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BACKGROUND: Indigenous populations are represented among the poor and disadvantaged in rural areas. High rates of infectious diseases are observed in indigenous child populations, and fever as a general symptom is common. OBJECTIVE: We aim to improve the skills of healers in rural indigenous areas in the South of Ecuador for managing children with fevers. METHOD: We performed participatory action research (PAR) for this study with 65 healers. RESULTS: The PAR focused on the following four phases: (1) 'observation,' eight focus groups were used. (2) 'planning' phase was developed, and with culturally reflective peer group sessions, a culturally adapted flowchart was constructed titled "Management of children with fever." In phase (3): 'action', the healers were trained to manage children with fever. Phase (4): 'evaluation', 50% of the healers used the flowchart. CONCLUSIONS: Explicit recognition of the need for traditional healers and health professionals in indigenous communities to work together to improve health indicators such as infant mortality exists. Additionally, strengthening the transfer system in rural areas is based on knowledge and cooperation between the community and the biomedical system." | Traditional Medicine Practitioners |
Four methods were compared as to their suitability for excluding IgA deficiency in the investigation of suspected anti-IgA transfusion reactions. The methods were radial immunodiffusion, passive hemagglutination inhibition, sandwich enzyme-linked immunosorbent assay, and membrane enzyme immunoassay. Parallel testing was performed on sera from 40 patients or blood donors previously found to have anti-IgA and low or undetectable levels of IgA. All test methods identified the 40 sera as having abnormally low IgA levels. The membrane enzyme immunoassay required 10 minutes or less for testing, as compared to 3 hours for passive hemagglutination inhibition, 4 hours for sandwich enzyme-linked immunosorbent assay, and 48 hours for radial immunodiffusion. The membrane enzyme immunoassay offers the potential for a rapid, instrument-free screen of IgA levels and therefore may be useful in identifying those patients with suspected anti-IgA anaphylactic transfusion reactions who are not IgA deficient and do not require IgA-deficient blood components for additional transfusions. | IgA Deficiency |
Cytochrome b5 was purified from detergent solubilized sheep liver microsomes by using three successive DEAE-cellulose, and Sephadex G-100 column chromatographies. It was purified 54-fold and the yield was 23.5% with respect to microsomes. The apparent Mr of cytochrome b5 was estimated to be 16,200 +/- 500 by SDS-PAGE. Absolute absorption spectrum of the purified cytochrome b5 showed maximal absorption at 412 nm and dithionite-reduced cytochrome b5 gave peaks at 557, 526.5 and 423 nm. The ability of the purified sheep liver cytochrome b5 to transfer electrons from NADH-cytochrome b5 reductase to cytochrome c was investigated. The K(m) and Vmax values were calculated to be 0.088 microM cytochrome b5 and 315.8 microM cytochrome c reduced/min/mg enzyme, respectively. Also the reduction of cytochrome b5 by reductase was studied and K(m) and Vmax values were determined to be 5 microM cytochrome b5 and 5200 nmol cytochrome b5 reduced/min/mg enzyme, respectively. The K(m) and Vmax values for the cofactor NADH in the presence of saturating concentration of cytochrome b5 were found to be 0.0017 mM NADH and 6944 nmol cytochrome b5 reduced/min/mg enzyme, respectively. NADH-cytochrome b5 reductase was also partially purified from the same source, detergent solubilized sheep liver microsomes, by using two successive DEAE-cellulose, and 5'-ADP-agarose affinity column chromatographies. It was purified 144-fold and the yield was 7% with respect to microsomes. The apparent monomer Mr of reductase was estimated to be 34,000 by SDS-PAGE. When ferricyanide was used as an electron acceptor, reductase showed maximum activity between 6.8 and 7.5. The K(m) and Vmax values of the enzyme for ferricyanide were calculated as 0.024 mM ferricyanide and 673 mumol ferricyanide reduced/min/mg enzyme, respectively. The K(m) and Vmax values for the cofactor NADH in the presence of saturating amounts of ferricyanide were found to be 0.020 mM NADH and 699 mumol ferricyanide reduced/min/mg enzyme, respectively. | Cytochromes b5 |
Placebos have been a component of healing since the beginning. Whether consciously or unconsciously given, they are largely responsible for the success of medicine before randomized trials. Yet, even in this era of evidence-based medicine," placebos remain enigmatic, and elicit mixed attitudes from divers disciplines. However, our ignorance is not total. There are a few facts to cling to and old myths to dispel. The effect of placebos seems to encompass such disparate elements as anxiety, conditioning, expectation, the healer's persona, and the attachment of meaning to illness. Placebos may obscure as well as illuminate the truth about treatment effectiveness. Moreover, it is easy to confuse their effect with the natural progression of the disease being treated. Those engaged in treatment trials must recognize and manage the reality of placebos rather than attempt to eliminate or disparage them. Factors that might influence the placebo effect such as age, gender, and social circumstances need prospective study. Meanwhile doctors, through honest and compassionate interactions with patients, should strive to maximize their treatments' benefits. This implies confident reassurance and the provision of some meaning to the person's symptoms." | Placebos |
PURPOSE: Depression is a common condition in patients with cancer, although there has been a relative paucity of research on the effectiveness of treatment in this population. This review summarizes the psychosocial and pharmacologic treatment of depression in patients with cancer based on a consideration of evidence regarding etiologic factors and treatment outcomes. METHODS: A review of the evidence base for psychosocial and pharmacologic interventions for depression in patients with cancer was performed, including original studies, systematic reviews, and meta-analytic studies in the literature. RESULTS: Recent evidence from randomized controlled trials has demonstrated the efficacy of psychosocial and pharmacologic treatments to alleviate depression in patients with cancer. Further research is needed to establish their relative and combined efficacy and their role in the treatment of depression that is less severe and occurs in association with more advanced disease. First-line recommendations for the treatment of depression in patients with cancer are difficult to derive based on current evidence, because comparative studies have not been conducted to support the superiority of one treatment modality over another in this population. CONCLUSION: Both psychosocial and pharmacologic interventions have been shown to be efficacious in treating depression in cancer, but further research is needed to establish their relative and combined benefit. Future research directions include the development and evaluation of novel interventions targeted to specific biologic and psychosocial risk factors. | Depression |
BACKGROUND: Canaliculitis is often misdiagnosed. There are several conservative and surgical treatment options. PATIENTS AND METHODS: Retrospective analysis of 14 canaliculotomies in 10 patients with canaliculitis. The overall length of the surgically induced opening was measured and compared to the corresponding untreated lacrimal punctae. Lacrimal duct concrements were liberated and sent for microbiological and histological analysis. Patient satisfaction and relief of symptoms were documented as well as clinical findings. RESULTS: Mean age was 59 +/- 10 years (36 - 73 years) with balanced gender distribution. Mean follow-up time was 13 +/- 8 months (4 - 27 months). Canaliculotomy was performed on 12 out of 14 inflamed canaliculi; in 2 cases, 3-snip punctoplasty was sufficient. The surgically induced length of the cuts was 1.7 +/- 0.9 mm (0.4 - 3.7 mm). In 13 out of 14 cases, macroscopic concrements were found intraoperatively and actinomyces was verified histologically. Nine patients were free of symptoms postoperatively, and one patient manifested markedly less epiphora. CONCLUSIONS: The canaliculi remained open within the long-term follow-up period without any drawbacks to the lacrimal outflow. No recurrent infections were seen. | Canaliculitis |
Colorectal cancer (CRC) is one of the most common cancers worldwide with a high incidence and mortality. Although many treatment options are available in stage IV disease, the clinical outcome is still minimal. The primary treatment problem in metastatic colorectal cancer (mCRC) is early liver metastases that occur in more than 50% of patients. First-line treatment in metastatic colorectal cancer (mCRC) is a combination of chemotherapy plus targeted therapies like Cetuximab or Bevacizumab depending on K-RAS status. The decision of which regimen to choose is difficult because almost half of the patients don't receive second-line treatment due to complications or death. To avoid exposing non-responding patients to inefficient and harmful therapies new robust biomarkers are needed. Ongoing studies have demonstrated constantly that microRNAs (miRNAs) could become suitable biomarkers for screening and treatment response. In CRC, miR-31-3p and miR-31-5p dysregulation seems to have a particular role in evaluating treatment response from anti-EGFR therapy. In this review, we will present up to date information on the role of miRNA-31-3p and miR-31-5p in CRC with a particular focus in treatment response of metastatic K-RAS wild-type CRC treated with anti-EGFR molecules. | Panitumumab |
2,4-bis(Isopropylamino)-6-methylthio-s-triazine (prometryn) poses a risk to aquatic environments in several countries, including China, where its use is widespread, particularly due to its chemical stability and biological toxicity. Vetiver grass (Chrysopogon zizanioides L.) was tested for its potential for phytoremediation of prometryn. Vetiver grass was grown in hydroponic media in a greenhouse, in the presence of prometryn, with appropriate controls. Plant uptake and removal of prometryn from the media were monitored for a period of 67 days. The results showed that the removal of the prometryn in the media was expedited by vetiver grass. The removal half-life (t1/2) was shortened by 11.5 days. Prometryn removal followed first-order kinetics (Ct = 1.8070e(-0.0601t)). This study demonstrated the potential of vetiver grass for the phytoremediation for prometryn. | Chrysopogon |
Offshore oil and gas activities can result in the discharge of large amounts of drilling muds. While these materials have generally been regarded as non-toxic to marine organisms, recent studies have demonstrated negative impacts to suspension feeding organisms. We exposed the arctic-boreal sponge Geodia barretti to the primary particulate components of two water-based drilling muds; barite and bentonite. Sponges were exposed to barite, bentonite and a natural reference sediment at a range of total suspended solid concentrations (TSS = 0, 10, 50 or 100 mg/L) for 12 h after which we measured a suite of biomarker responses (lysosomal membrane stability, lipid peroxidation and glutathione). In addition, we compared biomarker responses, organic energy content and metal accumulation in sponges, which had been continuously or intermittently exposed to suspended barite and natural sediment for 14 d at relevant concentrations (10 and 30 mg TSS/L). Lysosomal membrane stability was reduced in the sponges exposed to barite at 50 and 100 mg TSS/L after just 12 h and at 30 mg TSS/L for both continuous and intermittent exposures over 14 d. Evidence of compromised cellular viability was accompanied by barite analysis revealing concentrations of Cu and Pb well above reference sediments and Norwegian sediment quality guidelines. Metal bioaccumulation in sponge tissues was low and the total organic energy content (determined by the elemental composition of organic tissue) was not affected. Intermittent exposures to barite resulted in less toxicity than continuous exposure to barite. Short term exposures to bentonite did not alter any biomarker responses. This is the first time that these biomarkers have been used to indicate contaminant exposure in an arctic-boreal sponge. Our results illustrate the potential toxicity of barite and the importance of assessments that reflect the ways in which these contaminants are delivered under environmentally realistic conditions. | Geodia |
PURPOSE: Error reduction is an important concern in clinical medicine. Intensity-modulated radiotherapy (IMRT) is an important advancement in radiation oncology that increases the complexity of treatment, potentially increasing the error risk. We studied the frequency and severity of errors in a large multicenter practice to ascertain the impact of quality improvement interventions over time, IMRT, and type of practice. METHODS AND MATERIALS: We analyzed prospective data from three academic and 16 community practice sites with 24,775 courses of radiotherapy (9,210 IMRT courses and 15,565 non-IMRT) between January 2006 and December 2009. All IMRT treatment was performed using one centralized dose planning center for all sites. RESULTS: We prospectively identified various errors or potential errors in 0.14 % vs. 0.40 % of the IMRT vs. non-IMRT courses (13/9,210 vs. 62/15,565, p = 0.0004) and excluding potential errors: 0.03 % for IMRT vs. 0.21% for non-IMRT. We developed the Clinical Radiotherapy Error Severity Scale (CRESS) to classify error severity from 1 to 10, with 1 to 3 for potential or completely correctable errors, 4 to 5 for dose variations <5%, and 6 to 10 for dose variations >5%. Multivariate analyses of CRESS values, severity >4, and any error (including potential) correlated significantly reduced errors with IMRT (p = 0.0001-0.0024) but found no significant difference between the academic and community practice sites and no change in error frequency over time despite implementation of 39 system-wide policy changes by the centralized quality improvement committee. CONCLUSIONS: Despite the increase in complexity with IMRT compared with conventional radiotherapy, it can be delivered with reduced error frequency." | Radiotherapy, Intensity-Modulated |
Despite its fundamental nature, bacterial chromosome segregation remains poorly understood. Viewing segregation as a single process caused multiple proposed mechanisms to appear in conflict and failed to explain how asymmetrically dividing bacteria break symmetry to move only one of their chromosomes. Here, we demonstrate that the ParA ATPase extends from one cell pole and pulls the chromosome by retracting upon association with the ParB DNA-binding protein. Surprisingly, ParA disruption has a specific effect on chromosome segregation that only perturbs the latter stages of this process. Using quantitative high-resolution imaging, we demonstrate that this specificity results from the multistep nature of chromosome translocation. We propose that Caulobacter chromosome segregation follows an ordered pathway of events with distinct functions and mechanisms. Initiation releases polar tethering of the origin of replication, distinction spatially differentiates the two chromosomes, and commitment irreversibly translocates the distal centromeric locus. Thus, much as eukaryotic mitosis involves a sequence of distinct subprocesses, Caulobacter cells also segregate their chromosomes through an orchestrated series of steps. We discuss how the multistep view of bacterial chromosome segregation can help to explain and reconcile outstanding puzzles and frame future investigation. | Caulobacter |
