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The hemolytic, lecithinase or phosphatidylinositol-specific phospholipase C activities of Listeria monocytogenes can be used to differentiate this pathogenic bacteria from L. innocua, apathogenic, frequently isolated from environmental sources and food. However, the interpretation of these characteristics is problematic because of the variation in the expression of virulence factors by L. monocytogenes, which can be influenced by environmental conditions. We used a cheap, simple plate assay to monitor this expression in strains obtained from various sources and grown under different culture conditions. The results were increasingly significant and were obtained adding activated charcoal and different salts to the culture media, and in some cases changing the culture temperature, all with a rigorous control on the process of media sterilization." | Phosphatidylinositol Diacylglycerol-Lyase |
The received wisdom is that there is no known effective treatment for psychopathic disorders. Although outcome studies have not identified an effective programmatic treatment for psychopathic disorders, such studies tend to leave the question open. If behavioral science has not established that psychopathic disorders respond to a particular programmatic approach, neither are psychopathic disorders convincingly proven to be absolutely resistant to treatment. If no treatment is known to be effective in psychopathic disorders, then any treatment seems to squander resources. What is often missing from the discussion is effective therapeutic measures to treat other behaviors that often co-occur, if they do not represent a domain of pathology of psychopathic disorders, such as impulsive aggression. After a brief summary of results of programmatic treatment of psychopathic offenders, this review focuses on the pharmacotherapy of impulsive aggression in psychopathic disorders. If the impulsive aggression that occurs with psychopathic disorders can be better controlled, treatment can have substantial benefits and would be most appropriate." | Antisocial Personality Disorder |
Ubiquitin and ubiquitin-like modifiers, such as SUMO, exert distinct physiological functions by conjugating to protein substrates. Ubiquitination or SUMOylation of protein substrates determine the fate of modified proteins, including proteasomal degradation, cellular re-localization, alternations in binding partners and serving as a protein-binding platform, in a ubiquitin or SUMO linkage-dependent manner. DNA damage occurs constantly in living organisms but is also repaired by distinct tightly controlled mechanisms including homologous recombination, non-homologous end joining, inter-strand crosslink repair, nucleotide excision repair and base excision repair. On sensing damaged DNA, a ubiquitination/SUMOylation landscape is established to recruit DNA damage repair factors. Meanwhile, misloaded and mission-completed repair factors will be turned over by ubiquitin or SUMO modifications as well. These ubiquitination and SUMOylation events are tightly controlled by both E3 ubiquitin/SUMO ligases and deubiquitinases/deSUMOylases. In this review, we will summarize identified ubiquitin and SUMO-related modifications and their function in distinct DNA damage repair pathways, and provide evidence for responsible E3 ligases, deubiquitinases, SUMOylases and deSUMOylases in these processes. Given that genome instability leads to human disorders including cancer, understanding detailed molecular mechanisms for ubiquitin and SUMO-related regulations in DNA damage response may provide novel insights into therapeutic modalities to treat human diseases associated with deregulated DNA damage response. | DNA End-Joining Repair |
Within the next decade, we will see many gene therapy clinical trials for eye diseases, which may lead to treatments for thousands of visually impaired people around the world. To target retinal diseases that affect specific cell types, several recombinant adeno-associated virus (AAV) serotypes have been generated and used successfully in preclinical mouse studies. Because there are numerous anatomic and physiologic differences between the eyes of mice and men" and because surgical delivery approaches and immunologic responses also differ between these species, this study evaluated the transduction characteristics of two promising new serotypes, AAV7m8 and AAV8BP2, in the retinas of animals that are most similar to those of humans: non-human primates (NHPs). We report that while AAV7m8 efficiently targets a variety of cell types by subretinal injection in NHPs, transduction after intravitreal delivery was mostly restricted to the inner retina at lower doses that did not induce an immune response. AAV8BP2 targets the cone photoreceptors efficiently but bipolar cells inefficiently by subretinal injection. Additionally, transduction by both serotypes in the anterior chamber of the eye and the optic pathway of the brain was observed post-intravitreal delivery. Finally, we assessed immunogenicity, keeping in mind that these AAV capsids may be used in future clinical trials. We found that AAV8BP2 had a better safety profile compared with AAV7m8, even at the highest doses administered. These studies underscore the differences in AAV transduction between mice and primates, highlighting the importance of careful evaluation of therapeutic vectors in NHPs prior to moving to clinical trials." | Dependovirus |
OBJECTIVE: Hand osteoarthritis (OA) is associated with considerable disability, especially in the elderly patient population. Paraffin wax (PW) and prolotherapy (P) are non-pharmacological treatment methods used in this setting. This study aimed to compare the therapeutic efficacy of P and PW in hand osteoarthritis. PATIENTS AND METHODS: This study was designed as a single-center, randomized-controlled trial conducted at our Physical Medicine and Rehabilitation Clinic between February 2019 and July 2020. Patients with bilateral hand OA were divided into PW and P treatment groups. The PW group was treated 5 days per week for 2 weeks. The P group received an injection of dextrose solution into the ligaments of painful joints once weekly for three weeks. Visual analog scale (VAS), Duruoz Hand Index (DHI) scale, hand dynamometer for grip strength, and pinch meter for lateral pinch were used for baseline and post-treatment follow-up assessments. RESULTS: Overall, 42 patients were included. The VAS scores significantly decreased in both PW and P groups (p=0.024 and p=0.014). Baseline and third-month post-treatment VAS scores did not significantly differ (p=0.581). The DHI scores improved significantly in both groups (p<0.001 and p<0.001), being higher in the P than in the PW group (p=0.042). Right- and left-hand grip strength increased significantly in PW and P groups (p<0.001, p=0.001; p=0.013, p=0.002, respectively). CONCLUSIONS: Both treatment methods were effective regarding pain and grip strength; however, P improved the hand functions more significantly. | Paraffin |
Peltate glandular trichomes from Mentha spicata were purified on a Percoll gradient and soluble and membrane proteins were trypsinized and the peptides were separated by nano-LC fractionation and analyzed by MALDI-MS/MS. The vast majority of the 1666 proteins identified were housekeeping proteins or involved in the primary metabolism. However, 57 were predicted to be involved in the secondary metabolism. Of these, 21 were involved in the synthesis of phenylpropanoids and phenolics and 32 in terpenoid synthesis. Of the 14 membrane transporters identified, the 11 ATP-binding cassette transporters provide good material for assessing whether active transport is required for the transfer of monoterpenoid intermediates between cellular compartments and for the secretion of the final products into the subcuticular storage cavity. In conclusion, this proteome analysis of M. spicata peltate trichomes has identified several candidate proteins that might be involved in terpenoid synthesis and transport. The data have been deposited to the ProteomeXchange with identifier PXD000352 (http://proteomecentral.proteomexchange.org/dataset/PXD000352). | Mentha spicata |
OBJECTIVE: To experimentally test weight stigma and weight stigma by association in a parent-child relationship using a large, community-based sample. METHODS: We conducted a randomized experiment on Amazon Mechanical Turk using an online survey. Participants were randomly assigned to view a picture of a parent-child dyad, for which the parent and child's gender (male vs. female) and weight status (with obesity vs. without obesity) were manipulated. Participants read identical parenting descriptions that adhered to the American Academy of Pediatrics' parenting recommendations, then rated the parent's perceived effectiveness, helpfulness, and level of caring using a parenting questionnaire based on Barnhart et al (2013). RESULTS: Participants (N = 1862; Mage = 36.8 [11.2] years) rated parents of children with obesity as less effective compared to parents of children without obesity (P = .010) and parents with obesity as less effective compared to parents without obesity (P = .033). Participants also rated parents with obesity as less helpful compared to parents without obesity (P = .021). No differences emerged in perceived caring. Parenting evaluations did not differ across daughters versus sons or mothers versus fathers. CONCLUSIONS: Parents of children with obesity may experience weight stigma by association, which could have direct consequences for the parents, the children, and the parent-child relationship. | Family |
BACKGROUND: The uniform delivery of laser energy is particularly important for safe and effective laser hair removal (LHR) treatment. Although it is necessary to quantitatively assess the spatial distribution of the delivered laser, laser spots are difficult to trace owing to a lack of visual cues. This study proposes a novel preclinic tool to evaluate operator proficiency in LHR treatment and applies this tool to train novice operators and compare two different treatment techniques (sliding versus spot-by-spot). METHODS: A simulation bed is constructed to visualize the irradiated laser spots. Six novice operators are recruited to perform four sessions of simulation while changing the treatment techniques and the presence of feedback (sliding without feedback, sliding with feedback, spot-by-spot without feedback, and spot-by-spot with feedback). Laser distribution maps (LDMs) are reconstructed through a series of images processed from the recorded video for each simulation session. Then, an experienced dermatologist classifies the collected LDMs into three different performance groups, which are quantitatively analyzed in terms of four performance indices. RESULTS: The performance groups are characterized by using a combination of four proposed indices. The best-performing group exhibited the lowest amount of randomness in laser delivery and accurate estimation of mean spot distances. The training was only effective in the sliding treatment technique. After the training, omission errors decreased by 6.32% and better estimation of the mean spot distance of the actual size of the laser-emitting window was achieved. Gels required operators to be trained when the spot-by-spot technique was used, and imposed difficulties in maintaining regular laser delivery when the sliding technique was used. CONCLUSIONS: Because the proposed system is simple and highly affordable, it is expected to benefit many operators in clinics to train and maintain skilled performance in LHR treatment, which will eventually lead to accomplishing a uniform laser delivery for safe and effective LHR treatment. | Hair Removal |
Rock salt caverns are considered one of the best hosts to store oil, natural gas, radioactive and toxic wastes due to their low permeability, self-healing characteristics and wide distribution on the Earth. Stored nuclear waste in rock salts will radiate for many years. Therefore, the thermal energy and also temperature in the host environment will increase depending on time. In this study, P-wave velocity (Vp), Brazilian tensile strength (sigmat), uniaxial compression strength (sigmac) of Cankiri rock salt were investigated under different temperatures ranging from 20 degrees C to 250 degrees C since the temperature is a factor that causes changes in some physical and geo-mechanical properties of rocks. The acoustic emission technique was utilized during uniaxial compression strength tests, to monitor the crack accumulation. Additionally, X-ray micro-computed tomography technique was employed to observe the microstructure and determine the porosity of rock salt samples depending on the temperature. The Vp and the sigmat of Cankiri rock salt decrease with increasing temperatures of samples whereas the sigmac increases. The ductility of rock salt tends to increase with augmented temperature and the axial strain at the ultimate stress level is 2.96% at 20 degrees C whereas it reaches up to 6.29% at 250 degrees C. The AE activity of rock salt generates at the early stages of loading and AE count prominently increases with the increasing temperature of samples. Therefore, the stress levels of crack initiation (sigmai) and crack damage (sigmacd) thresholds were reached earlier than the previous one with each temperature increment. According to X-ray micro-CT images of rock salts, the number of cracks increased markedly in thermally treated rock salt samples and therewith the porosity increases from 1.12% to 2.73% with an increase in temperature from 50 degrees C to 250 degrees C. | Sodium Chloride |
One Sisymbrium officinale (L.) Scop. aqueous dry extract (SOE) and its polyphenolic fractions (Fb, Fc, Fd and Fe) were evaluated for their ability to inhibit the oxidative mutagenicity of tert-butylhydroperoxide in the Ames test. The possible involvement of desmutagenic and/or bioantimutagenic mechanisms was evaluated by applying a three-time based protocol (pre-treatment, co-treatment and post-treatment). Furthermore, some protective antioxidant mechanisms were investigated. The total polyphenol and flavonol amount was also determined, and the fingerprint was outlined by high-performance thin-layer chromatography and densitometry. SOE, Fb and Fe exhibited strong antimutagenicity against tert-butylhydroperoxide in all treatment protocols, this suggesting the involvement of both desmutagenic and bioantimutagenic mechanisms. These samples also showed antioxidant properties, including neutralization of the superoxide anion, lipid peroxidation inhibition and chelation and reduction of iron. Fb and Fe were rich in polyphenols and flavonols, so suggesting a possible role of these compounds in the antimutagenicity. Taking into account that oxidative stress is responsible for the damage of various environmental toxicants, particularly tobacco smoke, present results can support the traditional use of hedge mustard by smokers to restore the vocal cord function affected by the oxidative damage and suggest a possible application of SOE and its fractions as food supplements. Copyright (c) 2016 John Wiley & Sons, Ltd. | tert-Butylhydroperoxide |
