesgenii. In addition, three known lignans, sesamine, matairesinol dimethylether, and methylpluviatilol, were also identified. The structure of 1 was elucidated using spectroscopic methods. | Zanthoxylum |
This study explored relationships between perspective-taking, emotion understanding, and children's narrative abilities. Younger (23 5-/6-year-olds) and older (24 7-/8-year-olds) children generated fictional narratives, using a wordless picture book, about a frog experiencing jealousy. Children's emotion understanding was assessed through a standardized test of emotion comprehension and their ability to convey the jealousy theme of the story. Perspective-taking ability was assessed with respect to children's use of narrative evaluation (i.e., narrative coherence, mental state language, supplementary evaluative speech, use of subjective language, and placement of emotion expression). Older children scored higher than younger children on emotion comprehension and on understanding the story's complex emotional theme, including the ability to identify a rival. They were more advanced in perspective-taking abilities, and selectively used emotion expressions to highlight story episodes. Subjective perspective taking and narrative coherence were predictive of children's elaboration of the jealousy theme. Use of supplementary evaluative speech, in turn, was predictive of both subjective perspective taking and narrative coherence. | Jealousy |
BACKGROUND: Doxapram is used for the treatment of apnea of prematurity in dosing regimens only based on bodyweight, as pharmacokinetic data are limited. This study describes the pharmacokinetics of doxapram and keto-doxapram in preterm infants. METHODS: Data (302 samples) from 75 neonates were included with a median (range) gestational age (GA) 25.9 (23.9-29.4) weeks, bodyweight 0.95 (0.48-1.61) kg, and postnatal age (PNA) 17 (1-52) days at the start of continuous treatment. A population pharmacokinetic model was developed using non-linear mixed-effects modelling (NONMEM(R)). RESULTS: A two-compartment model best described the pharmacokinetics of doxapram and keto-doxapram. PNA and GA affected the formation clearance of keto-doxapram (CL(FORMATION KETO-DOXAPRAM)) and clearance of doxapram via other routes (CL(DOXAPRAM OTHER ROUTES)). For a median individual of 0.95 kg, GA 25.6 weeks, and PNA 29 days, CL(FORMATION KETO-DOXAPRAM) was 0.115 L/h (relative standard error (RSE) 12%) and CL(DOXAPRAM OTHER ROUTES) was 0.645 L/h (RSE 9%). Oral bioavailability was estimated at 74% (RSE 10%). CONCLUSIONS: Dosing of doxapram only based on bodyweight results in the highest exposure in preterm infants with the lowest PNA and GA. Therefore, dosing may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events. For switching to oral therapy, a 33% dose increase is required to maintain exposure. IMPACT: Current dosing regimens of doxapram in preterm infants only based on bodyweight result in the highest exposure in infants with the lowest PNA and GA. Dosing of doxapram may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events. Describing the pharmacokinetics of doxapram and its active metabolite keto-doxapram following intravenous and gastroenteral administration enables to include drug exposure to the evaluation of treatment of AOP. The oral bioavailability of doxapram in preterm neonates is 74%, requiring a 33% higher dose via oral than intravenous administration to maintain exposure. | Doxapram |
OBJECTIVE: Optimum detection of hypothermia in athletes during outdoor exposure events remains controversial. The aims of this study were firstly to assess whether temperature readings affected competitor discharge from the treatment station and secondly to assess agreement between oral and tympanic thermometer measurements. METHODS: All competitors treated for symptomatic hypothermia at an outdoor endurance event in the United Kingdom during January 2009 were included. Temperature readings were taken using oral (Digitemp digital oral thermometer) and tympanic (Braun Thermoscan IRT 4520 ExacTemp) thermometers, with a temperature <35 degrees C classifying hypothermia. RESULTS: From 4700 competitors, 64 (1.4%) were treated for symptomatic hypothermia. Of these, 92% were male, the mean age was 26 years, and the mean treatment time was 25 minutes. There was no severe/life-threatening hypothermia, and no competitors required transport to a hospital for hypothermia. At discharge, 19% of competitors were still classed as hypothermic in the oral group and 28% in the tympanic group, despite competitors only being discharged when no longer symptomatic. Oral readings at discharge were significantly lower than tympanic readings (33.8 degrees C [95% CI, 33.2 degrees C to 34.5 degrees C] vs 35.0 degrees C [95% CI, 34.6 degrees C to 35.3 degrees C], respectively, P = .003). CONCLUSIONS: The use of thermometers had a limited role in discharging competitors at this event, who were apparently safely discharged when no longer symptomatic. Treating clinicians and the thermometers did not always agree on whether a patient was hypothermic or not. Oral and tympanic thermometers had poor agreement. Routine thermometer readings at future events may be unnecessary, although screening competitors of concern will remain useful. | Hypothermia |
Age-related cataract is a result of crystallins, the predominant lens proteins, forming light-scattering aggregates. In the low protein turnover environment of the eye lens, the crystallins are susceptible to modifications that can reduce stability, increasing the probability of unfolding and aggregation events occurring. It is hypothesized that the alpha-crystallin molecular chaperone system recognizes and binds these proteins before they can form the light-scattering centres that result in cataract, thus maintaining the long-term transparency of the lens. In the present study, we investigated the unfolding and aggregation of (wild-type) human and calf betaB2-crystallins and the formation of a complex between alpha-crystallin and betaB2-crystallins under destabilizing conditions. Human and calf betaB2-crystallin unfold through a structurally similar pathway, but the increased stability of the C-terminal domain of human betaB2-crystallin relative to calf betaB2-crystallin results in the increased population of a partially folded intermediate during unfolding. This intermediate is aggregation-prone and prevents constructive refolding of human betaB2-crystallin, while calf betaB2-crystallin can refold with high efficiency. alpha-Crystallin can effectively chaperone both human and calf betaB2-crystallins from thermal aggregation, although chaperone-bound betaB2-crystallins are unable to refold once returned to native conditions. Ordered secondary structure is seen to increase in alpha-crystallin with elevated temperatures up to 60 degrees C; structure is rapidly lost at temperatures of 70 degrees C and above. Our experimental results combined with previously reported observations of alpha-crystallin quaternary structure have led us to propose a structural model of how activated alpha-crystallin chaperones unfolded betaB2-crystallin. | beta-Crystallin B Chain |
A collection of 68 Hafnia strains previously identified to the species level by 16S rRNA gene sequencing were investigated for simple phenotypic properties that could aid in their recognition in the clinical laboratory. Four tests, including malonate utilization, fermentation of salicin and d-arabinose, and expression of beta-glucosidase activity, correctly assigned each strain to either Hafnia alvei or H. paralvei. Antibiotic susceptibility profiles were generated for 35 H. alvei and H. paralvei isolates using Etest strips for 24 antibiotics. All strains were susceptible to aminoglycosides, quinolones, carbapenems, and monobactams. Most of the Hafnia isolates had a colistin MIC of >/=2 mug/ml. Sequencing of an internal ampC gene fragment allowed genotypic differentiation of the two Hafnia species. Approximately 70% of the hafniae tested additionally produced a cytolytic toxin active on Vero cells which may play a role in gastroenteritis. | Hafnia |
Recent characterization of radioactive particles indicate that a large percentage of the radioactivity observed during the Fukushima Daiichi nuclear meltdown was insoluble (137)Cs bound within silica microparticles. Therefore, much of the decontamination research performed prior to the Fukushima incident that used either soluble radionuclides deposited onto wet surfaces or large ( approximately 100â¯mum) particles characteristic of nuclear weapons fallout do not accurately represent the characteristics of potential contamination. Thus, the common practice of extrapolating radioactive decontamination methods generically to all radioactive release events is, at best, suspect. In response, a method to produce chemically-inert, radiolabeled silica particles was developed. Binding (152)Eu within a sodium silicate coating required proper temperature control and ethanol was beneficial as a volatile dispersant to limit residues. In the end, a step-wise method, which first deposited (152)Eu or (241)Am as a nitrate salt, decomposed the salt to a sesquioxide, and finally coated the surface with sodium silicate led to dispersed particles of the desired 2 or 0.5â¯mum diameters. Dynamic light scattering and scanning election microscopy confirmed the particle size was unchanged. Leaching studies into several common decontaminants were performed to ensure particle inertness. Our approach allows for substitution of other radionuclides making it a robust, simple, and novel method to produce inert particle surrogates for a release event that allows direct comparison of decontamination techniques and contaminant fate studies, greatly aiding the development of response and recovery plans. | Einsteinium |
The Physician Payment Review Commission's endorsement of the Resource-Based Relative Value Scale (RBRVS) represents a major step in reform of the Medicare payment system. Under this plan, cognitive services finally would be reimbursed at the same level for the work involved. The authors present a closer look at the commission's recommendations and discuss how these might substantially improve payment of primary care physicians. They also describe how to get ready." | Physician Payment Review Commission |
The author, a nurse guided by Parse's theory of human becoming, describes one way to focus on quality of life in person-centered practice with a group in the community, in contrast to traditional nursing practice with groups in which the focus is on problems, learning, and socially-defined responsibility. The author describes living true presence over a 10-week period in accord with Parse's practice method with a group of persons with genital herpes. Emerging patterns of health of the group are reported along with a loose agenda for community-based practice. | Herpes Genitalis |
