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Lymphangiosarcoma was seen in the subcutis of right chest in a 11-year-old female Poodle. No metastasis was observed clinically. Tumor cells were vimentin positive and formed irregular space or slit without erythrocytes in the tumor tissue. Lymphocytic foci and edema were seen in the stroma. Only a few tumor cells had factor VIII-related antigen. Electronmicroscopically, tumor cells did not accompany with basement membrane and intercellular junctional complex. | Lymphangiosarcoma |
OBJECTIVE: To establish whether karyometry was likely to detect change in the proportion of abnormal cells in random periareolar fine needle aspiration (RPFNA) specimens from high-risk women in a 6-month prevention trial with an aromatase inhibitor. STUDY DESIGN: Papanicolaou-stained ThinPrep slides of RPFNA samples from 11 of 42 women were digitally recorded at high resolution, with 200 cells measured per slide, at baseline (BL) and at the end of study (ES) after 6 months. The nuclear chromatin pattern characteristics were assessed by multivariate analytic techniques; determination of nuclear abnormalities was performed and cells that showed expression of abnormality were identified. RESULTS: The BL FNA samples contain approximately 90% cells with a chromatin pattern as expected in a normal cell population. A small subpopulation of cells had deviations from normal. At ES the proportion of these cells was reduced, to a statistically significant degree,from < 10% to 2-5%. CONCLUSION: Nuclear karyometry is a promising technique for characterizing the proportion of cells deviating from normal in cytologic specimens and should be explored further as an intermediate endpoint in prevention trials. | Karyometry |
Human immunodeficiency virus type 1 (HIV-1) needs to overcome cellular counter mechanisms such as to successfully propagate itself. Results of our recent studies show that overexpression of insulin-like growth factor II mRNA binding protein 1 (IMP1) inhibits production of infectious HIV-1 particles through adversely affecting virus maturation. Here, we report that IMP1 interacts with HIV-1 Rev protein and its ectopic expression causes relocation of Rev from the nucleus to the cytoplasm. In accordance with this observation, ectopic expression of IMP1 severely diminishes Rev-dependent expression of CAT enzyme and disturbs HIV-1 RNA expression by causing accumulation of the multiple spliced viral RNA. Results of mutagenesis analysis further reveal that the KH4 domain represents the key element of IMP1 in modulating HIV-1 RNA expression. Taken together, these data suggest, in addition to hampering virus assembly, that IMP1 also has an effect on Rev-dependent viral RNA expression." | rev Gene Products, Human Immunodeficiency Virus |
When compared to the approximately 22 other macaque species, Macaca arctoides has many unique phenotypes. These traits fall into various phenotypic categories, including genitalia, coloration, mating, and olfactory traits. Here we used a previously identified whole genome set of 690 outlier genes to look for possible genetic explanations of these unique traits. Of these, 279 genes were annotated miRNAs, which are non-coding. Patterns within the remaining outliers in coding genes were investigated using GO (n = 370) and String (n = 383) analysis, which showed many interconnected immune-related genes. Further, we compared the outliers to candidate pathways associated with M. arcotides' unique phenotypes, revealing 10/690 outlier genes that overlapped these four pathways: hedgehog signaling, WNT signaling, olfactory, and melanogenesis. Of these, genes in all pathways except olfactory had higher F(ST) values than the rest of the genes in the genome based on permutation tests. Overall, our results point to many genes each having a small impact on phenotype, working in tandem to cause large systemic changes. Additionally, these results may indicate pleiotropy. This seems to be especially true with the development and coloration of M. arctoides. Our results highlight that development, melanogenesis, immune function, and miRNAs may be heavily involved in M. arctoides' evolutionary history. | Macaca arctoides |
BACKGROUND: Pharyngoesophageal diverticula have many subtypes, with Zenker's diverticulum being the most common. First described in 1983, a Killian-Jamieson diverticulum is an outpouching in the anterolateral wall at the pharyngoesophageal junction. This is located inferiorly to the cricopharyngeus muscle, unlike Zenker's diverticula which occur superiorly. Killian-Jamieson diverticula are rare and are commonly misdiagnosed as Zenker's diverticula. Less than 30 reports of Killian-Jamieson diverticula have been described in the literature. CASE REPORT: A 69-year-old man presented with a 2-year symptomatic history, and was found to have simultaneous Zenker's diverticulum and Killian-Jamieson diverticulum. He was treated successfully with open surgical excision of both pouches. CONCLUSION: Zenker's diverticulum and Killian-Jamieson diverticulum are diagnosed using radiological studies and endoscopy. Their differentiation is important, as surgical management differs. This paper reviews the literature on Killian-Jamieson diverticula and the management options available. | Zenker Diverticulum |
BACKGROUND: Retinoblastoma (Rb) is a progressive cancer which mainly occurs in children, and which is caused by different genetic or epigenetic alterations that lead to inactivation of both alleles of the RB1 gene. Hereditary and non-hereditary forms of Rb do exist, and the hereditary form is associated with an increased risk of secondary malignancies. Metastasis to distant organs is a critical feature of many tumors, and may be caused by various molecular alterations at different stages. Recognition of these alterations and, thus, insight into the processes underlying the development of metastases may result in novel preventive as well as effective targeted treatment options. Rb is associated with metastases to various organs and tissues, including the bone marrow (BM). METHODS: Here, we provide an overview of mutations and other molecular changes known to be involved in Rb development and metastasis to the BM. This overview is based on a literature search ranging from 1990 to 2015. CONCLUSIONS: The various BM metastasis-related molecular changes identified to date may be instrumental for a better diagnosis, prognosis and classification of Rb patients, as well as for the development of novel comprehensive (targeted) therapies. | Genes, Retinoblastoma |
We describe a strategy for the mutagenesis of the free-living adult generation of Strongyloides ratti and selection of worms carrying new mutations in the subsequent F2 generation of infective larvae. We demonstrate that this strategy is successful via the selection of infective larvae that are resistant to the anthelmintic ivermectin at a concentration of 10 ng/ml. The majority of these larvae were unable to give rise to patent infections when used to infect parasite naive rats, implying that the majority of the ivermectin resistance mutations confer pleiotropic defects on parasitic, but not on free-living, development. | Strongyloides ratti |
Vitamin A is a fat-soluble micronutrient necessary for the growth of healthy skin and hair. However, both too little and too much vitamin A has deleterious effects. Retinoic acid and retinal are the main active metabolites of vitamin A. Retinoic acid dose-dependently regulates hair follicle stem cells, influencing the functioning of the hair cycle, wound healing, and melanocyte stem cells. Retinoic acid also influences melanocyte differentiation and proliferation in a dose-dependent and temporal manner. Levels of retinoids decline when exposed to ultraviolet irradiation in the skin. Retinal is necessary for the phototransduction cascade that initiates melanogenesis but the source of that retinal is currently unknown. This review discusses new research on retinoids and their effects on the skin and hair. | Carotenoids |
In this study, AB113 dye was successfully sequestered using a novel adsorbent made of mixed fish scales (MFS). The influence of adsorbent dosage, initial pH, temperature, initial concentration and contact time on the adsorption performance was investigated. The surface chemistry and morphology of the adsorbent were examined by FTIR, TGA and SEM. Amides, phosphate and carbonate groups were evidently responsible for the high affinity of MFS towards the dye. The adsorption equilibrium and kinetic were well described by Langmuir and pseudo-second-order models, respectively. The maximum adsorption capacities of MFS were 145.3-157.3mg/g at 30-50 degrees C. The adsorption of AB113 dye onto the adsorbent was exothermic and spontaneous as reflected by the negative enthalpy and Gibbs energy changes. The results support MFS asa potential adsorbent for AB113 dye removal. | Animal Scales |
The distribution of cancer antigen 125 (CA 125) has been investigated in normal tissues and carcinomas of the Mullerian duct by immunohistochemical methods using the monoclonal antibody OC 125. Detection of CA 125 was most intense in cryostat sections and decreased in formalin fixed and paraffin embedded tissues according to the duration of fixation. Enzymatic digestion with neuraminidase or alkaline hydrolysis abolished specific staining suggesting the antigen is a sialylsaccharide bound to protein by alkali-labile linkage. Immunohistochemical staining demonstrated the presence of CA 125 in all normal glandular epithelia of the endocervix, endometrium and fallopian tube in different distribution patterns. In normal endometrium the cellular distribution pattern was related to the menstrual cycle. In endocervical, endometrial and tubal adenocarcinomas CA 125 was found in 73% of cases. In glandular structures the antigen was concentrated at the luminal surface of the tumour cells, in solid tumour areas it was spread throughout the cytoplasm or concentrated in large cytoplasmic vacuoles. The expression of CA 125 was considerably lower in solid tumour areas. These data show that CA 125 is not a true tumour marker", but a product of female genital mucosae and of their cancerous derivates provided their synthesizing ability is not lost in the course of pathologic differentiation." | Genital Neoplasms, Female |
K(+) is the most abundant metal ion in cells, and changes of [K(+)] around cell membranes play important roles in physiological events. However, there is no practical method to selectively visualize [K(+)] at the surface of cells. To address this issue, we have developed a protein-coupled fluorescent probe for K(+), TLSHalo. TLSHalo is responsive to [K(+)] in the physiological range, with good selectivity over Na(+) and retains its K(+)-sensing properties after covalent conjugation with HaloTag protein. By using cells expressing HaloTag on the plasma membrane, we successfully directed TLSHalo specifically to the outer surface of target cells. This enabled us to visualize localized extracellular [K(+)] change with TLSHalo under a fluorescence microscope in real time. To confirm the experimental value of this system, we used TLSHalo to monitor extracellular [K(+)] change induced by K(+) ionophores or by activation of a native Ca(2+)-dependent K(+) channel (BK channel). Further, we show that K(+) efflux via BK channel induced by electrical stimulation at the bottom surface of the cells can be visualized with TLSHalo by means of total internal reflection fluorescence microscope (TIRFM) imaging. Our methodology should be useful to analyze physiological K(+) dynamics with high spatiotemporal resolution. | Potassium Ionophores |
The Authors report a case of diaphragmatic cyst. They remark the difficulty of clinical diagnosis and briefly discuss the hypothesis on its origin. | Subphrenic Abscess |
Entamoeba histolytica infection results in either asymptomatic colonization or invasion of host tissues leading generally to clinical symptoms. Zymodemes studies have demonstrated a correlation between isoenzyme profiles and clinical presentation. Thus, strains have been attributed to pathogenic or nonpathogenic groups according to their zymodeme. To determine the taxonomic relationship of these two groups, the isoenzyme profiles of 14 loci of 38 E. histolytica strains (pathogenic and nonpathogenic) and seven strains of other species of the same genus were analyzed. Genetic distance analysis clearly demonstrates the existence of two separate groups within the species E. histolytica. | Amoebozoa |
The cytoskeleton provides structural integrity to cells and serves as a key component in mechanotransduction. Tensins are thought to provide a force-bearing linkage between integrins and the actin cytoskeleton; yet, direct evidence of tensin's role in mechanotransduction is lacking. We here report that local force application to epithelial cells using a micrometer-sized needle leads to rapid accumulation of cten (tensin 4), but not tensin 1, along a fibrous intracellular network. Surprisingly, cten-positive fibers are not actin fibers; instead, these fibers are keratin intermediate filaments. The dissociation of cten from tension-free keratin fibers depends on the duration of cell stretch, demonstrating that the external force favors maturation of cten-keratin network interactions over time and that keratin fibers retain remarkable structural memory of a cell's force-bearing state. These results establish the keratin network as an integral part of force-sensing elements recruiting distinct proteins like cten and suggest the existence of a mechanotransduction pathway via keratin network. | Tensins |
BACKGROUND: We investigated the roles of stem cell factor (SCF)-c-kit and stromal derived factor-1 (SDF-1)-CXCR4 signaling axes in transmyocardial revascularization (TMR)-enhanced engraftment of transplanted bone marrow stem cells (BMSCs) in infarcted hearts. METHODS: 3 weeks after LAD ligation, female Lewis rats underwent 10-channel needle-TMR, followed by daily IV injections of 1 million male donor BMSC for 5 days, either wild type (WT) or with knockdown (K/D) of c-kit or CXCR4, accomplished via a shRNA + plasmid in a lentiviral vector (N = 6/group). RESULTS: In our rat infarct model, 3 days after last BMSC injection, the number of BMSCs that homed into infarct was affected by both TMR and donor cell type, with greater BMSC engraftment with TMR and with WT BMSC (TMR, cell type, and interaction, P < 0.05). At 1 week, these differences persisted (TMR and cell type, P < 0.05). At 3 days, TMR significantly upregulated transcription of c-kit (TMR, p < 0.05), SCF (TMR and cell type, P < 0.05), CXCR4 (TMR and cell type, p < 0.05), and SDF-1 (TMR and cell type, P < 0.05). At 1 week, we saw similar declines in expression of c-kit (cell type, P < 0.05), SCF (TMR, P < 0.05), CXCR4 (TMR and cell type, P < 0.05), and SDF-1 (TMR, P < 0.05). At 1 week, TMR improved LV ejection fraction (LVEF) (N = 5) when WT BMSCs were infused, but knockdown of either c-kit or CXCR4 completely abrogated this TMR-mediated augmentation of BMSC reparative effect (TMR and cell type, P < 0.05). CONCLUSIONS: Downregulation of either c-kit or CXCR4 in BMSC decreased engraftment of circulating BMSC and inhibited reparative effects of TMR." | Transmyocardial Laser Revascularization |