Light affects plant growth through assimilate availability and signals regulating development. The effects of light on growth of tomato fruit were studied using cuvettes with light-emitting diodes providing white, red or blue light to individual tomato trusses for different periods during daytime. Hypotheses tested were as follows: (1) light-grown fruits have stronger assimilate sinks than dark-grown fruits, and (2) responses depend on light treatment provided, and fruit development stage. Seven light treatments [dark, 12-h white, 24-h white, 24-h red and 24-h blue light, dark in the first 24 days after anthesis (DAA) followed by 24-h white light until breaker stage, and its reverse] were applied. Observations were made between anthesis and breaker stage at fruit, cell and gene levels. Fruit size and carbohydrate content did not respond to light treatments while cell division was strongly stimulated at the expense of cell expansion by light. The effects of light on cell number and volume were independent of the combination of light color and intensity. Increased cell division and decreased cell volume when fruits were grown in the presence of light were not clearly corroborated by the expression pattern of promoters and inhibitors of cell division and expansion analyzed in this study, implying a strong effect of posttranscriptional regulation. Results suggest the existence of a complex homeostatic regulatory system for fruit growth in which reduced cell division is compensated by enhanced cell expansion. | Cell Enlargement |
The journal Human Mutation has as its principal focus variants in the human genome, covering the entire spectrum from methods used to detect variants, to ways of answering the ultimate question: What are the consequences of carrying a variant for the health of the individual?" This comprehensive collection of articles provides an excellent perspective of the advancements in variant effect prediction in recent years, as well as some caveats and cautions in this developing field. We believe that this resource will help to drive further evolution of the variant effect prediction process toward more robust understanding of genotype-phenotype relationships through reliable variant classification." | Genome, Human |
OBJECTIVE: Timely availability of intravenous infusion pumps is critical for high-quality care delivery. Pumps are shared among hospital units, often without central management of their distribution. This study seeks to characterize unit-to-unit pump sharing and its impact on shortages, and to evaluate a system-control tool that balances inventory across all care areas, enabling increased availability of pumps. MATERIALS AND METHODS: A retrospective study of 3832 pumps moving in a network of 5292 radiofrequency and infrared sensors from January to November 2017 at The Johns Hopkins Hospital in Baltimore, Maryland. We used network analysis to determine whether pump inventory in one unit was associated with inventory fluctuations in others. We used a quasi-experimental design and segmented regressions to evaluate the effect of the system-control tool on enabling safe inventory levels in all care areas. RESULTS: We found 93 care areas connected through 67,111 pump transactions and 4 discernible clusters of pump sharing. Up to 17% (95% confidence interval, 7%-27%) of a unit's pump inventory was explained by the inventory of other units within its cluster. The network analysis supported design and deployment of a hospital-wide inventory balancing system, which resulted in a 44% (95% confidence interval, 36%-53%) increase in the number of care areas above safe inventory levels. CONCLUSIONS: Network phenomena are essential inputs to hospital equipment fleet management. Consequently, benefits of improved inventory management in strategic unit(s) are capable of spreading safer inventory levels throughout the hospital. | Infusion Pumps |
Late embryogenesis abundant (LEA) proteins are a large and highly diverse family of polypeptides that play important roles in plant growth, development and stress responses. At present, LEA gene families have been identified and systematically characterized in many plant species. However, the LEA gene family in tea plant has not been revealed, and the biological functions of the members of this family remain unknown. In this study, 33 CsLEA genes were identified from tea plant via a genome-wide study, and they were clustered into seven groups according to analyses of their phylogenetic relationships, gene structures and protein conserved motifs. In addition, expression analysis revealed that the CsLEA genes were specifically expressed in one or more tissues and significantly induced under cold and dehydration stresses, implying that CsLEA genes play important roles in tea plant growth, development and response to cold and dehydration stresses. Furthermore, a potential transcriptional regulatory network, including DREB/CBF, MYB, bZIP, bHLH, BPC and other transcription factors, is directly associated with the expression of CsLEA genes, which may be ubiquitous and important in the above mentioned processes. This study could help to increase our understanding of CsLEA proteins and their contributions to stress tolerance in tea plant. | Genes, Plant |
BACKGROUND: Numerous diseases come from streptococcal infection. The antistreptolysin O (ASO) test is the most widely used serological test for streptococcal infection applied for the clinical diagnosis. The aim of this study was to establish reference values for serum ASO in Han and Zhuang Chinese from a Chinese male population survey. METHODS: A cross-sectional study in which 1,762 serum samples were collected between September 2009 and December 2009 from Chinese men aged 20 to 69 years. The reference values for serum ASO were measured with the immunonephelometric method on the Hitachi 7600 autoanalyzer. RESULTS: Serum ASO values were not normally distributed but log normally distributed. The reference value was < or = 125.00 IU/mL for serum ASO. A significant decrease with age was found, and age-dependent reference values were calculated for serum ASO levels. The Zhuang and Han groups (p < 10(-3)) exhibited differences in serum ASO. There was no significant difference according to smoking (p = 0.718) and drinking (p = 0.388) in Zhuang. However, there was a significant difference between smoking and non-smoking (p < 10(-3)) in the Han ethnic group, whereas there was no significant difference between the non-drinking and drinking groups (p = 0.245). CONCLUSIONS: The reference values for serum ASO for healthy adult men showed a huge deviation compared to the currently used reference value (200 IU/mL). Thus, the reference values for serum ASO should be established for different ethnic groups and regions. | Antistreptolysin |
INTRODUCTION: Compressive rib fractures are considered to be indicative of non-accidental injury (NAI) in infants, which is a significant and growing issue worldwide. The diagnosis of NAI is often disputed in a legal setting, and as a consequence there is a need to model such injuries ex vivo in order to characterise the forces required to produce non-accidental rib fractures. However, current models are limited by type of sample, loading method and rate of loading. Here, we aimed to: i) develop a loading system for inducing compressive fractures in whole immature ribs that is more representative of the physiological conditions and mechanism of injury employed in NAI and ii) assess the influence of loading rate and rib geometry on the mechanical performance of the tissue. METHODS: Porcine ribs (5-6 weeks of age) from 12 animals (n=8 ribs/animal) were subjected to axial compressive load directed through the anterior-posterior rib axis at loading rates of 1, 30, 60 or 90 mm/s. Key mechanical parameters (including peak load, load and percentage deformation to failure and effective stiffness) were quantified from the load-displacement curves. Measurements of the rib length, thickness at midpoint, distance between anterior and posterior extremities, rib curvature and fracture location were determined from radiographs. RESULTS: This loading method typically produced incomplete fractures around the midpoint of the ribs, with 87% failing in this manner; higher loads and less deformation were required for ribs to completely fracture through both cortices. Loading rate, within the range of 1-90 mm/s, did not significantly affect any key mechanical parameters of the ribs. Load-displacement curves displaying characteristic and quantifiable features were produced for 90% of the ribs tested, and multiple regression analyses indicate that, in addition to the geometrical variables, there are other factors such as the micro- and nano-structure that influence the measured mechanical data. CONCLUSIONS: A reproducible method of inducing fractures in a consistent location in immature porcine ribs has been successfully developed. Fracture appearance may be indicative of the amount of load and deformation that produced the fracture, which is an important finding for NAI, where knowledge of the aetiology of fractures is vital. Characteristic rib behaviour independent of loading rate and, to an extent, rib geometry has been demonstrated, allowing further investigation into how the complex micro- and nano-structure of immature ribs influences the mechanical performance under compressive load. This research will ultimately enable improved characterisation of the loading pattern involved in non-accidental rib fractures. | Rib Cage |
The N-terminal SH3 domain of the Drosophila signal transduction protein drk was encapsulated in reverse micelles. Both the temperature of maximum stability and the melting temperature decreased on encapsulation. Dissecting the temperature-dependent stability into enthalpic and entropic contributions reveals a stabilizing enthalpic and a destabilizing entropic contribution. These results do not match the expectations of hard-core excluded volume theory, nor can they be wholly explained by interactions between the head groups in the reverse micelle and the test protein. We suggest that geometric constraints imposed by the reverse micelles need to be considered. | Protein Stability |
The relationship between subclinical hypothyroidism (SH) and Atherosclerotic (At) cardiovascular diseases (CVD) has been one of the most popular topics but causal connection between Hashimoto thyroiditis (HT), lipid profile and follicular epithelial molecular biology is controversial. We investigated 3 groups of patients (group I - HT, group II - HT+At, group III - At). All laboratory tests for thyroid function and lipid profile detection were used according to international guideline recommendations, coronary and femoral arteries intima-media thickness (IMT) were tested by high-resolution ultrasonography, thyroid gland histology and immunohistochemistry carried out by p63 and S100 protein expression control. The statistical analysis was performed using Microsoft Excel 7.0, SPSS-20 version, Mann-Whitney U-test and Pearson's correlation. Comparisons between groups and factors were made using Multiple Linear Regression model. With the results obtained, dyslipidemia and the diastolic hypertension accelerate the hypothyroidism in HT+At group to predispose carotid and femoral arteries IMT. TSH and anti-TPO antibody levels are directly linked to the cardiovascular complications. Biomarkers S100 and p63 data show negative feedback effects of hypercholesterolemia on the high morphological risk features in Hashimoto parenchyma, which may partially explain the significant trend and pathobiological link of HT with Papillary thyroid carcinoma." | Carotid Intima-Media Thickness |
BACKGROUND: Chemical matricectomy with sodium hydroxide is a method being used successfully in the treatment of ingrown toenail. OBJECTIVE: In this study, it was aimed to evaluate long-term recurrence rates after chemical matricectomy using sodium hydroxide application of different durations. MATERIALS AND METHODS: Two hundred two patients with ingrown nail edges were treated with either 1-minute (Group 1) or 2-minute (Group 2) applications of sodium hydroxide matricectomy. All patients were followed for at least 2 years. RESULTS: Chemical matricectomy with sodium hydroxide was applied to a total of 585 nail edges of 202 cases. The overall recurrence rates in Group 1 and Group 2 were 6.4% and 7.1%, respectively, during the average 7.5-year follow-up period. No statistically significant differences were detected in terms of recurrence between the 2 groups (p = .73). CONCLUSION: Chemical matricectomy with sodium hydroxide is an easy method in the treatment of ingrown nails, with low morbidity and high success rates. There was no difference between 1-minute and 2-minute applications in terms of recurrence during the long-term follow-up. Chemical matricectomy with 1-minute application of sodium hydroxide showed high success in terms of long-term follow-up results. | Sodium Hydroxide |
Because calcineurin inhibitor (CNI) immunosuppressive drugs induce arteriolar hyalinosis (ah) in kidney transplants, ah lesions can potentially provide information about drug exposure. We studied the relationship of ah lesions to findings and outcomes in 562 indication biopsies taken 3 days to 35 years after transplant. Prevalence of ah lesions increased with time of biopsy after transplant (TxBx). The ah scores correlated with arterial intimal thickening and atrophy-fibrosis but, unlike atrophy-fibrosis, did not increase until after 500 days because of a background of ah1 lesions in early biopsies reflecting donor aging. Correlation of ah scores with other features varied with TxBx-in early biopsies, donor age and related changes, and in very late biopsies, chronic antibody-mediated rejection and glomerulonephritis and associated lesions. After correction for TxBx, ah0 in intermediate time periods was associated with increased risk of T cell-mediated rejection and graft loss, probably because of underimmunosuppression and nonadherence. Thus, ah lesions in indication biopsies have multiple associations: donor age (early, usually ah1), chronic glomerular diseases (late, often ah2/3), and adequate exposure to CNIs at intermediate times. This threefold TxBx-dependent complexity must be considered when interpreting indication biopsies: ah lesions often indicate adequate CNI exposure, not toxicity, and unexpected ah0 should increase vigilance for nonadherence and underimmunosuppression. | Arteriolosclerosis |
BACKGROUND: Self-microemulsifying drug delivery systems provide a key technology to formulate challenging drugs. These formulations are commonly screened in early development by simple in vitro dilution tests. However, there is often a lack of rationale of how these tests are performed; so this article aims to improve this situation by studying critical concentrations in the dilution of self-microemulsifying formulations. METHODS: Dynamic laser light backscattering, conductivity measurements, and electron paramagnetic resonance spectroscopy were conducted. RESULTS: All model formulations exhibited profound changes at a similar aqueous dilution, which was interpreted as a percolation threshold of the formulation in water. It marked the change of a bicontinuous microemulsion to discrete micelles. The systems exhibited at this point maximal particle dispersion with a threshold of polydispersity. A marked change was also observed in the paramagnetic resonance spectra and with the conductivity measurements. This altered microenvironment can be relevant for solubilized drugs. CONCLUSIONS: Future dilution tests should include a formulation-to-water ratio of roughly 1:5 (w/w), which is in the proximity of the individual threshold concentration. Additional dilutions may be tested below and clearly above this value to reflect the physiological dilution process. | Emulsifying Agents |
