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There is insufficient evidence to recommend a specific protocol for treatment of infantile spasms (IS) and a lack of standardization among, and even within, institutions. Twice-daily dosing (for the first two weeks) of high-dose natural ACTH for IS is used by many centers and recommended by the National Infantile Spasms Consortium (NISC). Conversely, it is our practice to use once-daily dosing of high-dose natural ACTH for IS. In order to determine the effectiveness of our center's practice, we retrospectively reviewed 57 cases over the past four years at Boston Children's Hospital (BCH). We found that 70% of infants were spasm-free at 14days from ACTH initiation and 54% continued to be spasm-free at 3-month follow-up. Electroencephalogram showed resolution of hypsarrhythmia (when present on the pretreatment EEG) in all responders. Additionally, once-daily dosing of ACTH was well tolerated. We performed a meta-analysis to compare our results against the reports of published literature using twice-daily high-dose ACTH for treatment of IS. The meta-analysis revealed that our results were comparable to previously published outcomes using twice-daily ACTH administration for IS treatment. Our experience shows that once-daily dosing of ACTH is effective for treatment of IS. If larger prospective trials can confirm our findings, it would obviate the need for additional painful injections, simplify the schedule, and support a universal standardized protocol. | Adrenocorticotropic Hormone |
INTRODUCTION: Idiopathic CD4+ Lymphocytopenia (ICL) is a rare entity grouped in non- HIV-related syndromes. ICL is characterized by a marked low CD4 T cell count of <300 cells/mm3 with ambiguous natural history and prognosis. In addition, cryptococcal and nontuberculous mycobacterial infections are reported as known opportunistic infections. Therefore, management turns around vigilant follow-up and treatment of the current clinical scenario of these patients. CASE PRESENTATION: Here, a 55-year-old lady was referred with a history of diffuse headache and intermittent fever for two months, projectile vomiting, and altered mental status for five days. Nonpruritic maculopapular rashes and diffuse desquamation of the skin were noted. She had no significant previous medical history. Based on clinical findings and investigations, she was diagnosed with ICL having disseminated cryptococcosis. Unfortunately, the patient did not undergo specific treatment as she was recognized late, and unfortunately, she died. CONCLUSION: It is of paramount importance to recognize the clinical entity as early as possible to start appropriate treatment, which may positively impact the outcome. Therefore, the clinician must be aware of disseminated cryptococcosis associated with non-HIV states. | Lymphopenia |
In this article, the authors cover tools for financial modeling. Commonly used time lines and cash flow diagrams are discussed. Commonly used but limited terms such as payback and breakeven are introduced. The important topics of the time value of money and discount rates are introduced to lay the foundation for their use in modeling and in more advanced metrics such as the internal rate of return. Finally, the authors broach the more sophisticated topic of net present value. | Economics |
Protein mimotopes, or blocking peptides, are small therapeutic peptides that prevent protein-protein interactions by selectively mimicking a native binding domain. Inexpensive technology facilitates straightforward design and production of blocking peptides in sufficient quantities to allow preventive and therapeutic trials in both in vitro and in vivo experimental disease models. The kidney is an ideal peptide target, since small molecules undergo rapid filtration and efficient bulk absorption by tubular epithelial cells. Because the half-life of peptides is markedly prolonged in the kidneys compared with the bloodstream, blocking peptides are an attractive tool for treating diverse renal diseases, including ischemia, proteinuric states, such as membranous nephropathy and focal and segmental glomerulosclerosis, and renal cell carcinoma. Therapeutic peptides represent one of the fastest-growing reagent classes for novel drug development in human disease, partly because of their ease of administration, high binding affinity, and minimal off-target effects. This review introduces the concepts of blocking peptide design, production, and administration and highlights the potential use of therapeutic peptides to prevent or treat specific renal diseases. | Genitourinary Agents |
Primary ciliary dyskinesia is a genetic disorder causing dysfunctional motility of cilia and impaired mucociliary clearance, resulting in a myriad of clinical manifestations including recurrent sinopulmonary disease, laterality defects and infertility. The heterogenous clinical presentation of primary ciliary dyskinesia and the limitations of transmission electron microscopy to assess ultrastructural defects within the cilium often delay diagnosis. Recent advances in the understanding of the basic biology and function of the cilium have led to potential diagnostic alternatives, including ciliary beat analysis and nasal nitric oxide measurements. Moreover, the identification of disease-causing mutations could lead to the development of comprehensive genetic testing that may overcome many of the current diagnostic limitations. Although the clinical manifestations of primary ciliary dyskinesia have been recognised for over a century, there are few studies examining treatments and standards of care have yet to be established. Multicentre collaborative efforts have been established in North America and Europe, which should help to develop standardised approaches to the diagnosis and treatment of primary ciliary dyskinesia. | Ciliary Motility Disorders |
How a protein domain motion is coupled to the catalytic cycle is a current subject in enzymology. We render down a complicated domain motion in the 5'-deoxyadenosylcobalamin and pyridoxal-5'-phosphate codependent radical enzyme, lysine 5,6-aminomutase, into dominant contributions from Lys370alpha and Asp298alpha to the critical Co-C bond cleavage trigger and open-closed cycle transitions. | Clostridium sticklandii |
Selective disposal of a wide range of cellular entities by macroautophagy/autophagy is achieved through a special class of proteins called autophagy receptors, which link corresponding cargo to the membrane-bound autophagosomal protein Atg8/LC3. In pursuit of novel autophagy receptors and their cargo, we uncovered a previously undescribed autophagy pathway for removal of aberrant clathrin-mediated endocytosis (CME) protein condensates in S. cerevisiae. Of these CME proteins, Ede1 functions as an autophagy receptor, harboring distinct Atg8-binding domains and driving phase separation into condensates. The aberrant CME condensates at the plasma membrane (PM) exhibit a drop-like structure surrounded by a fenestrated ER, which are engulfed in pieces in an Ede1-dependent manner by autophagy. Thus, our work suggests that aberrant CME is a target for autophagic degradation, with the scaffold protein Ede1 serving as a built-in autophagy receptor that monitors the assembly status of the CME machinery. | Autophagy-Related Proteins |
Sororities have been identified as placing young women at risk for body image concerns due to a focus on traditional gender role norms and objectification of women. OBJECTIVE: This study assessed the relationship between conformity to feminine gender role norms, self-objectification, and body image surveillance among undergraduate women. PARTICIPANTS: In a random sample of undergraduates, the authors examined data from sorority and nonsorority women. METHODS: In a random sample of undergraduate women, the authors assessed the impact of traditional feminine gender role norms on self-objectification, body image, and feedback regarding physical appearance for sorority and nonsorority undergraduate women. RESULTS: Three linear regressions were conducted, and only conformity to feminine gender role norms contributed significantly in each regression model. CONCLUSIONS: Regardless of sorority membership, conformity to feminine gender role norms was found to significantly contribute to increased body consciousness, negative body image, and feedback on physical appearance." | College Fraternities and Sororities |
Hospitals have entered into a new era of capital planning. A number of factors will influence hospital buying behavior now that the Medicare capital regulations are being implemented. As purchasing responsibility for additional departments is continually folded into hospitals' central purchasing function there will be increased opportunities for group contracts. As resources shrink and demand for services increases, GPOs will be relied upon for their expertise and financial finesse. The emphasis will be on boosting the use of group contracts among existing members, rather then seeking additional members in a shrinking hospital market. Through effective purchasing, it is generally recognized that a hospital can recover and keep, at best, 5-10 percent of the cost of all purchased goods and services. Group purchasing organizations need to develop better strategies of cooperation with vendors, distributors and hospitals to help providers control capital costs. In this challenging environment, GPOs will aggressively target markets other than acute care as the source of their future growth, just as healthcare facilities are branching out. To accommodate changing needs, the strongest GPOs will continue their evolution into structures more like alliances, offering an array of other cooperative and support programs beyond the purchase of goods and services. | Purchasing, Hospital |
The author describes a new, unique, integrated suction-irrigation system for hydrodissection with bipolar instrumentation which has significantly facilitated the performance of advanced pelviscopic surgery on 350 patients in the department of gynecology between November 1, 1990 and October 31, 1992. | Culdoscopes |
Corn leaf aphid Rhopalosiphum maidis (Fitch) can feed on various cereal crops and transmit viruses that may cause serious economic losses. To test the impact of both host plant species and age on R. maidis, as well as the proteomic difference of diverse populations, we first investigated the survival and reproduction of six R. maidis populations (i.e., LF, HF, GZ, DY, BJ, and MS) via a direct observation method in the laboratory on 10 and 50 cm high maize seedlings, and 10 cm high barley seedlings. Then a proteomic approach was implemented to identify the differentially expressed proteins from both aphids and endosymbionts of BJ and MS populations. Results indicated that the BJ population performed significantly better than the others on both barley and 50 cm high maize seedlings, while no population could survive on 10 cm high maize seedlings. The proteomic results demonstrated that the expression levels of myosin heavy chain (muscle isoform X12) (spot 781) and peroxidase (spot 1383) were upregulated, while ATP-dependent protease Hsp 100 (spot 2137) from Hamiltonella defensa and protein SYMBAF (spot 2703) from Serratia symbiotica were downregulated in the BJ population when compared to expression levels of the MS population. We hypothesize that the fatalness observed on 10 cm high maize seedlings may be caused by secondary metabolites that are synthesized by the seedlings and the MS population of R. maidis should be more stress-resistant than the BJ population. Our results also provide insights for understanding the interaction between host plants and aphids. | Aphids |
The apt gene, coding for adenine phosphoribosyltransferase (APRT), has been isolated from the plant Arabidopsis thaliana. Data from both Southern analysis and characterization of apt clones isolated from a genomic library is consistent with the occurrence of one apt within the A. thaliana genome. Comparison of the nucleotide sequence of the apt gene with its corresponding cDNA indicates that the gene contains five introns, whereas all other apt isolated to date have fewer introns (four in mammals, two in Drosophila). The locations of the introns within the plant apt coding region are not consistent with the placement of introns in the previously isolated apt of murines, human and Drosophila species. In agreement with its expression pattern in vivo, the upstream region of this plant apt is able to express the beta-glucuronidase-encoding gene (gus) in an apparently constitutive manner in transgenic A. thaliana plants. The apt promoter region is notable for its lack of conventional promoter elements such as TATA, CCAAT or G+C-rich sequence elements." | Adenine Phosphoribosyltransferase |
BACKGROUND: Spiroplasma citri comprises a bacterial complex that cause diseases in citrus, horseradish, carrot, sesame, and also infects a wide array of ornamental and weed species. S. citri is transmitted in a persistent propagative manner by the beet leafhopper, Neoaliturus tenellus in North America and Circulifer haematoceps in the Mediterranean region. Leafhopper transmission and the pathogen's wide host range serve as drivers of genetic diversity. This diversity was examined in silico by comparing the genome sequences of seven S. citri strains from the United States (BR12, CC-2, C5, C189, LB 319, BLH-13, and BLH-MB) collected from different hosts and times with other publicly available spiroplasmas. RESULTS: Phylogenetic analysis using 16S rRNA sequences from 39 spiroplasmas obtained from NCBI database showed that S. citri strains, along with S. kunkelii and S. phoeniceum, two other plant pathogenic spiroplasmas, formed a monophyletic group. To refine genetic relationships among S. citri strains, phylogenetic analyses with 863 core orthologous sequences were performed. Strains that clustered together were: CC-2 and C5; C189 and R8-A2; BR12, BLH-MB, BLH-13 and LB 319. Strain GII3-3X remained in a separate branch. Sequence rearrangements were observed among S. citri strains, predominantly in the center of the chromosome. One to nine plasmids were identified in the seven S. citri strains analyzed in this study. Plasmids were most abundant in strains isolated from the beet leafhopper, followed by strains from carrot, Chinese cabbage, horseradish, and citrus, respectively. All these S. citri strains contained one plasmid with high similarity to plasmid pSci6 from S. citri strain GII3-3X which is known to confer insect transmissibility. Additionally, 17 to 25 prophage-like elements were identified in these genomes, which may promote rearrangements and contribute to repetitive regions. CONCLUSIONS: The genome of seven S. citri strains were found to contain a single circularized chromosome, ranging from 1.58 Mbp to 1.74 Mbp and 1597-2232 protein-coding genes. These strains possessed a plasmid similar to pSci6 from the GII3-3X strain associated with leafhopper transmission. Prophage sequences found in the S. citri genomes may contribute to the extension of its host range. These findings increase our understanding of S. citri genetic diversity. | Spiroplasma citri |
