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We report a case of fat-soluble vitamin deficiency in a 14-year old boy who had chronic duodenal obstruction. He presented with periodic unexplained bleeding tendency. The laboratory results showed positive fat globules in stool and prolonged prothrombin time. His further investigation revealed low plasma vitamin A and undetectable plasma vitamin E. After parenteral vitamin K and oral vitamin A and E supplement, these abnormalities resolved although he still had absent knee jerk. We propose that fat malabsorption and fat-soluble vitamin deficiency can occur after prolonged duodenal obstruction that induce bacterial overgrowth following by bile acid deconjugation. Despite very few case reports, screening for fat malabsorption and fat-soluble vitamin deficiency might be warranted in patients with chronic small bowel obstruction. | Steatorrhea |
This article examines the possibility of genetic discrimination in life insurance and discusses the inability of current Australian legislation to deal adequately with genetic test result information. Genetic information has certain features that distinguish it from other medical information and thus a specialist legislative package is required to regulate its use. This article outlines how current practices in the life insurance industry are inconsistent with notions of human rights. Several legislative options are suggested and examined. Given the negative and damaging impact that adverse selection is likely to have on the life insurance industry should the use of all genetic test results be prohibited, an approach which modifies the current regime is recommended. This includes a comprehensive review scheme and the introduction of additional insurance products tailored to individuals suffering from various genetic illnesses or predispositions to future disease. | Genetic Privacy |
Mini-implants are becoming increasingly popular in orthodontic practice. However, there is still controversy about the need for implant-site preparation. This article reviews the current literature to answer the question: is predrilling is necessary for orthodontic mini-implants?" | Dental Implantation, Endosseous |
The development of ultrasensitive in situ detection techniques for monitoring hypobromous acid (HBrO) levels in the biological systems is of great significance to reveal its complex pathological and physiological effects. A simple mitochondria-targetable hydrazine-based near-infrared (NIR) fluorescent probe (Mito-NIR) for detecting HBrO in the mitochondria of live cells is presented in this paper. Probe Mito-NIR displays the ultrafast (< 5 s) response for HBrO. It can detect HBrO with high sensitivity. Additionally, it shows high selectivity towards HBrO over other biologically important substances. Finally, it can monitor the changes of endogenous/exogenous HBrO levels in the mitochondria of live cells. A simple mitochondria-targetable NIR fluorescent probe with picomolar sensitivity for HBrO was developed to specifically track mitochondrial HBrO. | Bromine Compounds |
Invasive mucoepidermoid carcinoma of the conjunctiva of the left lower eyelid was diagnosed in an orbital exenteration specimen of a 57-year-old woman, after a biopsy of the same lesion was originally diagnosed as invasive squamous cell carcinoma. The woman was undergoing mitomycin C injections for ocular cicatricial pemphigoid, diagnosed in the same eye 2 years prior to identification of the neoplasm. The tumor invaded the cornea, sclera, lacrimal gland, regional small nerves, and lymphatics, but did not show intraocular involvement. The original biopsy specimen was reassessed with stains for mucin and found to be mucoepidermoid carcinoma of the conjunctiva. We reviewed 21 cases of mucoepidermoid carcinoma of the conjunctiva described to date in the English literature. We believe this number underestimates the true incidence of this condition, as it is frequently misdiagnosed both clinically and histopathologically. Evaluating suspected aggressive squamous cell carcinoma with special stains for mucin generally helps to identify mucoepidermoid carcinoma of the conjunctiva. More extensive surgical excision than that used for squamous cell carcinoma should be implemented in the management of mucoepidermoid carcinoma of the conjunctiva to prevent recurrence." | Pemphigoid, Benign Mucous Membrane |