Coronaviruses as well as influenza A viruses are widely spread in pig fattening and can cause high economical loss. Here we infected porcine precision-cut lung slices with porcine respiratory coronavirus and two Influenza A viruses to analyze if co-infection with these viruses may enhance disease outcome in swine. Ciliary activity of the epithelial cells in the bronchus of precision-cut lung slices was measured. Co-infection of PCLS reduced virulence of both virus species compared to mono-infection. Similar results were obtained by mono- and co-infection experiments on a porcine respiratory cell line. Again lower titers in co-infection groups indicated an interference of the two RNA viruses. This is in accordance with in vivo experiments, revealing cell innate immune answers to both PRCoV and SIV that are able to restrict the virulence and pathogenicity of the viruses." | Porcine Respiratory Coronavirus |
Allopolyploidization (hybridization and whole-genome duplication) is a common phenomenon in plant evolution with immediate saltational effects on genome structure and gene expression. New technologies have allowed rapid progress over the past decade in our understanding of the consequences of allopolyploidy. A major question, raised by early pioneer of this field Leslie Gottlieb, concerned the extent to which gene expression differences among duplicate genes present in an allopolyploid are a legacy of expression differences that were already present in the progenitor diploid species. Addressing this question necessitates phylogenetically well-understood natural study systems, appropriate technology, availability of genomic resources and a suitable analytical framework, including a sufficiently detailed and generally accepted terminology. Here, we review these requirements and illustrate their application to a natural study system that Gottlieb worked on and recommended for this purpose: recent allopolyploids of Tragopogon (Asteraceae). We reanalyse recent data from this system within the conceptual framework of parental legacies on duplicate gene expression in allopolyploids. On a broader level, we highlight the intellectual connection between Gottlieb's phrasing of this issue and the more contemporary framework of cis- versus trans-regulation of duplicate gene expression in allopolyploid plants. | Tragopogon |
Cis-9,trans-11 and trans-7,cis-9 CLA are the most prevalent CLA isomers in milkfat. The majority of cis-9,trans-11 CLA is synthesized endogenously by delta9-desaturase. We tested the hypothesis that trans-7,cis-9 CLA originates from endogenous synthesis by inhibiting delta9-desaturase with a source of cyclopropene FA (sterculic oil: SO) or with a trans-10,cis-12 CLA supplement. Experiment 1 (four cows; Latin square) involved four treatments: control, SO, partially hydrogenated vegetable oil (PHVO), and PHVO + SO. Milk, plasma, and rumen fluid were collected. Experiment 2 treatments (four cows) were 0 or 14.0 g/d of 10,12 CLA supplement; milk and plasma were collected. Samples were analyzed by GC and Ag+-HPLC to determine FA. In Experiment 1, SO decreased milkfat content of trans-7,cis-9 CLA by 68 to 71% and cis-9,trans-11 CLA by 61 to 65%. In Experiment 2, the 10,12 CLA supplement decreased milkfat content of trans-7,cis-9 CLA and cis-9,trans-11 by 44 and 25%, respectively. Correcting for the extent of treatment-induced inhibition of delta9-desaturase based on changes in myristic and myristoleic acids, endogenous synthesis of trans-7,cis-9 CLA represented 85 and 102% in Experiments 1 and 2, respectively. Similar corrected values were 77 and 58% for endogenous synthesis of cis-9,trans-11 CLA. Thus, milkfat cis-9,trans-11 CLA was primarily from endogenous synthesis with a minor portion from rumen escape. In contrast, trans-7,cis-9 CLA was not present in rumen fluid in significant amounts. Results indicate this isomer in milkfat is derived almost exclusively from endogenous synthesis via delta9-desaturase. | Linoleic Acid |
As fiscal restraints tighten around the Canadian health care sector, new graduates find it increasingly difficult to find full-time work. Even experienced nurses who have lost their jobs may find they have to take casual or part-time work. | Job Application |
Recurrent airway obstruction (RAO) represents a serious health problem and is traditionally classified as an allergic disease, where contact with an antigen can induce clinical airway inflammation, bronchial hyper-responsiveness and reversible airway obstruction. Previous studies have demonstrated the presence of the Th2 response in the lungs of human patients with asthma and horses with heaves. These cells are involved in the production of cytokines which regulate the synthesis of immunoglobulins. 40 horses were evaluated: 30 horses with RAO and 10 healthy animals. The expression levels of interferon-alpha 1 (IFN-alpha1), interferon-gamma (IFN-gamma), interleukin-1beta, (IL-1beta), IL-2, IL-4, IL-13 and tumor necrosis factor alpha (TNF-alpha) were measured in the serum obtained from control and RAO-susceptible horses during crisis. In all the patients, serum cytokine levels were detected. Serum median IL-13 and IFN-gamma levels were significantly higher in RAO-affected horses than in the healthy group (p < 0.001). The serum median IFN-alpha1, IL-1beta, IL-2, IL-4, and TNF-alpha levels were similar in both groups. These results indicate a low variability of the levels of cytokines and a high frequency of their detection in serum samples from horses with RAO. Immune mechanisms involved in equine RAO are more complex than those defined by a simple Th1/Th2 dichotomy. | Bronchoalveolar Lavage Fluid |
Engagement of host receptors is essential for viruses to enter target cells and initiate infection. Expression patterns of receptors in turn dictate host range, tissue tropism, and disease pathogenesis during infection. Mammalian orthoreovirus (reovirus) displays serotype-dependent patterns of tropism in the murine central nervous system (CNS) that are dictated by the viral attachment protein sigma1. However, the receptor that mediates reovirus CNS tropism is unknown. Two proteinaceous receptors have been identified for reovirus, junctional adhesion molecule A (JAM-A) and Nogo-66 receptor 1 (NgR1). Engagement of JAM-A is required for reovirus hematogenous dissemination but is dispensable for neural spread and infection of the CNS. To determine whether NgR1 functions in reovirus neuropathogenesis, we compared virus replication and disease in wild-type (WT) and NgR1(-/-) mice. Genetic ablation of NgR1 did not alter reovirus replication in the intestine or transmission to the brain following peroral inoculation. Viral titers in neural tissues following intramuscular inoculation, which provides access to neural dissemination routes, also were comparable in WT and NgR1(-/-) mice, suggesting that NgR1 is dispensable for reovirus neural spread to the CNS. The absence of NgR1 also did not alter reovirus replication, neural tropism, and virulence following direct intracranial inoculation. In agreement with these findings, we found that the human but not the murine homolog of NgR1 functions as a receptor and confers efficient reovirus binding and infection of nonsusceptible cells in vitro. Thus, neither JAM-A nor NgR1 is required for reovirus CNS tropism in mice, suggesting that other unidentified receptors support this function. IMPORTANCE Viruses engage diverse molecules on host cell surfaces to navigate barriers, gain cell entry, and establish infection. Despite discovery of several reovirus receptors, host factors responsible for reovirus neurotropism are unknown. Human NgR1 functions as a reovirus receptor in vitro and is expressed in CNS neurons in a pattern overlapping reovirus tropism. We used mice lacking NgR1 to test whether NgR1 functions as a reovirus neural receptor. Following different routes of inoculation, we found that murine NgR1 is dispensable for reovirus dissemination to the CNS, tropism and replication in the brain, and resultant disease. Concordantly, expression of human but not murine NgR1 confers reovirus binding and infection of nonsusceptible cells in vitro. These results highlight species-specific use of alternate receptors by reovirus. A detailed understanding of species- and tissue-specific factors that dictate viral tropism will inform development of antiviral interventions and targeted gene delivery and therapeutic viral vectors." | Junctional Adhesion Molecule A |
Methylation of adenine in replicating and nonreplicating DNA of the ciliate Tetrahymena thermophila was examined. In growing cells, 87% of the methylation occurred on the newly replicated daughter strand, but methylation was also detectable on the parental strand. Methylation of nonreplicating DNA from starved cells was demonstrated. | Tetrahymena |
BACKGROUND: Accurate diagnosis of mitral regurgitation (MR) severity is central to proper treatment. Although numerous approaches exist, an accurate, gold-standard clinical technique remains elusive. The authors previously reported on the initial development and demonstration of the automated three-dimensional (3D) field optimization method (FOM) algorithm, which exploits 3D color Doppler ultrasound imaging and builds on existing MR quantification techniques. The aim of the present study was to extensively validate 3D FOM in terms of accuracy, ease of use, and repeatability. METHODS: Three-dimensional FOM was applied to five explanted ovine mitral valves in a left heart simulator, which were systematically perturbed to yield a total of 29 unique regurgitant geometries. Three-dimensional FOM was compared with a gold-standard flow probe, as well as the most clinically prevalent MR volume quantification technique, the two-dimensional (2D) proximal isovelocity surface area (PISA) method. RESULTS: Overall, 3D FOM overestimated and 2D PISA underestimated MR volume, but 3D FOM error had smaller magnitude (5.2 +/- 9.9 mL) than 2D PISA error (-6.9 +/- 7.7 mL). Two-dimensional PISA remained superior in diagnosis for round orifices and especially mild MR, as predicted by ultrasound physics theory. For slit-type orifices and severe MR, 3D FOM showed significant improvement over 2D PISA. Three-dimensional FOM processing was technically simpler and significantly faster than 2D PISA and required fewer ultrasound acquisitions. Three-dimensional FOM did not show significant interuser variability, whereas 2D PISA did. CONCLUSIONS: Three-dimensional FOM may provide increased clinical value compared with 2D PISA because of increased accuracy in the case of complex or severe regurgitant orifices as well as its greater repeatability and simpler work flow." | Echocardiography, Doppler, Color |
Glucose level measurement is essential for the point-of-care diagnosis, primarily for persons with diabetes. A disposable electrochemical glucose sensor is constructed using flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH) and redox mediator for electron transfer from the enzyme to the electrode surface. Ideally, a suitable mediator should have high water solubility, high kinetic constant, high stability, and redox potential between -0.2 and 0.1 V vs. Ag|AgCl|sat. KCl. We designed and synthesized two new quinone-based water-soluble mediators: quinoline-5,8-dione (QD) and isoquinoline-5,8-dione (IQD). The formal potentials for both QD and IQD at pH 7.0 were -0.07 V vs. Ag|AgCl|sat. KCl. The logarithms of the electron exchange rate constants (k(2)/(M(-1) s(-1))) between QD/IQD and FAD-GDH were 7.7 +/- 0.1 and 7.4 +/- 0.1 for QD and IQD, respectively, which are the highest value among the water-soluble mediators for FAD-GDH reported to date. Disposable amperometric glucose sensors were fabricated by dropping FAD-GDH and QD or IQD onto a test strip. The sensor achieved a linear response up to glucose concentrations of 55.5 mM. The linear response was obtained even when the mediator loading was low (0.5 nmol/strip); loading was only 0.2 mol% of glucose. The results proved that the response current was primarily controlled by glucose diffusion. In addition, the sensor using QD exhibited high stability over 3 months at room temperature. | Glucose 1-Dehydrogenase |
Recent studies have shown that ethanol produces a widespread modulation of neuronal activity in the central nervous system. It is not fully understood, however, how ethanol changes nociceptive transmission. We investigated acute effects of ethanol on synaptic transmission in the substantia gelatinosa (lamina II of the spinal dorsal horn) and mechanical responses in the spinal dorsal horn. In substantia gelatinosa neurons, bath application of ethanol at low concentration (10 mM) did not change the frequency and amplitude of spontaneous inhibitory postsynaptic currents. At medium to high concentrations (20-100 mM), however, ethanol elicited a barrage of large amplitude spontaneous inhibitory postsynaptic currents. In the presence of tetrodotoxin, such enhancement of spontaneous inhibitory postsynaptic currents was not detected. In addition, ethanol (20-100 mM) increased the frequency of spontaneous discharge of vesicular GABA transporter-Venus-labeled neurons and suppressed the mechanical nociceptive response in wide-dynamic range neurons in the spinal dorsal horn. The present results suggest that ethanol may reduce nociceptive information transfer in the spinal dorsal horn by enhancement of inhibitory GABAergic and glycinergic synaptic transmission." | Inhibitory Postsynaptic Potentials |
PURPOSE: The perioperative management of lower airway injuries is a difficult clinical problem. Since few reviews present the management of this injury from an anaesthetic perspective, we undertook a literature review of this topic. SOURCES: A computerized search of the National Library of Medicine database using tracheal or bronchial injury as key words produced 140 English language citations. An eight-year chart review outlining our experience in an urban Canadian setting is also presented. FINDINGS: The most frequent findings in patients with injury to the lower airway are dyspnoea and surgical emphysema. Other findings include cough, haemoptysis, sucking neck or chest wounds, mediastinal emphysema or pneumothorax. Endoscopy with a fiberoptic scope is the technique of choice for diagnosis, airway management and as a preparatory step in planning of the surgical repair. An airway technique employing direct vision is preferable to blind attempts during tracheal intubation. The use of a double lumen endobronchial tube or selective endobronchial intubation may be needed to achieve adequate pulmonary ventilation. A number of prospective randomized clinical trials comparing conventional mechanical ventilation with high frequency jet ventilation in patients with acute lung injury have demonstrated no difference in effectiveness of ventilation or oxygenation. CONCLUSIONS: Patients with lower airway injuries usually present when they are least expected and are a challenge to manage. The clinical presentation of a lower airway injury may be overt or subtle. Resuscitation and anaesthetic management are directed towards control of the airway, maintenance of adequate pulmonary ventilation and management of blood loss. | Trachea |