Zoonotic avian influenza viruses pose severe health threats to humans. Of several viral subtypes reported, the low pathogenic avian influenza H7N9 virus has since February 2013 caused more than 1,500 cases of human infection with an almost 40% case-fatality rate. Vaccination of poultry appears to reduce human infections. However, the emergence of highly pathogenic strains has increased concerns about H7N9 pandemics. To develop an efficacious H7N9 human vaccine, we designed vaccine viruses by changing the patterns of N-linked glycosylation (NLG) on the viral hemagglutinin (HA) protein based on evolutionary patterns of H7 HA NLG changes. Notably, a virus in which 2 NLG modifications were added to HA showed higher growth rates in cell culture and elicited more cross-reactive antibodies than did other vaccine viruses with no change in the viral antigenicity. Developed into an inactivated vaccine formulation, the vaccine virus with 2 HA NLG additions exhibited much better protective efficacy against lethal viral challenge in mice than did a vaccine candidate with wild-type (WT) HA by reducing viral replication in the lungs. In a ferret model, the 2 NLG-added vaccine viruses also induced hemagglutination-inhibiting antibodies and significantly suppressed viral replication in the upper and lower respiratory tracts compared with the WT HA vaccines. In a mode of action study, the HA NLG modification appeared to increase HA protein contents incorporated into viral particles, which would be successfully translated to improve vaccine efficacy. These results suggest the strong potential of HA NLG modifications in designing avian influenza vaccines." | Influenza A Virus, H7N9 Subtype |
An anaerobic, psychrophilic bacterium, strain MO-SPC2(T), was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediments collected from off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. Cells were pleomorphic: spherical, annular, curved rod, helical and coccoid cell morphologies were observed. Motility only occurred in helical cells. Strain MO-SPC2(T) grew at 0-17 degrees C (optimally at 9 degrees C), at pH 6.0-8.0 (optimally at pH 6.8-7.2) and in 20-40 g NaCl l(-1) (optimally at 20-30 NaCl l(-1)). The strain grew chemo-organotrophically with mono-, di- and polysaccharides. The major end products of glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. The abundant polar lipids of strain MO-SPC2(T) were phosphatidylglycolipids, phospholipids and glycolipids. The major cellular fatty acids were C14 : 0, C16 : 0 and C16 : 1omega9. Isoprenoid quinones were not detected. The G+C content of the DNA was 32.3 mol%. 16S rRNA gene-based phylogenetic analysis showed that strain MO-SPC2(T) was affiliated with the genus Sphaerochaeta within the phylum Spirochaetes, and its closest relatives were Sphaerochaeta pleomorpha Grapes(T) (88.4 % sequence identity), Sphaerochaeta globosa Buddy(T) (86.7 %) and Sphaerochaeta coccoides SPN1(T) (85.4 %). Based on phenotypic characteristics and phylogenetic traits, strain MO-SPC2(T) is considered to represent a novel species of the genus Sphaerochaeta, for which the name Sphaerochaeta multiformis sp. nov. is proposed. The type strain is MO-SPC2(T) ( = JCM 17281(T) = DSM 23952(T)). An emended description of the genus Sphaerochaeta is also proposed. | Spirochaetaceae |
OBJECTIVE: The purpose of this study was to evaluate the indications and limits for intraoperative proximal segment positioning control by mobile cone-beam computerized tomography (CBCT). STUDY DESIGN: For mandible osteotomy in orthognathic surgery, the high oblique sagittal split osteotomy (HSSO) is our standard procedure. In 22 patients, positioning control of the proximal segment was performed during and after surgery to check this alternative osteotomy technique. RESULTS: The mean intercondylar distance increased 0.31 mm in all patients. No significant change of the condyle positions was found in the axial and coronal planes. In the sagittal plane a significant change was found. In 1 case, revision was required because of a lateral shifting of the condyles. CONCLUSIONS: Intraoperative positioning control with CBCT is an effective and reliable method to avoid condyle malpositions. Only minor position changes occur when using HSSO in orthognathic surgery, without compromising temporomandibular joint function postoperatively." | Osteotomy, Sagittal Split Ramus |
PURPOSE: : The purpose of this article is to compare vision therapy/orthoptics, pencil pushups, and placebo vision therapy/orthoptics as treatments for symptomatic convergence insufficiency in adults 19 to 30 years of age. METHODS: : In a randomized, multicenter clinical trial, 46 adults 19 to 30 years of age with symptomatic convergence insufficiency were randomly assigned to receive 12 weeks of office-based vision therapy/orthoptics, office-based placebo vision therapy/orthoptics, or home-based pencil pushups. The primary outcome measure was the symptom score on the Convergence Insufficiency Symptom Survey. Secondary outcome measures were the near point of convergence and positive fusional vergence at near. RESULTS: : Only patients in the vision therapy/orthoptics group demonstrated statistically and clinically significant changes in the near point of convergence (12.8 cm to 5.3 cm, p = 0.002) and positive fusional vergence at near (11.3Delta to 29.7Delta, p = 0.001). Patients in all three treatment arms demonstrated statistically significant improvement in symptoms with 42% in office-based vision therapy/orthoptics, 31% in office-based placebo vision therapy/orthoptics, and 20% in home-based pencil pushups achieving a score <21 (our predetermined criteria for elimination of symptoms) at the 12-week visit. DISCUSSION: : In this study, vision therapy/orthoptics was the only treatment that produced clinically significant improvements in the near point of convergence and positive fusional vergence. However, over half of the patients in this group (58%) were still symptomatic at the end of treatment, although their symptoms were significantly reduced. All three groups demonstrated statistically significant changes in symptoms with 42% in office-based vision therapy/orthoptics, 31% in office-based placebo vision therapy/orthoptics, and 20% in home-based pencil push-ups meeting our criteria for elimination of symptoms. | Orthoptics |
The anatomy of the lower urinary tract and the structures that surround it play an important role in our understanding of the urinary continence mechanism. This article discusses the functional anatomy of this region as it relates to gynecologic urology. | Urinary Tract |
A preliminary study was performed on the feasibility and validity of objective categorization of patients into basic 'treatment types'. The Reflex Metrograph was used for a three-dimensional cast analysis, and an H.P. 9874 A digitizer was used for a two-dimensional radiograph analysis. In both measurement techniques the method error was found to be acceptable. Using the Ricketts 10 Factor Analysis, it was found that by means of 'Clinical deviators' radiographs could be used to distinguish orthognathic cases from the other treatment groups. The three-dimensional study cast analysis showed promise, distinguishing a number of statistically significant factors within the lower arch and between simple and fixed appliance cases. A number of variables which might have been expected to be significant were confounded by their range of values within the groups. Further investigation is required with an improved technique of initial categorization of patients, perhaps by means of a panel of clinicians, and more sophisticated statistical techniques. | Malocclusion |
Since the suggestion that the mental handicap branch of nursing be disbanded 21 years ago, these nurses have refocused their vision and emerged as a new and exciting specialism. This article relates their experiences to the key issues now confronting nursing in general, in a changing social and political context. | Specialties, Nursing |
In psychiatry, comparative analyses of therapeutic options and the aggregation of data from clinical trials across different therapeutic approaches play an important role in clinical decision making, treatment guidelines, and health policy. This approach assumes that trials of pharmacological and behavioural therapies generally produce the same level of evidence when properly designed. However, trial design for behavioural interventions has some unique characteristics and control groups vary widely, which influence the effects observed in any given trial. In this Personal View, we review various control conditions typically used in psychiatry, outline their effect on the internal validity and expected effect size of a trial, and propose a decision framework for choosing a control condition depending on the risk to the patient population and the stage of development of the therapeutic intervention. We argue that the choice of control group and its justification need to be taken into consideration when comparing behavioural and pharmacological therapies. | Control Groups |
Cells keep their proteome functional by the action of the proteostasis network, composed of the chaperones, the ubiquitin-proteasome system and autophagy. The decline of this network results in the accumulation of protein aggregates and is associated with aging and disease. In this Cell Science at a Glance and accompanying poster, we provide an overview of the molecular mechanisms of the removal of protein aggregates by a selective autophagy pathway, termed aggrephagy. We outline how aggrephagy is regulated by post-translational modifications and via auxiliary proteins. We further describe alternative aggrephagy pathways in physiology and their disruption in pathology. In particular, we discuss aggrephagy pathways in neurons and accumulation of protein aggregates in a wide range of diseases. Finally, we highlight strategies to reprogram aggrephagy to treat protein aggregation diseases. | Macroautophagy |
This author suggests that myopia is related to psychogenic factors involving an unconscious representation of, and defense against tension. Further, the argument is made that such tension directly causes the extra-ocular muscles of the eyeball to tighten, ultimately creating the errors of refraction, which define the condition known as myopia. The author makes the case that the specific nature of the tension has to do with an interruption in the separation-individuation process that has occurred, in which the myopic individual experiences separation anxiety, and is now required" to stay close to the mother for fear of abandonment. Apparently, the only way myopes are then able to achieve some sort of psychological distance is through the development of high-level abstract conceptualization abilities. In addition to separation fears, this author notes that myopes exhibit significantly higher levels of castration anxiety as compared with normal-sighted individuals, matched in IQ. Tables showing empirical findings supporting the above psychoanalytic interpretations are provided for the readers review." | Anxiety, Castration |
Sign language recognition is challenged by problems, such as accurate tracking of hand gestures, occlusion of hands, and high computational cost. Recently, it has benefited from advancements in deep learning techniques. However, these larger complex approaches cannot manage long-term sequential data and they are characterized by poor information processing and learning efficiency in capturing useful information. To overcome these challenges, we propose an integrated MediaPipe-optimized gated recurrent unit (MOPGRU) model for Indian sign language recognition. Specifically, we improved the update gate of the standard GRU cell by multiplying it by the reset gate to discard the redundant information from the past in one screening. By obtaining feedback from the resultant of the reset gate, additional attention is shown to the present input. Additionally, we replace the hyperbolic tangent activation in standard GRUs with exponential linear unit activation and SoftMax with Softsign activation in the output layer of the GRU cell. Thus, our proposed MOPGRU model achieved better prediction accuracy, high learning efficiency, information processing capability, and faster convergence than other sequential models. | Sign Language |
Frankia BCU110601 (Da) and Frankia BCU110345 (Dc) were isolated from root nodules of Discaria articulata and Discaria chacaye, respectively; Frankia BCU110501 (Dt) was previously isolated from Discaria trinervis. The strains were identical at the 16S sequence and after analysis of RFLP of 16S and 23S rDNA intergenic region. Diversity was revealed at the molecular level after fingerprint analysis by BOX-polymerase chain reaction. The strains were infective and effective on the original host plants. A cross-inoculation assay intra Discaria genus, including D. trinervis, D. articulata, and D. chacaye, with each of these isolated Frankia strains caused effective symbioses with a similar dry weight in each plant species regardless of the inoculated strain. Nevertheless, a differential degree of recognition was revealed: Homologous symbiotic pairs in the case of D. chacaye-Frankia BCU110345 (Dc), D. articulata-Frankia BCU110601 (Da), and D. trinervis-Frankia BCU110501 (Dt) had faster nodulation rates than heterologous pairs. The differences in nodulation rate would suggest the existence of a subspecific level of recognition within a certain cross-inoculation group, pointing to subspecific adaptation occurring in this actinorhizal symbiosis. | Frankia |
The exposed hydrophobic patches of protein are widely detected through the binding by the fluorescent probes such as 1-anilino-8-naphthalene sulfonate (ANS), Nile Red (NR) and 1-(N-phenylamino) naphthalene, N-(1-Naphthyl) aniline (1NPN). Interestingly, at pH4, where the Toxoplasma gondii Ferredoxin-NADP(+) reductase (TgFNR) is stable, an exclusive binding and fluorescence emission was observed for ANS. To understand the underlying difference in the binding of ANS, NR and 1NPN; their effect on the protein structure was studied in detail. ANS was found to interact with TgFNR via electrostatic as well as hydrophobic interactions at pH4. NR and 1NPN did not show any such binding to TgFNR in the similar conditions, however showed strong hydrophobic interaction in the presence of NaCl or DSS (2, 2-dimethyl-2-silapentane-5-sulfonate). The subsequent structural studies suggest that ANS, NaCl and DSS induced partial unfolding of TgFNR by modulating ionic interactions of the enzyme, leading to the exposure of buried hydrophobic patches amicable for the binding by NR and 1NPN. The induced unfolding of TgFNR by ANS is unique and thus cautions to use the fluorescent dye as simple indicator to probe the exposed hydrophobic patches of the protein or its folding intermediates. | Anilino Naphthalenesulfonates |
Desogestrel is a new, potent progestogen with very low androgenic properties. When used as a contraceptive, it is a strong antiovulatory compound, even at low doses. The clinical efficacy is as good as that of the old progestogens. It has a low incidence of side effects and complications, similar to other progestogens. It may have a role as an anti-androgen in women with hyperandrogenic symptoms in need of adequate oral contraception. | Progesterone Congeners |