Several studies have demonstrated potential roles for apelin/APJ signaling in the regulation of oxidative stress associated with ischemia-reperfusion (I/R) injury in several organs. Objective was to assess the role of apelin/APJ signaling in the development of pressure ulcers (PUs) formation after cutaneous I/R injury in mice. We identified that cutaneous I/R injury increased the expression of apelin in the skin at I/R site. Administration of apelin significantly inhibited the formation of PUs. The reductions of blood vessels, hypoxic area and apoptosis in I/R site were inhibited by apelin injection. Oxidative stress signals in OKD48 mice and the expressions of oxidative stress related genes in the skin were suppressed by apelin injection. H(2)O(2)-induced intracellular ROS and apoptosis in endothelial cells and fibroblasts were suppressed by apelin in vitro. Furthermore, MM07, biased agonist of APJ, also significantly suppressed the development of PUs after cutaneous I/R, and the inhibitory effect of MM07 on PUs formation was higher than that in apelin. We conclude that apelin/APJ signaling may inhibit cutaneous I/R injury-induced PUs formation by protecting the reduction of vascularity and tissue damage via suppression of oxidative stress. Exogenous application of apelin or MM07 might have therapeutic potentials against the development of PUs. | Apelin |
Cypress pollen represents the primary cause of respiratory allergies in Mediterranean areas. Patients allergic to Cupressus sempervirens pollen (Cups) (CPA) can be discriminated on the basis of the immunoglobulin E (IgE) binding to a basic 14 kDa protein (BP14) or to high-molecular-weight (HMW) glycoproteins only. Specific IgE repertoires of two differentially exposed CPA cohorts, French and Italian, were investigated using an IgE microarray system (some known major allergens from several allergenic sources) and individual IgE immunoblotting (IB) of whole Cups pollen extract separated by SDS-PAGE (all allergens from one allergenic source: cypress pollen). The prevalence of sensitization to BP14 was higher in French (37 %) than in Italian patients (17 %) and major differences were observed in IgE reactivities to lipid transfer proteins (LTPs). Thirty percent of the Italian CPA (4 % in the French group) had specific IgE against the Parietaria pollen LTP, independently of IB subgroups. Regarding peach LTP sensitization, all Pru p 3+ Italian CPA (10 %) were in the HMW+ subgroup, while Pru p 3+ French CPA (20 %) were all included in the BP14+ subgroup. BP14 sensitization is likely a marker of Cups exposure and is, in French CPA, significantly correlated to Pru p 3 sensitization. The IgE immunoblot and microarray are complementary tools that highlight differences in the subtle sensitization profile between groups of patients in comparative studies. | Cupressus |
Based on conserved amino-acid regions predicted for the chitin synthases (Chs) of Saccharomyces cerevisiae, two different primer sets were synthesized and used in polymerase chain reactions (PCRs) to amplify 614-bp and 366-bp sequences from genomic DNA of the zoopathogenic fungus Phialophora verrucosa. DNA-sequencing and Southern-blotting analyses of the 614-bp DNA amplification products suggested that portions of two distinct P. verrucosa chitin synthase genes (PvCHS1, PvCHS2), coding for two different zymogenic-type PvChs isozymes, had been identified. The deduced amino-acid sequence of each fell into different Chs classes, namely class I and class II. In addition, the 366-bp DNA segment was shown to code for a conserved region having homology with the CSD2/CAL1 gene of S. cerevisiae, which encodes a nonzymogenic-type enzyme, Chs3, in that fungus. The amino-acid sequence derived from PvCHS3 exhibits 88.2% similarity and 78.4% identity to the same amino-acid region of the S. cerevisiae enzyme. These results provide a critical first step toward investigating the molecular and pathogenic importance of CHS gene regulation in this fungus and for exploring steps leading to Chs function as potential targets for the design of new therapeutic agents. | Phialophora |
Striatal-enriched protein tyrosine phosphatase (STEP) is a brain specific protein tyrosine phosphatase that has been implicated in many neurodegenerative diseases, such as Alzheimer's disease. We recently reported the benzopentathiepin TC-2153 as a potent inhibitor of STEP in vitro, cells and animals. Herein, we report the synthesis and evaluation of TC-2153 analogs in order to define what structural features are important for inhibition and to identify positions tolerant of substitution for further study. The trifluoromethyl substitution is beneficial for inhibitor potency, and the amine is tolerant of acylation, and thus provides a convenient handle for introducing additional functionality such as reporter groups. | Benzothiepins |