The current increase and severity of the natural disasters whose effects on the public health are likely to be even more extreme and complex, requires enhancing and developing the disaster preparedness on the population level. In order to be able to do so, it is inevitable and determinative to know the factors that affect people's preparedness on the population level. Therefore, the objective of this article is to present the results from assessing the factors related to the population preparedness for the disasters on a sample of citizens living from the Slovak Republic. Our research is based on the exploration of the questionnaire survey' results aimed at investigating the preparedness and preventive proactive behaviour of the population against the disasters. The search for the initiators of such a behaviour and assessment of the influence of various aspects (e.g., the respondents' experience with disasters, their vulnerability to disasters, the risk awareness, the perception of the disaster risks in the changing environment, etc.) on the respondents' behaviour against disasters is the main part of the article and is supported by the statistical analysis. The results of the survey suggest that the disaster risk awareness and overall disaster preparedness level is rather poor and the population is inactive. The proactive behaviour of the respondents against the disasters is partially affected by some of their personality and socio-economic characteristics, especially the younger respondents currently incline more to adopting the protective measures. In addition, other aspects, e.g., the negative experience with the disasters in the past influence the preparedness. However, the impacts must have been relatively serious for the proactive behaviour to be influenced. The influences of other aspects as well as the possible methods for improving the disaster preparedness and the possibilities of increasing the resilience of the population as a whole are also discussed in this article. | Extreme Weather |
Densoviruses are a group of arthropod-infecting viruses with a small single-stranded linear DNA genome. These viruses constitute the subfamily Densovirinae of the family Parvoviridae. While recombination in between vertebrate-infecting parvoviruses has been investigated, to date, no systematic analysis of recombination has been carried out for densoviruses. The aim of the present work was to study possible recombination events in the evolutionary history of densoviruses and to assess possible effects of recombination on phylogenies inferred using amino acid sequences of nonstructural (NS) and capsid (viral protein, VP) proteins. For this purpose, the complete or nearly complete genome nucleotide sequences of 40 densoviruses from the GenBank database were used to construct a phylogenetic cladogram. The viruses under study clustered into five distinct groups corresponding to the five currently accepted genera. Recombination within each group was studied independently. The RDP4 software revealed three statistically highly credible recombination events, two of which involved viruses of the genus Ambidensovirus, and the other, viruses from the genus Iteradensovirus. These recombination events led to mismatches between phylogenetic trees constructed using comparison of amino acid sequences of proteins encoded by genome regions of recombinant and non-recombinant origin (regulatory NS1 and NS3 proteins and capsid VP protein). | Densovirinae |
Type 1 interferons (including IFNalpha/beta) activate their cell surface receptor to induce the intracellular signal transduction pathways that play an important role in host defenses against infectious agents and tumors. The extent of cellular responses to IFNalpha is limited by several important mechanisms including the ligand-stimulated and specific serine phosphorylation-dependent degradation of the IFNAR1 chain of Type 1 IFN receptor. Previous studies revealed that acceleration of IFNAR1 degradation upon IFN stimulation requires activities of tyrosine kinase TYK2 and serine/threonine protein kinase D2 (PKD2), whose recruitment to IFNAR1 is also induced by the ligand. Here we report that activation of PKD2 by IFNalpha (but not its recruitment to the receptor) depends on TYK2 catalytic activity. PKD2 undergoes IFNalpha-inducible tyrosine phosphorylation on specific phospho-acceptor site (Tyr-438) within the plekstrin homology domain. Activated TYK2 is capable of facilitating this phosphorylation in vitro. Tyrosine phosphorylation of PKD2 is required for IFNalpha-stimulated activation of this kinase as well as for efficient serine phosphorylation and degradation of IFNAR1 and ensuing restriction of the extent of cellular responses to IFNalpha. | TYK2 Kinase |
The use of benzodiazepine anxiolytic therapy has sometimes been associated with certain adverse reactions. The authors discuss the extent to which the clinician is responsible for warning patients that benzodiazepine therapy may result in addiction, withdrawal problems, and/or impaired cognitive and motor skills. The development of new anxiolytics such as buspirone, which seem to exert less effect on cognitive and motor skills and lack addiction potential (and thus withdrawal problems), presents the clinician with a treatment alternative. The authors review two legal cases involving benzodiazepine-induced driving impairment and discuss whether the clinician is obligated to prescribe the agent that generally demonstrates the least interference with such common activities as driving. Primary issues that arise in the discussion of physician responsibility are informed consent (both verbal and written) and the documentation of all treatment decisions. The authors recommend quality care and individualized treatment to avoid liability. | Anti-Anxiety Agents |
We report 2 cases of pulmonary pleomorphic carcinoma. The patient in case 1 was a 44-year-old man who was admitted to our hospital complaining of dry cough and dyspnea on exertion. Chest radiography and CT showed a huge tumor with left pleural effusion. Percutaneous biopsy suggested malignancy. As distant metastasis was not found and as cytological examination of pleural effusion gave a result of class II, we attempted to perform left pneumonectomy. However, we performed partial resection of the tumor because it had invaded the aorta, pulmonary artery, pericardium and pleura. The pathological diagnosis was pleomorphic carcinoma, p-T4 N2 M0. After the operation, we performed systemic chemotherapy, including cisplatin and irinotecanm with little effect (PD). The patient died of progression of the tumor. Case 2 was a 34-year-old man who was admitted to our hospital complaining of fever and general malaise. Chest radiography and CT showed a tumor in the left upper lobe. As no distant metastasis was found, we tried left upper lobectomy. However, we performed left upper segmentectomy and lymph node dissection because of invasion of the aorta and the chest wall, and because of hypersegmentation of the left upper lobe. Pathological diagnosis was pleomorphic carcinoma, p-T4 N0 M0. After the operation, the mediastinum was subjected to radiation therapy. However, a metastatic tumor was found in the pelvis after this radiation was given. We performed systemic chemotherapy with substances including cisplatin, gemcitabine and vinorelbine, but with little effect (PD). The patient died of peritonitis and pleuritis due to the recurrence and progression of the tumor. Both cases had rapidly growing neoplasms showing little sensitivity to chemotherapy or radiotherapy. Pulmonary pleomorphic carcinoma is suggested to be type of lung cancer with a poor prognosis when the tumor is not resected in the early stages." | Neoplasms, Glandular and Epithelial |
The development of the mammalian visual system begins prenatally at distributed sites, where cells generated at different embryonic ages are destined to interconnect and form the visual pathways, and ends postnatally with the functional tuning of neuronal receptive-field properties. It is reasonable to assume that the earliest stages in this developmental sequence are completed prior to the onset of neural activity, and also that activity may play only a minor role or even none at all in primary axon outgrowth and pathway finding (Harris, 1981; Harris and Holt, 1990). However, recent evidence indicates that subsequent events in development, such as the sorting of axons at their targets, the cellular differentiation of target cells and the formation of synaptic contacts by developing axons, are all influenced by action potentials. Action potentials in the developing retino-geniculo-cortical pathway can be eliminated by blocking the voltage-gated sodium channel with tetrodotoxin. Prenatal blockade prevents the laminar segregation of retinogeniculate axons. Postnatal blockade interrupts the formation of retinogeniculate synaptogenesis, slows the cytoarchitectonic differentiation of the lateral geniculate nucleus and produces abnormalities in the responses of lateral geniculate neurons. In the visual cortex, the development of cells and synapses is retarded and the eye-specific separation of geniculocortical axons is halted, thereby blocking the formation of ocular dominance columns. While the cellular mechanisms underlying these effects are not understood, a partial restoration of normal development can be produced by stimulating blocked axonal pathways electrically. | Visual Pathways |
Methylmalonate semialdehyde dehydrogenase was purified from rat liver in order to define the distal portion of valine catabolism and related pathways in mammals. The purified enzyme is active with malonate semialdehyde and consumes both stereoisomers of methylmalonate semialdehyde, implicating a single semialdehyde dehydrogenase in the catabolism of valine, thymine, and compounds catabolized by way of beta-alanine. The oxidation of malonate and methylmalonate semialdehydes by this enzyme is CoA-dependent, the products being acetyl-CoA and propionyl-CoA, respectively. Expected activity with ethylmalonate semialdehyde as substrate was not found. Methylmalonate semialdehyde dehydrogenase was separated on DEAE-Sephacel into two isoforms which differ in mobility during nondenaturing polyacrylamide gel electrophoresis. The two forms are immunologically cross-reactive and exhibit the same N-terminal sequence, suggesting that one form is the product of the other. The monomer molecular mass, determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, was 58 kDa. The native molecular mass, estimated by gel filtration, was 250 kDa, suggesting a tetrameric structure." | Malonate-Semialdehyde Dehydrogenase (Acetylating) |
Postgastrectomy quality of life (QoL) is affected by various symptoms, and compared with the preoperative baseline QoL, is typically impaired for the first 6 mo after surgery. Thereafter, improvement to a stable QoL is observed at approximately 12 mo postoperatively. We consider the digestive tract reconstruction pattern to be a determining factor in postgastrectomy QoL among gastric cancer patients, and believe it requires further discussion. Proximal gastrectomy is associated with the worst postoperative QoL among gastrectomy procedures and should be performed cautiously. The trend of better QoL provided by the pouch procedure of total gastrectomy requires further robust support. Whether the use of Billroth-I gastroduodenostomy or Roux-en-Y gastrojejunostomy for distal gastrectomy is optimal remains controversial, but Roux-en-Y gastrojejunostomy is likely to be preferable. | Duodenostomy |
Mu wave suppression is thought to accompany the activation of the mirror neuron system which occurs when a human observes or imitates the behavior of others. Our investigation indicates a possible difference in mirror neuron system activation between passive and more active observation as suggested by mu wave activation levels. Participants were asked to observe four different videos each 80 s in duration. Each video was repeated once after a 30 s interval. The first video was of visual white noise and participants were instructed to passively observe the video. This was identified as the Baseline condition and served as a mu activation level baseline. The second video was of simple bouncing balls and the observer was again asked to passively observe the video (Ball condition). The third video was of a moving hand (Observation condition). The forth video was of the same moving hand and participants also imagined executing the observed hand movement (Imagination condition). As hypothesized, the Imagination condition activated the greatest level of mu suppression, while the Ball condition activated the lowest level of mu wave suppression. The Observation condition produced a slightly larger level of mu wave suppression than the Ball condition. This progressive increase in mu wave suppression supports the hypothesis that the activation of the mirror neuron system increases as the level of active observation increases. | Mirror Neurons |
The dramatic increase in use of contraception worldwide makes it imperative to understand the effects of contraceptives on the health of women using them. In this article, we review the literature on the relationships of modern nonsurgical contraception with pelvic inflammatory disease. Subsequently, we identify areas where further research is needed to better define the risks and benefits of these contraceptive methods in various settings. From our review, two new conclusions emerge. First, our reanalysis of published data on the risk of PID associated with intrauterine device (IUD) use compared with no contraceptive use shows, with one exception, less risk than the previous comparisons to all non-IUD use. Second, and probably most importantly, the studies, when taken together, strongly imply that oral contraceptives have a protective effect against PID. Only one study of 11 is equivocal on this point." | Contraceptives, Oral, Synthetic |
Painful conditions of the acromioclavicular joint without instability can be treated successfully with arthroscopic methods. The direct approach is best suited for isolated acromioclavicular pathology. It also can be used to address the acromioclavicular joint during shoulder arthroscopy and bursoscopy, but two additional acromioclavicular portals are needed. In patients with both subacromial and acromioclavicular joint pathology, the bursal approach to the acromioclavicular joint can be used. In some patients with narrow or medially inclined overriding clavicles, the distal clavicle is not easily resected with the bursal approach. The direct approach is an alternative in these situations. Either method has been shown to be an effective treatment and can return the patient to full activity much sooner than with a traditional open resection. | Acromioclavicular Joint |