Two novel Gram-stain-positive, aerobic, non-motile, and yellow-pigmented, irregular rod-shaped bacteria (JY.X269 and JY.X270(T)) were isolated from the near-surface sediments of river in Qinghai Province, P. R. China (32 degrees 37'13''N, 96 degrees 05'37''E) in July 2019. Both strains were shown to grow at 15-35 degrees C and pH 7.0-10.0, and in the presence of 0-6.0% (w/v) NaCl. The 16S rRNA gene sequence analysis showed that the isolates were closely related to Ornithinimicrobium cavernae CFH 30183( T) (98.6-98.8% 16S rRNA gene sequence similarity), O. ciconiae H23M54(T) (98.5-98.6%) and O. murale 01-Gi-040(T) (98.3-98.5%). The phylogenetic and phylogenomic trees based on the 16S rRNA gene and 537 core gene sequences, respectively, revealed that the two strains formed a distinct cluster with the above three species. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between our two isolates (JY.X269 and JY.X270(T)) and other Ornithinimicrobium species were within the ranges of 19.0-23.9% and 70.8-80.4%, respectively, all below the respective recommended 70.0% and 95-96% cutoff point. Furthermore, the major cellular fatty acids (> 10.0%) of strains JY.X269 and JY.X270(T) were iso-C(15:0), iso-C(16:0), and summed feature 9. Strain JY.X270(T) contained MK-8(H(4)) and ornithine as the predominant menaquinone and diagnostic diamino acid component within the cell wall teichoic acids. beta-cryptoxanthin (C(40)H(56)O) can be extracted from strain JY.X270(T), and its content is 6.3 microg/ml. Based on results from the phylogenetic, chemotaxonomic, and phenotypic analyses, the two strains could be classified as a novel species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium cryptoxanthini sp. nov. is proposed (type strain JY.X270(T) = CGMCC 1.19147(T) = JCM 34882(T)). | Beta-Cryptoxanthin |
BACKGROUND: Candida albicans is one of the microorganisms which harbor the oral cavity, especially in elderly. However, the incidence of existence of this increases in patients using removable dental prosthesis. There is therefore a need to test the anticandidal efficacy of these cost-effective, easily available products to be used as routine denture cleansers. AIM AND OBJECTIVES: (1) To evaluate antifungal properties of triphala churna on the heat cure denture base material. (2) To evaluate the antifungal effect of chlorhexidine gluconate on the heat cure denture base material. (3) To compare the antifungal effect of triphala churna and chlorhexidine gluconate with a control. (4) To evaluate which among triphala churna and chlorhexidine gluconate has a better antifungal property on the heat cure denture base material. MATERIALS AND METHODS: Study population consisted of sixty dentures wearers from those attending the Outpatient Department of Prosthodontics of the School of Dentistry, Krishna Institute of Medical Sciences Deemed University, Karad. Swabs were collected from the dentures before and after the use of triphala and chlorhexidine. The swabs were cultured on Sabouraud dextrose agar and the total Candida counts were determined. CONCLUSION: Triphala as an antifungal is shown to have more efficacy than the conventional chlorhexidine mouthwash. Resume Arriere-plan: Candida albicans est l'un des micro-organismes qui abritent la cavite buccale surtout chez les personnes agees. Cependant, l'incidence de l'existence de cette augmentation chez les patients utilisant des protheses dentaires amovibles. Il est donc necessaire de tester l'efficacite anticancedique de ces produits rentables et faciles a utiliser pour etre utilises comme nettoyants de routine pour protheses dentaires. Buts et Objectifs: (1) Evaluer les proprietes antifongiques de Triphala churna sur le materiau de base de la prothese thermo-durcissable. (2) Evaluer l'effet antifongique du gluconate de chlorhexidine sur le materiau de base de la prothese thermo-durcissable. (3) Comparer l'effet antifongique de Triphala churna et du gluconate de chlorhexidine avec un temoin. (4) Evaluer lequel parmi Triphala churna et le gluconate de chlorhexidine a une meilleure propriete antifongique sur le materiel de base de la prothese de durcissement a chaud. Materiaux et Methode: La population de l'etude etait constituee de soixante porteurs de protheses dentaires de ceux qui frequentaient le Departement de Prosthodontie de l'Ecole des Sciences Dentaires de l'Institut Krishna des Sciences Medicales de l'Universite de Karad. Des prelevements ont ete effectues sur les protheses avant et apres l'utilisation de Triphala et de chlorhexidine. On a cultive les ecouvillons sur de l'agar Sabouraud dextrose et on a determine le nombre total de candida. CONCLUSION: Triphala comme un anti fongique est demontre pour avoir plus d'efficacite que le lavage de la bouche classique chlorhexidine. | Denture Cleansers |
Concomitant with the increased prevalence of immunocompromised persons, invasive fungal infections have become considerably more frequent in the last 50 years. High mortality rates caused by invasive mycoses and high morbidity because of intractable mucosal infections have created an unmet need for innovative prophylactic and therapeutic strategies against fungal pathogens. Several immunotherapeutics and vaccines are in development to address this need, although one has yet to reach the clinic. This review focuses on past and current immunotherapeutic and vaccine strategies being tested to either prevent or treat fungal infections, as well as the challenges associated with their development. | Fungal Vaccines |
OBJECTIVE: To report the clinical experience and management of patients with small cell carcinoma (SCC) of the bladder, treated in the Anglia Cancer network from 1992 to 2007, and to review published studies, as SCC is a rare condition, accounting for <1% of all bladder tumours, and there is no established treatment strategy for managing these patients. PATIENTS AND METHODS: We analysed retrospectively data from all patients diagnosed with SCC of the urinary bladder between 1992 and 2007, with an emphasis on stage, treatment and overall survival. RESULTS: Twenty patients were identified with primary bladder SCC (male: female ratio 3:1; mean age 68 years; mean follow-up 15.8 months). Nine patients (45%) had extensive-stage disease at diagnosis. Four patients received best supportive care, three had a radical cystectomy, one radical radiotherapy and six sequential chemo-radiotherapy. In all, 13 patients were treated with chemotherapy, with six receiving cyclophosphamide, doxorubicin and vincristine, three receiving carboplatin and etoposide, and the remainder receiving alternative platinum-based regimens. For 12 patients with assessable disease, six had a complete response, three a partial response and three had progressive disease after chemotherapy. No patient received prophylactic cranial irradiation (PCI). At the time of analysis, 14 (70%) patients had died, with one (5%) developing brain metastasis. The median survival was 33 months for patients receiving chemotherapy, vs 3 months with no chemotherapy. CONCLUSIONS: SCC of the bladder tends to occur in an older population, more commonly in men. It is an aggressive tumour with a propensity for early metastasis. The response rate to chemotherapy is high but the overall prognosis is poor. Brain secondaries are less common than for SCC of the lung and currently the role of PCI is unclear. As there is no standard of care for these patients, they are treated according to local protocols. Further efforts should be made to develop more effective treatments and the role of PCI should be assessed in the setting of a clinical trial, in conjunction with other extrapulmonary SCCs. | Carcinoma, Small Cell |
OBJECTIVES: If patients are to reap the benefits of continued drug development, an understanding of why healthy participants take part in phase I clinical trials is imperative. The current study aimed to explore the nature of these underlying motivations which may, in turn, improve the overall participant experience and assist in the development of more effective recruitment and retention strategies. DESIGN: This study used a qualitative design based on the theory of planned behaviour. Specifically, it explored healthy participants' underlying behavioural, control and normative beliefs which influence their participation in phase I clinical trials. SETTING: This study took place at a company that specialises in conducting phase I and phase II clinical trials in the Australian state of Queensland. PARTICIPANTS: Participants (n=31) were either currently undergoing a phase I clinical trial or had previously taken part in a phase I clinical trial. RESULTS: Results showed that the motivations were varied and not solely centred on financial gains. Reported advantages of participation included altruism, while inconvenience was most often reported as a disadvantage. Friends were reported as those most likely to approve, while one's mother was reported as most likely to disapprove. Having a suitable time frame/flexible scheduling and feeling comfortable taking part in the trial were both the most commonly reported facilitators, while inflexible scheduling/time commitment was the most commonly reported barrier. CONCLUSIONS: Practical implications included the need for organisations involved in clinical trials to be mindful of inflexible scheduling and exploring the possibility of making educational materials available to family members who may be concerned about the risks associated with participation. Overall, it is anticipated that the results of this study will improve the understanding of factors that influence phase I clinical trial participation which may, ultimately, help develop new therapeutics to improve patient health. | Remuneration |
Co-culture conditions for Duboisia myoporoides-D. leichhardtii hybrid hairy root induction were investigated using leaf explants and Agrobacterium rhizogenes ATCC 15834. The bacteria density and duration of co-culture greatly affected the induction rate; the highest rate of 50% was obtained when the leaf explants were co-cultured for 2 d with 10(6) bacteria. One hairy root clone that showed the fastest root growth was selected and used for comparison study with adventitious roots cultured with 0.5 mg/l indole-3-acetic acid (IAA). The hairy roots cultured in Murashige and Skoog (MS) liquid medium grew well and yielded much more tropane alkaloids (35 mg/l scopolamine and 17 mg/l hyoscyamine) than adventitious roots cultured in 0.5 mg/l IAA after 6 weeks of culture at 25 degrees C in the dark. The hairy and adventitious roots (2.5 cm) grown in liquid media were divided into 5 parts (each 0.5 cm) along the root axis. Distribution of scopolamine and IAA was then determined by enzyme-linked immunosorbent assay (ELISA). Inverse relationship between contents of scopolamine and IAA was observed in the hairy roots; increase of scopolamine and decrease of IAA were proportional to the distance from the root meristem. In contrast, the contents of scopolamine and IAA were relatively constant in the adventitious roots. In shoot regeneration experiments, the hairy and adventitious root segments (1 cm) were placed onto 1/2 MS solid medium containing various concentrations of IAA and BA cultured at 25 degrees C under 16 h light. In adventitious roots, the shoots regenerated on media containing 6-benzyladenine (BA) (0.5 to 5 mg/l), and 100% regeneration was observed in medium with 0.1 mg/l IAA and 2 mg/l BA. On the other hand, shoot regeneration was only observed in 33% of hairy roots cultured on medium containing 5 mg/l BA. | Duboisia |
The aim of this research was to explore the acceptability of care delegation in skill-mix, using the views and experiences of patients and parents of children treated by dental therapists as a case study. A purposive sample of 15 adults whose care, or that of their children, had been delegated to dental therapists in English dental practices was interviewed using narrative and ethnographic techniques (July 2011 - May 2012). Experiences were overwhelmingly positive with the need for trust in clinicians and the health system emerging as a key factor in its acceptability. Perceptions of general and dental health services ranged from them being a collectivist public service to a more consumerist marketised service, with the former seemingly associated with notions of dentistry as a trusted system working for the social good. Interpersonal trust appeared built, sustained (and undermined) by the affective behaviour, perceived competence, and continuity of care with clinicians providing care, and contributed to trust in the system. It also appeared to compensate for gaps in knowledge needed for patient decision-making. Overall, where trust existed, delegation of care was acceptable. An increasingly marketised health system, and emphasis on the patient as a consumer, may challenge trust and acceptability of delegation, and undermine the notion of patient-centred health care. | Delegation, Professional |
BACKGROUND: Acanthocephalosis is an important cause of death in captive New World primates (NWP). Once established in a colony, it is extremely difficult to treat and control, quickly spreading among NWP with a high mortality rate. This study aimed to characterize the disease associated with infection with acanthocephalans according to its epidemiological, clinical, and anatomopathological aspects in a captive NWP population. METHODS: From 2010 to 2020, a Brazilian zoo had recurrent deaths of NWP associated to acanthocephalan parasitism. Clinical and pathological profiles of these animals were analyzed considering the host species, sex, age, weight, clinical signs, therapeutic protocols, and pathological findings. RESULTS: A total of 27 deaths associated with acanthocephalosis were recorded, all lethal cases affected tamarins and lion tamarins, corresponding to 67.5% of total deaths during the course of this study. Ten animals died with no previously detected clinical signs, whereas cases with noticeable clinical signs often had apathy and progressive weight loss, resulting in cachexia. Symptomatic NWP were treated with anthelmintic protocols, antibiotics, and support therapy. However, all hospitalized animals died and had grossly detectable adult acanthocephalans in the intestinal lumen that were identified as Prosthenorchis sp., which were associated with transmural and ulcerative enteritis. CONCLUSIONS: This report revealed the impact of acanthocephalosis in a naturally infected captive colony of NWP, particularly affecting tamarins (Saguinus spp.) and lion tamarins (Leontopithecus spp.), with failed treatment and control strategies. | Platyrrhini |
BACKGROUND: Double-outlet right ventricle (DORV) with a restrictive ventricular septum is a rare but highly morbid phenomenon that can be complicated by progressive left ventricular hypertrophy, arrhythmias, aneurysm formation, severe pulmonary hypertension, and death in the newborn. Surgical creation or enlargement of a ventricular septal defect (VSD) is palliative but may damage the conduction system or the atrioventricular valves in the newborn. This report presents a transcatheter approach to palliation for a newborn that had DORV with a restrictive ventricular septum. METHODS/RESULTS: A full-term infant girl (2.9 kg) referred for hypoxia (80% with room air) and murmur was found to have DORV, interrupted inferior vena cava, and restrictive VSD (95-mmHg gradient). Transhepatic access was performed, and an internal mammary (IM) catheter was advanced through the atrial septal defect and into the left ventricle. By transesophageal echocardiographic guidance, a Baylis radiofrequency perforation wire was used to cross the ventricular septum, and the defect was enlarged using a 4-mm cutting balloon. A bare metal stent then was deployed to maintain the newly created VSD. The patient did well after the procedure but required pulmonary artery banding 4 days later. She returned 5 months later with cyanosis and the development of obstructing right ventricle muscle bundles, requiring further surgical palliation. CONCLUSIONS: This report describes the first transcatheter creation of VSD in DORV with a restrictive ventricular septum in a newborn infant. Use of the radiofrequency catheter in combination with cutting balloon dilation and stent implantation is an efficient method for creating a VSD in such a patient. | Double Outlet Right Ventricle |