Background and objectives: The multidrug resistance protein 4 (MRP4) is a member of the ABC transporter, which has been extensively related to many types of cancer including leukemia. MRP4 overexpression and activity over the efflux of some chemotherapeutic drugs are the main causes of chemoresistance. 6-mercaptopurine (6-MP) is a chemotherapeutic drug widely used in the consolidation and maintenance phases of leukemia treatment. However, 6-MP is a substrate of MRP4, which decreases its chemotherapeutic efficacy. Current research is focused on the development of MRP4 inhibitors to combat chemoresistance by allowing the accumulation of the drug substrates inside the cells. To date, the only specific MRP4 inhibitor that has been developed is ceefourin-1, which has been reported to inhibit MRP4 in many cancer cells and which makes it an excellent candidate to enhance the activity of 6-MP in a combined treatment in vitro of leukemic cells. Materials and methods: in the present work, we determined the enhancing activity of ceefourin-1 on the antiproliferative and apoptotic effect of 6-MP in leukemic Jurkat cells by trypan blue assay and flow cytometry. Besides, we determined the 6-MP and ceefourin-1 binding sites into MRP4 by molecular docking and molecular dynamics. Results: ceefourin-1 enhanced the apoptotic activity of 6-MP in Jurkat cells, while in CRL-1991 cells both antiproliferative and apoptotic effect were significantly lower. Ceefourin-1 additively cooperates with 6-MP to induce apoptosis in leukemic cells, but normal lymphoblast CRl-1991 showed resistance to both drugs. Conclusion: ceefourin-1 and 6-MP cooperates to trigger apoptosis in leukemic Jurkat cells, but the full mechanism needs to be elucidated in further works. In addition, our perspective is to test the cooperation between ceefourin-1 and 6-MP in samples from patients and healthy donnors. | Mercaptopurine |
This study investigated the effects of pair housing on diurnal rhythms of heart rate and autonomic nervous activity in miniature swine. For this purpose, six adult Gottingen miniature swine were initially housed individually in an animal cage. Then, two of each swine were housed in a large cage together for 3 weeks. After that swine were separated into individual cages again. During this experimental procedure, electrocardiogram (ECG) was recorded with a Holter ECG recorder. Autonomic nervous activity was evaluated by power spectral analysis of heart rate variability. Heart rate and autonomic nervous activity clearly showed a diurnal rhythm in miniature swine housed in individual cages. When two swine were housed together, heart rate was significantly increased throughout the day and diurnal rhythm disappeared. Although these changes gradually recovered to basal levels, these parameters had not completely returned to basal levels even after 2 weeks. Heart rate was still higher than the initial level just after swine were re-housed in their own individual cages. Heart rate and autonomic nervous activity returned to basal levels about 2 weeks after re-housing. Further, heart rate in some swine decreased below their initial levels. These results suggest that it takes miniature swine at least 2 weeks to adapt to different circumstances. Furthermore, the power spectral analysis of heart rate variability can be used as a useful method in a study for answering controversial issues related to stress response. | Swine, Miniature |
Endometritis is defined as inflammation of the endometrium that may be acute or chronic, infectious, or non-infectious. Endometritis is an important cause of subfertility in mares. Considering the antimicrobial characteristics, immune-stimulating ability, and low cost of ozone (O(3)) therapy, we aimed to evaluate the effectiveness of intrauterine O(3) therapy as an alternative treatment for endometritis in mares. Twenty-five mares with a known reproductive history of uterine infection and inflammation were allocated into three groups: Group 1 (control; n = 7), uterine lavage with Ringer's lactate solution; Group 2 (O(3)-gas; n = 9), uterine lavage with Ringer's lactate solution followed by uterine insufflation with O(2)-O(3) gas mixture containing 40 microg O(3) mL(-1) for 10 minute; and Group 3 (O(3)-oil; n = 9), uterine infusion of ozonized sunflower oil. Uterine inflammation was evaluated through a uterine cytological examination (cytobrush) and uterine culture (swab) for microbiological content before and after all treatments. In assessments of uterine cytology, the average number of neutrophils/field changed from 9.14 +/- 3.02 to 7.71 +/- 3.59 in the control group, from 10.67 +/- 3.84 to 2.89 +/- 3.59 in the O(3)-gas group, and from 6.44 +/- 2.79 to 6.55 +/- 7.18 in the O(3)-oil group post-treatment. The pre- and post-treatment findings in the mares treated with ozonized gas were significantly different (P < .05), unlike the findings for the mares in the control and O(3)-oil groups. All mares (25/25) showed a positive uterine culture before treatment. After treatment, the percentage of mares showing positive culture results was 57%, 11%, and 22% in the control, O(3)-gas, and O(3)-oil groups, respectively. Our results showed the effectiveness of two groups (O(2)-O(3) gas mixture and ozonized sunflower oil) for the treatment of uterine infections in mares. Thus, direct intrauterine O(3) gas infusion has been shown to be effective in treating endometritis in mares, reducing both inflammation and uterine infection. | Endometritis |
The function of the ventricular specialized conduction system in the heart is to ensure the coordinated electrical activation of the ventricles. It is therefore critical to the overall function of the heart, and has also been implicated as an important player in various diseases, including lethal ventricular arrhythmias such as ventricular fibrillation and drug-induced torsades de pointes. However, current ventricular models of electrophysiology usually ignore, or include highly simplified representations of the specialized conduction system. Here, we describe the development of an image-based, species-consistent, anatomically-detailed model of rabbit ventricular electrophysiology that incorporates a detailed description of the free-running part of the specialized conduction system. Techniques used for the construction of the geometrical model of the specialized conduction system from a magnetic resonance dataset and integration of the system model into a ventricular anatomical model, developed from the same dataset, are described. Computer simulations of rabbit ventricular electrophysiology are conducted using the novel anatomical model and rabbit-specific membrane kinetics to investigate the importance of the components and properties of the conduction system in determining ventricular function under physiological conditions. Simulation results are compared to panoramic optical mapping experiments for model validation and results interpretation. Full access is provided to the anatomical models developed in this study. | Heart Conduction System |
The catecholamine dopamine (DA) plays an important role as a neurotransmitter in the brain in circuits linked to motor function, reward, and cognition. The presynaptic DA transporter (DAT) inactivates DA following release and provides a route for non-exocytotic DA release (efflux) triggered by amphetamines. The synaptic role of DATs first established through antagonist studies and more recently validated through mouse gene-knockout experiments, raises questions as to whether altered DAT structure or regulation support clinical disorders linked to compromised DA signaling, including drug abuse, schizophrenia, and attention deficit hyperactivity disorder (ADHD). As ADHD appears to have highly heritable components and the most commonly prescribed therapeutics for ADHD target DAT, studies ranging from brain imaging to genomic and genetic analyses have begun to probe the DAT gene and its protein for possible contributions to the disorder and/or its treatment. In this review, after a brief overview of ADHD prevalence and diagnostic criteria, we examine the rationale and experimental findings surrounding a role for human DAT in ADHD. Based on the available evidence from our lab and labs of workers in the field, we suggest that although a common variant within the human DAT (hDAT) gene (SLC6A3) is unlikely to play a major role in the ADHD, contributions of hDAT to risk maybe most evident in phenotypic subgroups. The in vitro and in vivo validation of functional variants, pursued for contributions to endophenotypes in a within family approach, may help elucidate DAT and DA contributions to ADHD and its treatment." | Dopamine Plasma Membrane Transport Proteins |
Amebic dysentery caused by Entamoeba histolytica accounts for significant morbidity in the non-human primates (NHP) at the Singapore Zoo. This includes the animals in the collection as well as a sizeable free-roaming wild crab-eating macaque (Macaca fascicularis) population. The disease is of great concern because of its zoonotic potential. Passive surveillance, both ante and post-mortem, of NHP displaying clinical symptoms and active surveillance of NHP assessed to be at a higher risk of infection were carried out via fecal real-time polymerase chain reaction (PCR) testing for 4 years. Treatment of the disease with 25 mg/kg metronidazole BID for 10 days followed by 15 mg/kg paromomycin BID for 7 days achieved good clinical resolution in most cases that tested positive. Three diseased NHP with severe clinical signs of weight loss, lethargy, and diarrhea were anesthetized for veterinary diagnostic investigation. Mesenteric lymphadenopathy was consistently seen on ultrasound examination in these severe cases of entamoebiasis. Two animals eventually died of severe chronic enteritis due to the disease. The eradication of entamoebiasis in the NHP at the Singapore Zoo may be complicated by the maintenance of a disease reservoir in wildlife, but a combination of timely treatment and efforts at maintaining biosecurity can help manage the disease in the collection. | Entamoebiasis |
STUDY OBJECTIVE: A variety of methods have been proposed and used in disaster triage situations, but there is little more than expert opinion to support most of them. Anecdotal disaster experiences often report mediocre real-world triage accuracy. The study objective was to determine the accuracy of several disaster triage methods when predicting clinically important outcomes in a large cohort of trauma victims. METHODS: Pediatric, adult, and geriatric trauma victims from the National Trauma Data Bank were assigned triage levels, using each of 6 disaster triage methods: simple triage and rapid treatment (START), Fire Department of New York (FDNY), CareFlight, Glasgow Coma Scale (GCS), Sacco Score, and Unadjusted Sacco Score. Methods for approximating triage systems were vetted by subject matter experts. Triage assignments were compared against patient mortality at hospital discharge with area under the receiver operator curve. Secondary outcomes included death in the emergency department, use of a ventilator, and lengths of stay. Subgroup analysis assessed triage accuracy in patients by age, trauma type, and sex. RESULTS: In this study, 530,695 records were included. The Sacco Score predicted mortality most accurately, with area under the receiver operator curve of 0.883 (95% confidence interval 0.880 to 0.885), and performed well in most subgroups. FDNY was more accurate than START for adults but less accurate for children. CareFlight was best for burn victims, with area under the receiver operator curve of 0.87 (95% confidence interval 0.85 to 0.89) but mistriaged more salvageable trauma patients to dead/black" (41% survived) than did other disaster triage methods ( approximately 10% survived). CONCLUSION: Among 6 disaster triage methods compared against actual outcomes in trauma registry patients, the Sacco Score predicted mortality most accurately. This analysis highlighted comparative strengths and weakness of START, FDNY, CareFlight, and Sacco, suggesting areas in which each might be improved. The GCS predicted outcomes similarly to dedicated disaster triage strategies." | Mass Casualty Incidents |