This review outlines the major prognostic factors as derived from the analysis of recent prospective trials. Disease extent, systemic symptoms, age, sex, and achievement of complete remission lasting longer than 12 months following chemotherapy, as well as certain treatment-related complications (e.g. acute leukemia), constitute the major variables affecting survival. Bulky lymphoma and inadequate primary irradiation are factors which have influence on relapse-free but not necessarily on total survival. Recent reports provide no evidence that minimalizing treatment (except salvage treatment), will demonstrably reduce treatment-related complications. Optimal treatment, giving patients the best chance to enter first durable complete remission, still seems to represent the best strategic approach. However, in given patient subsets, the impact of various treatment strategies on the 5-, 10-, and 15-year results is now being balanced against delayed morbidity, such as organ damage and second malignancies, produced by the intensity of treatment or the prolonged delivery of certain drugs. | Hodgkin Disease |
Despite advances in therapy, bleeding and thromboembolic events are frequent complications in patients with left ventricular assist device (LVAD) support. Maintaining warfarin in therapeutic range has been shown to be more challenging in this patient population compared to other indications. Patients with LVADs on warfarin typically are within goal international normalized ratio (INR) range 36-57% of the time, compared to about 65% for other indications. The goal of this study was to evaluate if an INR remote monitoring system along with the implementation of a standardized warfarin management protocol improves warfarin time in therapeutic range (TTR) for patients with LVADs. This single-center, retrospective, observational study included 78 patients with LVADs that were followed at our academic center from January 2015 to October 2017. In October 2016, we updated our warfarin management protocol and implemented a remote monitoring system with patients' weekly INR results monitored. The primary objective of the study was to determine the difference between TTRs in remote monitoring versus standard monitoring. We found that the average TTR was significantly higher in the remote monitoring group compared to the standard monitoring cohort (61.1% vs. 40.0%, p < 0.005). However, bleeding, thrombotic incidence, and hospital readmission rates were similar between the two patient cohorts. Remote monitoring improved warfarin TTR significantly in this study and may have the potential to improve anticoagulation-related outcomes in patients with LVADs." | International Normalized Ratio |
Flowering of many plants is induced by environmental signals, but these responses can depend on the age of the plant. Exposure of Arabidopsis thaliana to vernalization (winter temperatures) at germination induces flowering, whereas a close perennial relative Arabis alpina only responds if exposed when at least 5 weeks old. We show that vernalization of these older A. alpina plants reduces expression of the floral repressor PEP1 and activates the orthologs of the Arabidopsis flowering genes SOC1 (Aa SOC1) and LFY (Aa LFY). By contrast, when younger plants are vernalized, PEP1 and Aa SOC1 mRNA levels change as in older plants, but Aa LFY is not expressed. We demonstrate that A. alpina TFL1 (Aa TFL1) blocks flowering and prevents Aa LFY expression when young plants are exposed to vernalization. In addition, in older plants, Aa TFL1 increases the duration of vernalization required for Aa LFY expression and flowering. Aa TFL1 has similar functions in axillary shoots, thus ensuring that following a flowering episode vegetative branches are maintained to continue the perennial life cycle. We propose that Aa TFL1 blocks flowering of young plants exposed to vernalization by setting a threshold for a flowering pathway that is increased in activity as the shoot ages, thus contributing to several perennial traits. | Arabis |
French bulldogs (FBD) are reported to be at an increased risk of developing humeral condylar fractures (HCF). Spaniel breeds have been reported to be at increased risk of HCF due to a high prevalence of humeral intracondylar fissures (HIF), which can predispose to fracture. The aims of this retrospective, single center, observational study were twofold. First, to compare the signalment, fracture configuration, and etiology of populations of FBD and spaniel breeds presenting with HCF at a single hospital. Second, to evaluate the computed tomographic (CT) findings of the contralateral elbow joints of FBD and spaniel breeds presenting with HCF for concomitant pathology. FBDs were overrepresented for HCF, most commonly presenting when skeletally immature, with a median age of 3.7 months. Fractures of the lateral condyle were the most common configuration for both breed groups. Sclerosis at the fracture site was identified in 62% of FBD and 95% of spaniels undergoing CT scans. Humeral intracondylar fissures and intracondylar sclerosis were commonly observed in the contralateral elbows of FBD (44% and 50%, respectively) and spaniel breeds (58% and 95%, respectively). Medial coronoid pathology, elbow incongruency, and periarticular osteophytes were not identified in the contralateral elbows of FBD but were identified in 29%, 4%, and 20% of spaniels, respectively. The high prevalence of HIF in the FBD group may be a predisposing factor for HCF in this breed. | Sclerosis |