We present an account of Rhizopogon introduced from plantings of exotic pine plantations in Argentine Patagonia. Nuc rDNA internal transcribed spacer ITS1-5.8S-ITS2 (ITS) and nuc 28S rDNA (28S) sequences were used to identify specimens from Argentina and examine their relationships with geographically different Rhizopogon species. Based on phylogenetic analyses, we confirm that four species of Rhizopogon occur in pine plantations across Patagonia. Several Rhizopogon collections from Pinus ponderosa plantations across different provinces cluster with R. arctostaphyli, a species within R. subg. Amylopogon. The majority of Patagonian Rhizopogon, however, form three different lineages in R. subg. Roseoli. The first of these, R. roseolus sensu Trappe, includes numerous collections from Pinus ponderosa, P. contorta, and P. radiata stands of North American affiliation. The second, R. roseolus sensu Martin and Garcia from P. ponderosa plantations, clusters in clade IIIa of the R. roseolus complex, which also includes the holotype collection of R. mohelnensis from the Czech Republic. The third species in R. subg. Roseoli, and fourth species overall from Patagonia, is R. granuloflavus from Pinus ponderosa plantations. Multiplex polymerase chain reaction (PCR) of numerous Roseoli samples failed to produce an amplicon indicative of either Japanese or New Zealand shoro. | Pinus ponderosa |
High-throughput, human cell-based applications of RNA-mediated interference (RNAi) have emerged in recent years as perhaps the most powerful of a 'second wave' of functional genomics technologies. The available reagents and methodologies for RNAi screening studies now enable a wide range of different scopes and scales of investigation, from single-parameter assays applied to focused subsets of genes, to comprehensive genome-wide surveys based on rich, multiparameter readouts. As such, RNAi-based screens are offering important new avenues for the discovery and validation of novel therapeutic targets for several disease areas, including oncology. By enabling a 'clean' determination of gene function, that is the creation of direct causal links between gene and phenotype in human cells, RNAi investigations promise levels of pathophysiological relevance, efficiency, and range of applicability never before possible on this scale. The field of oncology, with its many assays using readily transfectable cell lines, has offered particularly fertile ground for showcasing the potential of RNAi-based genomics. However, like any other technology before it, RNAi is not without its own challenges, limitations, and caveats. Many of these issues stem directly from the choice of silencing reagent to be used in such studies, and the design of the overall screening strategy. Here, we discuss the basic design issues, potential advantages, and technical challenges of large-scale RNAi screens based on the use of chemically synthesized siRNA libraries. | RNA Interference |
An anaerobic, mesophilic, syntrophic benzoate-degrading bacterium, designated strain FB(T), was isolated from methanogenic sludge which had been used to treat wastewater from the manufacture of terephthalic acid. Cells were non-motile gram-positive rods that formed spores. The optimum temperature for growth was 35-40 degrees C, and the optimum pH was 7.0-7.2. A co-culture with the hydrogenotrophic methanogen Methanospirillum hungatei converted benzoate to acetate, carbon dioxide, and methane. Butyrate transiently accumulated at a high concentration of 2.5 mM during degradation. Besides benzoate, no other compound tested supported growth of the co-culture. Crotonate supported growth of strain FB(T) in pure culture. Furthermore, the strain degraded benzoate in pure culture with crotonate as co-substrate to produce acetate and butyrate. The strain was not able to utilize sulfate, sulfite, thiosulfate, nitrate, fumarate, or Fe(III) as electron acceptor. The G+C content of the DNA was 46.8 mol%. Strain FB(T) contained MK-7 as the major quinone and C(16:1) as the major fatty acid. 16S rDNA sequence analysis revealed that the strain was a member of the genus Sporotomaculum, even though it exhibited significant differences, such as the capacity for syntrophic growth, to the known member of the genus. Hence, we propose the name Sporotomaculum syntrophicum sp. nov. for strain FB(T). The type strain is strain FB(T) (DSM 14795, JCM 11475). | Methanospirillum |
The ability to regulate cellular gene expression is a key aspect of the lifecycles of a diverse array of viruses. In fact, viral infection often results in a global shutoff of host cellular gene expression; such inhibition serves not only to ensure maximal viral gene expression without competition from the host for essential machinery and substrates but also aids in evasion of immune responses detrimental to successful viral replication and dissemination. Within the herpesvirus family, host shutoff is a prominent feature of both the alpha- and gamma-herpesviruses. Intriguingly, while both classes of herpesviruses block cellular gene expression by inducing decay of messenger RNAs, the viral factors responsible for this phenotype as well as the mechanisms by which it is achieved are quite distinct. However, data suggest that the host shutoff functions of alpha- and gamma-herpesviruses are likely achieved both through the activity of virally encoded nucleases as well as via modulation of cellular RNA degradation pathways. This review highlights the processes governing normal cellular messenger RNA decay and then details the mechanisms by which herpesviruses promote accelerated RNA turnover. Parallels between the viral and cellular degradation systems as well as the known interactions between viral host shutoff factors and the cellular RNA turnover machinery are highlighted. | Herpesviridae |
It has been widely demonstrated that G protein-coupled receptors (GPCRs) can form dimers both in vivo and in vitro, a process that has functional consequences. These receptor-receptor interactions take place within a phospholipid bilayer, yet, generally, little is known of the requirements for specific lipids that mediate the dimerization process. Studying this phenomenon in vivo is challenging due to difficulties in modulating the lipid content of cell membranes. Therefore, in this chapter, we describe techniques for reconstitution of GPCRs into model lipid bilayers of defined composition. The concentrations of specific lipids and sterols can be precisely controlled in these liposomes, as well as maintaining an appropriate lipid-protein ratio to avoid artifactual interactions. Receptor dimerization in this system is monitored via Forster resonance energy transfer (FRET), which requires the use of fluorescently labeled receptors. We therefore also include protocols for labeling with appropriate fluorophores and determining the apparent FRET efficiency, a measurement of the extent of receptor dimerization. Understanding the lipid dependence of GPCR dimerization will be key in understanding how this process is regulated in the dynamic heterogeneous environment of the cell membrane. | Receptors, Neurotensin |
In the present study, the progression of gait impairment in a group of patients with primary degenerative cerebellar ataxias was observed over a period of 4 years. A total of 30 patients underwent an initial gait analysis study, and thereafter only 12 were evaluated because they completed the 2- and 4-year follow-up evaluations. Time-distance parameters, trunk and joint range of motion (RoM), and variability parameters (e.g., coefficients of variation) were measured at the baseline and at each follow-up evaluation. The scale for the assessment and rating of ataxia (SARA) was used to evaluate disease severity. We found a significant increase in the SARA score at both the 2- and 4-year follow-up evaluations. Almost all the gait variables changed significantly only at the 4-year follow-up. Particularly, we found a significant decrease in the step length and in the hip, knee, and ankle joint RoM values and noted a significant increase in the trunk rotation RoM and stride-to-stride and step length variability. Furthermore, a significant difference in ankle joint RoM was found between spinocerebellar ataxia and sporadic adult-onset ataxia patients, with the value being lower in the former group of patients. Our findings suggest that patients with degenerative cerebellar ataxias exhibit gait decline after 4 years from the baseline. Moreover, patients try to maintain an effective gait by adopting different compensatory mechanisms during the course of the disease in spite of disease progression. | Gait Ataxia |
The efficacy of using complementary and alternative medicine (CAM) is supported by the literature to decrease preoperative anxiety, postoperative pain and opioid requirements, as well as nausea and vomiting and to improve severity of headaches and increase wound healing. Nursing care includes interventions using CAs for treatment of a range of patient needs. Being supportive while educating parents and patients demonstrates altruism, which also is beneficial for improving health outcomes with CAM. | Perioperative Care |
ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Bl. (GE) is one of the rare Chinese medicinal materials with a long history of medicine and cooking. It consists of a variety of chemical components, including aromatic compounds, organic acids and esters, steroids, saccharides and their glycosides, etc., which has medicinal and edible value, and is widely used in various diseases, such as infantile convulsions, epilepsy, tetanus, headache, dizziness, limb numbness, rheumatism and arthralgia. It is also commonly used in health care products and cosmetics. Thus, its chemical composition and pharmacological activity have attracted more and more attention from the scientific community. AIM: In this review, the processing methods, phytochemistry and pharmacological activities of GE were comprehensively and systematically summarized, which provides a valuable reference for researchers the rational of GE. MATERIALS AND METHODS: A comprehensive search of published literature and classic books from 1958 to 2023 was conducted using online bibliographic databases PubMed, Google Scholar, ACS, Science Direct Database, CNKI and others to identify original research related to GE, its processing methods, active ingredients and pharmacological activities. RESULTS: GE is traditionally used to treat infantile convulsion, epilepsy, tetanus, headache, dizziness, limb numbness, rheumatism and arthralgia. To date, more than 435 chemical constituents were identified from GE including 276 chemical constituents, 72 volatile components and 87 synthetic compounds, which are the primary bioactive compounds. In addition, there are other biological components, such as organic acids and esters, steroids and adenosines. These extracts have nervous system and cardiovascular and cerebrovascular system activities such as sedative-hypnotic, anticonvulsant, antiepileptic, neuron protection and regeneration, analgesia, antidepressant, antihypertensive, antidiabetic, antiplatelet aggregation, anti-inflammatory, etc. CONCLUSION: This review summarizes the processing methods, chemical composition, pharmacological activities, and molecular mechanism of GE over the last 66 years, which provides a valuable reference for researchers to understand its research status and applications. | Gastrodia |
Quantification of protein binding to membrane proteins is challenging and a limited set of methods is available to study such systems. Here we employed backscattering interferometry (BSI), a free-solution label-free method with high sensitivity, to quantify the interaction of neuronal Ca(2+)-Sensor proteins with their targets operating in phototransduction. We tested direct binding of guanylate cyclase-activating proteins (GCAP1 and GCAP2) to their membrane target guanylate cyclase 1. The regulatory mechanism of GCAPs including their binding interface in the target is unresolved. Here we used a label-free, free-solution assay method based on BSI to determine binding constants of GCAP1 and GCAP2 to the full-length membrane-bound guanylate cyclase type 1. GCAP1 and GCAP2 bound to different regions on the target guanylate cyclase with submicromolar affinity (apparent K(D)-values of 663 +/- 121 nM and 231 +/- 63 nM for Ca(2+)-free GCAP1 and GCAP2, respectively). A guanylate cyclase construct containing the juxta-membrane and kinase homology domain harbored an exclusive binding site for GCAP1 with similar affinities as the full-length protein, whereas GCAP2 did not bind to this region. We provide a model in which GCAP1 and GCAP2 do not share a single binding site to the target, thus cannot exchange upon fluctuating Ca(2+) levels." | Guanylate Cyclase-Activating Proteins |
PURPOSE: Glaucoma is a worldwide leading cause of irreversible blindness. Standard treatments lower intraocular pressure (IOP). Novel treatments to prevent optic nerve (ON) degeneration are needed. Here, we investigate the hypothesis that sigma-1 receptor (S1R) agonist (+)-pentazocine (PTZ) is neuroprotective in a Brown Norway (BN) rat, microbead model of glaucoma. METHODS: BN rats (9-11 weeks, male and female) were treated by intraperitoneal injection, 3 times per week with (+)-PTZ (2 mg/kg) or vehicle (VEH) alone. Treatment started 1 week prior to intraocular injection of polystyrene microbeads to elevate IOP. IOP was measured 2-3 times per week. Five weeks post microbead injection, rats were euthanized. ONs were removed, then fixed and processed for 63x oil, light microscope imaging of toluidine blue stained ON cross sections. To facilitate comparison of ON morphology from VEH and (+)-PTZ treated rats with similar ocular hypertensive insults, rats were assigned to low (IOP </=15.8 mmHg), moderate (15.8 < IOP <28.0 mmHg), and high (IOP >/=28.0 mmHg) groups based on average IOP in the microbead injected eye. Axon numbers, axon density, axonal and glial areas, axon loss, and axon size distributions of naive, bead, and contralateral ONs were assessed using QuPath program for automated image analysis. RESULTS: (+)-PTZ treatment of BN rats protected ONs from damage caused by moderate IOP elevation. Treatment with (+)-PTZ significantly reduced axon loss and glial areas, and increased axon density and axonal areas compared to ONs from VEH treated rats with moderate IOP. (+)-PTZ-mediated neuroprotection was independent of IOP lowering effects. At average IOP >/=28.0 mmHg, (+)-PTZ treatment did not provide measurable neuroprotection. ONs from contralateral eyes exhibited subtle, complex changes in response to conditions in the bead eyes. CONCLUSIONS: S1R agonist (+)-PTZ shows promise as a neuroprotective treatment for glaucoma. Future studies to understand the complex molecular mechanisms by which (+)-PTZ provides this neuroprotection are needed. | Rats, Inbred BN |
