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INTRODUCTION: This present study aimed to isolate beneficial bacteria from honey bee pollen microbiota and to investigate the metabolite profiles of postbiotics exhibiting anti-microbial and anti-oxidant properties. METHODOLOGY: Pour plate technique was used to isolate bacteria from honey bee (Apis mellifera L.) pollen samples. Different colonies grown on agar plates were selected and screened for their anti-microbial activity against important pathogens using agar well diffusion assay. The isolates that exhibited remarkable inhibitory effects against all tested pathogens were identified by 16S rRNA sequence analysis. DPPH (2, 2-diphenyl-1-picrylhydrazil) free radical scavenging assays were used to assess the antioxidant capacity of their postbiotics. Besides, the total phenolic and total flavonoid compounds in postbiotics were determined as gallic acid and quercetin equivalents, respectively. The valuable metabolites in postbiotics were also profiled using chromatographic tools and Mass Spectrophotometry (MS) analysis. RESULTS: Twenty-seven strains were isolated from different honey bee pollen samples. 16 out of the 27 strains exhibited antagonistic activity against at least one reference strain of pathogens, tested. The most effective strains belonging to the genus Weissella were identified as W. cibaria and W. confusa. Postbiotics above 10 mg/mL exhibited higher radical scavenging activity and high total phenolic and total flavonoid contents. MS analysis demonstrated that metabolites in postbiotics derived from Weissella spp. were found very similar to the metabolites found in honeybee pollen. CONCLUSIONS: The outcomes of this study revealed that honey bee pollen could be considered a potential source for the bacteria which produce anti-microbial and anti-oxidant agents. The similarity with the nutritional dynamics of honey bee pollen also indicated that postbiotics could also be used as novel and sustainable food supplements. | Weissella |
Companies developing automated driving system (ADS) technologies have spent heavily in recent years to conduct live testing of autonomous vehicles operating in real world environments to ensure their reliable and safe operations. However, the unexpected onset and ongoing resurgent effects of the Covid-19 pandemic starting in March 2020 has serve to halt, change, or delay the achievement of these new product development test objectives. This study draws on data obtained from the California automated vehicle test program to determine the extent that testing trends, test resumptions, and test environments have been affected by the pandemic. The importance of government policies to support and enable autonomous vehicles development during pandemic conditions is highlighted. | Mechanical Tests |
Resistance to macrolides, lincosamides and streptogramin B antibiotics (MLSB) is not restricted to staphylococci from clinical samples but can also be present in staphylococci from the aquatic environment. Two coagulase-negative staphylococci-Staphylococcus xylosus and S. saprophyticus were obtained from sewage and receiving river water samples and were investigated for the genetic basis of inducible MLSB resistance by whole-genome sequencing. Two rRNA methylases encoded by erm(44) and a novel erm(44) variant were identified, which had only 84% amino acid identity. While fragments of phage DNA were found in the vicinity of the erm(44) gene of S. xylosus, no relics of mobile genetic elements were detected in the sequences flanking the erm(44) variant gene in the S. saprophyticus strain. The functionality of the erm genes was confirmed by cloning and transformation experiments. Based on the obtained sequences, specific PCR assays for both erm genes were developed and used to identify erm(44) in another 7 S. xylosus and 17 S. saprophyticus isolates from aquatic environments. | Streptogramin Group B |
INTRODUCTION: Acne vulgaris is the most common skin disease worldwide; yet, current treatment options, although effective, are associated with unwanted side effects, chronicity, relapses and recurrences. The adequate control of the four pathogenic mechanisms, involved in the appearance of acne lesions, is paramount to treatment success. AREAS COVERED: The authors discuss and evaluate the pathogenic pathways related to the mechanisms of action of novel molecules, which are currently under investigation for the treatment of acne vulgaris. The manuscript is based on comprehensive searches made through PubMed, GoogleScholar and ClinicalTrial.gov, using different combination of key words, which include acne vulgaris, pathogenesis, treatment, sebogenesis and Propionibacterium acnes. EXPERT OPINION: In the near future, more effective treatments with fewer side effects are expected. The use of topical antiandrogens, acetylcholine inhibitors and PPAR modulators seem to be promising options for controlling sebum production. Retinoic acid metabolism-blocking agents and IL-1alpha inhibitors have the potential to become legitimate alternative options to retinoid therapy in the management of infundibular dyskeratosis. Indeed, the authors believe that there will likely be a decline in the use of antibiotics for controlling P. acnes colonization and targeting the inflammation cascade. | Sebum |
Incorrect occlusion is a major cause of complete denture failure. Any technique which has the potential to solve this problem and consequently limit the number of review appointments must be worthy of consideration. The pre-occlusal or precentric check record is an accurate method of verifying the occlusion of complete dentures. Although the check record is taught in many teaching hospitals, it is not widely used in general practice. This is primarily due to the time-consuming nature of the conventional method. A variation on the standard technique is described, which is designed specifically for NHS complete denture practice. The materials used are inexpensive and the procedure takes approximately 10 minutes. | Denture Design |
Adult patients with sickle cell disease (SCD) are highly susceptible to stem cell transplant complications, including drug toxicity, graft versus host disease (GVHD), and graft rejection due to SCD-related tissue damage, endothelial activation, and inflammation. The scarcity of compatible stem cells for transplantation further limits treatment options, with only 43 cases of adult allogeneic peripheral blood stem cell transplantation (allo-PSCT) from human leukocyte antigen (HLA)-identical sibling donors reported in the international registry for the period 1986-2013. Herein we report remarkable outcomes in a cohort of adult SCD patients who underwent allo-PSCT using a fludarabine (Flu), busulfan (Bu), and anti-T-cell lymphocyte globulin (ATG)-based conditioning regimen in combination with very low dose total body irradiation (TBI), followed by post-transplant cyclophosphamide (Cy) and sirolimus as GVHD prophylaxis. We performed a single-center, retrospective study consisting of 20 consecutive patients (mean age 33.4 years) who underwent allo-PSCT from HLA-matched related donors with a conditioning regimen of Flu 150/Bu 3.2/Cy 29/ATG 30 (Fresenius)/TBI 200 between September 2013 and September 2017. Data were validated by an independent data audit group of the affiliated JACIE-accredited transplantation center. All patients experienced a sustained donor cell engraftment. Full donor chimerism (total cell) occurred within 180 days in all patients. Mean duration of follow-up was 13.8 months (range: 0.3-50 months), with 12 (60%) patients completing 12 months. No non-relapse mortality or graft rejection occurred. Successful treatment was achieved without the presence of graft loss, grade III-IV acute GVHD, extensive chronic GVHD, or other major complications. Allo-PSCT in combination with Flu 150/Bu 3.2/Cy 29/ATG 30(Fresenius)/TBI 200- Cy/Sirolimus therapy yielded encouraging outcomes with no mortality and low incidence of GVHD. Further controlled studies will be necessary to compare transplant protocols and long-term outcomes." | Peripheral Blood Stem Cell Transplantation |
Expansion of a polyalanine stretch from 10 to 12-17 residues in the N-terminus of the protein PABP2 has been implicated in the genetically acquired disease oculopharyngeal muscular dystrophy, characterized by nuclear protein deposits. Here we report a correlation between the structural properties and cell toxicity of two peptides mimicking the N-terminal domain of PABP2: one containing seven and the other 11 uninterrupted alanine residues. Consistent with earlier observations, the longer peptide (11-ala) was found to adopt beta-sheet structure while the shorter one (7-ala) formed alpha-helix over a wide range of concentrations ( approximately 20-500 microM). We observed that treatment with 11-ala resulted in significantly enhanced death of Chinese hamster V79 cells, compared to the effect of treatment with 7-ala, via the cytochrome c mediated apoptotic pathway. Increases in caspase 8 and caspase 3 activity were also observed in human cells (K562) treated with 11-ala. These results indicate that the toxicity of pathogenic peptides is directly linked to their beta-sheet structure and also support recent observations that small oligomeric species of peptides and proteins are the key toxic elements in causing protein aggregation diseases. | Poly(A)-Binding Protein II |
Protein disulfide isomerase (PDI) is a resident enzyme of the endoplasmic reticulum (ER) that was discovered over three decades ago. Contemporary biochemical and molecular biology techniques have revealed that it is present in all eukaryotic cells studied and retained in the ER via a -KDEL or -HDEL sequence at its C-terminus. However, evidence is accumulating that in certain cell types, PDI can be found in other subcellular compartments, despite possessing an intact retention sequence. A wide range of studies has established that in presence of a redox pair, PDI acts catalytically to both form and reduce disulfide bonds, therefore acting as a disulfide isomerase. Recent studies have focused on the mechanism of the isomerization process and the precise role of the two active site sequences (-CGHC-) in the process. In addition, prokaryotes have been shown to possess a set of proteins that function in a similar fashion, being able to generate disulfide bonds on polypeptides translocated into the periplasmic space. Following the recent discovery that PDI binds peptides, coupled with earlier findings that PDI is a subunit of at least two enzymatic complexes (prolyl 4-hydroxylase and microsomal triglyceride transfer protein), it seems that it may serve functions other than merely that of a disulfide isomerase. In fact, it is now clear that PDI can facilitate protein folding independently of its disulfide isomerase activity. A major challenge for the future is to define mechanistically how it accomplishes isomerization and the relationship between this process and the protein folding steps that culminate in the final, fully mature protein. | Isomerases |
Subclinical thyroid diseases are biologically defined: thyrotropin (TSH) decreased or increased with normal thyroid hormone concentrations. They are most often asymptomatics but carry a risk of long-term complications which can justify, in some cases, a treatment. The main complication of subclinical hyperthyroidism is atrial fibrillation, in particular after 60. Even if there is no controlled clinical trial available, treatment (usually with radioiodine) can be proposed to elderly subjects with autonomous thyroid disease (toxic adenoma or multinodular goitre) and TSH persistently below 0.1 mU/L. Subclinical hypothyroidism may be associated, particularly in subjects under 60, to a multifactorial increase of cardiovascular risk. An increase of TSH beyond 10 mU/L and positivity of antiTPO antibodies are the best predictors of the evolution toward overt hypothyroidism. In the elderly, there is no evidence of a risk associated with moderately increased TSH and treatment is probably not justified in most cases. | Thyrotoxicosis |
Alternatives to M-estimation for robust estimation of the median lethal dose in biological assays are developed. A class of link functions based on the Student-t distribution is proposed, where degrees of freedom are estimated from the data by maximum likelihood. Other alternatives include slash and finite mixture distributions. For bioassays from a pharmaceutical company, these methods extend the standard probit and logistic models, as well as the Huber's M-estimator. They are also applied to several standard examples from the literature. | Lethal Dose 50 |
Antimicrobial properties of essential oils predestine these substances to be used as ecological food preservatives. However, their activity is determined by variety of factors among which external conditions and food properties are highly important. Herein the influence of limonene on artificial membranes was studied to verify the effect of temperature on the incorporation of this compound into model bacterial membrane. The investigations were done on lipid monolayers and the experiments involved the surface pressure-area measurements, penetration studies and Brewster Angle Microscopy analysis. It was found that limonene incorporates into lipid monolayers causing their fluidization. However, the magnitude of alterations depends on limonene concentration, model membrane composition and, for a given composition, on system condensation. Moreover, the influence of limonene is stronger at lower temperatures and, in the light of collected data, this may be a consequence of strong volatility and evaporation of limonene increasing with temperature. | Food Preservatives |
The byproducts (seeds and peels) of an avocado cultivated in the south of Colombia were extracted with aqueous acetone and their antioxidant properties were measured with ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays, and total polyphenol content was determined by Folin-Ciocalteu method. A bioguided fractionation was performed, first by SPE (solid phase extraction) on Amberlite XAD-7, and then by size exclusion chromatography on Sephadex LH-20. The polyphenolic-rich extracts and their fractions were analyzed by ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS/MS), finding the presence of organic acids, hydroxycinnamic acids, catechins, free and glycosylated flavonoids, and dimeric and trimeric procyanidins. Catechin, epicatechin, six quercetin derivatives, four dimeric procyanidins (three type B and one type A), and three trimeric procyanidins (two type B and one type A) were detected in the most active fractions of avocado peel and seeds. The most antioxidant fractions contain the higher molecular weight phenolic compounds (condensed tannins). | Persea |
The Office of Minority Health (OMH) was established in 1986 to improve and protect the health of racial and ethnic minority populations in the United States through the development of health policies and programs that will eliminate health disparities. Since its initial congressional mandate, it has produced multiple programs, campaigns, publications, and educational materials promoting the health of ethnic minorities. However, its continued existence is by no means assured. Recently, it faced harsh criticism regarding the success of its programs, and congressional leaders have introduced legislation designed to modify the office and its minority focus. In this report, we review 1) the accomplishments and inefficiencies of the current office and 2) provide recommendations to improve OMH's effectiveness in reducing health disparities and addressing health issues in minority populations. | Minority Health |
Electroconvulsive therapy and concomitant lithium therapy remain a matter of debate because of increased rates of adverse events. Current recommendations include monitoring lithium levels and reducing lithium to minimally effective dose. We present a report on protracted effects of lithium intoxication as electroconvulsive therapy 8 days after intoxication and under normal lithium serum levels resulted in a prolonged seizure. Electroencephalogram recordings before stimulation showed electroencephalogram correlates of subsiding lithium intoxication most likely due to protracted lithium influx and efflux of the central nervous system. | Lithium Carbonate |