This study used data on currently married and cohabiting men aged 15 to 64 years from the 2003 Nigeria Demographic and Health Survey to examine the prevalence of and factors associated with extramarital sex. The results show that 16% engaged in extramarital sex in the 12 months preceding the survey and had an average of 1.82 partners. The results also show statistically significant association between extramarital sex and ethnicity, religion, age, age at sexual debut, education, occupation, and place of residence. Based on the study results, it could be concluded that significant proportions of Nigerians are exposed to HIV infection through extramarital sex. A fundamental behavioral change expected in the era of HIV/AIDS is the inculcation of marital fidelity and emotional bonding between marital partners. The promotion of condom use among married couples should be intensified to protect women, a large number of whom are exposed to HIV infection from their spouses who engage in unprotected extramarital sex. And, because of gender-based power imbalances within the family, a large number of the women are unable to negotiate consistent condom use by their partners. | Extramarital Relations |
The purpose of this study was to examine a mechanism which might explain the diminished erythropoiesis that occurs when tumor cells invade the bone marrow (myelophthisic anemia). To this end we compared 21 patients with neoplastic bone marrow invasion with seven normal subjects. When erythropoietin was added to bone marrow cell cultures from the normal subjects, the baseline rate of heme synthesis for a specific number of marrow erythroid cells increased 65%. In contrast, in patients with greater than 60% of the marrow replaced by tumor, the marrow cell culture response to erythropoietin was 14% above baseline. A significant inverse correlation was noted between the degree of marrow infiltration with tumor and the stimulation of heme synthesis with erythropoietin. It is proposed that marrow invasion with tumor may result in decreased marrow response to erythropoietin, and hence, diminished red cell production. | Anemia, Myelophthisic |
Transcription factor EVI1 is essential for normal hematopoiesis in embryos but is aberrantly elevated in bone marrow cells of myelodysplastic syndrome (MDS) patients. EVI1 and its downstream GATA-2 appear to be a possible therapeutic target of MDS. Here we found that treatment of EVI1-expressing K562 cells with arsenite (As(III)) reduced the mRNA and protein levels of EVI1 and GATA-2. A gel shift assay using the nuclear extract of K562 cells showed that As(III) suppressed the DNA-binding activity of EVI1. The DNA-binding activity of the recombinant EVI1 protein was also suppressed by As(III) but was recovered by excess amounts of dithiothreitol, suggesting the involvement of cysteine residues of EVI1. Since the 7th Zn finger domain of EVI1, having a motif of CCHC, is known to be involved in DNA-binding, the synthetic peptide of 7th Zn finger domain was reacted with As(III) and subjected to MALDI-TOF-MS analysis. The results showed that As(III) binds to this peptide via three cysteine residues. As(III)-induced reduction of the DNA-binding activity of the recombinant EVI1 was abolished by the mutations of each of three cysteine residues to alanine in the 7th Zn finger domain. These results demonstrate that As(III) causes the down-regulation of EVI1 and GATA-2 by inhibiting the transcriptional activity of EVI1 through the binding to the cysteine residues of CCHC-type Zn finger domain." | MDS1 and EVI1 Complex Locus Protein |
Genes of the major histocompatibility complex (MHC) in the mouse (H-2 complex) have been shown to be an important factor in determining the immune responsiveness of various strains of mice to isolated antigens (e.g., lysozyme). The role of MHC genes in controlling the responsiveness of mice to multiple alloantigens is less well-defined, and although non-MHC genes have been shown to be important in determining responsiveness in some systems (e.g., haptens), they have not been demonstrated as yet to influence the rejection of vascularized organ allografts. In this study, the responsiveness of mice to vascularized cardiac allografts transplanted across well-defined major (H-2) and minor (non-H-2) histocompatibility barriers was investigated using congenic mice in 32 different donor/recipient combinations. The results show that both H-2 and non H-2 gene products can act as target alloantigens for rejection. At the responder level, they may interact to effect responsiveness of a recipient strain to multiple alloantigens. In no case in this study has any one gene or group of genes been found to confer universal high or low responder status. | H-2 Antigens |
A specific GC method has been developed, optimized and validated for the determination of seven related substances namely N,N-dimethyl valpronamide, valeric acid, 2-methyl valeric acid, 2-ethyl valeric acid, 2-isopropyl valeric acid, 2-n-butyl valeric acid and 2-propyl-2-pentenoic acid in divalproex sodium (DPS) drug substance. Chromatographic separations of these seven impurities were achieved on DB-FFAP column (30 m x 0.53 mm, 1.0 mum), which consists nitroterephthalic acid modified polyethylene glycol material as stationary phase. DPS is a coordination complex of the sodium valproate and valproic acid (VPA). Nonanoic acid is used as internal standard. All the seven related substances, VPA and nonanoic acid were extracted into dichloromethane and monitored by GC with flame ionization detector. The performance of the developed method was assessed by evaluating specificity, linearity, sensitivity, precision, accuracy and robustness. Forced degradation experiments were conducted to evaluate the degradation behavior of DPS. The established limits of detection (LODs) and limits of quantification (LOQs) values for the related substances were in the ranges of 4-5 and 12-15 mug mL-1, respectively. Further, for VPA, LOD and LOQ values were 4 and 12 mug mL-1, respectively. The correction factors of these related substances with respect to VPA and lie between 0.92 and 1.44. The average recoveries were in the range of 92.4-108.4%. | Valerates |
CASE: An 18-year-old man sustained a peroneal nerve (PN) injury during an all-inside repair of the posterior horn of the lateral meniscus from the medial portal. Although he could dorsiflex his ankle actively after emergence from general anesthesia, he had a foot drop on the day after surgery. Exploration of the PN at 5 months postoperatively revealed that the nerve was entrapped by the suture. Fifteen months after a nerve repair using a sural nerve graft, he recovered from the foot drop. CONCLUSION: This case report highlights the risk of PN injury during an all-inside repair of the posterior horn of the lateral meniscus. | Peroneal Nerve |
The efficacy and safety of fleroxacin and ciprofloxacin were evaluated in a single-centre, prospective, randomised, blinded study of patients with complicated urinary infection in a spinal injury unit. Patients were randomised to receive oral fleroxacin 400 mg once daily (n = 68) or oral ciprofloxacin 500 mg twice daily (n = 65) for 10 days. Clinical cure assessed 5-9 days after therapy was obtained in 41 of 42 (98%) assessable patients in the fleroxacin group, and in 41 of 43 (95%) of the ciprofloxacin group, and was maintained at the 6-week follow-up visit in all but 1 patient in each group. Bacteriological eradication rates 5-9 days after therapy exceeded 88% in the fleroxacin group and 86% in the ciprofloxacin group, and 69 and 65%, respectively, 6 weeks after completion of therapy. Adverse events occurred in a similarly low percentage of patients (19 and 20%) in both treatment groups, and consisted primarily of nausea. Once daily fleroxacin appears to be as safe and effective as twice daily ciprofloxacin and both represent efficacious treatment in complicated urinary infection in spinal injury patients. | Fleroxacin |
OBJECTIVE: To study the chemical constituents of Callicarpa nudiflora. METHODS: The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. RESULTS: Eleven compounds were isolated from the leaves of Callicarpa nudiflora, whose structures were elucidated as 2alpha,3alpha-dihydroxyurs-12-en-28-oic acid (1), isorhamnetin (2), 2alpha,3beta,19alpha-trihydroxyurs-12-en-28-oic acid(3), 2alpha,3alpha,19alpha,23-tetrahydroxyurs-12-en-28-oic acid(4), 2alpha,3alpha,19alpha-trihyhydroxy-olean-12-en-28-O-alpha-D-glucopyranoside (5), benzyl-4'-hydroxy-benzoyl-3'-O-beta-D-glucopyranoside(6) (3S,5R,6R,7E,9S)-megastigman-7-ene-3,5,6,9-tetrol(7), philonotisflavone(8), 1, 6-di-O-caffeoyl-beta-D-glucopyranoside (9), luteolin-4'-O-(6-E-caffeoyl)-beta-D-glucopyranoside (10), and (6S, 9R)-roseoside(11). CONCLUSION: All compounds are isolated from this plant for the first time." | Phytochemicals |
Cerebral cavernous malformations, vascular abnormalities comprised of endothelial cells in the absence of connective tissue or muscle, are often epileptogenic and often treated initially with antiepileptic drugs. This chapter discusses the role of pharmacotherapy in managing focal epilepsy secondary to cavernous malformations in adults, children, and pregnant women. Several drugs are available and potentially efficacious in suppressing seizures stemming from cavernous malformations. In addition, antiepileptic pharmacotherapy following surgical resection is indicated to decrease the risk of postoperative seizures. Finally, potential novel therapeutics targeting cavernous malformations are discussed." | Hemangioma, Cavernous, Central Nervous System |
Previous studies indicate that in response to a step-ramp visual target movement, the saccade amplitude approximates target displacement 100 ms before saccade onset. This study examines whether the saccadic system takes target motion into consideration when computing saccadic amplitude, if target movement is seen by the subject before he is requested to make a saccade. In the first experiment, while the subject fixated at the target (laser dot) and maintained fixation, the target jumped to the left and moved to the right at a fixed velocity. At some predetermined site, the target jumped a step to the right and continued to move in that direction. After the target step, the subject had to make a saccade and follow target motion. In the second experiment, while the subject fixated at the target and maintained fixation, the target jumped to the right and up and moved down at a fixed velocity. At some predetermined site, an auditory signal was given, and the subject had to make a saccade and follow target motion. Results in both experiments showed that the eye position was statistically different from the target displacement at 100 ms before saccade onset, indicating that the saccadic system uses target velocity in computing saccade amplitude." | Ocular Physiological Phenomena |
White, beige, and brown adipocytes are developmentally and functionally distinct but often occur mixed together within individual depots. To target white, beige, and brown adipocytes for diagnostic or therapeutic purposes, a better understanding of the cell surface properties of these cell types is essential. Using a combination of in silico, in vitro, and in vivo methods, we have identified three new cell surface markers of adipose cell types. The amino acid transporter ASC-1 is a white adipocyte-specific cell surface protein, with little or no expression in brown adipocytes, whereas the amino acid transporter PAT2 and the purinergic receptor P2RX5 are cell surface markers expressed in classical brown and beige adipocytes in mice. These markers also selectively mark brown/beige and white adipocytes in human tissue. Thus, ASC-1, PAT2, and P2RX5 are membrane surface proteins that may serve as tools to identify and target white and brown/beige adipocytes for therapeutic purposes. | Receptors, Purinergic P2X5 |
A discrete-trial choice procedure was used to examine the reinforcing and subjective effects of four anorectic drugs (mazindol, benzphetamine, phenylpropanolamine and phenmetrazine) in groups of normal healthy adults. For each experiment, subjects first sampled placebo and a dose of one of the drugs (mazindol: 0.5, 1.0 and 2.0 mg; benzphetamine: 25 and 50 mg; phenylpropanolamine: 12.5, 25 and 50 mg; phenmetrazine: 25 and 50 mg; all p.o.). Subjects were then allowed to choose between drug and placebo on five separate occasions. The relative frequency with which active drug was chosen over placebo was used as an index of the drug's reinforcing efficacy. Subjective effects were measured with an experimental version of the Profile of Mood States, a short form of the Addiction Research Center Inventory and a series of visual analog scales. The rank order for reinforcing efficacy was benzphetamine approximately phenmetrazine greater than placebo greater than phenylpropanolamine much greater than mazindol. Ratings of drug liking were positively correlated with number of drug choices for each drug. Benzphetamine and phenmetrazine produced subjective effects characteristic of amphetamine-like drugs and increased ratings of drug liking. Mazindol produced only dysphoric subjective effects and decreased ratings of drug liking. Phenylpropanolamine had no significant effects on subjective measures or drug-liking ratings. These findings are consistent with the presumed dependence potential of these compounds, and demonstrate the validity of this experimental paradigm for assessing the reinforcing effects of anorectics in normal human volunteers. | Appetite Depressants |
PURPOSE OF REVIEW: This article discusses some of the unique features of dementia in the oldest old, including some of the most common diagnostic challenges, and potential strategies to overcome them. RECENT FINDINGS: Advances include new insight into the role of common risk factors and the effects of multiple underlying neuropathologic features for dementia in the oldest old. In addition, this article contains the latest age-specific normative data for commonly used neuropsychological tests for the oldest old. SUMMARY: The oldest old-people aged 90 years and older-are the fastest-growing segment of society and have the highest rates of dementia in the population. The risk factors, diagnostic challenges, and underlying neuropathologic features of dementia are strikingly different in the 90-years-and-older population compared to younger elderly. Special consideration of these unique features of dementia is necessary when evaluating oldest-old subjects with cognitive impairment. | Dementia |
Isolated mesenteric arteries, studied under 25-30 mg resting tension, responded to prolonged noradrenaline or electrical stimulation with a 50-500 mg increase in tension from which they subsequently escaped towards resting tension levels. | Mesenteric Arteries |
For the survival of the motile phototrophic microorganisms, being under proper light conditions is crucial. Consequently, they show photo-induced behaviors (or photobehavior) and alter their direction of movement in response to light. Typical photobehaviors include photoshock (or photophobic) response and phototaxis. Photoshock is a response to a sudden change in light intensity (e.g., flash illumination), wherein organisms transiently stop moving or move backward. During phototaxis, organisms move toward the light source or in the opposite direction (called positive or negative phototaxis, respectively). The unicellular green alga Chlamydomonas reinhardtii is an excellent organism to study photobehavior because it rapidly changes its swimming pattern by modulating the beating of cilia (a.k.a., flagella) after photoreception. Here, various simple methods are shown to observe photobehaviors in C. reinhardtii. Research on C. reinhardtii's photobehaviors has led to the discovery of common regulatory mechanisms between eukaryotic cilia and channelrhodopsins, which may contribute to a better understanding of ciliopathies and the development of new optogenetics methods. | Channelrhodopsins |