A decline in mitochondrial quality and activity has been associated with normal aging and correlated with the development of a wide range of age-related diseases. Here, we review the evidence that a decline in the levels of mitochondrial-derived peptides contributes to aging and age-related diseases. In particular, we discuss how mitochondrial-derived peptides, humanin and MOTS-c, contribute to specific aspects of the aging process, including cellular senescence, chronic inflammation, and cognitive decline. Genetic variations in the coding region of humanin and MOTS-c that are associated with age-related diseases are also reviewed, with particular emphasis placed on how mitochondrial variants might, in turn, regulate MDP expression and age-related phenotypes. Taken together, these observations suggest that mitochondrial-derived peptides influence or regulate a number of key aspects of aging and that strategies directed at increasing mitochondrial-derived peptide levels might have broad beneficial effects. | Growth and Development |
The antifungal activities of four tetracycline analogues in combination with amphotericin B (AmB) were determined against 20 strains of Candida albicans. When a microtiter checkerboard technique was used, minocycline (less than or equal to 10 microgram/ml) acted synergistically with AmB against all strains, whereas doxycycline had a reduced effect, and demeclocycline and tetracycline had no potentiating effect at this concentration. Killing-curve experiments with two strains of C. albicans demonstrated that the combination of minocycline and AmB produced a decrease in number of colony-forming units (cfu) of greater than 2 logs in 4 hr and a 4-log decrease in cfu in 24 hr at concentrations (minocycline, 0.64 microgram/ml; AmB, 0.1 microgram/ml) that were subinhibitory when each agent was used alone and that are readily achieved in human serum and body fluids with conventional doses. The killing-curve technique indicated that doxycycline had an intermediate degree of synergistic activity, whereas tetracycline had no synergistic activity at clinically relevant concentrations. | Naphthacenes |
The sequencing of large, complex genomes has become routine, but understanding how sequences relate to biological function is less straightforward. Although much attention is focused on how to annotate genomic features such as developmental enhancers and non-coding RNAs, there is still no higher eukaryote for which we know the correct exon-intron structure of at least one ORF for each gene. Despite this uncomfortable truth, genome annotation has made remarkable progress since the first drafts of the human genome were analysed. By combining several computational and experimental methods, we are now closer to producing complete and accurate gene catalogues than ever before. | Genome Components |
Fetal aspartylglucosaminuria (AGU) was studied during the first trimester of pregnancy in six at-risk pregnancies using chorionic villus samples. The activity of aspartylglucosaminidase (AGA) was high in five cases, indicating an unaffected fetus. This was confirmed through delivery of healthy newborns with a normal pattern of urinary oligosaccharides. Low enzyme activity in an uncultured biopsy specimen and in cultured amniotic fluid cells in one case demonstrated that the fetus was affected. The pregnancy was terminated and the prenatal diagnosis was confirmed by showing reduced AGA activity in cultured fibroblasts of the fetus. | Aspartylglucosaminuria |
In caring for dying patients, physicians and health team members face a number of decisions about how best to proceed with treatment. Many of these decisions carry implications for the life of the patient, either directly or indirectly. Recent discussions about the morality and wisdom of euthanasia provide an excellent stimulus to reexamine the ethical nature of these decisions. This paper reviews five ethical principles, and describes a process of decision-making that can result in two broad paths of action in relation to life-prolonging treatment. Case examples are presented for illustration. Appropriate ethical practice can be differentiated from acting with the primary intent to take life (euthanasia). | Double Effect Principle |
In many experiments, it is necessary to evaluate the effectiveness of a treatment by comparing the responses of two groups of subjects. This evaluation is often performed by using a confidence interval for the difference between the population means. To compute the limits of this confidence interval, researchers usually use the pooled t formulas, which are derived by assuming normally distributed errors. When the normality assumption does not seem reasonable, the researcher may have little confidence in the confidence interval because the actual one-sided coverage probability may not be close to the nominal coverage probability. This problem can be avoided by using the Robbins-Monro iterative search method to calculate the limits. One problem with this iterative procedure is that it is not clear when the procedure produces a sufficiently accurate estimate of a limit. In this paper, we describe a multiple search method that allows the user to specify the accuracy of the limits. We also give guidance concerning the number of iterations that would typically be needed to achieve a specified accuracy. This multiple iterative search method will produce limits for one-sided and two-sided confidence intervals that maintain their coverage probabilities with non-normal distributions. | Confidence Intervals |
BACKGROUND: For many applications in research, material development and testing, physical skin models are preferable to the use of human skin, because more reliable and reproducible results can be obtained. PURPOSE: This article gives an overview of materials applied to model physical properties of human skin to encourage multidisciplinary approaches for more realistic testing and improved understanding of skin-material interactions. METHODS: The literature databases Web of Science, PubMed and Google Scholar were searched using the terms 'skin model', 'skin phantom', 'skin equivalent', 'synthetic skin', 'skin substitute', 'artificial skin', 'skin replica', and 'skin model substrate.' Articles addressing material developments or measurements that include the replication of skin properties or behaviour were analysed. RESULTS: It was found that the most common materials used to simulate skin are liquid suspensions, gelatinous substances, elastomers, epoxy resins, metals and textiles. Nano- and micro-fillers can be incorporated in the skin models to tune their physical properties. CONCLUSION: While numerous physical skin models have been reported, most developments are research field-specific and based on trial-and-error methods. As the complexity of advanced measurement techniques increases, new interdisciplinary approaches are needed in future to achieve refined models which realistically simulate multiple properties of human skin. | Skin, Artificial |
Normal hemoglobin is made of a tetramer of 2 alpha-globin and 2 beta-globin polypeptide chains. Deletions in the beta-globin gene cluster can range from a few hundred base pairs to loss of the entire cluster resulting in rare, but clinically significant, thalassemias. One such entity is epsilonGgammaAgammadeltabeta0-thalassemia, a condition that presents within the first few weeks of life as a Coombs-negative hemolytic anemia and is not identified on routine newborn screening or hemoglobin electrophoresis. | delta-Thalassemia |
A minimally invasive variation of an established technique of colostomy is described. The method was originally published in 1977. In a setting where traditional celiotomy is not required, three ports are placed with the left lateral port used for the stoma. After initial peritoneal inspection, the colon segment and its mesentery are identified. A suture is passed forming a loop through the end of a soft latex drain, which is passed into the peritoneal cavity. Using the Goldfinger instrument, the mesentery is breached and the loop end of the drain is snared and brought back through the mesenteric defect. This maneuver enables the colon to be retracted through the port site for completion of the colostomy. Inserting the finger along the loop provides proximal and distal visual confirmation. The colon is stapled but not divided. Maturation of the stoma may be done immediately or delayed depending on the clinical circumstances. | Colostomy |
Purpose To investigate the predictive capacity of a new method for sound spectrum analysis of Doppler signals recorded from the umbilical artery in high-risk pregnancies. Material and Methods The retrospective study comprised 127 pregnant women with various pregnancy complications between 23 and 39 gestational weeks. Umbilical artery blood flow velocity waveforms were recorded with Doppler ultrasound and characterized by pulsatility index (PI) and blood flow class (BFC). Doppler audio signals were stored on a digital video recorder and the sound frequency at the energy level 15 dB below its peak (MAX(peak-15 dB)) was estimated off-line. The prediction of probability for composite adverse pregnancy outcome (operative delivery for fetal distress, admission to neonatal intensive care unit, perinatal death) was evaluated using the area under the curve (AUC) of the receiver operating characteristics (ROC) curve. Results With increasing umbilical artery BFC, the MAX(peak-15 dB) frequencies decreased (p < 0.0001) and the PI increased (p < 0.0001). The ROC AUCs for adverse outcome for MAX(peak-15 dB) and for PI were 0.842 and 0.836 (p = 0.88), respectively. For the combination of MAX(peak-15 dB) and PI, the corresponding AUC was 0.894, significantly higher than that of PI (p < 0.03) and of MAX(peak-15 dB) (p < 0.05). Conclusion Umbilical artery Doppler sound spectrum analysis might be a useful supplement to PI in the clinical evaluation of fetoplacental circulation. | Umbilical Arteries |
A promoter selection vector for Clostridium perfringens genes was constructed from a C. perfringens-Escherichia coli shuttle vector, pJIR418. The plasmid carries a promoterless chloramphenicol acetyltransferase gene (catP), derived from pIP401, downstream of the multiple cloning sites of pUC18. When a promoter region of the phospholipase C gene was inserted into one of the cloning sites, derivatives of C. perfringens strain 13 carrying the resultant plasmid acquired resistance to chloramphenicol. This plasmid should be useful reporter system for C. perfringens genes." | Chloramphenicol O-Acetyltransferase |