BACKGROUND: This article describes a preperiosteal midcheek lift technique performed by means of the midcheek soft-tissue spaces by precise release of the retaining ligaments that separate the spaces. METHODS: From November of 2009 to June of 2014, 184 patients underwent this procedure. A transcutaneous lower eyelid blepharoplasty incision was used to access the preseptal space. Medially, the orbicularis oculi origins and tear trough ligament are released sharply, connecting the dissection with the premaxillary space. More laterally, the orbicularis retaining ligament is released, connecting the dissection with the prezygomatic space. With this release, the entire midcheek can be effectively lifted. The fat pads were managed by transposition, excision, or with septal resets as indicated. Canthopexy is performed routinely to provide lower eyelid support. Superolateral traction on the orbicularis oculi elevates the entire midcheek, and this was secured to the lateral orbital rim periosteum. In patients with significant volume loss in the midcheek, structural fat grafting is performed. RESULTS: All patients demonstrated a significant rejuvenation of the midcheek with elimination of the eye bags and elevation of the lid-cheek junction and the cheek prominence and improvement of the nasolabial folds. The majority of the patients (96 percent) were satisfied with the procedure. Complication rates were low. Ectropion occurred in 1 percent of patients, and lower lid retraction occurred in 1 percent of patients. CONCLUSION: The midcheek lift by means of the facial soft-tissue spaces is safe, effective, and long lasting. As the dissection is atraumatic, recovery is quick and complications are minimized. | Cheek |
Addition of histidyl-peptides containing the glycyl-glycyl-L-histidyl sequence stimulated the catalysis of Ni(II) hydrogen peroxide reduction. Maximum bleaching of murexide or nitrosodimethylaniline was obtained with glycyl-glycyl-L-histidine. A decrease in the bleaching rates was observed upon addition of SOD or hydroxyl radical scavengers, showing that the hydrogen peroxide/Ni(II)/glycyl-glycyl-L-histidine system generated superoxide anions as well as hydroxyl radicals. In contrast, addition of glycyl-glycyl-L-histidine inhibited the Cu(II) hydrogen peroxide reduction. When peptides or proteins were exposed to oxygen radicals produced by Ni(II)/glycyl-glycyl-L-histidine catalysis of hydrogen peroxide reduction, the observed effects were similar to those produced by oxygen radicals generated by water radiolysis or by Fe(II) or Cu(II) mediated Fenton-reactions: hydroxylation of phenylalanine, interchange of disulfides, destruction of tryptophans and dityrosine formation. | Murexide |
A clinico-pathologic case of a black hidrocystoma of the left eyelid margin is reported in a 45-year-old female patient. Clinically, a black nodule was disclosed after eversion of the superior left lid. A surgical full thickness eyelid focal resection was performed to remove the cyst. Histopathology found a cyst covered with an epithelium with a double layer of cells and filled with a brownish granular content, typical of a black hidrocystoma. | Hidrocystoma |
Haemozoin (malaria pigment) was isolated from 2 strains of Plasmodium falciparum cultivated in vitro. The purest preparations contained 41 to 45% ferriprotoporphyrin IX and a glycine-rich polypeptide ('apohaemozoin') of approximately 14 kDa molecular weight which is synthesized by the parasite. In the two strains studied, NF54 and K1, it was calculated that about 15 and 18 iron porphyrin molecules, respectively, were associated with each molecule of apohaemozoin, which contained more hydrophobic amino acid residues in strain K1. One molecule of iron porphyrin was associated with every 9-10 amino acid residues in the haemozoin of both strains. Our observations support the idea that the intraerythrocytic malaria parasite, incapable of cleaving the haem ring, detoxifies the iron porphyrin residuum from haemoglobin digestion in a crystalline complex with a specially synthesized protein. | Pigments, Biological |
BACKGROUND: Osteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7), a member of the transforming growth factor-beta superfamily, has been shown to prevent kidney damage from ischemia/reperfusion injury in rats. The molecular events involved in OP-1 action on kidney are not yet understood. METHODS: In this study, we evaluated the biodistribution of (125)I-labeled OP-1 in rat kidneys. Adult rats received a single intravenous injection of 250 microg (125)I-labeled OP-1 per kg body wt, a dose that was effective in protecting kidneys from ischemic injury. Tissue localization, in situ hybridization, and immunostaining with a specific receptor antibody were performed to identify OP-1 cellular targets. Also, isolated plasma membranes from kidney cortex and medulla regions were analyzed to identify and characterize receptor structural components that recognize OP-1. RESULTS: At 10 and 180 minutes following injection, the relative uptake of (125)I-labeled OP-1 was consistently higher in kidney cortex than in medulla region. Upon autoradiography, kidney tissue sections revealed that OP-1 bound to the convoluted tubule epithelium, glomeruli, and collecting ducts. Moreover, in situ hybridization and immunostaining methods have shown localization of mRNA transcripts and the protein for BMP receptor type II in the cortex and medulla in similar areas as (125)I-labeled OP-1. Bulk membranes (enriched with plasma membranes) isolated from the cortex and medulla regions of kidney each bound specifically to (125)I-OP-1, and the binding of (125)I-labeled OP-1 was inhibited by unlabeled OP-1 in a dose-dependent manner. However, platelet-derived growth factor, transforming growth factor-beta, insulin-like growth factor, fibroblast growth factors, and other members of BMP family such as BMP-2 and cartilage-derived morphogenetic protein-1/growth and differentiation factor-5 (CDMP-1/GDF-5) failed to inhibit the binding of (125)I-labeled OP-1 to receptors, suggesting a high degree of specificity with which OP-1 bound to kidney receptors. Scatchard analysis of quantitative binding data indicated that the OP-1 receptors of kidney contained a single class of high-affinity binding sites for OP-1 with an association constant (Ka) of 2.26 x 109 mol/L-1 and a binding capacity of 1.01 pmol of OP-1 per mg membrane protein. When analyzed by a ligand blot technique, plasma membranes isolated from kidney cortex and medulla each showed the presence of a prominent specific band with a relative molecular mass (Mr) of 100 kD. Further analysis by Western blotting indicated that an antibody raised against BMP type II receptor effectively recognized the 100 kD OP-1 binding component of kidney plasma membranes. CONCLUSIONS: We demonstrated, to our knowledge for the first time, the presence of membrane-bound, specific, high-affinity OP-1 receptors in rat kidney tissues, which are likely to mediate OP-1 actions in the kidney. The major OP-1-binding component of the kidney appears to be a long form of BMP type II receptor with a Mr of 100 kD. In vivo and in vitro evidence suggests that the cellular targets for OP-1 are convoluted tubule epithelium, glomeruli, and collecting ducts. OP-1 does not share receptor binding properties with other growth factors, including BMP-2 and CDMP-1, suggesting that its mode of action in kidney appears to be specific." | Bone Morphogenetic Protein Receptors |
Itch is an extremely frequent and enervating symptom of many diseases. Current anti-itch therapy, which is based almost exclusively on an immunocentric" viewpoint, is often unsatisfactory. Recent studies show that this symptom is in fact the result of a complex interplay among skin, nervous system, endocrine system, and immune system. This explains the frequent failure of therapeutic strategies focused only on a single factor and suggests the usefulness of a polypharmacologic symptomatic treatment, designed on a case-by-case basis as a result of a multidisciplinary approach. We discuss the perspectives of anti-itch therapy in light of the new pathogenetic and pharmacologic acquisitions." | Antipruritics |
Many phthalate esters (PAEs) are chemicals of high production volume and of toxicological concern. The second-order rate constant for base-catalyzed hydrolysis ( k(B)) is a key parameter for assessing environmental persistence of PAEs. However, the k(B) values for most PAEs are lacking, and the experimental determination of k(B) encounters various difficulties. Herein, density functional theory (DFT) methods were selected by comparing empirical k(B) values of five PAEs and five carboxylic acid esters with the DFT-calculated ones. Results indicate that PAEs with cyclic side chains are more vulnerable to base-catalyzed hydrolysis than PAEs with linear alkyl side chains, followed by PAEs with branched alkyl side chains. By combining experimental and DFT-calculated second-order rate constants for base-catalyzed hydrolysis of one side chain in PAEs ( k(B_side chain)), quantitative structure-activity relationship models were developed. The models can differentiate PAEs with the departure of the leaving group (or the nucleophilic attack of OH(-)) as the rate-determining step in the hydrolysis and estimate k(B) values, which provides a promising way to predict hydrolysis kinetics of PAEs. The half-lives of the investigated PAEs were calculated and vary from 0.001 h to 558 years (pH = 7 approximately 9), further illustrating the necessity of prediction models for hydrolysis kinetics in assessing the environmental persistence of chemicals. | Density Functional Theory |
The abilities of the substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, p-chloroamphetamine (PCA) and fenfluramine to induce synaptosomal [3H]serotonin (5-HT) release were compared using a novel microassay system. The rank order of release potencies was found to be (+/-)PCA congruent to (+)-fenfluramine greater than (+)-MDMA much greater than (+)-methamphetamine. Combination of two drugs at their EC50 did not cause more release than either drug alone at an equivalent concentration. In addition, the 5-HT uptake blockers fluoxetine and cocaine inhibited the release induced by MDMA, methamphetamine, PCA and fenfluramine to the same percentage. However, threshold concentrations of the substituted amphetamines known to inhibit uptake did not attenuate the release caused by higher concentrations of these compounds. These results suggests that MDMA, methamphetamine, PCA and fenfluramine cause 5-HT release via a common mechanism. Furthermore, these results indicate that the 5-HT uptake blockade induced by these substituted amphetamines in vitro is different from that induced by either fluoxetine or cocaine. | p-Chloroamphetamine |
X-linked liver glycogenosis (XLG) is one of the most common glycogen storage diseases. We present the first case of a large PHKA2 gene deletion from intron 19 to intron 26 in an XLG patient. An aberrant cDNA with skipping of exons 20-26 was detected. Alu element-mediated unequal homologous recombination between an Alu-Jo in intron 19 and another Alu-Sg in intron 26 appears to be responsible for this deletion." | Glycogen Storage Disease Type VIII |
Alopecia areata (AA) is a common autoimmune disease manifesting varying degrees of hair loss. Rapidly progressive AA (RP-AA) is a severe subtype of AA and often resistant to skin-directed treatments. i.v. corticosteroid pulse therapy has been applied for RP-AA; however, the treatment outcome can only become evaluable several months after the intervention, discomposing the patients. In this study, we attempted to develop a scoring system to predict treatment outcomes based on statistical correlations between newly identified predictors and the recovery rates calculated by digital image analysis. Thirty RP-AA patients (15 men and 15 women) who underwent pulse therapy and demonstrated total hair loss during the clinical course were included. The percentages of hair regrowth (%HR) at 6 months after the treatment were quantitatively calculated by image analysis software. The correlation between %HR and clinicopathological and immunological variables were statistically assessed. The analysis identified four confirmatory contributors including female sex (P = 0.015), absence of previous AA history (P = 0.02), lower peripheral blood eosinophil count (P = 0.02) and mild to moderate cell infiltration around the hair bulb (P = 0.034), together with a potential contributor, namely absence of atopic dermatitis in their medical history (P = 0.08). The scoring system was developed by double counting confirmatory variables and single counting a potential variable. Importantly, the scores obtained by this system demonstrated significant correlation with %HR (r = 0.61, P < 0.001). The usefulness of this scoring system was further validated by assessing additional 20 cases of RP-AA. When combined with a recently published algorithm for early detection of self-healing subset, the current scoring system may help strategize the therapeutic approach for RP-AA. | Pulse Therapy, Drug |
Brugada syndrome is an inherited disease characterized by an increased risk of sudden cardiac death owing to ventricular arrhythmias in the absence of structural heart disease. Since the first description of the syndrome >20 years ago, considerable advances have been made in our understanding of the underlying mechanisms involved and the strategies to stratify at-risk patients. The development of repolarization-depolarization abnormalities in patients with Brugada syndrome can involve genetic alterations, abnormal neural crest cell migration, improper gap junctional communication, or connexome abnormalities. A common phenotype observed on the electrocardiogram of patients with Brugada syndrome might be the result of different pathophysiological mechanisms. Furthermore, risk stratification of this patient cohort is critical, and although some risk factors for Brugada syndrome have been frequently reported, several others remain unconfirmed. Current clinical guidelines offer recommendations for patients at high risk of developing sudden cardiac death, but the management of those at low risk has not yet been defined. In this Review, we discuss the proposed mechanisms that underlie the development of Brugada syndrome and the current risk stratification and therapeutic options available for these patients. | Brugada Syndrome |