BACKGROUND: Exercise rehabilitation is demonstrated to improve the prognosis of patients with coronary heart disease (CHD). Statins, as the key medicine to lower cholesterol in CHD, result in skeletal muscle injury and impair exercise training adaptation. Energy metabolism dysfunction is identified as the potential mechanism underlying statin-induced skeletal muscle injury. In this study, we investigated the effects of the metabolic modulator trimetazidine on skeletal muscle energy metabolism and statin-associated exercise intolerance. METHODS: High-fat fed apolipoprotein E knockout (ApoE(-/-) ) mice were given aerobic exercise and administrated simvastatin, trimetazidine, or simvastatin plus trimetazidine by gavage. Exercise capacity was evaluated at the end of the treatment by hanging grid test, forelimb grip strength, and running tolerance test. Plasma glucose, lipid, and creatine kinase concentrations were measured at the end of the treatment. After sacrifice, gastrocnemii were stored for assessment of muscle morphology and fibre type. Energy metabolism was estimated by plasma lactic acid concentration, ragged red fibres, and glycogen stores. Activities of mitochondrial complex III, citrate synthase activity, and membrane potential were measured to assess mitochondrial function. Oxidative stress was also evaluated by superoxide in mitochondria, superoxide dismutase activity, and glutathione redox state. RESULTS: In high-fat fed ApoE(-/-) mice, exercise training had no effect on lipid concentrations. Lower lipid concentrations with increased creatine kinase were observed with additional simvastatin treatment. Exercise capacity increased significantly in response to exercise training alone but was blunted by the addition of simvastatin. Similarly, cross-sectional area of muscle fibres and the proportion of slow-twitch fibres increased in the exercise group but decreased in the simvastatin plus exercise group. Additionally, simvastatin increased centronucleated fibres and induced energy metabolism dysfunction by inhibiting complex III activity and thus promoted oxidative stress in gastrocnemius. We demonstrated that trimetazidine could reverse simvastatin-induced exercise intolerance and muscle damages. We also found the ability of trimetazidine in restoration of muscle fibre hypertrophy and facilitating fast-to-slow type shift. The energy metabolism dysfunction and oxidative stress in gastrocnemii were rescued by trimetazidine. CONCLUSIONS: Trimetazidine alleviated statin-related skeletal muscle injury by restoration of oxidative phenotype and increasing fibre cross-sectional areas in response to exercise training. Correspondingly, the exercise training adaptation were improved in high-fat fed ApoE(-/-) mice. Moreover, trimetazidine is able to exert its positive effects without affecting the beneficial lipid-lowering properties of the statins. Thus, trimetazidine could be prescribed to remedy the undesirable statins-induced exercise intolerance during cardiac rehabilitation in patients with CHD. | Trimetazidine |
In 2011, recommendations for a multidisciplinary classification of lung adenocarcinoma were published under the auspices of the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society. The review was considered necessary due to emerging data on the radiological features, genetics and therapeutic approaches to lung adenocarcinoma, all underpinned by expanding the knowledge of the pathology of this common tumour. The existing WHO classification of 2004 was not really fit for this multidisciplinary focus on the disease. This review describes the recommendations made on the reporting of surgically resected lung cancers according to their predominant pattern, and argues the case for replacing the term bronchioloalveolar carcinoma (WHO 1999 and 2004 definition) with adenocarcinoma in situ and for the introduction of minimally invasive adenocarcinoma. There is also a discussion of diagnosis of non-small-cell lung carcinomas in the small biopsy or cytology setting, a practice that was inadequately addressed in WHO 2004, yet this is much more relevant to most pathologists' daily practice because 85% or so of adenocarcinomas are never resected. Predictive immunohistochemistry, used correctly, can reduce non-specific diagnosis to less than 10% of the cases. Finally, there is an overview of the emerging data on therapeutically relevant lung adenocarcinoma genetics, considering targetable mutations that are now the focus of much activity. The clinical relevance of these changes is discussed." | Adenocarcinoma, Bronchiolo-Alveolar |
This review is based on the results of 308 operations for unexplained, chronic groin pain suspected to be caused by an imminent, but not demonstrable, inguinal hernia: the 'sportsman's hernia' (SH). No differences in perioperative findings between cured and non-cured athletes were found. However, there was a remarkable difference between the various perioperative findings in the studies. It was characteristic that further clinical investigation of the noncured, operated athletes gave an alternative and treatable diagnosis in more than 80% of cases. Herniography was used consistently in the diagnostic process in all the studies on SH. However, in 49% of cases hernias were also demonstrated on the opposite, asymptomatic groin side. In conclusion, the final diagnosis (and treatment) often reflects the speciality of the doctor and the present literature does not supply proper evidence to the theory that SH constitutes a credible explanation for chronic groin pain. | Hernia, Inguinal |
BACKGROUND: To describe the clinical, radiologic, and histopathologic aspects of cystic lung disease occurring in patients with Birt-Hogg-Dube (BHD) syndrome, a rare, inheritable, multisystem disorder. METHODS: We retrospectively reviewed five patients with BHD syndrome evaluated at the Mayo Clinic Rochester from 1998 through 2005. RESULTS: Mean age (+/- SD) at the time of pulmonary evaluation was 56.4 +/- 4.8 years; four patients were men. Three patients had not received a diagnosis of BHD syndrome at the time of initial CT of the chest. Three patients had a smoking history, and two were nonsmokers. Two patients had a history of recurrent pneumothoraces. Pulmonary function tests available in four patients revealed normal results in one patient and mild airflow obstruction or nonspecific pattern of abnormalities in three patients. CT of the chest revealed cystic lung disease in all five patients; cysts were round to oval in shape, ranged widely in size, and were randomly distributed throughout the lungs, except for a predilection to involve the lung bases more extensively. Three patients with a smoking history had more severe cystic changes compared to nonsmokers and included both patients with recurrent pneumothoraces. Surgical lung biopsy available in one patient revealed emphysema-like changes. Follow-up CT scans available in four patients revealed relative stability over a median interval of 20 months (range, 3 to 66 months). CONCLUSION: We conclude that cystic lung disease in BHD syndrome varies widely in severity, mimics pulmonary lymphangioleiomyomatosis, and may be worsened by smoking. | Hamartoma Syndrome, Multiple |
BACKGROUND: The study objective was to develop a profile of characteristics and diagnostic indicators of agenesis of the corpus callosum (ACC) using a large sample of individuals with ACC and their siblings. Very few previous studies have been able to access large populations in order to develop a comprehensive profile. METHODS: Caregivers of 720 individuals with ACC and 219 siblings, the largest sample studied to date, provided surveys with data on diagnoses, physical characteristics, developmental patterns and physical functioning. RESULTS: Compared with siblings, individuals with ACC exhibited a pattern of delayed motor development, difficulty with balance and bimanual movements, large head size, poor muscle tone, poor depth perception, reduced pain perception, sleeping difficulties and an increased proportion of left and mixed handedness. CONCLUSIONS: These results extend previous descriptions but are also consistent with published reports that used small samples and single case studies. The data provide a profile that has implications for early detection and intervention of individuals with ACC as well as for highlighting future research directions to extend knowledge about ACC. | Acrocallosal Syndrome |
NRH:quinone oxidoreductase 2 (NQO2) is a flavoprotein that protects cells against radiation and chemical-induced oxidative stress. Disruption of the NQO2 gene in mice leads to gamma radiation-induced myeloproliferative diseases. In this report, we showed that the 20 S proteasome and NQO2 both interact with myeloid differentiation factor CCAAT-enhancer-binding protein alpha (C/EBPalpha). The interaction of the 20 S proteasome with C/EBPalpha led to the degradation of C/EBPalpha. NQO2, in the presence of its cofactor NRH, protected C/EBPalpha against 20 S degradation. Deletion and site-directed mutagenesis demonstrated that NQO2 and 20 S competed for the same binding region of S(268)GAGAGKAKKSV(279) in C/EBPalpha. Exposure of mice and HL-60 cells to gamma radiation enhanced the levels of NQO2, which led to an increased NQO2 interaction with C/EBPalpha and decreased 20 S interaction with C/EBPalpha. NQO2 stabilization of C/EBPalpha was independent of NQO1, even though both interacted with the same C/EBPalpha domain. NQO2(-/-) mice, deficient in NQO2, failed to stabilize C/EBPalpha. This contributed to the development of gamma radiation-induced myeloproliferative disease in NQO2(-/-) mice." | CCAAT-Enhancer-Binding Protein-alpha |
Bougainvillea L. (Nyctaginaceae) is a South American native woody flowering shrub of high ornamental, economic, and medicinal value which is susceptible to cold damage. We sequenced the complete chloroplast (cp) genome of B. glabra and B. spectabilis, two morphologically similar Bougainvillea species differing in cold resistance. Both genomes showed a typical quadripartite structure consisting of one large single-copy region, one small single-copy region, and two inverted repeat regions. The cp genome size of B. glabra and B. spectabilis was 154,520 and 154,542 bp, respectively, with 131 genes, including 86 protein-coding, 37 transfer RNA, and 8 ribosomal RNA genes. In addition, the genomes contained 270 and 271 simple sequence repeats, respectively, with mononucleotide repeats being the most abundant. Eight highly variable sites (psbN, psbJ, rpoA, rpl22, psaI, trnG-UCC, ndhF, and ycf1) with high nucleotide diversity were identified as potential molecular markers. Phylogenetic analysis revealed a close relationship between B. glabra and B. spectabilis. These findings not only contribute to understanding the mechanism by which the cp genome responds to low-temperature stress in Bougainvillea and elucidating the evolutionary characteristics and phylogenetic relationships among Bougainvillea species, but also provide important evidence for the accurate identification and breeding of superior cold-tolerant Bougainvillea cultivars. | Nyctaginaceae |
Cell-free systems are widely used to study mechanisms and regulation of translation, but the use of in vitro transcribed (IVT) mRNAs as translation substrates limits their efficiency and utility. Here, we present an approach for in vitro translation of messenger ribonucleoprotein (mRNP) complexes affinity purified in association with tagged mRNAs expressed in mammalian cells. We show that in vitro translation of purified mRNPs is much more efficient than that achieved using standard IVT mRNA substrates and is compatible with physiological ionic conditions. The high efficiency of affinity-purified mRNP in vitro translation is attributable to both copurified protein components and proper mRNA processing and modification. Further, we use translation inhibitors to show that translation of purified mRNPs consists of separable phases of run-off elongation by copurified ribosomes and de novo initiation by ribosomes present in the translation extracts. We expect that this in vitro system will enhance mechanistic studies of eukaryotic translation and translation-associated processes by allowing the use of endogenous mRNPs as translation substrates under physiological buffer conditions. | Ribonucleoproteins |
The concentrations and fluxes of airborne phthalates were measured from five types of polyvinyl chloride (PVC) consumer products (vinyl flooring, wallcovering, child's toy, yoga mat, and edge protector) using a small chamber (impinger) system. Airborne phthalates released from each of those PVC samples were collected using sorbent (Tenax TA) tubes at three temperature control intervals (0, 3, and 6â¯h) under varying temperature conditions (25, 40, and 90⯠degrees C). A total of 11 phthalate compounds were quantified in the five PVC products examined in this study. To facilitate the comparison of phthalate emissions among PVC samples, their flux values were defined for total phthalates by summing the average fluxes of all 11 phthalates generated during the control period of 6â¯h. The highest flux values were seen in the edge protector sample at all temperatures (0.40 (25⯠degrees C), 9.65 (40⯠degrees C), and 75.7â¯mugâ¯m(-2) h(-1) (90⯠degrees C)) of which emission was dominated by dibutyl isophthalate. In contrast, the lowest fluxes were found in wallcovering (0.01 (25⯠degrees C) and 0.05â¯mugâ¯m(-2) h(-1) (40⯠degrees C)) and child's toy (0.23â¯mugâ¯m(-2) h(-1) (90⯠degrees C)) at each temperature level. The information regarding phthalate composition and emission patterns varied dynamically with type of PVC sample, controlled temperature, and duration of control. | Polyvinyl Chloride |
This paper puts forward a method to describe an equation of the within-plate uncertainty (relative standard deviation (R.S.D.) of measurements) as a function of analyte concentration in sandwich enzyme-linked immunosorbent assay (ELISA). A kit for thyroid stimulating hormone is taken as an example. The pipetting procedures of analyte solution and chromogen-substrate solution and absorbance inherent to the wells of a microplate are identified as major error sources and their variability is included as parameters in the uncertainty equation. These parameters can be determined by the experiments with distilled water. The theoretical R.S.D. is shown to be in good agreement with the results of the repeated experiments using the real samples. Since the theory gives a continuous plot of R.S.D. against concentration, the uncertainty structure of the ELISA kit can be recognized over a wide concentration range and the detection limit and quantitation range can easily be determined on the plot. | Immunoenzyme Techniques |
BACKGROUND AND PURPOSE: Glucagon-like peptide 1 (GLP-1) is a hormone derived from preproglucagon. It is secreted by enteroendocrine cells in response to feeding and, in turn, acts as a critical regulator of insulin release. Modulating GLP-1 secretion holds promise as a strategy for controlling blood glucose levels. EXPERIMENTAL APPROACH: To dissect GLP-1 regulation and discover specific secretagogues, we engineered a reporter cell line introducing a luciferase within the proglucagon sequence in GLUTag cells. The assay was validated using western blotting and ELISA. A focused natural compounds library was screened. We measured luminescence, glucose uptake and ATP to investigate the mechanism by which newly found secretagogues potentiate GLP-1 secretion. KEY RESULTS: The newly created reporter cell line is ideal for the rapid, sensitive and quantitative assessment of GLP-1 secretion. The small molecule screen identified non-toxic GLP-1 modulators. Quercetin is the most potent newly found GLP-1 secretagogue, while other flavonoids also potentiate GLP-1 secretion. Quercetin requires glucose and extracellular calcium to act as GLP-1 secretagogue. Our results support a mechanism whereby flavonoids cause GLUTag cells to utilize glucose more efficiently, leading to elevated ATP levels, followed by K(ATP) channel blockade and GLP-1 exocytosis. CONCLUSION AND IMPLICATIONS: Our methodology enabled finding of new GLP-1 secretagogues. Quercetin is a potent, naturally occurring GLP-1 secretagogue. Mechanistic studies of newly found secretagogues are possible in newly created reporter cell line. Further validation in more physiological systems, such as primary L-cells or whole organisms, is needed. GLP-1 secretagogues might serve as leads for developing alternative glucose-lowering therapies. | Secretagogues |