BACKGROUND: Psychotic symptoms can occur during normal development, but they can also indicate the presence of or an increased risk of a psychotic disorder. By studying children who are at risk of developing a psychotic disorder we can obtain information that will help to distinguish more accurately between developmental phenomena and psychopathology. AIM: To present the current state of our knowledge about the development of psychotic symptoms and psychotic disorders and to discuss the importance of continuing research into subpopulations of children who are at risk of developing a psychotic disorder. METHOD: We give an epidemiological and clinical description of psychosis in childhood and we report on recent Dutch and international studies about children with an increased risk of developing psychotic disorders. RESULTS: Results so far indicate that these children tend to have an increased risk of developing not only psychotic disorders but also a wide range of psychopathological conditions in later life. The degree of risk depends on the nature and number of risk factors involved. CONCLUSION: More research is needed to follow the development of children with an increased risk of psychotic disorders. | Psychotic Disorders |
Pittard, James (University of Melbourne, Melbourne, Australia), and B. J. Wallace. Gene controlling the uptake of shikimic acid by Escherichia coli. J. Bacteriol. 92:1070-1075. 1966.-Mutants possessing an impaired ability to take up exogenously supplied shikimic acid were isolated. Mutants showing either a complete or partial loss of this activity were found. The mutations have been mapped on the Escherichia coli chromosome and occur in a single gene, situated near to the cluster of genes concerned with histidine biosynthesis. The uptake of dehydroshikimic acid was also affected by these mutations, suggesting a common mechanism for the uptake of these two related intermediates of aromatic biosynthesis. | Shikimic Acid |
The purpose of this study was to determine whether the blood vessels of transplanted neural tissue retain their functional characteristics. Quantitative autoradiography was used to measure local blood flow (F) with iodoantipyrine and the blood-to-tissue transfer constant (K) with alpha-aminoisobutyric acid in superior cervical ganglion (SCG) allografted to the surface of ventricle IV and into the cerebellum of the same rat. The F of the intraparenchymal grafts was slightly lower than that of the intraventricular grafts; F decreased between 1 and 4 weeks in SCG grafts at both sites. The permeability-surface area (PS) product of the microvessels and extraction fraction of AIB were calculated from these results and indicated restricted transvascular passage of the amino acid in both the in situ and grafted SCG. Surface area (S) and average length (L) of the microvessels were determined morphometrically and their permeability (P) was calculated from these data. Although K and PS decreased in the grafts compared to in situ SCG, a comparable decrease in S indicated that P was similar for the microvessels of both in situ and 1-week-old SCG transplants: 3.5-4.3 x 10(-6) cm/s. Between 1 and 4 weeks after transplantation, the P of the microvessels decreased to approximately 1.6-2.3 x 10(-6) cm/s without any change in S. Thus, the blood vessels of SCG grafts within or upon the brain initially retain the functional attributes of in situ SCG microvessels, but the average permeability of the graft microvessels decreases to approximately one half of the initial value by 4 weeks after transplantation. | Ganglia, Autonomic |
To understand the complex system of reimbursement for health care services, it is helpful to have a working knowledge of the historic context of diagnosis-related groups (DRGs), as well as their utility and increasing relevance. Congress implemented the DRG system in 1983 in response to rapidly increasing health care costs. The DRG system was designed to control hospital reimbursements by replacing retrospective payments with prospective payments for hospital charges. This article explains how these payments are calculated. Every inpatient admission is classified into one of several hundred DRGs that are based on the diagnosis, complications, and comorbidities. The Centers for Medicare & Medicaid Services (CMS) assigns each DRG a weight that the CMS uses in conjunction with hospital-specific data to determine reimbursement. A population's DRGs represent the resources needed to treat the medical disorders of that population. Hospital administrators use this information to budget and plan for the future. The Affordable Care Act and other recent legislation affect medical reimbursement by altering the DRG system. Radiologic procedures in particular are affected. This legislation will give DRGs an even larger role in determining reimbursements in the coming years." | Reimbursement, Disproportionate Share |
Codeine, tramadol, and hydrocodone have been associated with morbidity and death in children, secondary to respiratory depression. The aim of this paper is to increase awareness of this issue and to encourage clinicians to prescribe safer alternatives such as morphine, ibuprofen, or paracetamol." | Heterocyclic Compounds, Bridged-Ring |
Phytochemical investigation of the seeds of Embelia ribes Burm. resulted in the isolation of three new compounds identified as 3-(4-hydroxyoctadecanyloxy)-p-quinonyl-5-methylene-8-(10-pentanyloxy)-p-quinone (embelinol) (1), n-pentacosanyl-n-nonadeca-7'-en-9'-alpha-ol-1'-oate (embeliaribyl ester) (2) and 1,2,4,5-tetrahydroxy 3-undecanyl benzene (embeliol) (3) along with the known compound 2,5-dihydroxy-3-undecyl-2,5-cyclohexadiene-1,4-dione (embelin) (4). Their structures have been established on the basis of spectral data analyses and chemical reactions." | Embelia |
Co-amplification and co-overexpression of ErbB2 and Grb7 are frequently found in various cancers, including breast cancer. Biochemical and functional correlations of the two molecules have identified Grb7 to be a pivotal mediator downstream of ErbB2-mediated oncogenesis. However, it remains largely unknown how Grb7 is involve in the ErbB2-mediated tumorigenesis. In this study, we show that Grb7-mediated cell proliferation and growth are essential for the tumorigenesis that occurs in ErbB2-Grb7-overexpressing breast cancer cells. Intrinsically, EGF-induced de novo Grb7 tyrosine phosphorylation/activation recruits and activates Ras-GTPases and subsequently promotes the phosphorylation of ERK1/2, thereby stimulating tumor growth. Furthermore, we also found the anti-tumor effect could be synergized by co-treatment with Herceptin plus Grb7 knockdown in Sk-Br3 breast cancer cells. Our findings illustrate an underlying mechanism by which Grb7 promotes tumorigenesis through the formation of a novel EGFR-Grb7-Ras signaling complex, thereby highlighting the potential strategy of targeting Grb7 as an anti-breast cancer therapy. | GRB7 Adaptor Protein |
Our previous study showed that the Bombyx mori nucleopolyhedrovirus (BmNPV) F-like protein Bm14 is intrinsically related to the production of occlusion bodies, occlusion-derived virus (ODV) embedding and virulence in infected larvae. However, the exact mechanism by which Bm14 affects primary infection remains unknown. In this report, we characterized the detailed distribution and topology of Bm14 in occlusion bodies (OBs) and ODVs, and then further investigated the functional role of Bm14 in primary infection. A combination of Western blot and immunoelectron microscopy showed that Bm14 is mainly present on the surface of ODVs within OBs, but rarely in the OB matrix. Further phase separation and topology analysis of Bm14 by selective permeabilization revealed that Bm14 is a type I integral membrane protein with an N-terminus hidden in the endoplasmic reticulum (ER) lumen and a C-terminus exposed to the cytosol. In vivo assays demonstrated that the disruption of bm14 impaired the interactions of ODV with midgut epithelia, resulting in delayed spread in larval tissues. As the essential trigger of primary infection, some per os infectivity factors (PIFs) were verified to interact with Bm14 via a series of coimmunoprecipitation analyses. Further partially denaturing SDS-PAGE and BN-PAGE assays clearly showed that the deletion of bm14 did not affect the formation and presence of the PIF complex. In conclusion, Bm14 functions as a type I integral membrane protein to regulate ODV attachment to the midgut epithelial cells. | Occlusion Bodies, Viral |
Past studies have examined the ability of the Wisconsin Card Sorting Test (WCST) to discriminate valid from invalid performance in adults using both individual embedded validity indicators (EVIs) and multivariate approaches. This study is designed to investigate whether the two most stable of these indicators-failures to maintain set (FMS) and the logistical regression equation S-B(LRE)-can be extended to pediatric populations. The classification accuracy for FMS and S-B(LRE) was examined in a mixed clinical sample of 226 children aged 7 to 17 years (64.6% male, MAge = 13.6 years) against a combination of established performance validity tests (PVTs). The results show that at adult cutoffs, FMS and S-B(LRE) produce an unacceptably high failure rate (33.2% and 45.6%) and low specificity (.55-.72), but an upward adjustment in cutoffs significantly improves classification accuracy. Defining Pass as <2 and Fail as >/=4 on FMS results in consistently good specificity (.89-.92) but low and variable sensitivity (.00-.33). Similarly, cutting the S-B(LRE) distribution at 3.68 produces good specificity (.90-.92) but variable sensitivity (.06-.38). Passing or failing FMS or S-B(LRE) is unrelated to age, gender and IQ. The data from this study suggest that in a pediatric sample, adjusted cutoffs on the FMS and S-B(LRE) ensure good specificity, but with low or variable sensitivity. Thus, they should not be used in isolation to determine the credibility of a response set. At the same time, they can make valuable contributions to pediatric neuropsychology by providing empirically-supported, expedient and cost-effective indicators to enhance performance validity assessment. | Wisconsin Card Sorting Test |
Edible fungus is a large fungus with edible and medicinal value. Rapid detection of mycelium phenotypic characteristics is of great significance for edible fungus breeding and intelligent cultivation. Traditional method based on experienced observation easily led to make mistakes on distinguishing the growth stages, which impacted on the yield and quality of edible fungus. Therefore, in view of the lack of accurate and efficient detection technology during the growth stages of Pleurotus eryngii mycelium, a rapid detection method of Pleurotus eryngii mycelium at different growth stages is proposed based on the characteristics of near-infrared spectroscopy. First, the spectral data of mycelium of Pleurotus eryngii at six different growth stages were scanned. Second, the multivariate scattering correction method (MSC) was used to pre-process the raw spectral data, and then the competitive adaptive reweighted sampling algorithm (CARS) was adopted to detect the characteristic wave number of the effective variables for Pleurotus eryngii mycelium. In addition, the mathematical model between the mycelium of Pleurotus eryngii and the characteristic wave number of near-infrared spectrum was established by using feed forward neural network (BP). Finally, and the coding vector output by the network was used to detect to the growth stages. The results showed that the BP neural network structure of MSC-CARS-BP detection model was 86-85-85-95-6, and the accuracy of identifying different growth stages of Pleurotus eryngii mycelium was 99.67%. The research results could provide a new idea and technical support for the rapid detection of Pleurotus eryngii mycelium at different growth stages. | Mycelium |
It has been assumed that restriction of motor activity (hypokinesia) induces significant changes in body hydration homeostasis. Thus, the objective of this study was to measure body hydration level during prolonged hypokinesia (HK). The studies were done on 12 male Macaca Mulatta (rhesus monkeys) aged three to five years (4.75 to 6.96 kg) during a 15-day period of pre HK and a 90-day period of HK. All primates were divided equally into two groups: monkeys placed under vivarium conditions served as vivarium control primates (VCP) and monkeys subjected to HK served as hypokinetic primates (HKP). For simulation of the HK effect, the HKM group was kept for 90 days in small individual cages that restricted their movements in all directions without hindering food and water intakes. During the pre HK period of 15 days and the HK period of 90 days the following parameters were measured: total body water (TBW), extracellular fluid volume (EFV), intracellular fluid volume (IFV), circulating plasma volume (CPV) and interstitial fluid volume (IsFV), urinary and plasma sodium and potassium, fluid consumption and elimination in urine, and body weight. Significant (p < or = 0.01) decrease in the TBW, IFV, and CPV was observed in the HKP group when compared with the VCP group. In the HKP group EFV and IsFV decreased significantly (p < or = 0.01) when compared with the VCP group only in the initial seven days of the HK period, while after the 7th day progressive increase could be observed. Fluid loss, urinary electrolyte excretion and plasma electrolyte concentration increased significantly (p < or = 0.01), while fluid intakes decreased significantly (p < or = 0.01) in the HKP group when compared with the VCP group. In the HKP group body weight decreased significantly (p < or = 0.01) when compared with the VCP group. In the VCP group the measured parameters did not change significantly when compared with the baseline control values. It was concluded that prolonged exposure to HK induces significant changes in body hydration homeostasis while body dehydration in monkeys caused primarily due to decreased CPV. | Body Water |
This study reviews existing and potential clinical applications of laser scanning cytometry (LSC) and outlines possible future developments. LSC provides a technology for solid phase cytometry. Fluorochrome-labeled specimens are immobilized on microscopic slides that are placed on a conventional epifluorescence microscope and analyzed by one or two lasers. Data comparable to flow cytometry are generated. In addition, the position of each event is recorded, a feature that allows relocalization and visualization of each measured event. The major advantage of LSC compared with other cytometric methods is the combination of two features: (a) the minimal clinical sample volume needed and (b) the connection of fluorescence data and morphological information for the measured event. Since the introduction of LSC, numerous methods have been established for the analysis of cells, cellular compartments, and tissues. Although most cytometric methods use only two or three colors, the characterization of specimens with up to five fluorochromes is possible. Most clinical applications have been designed to determine ploidy and immunophenotype; other applications include analyses of tissue biopsies and sections, fluorescence in situ hybridization, and the combination of vital and nonvital information on a single-cell basis. With the currently available assays, LSC has proven its wide spectrum of clinical applicability in slide-based cytometry and can be introduced as a standard technology in multiple clinical settings. | Cytophotometry |