The Trail Making Test (TMT) is one of the most popular neuropsychological tests for executive functions (EFs) assessment. It presents several strengths: it is sensitive to executive dysfunction, it is easy to understand, and has a short administration. However, it has important limitations. First, the underlying EFs articulated during the task are not well discriminated, which makes it a test with low specificity. Second, the pen-and-paper version presents one trial per condition which introduces high variability. Third, only the total time is quantified, which does not allow for a detailed analysis. Fourth, it has a fixed spatial configuration per condition. We designed a computerised version of the TMT to overcome its main limitations and evaluated it in a group of neurotypical adults. Eye and hand positions are measured with high resolution over several trials, and spatial configuration is controlled. Our results showed a very similar performance profile compared to the traditional TMT. Moreover, it revealed differences in eye movements between parts A and B. Most importantly, based on hand and eye movements, we found an internal working memory measure that showed an association to a validated working memory task. Additionally, we proposed another internal measure as a potential marker of inhibitory control. Our results showed that EFs can be studied in more detail using traditional tests combined with powerful digital setups. The cTMT showed potential use in older adult populations and patients with EFs disorders. | Trail Making Test |
Adrenoleukodystrophy is a genetically determined disorder inherited as an X-linked recessive trait due to the defective peroxisomal oxydation of very long chain fatty acids (VLCFA). It is hallmarked by demyelination of the central nervous system and adrenal insufficiency. Even though the studies concerning the molecular basis of the disease are in progress, the role of VLCFA in the demyelination is still unclear. In this paper we report the most recent knowledges about genetics, pathogenesis and treatment of this disorder. 117 cases have been recognized in Italy in the period 1985-1997, but many cases could be missing due to the heterogeneus clinical manifestations that vary from mild to very severe forms. To control the devastating course of this disease two therapeutic approaches are under evaluation: bone marrow transplantation and dietary treatment based on a mixture of glyceroyl trioleate and glyceroyl trierucate. Nevertheless this dietary treatment provides normalization of plasma VLCFA, no significant modification of the natural course of the disease has been demonstrated. For what concerns bone marrow transplantation, in recent years a more accurate selection of patients and donors has been giving favourable results, but some strict criteria should be respected. | Adrenoleukodystrophy |
Cisatracurium (51W89) is one of the ten stereoisomers of atracurium, accounting for about 15% of the racemate. The ED95 of cisatracurium was determined to be about 50 micrograms/kg (cation, molecular weight 929), while the ED95 of atracurium (besylate salt, molecular weight 1245) was 250 micrograms/kg. Thus, on a molar basis in adult patients, cisatracurium is about 3.5 times as potent as the racemic atracurium mixture. We compared atracurium with cisatracurium in healthy adult patients and found an almost identical pharmacodynamic profile. In children, an ED95 of about 40 micrograms/kg was determined, while a 1-min-longer onset of cisatracurium was found in geriatric than in young adult patients. The presence of chronic renal failure did not prolong the duration of action of cisatracurium. The recovery of neuromuscular transmission from a cisatracurium infusion of up to 145 h was investigated in intensive care unit patients. Their time from the end of infusion to a train-of-four ratio > 0.7 (68 +/- 18 min) was on average only some 70% longer than after an infusion of cisatracurium for 2 h in normal surgical patients. In another study, no signs of histamine release nor any clinically relevant cardiovascular effects of cisatracurium were found in doses up to eight times ED95. | Atracurium |
Approximately 45% of on-duty related mortalities were due to sudden cardiac death, with many of these fatalities related to cardiovascular disease and overexertion, while performing emergency duties. Therefore, the aim of this systematic review was to determine the association between cardiovascular disease risk factors and cardiorespiratory fitness in firefighters. A literature search of PubMed, SCOPUS, Web of Science, Embase, EBSCOHost, and ScienceDirect was conducted; the Rayyan((R)) intelligent systematic review tool was used to screen and select studies for inclusion. The appraisal tool for cross-sectional studies and the Critical Appraisal Skills Programme toolkit were used for methodological assessment of included studies. Data were analyzed using the Review Manager 5.3 and MedCalc((R)) statistical softwares to determine the effects of obesity (Z = 10.29, p < 0.001) and aging (Z = 4.72, p < 0.001) on cardiorespiratory fitness. Furthermore, there was a significant effect for cardiorespiratory fitness level on systolic blood pressure (Z = 5.94, p < 0.001), diastolic blood pressure (Z = 2.45, p < 0.001), total cholesterol levels (Z = 3.80, p < 0.001), low-density lipoprotein cholesterol (Z = 4.44, p < 0.001), triglycerides (Z = 3.76, p < 0.001) and blood glucose concentration (Z = 4.78, p < 0.001). Cardiovascular disease risk factors and cardiorespiratory fitness were significantly and inversely associated in firefighters. Fire service departments should adopt behavioral intervention strategies to maintain optimum cardiovascular disease risk factor profiles and cardiorespiratory fitness among firefighters to ensure their occupational well-being. | Physical Fitness |
Only a few specific chemokines that mediate interactions between inflammatory and satellite cells in muscle regeneration have been identified. The chemokine CXCL16 differs from other chemokines because it has both a transmembrane region and active, soluble chemokine forms. Indeed, we found increased expression of CXCL16 and its receptor, CXCR6, in regenerating myofibers. Muscle regeneration in CXCL16-deficient (CXCL16KO) mice was severely impaired compared with regeneration in wild-type mice. In addition, there was decreased MyoD and myogenin expression in regenerating muscle in CXCL16KO mice, indicating impaired satellite cell proliferation and differentiation. After 1 month, new myofibers in CXCL16KO mice remained significantly smaller than those in muscle of wild-type mice. To understand how CXCL16 regulates muscle regeneration, we examined cells infiltrating injured muscle. There were more infiltrating neutrophils and fewer macrophages in injured muscle of CXCL16KO mice compared with events in wild-type mice. Moreover, absence of CXCL16 led to different expression of cytokines/chemokines in injured muscles: mRNAs of macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2 were increased, whereas regulated on activation normal T cell expressed and secreted, T-cell activation-3, and monocyte chemoattractant protein-1 mRNAs were lower compared with results in muscles of wild-type mice. Impaired muscle regeneration in CXCL16KO mice also resulted in fibrosis, which was linked to transforming growth factor-beta1 expression. Thus, CXCL16 expression is a critical mediator of muscle regeneration, and it suppresses the development of fibrosis. | Chemokine CXCL6 |
OBJECTIVE: To determine the prevalence of the Wernicke-Korsakoff syndrome (WKS) in Australia and compare this with previous studies. DESIGN AND SETTING: Prospective autopsy study at the New South Wales Institute of Forensic Medicine, 1996-1997. METHODS: Brains of deceased people (aged over 15 years) derived from 2212 sequential autopsies performed between 1 January 1996 and 31 December 1997 were studied macroscopically and microscopically to identify cases of WKS. MAIN OUTCOME MEASURES: Standard histological criteria for WKS and any available clinical data. RESULTS: Twenty-five cases of WKS were identified (prevalence, 1.1%), mostly among the 5.9% of the 2212 people who had a history suggestive of alcohol abuse. Only four cases (16%) had been diagnosed during life. CONCLUSIONS: There has been a significant reduction in the prevalence of WKS in Australia since the introduction of thiamine enrichment of bread flour. While the prevalence is still higher than in most other Western countries, further research is needed before adding thiamine to alcoholic beverages can be recommended. | Wernicke Encephalopathy |
Climate change is creating an increase in temperatures, which is harming the quality of life of people all over the world, particularly those with minimal financial resources. While 30% of the world's population is now vulnerable to extreme heat, estimates show that ratio will rise to 74% in the next 20 years, according to forecasts. Using the UrbClim climate model, this study examines the space-time variability of the heat stress index (HI) in different local climate zones (LCZs), as well as how heat wave conditions might affect this index based on land use and land cover. To that end, Seville, in Southern Spain, was investigated during the summer of 2017, when it had four heat waves. The following indices were considered for each urban sub-area: Normalized Difference Vegetation, Proportion Vegetation, Normalized Difference Built, and Urban Index. The goal is to conduct a statistical analysis of the link between the aforementioned elements and the heat stress index in order to recommend mitigation and resilience techniques. Our findings showed that compact and industrial LCZs (2, 3, and 10) are less resistant to HI than open and rural regions (5, 6, B, D, and G), which are more resistant to HI due to higher vegetation rates. The heat wave condition exacerbates the HI in all LCZs. As a result, initiatives such as enhancing open space, increasing green space, or using green roofs and facades might alleviate heat stress and improve people's quality of life. | Climate Models |
Atypical fibroxanthoma (AFX) with osteoclast-like giant cells is a rare entity. We present the case of an elderly woman who presented with a pink-purple dome-shaped nodule with central hyperkeratotic crust. Biopsy revealed a cellular, dermal-based tumor comprised of spindle, oval, and osteoclast-like giant cells with pleomorphism. The immunohistochemistry profile supported a diagnosis of AFX with osteoclast-like giant cells. We performed a literature review through PubMed and Google Scholar for AFX with osteoclast-like giant cell formation and found 16 previously reported cases. We aim to provide a review and discuss features of these cases. We also discuss the pathogenesis of these osteoclast-like cells as well as potential pitfalls in diagnosis. | Giant Cells |
The combination of electrogenerated chemiluminescence (ECL) and aptamer-gated indicator delivering (gAID) magnetic mesoporous silica nanoparticles embedded into glass fibre paper functionalised with poly(ethyleneglycol) and N-(3-triethoxysilylpropyl)diethanolamine allowed the development of a rapid test that detects penicillin directly in diluted milk down to 50+/-9 ppt in <5 min. Covalent attachment of the aptamer cap" to the silica scaffold enabled pore closure through non-covalent electrostatic interactions with surface amino groups, while binding of penicillin led to a folding-up of the aptamer thus releasing the ECL reporter Ru(bpy)(3)(2+) previously loaded into the material and letting it be detected after lateral flow by a smartphone camera upon electrochemical excitation with a screen printed electrode inserted into a 3D-printed holder. The approach is simple, generic and presents advantages with respect to sensitivity, measurement uncertainty and robustness compared with conventional fluorescence or electrochemical detection, especially for point-of-need analyses of challenging matrices and analytes at ultra-trace levels." | Reagent Strips |
The number of metrial gland cells in the maternal placental supply vessels was found to be greater in C57B1 than in Swiss Webster mice from the eleventh to the thirteenth day of gestation. Since it has been found previously that the number of these cells lodged in the labyrinth is greater in Swiss Webster than in C57B1 mice, it appears likely that more disintegrate in the C57B1 than in the Swiss Webster strain. However, some cells in both strains were found in the veins draining the placenta and uterine wall and have been observed previously in lung capillaries. Disintegration is not, therefore, the sole mechanism of loss. The increase, with time, in the number of metrial gland cells in the metrial gland portion of the placental supply vessels in both strains suggests that, although there is overlap, the decidua basalis is the early source of migrating metrial gland cells, and that the metrial gland later augments the flow. | Metrial Gland |
OBJECTIVES: In 2006, Medicare Part D transitioned prescription drug coverage for dual-eligible nursing home residents from Medicaid to Medicare and randomly assigned them to Part D prescription drug plans (PDPs). Because PDPs may differ in coverage, plans may be more or less generous for drugs that an individual is taking. Taking advantage of the fact that randomization mitigates potential selection bias common in observational studies, this study sought to assess the effect of PDP coverage on resident outcomes for three medication classes--antidepressants, antipsychotics, and cholinesterase inhibitors. DESIGN: Retrospective cohort study to examine the effect of coverage restrictions--including noncoverage and coverage with restrictions--on depression, hallucinations and delusions, aggressive behaviors, cognitive performance, and activities of daily living for dual-eligible nursing home residents randomized to PDPs in 2006 to 2008. The analyses further adjusted for baseline health status to address any residual imbalances in the comparison groups. SETTING: Linked data from Medicare claims, Minimum Data Set assessments, pharmacy claims, and PDP formulary information. PARTICIPANTS: Dual-eligible nursing home residents aged 65 and older living in facilities that contracted with a single pharmacy provider. RESULTS: PDP coverage restrictions in three medication classes of interest were not significantly associated with the resident outcomes examined. Although cholinesterase inhibitor users facing coverage restrictions had a 0.04-point lower depression rating score than residents facing no restrictions, this difference was not statistically significant after adjusting for multiple comparisons. CONCLUSION: The findings suggest that exogenous changes in coverage for three commonly used medication classes had no detectable effect on nursing home resident outcomes in 2006 to 2008. There are several possible explanations for this lack of association, including the role of policy protections for dual-eligible nursing home residents and the possibility that suitable clinical alternatives were identified or that previously used medications offered little clinical benefit." | Dual MEDICAID MEDICARE Eligibility |