We investigated interactions of bispyridinium para-aldoximes N,N'-(propano)bis(4-hydroxyiminomethyl) pyridinium bromide (TMB-4), N,N'-(ethano)bis(4-hydroxyiminomethyl)pyridinium methanosulphonate (DMB-4), and N,N'-(methano)bis(4-hydroxyiminomethyl)pyridinium chloride (MMB-4) with human erythrocyte acetylcholinesterase phosphorylated by tabun. We analysed aldoxime conformations to determine the flexibility of aldoxime as an important feature for binding to the acetylcholinesterase active site. Tabun-inhibited human erythrocyte acetylcholinesterase was completely reactivated only by the most flexible bispyridinium aldoxime - TMB-4 with a propylene chain between two rings. Shorter linkers than propylene (methylene or ethylene) as in MMB-4 and DMB-4 did not allow appropriate orientation in the active site, and MMB-4 and DMB-4 were not efficient reactivators of tabun-phosphorylated acetylcholinesterase. Since aldoximes are also reversible inhibitors of native acetylcholinesterase, we determined dissociation constants and their protective index against acetylcholinesterase inactivation by tabun. | Trimedoxime |
Plasma cell leukemia, occurring either de novo or in patients with long standing multiple myeloma, is the least common type of plasma cell dyscrasia. Histogenetically plasma cell leukemia is derived from terminally differentiated B cells. It is diagnosed by presence of absolute plasma cell count >2000/cm or >20% circulating plasma cells. Two cases of plasma-cell leukemia are reported here. Clinical spectrum and course of the disease, are discussed. Both cases (of primary plasma cell leukemia) had abrupt onset of disease, poor response to therapy and short survival time. Both presented with fatiguability and weakness. Evidence of organomegaly and radiological and hematological evidence of plasma cell leukemia, with thrombocytopenia and evidence of visceral involvement with leukemic cells, was seen in one case. | Leukemia, Plasma Cell |
Parvalbumin (PV) is a cytosolic Ca2+-binding protein acting as a slow-onset Ca2+ buffer modulating the shape of Ca2+ transients in fast-twitch muscles and a subpopulation of neurons. PV is also expressed in non-excitable cells including distal convoluted tubule (DCT) cells of the kidney, where it might act as an intracellular Ca2+ shuttle facilitating transcellular Ca2+ resorption. In excitable cells, upregulation of mitochondria in PV-ergic" cells in PV-/- mice appears to be a general hallmark, evidenced in fast-twitch muscles and cerebellar Purkinje cells. Using Gene Chip Arrays and qRT-PCR, we identified differentially expressed genes in the DCT of PV-/- mice. With a focus on genes implicated in mitochondrial Ca2+ transport and membrane potential, uncoupling protein 2 (Ucp2), mitocalcin (Efhd1), mitochondrial calcium uptake 1 (Micu1), mitochondrial calcium uniporter (Mcu), mitochondrial calcium uniporter regulator 1 (Mcur1), cytochrome c oxidase subunit 1 (COX1), and ATP synthase subunit beta (Atp5b) were found to be up-upregulated. At the protein level, COX1 was increased by 31 +/- 7%, while ATP-synthase subunit beta was unchanged. This suggested that these mitochondria were better suited to uphold the electrochemical potential across the mitochondrial membrane, necessary for mitochondrial Ca2+ uptake. Ectopic expression of PV in PV-negative Madin-Darby canine kidney (MDCK) cells decreased COX1 and concomitantly mitochondrial volume, while ATP synthase subunit beta levels remained unaffected. Suppression of PV by shRNA in PV-expressing MDCK cells led subsequently to an increase in COX1 expression. The collapsing of the mitochondrial membrane potential by the uncoupler CCCP occurred at lower concentrations in PV-expressing MDCK cells than in control cells. In support, a reduction of the relative mitochondrial mass was observed in PV-expressing MDCK cells. Deregulation of the cytoplasmic Ca2+ buffer PV in kidney cells was counterbalanced in vivo and in vitro by adjusting the relative mitochondrial volume and modifying the mitochondrial protein composition conceivably to increase their Ca2+-buffering/sequestration capacity." | Mitochondrial Size |
The widespread use of butylated hydroxyanisole (I) and butylated hydroxytoluene (II) as food antioxidants recently has been criticized by the Food and Drug Administration because of their pharmacological and toxicological effects. Interest also has arisen recently in the use of these compounds as anticancer agents. The purposes of this study were to evaluate the pharmacokinetics of I and II in rabbits and to compare their physicochemical properties with their disposition kinetics. It was found that I has a disposition half-life of approximately 1 hr, compared to 11 days for II. These differences are explained in terms of their lipid solubility and protein binding characteristics. | Butylated Hydroxyanisole |
We used an antibody prepared against Aplysia (mollusc) body-wall actin that specifically reacts with certain forms of cytoplasmic actin in mammalian cells to probe for the presence of actin at the neuromuscular junction. Immunocytochemical studies showed that actin or an actinlike molecule is concentrated at neuromuscular junctions of normal and denervated adult rat muscle fibers. Actin is present at the neuromuscular junctions of fibers of developing diaphragm muscles as early as embryonic day 18, well before postsynaptic folds are formed. These results suggest that cytoplasmic actin may play a role in the clustering or stabilization of acetylcholine receptors at the neuromuscular junction. | Motor Endplate |
Telocytes (TCs) are new interstitial cells, and they are involved in tissue regeneration, particularly in heart. Therefore, TCs are suggested to be a promising cell in regenerative medicine. However, the information of location structural characteristics and functions of TCs is still limited. In this study, cardiac TCs of the Chinese giant salamanders (Andrias davidianus) were identified by transmission electron microscopy. TCs were located in the interstitium between cardiomyocytes (CM). TCs possessed distinctive ultrastructural characteristics, including one to two very long and thin moniliform telopodes (Tps), emerging points from the cell body, caveolae, dichotomous branchings, labyrinthic systems, neighbouring exosomes and homo-cellular contacts between Tps. TCs/Tps were frequently observed in close proximity to cardiomyocytes. Moreover, Tps established hetero-cellular contacts with cardiomyocytes. Our results confirm the presence of TCs in the myocardium of the A. davidianus. This will help us to better understand roles of TCs in amphibian hearts. | Telopodes |
The hyoid bone supports the important functions of swallowing and speech. At birth, the hyoid bone consists of a central body and pairs of right and left lesser and greater cornua. Fusion of the greater cornua with the body normally occurs in adulthood, but may not occur at all in some individuals. The aim of this study was to quantify hyoid bone fusion across the lifespan, as well as assess developmental changes in hyoid bone density. Using a computed tomography imaging studies database, 136 hyoid bones (66 male, 70 female, ages 1-to-94) were examined. Fusion was ranked on each side and hyoid bones were classified into one of four fusion categories based on their bilateral ranks: bilateral distant non-fusion, bilateral non-fusion, partial or unilateral fusion, and bilateral fusion. Three-dimensional hyoid bone models were created and used to calculate bone density in Hounsfield units. Results showed a wide range of variability in the timing and degree of hyoid bone fusion, with a trend for bilateral non-fusion to decrease after age 20. Hyoid bone density was significantly lower in adult female scans than adult male scans and decreased with age in adulthood. In sex and age estimation models, bone density was a significant predictor of sex. Both fusion category and bone density were significant predictors of age group for adult females. This study provides a developmental baseline for understanding hyoid bone fusion and bone density in typically developing individuals. Findings have implications for the disciplines of forensics, anatomy, speech pathology, and anthropology. | Hyoid Bone |
Modern people who value healthy eating habits have shown increasing interest in plum (Prunus mume) fruits, primarily owing to their nutritiousness and proven efficacy. As consumption increases, it becomes important to monitor work to prevent Prunus mume fruits from falling out. Moreover, determining the growth status of Prunus mume is also crucial and is attracting increasing attention. In this study, convolutional neural network (CNN)-based deep learning object detection was developed using RGBD images collected from Prunus mume farms. These RGBD images consider various environments, including the depth information of objects in the outdoor field. A faster region-based convolutional neural network (R-CNN), EfficientDet, Retinanet, and Single Shot Multibox Detector (SSD) were applied for detection, and the performance of all models was estimated by comparing their respective computing speeds and average precisions (APs). The test results show that the EfficientDet model is the most accurate, and SSD MobileNet is the fastest among the four models. In addition, the algorithm was developed to acquire the growth status of P. mume fruits by applying the coordinates and score values of bounding boxes to the depth map. Compared to the diameters of the artificial Prunus mume fruits used as the experimental group, the calculated diameters were very similar to those of the artificial objects. Collectively, the results demonstrate that the CNN-based deep learning Prunus mume detection and growth estimation method can be applied to real farmlands. | Prunus |
The development of a sensitive enzyme-immunoassay for 20 alpha-dihydroprogesterone (20 alpha-DHP) and its use in determining reproductive status in black and white rhinoceroses is reported. 20 alpha-DHP in hydrolysed urine diluted in parallel to standards, and high-performance liquid chromatography (HPLC) confirmed the presence of 20 alpha-DHP and the absence of pregnanediol-3 alpha-glucuronide (PdG) in urine collected from rhinoceroses after oestrus. Conjugated oestrone was identified by HPLC as the major urinary oestrogen in the black rhineroceros and conjugated oestradiol-17 beta was the most abundant in the white rhinoceros. In African species, the black (Diceros bicornis), and northern (Ceratotherium simum cottoni) and southern (Ceratotherium simum simum) white rhinoceroses, excretion of 20 alpha-DHP and oestrogen followed a cyclic pattern. Excretion of 20 alpha-DHP was low before mating, at the time of peak oestrogen excretion, but high after oestrus. In the black rhinoceros, the follicular phase was 3-4 days and the luteal phase was 18 days, suggesting a cycle of 21-22 days. The interoestrus interval in the northern subspecies of white rhinoceros was 25 days, which correlated well with the interval between peaks of oestradiol-17 beta excretion. The interval between urinary oestrogen peaks in the southern subspecies of white rhinoceros suggested a cycle length of 32 days. This paper provides the first description of the pattern of excretion of urinary oestrogens and progesterone metabolites in African rhinoceroses. | 20-alpha-Dihydroprogesterone |
The SHARE program brings administrators, state hospital association officers, and others together in an effort to strengthen association work. | Societies, Hospital |
Neural crest cells of ectothermic vertebrates give rise to three types of pigment cells: melanophores, xanthophores, and iridophores. In early larval salamanders, these cells can combine to generate a variety of pigment patterns across taxa, including vertical bars and horizontal stripes. Such patterns offer an opportunity to study neural crest morphogenesis and differentiation, as well as the evolution of these processes and the morphologies that arise from them. This review examines the phylogenetic distribution of specific pigment patterns, our current understanding of the mechanisms underlying these patterns, and how evolutionary transformations of these mechanisms may have resulted in alternative pigment patterns across taxa. | Skin Pigmentation |
This article summarizes the current state and future needs of research into saline-filled and silicone gel breast implants. The authors describe recent investigations into possible causes and potential risk factors for silicone gel and saline implant failure. Also discussed are local complications of breast implantation and the need for revisional operations in augmentation and reconstruction patients. In addition, the effects that surgical, implant, and patient variables have on the aesthetic outcome of surgery are addressed. The last portion of the article lays out future research needs, such as determining the incidence rate of implant failure, reducing the frequency of revisional surgery, and the difficulty of designing better breast implants in the current strict regulatory climate. | Silicone Gels |
Jugulotympanic paragangliomas were first described approximately 75 years ago. Since that time, there has been considerable evolution in knowledge of tumor biology, methods of classification, and appropriate management strategies. This paper attempts to summarize these gains in information. | Glomus Jugulare Tumor |
Delivery to the brain is a challenging task due to its protection by the blood-brain barrier (BBB). Lipids and fatty acids are reported to affect the permeability of the BBB, although this has not been reported following oral administration. Cannabidiol (CBD) has high therapeutic potential in the brain, therefore, this work investigated CBD delivery to anatomical brain regions following oral administration in lipid-based and lipid-free vehicles. All formulations resulted in a short brain T(max) (1 h) and brain-plasma ratios >/= 3.5, with retention up to 18 h post administration. The highest CBD delivery was observed in the olfactory bulb and striatum, and the medulla pons and cerebellum the lowest. The lipid-free vehicle led to the highest levels of CBD in the whole brain. However, when each anatomical region was assessed individually, the long chain triglyceride-rich rapeseed oil formulation commonly showed optimal performance. The medium chain triglyceride-rich coconut oil formulation did not result in the highest CBD concentration in any brain region. Overall, differences in CBD delivery to the whole brain and various brain regions were observed following administration in different formulations, indicating that the oral formulation selection may be important for optimal delivery to specific regions of the brain. | Administration, Oral |
Cardiac surgery in the pregnant woman gives rise to several anesthetic challenges, as the mother, but mainly the fetus, have a risk of high morbidity and mortality. In this context, the cardiopulmonary bypass is the most complex period, owing to the risks of fetal hypoxia it entails. Due to the absence, for ethical reasons, of prospective trials that provide generally accepted guidelines in intraoperative management, it means that physicians have to work based on case reports in the literature. These procedures also require team coordination to be successful. The case is presented of a 19 weeks pregnant woman, who required a mitral valve replacement, which was achieved with success, and enabled her to complete her pregnancy without complications. Details are provided on the published references on which our management was based. | Chorea Gravidarum |