Small G proteins or GTPases comprise a growing family of signal transduction molecules with inducible properties dependent upon reversible interactions with guanine nucleotides. Activation status of the proteins is characterized by preferential affinity for triphosphorylated guanine nucleotides, initiating signaling events that control fundamental processes involved in cell migration and contraction. Termination of small G protein signaling activity is in part achieved through intrinsic GTPase activity, which catalyzes the removal of GTP and its replacement with functionally inactive GDP. Recent investigations have implicated various small G proteins as messengers that control cell-cell contact between scaffold proteins and the actin cytoskeleton, suggesting an intrinsic mechanism for the regulation of paracellular permeability in polarized epithelial and endothelial cells. This review will examine current evidence for the control of tight junction permeability by small G proteins, and speculate upon future directions that may be of value in further exploring the biological importance of these key mediators. | rab3 GTP-Binding Proteins |
Riboflavin (7,8-dimethyl-10-ribitylisoalloxazine; vitamin B2) is a water-soluble vitamin, cofactor derivatives of which (FAD, FMN) act as electron acceptors in the oxidative metabolism of carbohydrate, amino acids and fatty acids and which in the reduced state can donate electrons to complex II of the electron transport chain. This means that riboflavin is essential for energy generation in the aerobic cell, through oxidative phosphorylation. The classic effects of riboflavin deficiency on growth and development have generally been explained in terms of these functions. However, research also suggests that riboflavin may have specific functions associated with cell fate determination, which would have implications for growth and development. In particular, riboflavin depletion interferes with the normal progression of the cell cycle, probably through effects on the expression of regulatory genes, exerted at both the transcriptional and proteomic level. | Riboflavin Deficiency |
Seven new iboga-type alkaloids, ervaoffines A-D (1-4), (7S)-3-oxoibogaine hydroxyindolenine (5), ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 1-7 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed. | Tabernaemontana |
OBJECTIVE: India is a country sharing one fourth of the global incidence of tuberculosis. It is much easier to diagnose pulmonary cases, but challenges are with extrapulmonary cases. Genital tuberculosis is considered as an important cause of infertility in young females in India and difficult to diagnose. It requires incorporation of different modalities that should correctly, timely and rapidly diagnose the case. METHODS: This study was conducted retrospectively for a period of 12 months on 438 endometrial samples from females with history of infertility. Three modalities namely Ziehl-Neelsen staining, Automated liquid culture and Nucleic acid amplification technique (TB-PCR) were compared and their sensitivity in diagnosis of genital tuberculosis was ascertained. RESULTS: Out of 438 samples, 18 samples were found positive with at least one modality. TB-PCR positivity was 3.6% (16 cases) in comparison to culture where positivity was 1.59% (7 cases). Five samples were found culture and TB-PCR positive and only one sample was positive by all three diagnostic tests. CONCLUSION: Infertility in young female per se is usually heart breaking and distressing. Therefore, it is essential to diagnose and treat the cases of genital tuberculosis before irreversible damage of tube may happen. Although, advancement in diagnostic field is there from microscopy to molecular method, but still diagnosis of genital tuberculosis is challenging. Correct diagnosis prevents young female from mental trauma and toxicity of anti-tuberculosis drugs given on suspicion in high prevalence country like India. | Tuberculosis, Female Genital |
In this paper, we describe a protocol for a non-penetrating embedding matrix that can be used for frozen or vibratome sectioning of various formaldehyde-fixed tissue specimens. In our experiments, we wanted to prepare thin frozen sections from miniature specimens for fluorescent staining. As we could not achieve satisfactory results with any of the previously published methods, we have tried to modify the existing protocols, and systematically evaluated the effect of these modifications on the properties of the embedding matrix. The resulting protocol is simple, the matrix gets firmly attached to the tissues, does not cause autofluorescence and enables preparing extremely thin frozen sections. The matrix can be used for 1, embedding miniature specimens from problematic tissues to enable cutting very thin frozen sections, 2, grouping multiple specimens into one large block for simultaneous processing, and 3, dispersing single cells and preparing cell blocks for frozen sectioning. | Cryoultramicrotomy |