BACKGROUND: The cost-effectiveness of heart failure management programs (HF-MPs) is highly variable. We explored intervention and clinical characteristics likely to influence cost outcomes. METHODS: A systematic review of economic analyses alongside randomized clinical trials comparing HF-MPs and usual care. Electronic databases were searched for English peer-reviewed articles published between 1990 and 2013. RESULTS: Of 511 articles identified, 34 comprising 35 analyses met the inclusion criteria. Eighteen analyses (51%) reported a HF-MP as more effective and less costly; four analyses (11%), and five analyses (14%) also reported they were more effective but with no significant or an increased cost difference, respectively. Alternatively, five analyses (14%) reported no statistically significant difference in effects or costs, and one analysis (3%) reported no statistically significant effect difference but was less costly. Finally, two analyses (6%) reported no statistically significant effect difference but were more costly. Interventions that reduced hospital admissions tended to result in favorable cost outcomes, moderated by increased resource use, intervention cost and/or the durability of the intervention effect. The reporting quality of economic evaluation assessed by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist varied substantially between 5% and 91% (median 45%; 34 articles) of the checklist criteria adequately addressed. Overall, none of the study, patient or intervention characteristics appeared to independently influence the cost-effectiveness of a HF-MP. CONCLUSION: The extent that HF-MPs reduce hospital readmissions appears to be associated with favorable cost outcomes. The current evidence does not provide a sufficient evidence base to explain what intervention or clinical attributes may influence the cost implications. | Cost-Benefit Analysis |
In this review we sum-up the knowledge about bZIP G-box binding factors (GBFs), which possess an N-terminal, proline-rich domain. The GBF has been one of the most extensively studied transcription factor family. Based on protein sequence homology with yeast and animal basic leucine-zipper (bZIP) transcription factors, bioinformatic studies have identified their main structural domains (proline-rich, basic and leucine-zipper), which have been further functionally characterized by in vitro and in vivo experiments. Recent reports have led to the discovery of other GBF-specific short amino-acid sequences that may take part in the regulation of gene expression by post-transcriptional modifications or interaction with other proteins such as bZIP enhancing factors or plant 14-3-3-like proteins. We identified a GBF region, called the 'multifunctional mosaic region', that may be implicated in cytoplasmic retention, translocation to the nucleus and regulation of transcription. We also identified many conserved protein motifs that suggest a modular structure for GBFs. At the whole plant level, GBFs have been shown to be involved in developmental and physiological processes in response to major cues such as light or hormones. Nevertheless, it remains difficult to assign a physiological role to a particular GBF protein modular structure. Finally, bringing together these different aspects of GBF studies we propose a model describing the puzzling transduction pathway involving GBFs from cytoplasmic events of signal transduction to the regulation of gene expression in the nucleus. | G-Box Binding Factors |
Rasagiline is a selective and irreversible monoamine oxidase-B inhibitor. It is not metabolized to amphetamine derivatives. It has been shown to be safe and efficacious as monotherapy in early PD, as well as adjuvant therapy in levodopa-treated patients with mild motor complications. Rasagiline can be used with other antiparkinsonian drugs. Tolerance is good even in aged patients. Posology is simple and convenient (once a day). Its early use seems to improve the outcome of parkinsonian patients. Furthermore, a potential neuroprotective effect has been suggested in experimental studies. Results of the ADAGIO study are awaited with interest. Therefore, rasagiline is especially well suited as to be used as the initial treatment of PD. | Indans |
Vitamin K is essential for the process of coagulation. In its absence, severe and sometimes fatal bleeding events can occur, especially in newborns. Vitamin K prophylaxis at birth has been shown to prevent morbidity and mortality associated with vitamin K deficiency bleeding (VKDB) and is recommended by multiple organizations including the American Academy of Pediatrics and the World Health Organization. Pediatricians should feel comfortable explaining the risks and benefits of vitamin K prophylaxis to families and should be equipped to recognize signs of VKDB, especially given increasing rates of parental refusal. This article aims to improve understanding of VKDB, including prevention, early recognition, and treatment. [Pediatr Ann. 2023;52(2):e42-e45.]. | Vitamin K Deficiency Bleeding |
Galanin-like peptide (GALP) is a 60 amino acid neuropeptide originally discovered from porcine hypothalamus, and is involved in the regulation of food intake in mammals. Since its discovery, GALP and its receptors (GALR1 and GALR2) have been characterized in mammals, but no publications are available on GALP in fish and other non-mammals. The present study aimed to characterize brain and intestinal GALP and its receptors using immunohistochemistry in a teleost, the goldfish (Carassius auratus), and to study its effects on feeding behavior. Immunostaining of brain sections shows the presence of GALP- and GALR1- and GALR2-like immunoreactive cells in different encephalic areas, including the telencephalon, some hypothalamic nuclei, the optic tectum, the torus longitudinalis and the cerebellum. Signal for GALP was also observed in the fasciculus retroflexus. In the gut, GALP-and GALR1 and GALR2 immunoreactive cells were detected in the mucosa. Results from the feeding study demonstrate that intracerebroventricular administration of GALP (1ng/g bodyweight) increases goldfish food intake at 1h post-injection. These observations form the first report on the presence of GALP in the fish brain and gut, and also on its modulatory role on fish feeding behavior. GALP, as in mammals, appears to be a functional neuropeptide in goldfish. | Injections, Intraventricular |
PURPOSE: The aim of this study was to determine the expression of cellular FLICE-like inhibitory protein (cFLIP) in head and neck squamous cell carcinoma (HNSCC) and revealed its possible correlation to Fas protein and tumour clinical parameters. METHODS: The expression of cFLIP was analysed in 58 HNSCC samples and 30 morphologically normal tissues adjacent to the carcinomas using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Furthermore, its possible correlation to the expression of Fas protein and tumour clinicopathologic parameters were discussed. RESULTS: Cellular FLICE-like inhibitory protein was demonstrated to be up regulated in most HNSCC than in normal tissues by immunohistochemistry (p<0.01). Although the mRNA levels of both isoforms of cFLIP, long form (cFLIP(L)) and short form (cFLIP(S)), in HNSCC were higher than those in normal tissues (p<0.01), only cFLIP(L) protein could be detected by western blot. Furthermore, the expression of cFLIP(L) protein was significantly associated with tumour clinical stage (p<0.01) and lymph node metastasis (p=0.01). Since all of the tumours with Fas immunostaining also express cFLIP protein, there was no significant correlation between them (p>0.05). CONCLUSIONS: Overexpression of cFLIP(L) is a frequent event in HNSCC and HNSCC cells in vivo may need it to evade apoptosis mediated by Fas or other receptors, which might contribute to tumour development and progression." | CASP8 and FADD-Like Apoptosis Regulating Protein |
A case of chronic vitamin A intoxication is reported in an infant under 6 months of age. The features included hydrocephalus, usually described in acute hypervitaminosis A and the other cutaneous, hepatic and skeletal signs observed in chronic intoxication. | Hypervitaminosis A |
BACKGROUND: Patients with Parkinson disease (PD) treated with levodopa/carbidopa intestinal gel (LCIG) have higher prevalence of hyperhomocysteinemia and peripheral nerves damage. OBJECTIVE: The aim of our study was to test the effect of catechol-O-methyl transferase inhibitor tolcapone-as an add-on therapy to LCIG in patients with PD-on homocysteine (HCY) metabolism and nerve conduction study (NCS) parameters. METHODS: We evaluated NCS and serum B12, folic acid, and homocysteine in 16 patients with advanced PD on LCIG. Quality of life (QoL) was also assessed. Six subjects were treated with tolcapone add-on therapy (and LCIG dose reduction), 5 with B vitamin supplementation, and 5 without additional treatment. RESULTS: The level of HCY increased among patients without treatment (4.95 +/- 12.54), and decreased in the vitamin (-17.73 +/- 11.82) and tolcapone groups (-8.81 +/- 8.36). Patients with tolcapone demonstrated improvement in polyneuropathic symptoms and signs compared with patients treated with vitamins or those without additional treatment (-0.83, d = 0.961). Although the most robust improvement in NCS parameters were observed with tolcapone, the findings were inconsistent to prove the effect of any intervention. Only tolcapone treatment was associated with improvement in QoL (d = 1.089). CONCLUSION: Our study indicates potential of tolcapone add-on therapy in LCIG treated patients in control of homocysteine levels, and improvement of polyneuropathic symptoms, as well as QoL. | Tolcapone |
Rhodopsins, the major light-detecting molecules of animal visual systems [1], consist of opsin apoproteins that covalently bind a retinal chromophore with a conserved lysine residue [1, 2]. In addition to capturing photons, this chromophore contributes to rhodopsin maturation [3, 4], trafficking [3, 4], and stabilization [5], and defects in chromophore synthesis and recycling can cause dysfunction of the retina and dystrophy [6-9]. Indications that opsin apoproteins alone might have biological roles have come from archaebacteria and platyhelminths, which present opsin-like proteins that lack the chromophore binding site and are deemed to function independently of light [10, 11]. Light-independent sensory roles have been documented for Drosophila opsins [12-15], yet also these unconventional opsin functions are thought to require chromophore binding [12, 13, 15]. Unconjugated opsin apoproteins act as phospholipid scramblases in mammalian photoreceptor disks [16], yet chromophore-independent roles of opsin apoproteins outside of eyes have, to the best of our knowledge, hitherto not been described. Drosophila chordotonal mechanoreceptors require opsins [13, 15], and we find that their function remains uncompromised by nutrient carotenoid depletion. Disrupting carotenoid uptake and cleavage also left the mechanoreceptors unaffected, and manipulating the chromophore attachment site of the fly's major visual opsin Rh1 impaired photoreceptor, but not mechanoreceptor, function. Notwithstanding this chromophore independence, some proteins that process and recycle the chromophore in the retina are also required in mechanoreceptors, including visual cycle components that recycle the chromophore upon its photoisomerization. Our results thus establish biological function for unconjugated opsin apoproteins outside of eyes and, in addition, document chromophore-independent roles for chromophore pathway components. | Retinaldehyde |
BACKGROUND AND OBJECTIVE: In recent studies, ultrasonic diagnostic imaging has proved useful in the screening of the trajectory of the epidural needle. With regard to possible side-effects of spinal and epidural anaesthesia caused by vessel injury, we aimed to evaluate the usability of Colour Doppler imaging for the depiction of interspinous vessels in prepuncture examination. METHODS: Ultrasonic examination of the L3/4 interspace area was performed in 20 volunteers. Using a 4-MHz and a 7-MHz probe with B-mode and Colour Doppler imaging, respectively, we compared four settings for the quality of vessel depiction in the puncture area. Overall resolution was evaluated according to the distinction of landmarks. Vascular structures were identified by pulsation (B-mode) or blood flow (Doppler). RESULTS: Colour Doppler imaging of the L3/4 interspace was unachievable using the 7-MHz transducer. Vessel detection was possible in 50% of the B-mode images and in all of the 4-MHz Doppler images. Vessels were perceptible from a diameter of 0.5 mm. Veins were the predominantly visible structures. Overall vessel visibility was best using 4-MHz Colour Doppler. CONCLUSIONS: Prepuncture Doppler imaging can provide the epiduralist with information regarding the position of vessels in the needle trajectory. This might help to reduce complications in regional anaesthesia. | Epidural Space |
Despite advances in pharmacotherapy, diabetic kidney disease (DKD) remains associated with a high burden of micro- and macrovascular complications often leading to premature mortality. New therapies are highly desirable to mitigate the burden of this disease. However, there are a number of barriers that hamper drug development in DKD. These include, amongst others, the lengthy and complex clinical trials required to prove drug efficacy and safety, inefficiencies in clinical trial conduct, and the high costs associated with these development programs. In this review a number of aspects are discussed, aiming to identify opportunities to transform and innovate drug development for DKD. Many clinical trials in DKD, as well as in other areas, face difficulties in timely and efficient enrolment of participants. To address this issue a network of sites should be created that are continuously recruiting individuals with DKD and collecting crucial information that can be used to understand prognosis and prognostic factors, and more importantly to serve as a pool of participants for recruitment to randomized trials. Second, the current clinical endpoints are late events in the progression of DKD. Endpoints based on lesser declines in estimated glomerular filtration rate (eGFR) or changes in albuminuria can shorten follow-up and/or lead to smaller and cheaper trials. Enrichment by enrolling clinical trial populations based on biomarker profiles is another approach that may facilitate clinical trial efficiency and conduct. Biomarkers can be used to individualize treatment by targeting populations more likely to respond leading to smaller and more efficient trials. Finally, using new trial design such as basket, umbrella or more broadly platform trials to assess a number of therapies simultaneously offers the potential to transform the drug development process in DKD. There are a number of opportunities to transform development approaches for new therapies for DKD. Platform trials along with appropriate biomarker-based enrichment strategies offer the possibility to foster drug development in a precision medicine era. | Precision Medicine |