With phenotypic heterogeneity in whole cell populations widely recognised, the demand for quantitative and temporal analysis approaches to characterise single cell morphology and dynamics has increased. We present CellPhe, a pattern recognition toolkit for the unbiased characterisation of cellular phenotypes within time-lapse videos. CellPhe imports tracking information from multiple segmentation and tracking algorithms to provide automated cell phenotyping from different imaging modalities, including fluorescence. To maximise data quality for downstream analysis, our toolkit includes automated recognition and removal of erroneous cell boundaries induced by inaccurate tracking and segmentation. We provide an extensive list of features extracted from individual cell time series, with custom feature selection to identify variables that provide greatest discrimination for the analysis in question. Using ensemble classification for accurate prediction of cellular phenotype and clustering algorithms for the characterisation of heterogeneous subsets, we validate and prove adaptability using different cell types and experimental conditions. | Cell Tracking |
ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes macrocephala Koidz. (called Baizhu in China) is a medicinal plant that has long been used as a tonic agent in various ethno-medical systems in East Asia, especially in China, for the treatment of gastrointestinal dysfunction, cancer, osteoporosis, obesity, and fetal irritability. AIM OF THE REVIEW: This review aims to provide a systematic summary on the botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of A. macrocephala to explore the future therapeutic potential and scientific potential of this plant. MATERIALS AND METHODS: A literature search was performed on A. macrocephala using scientific databases including Web of Science, Google Scholar, Baidu Scholar, Springer, PubMed, SciFinder, and ScienceDirect. Information was also collected from classic books of Chinese herbal medicine, Ph.D. and M.Sc. dissertations, unpublished materials, and local conference papers on toxicology. Plant taxonomy was confirmed to the database The Plant List" (www.theplantlist.org). RESULTS: More than 79 chemical compounds have been isolated from A. macrocephala, including sesquiterpenoids, triterpenoids, polyacetylenes, coumarins, phenylpropanoids, flavonoids and flavonoid glycosides, steroids, benzoquinones, and polysaccharides. Crude extracts and pure compounds of A. macrocephala are used to treat gastrointestinal hypofunction, cancer, arthritis, osteoporosis, splenic asthenia, abnormal fetal movement, Alzheimer disease, and obesity. These extracts have various pharmacological effects, including anti-tumor activity, anti-inflammatory activity, anti-aging activity, anti-oxidative activity, anti-osteoporotic activity, neuroprotective activity, and immunomodulatory activity, as well as improving gastrointestinal function and gonadal hormone regulation. CONCLUSIONS: A. macrocephala is a valuable traditional Chinese medicinal herb with multiple pharmacological activities. Pharmacological investigations support the traditional use of A. macrocephala, and may validate the folk medicinal use of A. macrocephala to treat many chronic diseases. The available literature shows that much of the activity of A. macrocephala can be attributed to sesquiterpenoids, polysaccharides and polyacetylenes. However, there is a need to further understand the molecular mechanisms and the structure-function relationship of these constituents, as well as their potential synergistic and antagonistic effects. Further research on the comprehensive evaluation of medicinal quality, the understanding of multi-target network pharmacology of A. macrocephala, as well as its long-term in vivo toxicity and clinical efficacy is recommended." | Plant Preparations |
Fatty acid synthase (FASN), the enzyme that catalyzes de novo synthesis of fatty acids, is expressed in many cancer types. Its potential as a therapeutic target is well recognized, but inhibitors of FASN have not yet been approved for cancer therapy. Orlistat (ORL), an FDA-approved lipase inhibitor, is also an effective inhibitor of FASN. However, ORL is extremely hydrophobic and has low systemic uptake after oral administration. Thus, new strategies are required to formulate ORL for cancer treatment as a FASN inhibitor. Here, we report the development of a nanoparticle (NP) formulation of ORL using amphiphilic bioconjugates that are derived from hyaluronic acid (HA), termed Nano-ORL. The NPs were loaded with up to 20 wt % weight of ORL at greater than 95% efficiency. The direct inhibition of the human recombinant thioesterase domain of FASN by ORL extracted from Nano-ORL was similar to that of stock ORL. Nano-ORL demonstrated a similar ability to inhibit cellular FASN activity when compared to free ORL, as demonstrated by analysis of (14)C-acetate incorporation into lipids. Nano-ORL treatment also disrupted mitochondrial function similarly to ORL by reducing adenosine triphosphate turnover in MDA-MB-231 and LNCaP cells. Nano-ORL demonstrated increased potency compared to ORL toward prostate and breast cancer cells. Nano-ORL decreased viability of human prostate and breast cancer cell lines to 55 and 57%, respectively, while free ORL decreased viability to 71 and 79% in the same cell lines. Moreover, Nano-ORL retained cytotoxic activity after a 24 h preincubation in aqueous conditions. Preincubation of ORL dramatically reduced the efficacy of ORL as indicated by high cell viability (>85%) in both breast and prostate cell lines. These data demonstrate that NP formulation of ORL using HA-derived polymers retains similar levels of FASN, lipid synthesis, and ATP turnover inhibition while significantly improving the cytotoxic activity against cancer cell lines." | Fatty Acid Synthesis Inhibitors |
Interleukin-4 (IL-4) and interleukin-13 (IL-13) are structurally and functionally related cytokines which play an important role in the regulation of the immune response to infection. The functional similarity of IL-4 and IL-13 can be explained, at least in part, by the common components that form their cell surface receptors, namely the IL-4 receptor alpha-chain (IL-4Ralpha) and the IL-13 receptor alpha-chain (IL-13Ralpha). Soluble forms of the IL-4Ralpha have also been described and implicated in modulating the effect of IL-4. In this paper we describe the presence of a 45,000-50,000 Mr IL-13-binding protein (IL-13BP) in the serum and urine of mice. This protein binds IL-13 with a 100-300-fold higher affinity (KD = 20-90 pM) than does the cloned IL-13Ralpha (KD = 3-10 nM). In addition to this functional difference, the IL-13BP appears to be structurally and antigenically distinct from the IL-13Ralpha. Finally, unlike the cloned receptor, the IL-13BP acts as a potent inhibitor of IL-13 binding to its cell surface receptor, raising the possibility that it may be used to modulate the effects of IL-13 in vivo." | Interleukin-13 Receptor alpha1 Subunit |
The effects of bisphenol A (BPA) on placentation have not been fully determined. The aim of this study was to clarify the structural changes of the placenta, abortion rate, and survival of neonates after BPA administration in mice. BPA (10 mg/kg/day) was administered to pregnant mice (BPA mice) subcutaneously from the first day of pregnancy (Day 0) to Day 7 (8 days total). The number of embryos and weights of whole uteri were measured on Days 10 and 12. Morphological changes in the placentae were examined by light microscopy on the corresponding days of pregnancy. The number of neonates was also counted. Survival rates were periodically calculated for neonates from the first day after parturition (P-Day 0) to P-Day 56. The number of embryos and weight of the uterus on Days 10 and 12 were significantly decreased by BPA injection. No notable differences were recognized between the left and right uteri. The proportion of the labyrinthine zone per whole placenta in the BPA mice became lower than that in the controls, and that of the metrial gland was higher in the BPA mice. The intervillous spaces of the placenta were narrower in the BPA mice. Degenerative changes were found in the trophoblastic giant cells and spongiotrophoblast layers of the BPA mice. The number of BPA mouse neonates was drastically decreased within 3 days after birth, and no mice survived after P-Day 56. The results suggest that BPA not only disrupts placental functions and leads to abortion through chronic stimulation of gene expression by binding to DNA but that it also affects the mortality of neonates through indirect exposure of embryos. | Placentation |
Fucose-containing sulfated glycans (syn. fucoidans) from brown algae exhibit a wide range of bioactivities and are therefore considered promising candidates for health-supporting and medical applications. In this study, we investigated the pharmacological activities of fucoidan from Fucus vesiculosus and 18 gradually depolymerized fractions, which were obtained by hydrothermal and H(2)O(2) treatment, respectively. All the activities decreased with decreasing molecular mass (M(w)) but to a different extent resulting in some modified pharmacological profiles in dependence on the M(w) as well as on the degradation method. H(2)O(2) treatment was not only more efficient, simpler and cheaper than hydrothermal degradation, but also led to superior activity profiles and additionally eliminated co-extracted contaminants. Compared to heparin, the prime example of biologically active sulfated glycans, evenly sized H(2)O(2) fractions exhibited considerable effects being relevant for anti-inflammatory activity, however only negligible anticoagulant activity and FXII activating potency. Due to their improved biopharmaceutical characteristics and favorable activities, degraded fucoidan fractions are worth to be further investigated as anti-inflammatory and anticomplementary agents. | Fucus |
Strong mandibular angles and a heavy chin are perceived as masculine features, so surgical feminization of female or transgender faces may warrant mandibular base narrowing (borders and angles) and a reduction in chin width and height. With this in mind, we have devised an interdental midline osteotomy (triangular in shape and with a caudal base) to accompany a box-shaped impaction osteotomy of the chin symphysis and horizontal triangular resection of the lateral mandibular border. The reduction of the intergonial width and of the mandibular border and chin widths takes place upon closure of the midline defect. Between November 2016 and August 2017, five patients agreed to the mandibular feminization osteotomy and were followed up thereafter for 6-13 months. All expressed satisfaction with the results; no dental, periodontal, or temporomandibular joint-related complications were encountered. This technique is a viable alternative to buccal decortication, chin reduction osteotomy, and masseter reduction surgery. | Feminization |
Specimens from 28 wapiti (Cervus elaphus canadensis) were collected by hunters in southwestern Alberta in 1984. Various tests were performed to detect infections and conditions that could affect cattle sharing the range or cause disease in wapiti. Serum antibodies were present against leptospiral serovars autumnalis (25%), bratislava (4%), and icterohaemorrhagiae (8%), and the viruses of bovine virus diarrhea (52%), infectious bovine rhinotracheitis (45%), and parainfluenza type 3 (13%). No serological evidence of bovine respiratory syncytial virus, Brucella, Anaplasma, bluetongue virus, or epizootic hemorrhagic disease virus was found, nor were any lesions of vesicular diseases, necrotic stomatitis or nutritional myopathy evident. Focal interstitial nephritis and sarcocystosis were diagnosed histologically in 40% and 75%, respectively, of the wapiti tested. The prevalence of giant liver flukes (Fascioloides magna) was 50% and of lungworms (Dictyocaulus viviparus) 32%. Leptospiral serology on cattle in the area did not indicate that wapiti or cattle were a serious source of infection to each other. The giant liver fluke was the parasite most likely to be amplified by wapiti for cattle. Within the limits of this study, the results indicated that wapiti in the Waterton area do not pose a disease threat to the cattle with which they range, but periodic observational studies in these wapiti would be a useful means of early detection of any changes in the interspecies relationship. | Fascioloidiasis |
OBJECTIVE: Although past research has demonstrated a link between the quality of motivational interviewing (MI) counseling and client behavior change, this relationship has not been examined in the context of sexual risk behavior among people living with HIV/AIDS. We studied MI quality and unprotected anal/vaginal intercourse (UAVI) in the context of SafeTalk, an evidence-based secondary HIV prevention intervention. METHODS: We used a structured instrument (the MISC 2.0 coding system) as well as a client-reported instrument to rate intervention sessions on aspects of MI quality. Then we correlated client-reported UAVI with specific counseling behaviors and the proportion of interactions that achieved MI quality benchmarks. RESULTS/CONCLUSION: Higher MISC-2.0 global ratings and a higher ratio of reflections to questions both significantly predicted fewer UAVI acts at 8-month follow-up. Analysis of client ratings, which was more exploratory, showed that clients who rated their sessions higher in counselor acceptance, client disclosure, and relevance reported higher numbers of UAVIs, whereas clients who selected higher ratings for perceived benefit were more likely to have fewer UAVI episodes. PRACTICE IMPLICATIONS: Further research is needed to determine the best methods of translating information about MI quality into dissemination of effective MI interventions with people living with HIV. | Directive Counseling |
The E28D variant of dihydrofolate reductase from Moritella profunda was generated and found to have the same K (i) (within error) for the competitive inhibitor trimethoprim as the wild type enzyme. Contrary to a previous claim in the literature, Glu 28 is therefore not the cause of the reduced affinity for trimethoprim relative to dihydrofolate reductase from Escherichia coli. | Moritella |
The goal of this experiment was to investigate the protective effect and the molecular mechanism of Panax Notoginseng Saponins (PNS) on cisplatin-induced nephrotoxicity through mitochondrial pathway of apoptosis. The rats underwent intraperitoneal injection with a single dose of cisplatin, a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day for 8 days. At day 1, 4 and 8 after exposure to cisplatin, the concentrations of blood urea nitrogen (BUN), serum creatinine (Scr) and urinary N-acetyl-beta-D-Glucosaminidase (NAG) were determined using commercial kits. The pathological change of renal tissue were examined using H & E staining and transmission electron microscopy. The rate of apoptosis and the expression of Bcl-2 in rat renal tissue were detected by using TUNEL staining and Western bloting, respectively. And the expressions of Bax and caspases 9 were detected by immunnohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by the decrease in concentration of blood BUN, Scr and urinary NAG, as well as the attenuation of renal histopathological damage. Furthermore, PNS reduced the rate of apoptosis, and the mechanism studies showed that PNS inhibited the expression of Bax and caspase 9, while increased the expression of Bcl-2. This study first demonstrated that PNS can protect against cisplatin-induced nephrotoxicity and reduce renal tissue apoptosis via inhibiting the mitochondrial pathway. | Panax notoginseng |