In response to a national cry of nursing shortage, the federal government passed the Nurse Training Act of 1964. This article traces the history of this critical nursing legislation, examines its outcomes, and analyzes the effect of the Act on nursing in the future. | Legislation, Nursing |
Flaviviruses are responsible for yellow fever, Zika fever and dengue, all of which are major human diseases found in tropical regions of the globe. They are zoonoses with a transmission cycle that involves primates as reservoirs and mosquitoes of the genus Aedes as vectors. The recent upsurge of urban epidemics of yellow fever, Zika fever and dengue has involved human-to-human transmission with mosquitoes as the vector. This paper is primarily concerned with dengue, which has become the pre-eminent arbovirosis in terms of public health. | Flavivirus Infections |
The aim of the study was to compare the effectiveness of hyaluronic acid (HA) injection and arthrocentesis plus HA injection for treating disc displacement with reduction (DDwR) and disc displacement without reduction (DDwoR). In this randomized clinical trial, patients were divided into 2 main groups: group I (DDwR) and group II (DDwoR). Sub-groups were made depending on allocated treatment: group Ia (arthrocentesis plus HA), group Ib (single HA), group Ic (control), group IIa (arthrocentesis plus HA), group IIb (single HA), and group IIc (control). The primary outcome variable was maximum pain on chewing, while maximum pain at rest, maximum non-assisted and assisted mouth opening, chewing efficiency, temporomandibular joint (TMJ) sounds, quality of life, treatment tolerability, and treatment effectiveness were secondary outcomes. The influences of individual study variables (gender, involved side, and duration of symptoms) on clinical outcomes were also examined. The study consisted of 116 TMJs of 90 patients (n = 45 in both main groups, TMJs = 58) aged 15-82 years. At the 6-month follow-up, improvement in all parameters, except for TMJ sounds, was recorded in all treatment groups, with no improvements in control groups. Notably, arthrocentesis plus HA showed superior improvement in chewing efficiency (p = 0.041) and quality of life (p = 0.047) of group I and quality of life (p = 0.004) in group II, compared to single HA. Furthermore, the duration of symptoms correlated with clinical outcomes. Both procedures successfully improved the symptoms of DDwR and DDwoR patients, but arthrocentesis plus HA injection seemed superior. | Arthrocentesis |
Echinococcosis is a zoonotic disease caused by cestode species of the genus Echinococcus, which demonstrates considerable medical and veterinary concerns. The development of novel drugs for echinococcosis treatment is urgently needed. In this study, we demonstrated that lonidamine (LND) and 6-aminonicotinamide (6-AN) exhibited considerable in vitro effects against both larval- and adult-stage of E. granulosussensu stricto (s. s.) and E. multilocularis. The combination of LND and 6-AN exhibited a significantly higher activity than the single drug treatment. These results highlight the therapeutic potential of LND, 6-AN and the combination of LND and 6-AN for the treatment of echinococcosis. | Echinococcus multilocularis |
Antitumor efficiency of electrochemical lysis was evaluated on the model of M-1 sarcoma. At stage 1 of the study, the results of therapy with electrodes in different position were compared, at stage 2 various combination of electrochemical lysis parameters (current strength and duration of exposure) were evaluated. The increase in parameters was associated with the increase in the percentage of cases with complete regression of tumors, which was confirmed by morphological data. | Disease Models, Animal |