Seaweeds have attracted high interest in recent years due to their chemical and bioactive properties to find new molecules with valuable applications for humankind. Phenolic compounds are the group of metabolites with the most structural variation and the highest content in seaweeds. The most researched seaweed polyphenol class is the phlorotannins, which are specifically synthesized by brown seaweeds, but there are other polyphenolic compounds, such as bromophenols, flavonoids, phenolic terpenoids, and mycosporine-like amino acids. The compounds already discovered and characterized demonstrate a full range of bioactivities and potential future applications in various industrial sectors. This review focuses on the extraction, purification, and future applications of seaweed phenolic compounds based on the bioactive properties described in the literature. It also intends to provide a comprehensive insight into the phenolic compounds in seaweed. | Phenols |
Pagetoid reticulosis (PR) is a rare lymphoproliferative disorder with indolent behavior considered a variant of mycosis fungoides. It is characterized by marked epidermotropism of the neoplastic lymphocytes. Since its original description, five cases have been reported in children. We report a new case of PR with an immunohistochemical profile not previously described in children. | Pagetoid Reticulosis |
Sulfhemoglobin (SHb) and methemoglobin (MHb) formations by various aniline erivatives were examined by a single and three consecutive intraperitoneal administrations to mice. It was found that with a single administraion, methemoglobinemia was induced by aniline, 2-methylaniline, 3-methylaniline, 4-methylaniline, 3-trifluoromethylaniline (3-TFMA), 4-trifluoromethylaniline (4-TFMA), 2, 3-dichloroaniline, 2-aminopehnol, acetanilide (AA), 2-hydroxyacetanilide, N-methylaniline (NMA), N,N-dimethylaniline (NDMA), N-ethylaniline (NEA) and N,N-diethylaniline, and was not observed with 2, 3-dimethylanilnie, 2-trifluoromethylaniline, 3-aminophenol, 4-aminophenol, 2. 6-dichloroaniline, 3-hydroxyacetanilide (3-HAA), 4-hydroxyacetanilide (4-HAA), 2-aminobenzoic acid, 3-aminobenzoic acid, 4-aminobenzoic acid and 4-chloro-2-aminobenzoic acid. On the other hand, sulfhemoglobinemia which appeared much more delayed than MHb, with a single administration, was found to be induced by 3-TFMA, 4-TFMA and NMA. Furthermore, with three consecutive administrations, such was induced by AA, 3-HAA, NDMA and NEA even though SHb was not demonstrated with a single administration. Structure-SHb and MHb forming property relationships were discussed. | Sulfhemoglobinemia |
None of the current genetic Parkinson's disease (PD) models in mouse recapitulates all features of PD. Additionally, only a few of these models develop mild dopamine (DA) neurodegeneration. And the most parsimonious explanation for the lack of DA neurodegeneration in genetic PD models is a compensatory mechanism that results from adaptive changes during development, making it hard to observe the degenerative phenotype over the life span of mice. Here, we characterize DA neuron-specific autophagy-deficient mice and provide in vivo evidence for Lewy body formation. Atg7-deficient mice demonstrate typical Lewy pathology, including endogenous synuclein and neuronal loss, which resembles PD. Furthermore DA levels are affected by dopaminergic neuronal loss. The age-related motor dysfunction and pathology in DA neurons suggest that impairment of autophagy is a potential mechanism underlying the pathology of PD. | Autophagy-Related Protein 7 |
BACKGROUND: The diagnosis and management of psychogenic nonepileptic seizures (PNES) is often challenging and fraught with discord and disagreement between patients, parents, and physicians. Furthermore, there are ethical challenges when making the diagnosis, communicating this information, and instituting management. METHODS: We reviewed the current body of knowledge regarding the characteristic differences between epileptic seizures and PNES, and the high incidence of psychiatric comorbidities. An ethical analysis was made of diagnosis and management based on ethical principles, virtue ethics, and the social contract that health professionals have with patients. RESULTS: Key distinctions between PNES and epilepsy lie in both patient and seizure characteristics. Long duration, eye closure, asynchronous movements, frequent recurrence in the same context, intra-ictal awareness, and lack of post ictal state are useful in helping establish the diagnosis. Psychiatric comorbidities, history of abuse, cognitive impairment, and multiple non specific somatic complaints are some salient patient features that should increase suspicion for the diagnosis of PNES. However, definitive diagnosis rests on capturing the events on video EEG. CONCLUSION: Effective diagnosis and management of PNES requires the use of video EEG and an early collaborative approach between pediatricians, neurologists, psychiatrists, nursing staff, and other professional colleagues. Ethical questions that may arise should be addressed with the virtues of competence, courage, compassion, prudence, and honesty; and the principles of respect beneficence, and the avoidance of unnecessary harm. | Seizures |
BACKGROUND: Aicardi-Goutieres syndrome (AGS) is a genetically determined disorder with a variable phenotype. Since the original description of AGS, advances in gene sequencing techniques have resulted in a significant broadening of the phenotypic spectrum associated with AGS genes, and new clinical pictures have emerged beyond the classic presentation. The aim of this review is to provide a comprehensive analysis of the clinical spectrum of AGS and report currently available treatments and new immunosuppressive strategies. DATA SOURCES: Literature reviews and original research articles were collected from databases, including PubMed and ClinicalTrials.gov. Relevant articles about AGS were included. RESULTS: The involvement of the nervous system certainly represents the major cause of mortality and morbidity in AGS patients. However, other clinical manifestations, such as chilblains, hepatosplenomegaly, and hematological disturbances, may lead to the diagnosis and considerably impact the prognosis and overall quality of life of these patients. Therapeutic approaches of AGS are limited to interventions aimed at specific symptoms and the management of multiple comorbidities. However, advances in understanding the pathogenesis of AGS could open new and more effective therapies. CONCLUSIONS: The over-activation of innate immunity due to upregulated interferon production plays a critical role in AGS, leading to multi-organ damage with the main involvement of the central nervous system. To date, there is no specific and effective treatment for AGS. New drugs specifically targeting the interferon pathway may bring new hope to AGS patients." | Autoimmune Diseases of the Nervous System |
Topical atenolol (a beta1-adrenoceptive antagonist), pilocarpine, and placebo were tested in a randomised double-blind crossover trial of 8 patients with ocular hypertenion. Atenolol (2% 3 times a day) caused a fall in intraocular pressure (IOP) comparable to that achieved by topical application of pilocarpine (2% 3 times a day). The decrease in IOP by each compound was demonstrable on the second day of application and was significantly (P is less than 0.05) reduced on the seventh and 14th days of treatment. The combination of 2% pilocarpine and 2% atenolol administered 15 minutes apart (3 times a day) lowered the IOP significantly from the second day of treatment, and this reduction persisted throughout the trial period of 14 days. This combined of treatment, treatment lowered the IOP more than either substance alone. However, this further decrease was statistically significant only on the 14th day of treatment (atenolol versus atenolol + pilocarpine, P is less than 0.05). No change of the episcleral venous pressure was observed after 14 days' treatment with either atenolol or pilocarpine alone, or combined. | Atenolol |
GATA2 gene encodes a member of the GATA family of zinc-finger transcription factors that play a pivotal role during the transition of primitive blood forming cells into white blood cells. Mutation in GATA2 results in the loss of function or even gain of function, including abnormal proliferation of white blood cells that may predispose to acute myeloid leukemia. Our results showed that the codon usage in GATA2 has been influenced by GC mutation bias where nature has highly favored fourteen most over represented codons but disfavored the ATA codon across five mammals. Purifying natural selection has affected GATA2 gene in human and other mammals to maintain its protein function during the period of evolution. Our findings report an insight into the codon usage patterns in gaining the clues for codon optimization to alter the translational efficiency as well as for the functional conservation of gene expression and the significance of nucleotide composition in GATA2 gene within mammals. | GATA2 Transcription Factor |
Because of the separation of sexual function to male and female individuals, dioecious species have fewer pollen and seed bearers and thus experience disadvantages due to increased aggregation of reproductive function. Because of this disadvantage, models predict that dioecious females must have substantially more than twice the fecundity of hermaphrodites, yet empirical data suggest that female fecundity advantages are commonly much lower. Here, we incorporate animal foraging dynamics--and the heightened dispersal of seeds that may accompany increases in fecundity of dioecious females--into a spatially explicit mathematical model. We focus on the competition for germination sites with varying seed production, seed dispersal ability, and mortality, and we find that preferential foraging on dioecious females reduces the stringent fecundity requirements of dioecy to values in accordance with empirical estimates. This finding contributes to our understanding of the correlation between dioecy and fleshy fruits and highlights the importance of mutualist dispersers to dioecious species. | Fruit |
Adiposopathy is a pathological adipose tissue (AT) response to overfeeding characterized by reduced AT expandability due to impaired adipogenesis, which favors inflammation, insulin resistance (IR), and abnormal glucose regulation. However, it is unclear whether defective adipogenesis causes metabolic derangement also independently of an increased demand for fat storage. As galectin-3 has been implicated in both adipocyte differentiation and glucose homeostasis, we tested this hypothesis in galectin-3 knockout (Lgal3(-/-)) mice fed a standard chow. In vitro, Lgal3(-/-) adipocyte precursors showed impaired terminal differentiation (maturation). Two-month-old Lgal3(-/-) mice showed impaired AT maturation, with reduced adipocyte size and expression of adipogenic genes, but unchanged fat mass and no sign of adipocyte degeneration/death or ectopic fat accumulation. AT immaturity was associated with AT and whole-body inflammation and IR, glucose intolerance, and hyperglycemia. Five-month-old Lgal3(-/-) mice exhibited a more mature AT phenotype, with no difference in insulin sensitivity and expression of inflammatory cytokines versus WT animals, though abnormal glucose homeostasis persisted and was associated with reduced beta-cell function. These data show that adipogenesis capacity per se affects AT function, insulin sensitivity, and glucose homeostasis independently of increased fat intake, accumulation and redistribution, thus uncovering a direct link between defective adipogenesis, IR and susceptibility to diabetes. | Glucose Intolerance |
Selenium balance was determined in six young men fed for 45 days a formula depletion diet (33 to 36 micrograms Se/day) then fed for 25 days a repletion of diet (depletion diet plus 200 micrograms Se/day as high-Se wheat or wheat plus tuna fish). After 12 days of adaptation, Se balance during depletion was rather constant at -21 micrograms/day and Se losses in urine and feces were 54 micrograms/day. During repletion, Se balance was +64 micrograms/day for the first 12 days and +25 micrograms/day thereafter and the subjects regained all the Se lost during depletion. If the gastrointestinal absorption of the food Se in North Americans and New Zealanders is similar (80%), young North American men need a dietary Se intake of about 70 micrograms/day to replace losses and maintain body stores. | Selenium |
A procedure involving direct injection of whole plasma for analyses of drugs by an automated high-performance liquid chromatograph was developed. This system comprised two columns, two pumps, one detector, two programmable switching valves, an automatic sample injector with a cooling device for sample tubes and a microprocessor. Effluents from the first column, containing a drug of interest, were selectively introduced into the second column for further separation. The columns used were an aqueous gel chromatography column (column 1) and an ODS column (column 2). The solvent for column 1 must be weaker than that for column 2, so that the solutes from the former will be enriched at the top of the latter. The validity and applicability of this procedure for the study of drug metabolism were demonstrated with the antibiotic cefmetazole, the anticoagulant warfarin, the antitumour agent carboquone and the anaesthetic ketamine. | Carbazilquinone |
A recombinant strain producing a complex of extracellular enzymes including chitinase from Myceliophtora thermophila was created based on the fungus Penicillium verruculosum. The activity of the enzyme preparations obtained from the cultural fluid of the producer strain was 0.55, 0.53, and 0.66 U/mg protein with chitin and chitosans with the molecular weight of 200 and 1000 kDa, respectively. The temperature optimum for the recombinant chitinase was 52-65 degrees C; the pH optimum was 4.5-6.2, which corresponded to the published data for this class of the enzymes. The content of heterologous chitinase in the obtained enzyme preparations was 47% of total protein content in the cultural fluid. Enzyme preparations produced by the recombinant P. verruculosum XT403 strain and containing heterologous chitinase were able to degrade the mycelium of micromycetes, including phytopathogenic ones, and were very efficient in the bioconversion of microbiological industry waste. | Chitinases |