cDNA sequences for human uroplakins UPIa, UPIb, UPII, and UPIII were cloned and used to investigate uroplakin transcription by normal and neoplastic urothelial cells. Normal urothelium expressed mRNA for all four uroplakins, although UPIII could be detected only by ribonuclease protection assay. By in situ hybridization, UPIa and UPII were confined to superficial cells and UPIb was also expressed by intermediate cells. Cultured normal human urothelial cells showed a proliferative basal/intermediate cell phenotype and constitutive expression of UPIb only. Uroplakin expression by transitional cell carcinoma cell lines was related to their differentiated phenotype in vitro. RT4 cells expressed all uroplakins, VM-CUB-3 expressed three uroplakins, RT112 and HT1376 cells expressed only UPIb in high abundance, and COLO232, KK47, and EJ cells had no detectable expression. These results correlated with patterns of uroplakin expression in tumors. UPIa and UPII were detected superficially only in well differentiated transitional cell carcinoma papillae. UPIb was positive in seven of nine and overexpressed in five of nine noninvasive transitional cell carcinomas and was also present in four of eight invasive transitional cell carcinomas. Lymph node metastases retained the same pattern of UPIb expression as the primary tumor. Unlike the three differentiation-regulated uroplakins, UPIb may have an alternative role in urothelial cell/tissue processes. | Uroplakin Ia |
PURPOSE OF REVIEW: To discuss the recent applications of electrophysiological principles to the optimization and automation of the IVF laboratory. RECENT FINDINGS: There is growing evidence showing improvement of live birth rates following oocyte electro-activation. Novel applications using electrophysiological techniques are now employed to determine oocyte penetration and viability in real-time. SUMMARY: In this short review, we summarize the recent advances in the integration of electrophysiological techniques into the assisted reproductive technology laboratories. We describe the potential clinical applications and their advantages such as creation of reliable automated cell injection systems and novel manual intracytoplasmic sperm injection (ICSI) training platforms. We also discuss theoretical adverse effects and ways to mitigate them." | Sperm Injections, Intracytoplasmic |
Pseudoazurin (PAz), a well-characterized blue copper electron-transfer protein, is shown herein to be capable of mediating electron transfer to the nitrous oxide reductase (N(2)OR) from Achromobacter cycloclastes (Ac). Spectroscopic measurements demonstrate that reduced PAz is efficiently re-oxidized by a catalytic amount of N(2)OR in the presence of N(2)O. Fits of the kinetics resulted in K(M) (N(2)O) and k(cat) values of 19.1+/-3.8 muM and 89.3+/-4.2s(-1) respectively. The K(M) (PAz) was 28.8+/-6.6 muM. The electrochemistry of Ac pseudoazurin (AcPAz) in the presence of Ac nitrous oxide reductase (AcN(2)OR) and N(2)O displayed an enhanced cathodic sigmoidal current-potential curve, in excellent agreement with the re-oxidation of reduced AcPAz during the catalytic reduction of N(2)O by AcN(2)OR. Modeling the structure of the AcPAz-AcN(2)OR electron transfer complex indicates that AcPAz binds near Cu(A) in AcN(2)OR, with parameters consistent with the formation of a transient, weakly-bound complex. Multiple, potentially efficient electron-transfer pathways between the blue-copper center in AcPAz and Cu(A) were also identified. Collectively, the data establish that PAz is capable of donating electrons to N(2)OR in N(2)O reduction and is a strong candidate for the physiological electron donor to N(2)OR in Ac. | Achromobacter |
Fe deficiency genes are regulated in response to external supply of Fe as well as internal plant signals. Internal plant signals include plant hormones and systemic signals which coordinate shoot physiological requirements for Fe with local availability of Fe in roots. Induction of IRT1 and FRO2 gene expression can be used to monitor the Fe deficiency status of plant roots. Here, we investigated the role of jasmonate in the regulation of Fe deficiency responses and in the split root system. We found that jasmonate suppressed expression levels of IRT1 and FRO2 but not their inducibility in response to Fe deficiency. Analysis of the jasmonate-resistant mutant jar1-1 and pharmacological application of the lipoxygenase inhibitor ibuprofene supported an inhibitory effect of this plant hormone. Inhibition of IRT1 and FRO2 gene expression by jasmonate did not require the functional regulator FIT. By performing split root analyses we found that systemic down-regulation of Fe deficiency responses by Fe sufficiency of the shoot was not compromised by ibuprofene and in the jasmonate-insensitive mutant coi1-1. Therefore, we conclude that jasmonate acts as an inhibitor in fine-tuning Fe deficiency responses but that it is not involved in the systemic down-regulation of Fe deficiency responses in the root. | FMN Reductase |
A 4-week randomised, double-blind, cross-over study is described which compared the effects of a combination of emepronium bromide and flavoxate hydrochloride with placebo on incontinence and cystometrogram findings in 20 female patients aged 59 to 88 years. All patients initially had detrusor instability demonstrated on cystometrography: 14 patients completed the study; on placebo 10 still had unstable bladders and on active drugs seven were unstable. The number of wettings over a 48-h period before the study commenced and at the end each course of tablets showed no significant differences; also the patients' opinions about the effect on their incontinence indicated that the majority had the same opinion of each course. Active drugs significantly increased residual urine but did not significantly alter the values obtained for maximum cystometric capacity or effective cystometric capacity (the latter volume being maximum cystometric capacity minus the residual urine). No correlation was found, on either course of treatment, between the change to detrusor stability and the amount of improvement in incontinence. Some side effects are described. Despite evidence of a pharmacological effect on the bladder and patients' opinions tending to favour the active combination, nonetheless the main results of this small study do not suggest that the combination of emepronium bromide and flavoxate hydrochloride is an effective treatment of urinary incontinence associated with detrusor instability in elderly women. | Emepronium |
A description is made of the general and odontologic characteristics of Coffin-Lowry syndrome, with a review of the literature and the report of a clinical case. | Coffin-Lowry Syndrome |
Vascular endothelial growth factor-C (VEGF-C) is a key regulator in lymphangiogenesis, and is overexpressed in various malignancies. Integrin alpha4beta1, a new member of the VEGF-C/VEGF receptor pathway, was found to be overexpressed in melanoma tumors. However, little is known regarding the potential role of integrin alpha4beta1 in lymphangiogenesis and other solid tumors. The aim of this study was to investigate the expression patterns of integrin alpha4 and VEGF-C in relation to lymphangiogenesis and clinicopathological parameters in human colon cancer. The expression of integrin alpha4, VEGF-C, and VEGFR-3 was assessed in 71 human colon cancer tissues and 30 paracancerous normal tissues by immunohistochemical staining. Lymphatic microvessel density (LMVD) was measured after D2-40-labeling, and the correlations among different factors were statistically analyzed. The expression of integrin alpha4, VEGF-C, VEGFR-3, and LMVD was higher in colon cancer tissues compared with the normal paracancerous colon tissues. There was a positive correlation between the expression of integrin alpha4 and VEGF-C. Integrin alpha4 and VEGF-C were significantly associated with the clinicopathological parameters (LMVD, Duke's stage, and lymph node metastasis). Kaplan-Meier analyses indicated that patients with high integrin alpha4 or VEGF-C expression had significantly shorter overall survival and tumor-free survival time. Multivariate analyses suggested that integrin alpha4 and VEGF-C may serve as independent prognostic factors for human colon cancer. Both integrin alpha4 and VEGF-C are involved in lymphangiogenesis and lymphatic metastasis. Our results demonstrated that integrin alpha4 is a novel prognostic indicator for human colon cancer. Anat Rec, 299:741-747, 2016. (c) 2016 Wiley Periodicals, Inc. | Integrin alpha4 |
Edible insects have the potential to become one of the major future foods. In fact, they can be considered cheap, highly nutritious, and healthy food sources. International agencies, such as the Food and Agriculture Organization (FAO), have focused their attention on the consumption of edible insects, in particular, regarding their nutritional value and possible biological, toxicological, and allergenic risks, wishing the development of analytical methods to verify the authenticity, quality, and safety of insect-based products. Edible insects are rich in proteins, fats, fiber, vitamins, and minerals but also seem to contain large amounts of polyphenols able to have a key role in specific bioactivities. Therefore, this review is an overview of the potential of edible insects as a source of bioactive compounds, such as polyphenols, that can be a function of diet but also related to insect chemical defense. Currently, insect phenolic compounds have mostly been assayed for their antioxidant bioactivity; however, they also exert other activities, such as anti-inflammatory and anticancer activity, antityrosinase, antigenotoxic, and pancreatic lipase inhibitory activities. | Edible Insects |
Taxadiene synthase gene from Taxus brevifolia was constitutively expressed in the moss Physcomitrella patens using a ubiquitin promoter to produce taxa-4(5),11(12)-diene, the precursor of the anticancer drug paclitaxel. In stable moss transformants, taxa-4(5),11(12)-diene was produced up to 0.05% fresh weight of tissue, without significantly affecting the amounts of the endogenous diterpenoids (ent-kaurene and 16-hydroxykaurane). Unlike higher plants that had been genetically modified to produce taxa-4(5),11(12)-diene, transgenic P. patens did not exhibit growth inhibition due to alteration of diterpenoid metabolic pools. Thus we propose that P. patens is a promising alternative host for the biotechnological production of paclitaxel and its precursors. | Taxaceae |
BACKGROUND: The reasons for, and the extent of, misuse of prescribed substitution medication as well as parallel consumption of other drugs during substitution-based therapy have still not been adequately researched in Germany. METHODS: This study examines the use of substitution medication in German substitution clinics utilizing a nationwide survey with anonymised questionnaires. RESULTS: The analysis of the 605 questionnaires showed a 30-day consumption prevalence of 8.8% with regard to misuse of substitution substances. The lack of available heroin (38%) and the lack of open spots in treatment programs (21%) were quoted as being the main reasons for the misuse of substitution medication. CONCLUSION: Although the misuse of substitution medications is considered an important problem, our study showed that the current misuse was prevalent only among a minority of the patients. German regulations focused on the avoidance of misuse might be partially contributing to the problem. | Opiate Substitution Treatment |
The decision to contest another hospital's planning application is generally a business decision, not a legal one. This article outlines a procedure for hospitals to follow in opposing a planning application, as well as grounds for opposition and the recourses that are available if the planning agency's decision is unfavorable." | State Health Planning and Development Agencies |
This study investigated the machinability (ease of metal removal) of commercially pure (CP) titanium and Ti-6Al-4V alloy. Both CP Ti and Ti-6Al-4V were cast into magnesia molds. Two types of specimens (with alpha-case and without alpha-case) were made for CP Ti and Ti-6Al-4V. Machinability (n = 5) was evaluated as volume loss (mm3) by cutting/grinding the 3.0 mm surface using fissure burs and silicon carbide (SiC) under two machining conditions: (1) two machining forces (100 or 300 gf) at two rotational speeds (15000 or 30000 rpm) for 1 min, and (2) constant machining force of 100 gf and rotational speed of 15000 rpm for 1, 2, 5, 10, and 30 min. As controls, conventionally cast Co-Cr and Type IV gold alloys were evaluated in the same manner as the titanium. When fissure burs were used, there was a significant difference in the machinability between CP titanium with alpha-case and without alpha-case. On the other hand, there was no appreciable difference in the amount of metal removed for each tested metal when using the SiC points. | Alloys |
The hydrolysis of disodium p-nitrophenyl phosphate at pH 9.0 by slices of formaldehydee-fixed rat renal cortex was investigated by colorimetric estimation of the nitrophenol liberated. It was found that three types of activity could be identified on the basis of their responses to inhibitors and cations: (a) alkaline phosphatase sensitive to inhibition by L-tetramisole; (b) potassium-dependent phosphatase, probably identifiable with the phosphatase component of sodium-potassium-dependent transport adenosine triphosphatase (?Na-K-ATPase); and (c) alkaline phosphatase insensitive to L-tetramisole. It was found that in the presence of strontium ions, as used in Na-K-ATPase cytochemistry, the activities of the second and third types of enzyme were approximately equal. The implications of these findings for the cytochemical demonstration of Na-K-ATPase are discussed. | 4-Nitrophenylphosphatase |
Links between metabolism and components of fitness such as growth, reproduction and survival can depend on food availability. A high standard metabolic rate (SMR; baseline energy expenditure) or aerobic scope (AS; the difference between an individual's maximum and SMR) is often beneficial when food is abundant or easily accessible but can be less important or even disadvantageous when food levels decline. While the mechanisms underlying these context-dependent associations are not well understood, they suggest that individuals with a higher SMR or AS are better able to take advantage of high food abundance. Here we show that juvenile brown trout (Salmo trutta) with a higher AS were able to consume more food per day relative to individuals with a lower AS. These results help explain why a high aerobic capacity can improve performance measures such as growth rate at high but not low levels of food availability. | Salmoniformes |