CASE: We report a unique case of a combination of forearm fracture and traumatic radial artery pseudoaneurysm in an 8-year-old child. The fracture pattern was a Monteggia equivalent with a mid-diaphyseal ulnar fracture and a radial neck fracture with displacement of the distal radial diaphyseal fracture fragment. The pseudoaneurysm, which probably developed after vigorous manipulation by a bonesetter, thrombosed spontaneously, and the fracture was managed nonoperatively with a good outcome. CONCLUSION: Pseudoaneurysm of the radial artery is a rare phenomenon associated with fracture in a child. A history of vigorous manipulation of displaced fracture fragments in the vicinity of a major vessel should raise suspicion of this possible complication. | Closed Fracture Reduction |
Rhinophyma is a phenotypic subtype of rosacea affecting the nose. It is characterized by phymatous changes, skin thickening/fibrosis, glandular hyperplasia, and chronic inflammation. Treatment of severe rhinophyma is predominantly surgical excision with closure by secondary intention. Amniotic membrane has been used to promote wound healing, fibrosis, and inflammation. In this case study, the authors present a 63-year-old male with longstanding rhinophyma treated with surgical excision with intraoperative placement of amniotic membrane. | Rhinophyma |
Triphenylphosphonium (TPP(+)) species comprising multiple charges, i.e., bis-TPP(+), are predicted to be superior mitochondrial-targeting vectors and are expected to have mitochondrial accumulations 1000-fold greater than TPP(+), the current gold standard". However, bis-TPP(+) vectors linked by short hydrocarbon chains ( n < 5) are unable to be taken up by the mitochondria, thus hindering their development as mitochondrial delivery vectors. Through the incorporation of methylated TPP(+) moieties (T*PP(+)), we successfully enabled the accumulation of bis-TPP(+) with a short linker chain in isolated mitochondria, as measured by high performance liquid chromatography. These experimental results are further supported by molecular dynamics and ab initio calculations, revealing the strong correlations between mitochondria uptake and molecular volume, surface area, and chemical hardness. Most notably, the molecular volume has been shown to be a strong predictor of accumulation for both mono- and bis-TPP(+) salts. Our study underscores the potential of T*PP(+) moieties as alternative mitochondrial vectors to overcome low permeation into the mitochondria." | Organophosphorus Compounds |
INTRODUCTION: Antibiotherapy regimens for management of acute streptococcal pharyngitis traditionally last 10 days, but the development of resistance to different antimicrobials has motivated the exploration of shorter courses. MATERIAL AND METHODS: We selected patients given a diagnosis of streptococcal pharyngitis in 2 paediatric caseloads of 1 primary care centre between June 2016 and April 2020. We compared outcomes in patients treated with 8- to 10-day courses versus 5- to 7-day courses. RESULTS: The analysis included 350 care episodes (252 patients). Sixty-four percent were managed with 8- to 10-day courses of antibiotherapy (group 1) and 36% with 5- to 7-day courses (group 2). There were no significant differences in the incidence of streptococcal pharyngitis or scarlet fever in the 3 months that followed (OR, 0.98; 95% confidence interval [CI], 0.46-2.03), with similar percentages in both groups (9.8% vs 9.5%). Overall, without differentiating based on the type of infection (streptococcal pharyngitis, scarlet fever or other streptococcal infections), we found similar outcomes (OR, 0.81; 95% CI, 0.41-1.59): 13.4% in group 1 and 11.1% in group 2. We also found no differences in the frequency of adverse events documented in the health records (OR, 0.29; 95% CI, 0.04-2.44): 2.7% in group 1 and 0.8% in group 2. CONCLUSIONS: In our experience, a shorter antibiotic course (5-7 days) is not less effective or more unsafe for management of acute streptococcal pharyngitis than the traditional 10-day course. | Scarlet Fever |
Nuclear, cytoplasmic, and mitochondrial proteins are extensively modified by O-linked beta-N-acetylglucosamine (O-GlcNAc) moieties. This sugar modification regulates fundamental cellular processes in response to diverse nutritional and hormonal cues. The enzymes O-GlcNAc transferase (OGT) and O-linked beta-N-acetylglucosaminase (O-GlcNAcase) mediate the addition and removal of O-GlcNAc, respectively. Aberrant O-GlcNAcylation has been implicated in a plethora of human diseases, including diabetes, cancer, aging, cardiovascular disease, and neurodegenerative disease. Because metabolic dysregulation is a vital component of these diseases, unraveling the roles of O-GlcNAc in metabolism is of emerging importance. Here, we review the current understanding of the functions of O-GlcNAc in cell signaling and gene transcription involved in metabolism, and focus on its relevance to diabetes, cancer, circadian rhythm, and mitochondrial function. | Hexosamines |
The subcommissural organ of vertebrates secretes glycoproteins into the cerebrospinal fluid of the third cerebral ventricle. This material polymerizes in Reissner's fiber. During ontogenetic development, besides the subcommissural organ, the ependyma lining the pontine flexure constitutes an additional Reissner's fiber-secreting gland named flexural organ. We have studied the secretion of the flexural organ and the subcommissural organ in dogfish (Scyliorhinus canicula) embryos using three different antisera and the lectins concanavalin A and wheat germ agglutinin. AFRU is an antiserum against the bovine Reissner's fiber, Ab-600 is an antiserum against 600 kDa dogfish subcommissural organ glycoproteins; and APSO is an antiserum against immunoaffinity purified bovine subcommissural organ secretory glycoproteins. These three antisera immunostained the flexural organ indicating that it contains epitopes similar to those present in bovine and dogfish subcommissural organ glycoproteins. It seems highly probable that the flexural organ and the subcommissural organ of dogfish embryos secrete similar compound(s). Other ependymal regions were also immunostained with Ab-600 and APSO antisera. Then, Reissner's fiber-like glycoproteins were transiently expressed by most embryonary ependymal cells. These glycoproteins might play a role in the development of the central nervous system of vertebrates. | Dogfish |
Biological activity of a new series of potent GH-RH antagonists containing formyl or phenylacetyl group at the N-terminus of the sequence [D-Arg2,Phe(4-Cl)6,Nle27]hGH-RH(1-29)NH2, as well as various substitutions in positions 8, 15, or 28, and in some cases Agm in position 29, was evaluated in vivo. All five antagonists, administered at a 27-fold molar excess to rats, suppressed the GH-releasing effect of exogenous GH-RH(1-29)-NH2 by 64-75%. The inhibitory effects lasted for more than 15 min. The most potent analogue, PhAc-[D-Arg2,Phe(4-Cl)6,Abu15,Nle27]hGH-RH(1-28)Agm (MZ-5-156), showed an in vivo potency 7-16 times higher than the early antagonist [Ac-Tyr1,D-Arg2]hGH-RH(1-29)-NH2, which was used as standard. MZ-5-156 was capable of decreasing serum GH levels after intravenous, intraperitoneal, or intramuscular administration. In vitro, in the superfused rat pituitary cell system, MZ-5-156 induced a prolonged inhibition of GH release after continuous long-term administration and showed a potency more than 100 times greater than the standard antagonist. These results show that N-terminal acylation with phenylacetic acid of the sequence [D-Arg2,Phe(4-Cl)6,Nle27]hGH-RH(1-29)-NH2, containing modifications in positions 8, 15, 28, or 29, results in antagonists with high and protracted potency both in vivo and in vitro. In view of high antagonistic activity and prolonged duration of action, some of these antagonists of GH-RH may find clinical application for the treatment of IGF-dependent cancers. | Sermorelin |
BACKGROUND The aim of this study was to evaluate the effects of Nigella sativa (N. sativa) oil (NSO) on ovarian oxidative damage following ischemia-reperfusion injury, using a rat model of ovarian torsion. MATERIAL AND METHODS Forty-eight female albino Wistar rats were divided into six groups: (Group 1) laparotomy only; (Group 2) intraperitoneal NSO (2 ml/kg), 1 hour following laparotomy; (Group 3) 3 hours of ovarian ischemia; (Group 4) 3 hours of ovarian ischemia followed by 3 hours of reperfusion; (Group 5) 3 hours of ovarian ischemia and 2 ml/kg of NSO 1 hour before laparotomy; (Group 6) 3 hours of reperfusion after 3 hours of ovarian ischemia and 2 ml/mg of NSO 1 hour before laparotomy. RESULTS The antioxidant status, ceruloplasmin level, native thiol, total thiol, and disulfide levels of the control group (Group 1) were significantly increased compared with the ovarian ischemia-reperfusion group treated with NSO (Group 6) (p=0.003, p=0.002, p=0.006, p=0.001 and p=0.003, respectively); these levels in the ovarian ischemia group (Group 3) and ischemia-reperfusion group (Group 4) were statistically similar to those of the ovarian ischemia + NSO group (Group 5) and ovarian ischemia-reperfusion + NSO group (Group 6). CONCLUSIONS In this preliminary rat study, administration of NSO shortly after the onset of ovarian ischemia-reperfusion injury, did not significantly reduce levels of markers of oxidative injury. Further studies are required to evaluate the ovarian changes at the tissue level, and to determine the optimum dose of NSO. | Nigella sativa |
The extraordinary improvement of patient outcome after surgical treatment for vestibular schwannomas is relatively recent and has occurred mainly over the last 30 years. The introduction of microsurgical techniques has resulted in increasing degrees of precise anatomical and functional preservation of the facial and cochlear nerves. An expanded microsurgical technique accompanied by continuous electrophysiological monitoring has resulted in marked changes in the primary goals for this surgery. Whereas in the past the primary goal of vestibular schwannoma management was to preserve the patient's life, the objective in vestibular schwannoma treatment today is to preserve neurological function. Long-term follow-up examinations show negligible recurrence rates, indicating that the aim of preservation of nerve function does not limit the completeness of tumor removal with modern neurosurgical techniques. Despite these advances in preserving the anatomical integrity of, for example, the cochlear nerve, losses of function and even deafness may occur postoperatively in some cases. Current biological and technical research in experimental and clinical settings addresses these problems. In this article, the authors report in detail the developments achieved in vestibular schwannoma surgery and the great clinicians to whom these results can be credited." | Vestibulocochlear Nerve Injuries |
The protein family known as fp-1 provides mussel byssus with a protective outer coating and has drawn much attention for its water resistant bioadhesive properties in vitro. A new fp-l isolated from the green shell mussel Perna canaliculus (pcfp-1) reveals a composition dominated by only four amino acids: 3,4-dihydroxyphenyl-L-alanine (dopa), lysine, proline, and valine at approximately 20 mol % each. SDS-PAGE and MALDI-TOF mass spectrometry detected size variants at 48 and 52 kDa in preparations of purified Pcfp-1. The N-terminal sequence enabled construction of oligonucleotide primers for PCR and RACE-derived cDNAs from which the complete sequence of four variants was deduced. pcfp-1 deviates from all known homologues in other mussels in several notable respects: its mass is half, most of its sequence is represented by 75 tandem repeats of a tetrapeptide, i.e., PY*VK, in which Y* is dopa, prolines are not hydroxylated, and thiolate cysteines are clustered in homologous sequences at both the amino and carboxy termini. Amino acids in the repeat sequence show a striking resemblance to proline-rich cell wall proteins with tandemly repeated PPVYK pentapeptides [Hong, J. C., Nagao, R. T., and Key, J. L. (1987) J. Biol. Chem. 262, 8367-8376]. Cysteine plays a key role in cross-linking pcfp-1 by forming adducts with dopaquinone. Significant 5-S-cysteinyldopa and smaller amounts of 2-S-cysteinyldopa were detected in hydrolysates of the byssal threads of P. canaliculus. The cross-links could also be formed by oxidation of pcfp-1 in vitro using mushroom tyrosinase. Cysteinyldopa cross-links were present in trace amounts only in the byssus of other mussel species. | Cysteinyldopa |
NB2a/d1 neuroblastoma cells constitutively express multiple isoforms of the microtubule-associated protein tau and incorporate this protein into the axonal neurites elaborated during serum deprivation. To examine whether or not tau played an essential role in axonal outgrowth, cells cultured in serum-free medium were treated at 24 h intervals with antisense- and sense-oriented cDNA oligonucleotides (25 or 36 mers that span or are upstream of tau initiation codon) and were simultaneously serum deprived. Oligonucleotide uptake was confirmed by determination of intracellular levels of radiolabeled oligonucleotides. Treatment for 48 h with tau antisense oligonucleotides reversibly inhibited the expression of tau and the number of neurite-bearing cells compared with treatment with sense oligonucleotides. By contrast, tubulin expression was not affected. When cells were treated with antisense oligonucleotide simultaneously with serum deprivation, the initial outgrowth of neurites was unaffected, but continued neurite elongation was prevented. By contrast, neurite outgrowth at 4 h was inhibited when cells were pretreated with tau antisense 24 h before serum deprivation. Furthermore, intracellular delivery of anti-tau antiserum prevented neurite outgrowth and, in cells that had previously been deprived of serum for 24 h, induced retraction of existing neurites. These findings indicate that both the initiation and the continued outgrowth of neurites are dependent on tau and that pre-existing cytoplasmic pools of tau can mediate initial neuritogenesis. | DNA, Antisense |
Two redox-active crown ethers, (1,1'- bi-2-naphthyl)-23-crown-6 incorporating 9,10-anthraquinone (BNAQ) and 1,4-benzoquinone (BNBQ), were synthesized and employed in the selective binding of NH(4)(+) over K(+). Their applications to NH(4)(+) detection were studied by cyclic voltammetry and amperometry in aqueous media. The results showed that the magnitude of the quinone redox peak decreased linearly as the concentration of NH(4)(+) increased, indicating the formation of BNAQ-NH(4)(+) and BNBQ-NH(4)(+) complexes. Formation constants of BNAQ-NH(4)(+) and BNBQ-NH(4)(+) complexes were determined to be 4.3 x 10(3) and 4.0 x 10(3) M(-1), respectively, which were 2 orders of the magnitude greater than those of BNAQ-K(+) and BNBQ-K(+) complexes. The (1)H NMR titration method carried out in DMSO-d(6) showed that both complexes possessed 1:1 stoichiometry, and association constants were determined to be 648 +/- 35 and 600 +/- 47 M(-1) for BNAQ-NH(4)(+) and BNBQ-NH(4)(+), respectively. Interference effects from other alkali and alkaline earth metal ions in the analysis of NH(4)(+) were also investigated. The BNAQ-modified sensor showed a linear response from 1.0 microM to 1.0 mM for NH(4)(+), and the detection limit was determined to be 0.9 +/- 0.03 microM. | Crown Ethers |
The crystal structure and unambiguous absolute configuration of meleagrin (1) isolated from fungus Emericella dentata Nq45 is reported herein to first time on the bases of single crystal X-ray diffraction. Together with 1, haenamindole (2), isorugulosuvine (3), secalonic acid D (4), ergosterol (5) and cerebroside A (6) were obtained and their structures were determined by ESI MS and NMR data analysis. Diverse biological activity of meleagrin (1) was investigated. Compound 1 pronounced potent cytotoxicity against the human cervix carcinoma cell line KB-3-1 and its multidrug resistant sub-clone KB-V1 of IC(50) 3.07 and 6.07 microM, respectively, in comparison with the reference (+) - griseofulvin (IC(50) 19, 19.5 microM). Based on the antibiofilm activity, compound 1 displayed as well potent activity against Staphylococcus aureus with an MIC of 0.25 mg/mL. Isolation of the producing fungus and taxonomical characterization is stated as well. | Ovomucin |