Histamine receptor 2 (HR(H2)) blockers are used to treat peptic ulcers and gastric reflux. Chlorquinaldol and chloroxine, which contain an 8-hydroxyquinoline (8HQ) core, have recently been identified as blocking HR(H2). To gain insight into the mode of action of 8HQ-based blockers, here, we leverage an HR(H2)-based sensor in yeast to evaluate the role of key residues in the HR(H2) active site on histamine and 8HQ-based blocker binding. We find that the HR(H2) mutations D98A, F254A, Y182A, and Y250A render the receptor inactive in the presence of histamine, while HR(H2):D186A and HR(H2):T190A retain residual activity. Based on molecular docking studies, this outcome correlates with the ability of the pharmacologically relevant histamine tautomers to interact with D98 via the charged amine. Docking studies also suggest that, unlike established HR(H2) blockers that interact with both ends of the HR(H2) binding site, 8HQ-based blockers interact with only one end, either the end framed by D98/Y250 or T190/D186. Experimentally, we find that chlorquinaldol and chloroxine still inactivate HR(H2):D186A by shifting their engagement from D98 to Y250 in the case of chlorquinaldol and D186 to Y182 in the case of chloroxine. Importantly, the tyrosine interactions are supported by the intramolecular hydrogen bonding of the 8HQ-based blockers. The insight gained in this work will aid in the development of improved HR(H2) therapeutics. More generally, this work demonstrates that Gprotein-coupled receptor (GPCR)-based sensors in yeast can help elucidate the mode of action of novel ligands for GPCRs, a family of receptors that bind 30% of FDA therapeutics. | Chlorquinaldol |
Recent research has demonstrated that nitrogen oxides are transformed to nitrogen acids in indoor environments, and that significant concentrations of nitrous acid are present in indoor air. The purpose of the study reported in this paper has been to investigate the sources, chemical transformations and lifetimes of nitrogen oxides and nitrogen acids under the conditions existing in buildings. An unoccupied single family residence was instrumented for monitoring of NO, NO2, NOy, HONO, HNO3, CO, temperature, relative humidity, and air exchange rate. For some experiments, NO2 and HONO were injected into the house to determine their removal rates and lifetimes. Other experiments investigated the emissions and transformations of nitrogen species from unvented natural gas appliances. We determined that HONO is formed by both direct emissions from combustion processes and reaction of NO2 with surfaces present indoors. Equilibrium considerations influence the relative contributions of these two sources to the indoor burden of HONO. We determined that the lifetimes of trace nitrogen species varied in the order NO approximately HONO > NO2 > HNO3. The lifetimes with respect to reactive processes are on the order of hours for NO and HONO, about an hour for NO2, and 30 minutes or less for HNO3. The rapid removal of NO2 and long lifetime of HONO suggest that HONO may represent a significant fraction of the oxidized nitrogen burden in indoor air. | Nitrogen Dioxide |
OBJECTIVE: To determine the proportion of cats entering a Florida animal shelter with serum antibody titers against feline panleukopenia virus (FPV), feline herpesvirus 1 (FHV1), and feline calicivirus (FCV) and to identify factors associated with seropositivity. DESIGN: Cross-sectional study. ANIMALS: 347 cats admitted to a Florida animal shelter. PROCEDURES: Within 24 hours after admission to the animal shelter, blood samples were collected from all cats >/= 8 weeks of age. Serum antibody titers against FPV were determined via a hemagglutination inhibition assay, and those against FHV1 and FCV were determined via virus neutralization assays. Age, sex, environment (urban or rural), source (stray or previously owned), evidence of previous caregiving, health status (healthy or not healthy), and outcome (adoption, transfer, return to owner, or euthanasia) were evaluated as potential factors associated with antibody seropositivity. RESULTS: Of 347 cats, 138 (39.8%), 38 (11.0%), and 127 (36.6%) had antibody titers >/= 40, >/= 8, and >/= 32 (ie, seropositive) against FPV, FHV1, and FCV, respectively. Factors associated with seropositivity included being neutered, age >/= 6 months, and being relinquished by an owner. On multivariable analysis, health status at shelter admission, environment, vaccination at shelter admission, and outcome were not associated with seropositivity. CONCLUSIONS AND CLINICAL RELEVANCE: Most cats were seronegative for antibodies against FPV, FHV1, and FCV at the time of admission to an animal shelter. These findings supported current guidelines that recommend vaccination of all cats immediately after admission to animal shelters, regardless of the source or physical condition. | Feline Panleukopenia |
The luciferin/luciferase system of the firefly has been used in bioluminescent imaging to monitor biological processes. In order to enhance the efficiency and expand the application range, some efforts have been made to tune the light emission, especially the effort to obtain NIR light. However, those case-by-case studies have not together revealed the nature and mechanism of the color tuning. In this paper, we theoretically investigated the fluorescence of all kinds of typical oxyluciferin analogues. The present systematical modifications of both oxyluciferin and luciferase indicate that the essential factor affecting the emission color is the charge distribution (or the electric dipole moment) on the oxyluciferin, which impacts on the charge transfer to form the light emitter and, subsequently, influence the strength and wavelength of the emission light. More negative charge distributed on the thiazolone moiety" of the oxyluciferin or its analogues leads to a redshift. Based on this conclusion, we theoretically designed optimal pairs of luciferin analogue and luciferase for emitting NIR light, which could inspire new synthetic procedures and practical applications." | Luciferases, Firefly |
BACKGROUND: Human artificial chromosomes (HACs) are generated from the precursor DNA constructs containing alpha-satellite DNA with CENP-B boxes, and the process could be used for the incorporation of large genes in the HACs. Guanosine triphosphate cyclohydrolase I (GCH1) is the first and rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin, the essential co-factor of aromatic amino acid hydroxylases and nitric oxide synthase. RESULTS: We constructed HACs carrying a 180 kb genome segment encoding the human GCH1 gene and its control region from the bacterial artificial chromosome (BAC) with the GCH1 segment by co-transfection with the alpha-satellite DNA-containing BAC to a human fibroblast cell line. Two cell lines carrying a HAC with GCH1 genes were obtained. Both HACs were composed of multiple copies of precursor BACs and were maintained stably in human and mouse cell lines. The GCH1 activities of the HAC-carrying human fibroblast cell lines were elevated but still highly sensitive to IFN-gamma induction, mimicking the response of the gene expression from the authentic chromosomal genes. CONCLUSION: These HACs will provide a useful system for analysis of the complex regulatory circuit of the GCH1 gene in vivo and also function as a tool for gene delivery in animal models or in therapeutic trials." | Chromosomes, Artificial, Human |
BACKGROUND: The range of products stocked and their promotions in food retail outlets in healthcare settings can affect food choices by staff, patients and visitors. The innovative Scottish Healthcare Retail Standard (HRS) is a national mandatory scheme requiring all hospital food retail outlets to change the balance of food products stocked and their promotion to comply with nutritional criteria and promotional restrictions. The aim is to facilitate healthier food choices in healthcare settings. This study examined the implementation of HRS and the impact on foods stocked and promoted. METHODS: The study aimed to examine implementation process and changes to the retail environment in relation to food promotions and choice. A sample of hospital retail outlets (n = 17) including shops and trolley services were surveyed using a mixed methods design comprising: (a) structured observational audits of stock, layout and promotions (with a specific focus on chocolate and fruit product lines), and (b) face-to-face, semi-structured interviews with the shop manager or nominated members of staff (n = 32). Data were collected at Wave 1 (2016), at the beginning and during the early stages of HRS implementation; and Wave 2, 12 months later, after the HRS implementation deadline. RESULTS: All outlets, both commercial and not-for-profit, in the sample successfully implemented HRS. Implementation was reported to be more challenging by independent shop managers compared to chain store staff. Retail managers identified areas where more implementation guidance and support could have been provided. The number of chocolate product lines and promotions reduced substantially between Waves 1 and 2, but with no substantial increase in fruit product lines and promotions. Despite initial negative expectations of HRS's impact, managers identified some opportunities in the scheme and positive changes in the supply chain. CONCLUSIONS: Positive changes in food retail outlets occurred after hospital shops were required to implement HRS. By creating a consistent approach across hospital shops in Scotland, HRS changed the food retail environment for hospital staff, visitors and patients. HRS provides a regulatory template and implementation learning points for influencing retail environments in other jurisdictions and settings. | Hospital Shops |
Hypertensive diseases have long been recognized as a major medical problem in Australia, but until the 1950s measures for controlling hypertension were limited and of doubtful effectiveness. Great efforts were made to identify and deal with such remediable primary causes as unilateral renal disease, endocrine disorders of the adrenal cortex and medulla and coarctation of the aorta, but the yield was small and there was little to offer the great majority of patients who were suffering from essential hypertension, including its malignant form. Long holidays, especially sea cruises, sedation and venesection were widely prescribed but with little confidence and even less benefit. | Hypertension |
The Schiff base compounds (1 and 2) are synthesized by the condensation reactions of 2-furan-2-yl-methylamine with 2-hydroxy-3-methoxy- and 2-hydroxy-5-methoxy-benzaldehydes and reduced with NaBH(4) to give the new N/O-donor-type ligands (3 and 4). The monospirocyclotriphosphazenes containing 1,3,2-oxazaphosphorine rings (5 and 6) are prepared from the reactions of N(3)P(3)Cl(6) with 3 and 4, respectively. The reactions of 5 and 6 with excess pyrrolidine, morpholine, and 1,4-dioxa-8-azaspiro [4,5] decane (DASD) produce tetrapyrrolidino (5a and 6a), morpholino (5b and 6b), and 1,4-dioxa-8-azaspiro [4,5] deca (5c and 6c) spirocyclotriphosphazenes. The structural investigations of the compounds are examined by (1)H, (13)C, (31)P NMR, DEPT, HSQC, and HMBC techniques. The solid-state structures of 5, 5a, and 6 are determined using X-ray crystallography. The compounds 5a, 5b, 5c, 6a, 6b, and 6c are subjected to antimicrobial activity against six patojen bacteria and two yeast strains. In addition, interactions between these compounds and pBR322 plasmid DNA are presented by agarose gel electrophoresis. | Nitrogen Compounds |
Streptomyces is well known for synthesis of many biologically active secondary metabolites, such as polyketides and non-ribosomal peptides. Understanding the coupling mechanisms of primary and secondary metabolism can help develop strategies to improve secondary metabolite production in Streptomyces. In this work, Streptomyces albus ZD11, an oil-preferring industrial Streptomyces strain, was proved to have a remarkable capability to generate abundant acyl-CoA precursors for salinomycin biosynthesis with the aid of its enhanced beta-oxidation pathway. It was found that the salinomycin biosynthetic gene cluster contains a predicted 3-hydroxyacyl-CoA dehydrogenase (FadB3), which is the third enzyme of beta-oxidation cycle. Deletion of fadB3 significantly reduced the production of salinomycin. A variety of experimental evidences showed that FadB3 was mainly involved in the beta-oxidation pathway rather than ethylmalonyl-CoA biosynthesis and played a very important role in regulating the rate of beta-oxidation in S. albus ZD11. Our findings elucidate an interesting coupling mechanism by which a PKS biosynthetic gene cluster could regulate the beta-oxidation pathway by carrying beta-oxidation genes, enabling Streptomyces to efficiently synthesize target polyketides and economically utilize environmental nutrients." | 3-Hydroxyacyl-CoA Dehydrogenase |
Physiatrists are at elevated risk of burnout, a work-related exhaustion syndrome resulting from chronic stress associated with emotionally draining work demands. The high reported rate of burnout in physical medicine and rehabilitation led the Association of Academic Physiatrists Chair Council to convene a workgroup to address burnout among academic physical medicine and rehabilitation physicians. The council recognizes that leaders of departments are accountable for all organizational stakeholders, including faculty, trainees, and staff. Department leaders are expected to understand and effectively manage the drivers of burnout among stakeholders. The workgroup identified several opportunities, including identifying and disseminating effective burnout mitigation across US academic medical center physical medicine and rehabilitation programs. As a result, in 2019, a work group conducted a survey of US academic physical medicine and rehabilitation program leaders to ascertain the use of strategies for reducing physician burnout. With the aim of identifying, educating, and advancing the development of effective interventions to address burnout among academic physical medicine and rehabilitation departments, the Association of Academic Physiatrists Chair Council advocates for increased education and utilization of effective strategies aimed at promoting physician well-being across organizational levels (national, organizational, work unit, and individual). | Physiatrists |
Refineries are complex industrial systems that transform crude oil into more valuable subproducts. Due to the advances in sensors, easily measurable variables are continuously monitored and several data-driven soft-sensors are proposed to control the distillation process and the quality of the resultant subproducts. However, data preprocessing and soft-sensor modelling are still complex and time-consuming tasks that are expected to be automatised in the context of Industry 4.0. Although recently several automated learning (autoML) approaches have been proposed, these rely on model configuration and hyper-parameters optimisation. This paper advances the state-of-the-art by proposing an autoML approach that selects, among different normalisation and feature weighting preprocessing techniques and various well-known Machine Learning (ML) algorithms, the best configuration to create a reliable soft-sensor for the problem at hand. As proven in this research, each normalisation method transforms a given dataset differently, which ultimately affects the ML algorithm performance. The presented autoML approach considers the features preprocessing importance, including it, and the algorithm selection and configuration, as a fundamental stage of the methodology. The proposed autoML approach is applied to real data from a refinery in the Basque Country to create a soft-sensor in order to complement the operators' decision-making that, based on the operational variables of a distillation process, detects 400 min in advance with 98.925% precision if the resultant product does not reach the quality standards. | Hydrocarbons, Acyclic |