Urinary lithiasis is a worldwide very frequent disease, but its etiology is most frequently unclear. Calcium stones are predominant. The metabolic evaluation of urinary lithiasis may be difficult and inconclusive, but it can guide a specific treatment. Medical treatment depends on the nature of stone and the metabolic disease that might be found. The goal of this article is to simplify and summarize the etiopathology, metabolic evaluation and medical treatment of urinary stone disease. | Urinary Calculi |
Oscillatory activity is a prominent characteristic of the olfactory system. We previously demonstrated that beta and gamma oscillations occurrence in the olfactory bulb (OB) is modulated by the physical properties of the odorant. However, it remains unknown whether such odor-related modulation of oscillatory patterns is maintained in the piriform cortex (PC) and whether those patterns are similar between the anterior PC (aPC) and posterior PC (pPC). The present study was designed to analyze how different odorant molecular features can affect the local field potential (LFP) oscillatory signals in both the aPC and the pPC in anesthetized rats. As reported in the OB, three oscillatory patterns were observed: standard pattern (gamma + beta), gamma-only and beta-only patterns. These patterns occurred with significantly different probabilities in the two PC areas. We observed that odor identity has a strong influence on the probability of occurrence of LFP beta and gamma oscillatory activity in the aPC. Thus, some odor coding mechanisms observed in the OB are retained in the aPC. By contrast, probability of occurrence of different oscillatory patterns is homogeneous in the pPC with beta-only pattern being the most prevalent one for all the different odor families. Overall, our results confirmed the functional heterogeneity of the PC with its anterior part tightly coupled with the OB and mainly encoding odorant features whereas its posterior part activity is not correlated with odorant features but probably more involved in associative and multi-sensory encoding functions. | Piriform Cortex |
BACKGROUND: One of the most prevalent sleep disorders affecting the individual's daily life is obstructive sleep apnea (OSA), for which obesity is a major risk factor. Several novel lipid indices have been suggested to have associations with OSA, among which visceral adiposity index (VAI), atherogenic index of plasma (AIP), and lipid accumulation product (LAP) are the most important ones. Herein, the current study aimed to systematically investigate the association between these indices and OSA. METHODS: Four international databases, including PubMed, Scopus, the Web of Science, and Embase were searched in order to find relevant studies that investigated LAP, VAI, or AIP in OSA and compared them with non-OSA cases or within different severities of OSA. Random-effect meta-analysis was used to generate the standardized mean difference (SMD) and 95% confidence interval (CI) of the difference in lipid indices between OSA and non-OSA cases. Moreover, the pooled area under the receiver operating characteristic curves (AUCs) observed in individual studies for diagnosis of OSA based on these lipid indices were calculated by random-effect meta-analysis. RESULTS: Totally 14 original studies were included, comprised of 14,943 cases. AIP, LAP, and VAI were assessed in eight, five, and five studies, respectively. Overall, these lipid indices had acceptable diagnostic ability (AUC 0.70, 95% CI 0.67 to 073). Meta-analysis revealed that AIP was significantly higher in patients with OSA (SMD 0.71, 95% CI 0.45 to 0.97, P < 0.01). Moreover, AIP also increased in higher severities of OSA. Regarding LAP, a higher LAP was observed in OSA/patients with high risk for OSA rather than in controls/low risk for OSA (SMD 0.53, 95% CI 0.25 to 0.81, P < 0.01). VAI was also increased in OSA based on results from two studies. CONCLUSION: These findings suggest that composite lipid indices are increased in OSA. Also, these indices can have the potential beneficiary diagnostic and prognostic ability in OSA. Future studies can confirm these findings and enlighten the role of lipid indices in OSA. | Lipid Accumulation Product |
Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) are obligatory hibernators who can survive over 6 months of the year in underground burrows or laboratory hibernaculum without access to food or water [1]. Hibernation consists of prolonged periods of torpor, lasting up to 18 days, which are characterized by low body temperature and suppressed metabolism. This torpidity is interspersed with short periods of interbout arousal, lasting up to 48 h, during which squirrels temporarily return to an active-like state and lose small amounts of water to urination and evaporation [2]. Water is also lost during torpor due to a positive vapor pressure difference created by the slightly higher temperature of the body compared to its surroundings [2, 3]. Here, we investigate the physiological mechanism of survival during prolonged water loss and deprivation throughout hibernation. By measuring hydration status during hibernation, we show that squirrels remain hydrated during torpor by depleting osmolytes from the extracellular fluid. During brief periods of arousal, serum osmolality and antidiuretic hormone levels are restored, but thirst remains suppressed. This decoupling of thirst and diuresis enables water retention by the kidney while suppressing the drive to leave the safety of the underground burrow in search of water. An acute increase in serum osmolality reinstates water-seeking behavior, demonstrating preservation of the physiological thirst circuit during hibernation. Better mechanistic understanding of internal osmolyte regulation and thirst suppression could translate to advancements in human medicine and long-term manned spaceflight. VIDEO ABSTRACT. | Sciuridae |
The fatty acid composition of the seed oil of 23 Stachys taxa was analysed by GC/MS. The main compounds were found to be linoleic (27.1-64.3%), oleic (20.25-48.1%), palmitic (4.3-9.1%), stearic (trace to 5.2%) and 6-octadecynoic (2.2-34.1%) acids. The latter compound could be used as a chemotaxonomic marker of the genus Stachys. A cluster analysis was performed for comparison and characterisation of the seed oil from Stachys species. | Stachys |
OBJECTIVE: To retrospectively evaluate the clinical signs, imaging findings, and outcome of feline internal ophthalmoparesis/ophthalmoplegia. PROCEDURE: Medical records were reviewed from 2008 to 2015. Inclusion criteria included cats that presented with internal ophthalmoparesis/ophthalmoplegia, underwent diagnostic imaging, and had follow-up information available. RESULTS: Twelve cases of feline internal ophthalmoparesis/ophthalmoplegia were identified. Nine cats were unilaterally affected, and three cats were bilaterally affected. Affected cats had a median age of 10.54 years (range 5.75 to 13.17), and both sexes of varying breeds were affected (nine males; three females). Clinical signs including abnormal mental status (n = 9; 75%) and additional neurologic abnormalities (n = 10; 83%) were observed. Magnetic resonance imaging and/or computed tomography (MRI/CT) of the head were performed in ten cats, revealing a mass lesion in all cases with varying locations. Multicentric lymphoma was diagnosed in two cats via abdominal ultrasound and cytology. All twelve cats were euthanized due to deterioration of clinical signs and/or quality-of-life concerns. Median time from diagnosis to euthanasia was 3.5 days (range 0 to 80 days). CONCLUSIONS: Feline internal ophthalmoparesis/ophthalmoplegia rarely presents as the sole clinical sign in a referral hospital. Advanced imaging (MRI/CT) may be necessary to reach a definitive diagnosis in these cases. However, abdominal ultrasound would be advocated in cats with systemic clinical signs as a less expensive and less invasive diagnostic test to further investigate the possible etiology of internal ophthalmoparesis/ophthalmoplegia prior to advanced imaging. Feline cases with internal ophthalmoparesis/ophthalmoplegia associated with other intracranial signs and/or systemic clinical signs have a poor prognosis. | Ophthalmoplegia |
L-DOPA (L-3,4-dihydroxyphenylalanine) immunoreactivity was demonstrated in neurons of the cat ventral midbrain and its projection areas, using an immunohistochemical method in conjunction with a newly developed highly specific anti-L-DOPA serum. L-DOPA-immunoreactive (IR) neurons were found in the substantia nigra, retrorubral area and ventral tegmental area of Tsai. L-DOPA-labeled fibers and terminals were hardly detectable in the nigrostriatal pathway and in the caudate nucleus which showed very intense dopamine-immunoreactivity. In contrast, many short labeled processes were detectable in the central amygdala and, although very few in number, in the entorhinal cortex. | Tegmentum Mesencephali |
The Parent Cognition Scale (PCS; Snarr, Slep, & Grande, 2009) is a self-report measure of parental attributions of child behavior that has demonstrated validity in community samples. However, its psychometric properties have not been examined in a clinical sample of parents of children with disruptive behavior. Examining the psychometric properties of the PCS in this population is important given research linking parent attribution with childhood disruptive behavior. The present study aimed to: (a) examine the psychometric properties of the PCS in a sample of parents whose children were clinic-referred for disruptive behavior problems; and (b) investigate the concurrent validity of the PCS and its factors using correlations with parent reports of children's emotional and behavioral difficulties, and parenting skills (i.e., discipline, supervision). A confirmatory factor analysis was run on 225 parents' responses on the PCS, and revealed that a two-factor structure of the PCS fit the data well. Significant correlations were found between Parent Causal Attributions (Factor 1) and parent-reported parenting difficulties. Child Responsible Attributions (Factor 2) were correlated with elevations in children's emotion, attention, and conduct difficulties. The results provide information on the utility of the PCS for parents of children with disruptive behavior and its potential clinical relevance. | Child Behavior |
The antibody titres to the polioviruses after three doses of trivalent oral poliovirus vaccine were assessed in 77 Coloured children aged 3-9 months. Neutralizing antibody titres of 1 in 10 or greater to all three types were found in 59 (77%) of all children. The remaining 18 children lacked demonstrable antibody to one or more of the polioviruses. Antibody to types 1 and 3 was most commonly lacking. The possible reasons for the failure of vaccination in so many children is discussed. Studies of the effect of further doses of vaccine on serum antibody levels are recommended. | Poliovirus Vaccine, Oral |
The regulation, structure and function of monoamine oxidases (MAO's) have been a subject of my research for many years. Studies of the enzyme have moved from early biochemical experiments, where different forms were biochemically characterized, to the molecular biology revolution where the genes for MAO A and MAO B were cloned and sequenced. Analyses of the signal pathways of gene regulation and specific transcriptional repression of MAO gene expression followed, as did the elucidation of the role of MAO in apoptosis. And importantly, MAO's impact on behavioral states of both mice and human beings was discovered. It is fulfilling and humbling to see how our early experiments with tissue homogenates and MAO A and MAO B gene cloning built a foundation for so much subsequent understanding of the molecular and genetic components underlying certain behaviors. | Mice, Transgenic |
Prior research offers limited insight into the types of work experiences that promote leadership skill development and the ways that the person and context shape the developmental value of these experiences. In this article, the authors develop a series of hypotheses linking leadership skill development to features of the experience (developmental challenge), person (learning orientation), and context (feedback availability). Based on 225 on-the-job experiences across 60 managers, their results demonstrate that the relationship between developmental challenge and leadership skill development exhibits a pattern of diminishing returns. However, access to feedback can offset the diminishing returns associated with high levels of developmental challenge. | Personnel Management |
alpha-Glucosidase inhibitors (aGIs) have been used as an effective therapy for type-2 diabetes, which remains a global health issue. The aim of this study was to achieve bioactivity-guided isolation, identification and evaluation of hypoglycemic compounds from Euonymus laxiflorus Champ. trunk bark (ELCTB). Eleven active compounds were isolated and identified as walterolactone A/B beta-d-pyranoglucoside (1), 1-beta-d-glucopyranosyloxy-3,5-dimethoxy-4-hydroxybenzene (9), (-)-gallocatechin (10), schweinfurthinol 9-O-beta-d-pyranoglucoside (11), 1-O-(3-methyl)-butenoyl-myo-inositol (12), leonuriside (14), (+)-catechin (19), methyl galloate (20), (-)-catechin (23), and condensed tannins (5 and 18). Of these 11, novel 4 compounds (1, 11, 12, and 14) were found as new alpha-glucosidase inhibitors. Notably, in vitro results indicated that compounds 1, 5, 10(-)12, 18, and 19 showed potent activity (IC(50) = 0.076-31 microg/mL), and their activities were at a higher level than that of acarbose, a commercial inhibitor (IC(50) = 1345 microg/mL). In animal tests, the major inhibitor, condensed tannin (18), demonstrated significant reduction of plasma glucose in mice with no symptoms of diarrhea at the dose of 100 mg/kg bw. The results suggest that Euonymus laxiflorus Champ. is a rich source of bioactive compounds for development as health food or drugs with potent hypoglycemic effect. The results of this study also enriched the current novel biological activities of constituents from Euonymus laxiflorus species. | Euonymus |
Lujo virus is an emerging arenavirus circulating in Southern Africa. Although to date there has only been a single outbreak of the novel haemorrhagic disease resulting from human infection with this virus, the case-fatality rate of exposed individuals, including nosocomial transmission, was 80%. The ability to identify viral haemorrhagic fevers accurately, especially those capable of nosocomial transmission, is of critical importance. Timely identification of these diseases allow medical professionals to isolate patients and implement barrier nursing techniques in order to prevent onward transmission of the virus. While rapid diagnostic methods are published for most viral haemorrhagic fevers, at present there are no such virus specific protocols for Lujo haemorrhagic fever. This report details the first set of diagnostic molecular assays designed to identify Lujo viral RNA rapidly, and demonstrates the potential functionality of these assays for use in the clinical setting. Although these assays have been designed and validated against a solitary isolate of Lujo virus, this represents the entirety of strains detected to date, and offer quick, cheap and easy methods for use in diagnostic laboratories. | Lujo virus |