This tutorial review compiles recent experimental and theoretical studies on the formation of polyacetylenes (H(C identical withC)(n)H) and cyanopolyacetylenes (H(C identical withC)(n)CN) together with their methyl-substituted counterparts (CH(3)(C identical withC)(n)H, CH(3)(C identical withC)(n)CN) as probed under single collision conditions in crossed beam studies via the elementary reactions of ethynyl (CCH) and cyano radicals (CN) with unsaturated hydrocarbons. The role of these key reaction classes in the chemical evolution of Titan's orange-brownish haze layers is also discussed. We further comment on astrobiological implications of our findings with respect to proto-Earth and present a brief outlook on future research directions. | Polyynes |
BACKGROUND: Mirizzi syndrome was reported in 0.3-3% of patients undergoing cholecystectomy. The distortion of anatomy and the presence of cholecystocholedochal fistula increase the risk of bile duct injury during cholecystectomy. METHODS: A Medline search was undertaken to identify articles that were published from 1974 to 2004. Additional papers were identified by a manual search of the references from the key articles. RESULTS: A preoperative diagnosis was made in 8-62.5% of cases. Open surgical treatment gave good short-term and long-term results. There was a lack of good data in laparoscopic treatment. Conversion to open surgery rates was high, and bile duct injury rate varied from 0 to 22.2%. CONCLUSION: A high index of clinical suspicion is required to make a preoperative or intraoperative diagnosis, which leads to good surgical planning to treat the condition. Open surgery is the gold standard. Mirizzi syndrome should still be considered as a contraindication for laparoscopic surgery. | Common Bile Duct Diseases |
The form and function of the mouthparts in adult Lepidoptera and their feeding behavior are reviewed from evolutionary and ecological points of view. The formation of the suctorial proboscis encompasses a fluid-tight food tube, special linking structures, modified sensory equipment, and novel intrinsic musculature. The evolution of these functionally important traits can be reconstructed within the Lepidoptera. The proboscis movements are explained by a hydraulic mechanism for uncoiling, whereas recoiling is governed by the intrinsic proboscis musculature and the cuticular elasticity. Fluid uptake is accomplished by the action of the cranial sucking pump, which enables uptake of a wide range of fluid quantities from different food sources. Nectar-feeding species exhibit stereotypical proboscis movements during flower handling. Behavioral modifications and derived proboscis morphology are often associated with specialized feeding preferences or an obligatory switch to alternative food sources. | Lepidoptera |
Parthenium weed (Parthenium hysterophorus L.) is one of the most aggressive invasive weeds, threatening natural ecosystems and agroecosystems in over 30 countries worldwide. Parthenium weed causes losses of crops and pastures, degrading the biodiversity of natural plant communities, causing human and animal health hazards and resulting in serious economic losses to people and their interests in many countries around the globe. Several of its biological and ecological attributes contribute towards its invasiveness. Various management approaches (namely cultural, mechanical, chemical and biological control) have been used to minimise losses caused by this weed, but most of these approaches are ineffective and uneconomical and/or have limitations. Although chemical control using herbicides and biological control utilising exotic insects and pathogens have been found to contribute to the management of the weed, the weed nevertheless remains a significant problem. An integrated management approach is proposed here for the effective management of parthenium weed on a sustainable basis. | Plant Dispersal |
BACKGROUND AND OBJECTIVE: Retinal degeneration in birdshot chorioretinopathy (BSCR) has been assessed qualitatively using spectral-domain optical coherence tomography (SD-OCT). The purpose of this study was to determine whether these changes could be quantified. PATIENTS AND METHODS: The charts of 22 eyes of 11 patients with BSCR and 22 eyes of 22 controls were reviewed. SD-OCT was used to determine the photoreceptor outer segment (PROS) volume and choroidal thickness. RESULTS: PROS volume in patients with BSCR was lower than in controls (P < .003). Furthermore, the PROS volume in BSCR patients with abnormalities on electroretinography (ERG) was lower than the PROS volume in BSCR patients with normal ERGs (P < .02). There was no correlation between PROS volume and choroidal thickness (r = 0.27; P = .22). CONCLUSION: SD-OCT can be used to quantitate retinal degeneration in BSCR. The retinal and choroidal degeneration in BSCR are not correlated, suggesting that the inflammatory pathophysiology affecting these two structures may be different. | Birdshot Chorioretinopathy |
Chemical double mutant cycles have been used to quantify the interactions of halogens with the faces of aromatic rings in chloroform. The halogens are forced over the face of an aromatic ring by an array of hydrogen-bonding interactions that lock the complexes in a single, well-defined conformation. These interactions can also be engineered into the crystal structures of simpler model compounds, but experiments in solution show that the halogen-aromatic interactions observed in the solid state are all unfavourable, regardless of whether the aromatic rings contain electron-withdrawing or electron-donating substituents. The halogen-aromatic interactions are repulsive by 1-3 kJ mol(-1). The interactions with fluorine are slightly less favourable than with chlorine and bromine. | Hydrocarbons, Aromatic |
BACKGROUND: Pediculus humanus capitis or head louse is an obligate ectoparasite and its infestation remains a major public health issue worldwide. Molecular analysis divides head lice into six clades and intra-clade genetic differences have been identified. Several hypotheses have been formulated to elucidate the discrepancies of the variety of head lice among different regions of the world. It is currently concluded that head lice distribution might be associated with human migration history. This study aims to investigate genetic data of human head lice in Thailand. We believe that the analysis could help establish the correlation between local and global head lice populations. METHOD: We investigated mitochondrial cytochrome b (cytb) gene of the collected 214 head lice to evaluate genetic diversity from 15 provinces among 6 regions of Thailand. The head lice genes were added to the global pool for the phylogenetic tree, Bayesian tree, Skyline plot, and median joining network construction. The biodiversity, neutrality tests, and population genetic differentiation among the 6 Thailand geographic regions were analyzed by DNAsp version 6. RESULTS: The phylogenetic tree analysis of 214 collected head lice are of clade A and clade C accounting for roughly 65% and 35% respectively. The Bayesian tree revealed a correlation of clade diversification and ancient human dispersal timeline. In Thailand, clade A is widespread in the country. Clade C is confined to only the Central, Southern, and Northeastern regions. We identified 50 novel haplotypes. Statistical analysis showed congruent results between genetic differentiation and population migration especially with South Asia. CONCLUSIONS: Pediculosis remains problematic among children in the rural areas in Thailand. Cytb gene analysis of human head lice illustrated clade distribution and intra-clade diversity of different areas. Our study reported novel haplotypes of head lice in Thailand. Moreover, the statistic calculation provided a better understanding of their relationship with human, as an obligate human parasite and might help provide a better insight into the history of human population migration. Determination of the correlation between phylogenetic data and pediculicide resistance gene as well as residing bacteria are of interest for future studies. | Pediculus |
OBJECTIVE: To raise immunization coverage among children at risk for underimmunization, we evaluated the effectiveness and cost-effectiveness of immunization activities in the Special Supplemental Program for Women, Infants and Children (WIC). METHOD: A controlled intervention trial was conducted in seven WIC sites in Chicago between October 1990 and March 1994. At intervention sites, staff screened children for vaccination status at every visit, referred vaccine-eligible children to either an on-site WIC nurse, on-site clinic, or off-site community provider, and issued either a 3-month supply of food vouchers to up-to-date children or a 1-month supply to children not up-to-date--a usual practice for high-risk WIC children. Our primary measure of effectiveness was the change in the baseline percentage of up-to-date children at the second birthday; cost-effectiveness was approximated for each of the three referral interventions. RESULTS: After one year, up-to-date vaccination coverage increased 23% above baseline for intervention groups and decreased 9% in the control group. After the second year, up-to-date vaccination further increased to 38% above baseline in intervention groups and did not change in the control group. The total cost per additional up-to-date child ranged from $30 for sites referring children off-site to $73 for sites referring children on-site to a nurse. CONCLUSION: This controlled intervention trial of screening, referral, and a voucher incentive in the WIC program demonstrated a substantial increase in immunization coverage at a low cost. Continuing to design linkages between WIC and immunization programs by building on WIC's access to at-risk populations is worth the investment. | Immunization Programs |
Causes of bovine abortion were surveyed in Korea within a designated period from the cases submitted to the Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University. One hundred and eighty aborted fetuses and maternal sera were evaluated by necropsy, histopathology, bacteriology, virology, PCR, and serologic tests. The causes of abortion were identified in 108 (60%) cases, of which 38 (21.1%) were due to the infection with Neospora caninum. None of the 38 cases showed any co-infection with either virus or bacteria. Viral and bacterial causes were diagnosed in 28 (15.5%) and 13 (7.2%) aborted fetuses, respectively. Non-infectious causes such as multiple pregnancy, maternal weakness or torsion of umbilical cord were observed in 22 (12.3%) cases. Results of the present study suggest that N. caninum is believed to be the leading cause of bovine abortion in Korea. Thus, more attention should be paid to this emerging disease in Korea. However, the causes of many aborted fetuses remain undiagnosed in this study. Therefore, this enigma should be clarified through further studies such as chromosomal analysis. | Abortion, Veterinary |
The change in transmembrane potential of rat adipocytes was measured using the fluorescent probe 3,3'-diethylthiadicarbocyanine iodide, diS-C2-(5). The method was calibrated by altering the potassium ion concentration while keeping the sum of potassium and sodium ions at a constant concentration of 153 mM (Bailey et al: Bioelectrochem. Bioenergetics 21:333-42, 1989). Two insulin-mimetic agents, phospholipase C from Clostridium perfringens and concanavalin A, induced a dose dependent hyperpolarization of rat epididymal adipocytes, like insulin. Removal of endogenous adenosine with adenosine deaminase or adenosine receptor blockade with isobutylmethylxanthine following the initiation of insulin-induced hyperpolarization resulted in depolarization. These same agents induced hyperpolarization of -6 to -8 mV when added without insulin. The replacement of adenosine with its analogue, N6-phenylisopropyladenosine, plus insulin depolarized the cells toward the transmembrane potential established by insulin, -2.0 mV. These studies suggest that adenosine receptor occupancy is required to maintain insulin-induced hyperpolarization. | Dithiazanine |
The present review summarizes our classical and molecular cytogenetic investigations in the genus Zea. The results obtained from the meiotic behavior analysis of Zea species and hybrids, confirm the amphiploid nature of all species in the genus, with a basic number of x = 5 chromosomes. All species with 2n = 20 are diploidized allotetraploids, whereas Z. perennis (2n = 40) is an allooctoploid with four genomes somewhat divergent from one another. These analyses also revealed the existence of postzygotic reproductive isolation among Zea species. Our studies using genomic in situ hybridization (GISH) provide evidence about the evolutionary relationships among maize and its allied species, and reveal remarkable genomic divergences. Particularly, knob sequences were not completely shared between taxa previously considered to be closely related. Our data strongly suggest that the teosinte Z. mays parviglumis is not the only progenitor of cultivated maize. Introgression of Tripsacum into cultivated maize cannot be discarded. | Zea mays |
1,5-Anhydro-D-fructose (AF) was first found in fungi and red algae. It is produced by the degradation of glycogen, starch and maltosaccharides with alpha-1,4-glucan lyase (EC 4.2.2.13). In vivo, AF is metabolized to 1,5-anhydro-D-glucitol (AG), ascopyrone P (APP), microthecin and other derivatives via the anhydrofructose pathway. The genes coding for the enzymes in this pathway have been cloned, enabling the large-scale production of AF and related products in a cell-free reactor. The possible applications of these products in medicine have been evaluated using both in vitro and in vivo systems. Thus AF is a useful anticariogenic agent as it inhibits the growth of the oral pathogen Streptococcus mutans, impairing the production of plaque-forming polysaccharides and lactic acid. AF also shows anti-inflammatory and anticancer effects. AG is used as a diabetic marker for glycemic control. AG also stimulates insulin secretion in insulinoma cell lines. in vivo, APP has been shown to lengthen the life span of cancer-afflicted mice. It interferes with tumor growth and metastasis by its cidal effects on fast multiplying cells. Microthecin inhibits the growth of the human pathogen Pseudomonas aeruginosa PAO1, particularly under anaerobic conditions. The pharmaceutical usefulness of the other AF metabolites 1,5-anhydro-D-mannitol,1-deoxymannojirimycin, haliclonol, 5-epipentenomycin I, bissetone, palythazine, isopalythazine, and clavulazine remains to be investigated. In this review AF and its metabolites as the bioactive natural products for their pharmaceutical potentials are discussed. | Ketoses |
The DNA ligase from bacteriophage T4 is one of the most widely used enzymes in molecular biology. It has evolved to seal single-stranded nicks in double-stranded DNA, but not to join double-stranded fragments with cohesive or blunt ends. Its poor activity in vitro, particularly with blunt-ended substrates, can lead to failed or sub-optimal experimental outcomes. We have fused T4 DNA ligase to seven different DNA-binding proteins, including eukaryotic transcription factors, bacterial DNA repair proteins and archaeal DNA-binding domains. Representatives from each of these classes improved the activity of T4 DNA ligase, by up to 7-fold, in agarose gel-based screens for cohesive- and blunt-ended fragment joining. Overall, the most active variants were p50-ligase (i.e. NF-kappaB p50 fused to T4 DNA ligase) and ligase-cTF (T4 DNA ligase fused to an artificial, chimeric transcription factor). Ligase-cTF out-performed T4 DNA ligase by approximately 160% in blunt end 'vector + insert' cloning assays, and p50-ligase showed an improvement of a similar magnitude when it was used to construct a library for Illumina sequencing. The activity of the Escherichia coli DNA ligase was also enhanced by fusion to p50. Together, these results suggest that our protein design strategy is a generalizable one for engineering improved DNA ligases. | DNA Ligases |