BACKGROUND: To assess the impact of hospital and surgeon volume on mortality, morbidity, length of hospital stay and costs of radical prostatectomy (RP). METHODS: This systematic review identified relevant studies published between 1997 and June 2007. Inclusion of papers was established through application of a predetermined protocol, independent assessment by two reviewers, and a final consensus decision. RESULTS: Compared with low volume hospitals, the included studies showed high volume hospitals demonstrated lower rates of mortality, postoperative complications and readmissions, and lower overall hospital costs. High volume surgeons similarly showed lower rates of postoperative complications and shorter length of stay compared with low volume surgeons, but no difference in mortality. CONCLUSIONS: From the literature obtained, patients undergoing RP performed by high volume providers may have better outcomes compared to low volume providers; however, any move to centralize RP must be further evaluated. | Prostatectomy |
Amongst the clinical presentations of retinal artery occlusion, hemi-central retinal artery occlusion (Hemi-CRAO) is rarely described. This case series of four adults aged between 22 and 36 years attempts to describe the clinical profile, etiology and management of Hemi-CRAO. Case 1 had an artificial mitral valve implant. Polycythemia and malignant hypertension were noted in Case 2. The third patient had Leiden mutation while the fourth patient had Eisenmenger's syndrome. Clinical examination and fundus fluorescein angiography revealed a bifurcated central retinal artery at emergence from the optic nerve head, in all cases. Color Doppler examination of the central retinal artery confirmed branching of the artery behind the lamina cribrosa. It is hypothesized that bifurcation of central retinal artery behind the lamina cribrosa may predispose these hemi-trunks to develop an acute occlusion if associated with underlying risk factors. The prognosis depends upon arterial recanalisation and etiology of the thromboembolic event. | Retinal Artery Occlusion |
The blue mussel (Mytilus spp.) is widely used as a bioindicator for monitoring of coastal water pollution (mussel watch programs). Herein we provide a review of this study field with emphasis on: the suitability of Mytilus spp. as environmental sentinels; uptake and bioaccumulation patterns of key pollutant classes; the use of Mytilus spp. in mussel watch programs; recent trends in Norwegian mussel monitoring; environmental quality standards and background concentrations of key contaminants; pollutant effect biomarkers; confounding factors; particulate contaminants (microplastics, engineered nanomaterials); climate change; harmonization of monitoring procedures; and the use of deployed mussels (transplant caging) in pollution monitoring. Lastly, the overall state of the art of blue mussel pollution monitoring is discussed and some important issues for future research and development are highlighted. | Sentinel Species |
BACKGROUND: Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA- 617 for therapy of metastatic castration-resistant prostate cancer have underlined the clinical potential of targeted alpha therapy. OBJECTIVE AND CONCLUSION: This review describes methods for the production of 225Ac and its daughter nuclide 213Bi and summarizes the current clinical experience with both alpha emitters with particular focus on recent studies of targeted alpha therapy of bladder cancer, brain tumors, neuroendocrine tumors and prostate cancer. | Radioisotopes |
An NADP-dependent 7 beta-hydroxysteroid dehydrogenase was purified 11.5-fold over the activity in crude cell extracts prepared from Peptostreptococcus productus strain b-52, by using Sephadex G-200 and DEAE-cellulose column chromatography. 7 beta-Dehydrogenation was the sole transformation of bile acids catalyzed by the partially purified enzyme. The enzyme preparation (spec. act. 2.781 IU per mg protein) had an optimum pH of 9.8. Lineweaver-Burk plots showed a Michaelis constant (Km) value of 0.05 mM for 3 alpha, 7 beta-dihydroxy-5 beta-cholanoic acid whereas higher values were obtained with 3 alpha,7 beta-dihydroxy-5 beta-cholanoyl glycine (0.20 mM), and 3 alpha,7 beta-dihydroxy-5 beta-cholanoyl taurine (0.26 mM). NADP but not NAD could function as an electron acceptor, and had a Km value of 0.30 mM. A molecular weight of 64000 was determined by SDS-polyacrylamide gel electrophoresis. The addition of 0.4 mM of either bile acid to the growth medium suppressed not only cell growth, but also the enzyme yield. | Hydroxysteroid Dehydrogenases |
BACKGROUND/PURPOSE: Children with closed head injuries diagnosed as concussion alone or concussion with brief loss of consciousness are admitted routinely for observation despite a normal central nervous system finding, negative computed tomography (CT) scan, and a Glasgow Coma Score (GCS) of 15. Recent studies have questioned the necessity of such an admission. The purpose of this study was to review a large pediatric database and study the length of stay as well as any required procedures or complications in these children. The hypothesis was that routine admission is unnecessary in this population. METHODS: The National Pediatric Trauma Registry-Phase II was reviewed for the period from October 1988 to January 1996. Entry criteria included age less than 18 and an isolated closed head injury after blunt trauma with an admission GCS of 15. Variables studied included age, gender, mechanism of injury, length of stay, procedures, and outcome. RESULTS: A total of 1,033 children met criteria for this study. The average age was 8.3 years. Males predominated at 61.9%. Falls, sports, and motor vehicle crashes were the most common mechanisms of injury. The average length of stay was 1.19 days, and 60 children were not admitted. A total of 583 children had no procedures performed, whereas 386 received a CT scan, and 148 had x-rays. None required neurosurgical intervention, and all were discharged alive. CONCLUSION: These findings indicate that routine admission may not be necessary for children with isolated mild closed head injuries with a negative CT scan and a normal neurologic finding and allows for a prospective randomized trial to confirm this. | Head Injuries, Closed |
Past studies have shown that vision receiver operating characteristic curves plotted on normal-deviate coordinates fit straight lines for which the inverse of the slope is proportional to the index of detectability d'. This Communication offers a theoretical interpretation of that empirical relationship. | Vision, Ocular |
The consecutive steps of tumor growth, local invasion, intravasation, extravasation, invasion of anatomically distant sites, and immunosuppression are obligatorily perpetrated through specific interactions of the tumor cells with their microenvironment [...]. | Neoplasm Invasiveness |
A number of defense polypeptides from latent seeds of weed cereal barnyard grass (Echinochloa crusgalli L.) has been isolated and characterized using an acidic extraction and high performance liquid chromatography methods in combination with MALDI-TOF mass spectrometry and Edman sequencing. Members of three antimicrobial peptide families and two protease inhibitor families were found to be localized in barnyard grass seeds. Their biological activity concerning to Gram-Positive and Gram-Negative phytopathogenic bacteria, as well as oomycete Phytophthora infestans, has been investigated. Diversity of barnyard grass defense peptides is a significant factor that provides a resistance of E. crusgalli seeds to germination and latent phases. | Echinochloa |
Delayed puberty is defined arbitrarily on the basis of statistical consideration, when no signs of puberty have occurred at 2.0 SD (13.4 years in girls and 13.8 in boys) above the mean chronological age for the onset of puberty. The vast majority of these patients have no endocrine abnormality and their pubertal development and growth spurt are simply consequences of primary delay (constitutional delay of growth and puberty (CDGP)) or secondary delay due to a chronic disease of childhood, such as asthma. However, a small proportion may have pathological causes of delayed puberty which must be careful identified as specific management may be required. Associated with delayed puberty, the growth spurt is always delayed which is why the condition is described as delayed growth and puberty. Short stature and lack of sexual development may lead to emotional and social difficulties and in some patients their consequences can persist when 'normal' height and full sexual maturation are attained. Recent data also suggest that a delay in the 'tempo' of pubertal maturation may interfere with the normal bone accretion occurring during puberty, later causing osteoporosis. Such findings suggest that a new approach in delayed puberty may be necessary not only for psychological reasons but also for optimizing bone mass accretion. | Puberty, Delayed |
OBJECTIVE: To observe the protective effects on acute myocardial infarction of QDYX in dog. METHOD: The corconary ciculation and cardial oxygen metabolism, the degree and range of myocardial ischemia, myocardial infarct size, and the changes of the enzymes in serum were determined by using the acute myocardial infarction model of ligation of LAD in the anaesthetized open-chest dogs. RESULT: The coronary resistance and cardial oxygen consumption were decreased and the myocardial blood flow was increased in dogs treated with QDYX of 1.0,2.0 mg.kg-1. The degree and range of myocardial ischemia, myocardial infarct size and the activity of serum CK, LDH were decreased in acute myocardial infarcion dogs treated with QDYX of 1.0,2.0 mg.kg-1. CONCLUSION: QDYX can decrease cardial oxygen consumption in dogs, thus having protective effect on myocardial ischemia. | Ophiopogon |
BACKGROUND: Clinically, the low expression of wild-type aryl hydrocarbon receptor-interacting protein (AIP) in patients with sporadic growth hormone (GH)-secreting pituitary adenoma (GHPA) is associated with a more aggressive phenotype. However, the mechanism by which AIP expression is regulated in GHPA remains unclear. Herein, we investigated a transcription factor that regulates AIP expression and explored its role in tumor phenotypes. METHODS: General transcription factor IIB (GTF2B) was predicted by several bioinformatic tools to regulate AIP expression transcriptionally. Regulation by GTF2B was evaluated using chromatin immunoprecipitation (ChIP), reverse transcription PCR, luciferase reporter, and western blot experiments in SH-SY5Y cells. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, transwell invasive assay, ELISA, western blot, immunohistochemical staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to investigate the effects of GTF2B and AIP on tumor cell proliferation, apoptosis, growth hormone secretion, and invasiveness in GH3 cells and mouse xenograft models. Moreover, correlations between GTF2B and AIP expression were explored in GHPA cases. RESULTS: ChIP and luciferase reporter studies demonstrated that the regulation of AIP expression by GTF2B was dependent on the intergenic-5' untranslated region element of AIP and the initial residual S65 of GTF2B. In vitro and in vivo experiments indicated that GTF2B regulated AIP expression to impact the GHPA phenotype; this was confirmed by data from 33 GHPA cases. CONCLUSIONS: We determined the regulation by GTF2B of AIP transcription in GHPA and its impact on tumor phenotype. Our findings suggest that GTF2B may be a potential therapeutic target for GHPA with low AIP expression. | Transcription Factor TFIIB |
Glucocorticoids (GCs) potently inhibit pro-inflammatory responses and are widely used for the treatment of inflammatory diseases, such as allergies, autoimmune disorders, and asthma. Dual-specificity phosphatase 1 (DUSP1), also known as mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), exerts its effects by dephosphorylation of MAPKs, i.e., extracellular-signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Endogenous DUSP1 expression is tightly regulated at multiple levels, involving both transcriptional and post-transcriptional mechanisms. DUSP1 has emerged as a central mediator in the resolution of inflammation, and upregulation of DUSP1 by GCs has been suggested to be a key mechanism of GC actions. In this review, we discuss the impact of DUSP1 on the efficacy of GC-mediated suppression of inflammation and address the underlying mechanisms." | Dual Specificity Phosphatase 1 |
The metabolism and disposition of tri-p-cresyl phosphate (TPCP) were studied in the rat after a single oral administration of [methyl-14C] TPCP. At a dosage of 7.8 mg/kg, most of the administered radioactivity was excreted in the urine (41%) and feces (44%) in 7 days. For 3 days, the expiratory excretion as 14CO2 amounted to 18% of the radioactivity, but was reduced to 3% by treatment of the animal with neomycin. In separate rats, the biliary excretion amounted to 28% of the dose in 24 hr. At a dose of 89.6 mg/kg, the radioactivity was excreted in urine (12%) and feces (77%) in 7 days, and the expired air (6%) in 3 days. At 24, 72, and 168 hr after oral administration, the concentration of radioactivity was relatively high in adipose tissue, liver, and kidney. The major urinary metabolites were p-hydroxybenzoic acid, di-p-cresyl phosphate (DCP), and p-cresyl p-carboxyphenyl phosphate (1coDCP). The biliary metabolites were DCP, 1coDCP, and the oxidized triesters, di-p-cresyl p-carboxyphenyl phosphate (1coTPCP), and p-cresyl di-p-carboxyphenyl phosphate (2coTPCP). The main fecal metabolite was TPCP, and the others were similar to those of bile. Following oral administration, TPCP was absorbed from the intestine, distributed to the fatty tissues, and moderately metabolized to a variety of products of oxidation and dearylation of TPCP, which were then excreted in the urine, feces, bile, and expired air. The intestinal microflora appeared to play an important role in degrading biliary metabolites to 14CO2 through the enterohepatic circulation in rats. | Tritolyl Phosphates |
In the evaluation of an accelerated idioventricular rhythm (AIVR) case presented by an athlete, even though considered qualified for agonistic sport practice in compliance with the COCIS protocol, the authors made some considerations relative to such type of arrhythmia. AIVR are characterized by a wide oscillation of frequency (from 40 to 120 b/min) and are distinguished as active AIVR when the ventricular center exceeds the discharge frequency in a non depressed sinusal activity; and it's passive AIVR when an automatic ventricular center substitutes the physiological pacemaker in the presence of sinusal bradycardia. This leads to think that it could be two different phenomenons. The first is characterized by a low frequency and is determined by the activation of some automatic cells located under the His bundle, and the second arises with the extrasystolic modality. Moreover, AIVR manifest a parasystolic type of behaviour that complicates the diagnostic differentiation. Therefore it can be considered that the arrhythmia of ventricular genesis (AIVR, ventricular tachycardia, parasystole) represents the varied expression of the same electrogenic substratum with different discharge potentiality. Thus was formulated the proposal of unifying the ventricular rhythms in one group which includes: rhythm of ventricular escapement, AIVR, parasystole and ventricular tachycardia. | Parasystole |