A potentiometric method for determining the concentration of bromide in human urine is described. On account of its specificity and precision, this method is especially suited for the determination of slightly elevated bromide concentrations due to occupational exposure to alkyl bromides. The rate of recovery is 102.5 to 112.5%, and the variability coefficients lie between 5.8 and 8.6%. The detection limit is about 0.013 mmol/l. The concentrations of bromide in the urine of a group of normal persons lie between 0.059 and 0.162 mmol/l. | Bromides |
AIMS: Since dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, a high sodium intake can be expected to curtail life span. We tested this hypothesis by analysing the relationship between sodium intake and life expectancy as well as survival in 181 countries worldwide. METHODS AND RESULTS: We correlated age-standardized estimates of country-specific average sodium consumption with healthy life expectancy at birth and at age of 60 years, death due to non-communicable diseases and all-cause mortality for the year of 2010, after adjusting for potential confounders such as gross domestic product per capita and body mass index. We considered global health estimates as provided by World Health Organization. Among the 181 countries included in this analysis, we found a positive correlation between sodium intake and healthy life expectancy at birth (beta = 2.6 years/g of daily sodium intake, R2 = 0.66, P < 0.001), as well as healthy life expectancy at age 60 (beta = 0.3 years/g of daily sodium intake, R2 = 0.60, P = 0.048) but not for death due to non-communicable diseases (beta = 17 events/g of daily sodium intake, R2 = 0.43, P = 0.100). Conversely, all-cause mortality correlated inversely with sodium intake (beta = -131 events/g of daily sodium intake, R2 = 0.60, P < 0.001). In a sensitivity analysis restricted to 46 countries in the highest income class, sodium intake continued to correlate positively with healthy life expectancy at birth (beta = 3.4 years/g of daily sodium intake, R2 = 0.53, P < 0.001) and inversely with all-cause mortality (beta = -168 events/g of daily sodium intake, R2 = 0.50, P < 0.001). CONCLUSION: Our observation of sodium intake correlating positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries argues against dietary sodium intake being a culprit of curtailing life span or a risk factor for premature death. These data are observational and should not be used as a base for nutritional interventions. | Vital Statistics |
Satellite RNA depend for their multiplication on the co-infection of a host cell by a helper virus which can itself multiply independently of the satellite. Four types of satellite RNA have been distinguished on the basis of the size of the RNA and what sort, if any, of protein they encode. One of them, the B-type, comprises relatively large RNA which are messenger RNA for non-structural proteins. Many of these satellites are typified by having nepoviruses as helper viruses. In general, the presence of nepovirus mRNA satellites in a virus culture causes little or no modification to the symptoms of infection by the helper virus and has little effect on its yield. Some satellites appear to be highly specific to a strain of helper virus but others can be helped by heterologous viruses. The proteins encoded by nepovirus mRNA satellites have a M(r) of 38,000 to 48,000 and are relatively basic, in particular in the N-terminal and C-terminal parts of the molecules. However, there is little similarity in amino acid sequence between proteins encoded by different satellites and no peptide motif could be found in all satellite proteins. The results of reverse genetics experiments with satellites suggest that the satellite-encoded protein is essential for the multiplication of the satellite RNA. This system has considerable potential for the study of the mechanisms of replication both of satellite and helper virus RNA. | Nepovirus |
Tumor-associated macrophages (TAMs) constitute a plastic and heterogeneous cell population of the tumor microenvironment (TME) that can account for up to 50% of some solid neoplasms. Most often, TAMs support disease progression and resistance to therapy by providing malignant cells with trophic and nutritional support. However, TAMs can mediate antineoplastic effects, especially in response to pharmacological agents that boost their phagocytic and oxidative functions. Thus, TAMs and their impact on the overall metabolic profile of the TME have a major influence on tumor progression and resistance to therapy, de facto constituting promising targets for the development of novel anticancer agents. Here, we discuss the metabolic circuitries whereby TAMs condition the TME to support tumor growth and how such pathways can be therapeutically targeted. | Cellular Microenvironment |
An ovine testis cell line (OA3.Ts) was evaluated and compared with primary lamb kidney (LK) cells for its utility in capripoxvirus propagation and titration. A comparison of OA3.Ts cell growth kinetics and morphology at low (<33) and high (34-36) passage levels indicated a difference in both characteristics. However, viral titers determined in low and high passage OA3.Ts cells were comparable with those obtained using LK cells. Capripoxvirus infection of OA3.Ts and LK cells resulted in a similar cytopathic effect, which allowed for the detection of discrete viral plaques following immunostaining with capripoxvirus-specific antiserum. | Capripoxvirus |
In 2026, the first of the baby boomers, including Presidents Clinton and Bush, will reach the age of 80, the average age of residents currently in assisted living facilities. In her book The Denial of Aging: Perpetual Youth, Eternal Life, and Other Dangerous Fantasies, Muriel Gillick proposes that the baby boomers will seek assisted living as an alternative to nursing home care. But what about that portion of the population not able to afford the high cost of private assisted living? What option will be available to the low-asset/low-income population in lieu of nursing home care? | Assisted Living Facilities |
The administration separately and sequentially of carbenicillin and gentamicin eradicated Ps. aeruginosa infections, during the period over which they were given, in all of 25 critically ill patients. Electron microscopy revealed differences in the action of these two antibiotics against Ps. aeruginosa in vitro. Culture studies showed synergism between them and destruction by gentamicin of the carbenicillin-induced long, filamentous form of the organism. | Carbenicillin |
alpha-Tropomyosin (alphaTm) is central to Ca(2+)-regulation of cardiac muscle contraction. The familial hypertrophic cardiomyopathy mutation alphaTm E180G enhances Ca(2+)-sensitivity in functional assays. To investigate the molecular basis, we imaged single molecules of human cardiac alphaTm E180G by direct probe atomic force microscopy. Analyses of tangent angles along molecular contours yielded persistence length corresponding to ~35% increase in flexibility compared to wild-type. Increased flexibility of the mutant was confirmed by fitting end-to-end length distributions to the worm-like chain model. This marked increase in flexibility can significantly impact systolic and possibly diastolic phases of cardiac contraction, ultimately leading to hypertrophy. | Tropomyosin |
Onium salts have proved to be efficient sources of carbon-centered radicals. They can undergo homolytic reduction by single electron transfer (SET) and participate in subsequent synthetic transformations. This review aims to provide an overview on the behavior of onium salts including diazonium, sulfonium, selenonium, telluronium, phosphonium and iodonium cations toward various reductive methods such as radiolysis, electrolysis, photolysis or the use of SET reagents. Mechanistic and synthetic aspects are presented. Applications in polymers and materials science are not covered. | Onium Compounds |
This article focuses on the surface engineering of ventricular assist devices (VADs) for the treatment of heart failure patients, which involves the modification of surfaces contacting blood in order to improve the blood compatibility (hemocompatibility) of the VADs. Following an introduction to the categorization and the complications of VADs, this article pays attention on the hemocompatibility, applications and limitations of six types of surface coatings for VADs: titanium nitride coatings, diamond-like carbon coatings, 2-methacryloyloxyethyl phosphorylcholine polymer coatings, heparin coatings, textured surfaces and endothelial cell linings. In particular, diamond-like coatings and heparin coatings are the most commonly used for VADs owing to their excellent hemocompatibility, durability and technical maturity. For high performance and a long lifetime of VADs, surface modification with coatings to ensure hemocompatibility is as important as the mechanical design of the device." | Coated Materials, Biocompatible |
A 75-year-old woman attempted suicide by ingesting a large quantity of granular Di-Syston which is an organophosphate insecticide containing 5% disulfoton (ethylthiometon). On admission, the total plasma phosphorodithioate sulfone concentration (disulfoton and its metabolites, phosphorodithioate sulfoxide and its sulfone) determined by gas chromatography was 1095 ng/mL. After gastric lavage, the concentration gradually decreased to 505 ng/mL. However, it began to increase again 20 h after admission and reached the peak concentration (1322 ng/mL) at 56 h. It was concluded that the secondary elevation of the plasma concentration was due to the prolonged absorption of the organophosphate from the residual granules in the stomach, despite the early gastric lavage. Pralidoxime iodide administration temporarily restored erythrocyte cholinesterase activity to almost normal and inhibited the excessive, delayed reduction of cholinesterase activity. It is recommended that poisoning with the granular form of disulfoton should be treated with repetitive or prolonged gastric and intestinal lavage, charcoal, and a continuous intravenous infusion of pralidoxime iodide in addition to atropine sulfate. | Disulfoton |
Nucleotide sequences of small ruminant lentiviruses (SRLVs) were determined in sheep and goats, including progeny of imported animals, on a farm in Mexico. On the basis of gag-pol, pol, env and LTR sequences, SRLVs were assigned to the B1 subgroup, which comprises caprine arthritis-encephalitis virus (CAEV)-like prototype sequences mainly from goats. In comparison with CAEV-like env sequences of American and French origin, two putative recombination events were identified within the V3-V4 and V4-V5 regions of the env gene of a full length SRLV sequence (FESC-752) derived from a goat on the farm. | Genes, Viral |
Chlorella vulgaris was cultured on an ammonia-mineral salts medium until the nitrate reductase content reached a minimal level. These ammonia-grown cells were then induced by nitrate in the absence of molybdenum and of tungsten. A demolybdo nitrate reductase developed and reached high levels. This protein contained very little nitrate-reducing capacity, but had the full cytochrome c-reducing capacity of normal nitrate reductase. It was purified to homogeneity by the same procedures previously developed for the purification of nitrate reductase. The purified enzyme contained 1 molecule of heme and 1 molecule of FAD/subunit, but no detectable molybdenum or tungsten. This cytochrome c reductase was completely inhibited by antibodies raised against purified nitrate reductase of Chlorella. Mixtures prepared from normal nitrate reductase and the demolybdoenzyme could not be resolved by disc gel electrophoresis or by centrifugation in a density gradient. By a two-step enzyme induction (1, incubation with nitrate in absence of Mo; 2, incubation with Mo in absence of nitrate) the process of nitrate reductase synthesis could be cleanly separated from growth into two steps: Step 1, induction of cytochrome c reductase, was completely inhibited by cycloheximide. Step 2 was unaffected by cycloheximide, and most of the nitrate reductase synthesized accumulated in the form of the reversibly inactivated HCN complex of the enzyme. | Nitrate Reductases |
The mechanisms of the spread to the kidney and urinary tract of miliary tuberculosis which involves the urinary system with a rather high incidence, and, if not detected, may result in a functionless kidney for the often nonspecific symptomatology, are analyzed. These considerations account for the seriousness of the problem of urinary tuberculosis, whose great topical interest is unfortunately proven not only in the African continent where it is particularly common, but also in Europe. The lesions underlying the damage to the renal parenchyma and lower urinary tract are carefully examined for a correct interpretation of the radiologic signs. Most representative patterns of the various stages of urinary tuberculosis are described; the attention is focused on conventional radiology, still the most suitable imaging procedure for its early identification. The role of the other procedures which even if are not of first choice when urinary tuberculosis is suspected, in some cases may be useful in the approach to the disease. The mechanisms of the spread of genital tract tuberculosis, less frequent than urinary tuberculosis, but seemingly interesting for its clinical and diagnostic features, are considered. An accurate analysis of major patterns of tuberculosis of male and female genital tract is reported to better understand the various aspects of diagnostic imaging. | Tuberculosis, Extrapulmonary |
A Gram-stain-negative, oxidase- and catalase-positive bacterial strain that was motile by gliding and produced a pink pigment, designated DCY49(T), was isolated from soil of a ginseng field in a mountainous region of Chungbuk province, South Korea. 16S rRNA gene sequence analysis revealed that strain DCY49(T) belonged to the genus Pedobacter (93.0-96.3 % similarity). Strain DCY49(T) contained MK-7 as the predominant menaquinone. The major fatty acids were summed feature 3 (containing C16 : 1omega7c, C16 : 1omega6c and/or iso-C15 : 0 2-OH), iso-C15 : 0, iso-C17 : 0 3-OH and C16 : 0, and the main polar lipid was phosphatidylethanolamine. The G+C content of the genomic DNA of strain DCY49(T) was 40.5 mol%. Strain DCY49(T) differed from related Pedobacter species by a number of phenotypic characteristics. On the basis of data from the present polyphasic study, strain DCY49(T) is described as representing a novel species of the genus Pedobacter, for which the name Pedobacter ginsengiterrae sp. nov. is proposed. The type strain is DCY49(T) ( = KCTC 23317(T) = JCM 17338(T)). | Pedobacter |
A brief overview of biorepository sustainability from the perspective of a federated biorepository system at the University of Iowa Carver College of Medicine is presented. The ongoing evolution of the federation and the efforts to improve efficacy and efficiency are described. The key sustainability factors identified are adaptability, focus, collaboration/networking, and service improvement. | Biological Specimen Banks |