Ammocoetes-the filter-feeding larvae of modern lampreys-have long influenced hypotheses of vertebrate ancestry(1-7). The life history of modern lampreys, which develop from a superficially amphioxus-like ammocoete to a specialized predatory adult, appears to recapitulate widely accepted scenarios of vertebrate origin. However, no direct evidence has validated the evolutionary antiquity of ammocoetes, and their status as models of primitive vertebrate anatomy is uncertain. Here we report larval and juvenile forms of four stem lampreys from the Palaeozoic era (Hardistiella, Mayomyzon, Pipiscius, and Priscomyzon), including a hatchling-to-adult growth series of the genus Priscomyzon from Late Devonian Gondwana. Larvae of all four genera lack the defining traits of ammocoetes. They instead display features that are otherwise unique to adult modern lampreys, including prominent eyes, a cusped feeding apparatus, and posteriorly united branchial baskets. Notably, phylogenetic analyses find that these non-ammocoete larvae occur in at least three independent lineages of stem lamprey. This distribution strongly implies that ammocoetes are specializations of modern-lamprey life history rather than relics of vertebrate ancestry. These phylogenetic insights also suggest that the last common ancestor of hagfishes and lampreys was a macrophagous predator that did not have a filter-feeding larval phase. Thus, the armoured 'ostracoderms' that populate the cyclostome and gnathostome stems might serve as better proxies than living cyclostomes for the last common ancestor of all living vertebrates. | Lampreys |
The ancient classic work Yellow Emperor's Inner Canon has abundant expositions about the relationship between the acupuncture needle manipulation and pulse diagnosis. However, the relevant imparting and inheritance situations are relatively weaker nowadays probably due to the rapid development of modern diagnosis-therapeutic techniques and some faults or careless omission in understanding classical medical works. Qi, a core concept of the abundant expositions in Inner Canon, has seldom been thoroughly interpreted about its connotations. For this reason, in the present paper, the authors make a careful explanation about the connotations of Qi in Inner Canon from 1) the concept of Qikou (a superficial window of the body reflecting the functional state of internal organs), 2) pulse conditions, 3) its relationship with meridian-collateral diagnosis, and 4) the link between acupuncture needle stimulation and pulse diagnosis based on the scriptures and words description in combination with many scholars' doctrines, trying to explore its profound significance. In addition, the authors also expound its association with the effectiveness of distant treatment of acupuncture and the characteristics in relation to ancient medical scholars' thoughts. | Medicine, Chinese Traditional |
BACKGROUND: Adolescent and young adult (AYA) patients with cancer are poorly recruited to molecularly targeted trials and have not witnessed the advances in cancer treatment and survival seen in other age groups. We report here a pan-European proof-of-concept study to identify actionable alterations in some of the worst prognosis AYA cancers: bone and soft tissue sarcomas. DESIGN: Patients aged 12-29 years with newly diagnosed or recurrent, intermediate or high-grade bone and soft tissue sarcomas were recruited from six European countries. Pathological diagnoses were centrally reviewed. Formalin-fixed tissues were analysed by whole exome sequencing, methylation profiling and RNA sequencing and were discussed in a multidisciplinary, international molecular tumour board. RESULTS: Of 71 patients recruited, 48 (median 20 years, range 12-28) met eligibility criteria. Central pathological review confirmed, modified and re-classified the diagnosis in 41, 3, and 4 cases, respectively. Median turnaround time to discussion at molecular tumour board was 8.4 weeks. whole exome sequencing (n = 48), methylation profiling (n = 44, 85%) and RNA sequencing (n = 24, 50%) led to therapeutic recommendations for 81% patients, including 4 with germ line alterations. The most common were for agents targeted towards tyrosine kinases (n = 20 recommendations), DNA repair (n = 18) and the PI3K/mTOR/AKT pathway (n = 15). Recommendations were generally based on weak evidence such as activity in a different tumour type (n = 68, 61%), reflecting the dearth of relevant molecular clinical trial data in the same tumour type. CONCLUSIONS: We demonstrate here that comprehensive molecular profiling of AYA patients' samples is feasible and deliverable in a European programme. | Proof of Concept Study |
During the 19th century, dentistry was changing from a craft that was usually transmitted by a preceptor to a science that was taught in established schools. The first dental school, established in 1827 in Bainbridge, Ohio, was soon followed by a large number of proprietary and freestanding schools of dentistry. However, no matter what the status of the dental school, none would admit women. In contrast, the first woman to be admitted to a medical college graduated in 1849. The Ohio College of Dental Surgery was the first dental school to open its doors to a woman and granted a degree to Lucy Beaman Hobbs Taylor in 1866. Although the number of women to graduate from dental school increased, the number was small compared to the increase in male graduates. By 1893, about 200 women had graduated with degrees in dentistry, including a number who came from outside the United States. | Dentists, Women |
It is believed that hepatitis C virus (HCV) particles are released through the canonical secretory route: from the endoplasmic reticulum (ER), via the Golgi, to the plasma membrane. While the Golgi is important for HCV release per se, its direct involvement in the trafficking of assembled virions has not yet been established. In fact, data from studies analyzing HCV egress are compatible with several potential pathways of HCV secretion. Here, we summarize and discuss the current knowledge related to the HCV export pathway. Apart from the prototypical anterograde transport, possible routes of HCV release include ER-to-endosomal transport, secretory autophagy, and poorly described mechanisms of unconventional protein secretion. Studying HCV egress promises to shed light on unconventional cellular trafficking and secretory routes. | Virus Release |
The connection between cytoskeleton alterations and diseases is well known and has stimulated research on cell mechanics, aiming to develop reliable biomarkers. In this study, we present results on rheological, adhesion, and morphological properties of primary rat cardiac fibroblasts, the cytoskeleton of which was altered by treatment with cytochalasin D (Cyt-D) and nocodazole (Noc), respectively. We used two complementary techniques: quartz crystal microbalance (QCM) and digital holographic microscopy (DHM). Qualitative data on cell viscoelasticity and adhesion changes at the cell-substrate near-interface layer were obtained with QCM, while DHM allowed the measurement of morphological changes due to the cytoskeletal alterations. A rapid effect of Cyt-D was observed, leading to a reduction in cell viscosity, loss of adhesion, and cell rounding, often followed by detachment from the surface. Noc treatment, instead, induced slower but continuous variations in the rheological behavior for four hours of treatment. The higher vibrational energy dissipation reflected the cell's ability to maintain a stable attachment to the substrate, while a cytoskeletal rearrangement occurs. In fact, along with the complete disaggregation of microtubules at prolonged drug exposure, a compensatory effect of actin polymerization emerged, with increased stress fiber formation." | Quartz Crystal Microbalance Techniques |
Although X chromosome inactivation in female mammals evolved to balance the expression of X chromosome and autosomal genes in the two sexes, female embryos pass through developmental stages in which both X chromosomes are active in somatic cells. Bovine blastocysts show higher expression of many X genes in XX than XY embryos, suggesting that X inactivation is not complete. Here, we reanalyzed bovine blastocyst microarray expression data from a network perspective with a focus on interactions between X chromosome and autosomal genes. Whereas male-to-female ratios of expression of autosomal genes were distributed around a mean of 1, X chromosome genes were clearly shifted towards higher expression in females. We generated gene coexpression networks and identified a major module of genes with correlated gene expression that includes female-biased X genes and sexually dimorphic autosomal genes for which the sexual dimorphism is likely driven by the X genes. In this module, expression of X chromosome genes correlates with autosome genes, more than the expression of autosomal genes with each other. Our study identifies correlated patterns of autosomal and X-linked genes that are likely influenced by the sexual imbalance of X gene expression when X inactivation is inefficient. | X Chromosome |
Potentially inappropriate prescribing (PIP) is one of the major risk factors of adverse drug events in elderly patients. Pharmacotherapy assessment criteria may help reduce the instances of PIP among geriatric patients. This study aimed to verify the applicability of selected tools designed to assess prescribing appropriateness in elderly and to identify PIP in the study population. Based on pharmacist-led medication reviews that were performed among patients attending senior day-care centers based in Poland, aged 65 years and over, the following tools were applied for assessing the appropriateness of pharmacotherapy: PILA (patient-in-focus listing approach): STOPP/START v.2 and Amsterdam tool, DOLA (drug-oriented listing approach): PRISCUS list, and DOLA+: Beers criteria v.2019 and the EU(7)-PIM list-the criteria oriented on medications requiring indications. Fifty patients participated in the study. The prevalence of prescribing issues in the study population was very high and ranged from 28% to 100%, depending on the criteria applied. The highest number of PIP cases was identified based on the PILA criteria: STOPP/START v.2 (171, a mean of 3.4 PIP cases per patient), and the Amsterdam criteria (124, a mean of 2.5 PIP cases per patient). The lack of protective vaccinations against pneumococci identified using the START criterion was found to be the most common PIP (identified in 96% of the patients). Proton-pump inhibitors (PPIs) were identified as the most problematic group of medications. The STOPP, EU(7)-PIM and Beers criteria revealed cases of inappropriate prolonged PPI use, whereas the Amsterdam tool identified cases where PPIs should have been prescribed but were not. The highest number of PIP cases in the study population were identified with the PILA tools, and on this basis the most comprehensive assessment of pharmacotherapy appropriateness in geriatric patients was conducted. Further studies should be designed, covering a larger group of patients across different healthcare settings (inpatient and outpatient), with access to comprehensive patient data. | Medication Review |
BACKGROUND: Upon oxidation of the polyunsaturated fatty acids in fish oil, either before ingestion or, as recently shown, during the gastro-intestinal passage, a cascade of potentially cytotoxic peroxidation products, such as malondialdehyde and 4-hydroxy-2-hexenal, can form. In this study, we digested fresh and oxidised cod liver oils in vitro, monitored the levels of lipid peroxidation products and evaluated oxidative, proteomic and inflammatory responses to the two types of digests in the yeast Saccharomyces cerevisiae and human monocyte-derived dendritic cells. RESULTS: Digests of cod liver oil with 22-53 micromol L(-1) malondialdehyde and 0.26-3.7 micromol L(-1) 4-hydroxy-2-hexenal increased intracellular oxidation and cell energy metabolic activity compared to a digested blank in yeast cells and the influence of digests on mitochondrial protein expression was more pronounced for oxidised cod liver oil than fresh cod liver oil. The four differentially expressed and identified proteins were related to energy metabolism and oxidative stress response. Maturation of dendritic cells was affected in the presence of digested fresh cod liver oil compared to the digested blank, measured as lower CD86 expression. The ratio of secreted cytokines, IL-12p40/IL-10, suggested a pro-inflammatory effect of the digested oils in relation to the blank (1.47-1.67 vs. 1.07). CONCLUSION: Gastro-intestinal digestion of cod liver oil increases the amount of oxidation products and resulting digests affect oxidation in yeast and immunomodulation of dendritic cells. | Cod Liver Oil |
Genetic and biochemical data demonstrate a pivotal role for S-nitrosothiols (SNOs) in mediating the actions of nitric oxide synthases (NOSs). SNOs serve to convey NO bioactivity and to regulate protein function. This understanding is of immediate interest to the pulmonary clinical and research communities. This article reviews the following: (1) biochemical and cellular evidence that SNOs in amino acids, peptides, and proteins elicit NOS-dependent signaling in the respiratory system and (2) studies that link SNO signaling to pulmonary medicine. SNO-mediated signaling is involved in the regulation of minute ventilation, ventilation-perfusion matching, pulmonary arterial pressure, basal airway tone, and respiratory and peripheral muscle function. Derangements in SNO signaling are implicated in many disorders relevant to pulmonary and critical care medicine, including apnea, hypoxemia, pulmonary hypertension, asthma, cystic fibrosis, pneumonia, and septic shock. | S-Nitrosothiols |
Archival Pneumocystis jirovecii specimens from 84 patients monitored at Rennes University Hospital (Rennes, France) were assayed at the dihydropteroate synthase (DHPS) locus. No patient was infected with mutants. The results provide additional data showing that P. jirovecii infections involving DHPS mutants do not represent a public health issue in Brittany, western France. | Pneumocystis carinii |
Genome sequencing projects on two relapsing fever spirochetes, Borrelia hermsii and Borrelia turicatae, revealed differences in genes involved in purine metabolism and salvage compared to those in the Lyme disease spirochete Borrelia burgdorferi. The relapsing fever spirochetes contained six open reading frames that are absent from the B. burgdorferi genome. These genes included those for hypoxanthine-guanine phosphoribosyltransferase (hpt), adenylosuccinate synthase (purA), adenylosuccinate lyase (purB), auxiliary protein (nrdI), the ribonucleotide-diphosphate reductase alpha subunit (nrdE), and the ribonucleotide-diphosphate reductase beta subunit (nrdF). Southern blot assays with multiple Borrelia species and isolates confirmed the presence of these genes in the relapsing fever group of spirochetes but not in B. burgdorferi and related species. TaqMan real-time reverse transcription-PCR demonstrated that the chromosomal genes (hpt, purA, and purB) were transcribed in vitro and in mice. Phosphoribosyltransferase assays revealed that, in general, B. hermsii exhibited significantly higher activity than did the B. burgdorferi cell lysate, and enzymatic activity was observed with adenine, hypoxanthine, and guanine as substrates. B. burgdorferi showed low but detectable phosphoribosyltransferase activity with hypoxanthine even though the genome lacks a discernible ortholog to the hpt gene in the relapsing fever spirochetes. B. hermsii incorporated radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did B. burgdorferi. This complete pathway for purine salvage in the relapsing fever spirochetes may contribute, in part, to these spirochetes achieving high cell densities in blood." | Ribonucleoside Diphosphate Reductase |