This investigation reviews the effectiveness of anti-stigma interventions employed at educational institutes; to improve knowledge, attitude and beliefs regarding mental health disorders among students. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist guidelines were followed and protocol was registered in PROSPERO (CRD42018114535). Forty four randomized controlled trials were considered eligible after screening of 104 full-text articles against inclusion and exclusion criteria.Several interventions have been employed to tackle stigma toward psychiatric illnesses, including education through lectures and case scenarios, contact-based interventions, and role-plays as strategies to address stigma towards mental illnesses. A high proportion of trials noted that there was a significant improvement for stigma (19/25, 76%), attitude (8/11, 72%), helping-seeking (8/11, 72%), knowledge of mental health including recognition of depression (11/14, 78%), and social distance (4/7, 57%). These interventions also helped in reducing both public and self-stigma. Majority of the studies showed that the anti-stigma interventions were successful in improving mental health literacy, attitude and beliefs towards mental health illnesses. | Psychosocial Intervention |
BACKGROUND: Treadmill testing is usually preferred over cycle ergometry because of the greater sensitivity in diagnosing coronary artery disease. Treadmill testing has only recently been used with radionuclide angiography (RNA) because patient motion makes RNA imaging difficult. In this study we evaluate the comparability of treadmill and cycle exercise RNA with a dual isotope motion correction technique. METHODS AND RESULTS: Volunteer patients (n = 27) performed first-pass RNA during maximal exercise using both cycle ergometer and treadmill. Exercise capacity was greater during treadmill exercise (8.1 +/- 2.4 vs 7.5 +/- 2.2 METs). Twenty-three of 27 treadmill and all cycle ergometer exercise studies were technically adequate. Maximal heart rate was greater during treadmill exercise (150 +/- 24 vs 143 +/- 25 beats * min-l), however, systolic blood pressure was greater during cycle ergometry (174 +/- 23 vs 188 +/- 25 mmHg), resulting in no difference in heart rate times systolic blood pressure (25.7 +/- 7.2 vs 26.9 +/- 6.0). There were no differences between treadmill and cycle ergometer for peak exercise left ventricular ejection fraction (56% +/- 13% vs 57% +/- 14%) (r = 0.89). Calculated left ventricular end-diastolic volume was not different at rest (183 +/- 42 ml vs 176 +/- 44 ml) but differed significantly at peak exercise (282 +/- 75 ml vs 231 +/- 60 ml). The clinical impression, based on wall motion and left ventricular ejection fraction was very similar between treadmill and cycle ergometer. CONCLUSION: Treadmill exercise RNA is feasible, with about 85% of studies likely to be technically adequate. The overall clinical results are very similar to cycle exercise RNA, although the ordinarily expected advantages of treadmill exercise were largely absent. | Ventriculography, First-Pass |
Knowledge of the functioning, health state, and capacity for recovery of marine benthic organisms and assemblages has become essential to adequately manage and preserve marine biodiversity. Molecular tools have allowed an entirely new way to tackle old and new questions in conservation biology and ecology, and sponge science is following this lead. In this review, we discuss the biological and ecological studies of sponges that have used molecular markers during the past 20 years and present an outlook for expected trends in the molecular ecology of sponges in the near future. We go from (1) the interface between inter- and intraspecies studies, to (2) phylogeography and population level analyses, (3) intra-population features such as clonality and chimerism, and (4) environmentally modulated gene expression. A range of molecular markers has been assayed with contrasting success to reveal cryptic species and to assess the genetic diversity and connectivity of sponge populations, as well as their capacity to respond to environmental changes. We discuss the pros and cons of the molecular gene partitions used to date and the prospects of a plentiful supply of new markers for sponge ecological studies in the near future, in light of recently available molecular technologies. We predict that molecular ecology studies of sponges will move from genetics (the use of one or some genes) to genomics (extensive genome or transcriptome sequencing) in the forthcoming years and that sponge ecologists will take advantage of this research trend to answer ecological and biological questions that would have been impossible to address a few years ago. | Porifera |
RATIONALE, AIMS, AND OBJECTIVES: Increasing the appropriateness of prescribing has long been a focus of government, non-government, and professional organizations. Progress towards this is made difficult by the fact appropriate prescribing remains inconsistently defined and is the subject of ongoing intense disagreement. In this study, we attempted to understand why this is the case within the context of oncology and haematology. METHODS: We performed a qualitative empirical analysis of semi-structured interviews with 16 Australian oncologists and haematologists. RESULTS: We found that oncologists framed appropriate prescribing in terms of the following inter-related, and at times opposed, values: civic mindedness, hope and compassion, realism, and virtue in motivation. CONCLUSIONS: These values cannot be ranked a priori, and therefore, any definition of appropriate prescribing must be aligned with what communities want from their health system. When one value is privileged over another in any specific context, a compelling argument must be provided to justify the choice. In an era of shared decision making, patient rights, and high-cost medicines, we need to reassess what we mean by appropriate prescribing in cancer care. | Fantasy |
The basal forebrain comprises several heterogeneous neuronal subgroupings having modular projection patterns to discrete sets of cortical subregions. Each cortical region forms recurrent projections, via prefrontal cortex, that reach the specific basal forebrain subgroups from which they receive afferents. This architecture enables the basal forebrain to selectively modulate cortical responsiveness according to current processing demands. Theoretically, optimal functioning of this distributed network would be enhanced by temporal coordination among coactive basal forebrain neurons, or the emergence of cell assemblies." The present work demonstrates assembly formation in rat basal forebrain neuronal populations during a selective attention task. Neuron pairs exhibited coactivation patterns organized within beta-frequency time windows (55 ms), regardless of their membership within distinct bursting versus nonbursting basal forebrain subpopulations. Thus, the results reveal a specific temporal framework for integration of information within basal forebrain networks and for the modulation of cortical responsiveness." | Basal Forebrain |
Guttaviridae is a family of enveloped viruses infecting hyperthermophilic archaea. The virions are ovoid or droplet-shaped, with a diameter of 55-80 nm and a length of 75-130 nm. The genome is a circular dsDNA molecule of around 14-20 kbp. The droplet-shaped morphology is unprecedented among viruses of bacteria and eukaryotes and represents a group of archaea-specific virion morphotypes. The family includes two genera, Alphaguttavirus and Betaguttavirus, each with a single species. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of Guttaviridae, which is available at www.ictv.global/report/guttaviridae. | Guttaviridae |
To evaluate the applicability of 23 autosomal STR loci (D10S1248, D11S4463, D12ATA63, D14S1434, D17S1301, D18S853, D1GATA113, D1S1627, D6S1017, D20S1082, D20S482, D17S974, D22S1045, D1S1677, D2S1776, D2S441, D3S4529, D4S2408, D9S1122D5S2500, D6S474, D18S51, D9S2157) included in DNA Typer 25 Kit for individual identification and parentage testing, allele frequencies and forensic efficiency parameters were first obtained from healthy, unrelated 506 Chongqing Tujia individuals. A total of 1012 alleles were identified in 23 STR loci, and allele frequencies ranged from 0.001 to 0.5761. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) of the 23 STR loci were 0.999999999999999999999753 and 0.99999967, respectively. These results suggested that 23 autosomal STR loci could be used as an effective tool for forensic application in Chongqing Tujia population. Comprehensive comparisons were conducted based on the analysis of genetic distance, principal component analysis (PCA), multidimensional scaling plot (MDS), and phylogenetic tree to explore the interpopulation genetic relationship. Our results revealed that Chongqing Tujia keeps the more relatively genetic similarity with Hunan Han, Hubei Tujia, and Sichuan Han, which could be interpreted by that those populations were originated from the same ethnic ancestor or genetic communication were happened in adjacent areas." | Multidimensional Scaling Analysis |
BACKGROUND: Cerebral hemodynamics and venous outflow from the brain may be altered during exposure to microgravity or head-down tilt (HDT), an analog of microgravity, as well as by increased ambient CO2 exposure as experienced on the International Space Station. METHODS: Six healthy subjects underwent baseline tilt table testing at 0 degrees , 6 degrees , 12 degrees , 18 degrees , 24 degrees , and 30 degrees HDT. The right internal jugular (IJ) vein cross-sectional area (CSA) was measured at four intervals from the submandibular to the clavicular level and IJ volume was calculated. Further measurements of the IJ vein were made after approximately 26 h of 12 degrees HDT bed rest with either ambient air or 0.5% CO2 exposure, and plasma and blood volume were assessed after 4 h, 24 h, and 28.5 h HDT. RESULTS: IJ vein CSA and volume increased with progressively steeper HDT angles during baseline tilt table testing, with more prominent filling of the IJ vein at levels closer to the clavicle. Exposure to 26 h of 12 degrees HDT bed rest with or without increased CO2, however, had little additional effect on the IJ vein. Further, bed rest resulted in a decrease in plasma volume and blood volume, although changes did not depend on atmospheric conditioning or correlate directly with changes in IJ vein CSA or volume. DISCUSSION: The hydrostatic effects of HDT can be clearly determined through measurement of the IJ vein CSA and volume; however, IJ vein dimensions may not be a reliable indicator of systemic fluid status during bed rest.Marshall-Goebel K, Stevens B, Rao CV, Suarez JI, Calvillo E, Arbeille P, Sangi-Haghpeykar H, Donoviel DB, Mulder E, Bershad EM, the SPACECOT Investigators Group. Internal jugular vein volume during head-down tilt and carbon dioxide exposure in the SPACECOT Study. Aerosp Med Hum Perform. 2018; 89(4):351-356. | Head-Down Tilt |
The current management of acute post-operative endophthalmitis relies on microbial confirmation, intravitreal antibiotics, and vitrectomy. The endophthalmitis vitrectomy study (EVS) demonstrated that systemic antibiotics are not necessary in post-cataract/secondary intraocular lens (IOL) acute bacterial endophthalmitis, and that vitrectomy could be required only for eyes with presenting vision of light perception. Since the publication of the EVS newer tests are available for microbial confirmation, and many new and effective antibiotics are discovered for systemic therapy. We have studied large numbers of patients with endophthalmitis over several years. Perhaps our experience represents the endophthalmitis status in the developing countries. The article is a synthesis of recent publications in the world literature. Finally the authors have suggested a management strategy for acute post-cataract acute bacterial endophthalmitis. | Endophthalmitis |