BACKGROUND: The study aimed to observe the effects of pacing on the atrial effective refractory period (AERP), inducibility of atrial fibrillation (AF), and changes of atrial autonomic neural remodeling (ANR) by rosuvastatin intervention on the acute model of rapid-pacing-induced AF. METHODS: Thirty rabbits were randomly divided into a control group (C, n = 10), rapid-pacing group (P, n = 10), and rosuvastatin-intervention group (R, n = 10). AERP and inducibility of AF were measured for all groups. The sympathetic and parasympathetic nerves of left atrium, right atrium, and atrial septum labeled with tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) were detected by immunohistochemistry and Western blot. RESULTS: The AERP in group R was prolonged, and AF could not be induced as easily (P < 0.05). Immunohistochemistry showed that the densities and heterogeneity of TH and ChAT positive nerves of the atrium in group P were significantly higher than those in group C (ranked as right atrium > atrial septum > left atrium), whereas those in group R were decreased (P < 0.05). Western blot showed that TH and ChAT protein expression in group P was significantly increased compared with group C, but decreased in group R (P < 0.05). CONCLUSIONS: Persistent rapid atrial pacing can lead to heterogeneous ANR in different parts of the rabbit atrium and may cause AF, which can be reversed by rosuvastatin. The inhibitory function of rosuvastatin may be associated with its role in reversing atrial ANR. | Atrial Remodeling |
Quinine produces haemolysis of rabbit and human red blood cells in concentrations up to 1 in 700. In a concentration of 1 in 10,000 it increases the degree of haemolysis produced by various haemolytic agents like saponin, bile salts and digitonin in vitro. Quinine when injected intravenously in 35 mg./kg. dose in rabbits increases the susceptibility of red blood cells to the haemolytic action of saponin. Intravascular haemolysis following the administration of quinine is seen in cases of blackwater fever, and on the basis of experimental work described in the paper it is suggested that quinine precipitates these haemolytic episodes by rendering the red blood cells more susceptible to the action of tissue lytic factors. | Hemolytic Agents |
We report two cases of unusual and undeclared oesophageal foreign bodies. A small double-rounded calabash or bottle gourd Lagenaria siceraria, stuffed with traditional medicine designed to acquire spiritual power. A whole tricotyledonous kola nut Cola nitida also designed to make medicine to gain love from a woman after passing it out in stool. Each case presented with a sudden onset of total dysphagia and history of ingestion of foreign bodies was not volunteered by any despite direct questioning. Plain radiograph of the neck and chest in either case did not reveal presence of foreign body. Both were successfully removed through rigid oesophagoscopy. | Foreign Bodies |
BACKGROUND AND AIMS: Diverticular disease represents a leading cause of gastrointestinal-related hospitalizations. We sought to identify the adverse consequences of obesity on acute diverticulitis (AD) hospital admissions. By age 85, approximately two-thirds of individuals will develop diverticular disease and up to 25% will develop AD. Generally, obesity confers an increased risk of morbidity and mortality; however, its impact on hospitalized patients with AD are lacking. METHODS: Utilizing ICD-9-CM codes from the National Inpatient Sample (January 2012 - October 2015) we identified patients with a primary discharge diagnosis of AD including 660,820 hospitalizations and 115,785 with obesity. Primary outcomes were mortality, length of stay, and hospitalization cost. Secondary outcomes were AD complications and the need for surgical interventions. RESULTS: On multivariate analysis, obesity was not associated with an increased risk of mortality (OR=1.1, 95%CI: 0.87-1.41; p= 0.43). However, morbid obesity (BMI > 40 kg/m2) showed a significant increased risk of mortality (OR=1.69, 95%CI: 1.23-2.31; p<0.001). Obesity was associated with prolonged hospitalizations length of stay by 0.61 days (0.55-0.68; p <10-6), higher hospital charges $6,320 ($ 5,500-7,140; p<10-6), increased complicated diverticulitis 1.05 (1.01-1.1; p < 0.010) and required more surgical interventions for diverticulitis (OR=1.19, 95%CI: 1.15-1.23; p<10-6). CONCLUSION: Morbid obesity increases risk for mortality while obesity leads to longer hospitalization stays and greater healthcare cost as well as adverse clinical outcomes and more surgical interventions. Further interventions are required to address obesity and weight loss for patients with diverticulitis to improve clinical outcomes. | Diverticulitis |
C(4) photosynthesis depends on the strict compartmentalization of CO(2) assimilatory enzymes. cis-regulatory mechanisms are described that ensure mesophyll-specific expression of the gene encoding the C(4) isoform of phosphoenolpyruvate carboxylase (ppcA1) of the C(4) dicot Flaveria trinervia. To elucidate and understand the anatomy of the C(4) ppcA1 promoter, detailed promoter/reporter gene studies were performed in the closely related C(4) species F. bidentis, revealing that the C(4) promoter contains two regions, a proximal segment up to -570 and a distal part from -1566 to -2141, which are necessary but also sufficient for high mesophyll-specific expression of the beta-glucuronidase reporter gene. The distal region behaves as an enhancer-like expression module that can direct mesophyll-specific expression when inserted into the ppcA1 promoter of the C(3) plant F. pringlei. Mesophyll expression determinants were restricted to a 41-bp segment, referred to as mesophyll expression module 1 (Mem1). Evolutionary and functional studies identified the tetranucleotide sequence CACT as a key component of Mem1. | Flaveria |
Human epidermal growth factor receptor 2 (HER2) is a member of epidermal growth factor receptors with tyrosine kinase functionality. The dimerization of HER2 leads to the autophosphorylation of tyrosine residues within its cytoplasmic domain, resulting in hyperactivation of several downstream signal transduction pathways that play an important role in tumorigenesis, cancer aggressiveness and cell proliferation. Amplification or overexpression of HER2 has been found in approximately 15-30% of breast cancers. Hence, HER2 serve as a therapeutic biomarker in breast cancer. Herein, we applied structural bioinformatics techniques via molecular docking, molecular dynamics simulations, Molecular mechanics/generalized Born surface area (MM/GBSA) calculations and pharmacokinetic models to identify putative HER2 inhibitors. Application of stringent molecular docking results in the identification of bioactive compounds from Mangifera indica as selective, potent inhibitors of HER2. However, only the top three compounds with the highest negative docking score (< -9kcal/mol) was considered in reference to neratinib (-8.601 kcal/mol) for computational analysis. The molecular dynamics simulations and post-simulation analysis of docked HER2-ligand complexes unveil the substantial stability for M. indica ligands over the 100 ns simulation period. Additionally, MM/GBSA binding free energy calculation supports the inhibitory potential for the docked ligands, which exclusively revealed the highest binding energy for selected M. indica ligands than the reference compound (neratinib). The pharmacokinetic model showed that M. indica ligands are promising therapeutic agents. Conclusively, bioactive compounds from M. indica may serve as lead molecules that could be developed into potent and effective HER2 inhibitors for breast cancer treatment.Communicated by Ramaswamy H. Sarma. | Mangifera |
To investigate factors associated with gastrointestinal (GI) carcinomas metastasizing to ovaries to form Krukenberg tumor. Among the 102 cases of Krukenberg tumor due to GI cancers, there were 41 cases synchronously diagnosed, 43 cases with primary tumor identified first and 18 cases with ovarian tumor identified first. Metastatic factors of 43 cases of metachronous Krukenberg tumor were analyzed with univariate and multivariate methods. Of the 43 patients, the median age at diagnosis of Krukenberg tumor was 42 years (range, 21-72). Stomach is the most common primary site (58.1%), followed by colon (25.6%) and rectum (16.3%). Most of the patient was in premenopausal state (81.4%) and had bilateral ovaries involved (67.4%). The overall median metastasis-free time in T3 group (17.0 months) was significantly longer than that in T4 group (10.0 months) (P=0.003). Univariate analysis identified tumor invasion depth and ascites as significant factors for metastasis. Multivariate analysis confirmed that invasion depth was the only significant metastatic factor (Relative Risk: 3.2, P=0.004). Primary carcinomas T stage is the most important predictor of Krukenberg tumor from GI cancer. | Krukenberg Tumor |
A simple, rapid, sensitive and low-cost method using capillary electrophoresis (CE) coupled with field-amplified sample stacking (FASS) has been developed and validated for the simultaneous determination of strychnine and brucine residues in human urine. Before sample loading, a water plug (3.5 kPa, 3 s) was injected to contain sample cations and to permit FASS. Electrokinetic injection at a voltage (20 kV, 25 s) was then used to introduce cations. Separation was performed using 20 mM acetate buffer (pH 3.8) with an applied voltage of 20 kV. The calibration curves were linear over a range of 8.00-2.56 infinity 10(2) ng/mL (r = 0.9995) for strychnine and 10.0-3.20 x 10(2) ng/mL (r = 0.9999) for brucine. Extraction recoveries in urine were greater than 79.6 and 82.8% for strychnine and brucine, respectively, with an RSD of less than 4.9%. The detection limits (signal-to-noise ratio 3) for strychnine and brucine were 2.00 and 2.50 ng/mL, respectively. A urine sample from one healthy female volunteer (26 years old, 50 kg) was pretreated and analyzed. Strychnine and brucine levels in urine could be detected 24 h after administration. On these grounds, this method was feasible for application to preliminary screening of trace levels of abused drugs for both doping control and forensic analysis. | Strychnos nux-vomica |
The interaction of alpha MSH and beta-endorphin on the secretion of PRL, GH, and LH was determined in the ovariectomized rat. The potent stimulatory effect on PRL release of injection of 20 ng (5.8 pmol) beta-endorphin into the third cerebral ventricle was completely blocked by 100 ng (60 pmol) alpha MSH. The same dose of alpha MSH partially blocked the effect of 150 ng (44 pmol) beta-endorphin on PRL secretion. Intraventricular injection of either 20 ng beta-endorphin or 100 ng alpha MSH had no effect by itself on plasma LH. However, coinjection of these doses of beta-endorphin and alpha MSH suppressed plasma LH levels significantly within 15 min. beta-Endorphin (150 ng) produced a significant suppression of plasma LH levels. Furthermore, coadministration of 100 ng alpha MSH with 150 ng beta-endorphin lowered plasma LH for a longer period of time than this dose of beta-endorphin alone. Low doses of beta-endorphin (20 ng) or alpha MSH (100 ng) alone or in combination did not alter plasma GH levels. A higher dose of 150 ng beta-endorphin produced a slight elevation of plasma GH. This effect was potentiated 5-fold when 150 ng beta-endorphin were injected in combination with 100 ng alpha MSH. These results indicate that alpha MSH acts as an antagonist to beta-endorphin in regard to the secretion of PRL, whereas it potentiates the effect of beta-endorphin in stimulation of GH and inhibition of LH secretion. | Pituitary Hormones, Anterior |
In this review, most of the known and postulated mechanisms of osteopontin (OPN) and its role in bone remodeling and orthodontic tooth movement are discussed based on available literature. OPN, a multifunctional protein, is considered crucial for bone remodeling, biomineralization, and periodontal remodeling during mechanical tension and stress (orthodontic tooth movement). It contributes to bone remodeling by promoting osteoclastogenesis and osteoclast activity through CD44- and alphavbeta3-mediated cell signaling. Further, it has a definitive role in bone remodeling by the formation of podosomes, osteoclast survival, and osteoclast motility. OPN has been shown to have a regulatory effect on hydroxyapatite crystal (HAP) growth and potently inhibits the mineralization of osteoblast cultures in a phosphate-dependent manner. Bone remodeling is vital for orthodontic tooth movement. Significant compressive and tensional forces on the periodontium induce the signaling pathways mediated by various osteogenic genes including OPN, bone sialoprotein, Osterix, and osteocalcin. The signaling pathways involved in the regulation of OPN and its effect on the periodontal tissues during orthodontic tooth movement are further discussed in this review. A limited number of studies have suggested the use of OPN as a biomarker to assess orthodontic treatment. Furthermore, the association of single nucleotide polymorphisms (SNPs) in OPN coding gene Spp1 with orthodontically induced root resorption remains largely unexplored. Accordingly, future research directions for OPN are outlined in this review. | Bone Remodeling |
Hypaphorine, an alpha-N,N,N-trimethyltryptophan betaine, was isolated, for the first time, from Astragalus lusitanicus Lam. (Fabaceae), a plant highly toxic for lambs and goats. This alkaloid was characterized by NMR and MS analysis. Hypaphorine was previously reported to be a convulsive poison. To confirm the toxicity, it was synthesized and tested in goats. Hypaphorine was shown to be non-toxic for goats even at a high dose of 2 g kg(-1) by oral administration. | Astragalus Plant |
Brevibacillus sp. SPR20 produced potentially antibacterial substances against methicillin-resistant Staphylococcus aureus (MRSA). The synthesis of these substances is controlled by their biosynthetic gene clusters. Several mutagenesis methods are used to overcome the restriction of gene regulations when genetic information is absent. Atmospheric and room temperature plasma (ARTP) is a powerful technique to initiate random mutagenesis for microbial strain improvement. This study utilized an argon-based ARTP to conduct the mutations on SPR20. The positive mutants of 40% occurred. The M27 mutant exhibited an increase in anti-MRSA activity when compared to the wild-type strain, with the MIC values of 250-500 and 500 mug/mL, respectively. M27 had genetic stability because it exhibited constant activity throughout fifteen generations. This mutant had similar morphology and antibiotic susceptibility to the wild type. Comparative proteomic analysis identified some specific proteins that were upregulated in M27. These proteins were involved in the metabolism of amino acids, cell structure and movement, and catalytic enzymes. These might result in the enhancement of the anti-MRSA activity of the ARTP-treated SPR20 mutant. This study supports the ARTP technology designed to increase the production of valuable antibacterial agents. | Brevibacillus |
Neuroleptic drugs are widely applied in effective treatment of schizophrenia and related disorders. The lipophilic character of neuroleptics means that they tend to accumulate in the lipid membranes, impacting their functioning and processing. In this paper, the effect of four drugs, namely, thioridazine, olanzapine, sulpiride, and amisulpride, on neutral and negatively charged lipid bilayers was examined. The interaction of neuroleptics with lipids and the subsequent changes in the membrane physical properties was assessed using several complementary biophysical approaches (isothermal titration calorimetry, electron paramagnetic resonance spectroscopy, dynamic light scattering, and zeta potential measurements). We have determined the thermodynamic parameters, that is, the enthalpy of interaction and the binding constant, to describe the interactions of the investigated drugs with model membranes. Unlike thioridazine and olanzapine, which bind to both neutral and negatively charged membranes, amisulpride interacts with only the negatively charged one, while sulpiride does not bind to any of them. The mechanism of olanzapine and thioridazine insertion into the bilayer membrane cannot be described merely by a simple molecule partition between two different phases (the aqueous and the lipid phase). We have estimated the number of protons transferred in the course of drug binding to determine which of its forms, ionized or neutral, binds more strongly to the membrane. Finally, electron paramagnetic resonance results indicated that the drugs are localized near the water-membrane interface of the bilayer and presence of a negative charge promotes their burying deeper into the membrane. | Amisulpride |