Typhoid fever continues to escape swift diagnosis, even in an endemic country, and its multi-system nature led to delayed diagnosis in 25% of the patients in this study. This may have been an avoidable factor, leading to death in some patients through delay in instituting appropriate antimicrobial therapy. Neurological features and diarrhoea were particularly common in this paediatric population. Relative bradycardia has been shown to be a highly statistically significant finding for our group as a whole. Amoxycillin remains an effective and useful alternative to chloramphenicol. The mortality rate of 2.5% remains unchanged over the last 10 years. The relative inaccessibility to good primary health care, acceptable water supplies and sanitation that the black South African child encounters cannot be ruled out as a co-factor. | Typhoid Fever |
We have reexamined the heterogeneity shown by histidine in its uptake by the Ehrlich ascites tumor cell, in the face of a contradiction of our earlier interpretation. We again find the fraction of histidine uptake at neutral pH inhibitable by the model substrate for System A, 2-(methylamino)-isobutyric acid, to be fully dependent on the presence of Na+ or Li+. The small Na+ -independent component not attributable to System L can be identified with System Ly+ through its inhibitability by homoarginine. This component increases as the pH is lowered with an apparent pK' a of 6.1. The simultaneous decrease in the uptake by the neutral systems could be identified, for System L, with the same titration of histidine to its cationic form, but for System A the sharp decrease is identified with the protonation of a structure on the membrane rather than one on the substrate. The action of H+ in the latter case proved approximately non-competitive with Na+ when tested with ordinary substrates. | Aminoisobutyric Acids |
Experiments were performed to examine the effect of metyrapone, an inhibitor of corticosterone synthesis, on the level of dopamine D1 receptors and their transcripts in the caudate-putamen, nucleus accumbens and olfactory tubercle of the rat brain. The binding to dopamine D1 receptors was measured by receptor autoradiography using the specific D1 receptor antagonist [3H]SCH 23390. The level of dopamine D1 receptor messenger RNA was determined by in situ hybridization histochemistry. The results obtained have shown that metyrapone (two injections of 150 and 50 mg/kg, i.p., given 20 and 3 h before killing, respectively) induced a decrease in the D1 receptor-specific binding in the studied areas of the rat brain. In the caudate putamen, the decrease in [3H]SCH 23390 binding was stronger in the medial (31-39%) than in the lateral part (24-27%). Decreases similar to those in the caudate-putamen were observed in the nucleus accumbens (21%) and olfactory tubercle (32%). Furthermore, metyrapone decreased the level of dopamine D1 receptor messenger RNA in the caudate putamen (17-28%), nucleus accumbens (20%) and olfactory tubercle (18%). In conclusion, our study indicates that glucocorticoids might be involved in the regulation of dopamine D1 receptor level in the rat brain. since metyrapone (which inhibits the synthesis of these hormones) decreases the messenger RNA encoding D1 receptor synthesis, as well as the specific binding to this receptor. | Metyrapone |
Host genetic determinants that underpin variation in susceptibility to systemic fungal infection are poorly understood. Genes responsible for complex traits can be identified by correlating variation in phenotype with allele in founder strains of wild mice with known genetic variation, assembled in genetic reference panels. In this work, we describe wide natural variation in both primary and acquired resistance to experimental pulmonary blastomycosis in eight founder strains, including 129, A/J, BL/6, CAST, NOD, NZO, PWK, and WSB of the Collaborative Cross collection, and the inbred DBA strain. These differences in susceptibility across strains were accompanied by sharp differences in the accumulation and function of immune cells in the lungs. Immune perturbations were mapped by identifying reagents that phenotypically mark immune cell populations in the distinct strains of mice. In particular, we uncovered marked differences between BL/6 and DBA/2 mouse strains in the development of acquired resistance. Our findings highlight the potential value in using genetic reference panels of mice, and particularly the BXD (recombinant inbred strains of mice from a cross of C57BL/6J and DBA/2J mice) collection harboring a cross between resistant BL/6 and susceptible DBA/2 mice, for unveiling genes linked with host resistance to fungal infection. IMPORTANCE Host genetic variation significantly impacts vulnerability to infectious diseases. While host variation in susceptibility to fungal infection with dimorphic fungi has long been recognized, genes that underpin this variation are poorly understood. We used a collection of seven mouse strains that represent nearly 90% of the genetic variation in mice to identify genetic variability among the strains in resistance to pulmonary infection with the dimorphic fungus Blastomyces dermatitidis. We analyzed differences between the strains in innate resistance by infecting naive mice and in acquired resistance by infecting vaccinated mice. We identified extreme variations in both innate and acquired resistance among the strains. In particular, we found sharp differences between C57BL/6 and DBA/2 strains in the ability to acquire vaccine-induced resistance. We also identified commercial reagents that allowed the phenotyping of immune cells from this strain collection of mice. Because there are additional mice harboring a genetic cross of the C57BL/6 and DBA/2 strains (BXD collection), such mice will permit future investigations to identify the genes that underlie differences in the ability to acquire resistance to infection. | Blastomyces |
The structures of acetic acid (AA), trifluoroacetic acid (TFA), and their aqueous mixtures over the entire range of acid mole fraction xA have been investigated by using large-angle X-ray scattering (LAXS) and NMR techniques. The results from the LAXS experiments have shown that acetic acid molecules mainly form a chain structure via hydrogen bonding in the pure liquid. In acetic acid-water mixtures hydrogen bonds of acetic acid-water and water-water gradually increase with decreasing xA, while the chain structure of acetic acid molecules is moderately ruptured. Hydrogen bonds among water molecules are remarkably formed in acetic acid-water mixtures at xA<or=approximately 0.4, and water clusters eventually predominate in the mixtures at xA<or=approximately 0.18. The LAXS results have revealed that TFA molecules form not a chain structure but cyclic dimers through hydrogen bonding in the pure liquid. In TFA-water mixtures O...O hydrogen bonds among water molecules gradually increase when xA decreases, and hydrogen bonds among water molecules are significantly formed in the mixtures at xA<or=approximately 0.6. It has also been shown that TFA molecules are considerably dissociated to hydrogen ions and trifluoroacetate in the mixtures. 1H, 13C, and 19F NMR chemical shifts of acetic acid and TFA molecules for acetic acid-water and TFA-water mixtures have indicated strong relationships between a structural change of the mixtures and the acid mole fraction. On the basis of both LAXS and NMR results, the structural changes of acetic acid-water and TFA-water mixtures with decreasing acid mole fraction and the effects of fluorination of the methyl group on the structure are discussed at the molecular level. | Trifluoroacetic Acid |
Ecophysiological investigations on the salinity acclimation of the cyanobacterium Prochlorothrix hollandica SAG 10.89 led to significantly revised salinity tolerance limits. Besides potential effects of cultivation techniques, clear ion composition effects mainly explain formerly described hypersensitivity to NaCl-mediated salinity and lack of osmolyte detection. An extraordinarily broad plasticity of cellular chlorophyll a/b ratios occurred with variations of NaCl-induced salinity. Photosynthesis characteristics, pigment regulation, respiration, and biomass yield in growth medium with field-like ion composition indicated generally reduced acclimation pressure. A simultaneously significant increase in osmolyte (sucrose) accumulation indicated more efficient osmotic acclimation. Minor growth inhibition up to salinities of 10 practical salinity units enlarged the potential habitat of P. hollandica but at the most to about 300,000 km2 in the Baltic Sea. This supports probable observations of Prochlorothrix sp. in phytoplankton assemblages of open waters in Baltic Sea-monitoring studies. Brackish habitats differ from so far known habitats of Prochlorothrix spp. in turbidity, productivity, and plankton composition. Adjusted physiological features dispel fundamental doubts on the establishment of filamentous prochlorophytes in brackish waters. | Prochlorothrix |
INTRODUCTION: Chymase is primarily found in mast cells (MCs), fibroblasts, and vascular endothelial cells. MC chymase is released into the extracellular interstitium in response to inflammatory signals, tissue injury, and cellular stress. Among many functions, chymase is a major extravascular source for angiotensin II (Ang II) generation. Several recent pre-clinical and a few clinical studies point to the relatively unrecognized fact that chymase inhibition may have significant therapeutic advantages over other treatments in halting progression of cardiac and vascular disease. AREAS COVERED: The present review covers patent literature on chymase inhibitors for the treatment of cardiac diseases registered between 2010 and 2018. EXPERT OPINION: Increase in cardiac MC number in various cardiac diseases has been found in pathological tissues of human and experimental animals. Meta-analysis data from large clinical trials employing angiotensin-converting enzyme (ACE) inhibitors show a relatively small risk reduction of clinical cardiovascular endpoints. The disconnect between the expected benefit associated with Ang II blockade of synthesis or activity underscores a greater participation of chymase compared to ACE in forming Ang II in humans. Emerging literature and a reconsideration of previous studies provide lucid arguments to reconsider chymase as a primary Ang II forming enzyme in human heart and vasculature. | Chymases |
Human Antigen Leukocyte-G (HLA-G) gene encodes an immune checkpoint molecule that has restricted tissue expression in physiological conditions; however, the gene may be induced in hypoxic conditions by the interaction with the hypoxia inducible factor-1 (HIF1). Hypoxia regulatory elements (HRE) located at the HLA-G promoter region and at exon 2 are the major HIF1 target sites. Since the G allele of the -964G > A transversion induces higher HLA-G expression when compared to the A allele in hypoxic conditions, here we analyzed HIF1-HRE complex interaction at the pair-atom level considering both -964G > A polymorphism alleles. Mouse HIF2 dimer crystal (Protein Data Bank ID: 4ZPK) was used as template to perform homology modelling of human HIF1 quaternary structure using MODELLER v9.14. Two 3D DNA structures were built from 5'GCRTG'3 HRE sequence containing the -964G/A alleles using x3DNA. Protein-DNA docking was performed using the HADDOCK v2.4 server, and non-covalent bonds were computed by DNAproDB server. Molecular dynamic simulation was carried out per 200 ns, using Gromacs v.2019. HIF1 binding in the HRE containing -964G allele results in more hydrogen bonds and van der Waals contact formation than HRE with -964A allele. Protein-DNA complex trajectory analysis revealed that HIF1-HRE-964G complex is more stable. In conclusion, HIF1 binds in a more stable and specific manner at the HRE with G allele. | HLA-G Antigens |
Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin(R), the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history. | Antipyretics |
An infant with acrodermatitis enteropathica was studied before and after starting zinc therapy. Clinical recovery was rapid, and the plasma zinc, serum and mucosal alkaline phosphatase activities returned to normal. Light microscopy of small intestinal biopsies showed normal mucosa. Electron microscopy of the Paneth cells initially revealed abnormal inclusion bodies which disappeared during therapy, suggesting that the abnormality is secondary to zinc deficiency, and not a primary defect. These abnormal inclusions may represent altered secretory granules and a proliferation of lysosomes. We were unable to define the heterozygous state biochemically or histologically. | Acrodermatitis |
BACKGROUND: Sniffer dogs are able to detect certain chemical particles and are suggest to be capable of helping diagnose some medical conditions and complications, such as colorectal cancer, melanoma, bladder cancer, and even critical states such as hypoglycemia in diabetic patients. With the global spread of COVID-19 throughout the world and the need to have a real-time screening of the population, especially in crowded places, this study aimed to investigate the applicability of sniffer dogs to carry out such a task. METHODS: Firstly, three male and female dogs from German shepherd (Saray), German black (Kuzhi) and Labrador (Marco) breeds had been intensively trained throughout the classical conditioning method for 7 weeks. They were introduced to human specimens obtained from the throat and pharyngeal secretions of participants who were already reported positive or negative for SARS-COV-2 infection be RT-PCR. Each dog underwent the conditioning process for almost 1000 times. In the meantime another similar condition process was conducted on clothes and masks of COVID-19 patient using another three male and female dogs from Labrador (Lexi), Border gypsy (Sami), and Golden retriever (Zhico) breeds. In verification test for the first three dogs, 80 pharyngeal secretion samples consisting of 26 positive and 54 negative samples from different medical centers who underwent RT-PCR test were in a single-blind method. In the second verification test for the other three dogs, masks and clothes of 50 RT-PCR positive and 70 RT-PCR negative cases from different medical center were used. RESULTS: In verification test using pharyngeal secretion, the sniffer dogs' detection capability was associated with a 65% of sensitivity and 89% of specificity and they amanged to identify 17 out of the 26 positive and 48 out of the 54 true negative samples. In the next verification test using patients' face masks and clothes, 43 out of the 50 positive samples were correctly identified by the dogs. Moreover, out of the 70 negative samples, 65 samples were correctly found to be negative. The sensitivity of this test was as high as 86% and its specificity was 92.9%. In addition, the positive and negative predictive values were 89.6 and 90.3%, respectively. CONCLUSION: Dogs are capable of being trained to identify COVID-19 cases by sniffing their odour, so they can be used as a reliable tool in limited screening. | Working Dogs |
A method is described for isoelectric focusing of proteins, using an ultrathin-layer polyacrylamide gel on cellophane, followed by electrophoretic transfer of separated proteins onto a nitrocellulose membrane. The polyacrylamide gel is firmly attached to the cellophane and thus protected from mechanical damage; such gels are easily manipulated. Cellophane is permeable to ions and application of this gel support overcomes difficulties resulting from the removal of ultrathin gels from a plastic support on electroblotting. Proteins separated under nondenaturing conditions were transferred onto a nitrocellulose membrane and detected by the concanavalin A-peroxidase technique. The proposed approach makes it possible to analyze the variability of nondenatured proteins and glycoproteins of different origin. | Cellophane |