The Secretary of the Department of Health and Human Services (HHS) adopts this interim final rule to conform the enforcement regulations promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPAA) to the effective statutory revisions made pursuant to the Health Information Technology for Economic and Clinical Health Act (the HITECH Act), which was enacted as part of the American Recovery and Reinvestment Act of 2009 (ARRA). More specifically, this interim final rule amends HIPAA's enforcement regulations, as they relate to the imposition of civil money penalties, to incorporate the HITECH Act's categories of violations, tiered ranges of civil money penalty amounts, and revised limitations on the Secretary's authority to impose civil money penalties for established violations of HIPAA's Administrative Simplification rules (HIPAA rules). This interim final rule does not make amendments with respect to those enforcement provisions of the HITECH Act that are not yet effective under the applicable statutory provisions. Such amendments will be subject to forthcoming rulemaking(s)." | American Recovery and Reinvestment Act |
BACKGROUND, AIM, AND SCOPE: The behavior of polycyclic aromatic hydrocarbons (PAHs) is affected by dissolved organic matter (DOM) present in pore water of soils and sediments. Since partitioning to DOM reduces the bioavailable or freely dissolved PAH concentration in pore water, it is important to assess the effect of environmental variables on the magnitude of dissolved organic matter to water partition coefficients (K (DOC)). The objective of this study was to apply passive samplers to measure freely dissolved PAHs allowing depletion from the aqueous phase. The method was applied to determine K (DOC) at different temperatures for a selection of PAHs with natural DOM of very different origin. MATERIALS AND METHODS: Freely dissolved concentrations of (spiked) phenanthrene, anthracene, fluoranthene, pyrene, and benzo[e]pyrene were determined by exposing polydimethylsiloxane (PDMS) fibers to aqueous solutions containing DOM extracted from freshwater sediments from Finland and the Netherlands. The K (DOC) values were subsequently calculated at different temperatures (3.2, 20, and 36 degrees C) by including temperature-dependent PDMS to water partition coefficients (K (PDMS)) in a mass balance. Furthermore, the effect of temperature on partitioning of PAHs to PDMS fibers or DOM was assessed by comparing the enthalpy of sorption to the excess enthalpy of dissolution of liquid PAHs. RESULTS AND DISCUSSION: Partitioning to DOM resulted in a decrease of freely dissolved concentrations with increasing DOM concentrations and a large range in log K (DOC) values at 20 degrees C for benzo[e]pyrene was observed (log K (DOC) = 4.93-6.60 L kg(-1) organic carbon). An increase of 10 degrees C in temperature resulted in a decrease of K (PDMS) by 0.09 to 0.13 log units for phenanthrene to pyrene and a decrease of K (DOC) by 0.13 log units for pyrene. The calculated enthalpies of sorption were less exothermic than the (negative) excess enthalpies of dissolution as expected for non-specific interactions between PAHs and PDMS or DOM. CONCLUSIONS: The bioavailability of PAHs in sedimentary pore waters can be accurately determined by application of PDMS fibers (without requiring negligible depletion) in the presence of natural DOM with different sorption affinity for PAHs. The observed natural variability in log K (DOC) values for different sediments shows that large differences can occur in freely dissolved PAH concentrations in pore water and properties of DOM should be taken into account in predicting the bioavailability of PAHs. Furthermore, the effect of temperature on the partitioning behavior of PAHs shows that interactions between PAHs and environmental sorbents are comparable to interactions between PAHs in their pure condensed liquid phase and calculated excess enthalpies can be safely used to directly correct partition coefficients for temperature. RECOMMENDATIONS AND PERSPECTIVES: The application of PDMS fibers in measuring freely dissolved PAH concentrations can be used to study structural and thermodynamic aspects of PAH sorption to natural DOM as well as other environmental processes such as enhanced diffusion phenomena in pore water that are dependent on the amount (or concentration) of DOM, sorption affinity of DOM, and hydrophobicity of PAHs. These environmental factors will therefore give further insight into the site-specific exposure to freely dissolved PAH concentrations in soil and sedimentary pore water." | Polycyclic Aromatic Hydrocarbons |
Currently, pseudorabies virus (PRV) variant strains are outbreaking in China; these variants belong to genotype II PRV. The traditional Bartha-K61 vaccine has failed to provide complete protection against the emergent variant strains. Therefore, rapid attenuation of current epidemic strains is needed for effective PRV control. In this study, we report a rapid method for editing the PRV genome using the CRISPR-Cas9 system. We developed a triple gE/gI/TK gene-inactivated HeN1 PRV strain, because mice were more susceptible to PRV infection, we then evaluated the attenuation of PRV in the mice and demonstrated that modified PRV was fully attenuated. Furthermore, the attenuated strain also induced immune protection in response to a parental PRV challenge. Overall, we showed that PRVs can be rapidly attenuated using CRISPR-Cas9 technology, which will be critical for PRV control, especially when new variant PRV strains emerge. | Pseudorabies Vaccines |
The unusual structure of clathrin, combined with its ability to assemble and disassemble rapidly in cells provides a model system for us to learn about the ways in which proteins can contribute mechanically to a functioning cell. In this article, we discuss the structural properties of clathrin cages and the triskelions which assemble to form them. The function of clathrin depends on the structure of these triskelions and the interactions they make both with each other during assembly and with the adaptor protein network that drives coated vesicle formation. The atomic resolution structure of clathrin domains has been revealed by X-ray crystallography while scattering studies have enabled the shape of a triskelion in solution to be deduced. Cryo-electron microscopy maps have shown the secondary structure of entire cages, how individual triskelion legs are arranged to form a cage and enabled some bound adaptor proteins to be located. Cage formation itself is energetically finely balanced and requires specific interactions between triskelion legs to be productive, as biochemical studies and in silico modeling have shown. Theoretical, structural and cell biological investigations over many years have contributed to our knowledge of clathrin structure and assembly. It now remains to determine the precise nature of the interactions which occur between clathrin triskelions, light chain and heavy chain and the adaptor protein network. | Clathrin |
The rapid increase of the number of sequenced genomes asks for the functional annotation of the encoded enzymes. We used a combined computational-structural approach to determine the function of the TrpB2 subgroup of the tryptophan synthase beta chain/beta chain-like TrpB1-TrpB2 family (IPR023026). The results showed that TrpB2 enzymes are O-phospho-l-serine dependent tryptophan synthases, whereas TrpB1 enzymes catalyze the l-serine dependent synthesis of tryptophan. We found a single residue being responsible for the different substrate specificities of TrpB1 and TrpB2 and confirmed this finding by mutagenesis studies and crystallographic analysis of a TrpB2 enzyme with bound O-phospho-l-serine. | Tryptophan Synthase |
We examined the relationship between the ambient illuminant chromaticity and changes in the sensitivity balance of the visual system, using illuminants of various chromaticities. The sensitivity of observers was measured in a room with a variable-chromaticity illuminant. The observer's state of chromatic adaptation was measured with unique-white settings. Our results showed that the change in visual sensitivity has a nonlinear correlation with the change in illuminant chromaticity; chromatic adaptation was nearly complete for desaturated illuminants, but the degree of chromatic adaptation became worse as the illuminant became more saturated. We defined a new index, relative cone weights, which represents this relationship well. To measure the role of chromatic induction from the immediate-surround area of the matching stimulus, we performed additional experiments by presenting the test inside a colored or black immediate surround. The results showed that the unique-white settings were not disturbed by the change in immediate-surround color. Our results imply that the room illuminant chromaticity was the primary factor in changing the observer's state of chromatic adaptation. | Color Perception |
MyoD is a key regulator of skeletal myogenesis that directs contractile protein synthesis, but whether this transcription factor also regulates skeletal muscle metabolism has not been explored. In a genome-wide ChIP-seq analysis of skeletal muscle cells, we unexpectedly observed that MyoD directly binds to numerous metabolic genes, including those associated with mitochondrial biogenesis, fatty acid oxidation, and the electron transport chain. Results in cultured cells and adult skeletal muscle confirmed that MyoD regulates oxidative metabolism through multiple transcriptional targets, including PGC-1beta, a master regulator of mitochondrial biogenesis. We find that PGC-1beta expression is cooperatively regulated by MyoD and the alternative NF-kappaB signaling pathway. Bioinformatics evidence suggests that this cooperativity between MyoD and NF-kappaB extends to other metabolic genes as well. Together, these data identify MyoD as a regulator of the metabolic capacity of mature skeletal muscle to ensure that sufficient energy is available to support muscle contraction. | Transcription Factor RelB |
Nanoparticles must recognize, adhere to, and/or traverse multiple barriers in sequence to achieve cytosolic drug delivery. New nanoparticles often exhibit a unique ability to cross a single barrier (i.e. the vasculature, cell membrane, or endosomal compartment), but fail to deliver an adequate dose to intracellular sites of action because they cannot traverse other biological barriers for which they were not optimized. Here, we developed poly(acrylamide-co-methacrylic acid) nanogels that were modified in a modular manner with bioactive peptides. This nanogel does not recognize target cells or disrupt endosomal vesicles in its unmodified state, but can incorporate peptides with molecular recognition or environmentally responsive properties. Nanogels were modified with up to 15 wt% peptide without significantly altering their size, surface charge, or stability in aqueous buffer. Nanogels modified with a colon cancer-targeting oligopeptide exhibited up to a 324% enhancement in co-localization with SW-48 colon cancer cells in vitro, while influencing nanogel uptake by fibroblasts and macrophages to a lesser extent. Nanogels modified with an endosome disrupting peptide failed to retain its native endosomolytic activity, when coupled either individually or in combination with the targeting peptide. Our results offer a proof-of-concept for modifying synthetic nanogels with a combination of peptides that address barriers to cytosolic delivery individually and in tandem. Our data further motivate the need to identify endosome disrupting moieties which retain their activity within poly(acidic) networks. | Nanogels |