Endocannabinoids, which are typically released by principal cells in response to prolonged depolarization, act as retrograde messengers to inhibit synaptic transmission. A recent study shows that in a specific subtype of cortical interneuron, endocannabinoids released under similar circumstances can also act cell-autonomously. Here, endocannabinoids endow these neurons with a memory of their own activity in the form of a long-term change in excitability. | Autocrine Communication |
Various experiments are described which show the locus of action of ultraviolet radiation and of x-ray in delaying cell division of the fertilized egg of Arbacia punctulata to be in the nucleus. Photorecovery following ultraviolet radiation has its locus in the egg cytoplasm. Analogy is drawn with the action of ultraviolet radiation and photorecovery on the E. coli-bacteriophage system, and certain suggestions are made regarding a common mechanism. Photorecovery after x-ray exposure could not be demonstrated. | Arbacia |
The machine learning (ML) research community has landed on automated hate speech detection as the vital tool in the mitigation of bad behavior online. However, it is not clear that this is a widely supported view outside of the ML world. Such a disconnect can have implications for whether automated detection tools are accepted or adopted. Here we lend insight into how other key stakeholders understand the challenge of addressing hate speech and the role automated detection plays in solving it. To do so, we develop and apply a structured approach to dissecting the discourses used by online platform companies, governments, and not-for-profit organizations when discussing hate speech. We find that, where hate speech mitigation is concerned, there is a profound disconnect between the computer science research community and other stakeholder groups-which puts progress on this important problem at serious risk. We identify urgent steps that need to be taken to incorporate computational researchers into a single, coherent, multistakeholder community that is working towards civil discourse online. | Hate |
pH-Zone-refining counter-current chromatography was successfully applied for the preparative separation of alkaloids from Dactylicapnos scandens. The two-phase solvent system was composed of petroleum ether-ethyl acetate-methanol-water (3:7:1:9, v/v), where 20 mM of triethylamine (TEA) was added to the upper phase as a retainer and 5 mM of hydrochloric acid (HCl) to the aqueous phase as an eluter. In this experiment, the apparatus with an adjustable length of the separation column was used for the separation of alkaloids from D. scandens and the resolution of the compounds can be remarkably improved by increasing the length of the separation column. As a result, 70 mg protopin, 30 mg (+) corydine, 120 mg (+) isocorydine and 40 mg (+) glaucine were obtained from 1.0 g of the crude extracts and each with 99.2%, 96.5%, 99.3%, 99.5% purity as determined by HPLC. The chemical structures of these compounds were confirmed by positive ESI-MS and (1)H NMR. | Fumariaceae |
Cardiovascular diseases (CVD) are the primary cause of death globally. Activation of oxidative stress and inflammatory pathways are contributory to the development of CVD. Pharmacological activities of vanillic acid have been investigated suggesting that they may have therapeutic utility clinically. Given its phenolic nature, the anti-inflammatory and antioxidant properties of vanillic acid have been shown to exert potent inhibitory activity against Adenosine Monophosphate-Activated Protein Kinase (AMPK), Nuclear Factor Kappa B (NF- kappaB), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Nod-like receptor family protein (NLRP), Toll-like receptors (TLRs), Mitogen-Activated Signaling Proteins (MAPK) and Mammalian Target of Rapamycin (mTOR) signaling pathways. Vanillic acid has been shown to block pro-inflammatory cytokines and suppress inflammatory cascades. The inhibitory impact of vanillic acid on reactive oxygen species (ROS) and nitric oxygen synthase (iNOS) expression has also been demonstrated. Vanillic acid reduces oxidative-related markers such as superoxide dismutase (SOD), glutathione (GSH), Heme Oxygenase 1 (HO-1), and glutathione peroxidase (GSH-Px). Here, we review the cardioprotective effects and mechanisms of action of vanillic acid in CVD. Current potential applications of vanillic acid in CVD are discussed concerning preclinical and clinical studies. | Hydroxybenzoate Ethers |
Nowadays, patients with hemophilia A receive a high standard of care; therefore, the most challenging complication of factor VIII (FVIII) replacement therapy has become the development of FVIII inhibitors, which render the concentrate infusion ineffective and expose patients to an increased risk of morbidity and mortality. Among environmental risk factors influencing inhibitor development, the type of FVIII products has always drawn the attention of investigators. Conflicting results are reported in the literature concerning rates of inhibitor development after either plasma-derived or recombinant FVIII concentrates. To help elucidate this controversial issue, we have performed a systematic review and meta-analysis of prospective studies evaluating the incidence of inhibitors in previously untreated patients with severe hemophilia A receiving plasma-derived or recombinant FVIII products. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS), the STrenghtening the Reporting of OBservational studies in Epidemiology and an ad hoc quality score. Overall, 28 prospective studies, including 1,421 patients with hemophilia A, fulfilled our selection criteria and were included in the systematic review. No statistically significant differences were observed in the inhibitor incidence between plasma-derived and recombinant FVIII concentrates considering all (weighted means: 23%, 95% CI: 15-33% vs. 29%, 95% CI: 26-32%) and high titer (16%, 95% CI: 10-26% vs. 18%, 95% CI: 15-21%) inhibitors. Similarly, no significant differences were found in the inhibitor incidence among the different classes of recombinant products. In conclusion, the results of our meta-analysis show that the different types of FVIII products are not associated with different risks of inhibitor development. | Factor VIII |
This study compared the changes in an animal's jump threshold with changes in monoamine content of telencephalon after damage to the lateral hypothalamus produced either by electrolytic lesions or by infusions of 6-hydroxydopamine (6-HDA) and 5,7-dihydroxytryptamine (5,7-DHT). Electrolytic lesions produced significant decreases in jump threshold and in telencephalic content of serotonin, norepinephrine, and dopamine. Infusions of 5,7-DHT, with or without pretreatment with desmethylimipramine, always reduced both jump thresholds and serotonin content even when there was no effect on the content of norepinephrine or dopamine. In contrast, 6-HDA had no effect on jump thresholds or serotonin content, even though both norepinephrine and dopamine were greatly reduced. Nonspecific neural damage produced by infusion of neurotoxins was quite small and did not differ in locus or size from that produced by infusion of vehicle. These results suggest that the increased sensitivity to footshock was solely due to the interruption of ascending serotonergic pathways within the lateral hypothalamus and was not a result of damage either to norepinephrine and dopamine pathways or to some other neural system. | Medial Forebrain Bundle |
Plasma membrane H(+)-ATPase is thought to mediate hypocotyl elongation, which is induced by the phytohormone auxin through the phosphorylation of the penultimate threonine of H(+)-ATPase. However, regulation of the H(+)-ATPase during hypocotyl elongation by other signals has not been elucidated. Hypocotyl elongation in etiolated seedlings of Arabidopsis thaliana was suppressed by the H(+)-ATPase inhibitors vanadate and erythrosine B, and was significantly reduced in aha2-5, which is a knockout mutant of the major H(+)-ATPase isoform in etiolated seedlings. Application of the phytohormone ABA to etiolated seedlings suppressed hypocotyl elongation within 30 min at the half-inhibitory concentration (4.2 microM), and induced dephosphorylation of the penultimate threonine of H(+)-ATPase without affecting the amount of H(+)-ATPase. Interestingly, an ABA-insensitive mutant, abi1-1, did not show ABA inhibition of hypocotyl elongation or ABA-induced dephosphorylation of H(+)-ATPase. This indicates that ABI1, which is an early ABA signaling component through the ABA receptor PYR/PYL/RCARs (pyrabactin resistance/pyrabactin resistance 1-like/regulatory component of ABA receptor), is involved in these responses. In addition, we found that the fungal toxin fusiccocin (FC), an H(+)-ATPase activator, induced hypocotyl elongation and phosphorylation of the penultimate threonine of H(+)-ATPase, and that FC-induced hypocotyl elongation and phosphorylation of H(+)-ATPase were significantly suppressed by ABA. Taken together, these results indicate that ABA has an antagonistic effect on hypocotyl elongation through, at least in part, dephosphorylation of H(+)-ATPase in etiolated seedlings. | Etiolation |
Coelomomyces utahensis is a fungal parasite of several genera of mosquitoes that inhabit rock-pools in southern Utah. Studies of the biology of Coelomomyces and their potential use in biological control of mosquitoes have been hindered by their complex life history, lack of axenic culture methods, and logistical problems producing their arthropod hosts for in vivo culture. In the case of C. utahensis, we have identified the alternate microcrustacean host as Potamocypris unicaudata, which is an ostracod that can be easily reared in abundance and stored for long periods. Described here are the life cycle and culturing of C. utahensis. | Coelomomyces |
What are some take-home lessons on the syndrome of unexplained chest pain? Carefully exclude heart disease, which--unlike esophageally caused chest pain--may be life-threatening. Noncardiac chest pain is a common problem: at least 25% of chest pain patients in coronary care units or emergency rooms rule out" for heart disease. It is a problem that has been vexing physicians for at least 100 years. The pain patterns in ischemic heart disease and in the unexplained pain syndromes, particularly reflux, may be identical. The mechanism may be an "irritable" esophagus, in which the visceral pain threshold is lowered. Look carefully for gastroesophageal reflux, and treat it aggressively. Finally, in all cases, try to establish a diagnosis if at all possible. When patients are told they don't have heart disease and no further workup is pursued, more than half of them continue to have significant morbidity from their chest pain, utilizing health care facilities and visiting doctors (34,35). Research over the past two decades has enlightened us about many patients with unexplained chest pain, but unfortunately we are still confused about many others, and for this group of patients a conservative therapeutic approach may be best." | Chest Pain |
To determine the virulence factors of Mexican wild-type strains of Campylobacter jejuni and Campylobacter coli, 31 wild-type strains were isolated from food and from humans. The production of cytolethal distending toxin and the adherence and invasion capabilities of these strains were assayed in Vero cells. Hard agar plugs with repellents and attractants were used to examine chemotaxis. Mueller-Hinton agar with supplements was used for motility analysis and to measure hemolytic activity. Nine strains of C. jejuni and eight strains of C. coli exhibited motility, most within a diameter of 2 to 13 mm. Most of the strains reacted to the repellent compounds analyzed, and alpha- and beta-like hemolysis and cytotoxicity in Vero cells were observed for all strains. Isolates adhered to and invaded Vero cells to various degrees. Although strains of C. jejuni exhibited stronger adherence but less invasion compared with strains of C. coli, the difference was not significant (P > 0.05). The strains of C. jejuni and C. coli isolated from food and from patients in Mexico could have major impacts on public health. | Epsilonproteobacteria |
Most bioluminescent fishes are self-luminescent, but a substantial minority of bioluminescent teleosts produce light that is due to symbiotic luminous bacteria housed in elaborate light organs. The majority of symbiotically bioluminescent fishes (ten families in five orders) harbors common free-living species of marine luminous bacteria: Photobacterium phosphoreum, P. leiognathi, and P. fischeri (= Vibrio fischeri). Others, associated with the beryciform family Anomalopidae and nine families in the lophiiform suborder Ceratioidei, have apparently obligate symbionts that have recently been identified by small subunit (16S) rRNA analysis as new groups within the genus Vibrio. This article summarizes what is currently known about relationships between light organ symbionts and their hosts, including characteristics of light organ environments, physiology of light organ symbionts, and the evolution of light organ symbionts and their associations. | Vibrionaceae |
Dipfluzine (Dip) is a new derivative of cinnarizine (Cin) first developed by Department of Chemistry, Beijing University. Dip showed a dose-dependently inhibitory effect on both KCl- and NE-induced contraction in the rabbit aortic rings. It was more effective in suppressing the contractile response evoked by KCl than that by NE. Dip also inhibited the KCl-induced contraction in porcine basilar, coronary and radial arteries. Their pD2' values were 5.7 +/- 0.6, 5.4 +/- 0.4 and 4.6 +/- 0.5 respectively. The selectivity of Dip for vasodilation was proved by higher pD2' value of the basilar artery than that of the coronary and radial arteries, and this selectivity of Dip was more significant than that of Cin. The acute iv LD50 of Dip and Cin in mice were 37 and 36 mg/kg, respectively. | Cinnarizine |