Thirty-six women with endometriosis externa were treated with danazol (Ladogar; Winthrop Laboratories, Division of Sterling Drug (SA) (Pty) Ltd) for 6 months. In 15 cases treatment was combined with conservative surgery. Of these patients 34 presented with the complaint of infertility. The results were evaluated by means of repeat laparoscopy and biopsy. Of 21 patients treated with danazol only 9 (42,9%) were completely healed, and 10 (47,6%) showed a good response, giving an overall response of 90,5% and a corrected conception rate of 52,9%. Of the 15 patients who were treated with danazol combined with conservative surgery, 9 (60%) have completely healed, and 3 had a recurrence of endometriosis. This group had a corrected pregnancy rate of 30,8%. The majority of conceptions (61,5%) occurred during the first 6 months after treatment, 92,3% within the 1st year and 1 a year after conclusion of treatment. Of the 13 conceptions, 11 were successful, 1 ended in an abortion and 1 in an ectopic pregnancy, and 1 small-for-gestational-age infant was delivered. | Danazol |
Recent research has primarily focused on the utilization of reductants as activators for Fe(VI) to generate high-valent iron species (Fe(IV)/Fe(V)) for the degradation of emerging organic contaminants (EOCs). However, a significant drawback of this approach arises from the reaction between reductants and ferrates, leading to a decrease in oxidation capacity. This study introduces a novel discovery that highlights the potential of the iron(III)-(1,10-phenanthroline) (Fe(III)-Phen) complex as an activator, effectively enhancing the degradation of EOCs by Fe(VI) and augmenting the overall oxidation capacity of Fe(VI). The degradation of EOCs in the Fe(VI)/Fe(III)-Phen system is facilitated through two mechanisms: a direct electron transfer (DET) process and electron shuttle action. The DET process involves the formation of a Phen-Fe(III)-Fe(VI)* complex, which exhibits a stronger oxidation ability than Fe(VI) alone and can accept electrons directly from EOCs. On the other hand, the electron shuttle process utilizes Fe(III)-Phen as a redox mediator to transfer electrons from EOCs to Fe(VI) through the Fe(IV)/Fe(III) or Fe(IV)/Fe(II)/Fe(III) cycle. Moreover, the Fe(III)-Phen complex can improve the utilization efficiency of Fe(V) by preventing its self-decay. This study's findings may present a viable option for utilizing an effective catalyst to enhance the oxidation of EOCs by Fe(VI) and Fe(V). | Reducing Agents |
BACKGROUND: Few data are available on quarterly 11.25 mg GnRH analog treatment in central precocious puberty (CPP). AIM: To assess the efficacy of triptorelin 11.25 mg in children with CPP. PATIENTS: 17 patients (16 females) with CPP (7.9 +/- 0.9 years) were treated with triptorelin 11.25 mg/90 days. METHODS: Gonadotropins, basal-, and GnRH-stimulated peak, gonadal steroids, and pubertal signs were assessed at preinclusion and at inclusion visit, 3 months, 6 months, and 12 months of treatment. Results. At 3, 6, and 12 months, all patients had suppressed LH peak (<3 IU/L after GnRH stimulation), as well as prepubertal oestradiol levels. Mean LH peak values after GnRH test significantly decreased from 25.7 +/- 16.5 IU/L at baseline to 0.9 +/- 0.5 IU/L at M3 (P < 0.0001); they did not significantly changed at M6 and M12. CONCLUSIONS: Triptorelin 11.25 mg/90 days efficiently suppressed the pituitary-gonadal axis in children with CPP from first administration. | Luteolytic Agents |
This survey describes some general problems of medical classifications and their historical development at international and national levels. The emphasis is on the "International Statistical Classification of Diseases and Related Health Problems (ICD)" of the World Health Organization (WHO). Evolving from an "International List of Causes of Death", initiated more than 100 years ago, particularly since 1948 the ICD has increasingly developed into an internationally essential classification also for all problems of morbidity. In Germany, the implementation for the mandatory coding of diagnoses of inpatients began with ICD-8 in 1968. With the 10th revision (ICD-10) the coding of diagnoses of all inpatient and outpatient cases became mandatory in the year 2000. Since 2004 this specific German version is called ICD-10-GM and revised yearly. No internationally valid classification is available for operations and other medical procedures. "The International Classification of Procedures in Medicine (ICPM)", published by the WHO in 1978, has not been revised since, but served as a model for several national classifications. Also the German "Operationen- und Prozedurenschlussel (OPS)" (Code of Operations and Procedures), initially published in 1994, derives from the ICPM. Since 2004 both the ICD-10-GM und the OPS are revised yearly. This paper shows historical development, contents and areas of application for ICD-10-GM and OPS. In the case of inpatient treatment, the classifications are mainly used for reimbursement based on the German G-DRG System, in the case of outpatient treatment for the legally required coding of diagnoses and other reasons for medical treatment and of selected surgical procedures for reimbursement purposes." | Healthcare Common Procedure Coding System |
Using Langevin dynamic simulations, a simple coarse-grained model of a DNA protein construct is used to study the DNA rupture and the protein unfolding. We identify three distinct states: (i) zipped DNA and collapsed protein, (ii) unzipped DNA and stretched protein, and (iii) unzipped DNA and collapsed protein. Here, we find a phase diagram that shows these states depending on the size of the DNA handle and the protein. For a less stable protein, unfolding is solely governed by the size of the linker DNA, whereas if the protein's stability increases, complete unfolding becomes impossible because the rupture force for DNA has reached a saturation regime influenced by the de Gennes length. We show that unfolding occurs via a few intermediate states by monitoring the force-extension curve of the entire protein. We extend our study to a heterogeneous protein system, where similar intermediate states in two systems can lead to different protein unfolding paths. | Protein Unfolding |
This study investigated the frequency of periapical lesions following pulpal necrosis in vital teeth used as abutments in periodontal-prosthetic therapy. The study was conducted on a continuative series of 1000 teeth treated at least 2 years before the start of the investigation. 500 teeth were treated by specialist and 500 by general practitioners. The dental records of this sample were stored into a computer, analyzed and compared, and the chi-square index was calculated. Periapical lesions were found in 22.6% of the teeth. Maxillary incisors had the highest number of lesions (36.8%). The percentage of lesions increased as periodontal involvement became more severe (37.2%) with severe involvement as opposed to 18.5% with moderate involvement). The frequency of lesions was lower in the group of teeth treated by specialists than in the group treated by general practitioners (13.8% as opposed to 31.4%). | Periodontal Prosthesis |
BACKGROUND: All typically developing children are born with flexible flat feet, progressively developing a medial longitudinal arch during the first decade of their lives. Whilst the child's foot is expected to be flat, there is currently no consensus as to how flat this foot should be. Furthermore, whilst feet are observed to decrease in flatness with increasing age, it is not known how flat they should be at each age increment. The objective of this systematic review is to define the postural characteristics of the 'typically' developing paediatric foot. METHODS: The PRISMA protocol was applied to compare all data currently published describing the typical development of the paediatric foot. The Epidemiological Appraisal Instrument (EAI) was used to assess the risk of bias of the included studies. RESULTS: Thirty four epidemiological papers pertaining to the development of the paediatric foot were graphically compared. Sixteen different foot posture assessments were identified of which footprint based measures were the most reported outcome. CONCLUSION: Firstly, the use of the term normal in relation to foot posture is misleading in the categorisation of the paediatric foot, as indeed a flat foot posture is a normal finding at specific ages. Secondly, the foot posture of the developing child is indeed age dependent and has been shown to change over time. Thirdly, no firm conclusion could be reached as to which age the foot posture of children ceases to develop further, as no two foot measures are comparable, therefore future research needs to consider the development of consensus recommendations as to the measurement of the paediatric foot, using valid and reliable assessment tools. | Foot |
Encephalomyocarditis virus (EMCV) is a zoonotic pathogen that has a wide spectrum of host range. The virus has been discovered on swine farms worldwide and can cause acute fatal myocarditis in piglets and reproductive disorders in sows. Although EMCV infection has been documented in farmed pigs in China, seroprevalence in humans has not been reported. In this study, we conducted nationwide serological surveys for EMCV in humans and farmed pigs in China in 2013, by the use of a double antigen sandwich ELISA method. A total of 3305 serum samples from healthy people were obtained from seven geographical regions in China, of which 1010 samples (30.56%) were positive for EMCV antibodies. The overall seroprevalence for EMCV in the age groups of 0-20, 21-40, 41-60 and >60 years were 13.5%, 30.25%, 36.83% and 38.71% respectively, showing a tendency of increasing with age (P = 0.000). A total of 3470 serum samples from farmed pigs were collected and tested for antibodies to EMCV. A high seroprevalence of 77% was recorded, and significant regional differences were observed. It was concluded that people and pigs in China were commonly infected by EMCV. In addition, in order to characterize changes of seroprevalence during natural EMCV infection in pigs, 240 serial serum samples were collected from 30 pigs (at 0, 15, 30, 60, 75, 90, 120, and 150 days of age) in a farrow-to-finish farm in China. The data showed that there were two EMCV antibody peaks: the first peak appeared at day 30, followed by a decrease in EMCV antibody titer, and the second occurred after day 75. Thus, the most susceptible period of pigs for EMCV infection was between day 30 and day 75 of age. | Encephalomyocarditis virus |
The World Health Organization (WHO) classification of myeloid disorders has provided updated parameters for the consistent diagnosis of two previously less than optimally defined chronic myeloid disorders, CNL and CMML. The classification of these disorders, which had been controversial, is now better defined and provides more clinically and biologically relevant disease definitions to enable uniform diagnosis and a framework to evaluate natural history and therapeutic interventions. CNL is now recognized as a distinct entity among the chronic myeloproliferative disorders and CMML is included within the new category of 'myelodysplastic/myeloproliferative diseases' (MDS/MPD). Predominant neutrophilia defines CNL whereas CMML is defined by predominant and monocytosis. In each case these defining features must be distinguished from reactive causes for the same in the absence of clear evidence of myeloid clonality (CNL and CMML) or dysplasia (CMML). The exclusion of underlying bcr/abl-driven oncogenesis is an essential component in the diagnosis of these chronic leukemic processes. The optimal therapy for both CNL and CMML remains uncertain. Current management decisions are based on small studies or extrapolated from therapeutic strategies that are effective in similar chronic, clonal myeloid disorders. Given the potential for evolution to acute leukemia or progressive refractory leucocytosis or cytopenias, allogeneic stem cell transplantation might be appropriate for younger patients. Continued reporting and investigation of specific therapeutic strategies and responses must be encouraged." | Leukemia, Myelomonocytic, Chronic |
The sensibility to erythropoietin oferythroblastic islands of bone marrow which were made in different terms after the creation of transfusion polycytemia is researched. It turned out that the central macrophags of involuting erythroblastic islands are more sensible to erythropoietin than residual macrophags of bone marrow. The capability of residual macrophags to form erythroblastic islands is opened to the bigger inhibitory influence during the development of transfusion polycytemia than to the central macrjphags of involuting erythroblastic islands. | Erythroblasts |
Despite the recent success of coupling anion exchange chromatography with native mass spectrometry (AEX-MS) to study anionic proteins, the utility of AEX-MS methods in therapeutic monoclonal antibody (mAb) characterization has been limited. In this work, we developed and optimized a salt gradient-based AEX-MS method and explored its utility in charge variant analysis of therapeutic mAbs. We demonstrated that, although the developed AEX-MS method is less useful for IgG1 molecules that have higher isoelectric points (pIs), it is an attractive alternative for charge variant analysis of IgG4 molecules. By elevating the column temperature and lowering the mAb pI through PNGase F-mediated deglycosylation, the chromatographical resolution from AEX separation can be significantly improved. We also demonstrated that, after PNGase F and IdeS digestion, the AEX-MS method exhibited excellent resolving power for multiple attributes in the IgG4 Fc region, including unprocessed C-terminal Lys, N-glycosylation occupancy, and several conserved Fc deamidations, making it ideally suited for multiple attribute monitoring (MAM). Through fractionation and peptide mapping analysis, we also demonstrated that the developed AEX-MS method can provide site-specific and isoform-resolved separation of Fc deamidation products, allowing rapid and artifact-free quantitation of these modifications without performing bottom-up analysis." | Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase |
BACKGROUND: Risk of pelvic inflammatory disease associated with Chlamydia trachomatis and Mycoplasma genitalium is increased after termination of pregnancy (TOP) and may be increased after insertion of intrauterine devices (IUDs). Screening prior to these procedures is recommended only for C. trachomatis. We examined C. trachomatis and M. genitalium prevalence and associated factors among women presenting to a pregnancy termination and contraception service over 10 years. METHODS: Retrospective analysis of clinical data collected from 17 573 women aged 15-45 years in 2009-2019 and for 266 M. genitalium positive women tested for macrolide resistance-associated mutations in 2016-2019. RESULTS: C. trachomatis and M. genitalium prevalence was 3.7% and 3.4%, respectively. In multivariable analyses, shared risk factors were younger age (p<0.001, for both C. trachomatis and M. genitalium), socioeconomic disadvantage (p=0.045 and p=0.008, respectively) and coinfection (p<0.001, for both sexually transmitted infections), with 10.1% of C. trachomatis positive women also positive for M. genitalium. Additional risk factors were earlier year of visit (p=0.001) for C. trachomatis and for M. genitalium residing outside a major city (p=0.013). The proportion of M. genitalium infections tested between 2016 and 2019 with macrolide resistance-associated mutations was 32.7%. CONCLUSIONS: Given the high level of antimicrobial resistance and the prevalence of coinfection, testing C. trachomatis positive women for M. genitalium could be considered in this setting to prevent further spread of resistant infections. Further research is required into the causal link between M. genitalium and pelvic inflammatory disease in women undergoing TOP and IUD insertion. | Mycoplasma genitalium |