BACKGROUND: MECP2 Duplication syndrome (MDS) is a rare X-linked genomic disorder that is caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2 gene. Although phenotypic features in MDS have been described, there is a limited understanding of the range of severity of these features, and how they evolve with age. METHODS: The cross-sectional results of N = 69 participants (ages 6 months-33 years) enrolled in a natural history study of MDS are presented. Clinical severity was assessed using a clinician-report measure as well as a parent-report measure. Data was also gathered related to the top 3 concerns of parents as selected from the most salient symptoms related to MDS. The Child Health Questionnaire was also utilized to obtain parental reports of each child's quality of life to establish disease burden. RESULTS: The results of linear regression from the clinician-reported measure show that overall clinical severity scores, motor dysfunction, and functional skills are significantly worse with increasing age. Top concerns rated by parents included lack of effective communication, abnormal walking/balance issues, constipation, and seizures. Higher levels of clinical severity were also related to lower physical health quality of life scores as reported by parents. CONCLUSIONS: The data suggest that increasing levels of clinical severity are noted with older age, and this is primarily attributable to motor dysfunction, and functional skills. The results provide an important foundation for creating an MDS-specific severity scale highlighting the most important domains to target for treatment trials and will help clinicians and researchers define clinically meaningful changes. | Genetic Diseases, X-Linked |
Allergic fungal rhinosinusitis (AFRS) forms a significant group of patients presenting with the commonest health problem encountered in rhinology. Patients commonly present with typical symptoms of sinusitis, and the diagnosis is often made after imaging and/or intraoperatively. Infections caused by Chrysosporium species are very rare and are very rarely been reported to cause sinusitis in humans. Usually, human chrysosporial infections are mild and unmarked by symptoms. We report a rare case of allergic fungal sinusitis (AFS) caused by Chrysosporium species in a 41-year-old male with the history of diabetes mellitus. | Allergic Fungal Sinusitis |
Inspired by the initial mineralization process in bone matrix vesicles (MVs), we used Dulbecco's Modified Eagle's Medium (DMEM) to establish the similar physiological environment to that in MVs for biomimetic mineralization on alginate (ALG) microspheres. The results showed that HA crystals were firstly formed and anchored on the membrane of microspheres like the initial deposition of hydroxyapatite crystals inside MVs. With the continuous growth and accumulation of mineral crystals, HA coating was finally formed on ALG microspheres. The mineralized ALG microspheres (M-ALG microspheres) show good biocompatibility and osteogenic performance. The HA coating is also conducive to the active migration of osteoblasts to the surface of M-ALG microspheres. Collectively, bone-like HA crystals anchored on ALG microspheres may provide a good prospect to promote the repair of bone defects. | Durapatite |
We describe a patient in whom the combination of excessive air in the maxillary sinus and the presence of a patent nasopalatine duct led to misdiagnosis and subsequent treatment of a non-existent oroantral perforation. When a radiograph indicates that antral involvement during removal of a maxillary molar is unlikely, and yet a routine postoperative nose-blowing test contradicts this, the possible presence of a pre-existent oronasal communication such as a patent nasopalatine duct should be considered. | Oroantral Fistula |
A 37-year-old homosexual man suffering from AIDS (= Acquired Immune Deficiency Syndrome) is described. This man died from disseminated Kaposi-sarcomas about one year after establishing the diagnosis. | Sarcoma, Kaposi |
We present the functional and structural characterization of the first archaeal thermostable NADP-dependent aldehyde dehydrogenase AlDHPyr1147. In vitro, AlDHPyr1147 catalyzes the irreversible oxidation of short aliphatic aldehydes at 60-85 degrees capital ES, Cyrillic, and the affinity of AlDHPyr1147 to the NADP+ at 60 degrees capital ES, Cyrillic is comparable to that for mesophilic analogues at 25 degrees capital ES, Cyrillic. We determined the structures of the apo form of AlDHPyr1147 (3.04 A resolution), three binary complexes with the coenzyme (1.90, 2.06, and 2.19 A), and the ternary complex with the coenzyme and isobutyraldehyde as a substrate (2.66 A). The nicotinamide moiety of the coenzyme is disordered in two binary complexes, while it is ordered in the ternary complex, as well as in the binary complex obtained after additional soaking with the substrate. AlDHPyr1147 structures demonstrate the strengthening of the dimeric contact (as compared with the analogues) and the concerted conformational flexibility of catalytic Cys287 and Glu253, as well as Leu254 and the nicotinamide moiety of the coenzyme. A comparison of the active sites of AlDHPyr1147 and dehydrogenases characterized earlier suggests that proton relay systems, which were previously proposed for dehydrogenases of this family, are blocked in AlDHPyr1147, and the proton release in the latter can occur through the substrate channel. | Pyrobaculum |
Dermatophytes are causing superficial mycosis in animals and humans. Depending on the geophilic, zoophilic or anthropophilic origin of the fungus but also on the immunological status of the patient, symptomatology can widely differ. Nevertheless, each species is currently associated with typical clinical manifestations, even if atypical localizations and/or clinical pictures are sometimes also reported. Diagnostic tools applied to species identification have been changing since the last two decades with the more frequent use of molecular methods currently considered nowadays as reference methods for species identification. It becomes obvious that the algorithm used for the distinction of closely related species needs to combine phenotypic and genomic methods. All these different points are discussed, and the most recent novel species causing or involved in human dermatophytosis are reported. | Onygenales |
Mycobacteria have a distinct secretion system, termed type VII (T7SS), which is encoded by paralogous chromosomal loci (ESX) and associated with pathogenesis, conjugation, and metal homeostasis. Evolution of paralogous gene families is of interest because duplication is an important mechanism by which novel genes evolve, but there are potential conflicts between adaptive forces that stabilize duplications and those that enable evolution of new functions. Our objective was to delineate the adaptive forces underlying diversification of T7SS. Plasmid-borne ESX were described recently, and we found evidence that the initial duplication and divergence of ESX systems occurred on plasmids and was driven by selection for advantageous mutations. Plasmid conjugation has been linked to T7SS and type IV secretion systems (T4SS) in mycobacteria, and we discovered that T7SS and T4SS genes evolved in concert on the plasmids. We hypothesize that differentiation of plasmid ESX helps to prevent conjugation among cells harboring incompatible plasmids. Plasmid ESX appear to have been repurposed following migration to the chromosome, and there is evidence of positive selection driving further differentiation of chromosomal ESX. We hypothesize that ESX loci were initially stabilized on the chromosome by mediating their own transfer. These results emphasize the diverse adaptive paths underlying evolution of novelty, which in this case involved plasmid duplications, selection for advantageous mutations in the mobile and core genomes, migration of the loci between plasmids and chromosomes, and lateral transfer among chromosomes. We discuss further implications for the choice of model organism to study ESX functions in Mycobacterium tuberculosis. | Type VII Secretion Systems |
Dirofilariaeformia pulmoni sp. n. from the eastern gray squirrel (Sciurus carolinensis Gmelin) is differentiated from other species of the genus by its smaller body size, shorter spicules, arrangement of caudal papillae, and morphology of microfilariae. Adult filarids were found in the pulmonary artery and its branches, and the microfilariae occurred in the blood. A large antemortem thrombus that occluded approximately two-thirds of the lumen of the artery was associated with infection in one squirrel. | Filarioidea |
This study sought to characterize the effects of removing the nuclei of primary importance in relaying the thalamic head direction signal to the hippocampal formation (the anterior dorsal [AD] and lateral dorsal [LD] nuclei) on the performance of a variety of spatial and nonspatial tasks. The results indicate that combined excitotoxic lesions of the AD and LD nuclei produce marked deficits on a variety of spatial tasks. These tasks included T-maze alternation and the ability to locate a hidden platform set at a fixed distance and fixed direction from a beacon in a Morris water maze. Although object recognition appeared unaffected, marked impairments were found in the ability to detect when an object was placed in a novel position (object-in-place memory). | Anterior Thalamic Nuclei |
Acute kidney injury (AKI) is frequently associated with alterations in fluid balance making accurate assessment of hemodynamics a vital component of patient management. Unfortunately, conventional parameters such as history, physical examination, vital signs, weight, natriuretic peptides have limitations in this regard. Point of care ultrasonography (POCUS) is a clinician-performed limited ultrasound study intended to answer focused clinical questions at the bedside. In the past several years, it has evolved as an extension of physical examination in various medical specialties. Herein, we describe a case of AKI where nephrologist-performed multi-organ POCUS aided in accurate diagnosis of fluid overload state. In addition, we describe how venous Doppler (VExUS) evaluation can be used to monitor the efficacy of decongestive therapy in real-time. Nephrologists should adopt a multi-parametric approach integrating all the pieces of hemodynamic puzzle when evaluating patients with AKI and fluid/electrolyte disorders. | Nephrologists |