Carotid arteriosclerotic disease is the most readily treatable type of lesion leading to stroke. Its management involves lowering those risk factors over which the patient has control. Patients should regulate hypertension, quit smoking, seek medical attention for treatable cardiac abnormalities, and take steps to reduce increased blood lipids. For symptomatic carotid disease, regardless of whether surgery is offered, platelet inhibitors are obligatory. The recommended dose is 650 mg aspirin per day (or up to 1300 mg, if tolerated). For patients whose symptoms continue despite aspirin therapy or who are aspirin intolerant, ticlopidine is the only recommended platelet inhibitor. Cerebral arterial bypass surgery is not an effective treatment for carotid arteriosclerosis. Carotid endarterectomy helps patients with > or = 70% stenosis as determined by strict arteriographic measurements. We do not yet have sufficient data to determine whether endarterectomy would benefit patients with lower levels of carotid stenosis or asymptomatic patients with any degree of stenosis. | Carotid Stenosis |
Torque teno viruses (TTV) are small DNA viruses widespread among humans and pigs. The clinical significance of TTV infections in either humans or pigs is uncertain. In fact, TTV viremia is highly prevalent in patients with different pathologies, but it can also be frequently observed in healthy subjects. Virus infection in pigs is considered a putative cofactor in several diseases; despite being detected frequently in healthy animals, its role still remains unknown. The present study aimed to investigate the presence of Torque teno sus virus (TTSuV) in 62 bile samples collected from pigs at slaughterhouse and in 36 fresh pork liver sausages bought at point of sale. Quantitative Real-Time PCR, confirmed that 19.4 and 58.3 % of bile and sausage samples tested positive for TTSuV, respectively. The mean viral load was established as 5.6 x 10(4) GE/microl for bile and 7.16 x 10(3) GE/g for sausages. TTSuV nucleotide sequence analysis confirmed a wide heterogeneity among the circulating TTSuV strains, which included both TTSuV1 and TTSuV2. | Torque teno virus |
To demonstrate the potential of nuclear magnetic resonance (NMR) spectroscopy for investigating detailed structural properties in ferromagnetic materials, three different particle sized cobalt (Co) powders have been ball milled for 24h are accurately characterised by internal-field (59)Co NMR. The (59)Co NMR spectra show distinct resonance bands corresponding to the different Co sites, face-centred-cubic (fcc), hexagonal-close-packed (hcp) and stacking faults (sfs), in Co metal powders. The hcp+fcc-->hcp phase transition encouraged by ball-milling was observed and quantitative values for each Co environment were obtained. | Cobalt Isotopes |
OBJECTIVE: The aim of this study was to construct a consensus on the undergraduate learning objectives and topics for public health nursing (PHN) in Turkey. DESIGN: A three-round e-mail-based Delphi study was conducted between May and July 2015 with a national sample. SAMPLE: Ninety-one academics from 54 universities were invited as experts to participate by e-mail. Fifty-nine academics from 43 universities participated in the study. MEASUREMENTS: Data were analyzed by computing the median, quartiles one and three, and the interquartile range for each learning outcome and topic. Consensus was considered as less than the interquartile range of 1.2. RESULTS: Experts who participated in the study added 70 learning outcomes, eight main topics, and 278 sub-topics during the first round. Round I generated 170 learning outcomes, 28 main topics, and 385 sub-topics. At the end of Round II, consensus was reached on 126 learning outcomes, 22 main topics and 168 sub-topics. At the end of Round III, consensus was achieved for 126 learning outcomes, 22 main topics, and 169 sub-topics. CONCLUSION: The learning outcomes and topics that were decided upon through a consensus process will contribute to the standardization and development of PHN education. | Public Health Nursing |
Tumor-derived DNA, found in body fluids (liquid biopsy) of cancer patients as part of cell-free DNA (cfDNA), lends itself for noninvasive cancer detection and monitoring. Advantages of cfDNA as analytical target have evoked a burst of sophisticated techniques, providing clinically relevant information. Each cell type carries a unique DNA modification profile consisting mainly of patterns of 5-methylcytosine in CpG dinucleotides, which are critical for establishing and maintaining cellular identity and which are frequently disturbed in cancer. Assessment of the tumor-derived cfDNA modifications combined with high-throughput analysis techniques holds promise for developing highly specific noninvasive diagnostic tests. This review highlights recent advances in locus-specific and whole-genome analysis of cfDNA, with a specific focus on epigenetic phenomena and their clinical value. | Sulfites |
This study evaluated microwave-assisted extraction (MAE) for four pentacyclic triterpenes as well as developed a method for preparing a pentacyclic triterpenene rich extract from Centella asiatica. MAE was capable of increasing the yield of the pentacyclic triterpenes up to twice that produced by the heat reflux method, and it was also much less time consuming. The optimal conditions of MAE employed were extraction with absolute ethanol as solvent, an irradiation power of 600 W, at 75 degrees C, four irradiation cycles and four extraction times. Here, we provide a simple method for the preparation of the pentacyclic triterpene rich C. asiatica extracts, which contained not less than 65% w/w total pentacyclic triterpenes. The method involved a macroporous resin (Diaion(R) HP-20) column eluted with ethanol and a decolourisation step with activated charcoal. | Pentacyclic Triterpenes |
New information and understanding about the physiology of oxytocin (OT) have provided the bases of novel and rational approaches to the induction and augmentation of labor with OT. Based on a half-life of 8-10 min and time to steady state of 20 min, the interval between intravenous OT dose increments during uterine stimulation should be 20-30 min. Feto-maternal blood plasma gradients of OT concentration in spontaneous labor at term indicate a feto-uterine flow of 2-4mU OT/min. Labor can be successfully induced in most women with such physiological doses (2-6 mU/min) of OT given intravenously. Direct and indirect evidence show that OT is released in pulses with the frequency and/or amplitude of the pulses increasing with or during spontaneous labor. Further OT interaction with its receptor renders it occupied and temporarily unavailable. We have therefore employed these observations to induce and augment labor with pulsatile intravenous administration of OT. In a prospective randomized study of 106 patients undergoing labor induction with pulsatile versus continuous administration of OT, the total dose, the average dose/min, and the peak or highest dose required/min were significantly reduced with pulsatile OT compared with continuous OT. These significant differences remained when controlled for parity, Bishop's score of cervical ripeness, and the number of days for induction. Similarly in a prospective randomized study on augmentation of labor by intravenous OT, we found the dose of OT for successful augmentation was significantly reduced with pulsatile OT compared with continuous OT. Thus, pulsatile OT not only is safe and requires less OT for uterine stimulation, but also constitutes a more physiological basis for uterine stimulation. | Uterine Contraction |
BACKGROUND: In 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias. OBJECTIVE: To use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States. DESIGN: Population-based study. SETTING: 42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers. PATIENTS: Patients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013. MEASUREMENTS: Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival. RESULTS: Median age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P < 0.001). On the basis of contemporary data from 2009 to 2013, the median age of survival in Canada was 10 years greater than in the United States (50.9 vs. 40.6 years, respectively). The adjusted risk for death was 34% lower in Canada than the United States (hazard ratio, 0.66 [95% CI, 0.54 to 0.81]). A greater proportion of patients in Canada received transplants (10.3% vs. 6.5%, respectively [standardized difference, 13.7]). Differences in survival between U.S. and Canadian patients varied according to U.S. patients' insurance status. LIMITATION: Ascertainment bias due to missing data or nonrandom loss to follow-up might affect the results. CONCLUSION: Differences in cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private-insurance status among U.S. patients. Differential access to transplantation, increased posttransplant survival, and differences in health care systems may, in part, explain the Canadian survival advantage. PRIMARY FUNDING SOURCE: U.S. Cystic Fibrosis Foundation. | Single-Payer System |
Ptosis is one of the most common involutional changes of the eyelid. It frequently occurs concomitantly with dermatochalasis. The surgeon must be aware of the likelihood of this association when evaluating a patient for blepharoplasty because failure to develop an appropriate surgical plan will lead to an imperfect outcome. Ptosis correction can be undertaken at the same time as upper lid blepharoplasty. The many types of ptosis have a complex underlying anatomy and pathology, however, and the variety of surgical alternatives for ptosis repair are associated with a certain degree of unpredictability. The focus of this discussion is the management of acquired ptosis of aponeurogenic origin, which is most commonly associated with dermatochalasis. A surgeon who is conversant with the underlying anatomy of the ptotic lid and the general guidelines for ptosis repair will be prepared to manage combined dermatochalasis and ptosis. | Blepharoptosis |
Avicennia marina (family Acanthaceae) is a halotolerant woody shrub that grows wildly and cultivated in the coastal regions. Despite its importance, the species suffers from lack of genomic datasets to improve its taxonomy and phylogenetic placement across the related species. Here, we have aimed to sequence the plastid genome of A. marina and its comparison with related species in family Acanthaceae. Detailed next-generation sequencing and analysis showed a complete chloroplast genome of 150,279 bp, comprising 38.6% GC. Genome architecture is quadripartite revealing large single copy (82,522 bp), small single copy (17,523 bp), and pair of inverted repeats (25,117 bp). Furthermore, the genome contains 132 different genes, including 87 protein-coding genes, 8 rRNA, 37 tRNA genes, and 126 simple sequence repeats (122 mononucleotide, 2 dinucleotides, and 2 trinucleotides). Interestingly, about 25 forward, 15 reversed and 14 palindromic repeats were also found in the A. marina. High degree synteny was observed in the pairwise alignment with related genomes. The chloroplast genome comparative assessment showed a high degree of sequence similarity in coding regions and varying divergence in the intergenic spacers among ten Acanthaceae species. The pairwise distance showed that A. marina exhibited the highest divergence (0.084) with Justicia flava and showed lowest divergence with Aphelandra knappiae (0.059). Current genomic datasets are a valuable resource for investigating the population and evolutionary genetics of family Acanthaceae members' specifically A. marina and related species. | Acanthaceae |
Clinical management of constipation has evolved from the prescription of dietary supplements, to potent stimulant laxatives, to corrective surgeries for organic blockage. Yet constipation does not respond to a one-size-fits-all treatment. In recent decades, the Bristol Stool Form Scale and Rome III diagnostic criteria have allowed for algorithmic diagnosis, yet these criteria could benefit from further extension and meaningful discussion. This review incorporates pertinent clinical updates and uses the anatomy and physiology of constipation as helpful signposts for the practicing clinician. | Intestine, Large |
Vitamin D3, combined with its nuclear receptor, regulates more than 900 genes, which is the reason why its effect is pleiotropic. Among other effects, it influences the immunological system. Its deficit may be one of the environmental factors taking part in the development of auto-immunological diseases. The studies reveal that, among others things, inflammatory bowel diseases occur in higher latitudes, with lower exposure to solar radiation and with decreased production of vitamin D3 in the skin. Patients with inflammatory bowel disease have vitamin D3 deficiency more frequently. The application of vitamin D3, especially among adults with inflammatory bowel diseases, positively influences bone turnover markers and mostly due to its influence on immunological processes, vitamin D3 may be useful in the treatment of the primary health condition. It is necessary to determine the dosage range, as well as the optimal level of vitamin D3 metabolite-25OHD3, where the immunosuppressant effect is the best, with no toxic effects. Studies of vitamin D3 analogues deprived of the hypercalcemic influence, but with other merits of the basic substance remaining intact, are particularly promising. | Cholecalciferol |
Infection and inflammation in the gastrointestinal (GI) tract induces a number of changes in the GI physiology of the host. Experimental infections with parasites represent valuable models to study the structural and physiological changes in the GI tract. This review addresses research on the interface between the immune system and GI physiology, dealing specifically with 2 major components of intestinal physiology, namely mucin production and muscle function in relation to host defence, primarily based on studies using the mouse-Trichinella spiralis system. These studies demonstrate that the infection-induced T helper 2 type immune response is critical in generating the alterations of infection-induced mucin production and muscle function, and that this immune-mediated alteration in gut physiology is associated with host defence mechanisms. In addition, by manipulating the host immune response, it is possible to modulate the accompanying physiological changes, which may have clinical relevance. In addition to enhancing our understanding of immunological control of GI physiological changes in the context of host defence against enteric infections, the data acquired using the mouse-T. spiralis model provide a basis for understanding the pathophysiology of a wide range of GI disorders associated with altered gut physiology. | Trichinella spiralis |
The dose-response analyses of cancer and noncancer health effects of aldrin and dieldrin were evaluated using current methodology, including benchmark dose analysis and the current U.S. Environmental Protection Agency (U.S. EPA) guidance on body weight scaling and uncertainty factors. A literature review was performed to determine the most appropriate adverse effect endpoints. Using current methodology and information, the estimated reference dose values were 0.0001 and 0.00008 mg/kg-day for aldrin and dieldrin, respectively. The estimated cancer slope factors for aldrin and dieldrin were 3.4 and 7.0 (mg/kg-day)(-1), respectively (i.e., about 5- and 2.3-fold lower risk than the 1987 U.S. EPA assessments). Because aldrin and dieldrin are no longer used as pesticides in the United States, they are presumed to be a low priority for additional review by the U.S. EPA. However, because they are persistent and still detected in environmental samples, quantitative risk assessments based on the best available methods are required. Recent epidemiologic studies do not demonstrate a causal association between aldrin and dieldrin and human cancer risk. The proposed reevaluations suggest that these two compounds pose a lower human health risk than currently reported by the U.S. EPA. | Aldrin |