PURPOSE: To assess bicycle helmet laws' effect on helmet and bicycle use among U.S. high school students in urban jurisdictions. METHODS: Log-binomial models were fit to Youth Risk Behavior Survey data from five jurisdictions. Adjusted helmet and bicycle use proportions were calculated with post-regression marginal effects. Difference-in-differences were estimated, comparing intervention to concurrent controls. A placebo outcome was used to falsify possible confounding or selection effects. RESULTS: In San Diego and Dallas, helmet use increase increased 10.6 (95% confidence interval [CI] 6.5 to 14.7, p < .001) and 8.1 (95% CI 4.3 to 12.0, p < .001) percentage points more than out-of-jurisdiction controls. Increases in Florida counties were 5.0 (95% CI 1.8 to 8.2, p = .003) and 4.0 (95% CI -.7 to 8.8, p = .098) points against age-based and out-of-jurisdiction controls, respectively. Bicycle use fell 5.5 points in both San Diego (95% CI -9.8 to -1.1, p = .015) and the Florida counties (95% CI -11.5 to .5, p = .075) against out-of-jurisdiction controls, but other comparisons had no significant changes. The placebo outcome never changed significantly. CONCLUSIONS: Laws increased helmet use in all jurisdictions, with limited evidence of reduced cycling. Although sound health policy, laws should be coupled with physical activity promotion. | Head Protective Devices |
Psammosilene tunicoides is one of the main ingredients of the Yunnan Baiyao". P. tunicoides is an endangered species included in the secondary protection list in China Plant Red Data Book as well as the endemic species in Southwest China. Its natural resources could not meet the needs of pharmaceutical production. Construction of core collection of P. tunicoides will lay the foundation for germplasm improvement and molecular breeding. The sequence variation of the key enzymes gene locus (beta-AS) were carried out to survey the population structure and population history of the species. Among the 11 populations across its geographical range, 36 haplotypes were identified. The levels of haplotype diversity (Hd=0.905) were high, while the levels of population differentiation (GST=0.280) were low. Analysisof molecular variance (AMOVA) indicated that a significantly greater proportion of total genetic variationpartitioned among populations thanwithin populations (values of 77.43% and 22.57%, respectively). These results in combination with the star-like phylogenetic network analysis indicate that Hap1 as an ancestral haplotypewas shared in four populations, Hap2, Hap4, Hap15 and Hap16 are occurred in two populations, the remains as private haplotype only distributed in single population. The strategy of core collection was constructed in order to maximumpreserve genetic diversity of P. tunicoides." | Caryophyllaceae |
The low affinity Na+/sulfate cotransporter, NaSi-1, belongs to the SLC13 family that also includes the Na+/dicarboxylate cotransporters, NaDC. Two serine residues in hNaSi-1, at positions 260 and 288, are conserved in all of the sulfate transporters in the family whereas the NaDC contain alanine or threonine at those positions. Therefore, the functional roles of serines 260 and 288 in substrate and cation binding by hNaSi-1 were investigated. These two serine residues were first mutated to alanine and the mutants were characterized in Xenopus oocytes. Alanine substitution of Ser-260 resulted in increased Km values for both substrate and Na+ whereas alanine replacement at Ser-288 resulted in a broadened cation selectivity, indicating that these two serines might play important roles in cation and/or substrate binding of hNaSi-1. The two serines and 12 surrounding residues were further mutated to cysteine and studied using a thiol-reactive compound, [2-(trimethylammonium)ethyl]methane-thiosulfonate (MTSET). Four mutants surrounding Ser-260 (T257C, T259C, T261C, and L263C) were sensitive to MTSET inhibition. The sensitivity to MTSET was dependent on the presence of substrate, suggesting that the accessibility of these substituted cysteines depends on the conformational state of the transporter. Because the four residues are located in transmembrane domain 5, this transmembrane domain is likely to participate in the conformational movements during the transport cycle of hNaSi-1. | Sodium Sulfate Cotransporter |
Studied were the values of 26 linear measurements of the udder in 50 normal cows and in 50 cows affected with subclinical mastitis, the animals used being of the Bulgarian Brown breed. A total of 19 indexes were established for each group. | Mastitis, Bovine |
PURPOSE: ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via purinergic P2 receptors. This study investigated the role of P2 receptors in exercise hyperemia in miniature swine. METHODS: We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and after arterial infusion of the P2 receptor antagonist reactive blue 2 during treadmill exercise (5.2 km/h, ~60 % VO2max) and arterial ATP infusion in female Yucatan miniature swine (~29 kg). RESULTS: Mean blood flow during exercise from the 16 sampled skeletal muscle tissues was 138 +/- 18 mL/min/100 g (mean +/- SEM), and it was reduced in 11 (~25 %) of the 16 sampled skeletal muscles after RB2 was infused. RB2 also lowered diaphragm blood flow and kidney blood flow, whereas lung tissue blood flow was increased (all P < 0.05). Infusion of RB2 increased arterial lactate concentration during exercise from 1.6 +/- 0.5 to 3.4 +/- 0.6 mmol/L and heart rate from 216 +/- 12 to 230 +/- 9 beats/min, whereas blood pressure was unaltered. Arterial ATP infusion caused a ~twofold increase in blood flow in 15 of the 16 sampled muscle tissues and this effect was abolished after RB2 infusion. CONCLUSIONS: These results indicate that P2 receptors play a role in regulating skeletal muscle blood flow during exercise in miniature swine." | Purinergic P2Y Receptor Antagonists |
BACKGROUND: Reports from experienced heroin users about an alternative and appreciated but harmful so-called Turkish" heroin preparation technic led to the chemical investigation of the compounds produced during this process and investigation of the presence of other psychoactive contaminants. METHODS: Comparison of diacetylmorphine, 6-monoacetylmorphine, morphine, paracetamol and caffeine concentrations were performed in the non-processed material, after processing according to the standard and to the alternative preparation methods using liquid chromatography coupled to quadrupole time of flight mass spectrometry followed by statistical evaluation of the results. RESULTS: The two preparation methods had in common a diminution of diacetylmorphine as compared to the starting material but significantly more 6-monoacetylmorphine was produced using the "Turkish" preparation method as compared to the standard method. CONCLUSION: The high amount of psychoactive 6-monoacetylmorphine may have an impact on the reported effects of heroin using the "Turkish" preparation procedure." | Morphine Derivatives |
An LC-MS/MS method is presented for screening five tetracyclines and their epimers in a broad range of food products. The scope of matrices includes meat-, fish-, seafood-based products, various dairy ingredients, infant formulae and fats. The method principle is based on a liquid-liquid extraction with aqueous ethylenediaminetetraacetic acid (EDTA) and acetonitrile followed by a freezing step to promote phase separation at low temperature. After defatting with hexane, sample extracts were evaporated and reconstituted before injection onto the LC-MS/MS system. The addition of oxalic acid in the aqueous mobile phase was mandatory to maintain good peak shape and sensitivity over the run. The screening is based upon a double preparation of each sample, one 'as such' and a second one with the analytes spiked in the sample, in order to mitigate the risk of false negative response. The method was validated according to the European Community Reference Laboratories Residues Guidelines. A total of 93 samples were included in the validation by two independent laboratories giving both false-negative and false-positive rates at 0% for all compounds. Over the last two years, 2600 samples were analysed routinely and only one chicken sample was found above the regulatory limit. | Tetracyclines |
To unveil the evolution of mitochondrial RNA editing in gymnosperms, we characterized mitochondrial genomes (mitogenomes), plastid genomes, RNA editing sites, and pentatricopeptide repeat (PPR) proteins from 10 key taxa representing four of the five extant gymnosperm clades. The assembled mitogenomes vary in gene content due to massive gene losses in Gnetum and Conifer II clades. Mitochondrial gene expression levels also vary according to protein function, with the most highly expressed genes involved in the respiratory complex. We identified 9132 mitochondrial C-to-U editing sites, as well as 2846 P-class and 8530 PLS-class PPR proteins. Regains of editing sites were demonstrated in Conifer II rps3 transcripts whose corresponding mitogenomic sequences lack introns due to retroprocessing. Our analyses reveal that non-synonymous editing is efficient and results in more codons encoding hydrophobic amino acids. In contrast, synonymous editing, although performed with variable efficiency, can increase the number of U-ending codons that are preferentially utilized in gymnosperm mitochondria. The inferred loss-to-gain ratio of mitochondrial editing sites in gymnosperms is 2.1:1, of which losses of non-synonymous editing are mainly due to genomic C-to-T substitutions. However, such substitutions only explain a small fraction of synonymous editing site losses, indicating distinct evolutionary mechanisms. We show that gymnosperms have experienced multiple lineage-specific duplications in PLS-class PPR proteins. These duplications likely contribute to accumulated RNA editing sites, as a mechanistic correlation between RNA editing and PLS-class PPR proteins is statistically supported. | RNA, Mitochondrial |
Enamel microabrasion is used to eliminate superficial enamel discoloration defects. This article presents a comprehensive review of the enamel microabrasion method and its results. Current technique and materials are described and six cases are used to illustrate various aspects of the procedure. The learning objective of this article is to familiarize the reader with the state-of-the-art of enamel microabrasion and to report the latest laboratory research in the field. | Dentifrices |
Endoscopic ultrasonography (EUS) has been widely used for evaluating the nature of diseases of various organs. The possibility of applying EUS for esophageal motility diseases has not been well discussed despite its versatility. At present, peroral endoscopic myotomy (POEM) for esophageal achalasia and related diseases has brought new attention to esophageal diseases because POEM provides a more direct approach to the inner structures of the esophageal wall. In the present study, we discuss the clinical utility of EUS in evaluating and treating esophageal motility diseases such as esophageal achalasia and related diseases. | Esophageal Achalasia |
Glutaric aciduria type I, an inherited deficiency of glutaryl-coenzyme A dehydrogenase localized in the final common catabolic pathway of L-lysine, L-hydroxylysine and L-tryptophan, leads to accumulation of neurotoxic glutaric and 3-hydroxyglutaric acid, as well as non-toxic glutarylcarnitine. Most untreated patients develop irreversible brain damage during infancy that can be prevented in the majority of cases if metabolic treatment with a low L-lysine diet and L-carnitine supplementation is started in the newborn period. The biochemical effect of this treatment remains uncertain, since cerebral concentrations of neurotoxic metabolites can only be determined by invasive techniques. Therefore, we studied the biochemical effect and mechanism of metabolic treatment in glutaryl-coenzyme A dehydrogenase-deficient mice, an animal model with complete loss of glutaryl-coenzyme A dehydrogenase activity, focusing on the tissue-specific changes of neurotoxic metabolites and key enzymes of L-lysine metabolism. Here, we demonstrate that low L-lysine diet, but not L-carnitine supplementation, lowered the concentration of glutaric acid in brain, liver, kidney and serum. L-carnitine supplementation restored the free L-carnitine pool and enhanced the formation of glutarylcarnitine. The effect of low L-lysine diet was amplified by add-on therapy with L-arginine, which we propose to result from competition with L-lysine at system y(+) of the blood-brain barrier and the mitochondrial L-ornithine carriers. L-lysine can be catabolized in the mitochondrial saccharopine or the peroxisomal pipecolate pathway. We detected high activity of mitochondrial 2-aminoadipate semialdehyde synthase, the rate-limiting enzyme of the saccharopine pathway, in the liver, whereas it was absent in the brain. Since we found activity of the subsequent enzymes of L-lysine oxidation, 2-aminoadipate semialdehyde dehydrogenase, 2-aminoadipate aminotransferase and 2-oxoglutarate dehydrogenase complex as well as peroxisomal pipecolic acid oxidase in brain tissue, we postulate that the pipecolate pathway is the major route of L-lysine degradation in the brain and the saccharopine pathway is the major route in the liver. Interestingly, treatment with clofibrate decreased cerebral and hepatic concentrations of glutaric acid in glutaryl-coenzyme A dehydrogenase-deficient mice. This finding opens new therapeutic perspectives such as pharmacological stimulation of alternative L-lysine oxidation in peroxisomes. In conclusion, this study gives insight into the discrepancies between cerebral and hepatic L-lysine metabolism, provides for the first time a biochemical proof of principle for metabolic treatment in glutaric aciduria type I and suggests that further optimization of treatment could be achieved by exploitation of competition between L-lysine and L-arginine at physiological barriers and enhancement of peroxisomal L-lysine oxidation and glutaric acid breakdown. | 2-Aminoadipate Transaminase |
Streptococcus bovis HC5 produces a broad spectrum lantibiotic (bovicin HC5), but S. bovis JB1 does not have antimicrobial activity. Preliminary experiments revealed an anomaly. When S. bovis JB1 cells were washed in stationary phase S. bovis HC5 cell-free culture supernatant, the S. bovis JB1 cells were subsequently able to inhibit hyper-ammonia producing ruminal bacteria (Clostridium sticklandii, Clostridium aminophilum and Peptostreptococcus anaerobius). Other non-bacteriocin producing S. bovis strains also had the ability to bind and transfer semi-purified bovicin HC5. Bovicin HC5 that was bound to S. bovis JB1 was much more resistant to Pronase E than cell-free bovicin HC5, but it could be inactivated if the incubation period was 24 h. Acidic NaCl treatment (100 mM, pH 2.0) liberates half of the bovicin HC5 from S. bovis HC5, but it did not prevent bovicin HC5 from binding to S. bovis JB1. Acidic NaCl liberated some bovicin HC5 from S. bovis JB1, but the decrease in activity was only 2-fold. Bovicin HC5 is a positively charged peptide, and the ability of S. bovis JB1 to bind bovicin HC5 could be inhibited by either calcium or magnesium (100 mM). Acidic NaCl-treated S. bovis JB1 cells were unable to accumulate potassium, but they were still able to bind bovicin HC5 and prevent potassium accumulation by untreated S. bovis JB1 cells. Based on these results, bovicin HC5 bound to S. bovis JB1 cells still acts as a pore-forming lantibiotic. | Streptococcus bovis |
There has been an explosive growth in the development of statistical methodology over the past several decades. Research in both medicine and public health, in which the involvement of biostatisticians has increased dramatically during this period, has been both a beneficiary of this new methodology as well as a source of new problems. The contributions of statistical methodology in design, implementation, and analysis as they relate to the role that biostatistics and biostatisticians now play in the field of medical research are addressed. We comment on: (1) the acceptance by the medical community that biostatistical concepts are an integral part of sound medical research; (2) the sometimes unrealistic expectations placed on biostatistics and biostatisticians given limited resources and/or limited control; (3) some controversies among biostatisticians; and (4) the need for emphasizing the design and implementation phases of medical investigations. | Biometry |
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