The neuroleptics are characterised by the large number of pharmacological effects they develop. When they are associated with other substances, it is frequent for the latter to have with neuroleptics one or several common sites of action. At this level, they develop phenomena of drug interaction, for example, synergy with depressors of the central nervous system or, in the periphery, with alpha-adrenolytic or parasympatholytic drugs. This type of interaction is used in anesthesia to obtain more intense effects with lesser doses of each component and also avoid the toxic effects of efficacious doses of general anesthetics used alone. However, although certain interactions are useful, others may prove harmful. This is in particular the case where neuroleptic drugs are administered after ingestion of alcohol. Various mechanisms, central and peripheral, explain the marked depression of the central nervous system which results. Potentialisation of the effects of tricyclic antidepressor drugs by neuroleptics raises a difficult problem for the anesthetist, the elimination of tricyclic antidepressor drugs is slow and requires several weeks after stopping treatment. During this period, the tissue and plasma concentrations become reduced gradually. They are pharmacologically insufficient, but are potentialised by injection of neuroleptic drugs, and may become active again, and even toxic. It seems to us advisable to avoid the use of neuroleptic drugs in patients treated with tricyclic antidepressor drugs and, if necessary, to use another method of anesthesia. | Tranquilizing Agents |
People of all ages are increasingly consuming larger portions of food. Governments worldwide are involved in the regulation of many aspects of the food supply; however, policies and programs related to serving sizes for children vary or are not clearly communicated. This paper reviews U.S. federal and state government recommendations, policies, and laws related to serving size for children and suggests directions for future policy objectives and outstanding research needed to support the enactment of laws based on the best science. Specifically, this paper reviews federal dietary recommendations and requirements for nutrition programs, packaged food labels and restaurant menus; state regulation of retail environments and child care settings; food companies' self-regulatory options; and directions for future research and policy initiatives. The paper concludes that there are many opportunities for government to revise its policies and programs to better support healthy portion sizes for children and create a more transparent information environment to assist caretakers to do the same. | Portion Size |
The growth of twelve methanotrophic strains within the genus Methylomonas, including the type strains of Methylomonas methanica and Methylomonas koyamae, was evaluated with 40 different variations of standard diluted nitrate mineral salts medium in 96-well microtiter plates. Unique profiles of growth preference were observed for each strain, showing a strong strain dependency for optimal growth conditions, especially with regards to the preferred concentration and nature of the nitrogen source. Based on the miniaturized screening results, a customized medium was designed for each strain, allowing the improvement of the growth of several strains in a batch setup, either by a reduction of the lag phase or by faster biomass accumulation. As such, the maintenance of fastidious strains could be facilitated while the growth of fast-growing Methylomonas strains could be further improved. Methylomonas sp. R-45378 displayed a 50 % increase in cell dry weight when grown in its customized medium and showed the lowest observed nitrogen and oxygen requirement of all tested strains. We demonstrate that the presented miniaturized approach for medium optimization is a simple tool allowing the quick generation of strain-specific growth preference data that can be applied downstream of an isolation campaign. This approach can also be applied as a first step in the search for strains with biotechnological potential, to facilitate cultivation of fastidious strains or to steer future isolation campaigns. | Methylococcaceae |
Limb lymphedema is frequent and not well-known. Clinical classification distinguishes primary lymphedemas due to developmental disorders of the lymphatic system (hereditary or not, sometimes associated with other malformations) and secondary lymphedemas. Primary lymphedema is a lymphedema without a cause to explain lymphatic impairment. It is due to an abnormal lymphangiogenesis in utero. It is often associated with mutation in a gene involved in lymphangiogenesis (FOX C2, VEGFR 3, SOX18, PROX 1...). To assess clinical diagnosis, non-invasive techniques are able to study structure and function of the lymphatic system (mainly isotopic lymphography). Treatment is the complex decongestive therapy which associates manual lymphatic drainage and bandage. Predisposing or precipitating factors have to be treated (particularly streptococcal infections). Surgical treatment has precise and rare indication. | SOXF Transcription Factors |
PURPOSE: While sinusitis carries a seasonal variation, the temporal features of sinusitis-related orbital cellulitis (SRC) are unclear. This study analyzes the incidence, seasonality, management, and outcomes of SRC in northeastern New York. METHODS: A retrospective review of 79 patients was performed from January 2008 - December 2018. Cases of orbital cellulitis without comitant sinusitis were excluded. Demographic, radiographic, clinical features, month at presentation, interventions (surgical and nonsurgical), microbiology, and hospitalization duration were recorded. Fisher-exact test, Mann-Whitney test, and Kruskal Wallis test statistical analyses were performed in consultation with our institution's statistician via a dedicated software package (vassarstats.net). RESULTS: 79 patients were admitted for SRC. 25 patients were treated with antibiotics only, 31 underwent orbitotomy exclusively and 23 received combined orbitotomy and functional endoscopic sinus surgery (FESS). Of the 31 patients who underwent orbitotomy only, 8 (26%) returned to the operating room. In contrast, of those who underwent concomitant orbitotomy and FESS, only one patient (4.3%) required re-operation (fisher exact test, p = .021). The median length of stay for the antibiotic-only group (4 days), orbitotomy-only group (6 days), and combined surgery group (5 days) were statistically different (Kruskal Wallis, p = .004, Figure 3). Interestingly, there was no significant relationship of incidence or severity of SRC related to seasonality (fisher-exact test, p = .76). CONCLUSION: Our findings suggest that cases requiring surgical management for SRC should undergo coinitial orbitotomy with FESS to reduce re-operation rates. Additionally, SRC incidence and severity did not correlate with season. | Orbital Cellulitis |
Work on the estrogen receptor and glucocorticoid receptor laid the foundation for the discovery of a family of receptors known as the nuclear receptors. Discovery of these receptors has expanded our understanding of many hormonal and nonhormonal substances, which act through the nuclear receptors. These receptors are actually ligand-binding intracellular transcription factors, which induce nuclear expression of specific mRNAs, leading to synthesis of specific proteins with biological activity. This review for the benefit of gynecologists and reproductive physiologists focuses on the work of 3 scientists who were pioneers in the work on the estrogen, glucocorticoid, and progesterone receptors, which has had a major impact on our understanding of reproductive physiology and on the field of nuclear receptors. | Receptors, Steroid |
The detailed morphology of pulmonary neuroendocrine (NE) cells has been defined only during the last decade. The purpose of this paper is to review the main morphologic features of the NE cells, to review the methods and techniques used for their identification, and to discuss the development and functional significance of these cells. The main emphasis is on NE cells in human lung, but where appropriate, studies in animal lungs are also included. NE cells are present in the airway epithelium of human and various animal species and occur singly as well as in clusters called neuroepithelial bodies (NEB). The general cytochemical features (common to both single NE cells and NEB) include cytoplasmic argyrophilia, fluorogenic amine content, positive staining with lead-hematoxylin, and masked metachromasia. These staining properties are similar to those found in APUD cells scattered in various tissues. More specific cell markers are immunoreactivity to peptide hormones (bombesin, calcitonin, leu-enkephalin) identified so far in NE cells of human lung, and immunoreactivity to serotonin found in both human and animal lungs. At the ultrastructural level, NE cells are characterized by the presence of cytoplasmic dense core granules (90-150 nm in diameter), which are considered the storage site of amine and peptide hormones. The distinctive feature of NEB, not found with single NE cells, is the presence of nonmyelinated nerve endings in contact with granulated cells, and positive staining for acetylcholinesterase. The single NE cells are scattered throughout the tracheobronchial epithelium, whereas NEB are found only within the intrapulmonary airways. In postnatal lungs, both the single NE cells and NEB appear concentrated in small peripheral airways. In developing human lung, the first NE cells appear at 8 weeks' gestation, when all other epithelial cells are still undifferentiated. The development and cytodifferentiation of NE cells progresses in a centrifugal direction. By the end of the glandular period, single and groups of NE cells are found along the entire length of primitive bronchial epithelium. Based on differences in the size and morphology of cytoplasmic granules, three distinct types of NE cells can be recognized. During terminal stages of development, NE cells appear in small peripheral airways and primitive saccules. The functional considerations include the possible role of NE cells as endocrine, paracrine, or receptosecretory cells involved in neurohormonal regulation of pulmonary vascular or bronchial responses, and possible function of NEB as intrapulmonary hypoxia-sensitive chemoreceptors. | APUD Cells |
Until recently, prebiotic precursors to metabolic pathways were not known. In parallel, chemistry achieved the synthesis of amino acids and nucleotides only in reaction sequences that do not resemble metabolic pathways, and by using condition step changes, incompatible with enzyme evolution. As a consequence, it was frequently assumed that the topological organisation of the metabolic pathway has formed in a Darwinian process. The situation changed with the discovery of a non-enzymatic glycolysis and pentose phosphate pathway. The suite of metabolism-like reactions is promoted by a metal cation, (Fe(II)), abundant in Archean sediment, and requires no condition step changes. Knowledge about metabolism-like reaction topologies has accumulated since, and supports non-enzymatic origins of gluconeogenesis, the S-adenosylmethionine pathway, the Krebs cycle, as well as CO(2) fixation. It now feels that it is only a question of time until essential parts of metabolism can be replicated non-enzymatically. Here, I review the 'accidents' that led to the discovery of the non-enzymatic glycolysis, and on the example of a chemical network based on hydrogen cyanide, I provide reasoning why metabolism-like non-enzymatic reaction topologies may have been missed for a long time. Finally, I discuss that, on the basis of non-enzymatic metabolism-like networks, one can elaborate stepwise scenarios for the origin of metabolic pathways, a situation that increasingly renders the origins of metabolism a tangible problem. | Energy Metabolism |