Arthritic pain is a common and disabling problem for many older adults. There is widespread evidence that despite its prevalance and debilitating effects on the physical, emotional and cognitive status of older adults, arthritic pain remains under-treated in those age 65 and older. This condition significantly and negatively impacts older adults' quality of life and is a critical problem that requires the attention of gerontological social work. This chapter provides a brief summary of arthritic pain in older adults. It also discusses the treatment efficacy of cognitive-behavioral therapy and psycho-educational programs for older adults with this type of pain. | Arthritis |
The aim of our study was to comprehensively review and critically appraise the cost domains used in economic evaluations of the rheumatic diseases and to use this information to propose standardization of cost domains. The literature search identified 210 abstracts, 32 of which included original cost data. The listed cost categories were grouped into 3 major areas: (direct) health care costs, other (direct) disease related costs, and productivity costs (indirect costs). The number of individual cost categories was reduced by considering the following criteria: (1) inclusion of all relevant cost domains; (2) avoidance of double counting; (3) summarizing of related categories under one representative heading; (4) feasibility of level of aggregation. After adjustment for synonymous labeling, 38 cost categories remained. The subsequent development of a classification scheme of cost categories led to a set of 19 separate cost domains including 7 outpatient, 3 inpatient, 6 other disease related, and 3 productivity cost domains. This literature review indicates that cost assessment in economic evaluations in rheumatoid arthritis lacks standardization. A preliminary scheme to categorize cost assessment in rheumatic conditions is presented. The adoption of standards for economic evaluation would greatly facilitate national and international comparisons. | Direct Service Costs |
Covering: 2015 to 2020The ent-kaurane diterpenoids are integral parts of tetracyclic natural products that are widely distributed in terrestrial plants. These compounds have been found to possess interesting bioactivities, ranging from antitumor, antifungal and antibacterial to anti-inflammatory activities. Structurally, the different tetracyclic moieties of ent-kauranes can be seen as the results of intramolecular cyclizations, oxidations, C-C bond cleavages, degradation, or rearrangements, starting from their parent skeleton. During the past decade, great efforts have been made to develop novel strategies for synthesizing these natural products. The purpose of this review is to describe the recent advances in the total synthesis of ent-kaurane diterpenoids covering the period from 2015 to date. | Diterpenes, Kaurane |
Infections have represented for a long time the leading cause of death in humans. During the 19th century, pneumonia, tuberculosis, diarrhea and diphtheria were considered the main causes of death in children and adults. Only in the late 19th century did it become possible to correlate the existence of microscopic pathogens with the development of various diseases. Within a few years the introduction of antiseptic procedures had begun to reduce mortality due to postsurgical infections. Sanitation and hygiene played a significant role in the reduction of the mortality due to several infectious diseases. The introduction of the first compounds with antimicrobial activity succeeded in conquering many diseases. In this review we analyzed, from a historical perspective, the development of antibiotics and the circumstances that led to their discovery. The first compound with antimicrobial activity was introduced in 1911 by Erlich. He focused his research activity on the discovery of a magic bullet" to treat syphilis. Afterwards, Foley and colleagues brought penicillin to the forefront. Streptomycin represents the first drug discovered for the treatment of tuberculosis, and its development included the first use of clinical trials. Finally, with the development of cephalosporins, the introduction of new antimicrobial compounds with broad activity against gram-positive and also some gram-negative bacteria began." | Arsphenamine |
Monarda fistulosa essential oil characterized by pronounced therapeutic effects is proposed for the treatment of seborrhea. Studies of its antibacterial, antimycotic, and antiinflammatory activities showed that it inhibits microorganism growth and is superior to hydrocortisone in combination with vitamin B6 by its antiinflammatory activity. | Monarda |
The disease San Joaquin Valley Fever (coccidioidomycosis) is caused by the inhalation of Coccidioides arthroconidia. In vivo, arthroconidia transform into pathogenic structures termed spherules. Exposure to the host milieu triggers spherule development; however, the molecular mechanisms responsible for the morphological shift are not well characterized. This study compared the morphogenesis of five strains of both species of Coccidioides in two media types to improve the in vitro model of dimorphism that can be easily reproduced, and is amenable to tissue culture. We also sought to establish a modern record of the morphological switch among commonly used lab strains through a detailed account of growth under various conditions. Spherules from five strains were grown in standard (Converse) and experimental media (RPMI-sph). Strain behavior was quantified by median spherule size and spherule concentration, beginning 3 days after inoculation and followed for 10 days of growth. There were significant differences observed among Coccidioides immitis and C. posadasii strains, as well as differences between the in vitro systems. | Coccidioides |
Phytohormone abscisic acid (ABA) inhibits root nodule formation of leguminous plants. LjGlu1, a beta-1,3-glucanase gene of Lotus japonicus, has been identified as an ABA responsive gene. RNA interference of LjGlu1 increased nodule number. This suggests that LjGlu1 is involved in the regulation of nodule formation. Host legumes control nodule number by autoregulation of nodulation (AON), in which the presence of existing root nodules inhibits further nodulation. For further characterization of LjGlu1, we focused on the expression of LjGlu1 in relation to AON. In a split-root system, LjGlu1 expression peaked when AON was fully induced. Hairy roots transformed with LjCLE-RS1, a gene that induces AON, were generated. Expression of LjGlu1 was greater in the transgenic roots than in untransformed roots. LjGlu1 was not induced in a hypernodulating mutant inoculated with Mesorhizobium loti. These results suggest that the expression of LjGlu1 is involved in the system of AON. However, neither hypernodulation nor enlarged nodulation zone was observed on the transgenic hairy roots carrying LjGlu1-RNAi, suggesting that LjGlu1 is not a key player of AON. Recombinant LjGlu1 showed endo-beta-1,3-glucanase activity. LjGlu1-mOrange fusion protein suggested that LjGlu1 associated with M. loti on the root hairs. Exogenous beta-1,3-glucanase inhibited infection thread formation by both the wild type and the mutant, and nodule numbers were reduced. These results suggest that LjGlu1 is expressed in response to M. loti infection and functions outside root tissues, resulting in the inhibition of infection. | Mesorhizobium |
To determine whether a correlation exists between the genomic HLA class II DP DNA polymorphism and cell surface expression and to detect the DP epitopes responsible for alloreactivity, anti-DP T-cell clones were generated against new PLT blank RFLP DPa and DPb-defined specificities. The clones were tested on the 10th IHWS B-LCLs and on local panel cells. Oligotyping of the tested cells made it possible to (a) correlate the DPa specificity with the DPB1*0402 specificity and (b) split DPb into DPB1*1001 and DPB1*1401. By comparing DNA sequences of the second exon to panel reactivity, the epitopes responsible for DPB1*1001 and 1401 were defined and attributed to beta-chain residues contributing to peptide selection inside the HLA groove. However, DNA sequences could not explain anti-DPa allospecificity, indicating that another structure not yet definable may be involved. | HLA-DP Antigens |
Construction of not in my back yard (NIMBY) facility Public Private Partnership (PPP) projects are feasible measures to realize sustainable urbanization. In order to ensure the smooth development of the NIMBY facility PPP projects, the problem of choosing the most suitable operation mode among many PPP modes is still scarce and unscientific. In order to select the operation mode of the PPP projects that best fits the characteristics of the project, this paper constructs the operation mode selection of the NIMBY facility PPP project. Firstly, the index system of operation mode selection of the NIMBY facility PPP project is determined. G1 subjective weighting method and information entropy objective weighting method are introduced to solve the optimal weight of each index. Grey correlation theory is used to improve TOPSIS method, and the calculation form of relative proximity degree is optimized to determine the most suitable operation mode for the project. In this paper, combined weighting and TOPSIS method are applied to the research of NIMBY facility PPP project, and the operation mode selection of NIMBY facility PPP project is established, which makes up the blank of this part. Finally, a PPP project in Qingdao, Shandong Province, China, is taken as an example to verify the applicability of the model. The effectiveness of this model was tested by comparing the results of TOPSIS method, Grey target model, Extended matter-element mode and GRA-TOPSIS. It is hoped to provide useful reference for the operation mode selection of NIMBY facility PPP project." | Public-Private Sector Partnerships |
In this work, biodegradable biomaterial films for sulindac (SLD) recognition are synthesized from mungbean starch (MBS), PVA, and plasticizers by using UV irradiation process and casting methods. The optimal UV irradiation time for the preparation of SLD imprinted biomaterials films was about 30 min. Mechanical properties, recognition ability, and SLD release property for prepared films were investigated. From the results of recognition ability, we verified that these SLD imprinted biomaterial films have the binding site for SLD. The release properties of SLD was examined with the change of pH and temperature. The results indicate that the SLD release in pH 10.0 was higher than in pH 4.0. SLD release was also evaluated using an artificial skin. Results of the artificial skin test verified that SLD was released constantly for 20 days. | Sulindac |
BACKGROUND: The epidemic growth of morbid obesity has led to an increase in the number of bariatric interventions. During the distribution process of bariatric surgical interventions, the risk for severe nutritious complications such as bariatric beriberi can rise. METHODS: By means of systematic literature review, epidemiological data, clinical characteristics and diagnostic as well as therapeutic recommendations for bariatric beriberi were elicited. Databases and registries such as PubMed, Cochrane and Ovid were searched for a defined time period with the key words 'lack of thiamine' / 'Wernicke-Korsakoff syndrome' / 'encephalopathy' after bariatric surgical interventions. RESULTS: Up to December 2013, overall 255 patients had been found as published cases, indicating that the risk for the postoperative occurrence of thiamine deficiency and Wernicke-Korsakoff syndrome is increased in women. In addition, the risk correlates with patient's age. The majority of patients developed symptoms of a dry beriberi with peripheral neuritis, ataxia and paraplegia, indicating an advanced stage of disease approximately 4-12 weeks postoperatively. Laboratory analysis in case of a suspicious clinical finding is the appropriate diagnostics. As treatment, prompt initiation of parenteral thiamine substitution under clinical monitoring is required. CONCLUSION: Bariatric beriberi can occur within the first 1-3 postoperative months. To minimize the risk of severe consequences, immediate substitution of thiamine in clinical suspicion or prolonged parenteral nutrition is necessary. A delayed diagnosis or missing the correct diagnosis can lead to irreversible damages of the CNS with coma and fatal outcome. Knowledge on the subject, including development of thiamine deficiency, symptomatology and emergency treatment, are considered essential for bariatric surgeons but also for further medical disciplines involved in treatment. | Beriberi |
The single most important element to consider when evaluating clinical information systems for a practice is workflow. Workflow can be broadly defined as an orchestrated and repeatable pattern of business activity enabled by the systematic organization of resources into processes that transform materials, provide services, or process information. | Pathology, Surgical |
Our previous studies have shown that microRNA-383 (miR-383) is one of the most down-regulated miRNA in TGF-beta1-treated mouse ovarian granulosa cells (GC). However, the roles and mechanisms of miR-383 in GC function during follicular development remain unknown. In this study, we found that miR-383 was mainly expressed in GC and oocytes of mouse ovarian follicles. Overexpression of miR-383 enhanced estradiol release from GC through targeting RNA binding motif, single stranded interacting protein 1 (RBMS1). miR-383 inhibited RBMS1 by affecting its mRNA stability, which subsequently suppressed the level of c-Myc (a downstream target of RBMS1). Forced expression of RBMS1 or c-Myc attenuated miR-383-mediated steroidogenesis-promoting effects. Knockdown of the transcription factor steroidogenic factor-1 (SF-1) significantly suppressed the expression of Sarcoglycan zeta (SGCZ) (miR-383 host gene), primary and mature miR-383 in GC, indicating that miR-383 was transcriptionally regulated by SF-1. Luciferase and chromatin immunoprecipitation assays revealed that SF-1 specifically bound to the promoter region of SGCZ and directly transactivated miR-383 in parallel with SGCZ. In addition, SF-1 was involved in regulation of miR-383- and RBMS1/c-Myc-mediated estradiol release from GC. These results suggest that miR-383 functions to promote steroidogenesis by targeting RBMS1, at least in part, through inactivation of c-Myc. SF-1 acts as a positive regulator of miR-383 processing and function in GC. Understanding of regulation of miRNA biogenesis and function in estrogen production will potentiate the usefulness of miRNA in the control of reproduction and treatment of some steroid-related disorders. | Steroidogenic Factor 1 |
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