In this study, we examine the telomeric functions of the mammalian Mre11 complex by using hypomorphic Mre11 and Nbs1 mutants (Mre11(ATLD1/ATLD1) and Nbs1(Delta)(B/)(DeltaB), respectively). No telomere shortening was observed in Mre11(ATLD1/ATLD1) cells after extensive passage through culture, and the rate of telomere shortening in telomerase-deficient (Tert(Delta)(/)(Delta)) Mre11(ATLD1/ATLD1) cells was the same as that in Tert(Delta)(/)(Delta) alone. Although telomeres from late-passage Mre11(ATLD1/ATLD1) Tert(Delta)(/)(Delta) cells were as short as those from Tert(Delta)(/)(Delta), the incidence of telomere fusions was reduced. This effect on fusions was also evident upon acute telomere dysfunction in Mre11(ATLD1/ATLD1) and Nbs1(Delta)(B/)(DeltaB) cells rendered Trf2 deficient by cre-mediated TRF2 inactivation than in wild-type cells. The residual fusions formed in Mre11 complex mutant cells exhibited a strong tendency toward chromatid fusions, with an almost complete bias for fusion of telomeres replicated by the leading strand. Finally, the response to acute telomere dysfunction was strongly impaired by Mre11 complex hypomorphism, as the formation of telomere dysfunction-induced DNA damage foci was reduced in both cre-infected Mre11(ATLD1/ATLD1) Trf2(F/)(Delta) and Nbs1(Delta)(B/)(DeltaB) Trf2(F/F) cells. These data indicate that the Mre11 complex influences the cellular response to telomere dysfunction, reminiscent of its influence on the response to interstitial DNA breaks, and suggest that it may promote telomeric DNA end processing during DNA replication. | MRE11 Homologue Protein |
This study was prompted by the observation that an Aspergillus niger transformant with a multicopy bphA (benzoate-4-hydroxylase gene) insert did not grow on benzoate, whereas a transformant with only one extra copy could grow. Therefore, an extensive survey has been made for other genes involved in the conversion of benzoate into 4-hydroxy-benzoate. A transformant with two copies of the bphA gene was used in part of the mutation experiments in order to avoid the isolation of many bphA mutants. Filtration enrichment was used to isolate mutants defective in the conversion of benzoate. The Bph mutants that have been isolated belong to six complementation groups. Mutants with a defected structural gene (bphA) were again predominantly found but, in addition, five other groups of mutants that could not grow on benzoate were isolated. Genetic analysis of the mutants showed that the six genes were localized in different parts of the genome. This was used as an additional proof that some mutants involved different genes. Diploids with seven copies of the bphA gene and heterozygous for one of the other bph genes were constructed. No indication has been obtained that any one of the mutant classes is responsible for the growth-limiting factor in bphA multicopy transformants. This study shows that the p-hydroxylation of benzoate is very complex, although the metabolic pathway is straight forward. | Benzoate 4-Monooxygenase |
We present two cases wherein vitiligo developed after the onset of halo formation involving congenital melanocytic nevi to emphasize the possibility of this finding as a potential albeit unusual presentation of vitiligo. | Nevus, Halo |
BACKGROUND: We developed a novel balloon-based endobiliary radiofrequency ablation (RFA) system to overcome the limitations of conventional RFA in treating malignant biliary strictures. This study aimed to evaluate the histological effects of balloon-RFA in porcine bile ducts. METHODS: Balloon-RFA of intrahepatic bile ducts from freshly resected porcine livers was performed for 60 s at 50, 60 and 70 degrees C. The specimens were subsequently sectioned for histological analysis and the slides were digitally scanned. Pseudo-coloring was applied based on the intensity of the ablation effect, and the area and estimated volume of ablation were measured. RESULTS: All samples showed epithelial sloughing and coagulative necrosis, and the entire internal circumference of the bile duct was evenly ablated. Complete transmural necrosis and involvement beyond the wall were found in 0% of samples ablated at 50 degrees C, in 33% at 60 degrees C and 100% at 70 degrees C. The mean depth and estimated volume of the ablation areas were 1.29 mm and 353.84 mm(3), 1.44 mm, and 505.54 mm(3) and 1.81 mm and 702.52 mm(3) at 50, 60 and 70 degrees C, respectively. CONCLUSIONS: Balloon-RFA leads to sloughing of the mucosa and coagulative necrosis. Ablation depth and volume increased in proportion to target temperature. | Radiofrequency Therapy |
Many research areas, e.g., basic research but also applied fields of biotechnology, biomedicine, and diagnostics often suffer from the unavailability of metabolic compounds. This is mostly due to missing easy and efficient synthesis procedures. We herein describe the biocatalytic/enzymatic production of 2-keto-3-deoxy-D-gluconate, an intermediate of central metabolic pathways in all three domains of life and also of bacterial polysaccharides, lipopolysaccharides, and cell wall components. The method is based on the gluconate dehydratase from the hyperthermophilic crenarchaeon Thermoproteus tenax, which can be easily recombinantly overproduced in Escherichia coli and-due to its intrinsic thermostability-rapidly be purified by two precipitation steps. The enzyme completely converts D-gluconate to solely stereochemically pure KDG, taking benefits from the enol-keto-tautomerism of the primary reaction product. The final product can then easily be separated from the protein by ultrafiltration. The simple one-step procedure, which is suitable at least for the lab-scale/gram-scale production of KDG, replaces lengthy multi-step reactions and is easily scalable. This approach also illustrates the great application potential of Archaea with their unusual metabolic pathways and enzymes for the synthesis of added value products. | Thermoproteales |
In bilaterally symmetric animals, the precise assembly of neural circuitry at the midline is essential for coordination of the left and right sides of the body. Commissural axons must first be directed across the midline and then be prevented from re-crossing in order to ensure proper midline connectivity. Here, we review the attractants and repellents that direct axonal navigation at the ventral midline and the receptors on commissural neurons through which they signal. In addition, we discuss the mechanisms that commissural axons use to switch their responsiveness to midline-derived cues, so that they are initially responsive to midline attractants and subsequently responsive to midline repellents. | Commissural Interneurons |
The pyrrole-2-aminoimidazole (P-2-AI) alkaloids are a growing family of marine alkaloids, now numbering well over 150 members, with high topographical and biological information content. Their intriguing structural complexity, rich and compact stereochemical content, high N to C ratio (~1 : 2), and increasingly studied biological activities are attracting a growing number of researchers from numerous disciplines world-wide. This review surveys advances in this area with a focus on the structural diversity, biosynthetic hypotheses with increasing, but still rare, verifying experimental studies, asymmetric syntheses, and biological studies, including cellular target receptor isolation studies, of this stimulating and exciting alkaloid family. | Pyrroles |
The effects of selective D1 (SCH23390) and D2 (spiperone) dopamine antagonists, as well as of haloperidol, were examined on nicotine self-administration, food-maintained responding, and locomotor activity in rats. Antagonists reduced both operant responding and locomotor activity. Response patterns indicated that motor impairment was not the cause of the decreases, since responding was attenuated only in the latter half of operant sessions. Locomotor activity scores were significantly reduced by SCH23390, but not by spiperone. The effects of dopamine antagonists on nicotine self-administration are different from the effects of these antagonists on cocaine self-administration. Results are discussed in terms of the role of dopamine in drug reinforcement versus its role in sensorimotor integration. | Spiperone |
From 1993 to 1998, 29 pyogenic psoas abscesses occurring in 27 patients were seen in Taichung Veterans General Hospital. Their age range was 25 to 85 years. Diabetes mellitus was the leading underlying disease. Fever and pain in the flank area, back and hip were the usual manifestations. The duration of symptoms prior to the diagnosis ranged from 3 days to 6 months. Most abscesses were diagnosed by computed tomography (CT) images and proven by abscess cultures, which were divided into primary and secondary types. Eighteen of 29 abscesses were regarded as primary. Staphylococcus aureus was the most common pathogen in the primary abscesses, followed by Streptococcus agalactiae, Escherichia coli, viridans streptococci, S. epidermidis, and Salmonella spp.. In the secondary abscess category, E. coli was the leading organism in this series, followed by S. aureus, Klebsiella pneumoniae, viridans streptococci and Candida albicans. The associated conditions included epidural abscess, osteomyelitis, septic arthritis, perirenal abscess, pulmonary tuberculosis, empyema, hydronephrosis and trauma history. The initial empiric therapy comprised mostly of cefazolin or oxacillin with or without an aminoglycoside. Thirteen patients underwent percutaneous drainage, while six received surgical debridement, including two with a recurrent abscess. One patient had both drainage and debridement. Others received medical treatment only. Two of the patients with primary abscess died in spite of percutaneous drainage. Therefore, open drainage, besides appropriate antibiotic treatment, is still required to control complex abscesses with sepsis. | Psoas Abscess |
The uptake of stable cesium ((133)Cs) by Calla palustris was evaluated from four different substrates: water, soil, keramzit (a clay granule) and water with the addition of a potassium compound, after an eight days exposure to a solution of 0.5mM cesium chloride. Stable cesium was used because it is commonly supposed that its uptake by plants is the same of that of radiocesium ((137)Cs). The plants were differentiated in their parts (roots, healthy leaves, dead leaves and flowers) and analyzed with ICP-MS. The lowest average concentration of absorbed Cs was found in plants exposed in soil (0.7mg/kg, S.D.=96.8), while the highest in plants exposed in water (147mg/kg, S.D.=51.7). During the experiment the water planted plants removed 31.6% of provided Cs while those planted in soil removed only 0.06%. The addition of potassium to water was tested because of the competition effect that arises between these two elements: this effect was confirmed with the result that the average uptake in the presence of potassium was lower (41mg/kg in exposed plants, S.D.=76.1). The uptake was also lower in the solid-based substrates (soil and keramzit), because of the known tendency of Cs to bind with soil particles, thus becoming less available to plants. There was no evidence that the different parts of the plant showed different uptake effectiveness, or that the health of the plant (evaluated with a qualitative method) had any effect on the uptake of Cs. | Calla Plant |
Using glucose oxidase (GOx) and alpha-Zr(IV) phosphate nanoplates (alpha-ZrP) as a model system, a generally applicable approach to control enzyme-solid interactions via chemical modification of amino acid side chains of the enzyme is demonstrated. Net charge on GOx was systematically tuned by appending different amounts of polyamine to the protein surface to produce chemically modified GOx(n), where n is the net charge on the enzyme after the modification and ranged from -62 to +95 electrostatic units in the system. The binding of GOx(n) with alpha-ZrP nanosheets was studied by isothermal titration calorimetry (ITC) as well as by surface plasmon resonance (SPR) spectroscopy. Pristine GOx showed no affinity for the alpha-ZrP nanosheets, but GOx(n) where n >/= -20 showed binding affinities exceeding (2.1 +/- 0.6) x 10(6) M(-1), resulting from the charge modification of the enzyme. A plot of GOx(n) charge vs Gibbs free energy of binding (DeltaG) for n = +20 to n = +65 indicated an overall increase in favorable interaction between GOx(n) and alpha-ZrP nanosheets. However, DeltaG is less dependent on the net charge for n > +45, as evidenced by the decrease in the slope as charge increased further. All modified enzyme samples and enzyme/alpha-ZrP complexes retained a significant amount of folding structure (examined by circular dichroism) as well as enzymatic activities. Thus, strong control over enzyme-nanosheet interactions via modulating the net charge of enzymes may find potential applications in biosensing and biocatalysis. | Glucose Oxidase |
Glanders is a fatal bacterial infection of equids caused by Burkholderia mallei. The infection can be transmitted to humans through prolonged direct contact with glanderous equids. Recently, reemergence of equine glanders has been reported in many countries. To investigate zoonotic transmission of B mallei infection, sera were collected from 538 humans including equine handlers and veterinary professionals exposed to glanderous equids. Samples were tested by ELISA (enzyme-linked immunosorbent assay) and complement fixation test and found negative for B mallei-specific antibodies. Even though there was no incidence of human glanders during this survey period, occupational exposure will continue to remain a serious concern and a key risk factor. Therefore, we emphasize the need for intersectoral collaboration and coordination among veterinary, human, and public health authorities for continuous surveillance and monitoring of human glanders under one health concept. | Burkholderia mallei |
In this work, an alkalophilic bacterium (LVX-4) capable of using p-cresol as sole source of carbon and energy was screened and isolated from soil polluted by used oil. Phylogenetic (16S rRNA) and phenotypic characterization using Biolog GN microplates and API 20NE strips indicated that LVX-4 strain is a new Advenella species. It showed both the capability to degrade of p-cresol at high concentrations (750 mg/L) and to use p-cresol for growth in a pH from 7 to 10, although the optimum pH was 9. Moreover bioaugmentation of activated sludge with this strain lead to the complete removal of p-cresol in less than 100 h. This is the first study that shows the potential of Advenella sp. to be bioaugmented in activated sludge system for p-cresol biodegradation. | Alcaligenaceae |
The authors report the case of a rare manifestation by vertebral artery dissection. A 15-year-old boy who presented with left shoulder weakness and numbness of the left arm was admitted to our hospital. Neurological examination on admission revealed muscle weakness of the left deltoid muscle and sensory disturbance of the left C5 area. MRI/MRA and 3D-CT angiography demonstrated an aneurysm-like dilatation of the left vertebral artery mainly at the C4/5 level. Partial thrombosis was noted in the dilated artery. The left vertebral angiogram showed that the second and third portions of the left vertebral artery had a dilated pseudo-lumen due to arterial dissection. The pseudo-lumen of the dissected vertebral artery was largest in diameter at the C4/5 level. The patient successfully underwent proximal occlusion of the dissected vertebral artery using detachable balloon and Guglielmi detachable coils. Proximal vertebral artery occlusion using an intravascular technique was regarded as a non-invasive and effective option for patients with a cervical radiculopathy due to cervical vertebral artery dissection. | Vertebral Artery Dissection |