OBJECTIVE: The present study aimed to test the effect of the electrode position and inter-electrode distance on the evoked force by neuromuscular electrical stimulation (NMES) with a low current intensity and a single pair of electrodes. Knee extensor forces during NMES to quadriceps femoris muscles were compared among four different electrode configurations in seven healthy men. Electrodes were located at 10 cm proximal and 15 cm distal (P10-D15), 10 cm proximal and 10 cm distal (P10-D10), 5 cm proximal and 15 cm distal, and 5 cm proximal and 10 cm distal (P5-D10) to the center of the longitudinal axis of the quadriceps femoris muscles. RESULTS: The evoked force-time area for P5-D10 was significantly higher than those for P10-D15 and P10-D10 (p < 0.05). When using NMES devices with a low current intensity, a shorter inter-electrode distance and relatively distal locations can promote greater evoked forces in the quadriceps femoris muscles. | Quadriceps Muscle |
Grapevine downy mildew is an important disease affecting crop production leading to severe yield losses. This study aims to identify the grapevine cultivar-specific adjustments of leaf proteome that allow the discrimination between resistance and susceptibility towards P. viticola (constitutive (0h) and in after inoculation (6, 12 and 24h). Leaf proteome analysis was performed using 2D difference gel electrophoresis followed by protein identification via mass spectrometry. In addition, we analysed ROS production, antioxidant capacity, lipid peroxidation and gene expression. Proteins related to photosynthesis and metabolism allowed the discrimination of resistant and susceptible grapevine cultivars prior to P. viticola inoculation. Following inoculation increase of hydrogen peroxide levels, cellular redox regulation, establishment of ROS signalling and plant cell death seem to be key points differentiating the resistant genotype. Lipid associated signalling events, particularly related to jasmonates appear also to play a major role in the establishment of resistance. The findings from this study contribute to a better understanding of genotype-specific differences that account for a successful establishment of a defence response to the downy mildew pathogen. BIOLOGICAL SIGNIFICANCE: Here, we present for the first time grapevine cultivar-specific adjustments of leaf proteome that allow the discrimination between resistance and susceptibility towards P. viticola (constitutive (0h) and in after inoculation (6, 12 and 24h). We have highlighted that, following inoculation, the major factors differentiating the resistant from the susceptible grapevine cultivars are the establishment of effective ROS signalling together with lipid-associated signalling events, particularly related to jasmonates. It is believed that plants infected with biotrophic pathogens suppress JA-mediated responses, however recent evidences shown that jasmonic acid signalling pathway in grapevine resistance against Plasmopara viticola. Our results corroborate those evidences and highlight the importance of lipid- signalling for an effective resistance response against the downy mildew pathogen. | Peronospora |
The cortical bone that forms the structure of the cochlea, part of the osseous labyrinth of the inner ear, is now one of the most frequently used skeletal elements in analyses of human ancient DNA. However, there is currently no published, standardized method for its sampling. This protocol describes the preparation of bone powder from the cochlea of fragmented skulls in which the petrous pyramid of the temporal bone is accessible. Using a systematic process of bone removal based on distinct anatomical landmarks and the identification of relevant morphological features, a petrous pyramid is cleaned with a sandblaster, and the cochlea is located, isolated, and reduced to a homogeneous bone powder. All steps are carried out in dedicated ancient DNA facilities, thus reducing the introduction of contamination. This protocol requires an understanding of ancient DNA clean-room procedures and basic knowledge of petrous pyramid anatomy. In 50-65 min, it results in bone powder with endogenous DNA yields that can exceed those from teeth and other bones by up to two orders of magnitude. Compared with drilling methods, this method facilitates a more precise targeting of the cochlea, allows the user to visually inspect the cochlea and remove any residual sediment before the generation of bone powder, and confines the damage to the inner ear region and surface of the petrous portion of fragmentary crania. | DNA, Ancient |
The determinants of vaccine hesitancy remain complex and context specific. Betrayal aversion occurs when an individual is hesitant to risk being betrayed in an environment involving trust. In this pre-registered vignette experiment, we show that betrayal aversion is not captured by current vaccine hesitancy measures despite representing a significant source of unwillingness to be vaccinated. Our survey instrument was administered to 888 United States residents via Amazon Mechanical Turk in March 2021. We find that over a third of participants have betrayal averse preferences, resulting in an 8-26% decline in vaccine acceptance, depending on the betrayal source. Interestingly, attributing betrayal risk to scientists or government results in the greatest declines in vaccine acceptance. We explore an exogenous message intervention and show that an otherwise effective message acts narrowly and fails to reduce betrayal aversion. Our results demonstrate the importance of betrayal aversion as a preference construct in the decision to vaccinate. | Betrayal |
The enteric nervous system is the largest subdivision of the peripheral nervous system that plays a critical role in digestive functions. Despite considerable progress over the last 15 years in understanding the molecular and cellular mechanisms that control the development of the enteric nervous system, several questions remain unanswered. The present review will focus on recent progress on understanding the development of the mammalian enteric nervous system and highlight interesting directions of future research. | Cadherin Related Proteins |
Calcium-dependent secretion activator 2 (CAPS2) regulates the trafficking and exocytosis of neuropeptide-containing dense-core vesicles (DCVs). CAPS2 is prominently expressed in the medial habenula (MHb), which is related to depressive behavior; however, how MHb neurons cause depressive symptoms and the role of CAPS2 remains unclear. We hypothesized that dysfunction of MHb CAPS neurons might cause defects in neuropeptide secretion and the activity of monoaminergic centers, resulting in depressive-like behaviors. In this study, we examined (1) CAPS2 expression in the habenula of depression animal models and major depressive disorder patients and (2) the effects of down-regulation of MHb CAPS2 on the animal behaviors, synaptic transmission in the interpeduncular nucleus (IPN), and neuronal activity of monoamine centers. Habenular CAPS2 expression was decreased in the rat chronic restraint stress model, mouse learned helplessness model, and showed tendency to decrease in depression patients who died by suicide. Knockdown of CAPS2 in the mouse habenula evoked despair-like behavior and a reduction of the release of DCVs in the IPN. Neuronal activity of IPN and monoaminergic centers was also reduced. These results implicate MHb CAPS2 as playing a pivotal role in depressive behavior through the regulation of neuropeptide secretion of the MHb-IPN pathway and the activity of monoaminergic centers. | Dense Core Vesicles |
Hyperthermia is a known apoptotic inducer and has been recently utilized in combination with chemo-and/or radiotherapy in cancer treatment. In this study we have described its effect on SK-N-MC human neuroblastoma tumor cells, a line which grows as a double adherent and floating population. Considering this particular culture behavior, we also investigated the relationship between hyperthermia and cell adhesiveness by evaluating integrin expression, namely CD11a, which is, as known, closely correlated to cell adhesion properties. By a multiple, ultrastructural and flow cytometrical approach, we have demonstrated that hyperthermia, while triggering apoptosis, also determines a CD11a surface expression decrease in apoptotic and living cells. We thus suggest a further role for this treatment, which, affecting adhesion mechanisms, could down-regulate metastatic diffusion. | CD11a Antigen |
The treatment of chronic pain is poorly managed by current analgesics, and there is a need for new classes of drugs. We recently developed a series of bioactive lipids that inhibit the human glycine transporter GlyT2 (SLC6A5) and provide analgesia in animal models of pain. Here, we have used functional analysis of mutant transporters combined with molecular dynamics simulations of lipid-transporter interactions to understand how these bioactive lipids interact with GlyT2. This study identifies a novel extracellular allosteric modulator site formed by a crevice between transmembrane domains 5, 7, and 8, and extracellular loop 4 of GlyT2. Knowledge of this site could be exploited further in the development of drugs to treat pain, and to identify other allosteric modulators of the SLC6 family of transporters." | Plasma Membrane Neurotransmitter Transport Proteins |
The mutagenic consequences of damage to DNA produced by low pH and high temperature have been determined in a forward mutational system capable of detecting all classes of mutagenic events. When damaged single-stranded DNA from bacteriophage M13mp2 is used to transfect competent Escherichia coli cells, a 15-fold increase in mutation frequency, measured as loss of alpha-complementation by the lac DNA in the phage, is observed compared with an untreated DNA control transfection. The enhanced mutagenicity is largely dependent on induction of the error-prone SOS response and is proportional to the number of lethal hits introduced into the DNA. The effect is abolished by treatment of the damaged DNA before transfection with either apurinic/apyrimidinic endonuclease or alkali. Based on these observations and the rate constants for formation of the known heat/acid-produced lesions in DNA, it is concluded that the majority of the induced mutagenesis results from apurinic sites. DNA sequence analysis of 87 spontaneous and 124 induced mutants indicates that the major effect is on single base-substitution mutagenesis with a small increase in (deletion) frame-shift frequency. Approximately 80% of the base-substitution mutations occur at purine positions in the viral strand, consistent with depurination as the predominant premutagenic lesion. The preference of guanine over adenine sites mutated is consistent with the preference for depurination of guanine over adenine. Transversions are observed for 57 of 79 (72%) induced base substitutions, with a strong preference for insertion of adenine residues opposite the putative apurinic site. These data in a forward mutational system provide insight into the mechanisms used by a cell to replicate DNA containing noncoding lesions. | Apurinic Acid |
The immunogenicity of X-irradiated hybrid cells derived from fusion of ASL-1 leukemia (A origin) and LM (TK-) fibroblasts (C3H origin) was compared to X-irradiated parental ASL-1 leukemia cells maintained in vivo (V-ASL-1) and to X-irradiated ASL-1 leukemia cells maintained in vitro (C-ASL-1). Immunization with hybrid cells induced transplantation resistance against tumor rechallenge with V-ASL-1 more effectively than did immunization with V-ASL-1 tumor cells. Immunization with X-irradiated C-ASL-1 cells produced the same, or slightly stronger level of transplantation resistance than that with X-irradiated hybrid cells. These findings were observed both in A/J and in (C3H/HeJ X A/J)F1 mice. These results raise a question about whether the apparent increased immunogenicity of hybrid cells is due to a result of cell fusion or a result of their growth in vitro. | Hybrid Cells |
The spectroscopic ellipsometry (SE), and attenuated internal reflection spectroscopic ellipsometry (TIRE) are promising methods in label-free biosensing applications. An ellipsometer running under surface plasmon resonance (SPR) conditions has unique advantages over other SPR-based methods in terms of sensitivity and real-time/label-free measurement capability. In this study, both SE and TIRE-based brevetoxin B (BTX) sensors were developed using two anti-BTX aptamers reported before. A new aptamer sequence was also derived from these two antiBTX aptamers using predictive modeling tools and an exclusion method. All three antiBTX aptamers' analytical performances were quite competitive in terms of both detecting range and detection limits. However, the selectivity of the previously reported aptamers against analogs of BTX was poor at low detection ranges, especially for okadaic acid. Furthermore, the selectivity of the derived aptamer was lower than its predecessors. The sensors were capable of detecting BTX in the range of 0.05 nM-1600 nM in the TIRE and 0.5 nM-2000 nM in the SE configuration. The detection limits of the sensors were 1.48 nM (1.32 ng/mL) and 0.80 nM (0.72 ng/mL) for SE and TIRE configurations, respectively. Both configurations have been used successfully to detect BTX standards spiked into real fish and shrimp samples. | Oxocins |
A computational protocol aimed to design new antioxidants with versatile behavior is presented. It is called Computer-Assisted Design of Multifunctional Antioxidants and is based on chemical properties (CADMA-Chem). The desired multi-functionality consists of in different methods of antioxidant protection combined with neuroprotection, although the protocol can also be used to pursue other health benefits. The dM38 melatonin derivative is used as a study case to illustrate the protocol in detail. This was found to be a highly promising candidate for the treatment of neurodegeneration, in particular Parkinson's and Alzheimer's diseases. This also has the desired properties of an oral-drug, which is significantly better than Trolox for scavenging free radicals, and has chelates redox metals, prevents the (âÂÂ)OH production, via Fenton-like reactions, repairs oxidative damage in biomolecules (lipids, proteins, and DNA), and acts as a polygenic neuroprotector by inhibiting catechol-O-methyl transferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase B (MAOB). To the best of our best knowledge, CADMA-Chem is currently the only protocol that simultaneously involves the analyses of drug-like behavior, toxicity, manufacturability, versatile antioxidant protection, and receptor-ligand binding affinities. It is expected to provide a starting point that helps to accelerate the discovery of oral drugs with the potential to prevent, or slow down, multifactorial human health disorders. | Computational Chemistry |
Taenia solium is the aetiological agent of cysticercosis, a zoonosis that causes severe health and economic losses across Latin America, Africa and Asia. The most serious manifestation of the disease is neurocysticercosis, which occurs when the larval stage (cysticercus) establishes in the central nervous system. Using Taenia crassiceps as an experimental model organism for the study of cysticercosis, we aimed to identify the in vitro conditions necessary to allow parasite development at the short- and long terms. First, cysticerci were incubated for 15 days in different media and parasite densities. The number of buddings and cysticerci diameter were measured to evaluate asexual multiplication and parasite growth, respectively. Vitality was determined by trypan blue staining and morphology analysis. As a result, high cysticerci density and medium containing FBS and the excretion/secretion (E/S) products of feeder cells induced parasite survival, growth and multiplication. Then, the long-term (5 weeks) incubation of the parasites in co-culture with feeder cells was evaluated. Consequently, the mammalian cell lines induced a significant increase in total parasite volume while axenic cultures did not show any statistically significant change over time. In this study, the proper conditions to maintain T. crassiceps in vitro are described for the first time in a simpler and more controlled setting other than experimental infections. In addition, it was shown that cysticerci growth, survival and asexual multiplication depend on a complex network of secreted factors from both parasite and host. | Taenia |