Ferroptosis is a form of regulated cell death resulting from iron accumulation and lipid peroxidation. While impaired ferroptosis is tightly linked to human diseases and conditions, the mechanism and regulation of ferroptosis remain largely unknown. Here, we demonstrate that STAT3 is a positive regulator of ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cell lines. Activation of the MAPK/ERK pathway, but not inhibition of system Xc(-), was required for STAT3 activation during erastin-induced ferroptosis. Importantly, pharmacological inhibition and genetic silencing of STAT3 through small molecules (e.g., cryptotanshinone and S3I-201) or siRNA blocked erastin-induced ferroptosis in PDAC cells. Mechanically, STAT3-mediated cathepsin B expression was required for ferroptosis. Consequently, inhibition of lysosome-dependent cell death by pharmacological blockade of cathepsin activity (using CA-074Me) or vacuolar type H+-ATPase (using bafilomycin A1) limited erastin-induced ferroptosis. These studies indicate that ferroptosis is a lysosomal cell death process. | Lysosomes |
BACKGROUND: Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. OBJECTIVES: We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. RESULTS: Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. CONCLUSIONS: This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative. | Theobromine |
OBJECTIVE: To investigate the value of serum presepsin concentration measurement in the clinical diagnosis and treatment of patients with pesticide poisoning patients. METHODS: A total of 160 patients with pesticide poisoning were enrolled as study subjects and divided into moderate organophosphate pesticide poisoning group (40 patients) , severe organophosphate pesticide poisoning group (40 patients) , abamectin pesticide poisoning group (40 patients) , and paraquat poisoning group (40 patients). A total of 20 healthy volunteers were enrolled as the control group. All the patients with poisoning received conventional treatment of pesticide poisoning immediately after admission, and serum presepsin concentration was measured on days 1 (within 24 hours after poisoning) , 3, and 7 of admission, and biochemical and radiological parameters related to the patient's condition were also examined. The patients with a Presepsin concentration of >800 pg/ml on day 1 of admission were randomly divided into conventional treatment group and ulinastatin treatment group, and the treatment outcome was compared between the two groups. RESULTS: Compared with the healthy control group, the groups with pesticide poisoning showed significant increases in serum Presepsin concentrations, with the highest degree of increase on day 1 (P <0.05). The serum Presepsin concentration was positively correlated with alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase MB, lactate dehydrogenase, serum creatinine, blood urea nitrogen, interleukin-18, and white blood cell count, but negatively correlated with cholinesterase. In the conventional treatment group and ulinastatin treatment group, the overall response rate was 68% and 78.8%, respectively, with a significant difference between the two groups (P<0.05). In 40 patients with paraquat poisoning, 32 experienced an increase in serum presepsin concentration, and among these 32 patients, 27 (83%) experienced exudation on lung CT. CONCLUSION: Serum Presepsin concentration measurement can assist early diagnosis, evaluation of disease severity, and guidance for clinical medication in patients with pesticide poisoning, especially in those with severe pesticide poisoning and a tendency to multiple organ failure." | Phosphotransferases (Nitrogenous Group Acceptor) |
OBJECTIVES: Recent literature has highlighted histological types of ovarian carcinoma as distinct diseases, each with unique clinical and molecular features. Historically, the diagnosis of ovarian clear cell carcinoma (CCC) has been of concern to both patients and physicians due to reports that CCC is associated with a worse prognosis than the more common serous type of ovarian carcinoma (HGSC). This review discusses the unique features of ovarian CCC. METHODS: In June of 2010, a group of researchers and clinicians convened in Vancouver to review and discuss the clinical, pathological, molecular, and treatment-related features of CCC. RESULTS: CCC is the second most common type of ovarian epithelial cancer, representing 5-25% of ovarian carcinomas. It is characterised by its association with endometriosis, and frequent mutations of ARID1A and PIK3CA. Low-stage CCC appears to have a better outcome than stage matched HGSC, while the opposite is true for high-stage disease, suggesting that the current standard treatments applied to HGSC are ineffective for CCC. CONCLUSIONS: Ovarian CCC is highly distinct from HGSC, and a clearer understanding of the basic biology of this disease is needed. Alternative therapies should be explored: irradiation and targeting disease-specific molecular markers should be examined in greater detail. Finally, novel approaches to clinical trial design are needed due to the smaller numbers of patients affected. | Adenocarcinoma, Clear Cell |
Lichens occur in most terrestrial ecosystems; they are often present as minor contributors, but in some forests, drylands and tundras they can make up most of the ground layer biomass. As such, lichens dominate approximately 8% of the Earth's land surface. Despite their potential importance in driving ecosystem biogeochemistry, the influence of lichens on community processes and ecosystem functioning have attracted relatively little attention. Here, we review the role of lichens in terrestrial ecosystems and draw attention to the important, but often overlooked role of lichens as determinants of ecological processes. We start by assessing characteristics that vary among lichens and that may be important in determining their ecological role; these include their growth form, the types of photobionts that they contain, their key functional traits, their water-holding capacity, their colour, and the levels of secondary compounds in their thalli. We then assess how these differences among lichens influence their impacts on ecosystem and community processes. As such, we consider the consequences of these differences for determining the impacts of lichens on ecosystem nutrient inputs and fluxes, on the loss of mass and nutrients during lichen thallus decomposition, and on the role of lichenivorous invertebrates in moderating decomposition. We then consider how differences among lichens impact on their interactions with consumer organisms that utilize lichen thalli, and that range in size from microfauna (for which the primary role of lichens is habitat provision) to large mammals (for which lichens are primarily a food source). We then address how differences among lichens impact on plants, through for example increasing nutrient inputs and availability during primary succession, and serving as a filter for plant seedling establishment. Finally we identify areas in need of further work for better understanding the role of lichens in terrestrial ecosystems. These include understanding how the high intraspecific trait variation that characterizes many lichens impacts on community assembly processes and ecosystem functioning, how multiple species mixtures of lichens affect the key community- and ecosystem-level processes that they drive, the extent to which lichens in early succession influence vascular plant succession and ecosystem development in the longer term, and how global change drivers may impact on ecosystem functioning through altering the functional composition of lichen communities. | Lichens |
At present, flash droughts are poorly understood. Mature prevention and control measures are not available. This study aims to thoroughly explore the evolution characteristics of flash droughts in grassland ecosystems and to determine the meteorological driving conditions for inducing and relieving flash droughts. We propose the concept of the strong evapotranspiration flash drought (SEFD), a new type of flash drought in mid-temperate grasslands. The frequency of SEFDs is lower than that of heat wave flash droughts (HWFDs), but the intensity and impact of SEFDs are greater than those of HWFDs. Flash droughts in grasslands exhibit a high outbreak period from May to August, with the intensity basically above that of moderate drought. HWFDs occur most frequently in June and SEFDs in May. Meadow grasslands are the type of grassland with the highest risk of flash drought. Typical grasslands are more prone to HWFDs, while desert grasslands are more prone to SEFD outbreaks. In this study, a multifactor method was established to quantitatively evaluate the key influencing factors inducing flash droughts of different intensities in different time periods and to quantitatively predict the evolution of flash droughts into seasonal droughts. The temperature, water vapor pressure, precipitation, and wind speed were the key influencing factors of flash droughts and that the most important period in terms of inducing flash droughts is one pentad before the onset of flash drought. The outbreak rate and threshold of key influencing factors are the driving conditions for inducing flash droughts, and the recovery rate can be used as the basis for predicting whether an flash drought will evolve into a seasonal drought. The results showed that the characteristics and driving conditions of flash droughts are different in different types of grasslands and different time periods and are different for different types of flash droughts. In the future, the impact of flash droughts will become more severe. | Grassland |
AIMS: Glioblastoma multiforme (GBM) is the most aggressive type of human brain tumor, with a poor prognosis and a median overall survival of fewer than 15 months. Glioma stem cells (GSCs) have recently been identified as a key player in tumor initiation and therapeutic resistance in GBM. ADAMTS family of metalloproteinases is known to cleave a wide range of extracellular matrix substrates and has been linked to tissue remodeling events in tumor development. Here, we investigate that ADAMTS3 regulates GSC proliferation and self-renewal activities, and tumorigenesis in orthotopic xenograft models. METHODS: ADAMTS3 mRNA expression levels in normal human astrocyte (NHA), glioma, and GSCs cell lines were compared. After knockdown of ADAMTS3, alamarBlue assay, in vitro limiting dilution, and orthotopic xenograft assays were performed. To investigate the tumor-associated roles of ADAMTS3, several statistical assays were conducted using publicly available datasets. RESULTS: ADAMTS3 level was remarkably higher in GSCs than in NHA, glioma cell lines, and their matched differentiated tumor cells. Interestingly, knockdown of ADAMTS3 disrupted GSC's proliferation, self-renewal activity, and tumor formation in vivo. Furthermore, ADAMTS3 could be used as an independent predictor of malignancy progression in GBM. CONCLUSION: We identified ADAMTS3 as a potential therapeutic target for GBM. | ADAMTS Proteins |
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