A preparation with fructose-1,6-bisphosphatase (FBPase) activity has been isolated as a result of the five-stage treatment of the culture liquid obtained after growing the agent of pale-green dwarfness of cereals on the medium CM IMB-72. After this enzyme treatment by means of hydrophobic chromatography on the column from Toyopearl HW-60 (the enzyme was obtained from the column with decrease of ammonium sulphate (AS) concentration in the eluating buffer to 0.8 M), the preparation deprivation of AS on the column with Sephadex G-10 and substrate-dependent chromatography on the column with CM-sepharose the extracellular 176-fold purified FBPase. Acholeplasma laidlawii var. granulum strain 118 was obtained--the main pathogenicity factor for the agent of cereals yellow. | Fructose-Bisphosphatase |
Alpinia katsumadai Hayata (Zingiberaceae) has been used as an anti-emetic medicine and to treat gastric disorders in Oriental Medicine. Previous phytochemical investigations of this plant have resulted in the isolation of various diarylheptanoids, kavalactones, flavonoids, stilbenes, monoterpenes, and sesquiterpenes. Some of these compounds have antioxidant, anti-emetic, antiviral, and cytoprotective effects. This review paper discusses the structural characterization of the chemical constituents of A. katsumadai, as well as the biological activity of pure constituents of this plant material. | Alpinia |
The purpose of this study was to investigate whether sporulated Neospora caninum oocysts, which had been stored for 46 mo in a 2% sulfuric acid solution at 4 degrees C, remain morphologically viable and infective to gerbils (Meriones unguiculatus). Six gerbils were orally inoculated with doses of 400 or 1,200 oocysts. Two mo after inoculation, the animals did not show any clinical signs, had no histological lesions, and were seronegative for N. caninum at 1: 50 in an immunofluorescent antibody test. PCR using the brain from each gerbil did not reveal N. caninum specific DNA. We conclude that oocysts preserved for 46 mo are not infective, despite being morphologically intact. | Neospora |
Osteoporosis (OP) is a metabolic bone disease that leads to decrease of bone strength and increase bone brittle and fracture. Dexamethasone (DXMS) usage is a common risk factor of OP. In present study, we found that the Epimedin C protect the DXMS-induced OP, Ras Homolog Family Member A transforming protein (RhoA) was increased in osteoblasts (OBs) and OP models. We further revealed that Nrf1 is a transcription factor that responds to Epimedin C and DXMS in modulating RhoA promoter. The results collectively demonstrate that Epimedin C functions as a positive modifier of RhoA via alteration of Nrf1 transcriptional activity on RhoA promoter, thereby, protecting OBs against OP. Our work is the first study identifying the Epimedin C function in balancing the OBs in OP model via Nrf1-RhoA. | Nuclear Respiratory Factor 1 |
INTRODUCTION: Clinical and bacteriological features of cobra (Naja) bites are still relatively unknown in Vietnam. This study aimed to characterize the clinical and bacteriological characteristics of local wounds in patients with presumed Naja spp bite, as well as their antibiotic treatment. METHODS: A cross-sectional study was performed on presumed Naja bite patients who were admitted to Bach Mai Hospital in Hanoi, Vietnam. In vitro bacterial isolation, blood tests, and lesion measure were conducted, and antibiotic susceptibilities of localized bite wounds were assessed. The Mann-Whitney test was used to examine the difference in clinical characteristics between patients experiencing presumed Naja atra bites and Naja kaouthia bites. Data are presented as percentages or median with interquartile range, as appropriate. Statistical significance was accepted at P<0.05. RESULTS: Among 46 patients, all had typical clinical features of Naja bite. The median bite-to-hospital time was 6 h (interquartile range 4.0-11.3). The dominant organisms isolated from local wounds were Morganella morganii (11/36) and Enterococcus faecalis (25/36). All cultures were susceptible to ciprofloxacin. No difference was found with regard to pain, swelling circumference, swelling spread, or necrotic area between patients bitten by presumed Naja atra and Naja kaouthia (P>0.05). CONCLUSIONS: Wound necrosis and infection were important clinical issues in presumed Naja spp snake bites. Morganella morganii and Enterococcus faecalis were dominant in local wound swabs of such cases. Ciprofloxacin should be an effective first-line antibiotic for patients with presumed Naja bite. | Naja |
The synthesis of a panel of oligosaccharides containing C-5 arabinofuranosyl residues (9-20) is described. These compounds are of interest as potential inhibitors of the alpha-(1-->5)-arabinosyltransferase involved in the assembly of mycobacterial cell-wall arabinan. In the series of compounds prepared, the 5-OH group on the nonreducing residue(s) is replaced, independently, with an amino, azido, fluoro, or methoxy functionality. The synthesis of the target compounds involved the preparation of a series of C-5 modified arabinofuranosyl thioglycosides (24-26) and their subsequent coupling to the appropriate acceptor species (21-23). Deprotection of the glycosylation products afforded the azido, fluoro, or methoxy analogs directly. The amino derivatives were obtained in one additional step by reduction of the azido compounds. | Trisaccharides |
CpG island promoters often lack canonical core promoter elements such as the TATA box, and have dispersed transcription initiation sites. Despite the prevalence of CpG islands associated with mammalian genes, the mechanism of transcription initiation from CpG island promoters remains to be clarified. Here we investigate the mechanism of transcription initiation of the CpG island-associated gene, insulin-degrading enzyme (IDE). IDE is ubiquitously expressed, and has dispersed transcription initiation sites. The IDE core promoter locates within a 32-bp region, which contains three CGGCG repeats and a nuclear respiratory factor 1 (NRF-1) binding motif. Sequential mutation analysis indicates that the NRF-1 binding motif is critical for IDE transcription initiation. The NRF-1 binding motif is functional, because NRF-1 binds to this motif in vivo and this motif is required for the regulation of IDE promoter activity by NRF-1. Furthermore, the NRF-1 binding site in the IDE promoter is conserved among different species, and dominant negative NRF-1 represses endogenous IDE expression. Finally, TATA-box binding protein (TBP) is not associated with the IDE promoter, and inactivation of TBP does not abolish IDE transcription, suggesting that TBP is not essential for IDE transcription initiation. Our studies indicate that NRF-1 mediates IDE transcription initiation in a TBP-independent manner, and provide insights into the potential mechanism of transcription initiation for other CpG island-associated genes. | Nuclear Respiratory Factors |
PURPOSE OF REVIEW: The management of testicular cancer has evolved over time with multimodal therapy. Retroperitoneal lymph node dissection (RPLND), which is a complex and potentially morbid treatment option, remains the mainstay in surgical treatment. This article reviews the surgical template, approach and anatomical considerations with regards to nerve spare in RPLND. RECENT FINDINGS: The standard full bilateral RPLND template has evolved over time to include the area between the renal hilum, bifurcation of the common iliac vessels, and the ureters. Morbidity with regards to ejaculatory dysfunction has led to further refinements in this procedure. Advancements in anatomical understanding of the retroperitoneal structures and their relationship to the sympathetic chain and hypogastric plexus has allowed for modification of surgical templates. Further refinements in surgical nerve sparing techniques have improved functional outcomes without sacrificing oncological outcomes. Finally, extraperitoneal access to the retroperitoneum and minimally invasive platforms have been implemented to further reduce morbidity. SUMMARY: RPLND requires strict adherence to oncological surgical principles regardless of template, approach and technique. Contemporary evidence shows that outcomes are best for advanced testis cancer patients when managed at high volume tertiary care facilities with surgical expertise and access to multidisciplinary care. | Retroperitoneal Space |
BACKGROUND: Currently, numerous animal studies have shown that exposure to commonly used general anesthetics during pregnancy may cause neurocognitive impairment in the offspring. Reportedly, exposure to sevoflurane during mid-trimester of pregnancy can inhibit proliferation of neural stem cells (NSCs) and lead to early apoptosis. Whether exposure to sevoflurane during pregnancy affects the differentiation of NSCs remains unclear. METHODS: In the present study, pregnant rats were exposed to 3% sevoflurane once for 2 h on gestational day 14 (G14) or 3 times for 2 h on G13, G14, and G15. Next, the differentiation of NSCs was measured using neuron marker beta-tubulin III and astrocyte marker glial fibrillary acidic protein (GFAP) in fetal brain tissues 24 h and 72 h after anesthesia and in hippocampus on postnatal day 28. Primary cultured rat NSCs were exposed to 4.1% sevoflurane to explore the mechanism. RESULTS: The results showed that during mid-trimester, multiple exposures to sevoflurane can cause premature differentiation of NSCs in developing brains of offspring and lead to long-term neuron reduction and astrocyte proliferation in hippocampus. The data from the present study indicated that repeated exposure to sevoflurane downregulated atrophin-1 (ATN1) expression and caused early differentiation of NSCs. Overexpression of ATN1 via lentivirus transfection attenuated the influence of sevoflurane. Using dual luciferase assay, ATN1 was found to be a target gene of microRNA-410-3p (miR-410-3p). MiR-410-3p suppression via lentivirus transfection recovered the ATN1 expression and differentiation of NSCs. CONCLUSIONS: The results from the present study demonstrated that repeated exposure to sevoflurane leads to early differentiation of NSCs and long-term effects via the miR-410-3p/ATN1 pathway. | Sevoflurane |
In pharmacological test models providing repeated daily administrations of steroid hormones, differing time courses of the drug level depending upon the pharmacokinetics can be observed often. The present study should make a contribution to the question whether the time course of the drug level can have an influence on the effectiveness of a given dose of a synthetic gestagen. On the basis of existing pharmacokinetic and pharmacodynamic data in the beagle dog, levonorgestrel (LN) was selected as progestogen. LN was administered daily in equal dosages (0.1 mg) over a period of 14 days subcutaneously (s.c.) and intravenously (i.v.). The gestagenic potency of LN was assessed in an established bioassay by the histological evaluation of the endometrial transformation. Whereas the s.c. administration resulted in a low, but almost constant, LN level, high peaks of short duration could be determined after i.v. administration. Following s.c. injection, LN was released only to a degree of 60% in the observation period compared with 100% after i.v. administration. Nevertheless, 0.1 mg LN given s.c. had stronger endometrial effects than 0.1 mg LN given as bolus i.v. | Norgestrel |
OBJECTIVES: (1) Evaluation of the influence of hemostatic disorders on renal function in patients with FIGO stage IIB-IIIB cervical cancer treated with radiochemotherapy. (2) Identifying methods of improving renal function in this patients group. METHODS: Treatment design assumes the administration of a total radiation dose of 46-65 Gy and, additionally, cisplatin 40 mg/m2 every 7 days in patients with normal plasma creatinine level. Renal function was assessed with the aid of dynamic scintigraphy with glomerular filtration rate (GFR) evaluation. Analysis of serum hemostatic system covered D-dimers, PAP, PAI-1, tPA, FDP, F1+2 and TAT. The same hemostatic parameters were also evaluated in urine. The patients were divided into two groups: the study group - i.e. patients with affected GFR and the control group - with normal GFR. Half of study group patients, throughout the entire treatment, receive nadroparine 2850 units aXa/0.3 ml every 24 h during and 6 weeks after the treatment. RESULTS: There are significant decreases of GFR in control (median -9.7%) and study group without nadroparine (median -9.9%) and increase in the GFR (median 22.3%) in study group with nadroparine (p=0.0001). Plasma and urine hemostatic parameter analysis showed activation of fibrinolysis in patients treated with nadroparine and fibrinolysis inhibition in remaining groups. CONCLUSIONS: (1) Inhibition of fibrinolysis may cause subclinical renal insufficiency in patients with advanced cervical cancer. (2) Insufficiency increases after the end of radiochemotherapy in patients, as well with normal GFR as, with primary decreased GFR. (3) Application of nadroparine causes fibrinolysis activation, and increase in the GFR. | Nadroparin |
Detection threshold for an orientation-texture-defined (OTD) test grating was elevated after adapting to an OTD grating of high orientation contrast. Threshold elevation was greatest for a test grating parallel to the adapting grating, and fell to zero for a test grating perpendicular to the adapting grating. We conclude that the human visual system contains an orientation-tuned neural mechanism sensitive to OTD form, and propose a model for this mechanism. We further propose that orientation discrimination for OTD bars and gratings is determined by the relative activity of these filters for OTD form. | Form Perception |
The anatomical and functional mapping of lateral hypothalamic circuits has been limited by the numerous cell types and complex, yet unclear, connectivity. Recent advances in functional dissection of input-output neurons in the lateral hypothalamus have identified subset of inhibitory cells as crucial modulators of both sleep-wake states and metabolism. Here, we summarize these recent studies and discuss the multi-tasking functions of hypothalamic circuitries in integrating sleep and metabolism in the mammalian brain. | Hypothalamic Area, Lateral |
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