Floods are among the most serious and devastating phenomena of natural disasters. Cities adjacent to flood-prone areas in the last decades have played a major role in increasing the potential adverse effects of flood damage. This research study aims to evaluate and mitigate the risks of flood events in the El Bayadh region, which suffers from poor infrastructure and drained networks. To achieve this, it is necessary to evaluate rainfall intensities and their limits for durations from 0.167 to 24 h with return periods from 2 to 1000 years. Eight different frequency analysis distributions were fit to the historical rainfall data series over 43 years (1970-2012) using hypothesis-based goodness tests and information-based criteria. The most appropriate distributions were used to develop the rainfall intensity-duration-frequency (IDF) and flood risk-duration-frequency (RDF) curves for the study area. The results show that high-intensity rainfall values last for short durations, while high flood risk values last for intermediate durations. The results of the flood RDF curves can provide useful information for policy makers to make the right decisions regarding the effectiveness of the region's protection structures against future flood risks." | Risk Evaluation and Mitigation |
Multivariate time-series (MTS) data are prevalent in diverse domains and often high dimensional. We propose new random projection ensemble classifiers with high-dimensional MTS. The method first applies dimension reduction in the time domain via randomly projecting the time-series variables into some low-dimensional space, followed by measuring the disparity via some novel base classifier between the data and the candidate generating processes in the projected space. Our contributions are twofold: (i) We derive optimal weighted majority voting schemes for pooling information from the base classifiers for multiclass classification and (ii) we introduce new base frequency-domain classifiers based on Whittle likelihood (WL), Kullback-Leibler (KL) divergence, eigen-distance (ED), and Chernoff (CH) divergence. Both simulations for binary and multiclass problems, and an Electroencephalogram (EEG) application demonstrate the efficacy of the proposed methods in constructing accurate classifiers with high-dimensional MTS. | Time Factors |
Measurements of venoarterial concentration differences across the ovary in anesthetized sheep have demonstrated that the ovary secretes ovine neurophysin I/II (oNP I/II) and that this process is stimulated by the prostaglandin F2 alpha analogue, cloprostenol. A parallel increase in the secretion of oxytocin (OT) was observed in response to cloprostenol, and the mean molar ratio of oNP I/II to OT secreted was 1.2. There was no detectable ovarian secretion of oNP III. Secretion of oNP I/II and OT was absent after hysterectomy. The data support other evidence indicating that the corpus luteum synthesizes OT, and confirm that the neurophysin associated with OT in the sheep is oNP I/II. | Neurophysins |
The P1 plasmid partition locus, P1 par, actively distributes plasmid copies to Escherichia coli daughter cells. It encodes two DNA sites and two proteins, ParA and ParB. Plasmid P7 uses a similar system, but the key macromolecular interactions are species specific. Homolog specificity scanning (HSS) exploits such specificities to map critical contact points between component macromolecules. The ParA protein contacts the par operon operator for operon autoregulation, and the ParB contacts the parS partition site during partition. Here, we refine the mapping of these contacts and extend the use of HSS to map protein-protein contacts. We found that ParB participates in autoregulation at the operator site by making a specific contact with ParA. Similarly, ParA acts in partition by making a specific contact with ParB bound at parS. Both these interactions involve contacts between a C-terminal region of ParA and the extreme N-terminus of ParB. As a single type of ParA-ParB complex appears to be involved in recognizing both DNA sites, the operator and the parS sites may both be occupied by a single protein complex during partition. The general HSS strategy may aid in solving the three-dimensional structures of large complexes of macromolecules. | Bacteriophage P1 |
OBJECTIVE: Patients with severe tricuspid regurgitation and persistent atrial fibrillation may not be good candidates for maze procedure due to preoperative atrial remodeling and various comorbidities. We attempted to evaluate the rhythm and clinical outcomes of maze procedure in these patients. METHODS: Patients with severe tricuspid regurgitation and persistent atrial fibrillation who underwent tricuspid valve surgery between January 1994 and December 2017 at a single tertiary center were analyzed. The primary end point was sinus rhythm restoration. The key secondary end point was major adverse cardiovascular and cerebrovascular event rate, which is the composite event of stroke, cardiac death, major bleeding, and readmission for heart failure. Propensity score matching analysis was used. RESULTS: A total of 388 patients underwent tricuspid valve surgery, and among them 172 patients (44%) underwent concomitant maze procedure. The maze group had sinus rhythm restoration rate of 56% in 9 years. Further, in the matched cohort, the maze group had higher freedom from major adverse cardiovascular and cerebrovascular event rate at 10 years than the nonmaze group (55.6% vs 36.2%; P = .047). Preoperative left atrial diameter (hazard ratio, 1.022; 95% CI, 1.012-1.033; P < .001) and right atrial diameter (hazard ratio, 1.012; 95% CI, 1.003-1.022; P = .013) were independent risk factors for failure of sinus rhythm. CONCLUSIONS: Maze procedure in severe tricuspid regurgitation and persistent atrial fibrillation had acceptable rates of sinus rhythm restoration and reduced major adverse cardiovascular and cerebrovascular events in the long-term. Careful patient selection considering preoperative atrial diameters is needed to enhance maze success rate and long-term clinical outcomes. | Maze Procedure |
Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgenomics.org), obtained over three different years. We compared bacteria- and fungi-induced cytokine profiles and found that most cytokine responses were organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide single-nucleotide polymorphism (SNP) genotypes with cytokine abundance and identified six cytokine quantitative trait loci (QTLs). Among them, a cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. Furthermore, the cytokine QTLs that we identified were enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens." | N-Terminal Acetyltransferase C |
Succinate esters, although frequently employed as water-soluble prodrugs of poorly soluble parent drugs, are not sufficiently stable to allow long-term storage in solution. Intramolecular catalysis of ester hydrolysis by the terminal succinate carboxyl group is a contributing factor to this instability. Methylprednisolone 21-succinate has recently been reported to undergo both hydrolysis and 21 in equilibrium 17 acyl migration in aqueous solutions. Intramolecular catalysis by the terminal carboxyl group is seen in both reactions, but the catalytic mechanisms are not well understood. While acyl migration can only be catalyzed via the carboxyl group acting as a general acid or general base, hydrolysis may undergo either nucleophilic or general acid-base catalysis. To gain further insight into the catalytic mechanism, hydrolysis of methylprednisolone 21-succinate was carried out in aniline buffers to trap any succinic anhydride (as the anilide) that would form if the catalysis were nucleophilic. The nucleophilic mechanism was shown to account for only 15-20% of the overall catalysis. Comparisons of the rates of the intramolecularly catalyzed reactions of methylprednisolone 21- and 17-succinate were made with the same reactions of methylprednisolone 21- and 17-acetate catalyzed intermolecularly by acetate ion. Interestingly, intramolecular catalysis appears to favor acyl migration over hydrolysis. Hence, the hydrolysis of methylprednisolone 21-succinate is faster in basic solutions (pH greater than 7.4), while acyl migration becomes the dominant reaction in the catalyzed region of the pH profile between pH 3.6 and 7.4. Arguments are presented to account for these differences in catalytic efficiency in terms of the transition-state structures for the two reactions. | Prednisolone |
PLA2 (phospholipase A2) group III is an atypical sPLA2 (secretory PLA2) that is homologous with bee venom PLA2 rather than with other mammalian sPLA2s. In the present paper, we show that endogenous group III sPLA2 (PLA2G3) is expressed in mouse skin and that Tg (transgenic) mice overexpressing human PLA2G3 spontaneously develop skin inflammation. Pla2g3-Tg mice over 9 months of age frequently developed dermatitis with hyperkeratosis, acanthosis, parakeratosis, erosion, ulcer and sebaceous gland hyperplasia. The dermatitis was accompanied by infiltration of neutrophils and macrophages and by elevated levels of pro-inflammatory cytokines, chemokines and prostaglandin E2. In addition, Pla2g3-Tg mice had increased lymph aggregates and mucus in the airway, lymphocytic sialadenitis, hepatic extramedullary haemopoiesis, splenomegaly with increased populations of granulocytes and monocytes/macrophages, and increased serum IgG1. Collectively, these observations provide the first demonstration of spontaneous development of inflammation in mice with Tg overexpression of mammalian sPLA2. | Group III Phospholipases A2 |
BACKGROUND: Laryngeal cancer has a significant impact on patients. This study compared the Voice-Related Quality of Life (V-RQOL) outcomes specific to 3 different postlaryngectomy voice rehabilitation methods. METHODS: We conducted a retrospective review of 75 patients with laryngectomy from our V-RQOL questionnaire database. RESULTS: The database included 18 electrolaryngeal speech (ELS), 15 esophageal speech (ES), and 42 tracheoesophageal speech (TES) patients. Pairwise comparisons of V-RQOL outcomes showed that TES was perceived to be better than ELS (p < .001). ES was perceived as better than ELS, but this was driven by a difference in the total and social-emotional V-RQOL scores (p < .05). There was no difference between TES and ES groups. Only ELS showed a positive correlation with time after surgery and older age. CONCLUSIONS: Patients using TES had similar V-RQOL outcomes compared to ES and both performed significantly better than ELS. For ELS, the total V-RQOL score was better with longer time after surgery and older age. | Speech, Esophageal |
A Gram-negative, rod-shaped, non-motile, non-spore forming, aerobic, orange-pigmented bacterium, designated strain 6P(T), was isolated from a soil sample collected from the Hoh Xil basin, China. Strain 6P(T) grew optimally at 25 degrees C, pH 7.0-7.5 and NaCl concentration of 0-1 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 6P(T) belongs to the genus Sphingomonas, with high sequence similarity (97.1 %) to Sphingomonas fennica. The DNA-DNA hybridization homology with S. fennica DSM 13665(T) was 45.3 %. The DNA G+C content of the novel strain is 65.3 mol%. The isolate contained Q-10 as the only respiratory quinone. The major polar lipids are diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC) and sphingoglycolipid (SGL). C18:1 omega7c and C16:1 omega7c are the major fatty acids. On the basis of the polyphasic evidence presented, strain 6P(T) represents a novel species of the genus Sphingomonas, for which the name Sphingomonas arantia sp. nov. is proposed. The type strain is 6P(T) (=CGMCC 1.12702(T) = JCM 19855(T)). | Sphingomonas |
BACKGROUND: Concurrent septorhinoplasty (SRP) and functional endoscopic sinus surgery (FESS) has been a controversial topic in the literature over the last decade. Warnings and admonitions about the risks of performing these procedures together in a single surgery are both published and voiced at national meetings. Although pros and cons have been discussed in the literature, there have been no guidelines published based solely on a review of the level of evidence. METHODS: A systematic review of the literature was performed and the Clinical Practice Guideline Manual, Conference on Guideline Standardization (COGS), and the Appraisal of Guidelines and Research Evaluation (AGREE) instrument recommendations were followed. Study inclusion criteria were an adult population >18 years old, description or implication of study design available, concurrent FESS and SRP performed without additional procedures, and report of complications included in the study. RESULTS: We identified and evaluated the literature meeting those criteria: 11 retrospective studies. The literature was reviewed for both quality of research design as well as benefit and harm of the proposed interventions. CONCLUSION: If a patient is in need of FESS and SRP, either for functional or cosmetic reasons, and is found on the risk matrix to either have low or moderate risk, that patient is a good candidate for a concurrent procedure. If the patient is found to have higher risk, it is not an absolute contraindication, but the surgeon must use best clinical judgment when deciding to move forward and must counsel the patient preoperatively about possible increased risks. | Nasal Surgical Procedures |
In hemodialysis patients who reuse formaldehyde-sterilized dialysers we found that antibodies agglutinating native NN red cells belonged exclusively to the IgM fraction of immunoglobulins. In the same patients antibodies directed against formaldehyde-altered NN red cells proved to be mainly IgG in addition to IgM. Three stages of formaldehyde-dependent RBC immunization could be distinguished serologically. The production of these antibodies was dependent on the time of hemodialysis treatment. We found antibodies which could bind complement in the presence of soluble antigen. These antibodies are supposed to damage the patient's red cells immediately after contact to minute amounts of formaldehyde during hemodialysis. | Isoantibodies |
The concentrations of prostaglandin F2alpha 15-keto-13, 14-dihydro-PGF2alpha, and 13,14-dihydro-PGF2alpha were determined in plasma and in endometrial specimens taken from both dysmenorrheic and normal women at the time of their menstruation. The estimations were carried out by means of the gas chromatography-mass spectrometry method. The plasma levels of 15-keto-13,14-dihydro-PGF2alpha in dysmenorrheic women ranged between 32 and 105 pg. per milliliter, which are significantly higher than the corresponding levels in eumenorrheic women, 20 to 33 pg. per milliliter. On the first day of menstrual bleeding the concentration of PGF2alpha in the endometrium was approximately 4 times higher (300 to 2,600 pg. per milligram) in cases of dysmenorrhea than in normal subjects. Treatment with either oral contraceptives or prostaglandin synthetase inhibitors lowered the concentrations significantly and the majority of patients became symptom free. | Prostaglandins F |
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