PURPOSE: The transcription factor TWIST is an important factor in regulation of the epithelial-mesenchymal transition (EMT), which represents the primary stages during the metastasis of tumors. To identify the role of TWIST in the regulation of metastasis in laryngeal carcinoma Hep-2 cells, we investigated whether the alteration of TWIST has an effect on the Hep-2 cells morphology and whether the alteration of TWIST has an effect on the expression of E-cadherin, N-cadherin as well as the ability of cell motion, migration, and invasion. METHODS: Morphological changes of Hep-2 cells that were transfected a mircoRNA against TWIST vector were observed by the reserved microscope. Reverse transcription-polymerase chain reaction was performed in order to examine the mRNA expression of TWIST, E-cadherin, and N-cadherin. Western blotting was performed to examine the protein expression of TWIST, E-cadherin, and N-cadherin. Cell motion ability was examined by Scratch-wound assay. Transwell() chamber assays were used to determine cell migration and invasion. RESULTS: Transfecting a mircoRNA down-regulated TWIST expression at mRNA and protein levels. Down-regulation of TWIST expression induced morphological changes, such as the inversion of the EMT. Moreover, down-regulation of TWIST expression up-regulated E-cadherin and down-regulated N-cadherin expressions at mRNA and protein levels, respectively. Furthermore, we confirmed that down-regulation of TWIST expression decreased the motion, invasion, and migration ability of the Hep-2 cells. CONCLUSIONS: Down-regulation of TWIST expression decreases migration and invasion of laryngeal carcinoma Hep-2 cells by regulation of the E-cadherin, N-cadherin expression. | Twist Transcription Factors |
OBJECTIVES/HYPOTHESIS: To determine whether the presence of aural discharge at the time of surgery adversely affects the success rate of myringoplasty operations. STUDY DESIGN: Case series comparing the success rate of surgery in active and inactive ears. METHODS: Data pertaining to 268 operations involving repair of the tympanic membrane without ossiculoplasty carried out in Edinburgh, United Kingdom, between 1999 and 2009 by one senior surgeon and trainees working under his supervision were collected prospectively. Other factors that might potentially influence the outcome of the surgery were investigated using logistical regression analysis. The main outcome measure was number of patients with an intact tympanic membrane 6 months after surgery in the two groups (active and inactive). RESULTS: Of the 268 operations carried out, 203 were successful, with an intact tympanic membrane, 6 months postoperatively, 43 had persistent perforations, and 22 patients were lost to follow-up before 6 months. The success rates for closure of the perforation at 6 months after surgery were 83% for inactive and 82% for active ears (P = .9). CONCLUSIONS: There is no clinically significant difference in the success rate for myringoplasty in patients whose ears are active or inactive at the time of surgery. | Myringoplasty |
Monkey B virus (Macacine herpesvirus 1; BV) is endemic in macaques. BV (a BSL4 agent) is the primary zoonotic concern for persons working with macaques in research, and human BV infections frequently are fatal. We assessed the use of a BSL2 baboon herpesvirus (Papiine herpesvirus 1; HVP2) for predicting the drug sensitivity of BV by comparing the sensitivity of the 2 viruses to 12 antiherpetic drugs. Plaque reduction assays showed that 4 drugs (HBPG, BVdU, PFA, and BrdU) were ineffective against both viruses. Of the 8 effective drugs, both viruses were most sensitive to TFT, whereas sensitivity to the remaining 7 drugs varied between BV and HVP2 as well as between strains of HVP2. In addition, the efficacy of 5 drugs (ACV, PCV, GCV, CDV, and EDU) was tested by using a murine model. ACV and EDU were completely ineffective against both HVP2 and BV, and high doses of PCV only delayed death by a few days. GCV and CDV both protected mice against death, and CDV also prevented the development of neurologic symptoms. When the initiation of drug therapy was delayed until after virus gained access to the CNS, both GCV and CDV were ineffective. The similarity of the drug sensitivities of HVP2 and BV in both models validates the use of HVP2 as a BSL2 level model that can be used to predict drug sensitivity of BV. The greater efficacy of CDV relative to GCV suggests the potential for use of CDV in the treatment of zoonotic BV infections. | Herpesvirus 1, Cercopithecine |
The synthesis and biological evaluation of structurally simplified, metabolically stable cyclopamine-like Sonic Hedgehog (SHH) signaling inhibitors, i.e., 5, is described in four chemical steps from commercially available steroidal precursors. Biological evaluation of this cyclopamine analogue in two different systems establishes the high potency of 5 as a SHH signaling inhibitor. This approach provides important new lead structures for the development of new cancer chemotherapeutic agents based on the inhibition on SHH signaling. | Veratrum Alkaloids |
The net rate of liquid flow and Na+ flux across the pleura was determined in anesthetised rabbit during hydrothoraces 0.5 to 5 ml in size, without and with amiloride. In the hydrothoraces with amiloride the net liquid flow and Na+ flux reversed when the volume injected approached zero. This indicates that the active Na+ transport and the consequent liquid absorption occur also under physiological conditions. The difference between the data obtained without and with amiloride provides the net solute-coupled liquid outflow and active Na+ efflux. These parameters increased linearly with the hydrothorax size up to 2 ml (0.39 ml/h and 54 muEq/h, respectively), and then levelled off. The linear relationship allowed their extrapolation to physiological conditions: 0.15 ml/h (0.07 ml.h-1.kg-1) and 21 muEq/h (0.1 muEq.h-1.cm-2). The increase in these parameters with the hydrothorax size seems due to the protein dilution caused by the Ringer injection, because it did not occur if Ringer was added with albumin to keep the protein concentration in the pleural liquid similar to that under physiological conditions. | Biological Transport, Active |
There is increasing interest in the effects of reactive oxygen species ('free radicals') in ageing, both in the body overall and specifically in the eye. Cataract and age-related macular degeneration (AMD) are two major causes of blindness, with cataract accounting for 48 per cent of world blindness and AMD accounting for 8.7 per cent. Both cataract and AMD affect an older population (over 50 years of age) and while cataract is largely treatable provided resources are available, AMD is a common cause of untreatable, progressive visual loss. There is evidence that AMD is linked to exposure to short wavelength electromagnetic radiation, which includes ultraviolet, blue and violet wavelengths. The ageing crystalline lens provides some protection to the posterior pole because, as it yellows with age, its spectral absorption increasingly blocks the shorter wavelengths of light. Ultraviolet blocking intraocular lenses (IOLs) have been the standard of care for many years but a more recent trend is to include blue-blocking filters based on theoretical benefits. As these filters absorb part of the visible spectrum, they may affect visual function. This review looks at the risks and the benefits of filtering out short wavelength light in pseudophakic patients. | Night Vision |
The severe acute respiratory syndrome (SARS)-associated coronavirus causes severe disease, is transmissible to the community and there is no effective prophylaxis or treatment--perhaps fulfilling the criteria for biohazard group 3 or 4. The recommendation to use Biosafety Level (BSL)3 practices within a BSL2 environment appears to have been a practical decision based on available resources; most diagnostic laboratories operate at BSL2. Safety is achieved with controls in administration, engineering and personal protective equipment/behaviour. At the heart of every safety policy is a risk assessment based on the exact manipulations employed. Excessive administrative and engineering controls are less important than the training and personal attitudes, abilities and understanding of the staff. The SARS outbreak focused our attention on the safety aspects of common mundane tasks, such as decapping blood tubes. Laboratories often claim they follow certain practices but casual observation does not always support these claims. Guidelines differed and created uncertainty. This was stressful for laboratory staff held accountable for their implementation. Attempts to categorise risks and their management into neatly wrapped parcels are attractive, but closer inspection reveals a subjective element that allows doubt to creep in with varying interpretations of the literature. Staff most at risk were those handling respiratory samples. Staff receiving samples via pneumatic tubes had least control over their exposure and were potentially exposed to aerosols from leaking samples. Risk assessment remains a balance between cost and benefit. | Containment of Biohazards |
A new emulsion-gelation method to prepare oil-entrapped calcium pectinate gel (CaPG) beads capable of floating in the gastric condition was designed and tested. The gel beads containing edible oil were prepared by either being gently mixed or homogenized an oil phase and a water phase containing pectin, and then extruded into calcium chloride solution with gentle agitation at room temperature. The gel beads formed were then separated, washed with distilled water, and dried at 37 degrees C for 12 hours. A model of the emulsion-gelation process to illustrate the formation of oil-entrapped CaPG beads was proposed. The effect of selected factors, such as type of oil, percentage of oil, and type of pectin on morphology and floating properties was investigated. The oil-entrapped calcium pectinate gel beads floated if a sufficient amount of oil was used. Scanning electron photomicrographs demonstrated very small pores, ranging between 5 and 40 microm, dispersed all over the beads. The type and percentage of oil play an important role in controlling the floating of oil-entrapped CaPG beads. The results suggested that oil-entrapped CaPG beads were promising as a carrier for intragastric floating drug delivery. | Dosage Forms |
PURPOSE OF REVIEW: This article reviews the current literature for the purpose of developing a practical approach for the diagnosis and management of primary tracheal tumors. RECENT FINDINGS: Because of nonspecific symptoms, tracheal tumors remain a diagnostic challenge. Currently available management strategies are not being optimally utilized due to lack of physician awareness and knowledge. The use of newer diagnostic modalities has increased diagnostic accuracy resulting in earlier detection in recent years. This review describes currently available diagnostic modalities along with relatively newer ones such as virtual bronchoscopy, anatomic Optical Coherence Tomography, spectroscopic techniques, and endobronchial ultrasonography. We will review and discuss management strategies including surgical options, adjuvant therapies, and interventional pulmonary techniques including their role in palliation. SUMMARY: Early detection along with improved surgical and interventional pulmonology techniques has led to a decline in the death rates from tracheal cancer in recent years. However, further studies are required to define the role of chemotherapeutic agents, combination therapies, and novel techniques such as tracheal transplantation, in the management of primary tracheal tumors. More robust evidence-based studies are needed to provide evidence for clinical practice guidelines for the treatment of primary tracheal tumors. | Tracheal Neoplasms |
To explore the response of beta globin locus with established chromatin domains upon their exposure to new transcriptional environments, we transferred the chromatin-packaged beta globin locus of undifferentiated human embryonic stem cells (hESCs) or hESC-derived erythroblasts into an adult transcriptional environment. Distinct globin expression patterns were observed. In hESC-derived erythroblasts where both epsilon and gamma globin were active and marked by similar chromatin modifications, epsilon globin was immediately silenced upon transfer, whereas gamma globin continued to be expressed for months, implying that different transcriptional environments were required for their continuing expression. Whereas beta globin was silent both in hESCs and in hESC-derived erythroblasts, beta globin was only activated upon transfer from hESCs, but not in the presence of dominant gamma globin transferred from hESC-derived erythroblasts, confirming the competing nature of gamma versus beta globin expression. With time, however, silencing of gamma globin occurred in the adult transcriptional environment with concurrent activation of beta-globin, accompanied by a drastic change in the epigenetic landscape of gamma and beta globin gene regions without apparent changes in the transcriptional environment. This switching process could be manipulated by overexpression or downregulation of certain transcription factors. Our studies provide important insights into the interplay between the transcription environment and existing chromatin domains, and we offer an experimental system to study the time-dependent human globin switching. | epsilon-Globins |
Triglycerides (TGs) are the major transporters of dietary fats throughout the bloodstream. Besides transporting fat, TGs also act as stored fat in adipose tissue, which is utilized during insufficient carbohydrates supply. TG level is below 150mg/dL in healthy persons. Elevated TGs level in blood over 500mg/dL is a biomarker for cardiovascular diseases, Alzheimer disease, pancreatitis and diabetes. Numerous methods are accessible for recognition of TGs, among them, most are cumbersome, time-consuming, require sample pre-treatment, high cost instrumental set-up and experienced personnel to operate. Biosensing approach overcomes these disadvantages, as these are highly specific, fast, easy, cost effective, and highly sensitive. This review article describes the classification, operating principles, merits and demerits of TG biosensors, specifically nanomaterials based biosensors. TG biosensors work ideally within 2.5-2700s, in pH range, 6.0-11.0, temperature 25-39.5 degrees C and TG concentration range, 0.001-100mM, the detection limits being in the range, 0.1nM to 0.56mM, with working potential - 0.02 to 1.2V. These biosensors measured TG level in fruit juices, beverages, sera and urine samples and reused upto 200 times over a period of 7-240 days, while stored dry at 4 degrees C. Future perspective for further improvement and commercialization of TG biosensors are discussed. | Triglycerides |
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