We identified a novel amino acid transporter designated Asc-2 (for asc-type amino acid transporter 2). Asc-2 exhibited relatively low but significant sequence similarity to the members of the heterodimeric amino acid transporters. The cysteine residue responsible for the disulfide bond formation between transporters (light chains) and heavy chain subunits in the heterodimeric amino acid transporters is conserved for Asc-2. Asc-2 is, however, not colocalized with the already known heavy chains such as 4F2 heavy chain (4F2hc) or related to b(0,+) amino acid transporter (rBAT) in mouse kidney. Because Asc-2 solely expressed or coexpressed with 4F2hc or rBAT did not induce functional activity, we generated fusion proteins in which Asc-2 is connected with 4F2hc or rBAT. The fusion proteins were sorted to the plasma membrane and expressed the function corresponding to the Na(+)-independent small neutral amino acid transport system asc. Distinct from the already identified system asc transporter Asc-1 which is associated with 4F2hc, Asc-2-mediated transport is less stereoselective and did not accept some of the high affinity substrates of Asc-1 such as alpha-aminoisobutyric acid and beta-alanine. Asc-2 message was detected in kidney, placenta, spleen, lung, and skeletal muscle. In kidney, Asc-2 protein was present in the epithelial cells lining collecting ducts. In the Western blot analysis on mouse erythrocytes and kidney, Asc-2 was detected as multiple bands in the nonreducing condition, whereas the bands shifted to a single band at lower molecular weight, suggesting the association of Asc-2 with other protein(s) via a disulfide bond. The finding of Asc-2 would lead to the establishment of a new subgroup of heterodimeric amino acid transporter family which includes transporters associated not with 4F2hc or rBAT but with other unknown heavy chains." | Fusion Regulatory Protein 1, Heavy Chain |
To examine the capability of genetic regulatory systems for complex dynamic activity, we developed simple kinetic models that incorporate known features of these systems. These include autoregulation and stimulus-dependent phosphorylation of transcription factors (TFs), dimerization of TFs, crosstalk, and feedback. The simplest model manifested multiple stable steady states, and brief perturbations could switch the model between these states. Such transitions might explain, for example, how a brief pulse of hormone or neurotransmitter could elicit a long-lasting cellular response. In slightly more complex models, oscillatory regimes were identified. The addition of competition between activating and repressing TFs provided a plausible explanation for optimal stimulus frequencies that give maximal transcription. Such optimal frequencies are suggested by recent experiments comparing training paradigms for long-term memory formation and examining changes in mRNA levels in repetitively stimulated cultured cells. In general, the computational approach illustrated here, combined with appropriate experiments, provides a conceptual framework for investigating the function of genetic regulatory systems. | Genes, Regulator |
A new multidisciplinary treatment for head and neck cancer was shown by focusing on the maxillary and oropharyngeal carcinoma. Neo-adjuvant chemotherapy which consists of cisplatin and peplomycin was incorporated into it. In terms of maxillary carcinoma, 2 courses of chemotherapy were given with an interval of 2 weeks, followed by radiotherapy (40 Gy) combined with intraarterial chemotherapy (5-FU). When no cancer cells were detected at the completion of this therapy, adjuvant chemoimmunotherapy was given. When an apparent tumor was still revealed by CT, radical surgery was performed. When cancer cells were detected only by histological examination, additional radiotherapy up to 60 Gy was given by Linac. The results obtained were analysed in 14 cases. We also presented another type of multidisciplinary treatment in oropharyngeal carcinoma. | Peplomycin |
OBJECTIVE: To demonstrate the equivalent efficacy of temazepam 7.5 mg and temazepam 15 mg for the treatment of transient insomnia. RESEARCH DESIGN AND METHODS: This was a double-blind, parallel group, multicenter study. Healthy male and female subjects with previous but not current complaints of transient insomnia were enrolled. Transient insomnia was induced in the sleep laboratory by means of the 'first night' effect and by implementing a 2-h phase advance. The effects of both doses of temazepam on polysomnographic (PSG) measures of sleep were evaluated for one night. Latency to persistent sleep (LPS) and total sleep time (TST) were designated as the primary efficacy endpoints. RESULTS: One hundred and thirty-one subjects completed the study: 65 received the 7.5-mg dose, and 66 received the 15-mg dose. Treatment groups begin with the lowest effective dose, i.e., 7.5 mg. were well matched based on background demographics. No statistically significant differences between doses were detected for LPS, TST,or any other objective (PSG) measure of sleep. Furthermore, both doses were found to be clinically equivalent for LPS and TST based on predetermined criteria. Temazepam was well tolerated, and no significant differences between doses were found for adverse event (AE) incidence, mean score on the Digit Symbol Substitution Task, or mean scores on questions related to tolerability from the Leeds Sleep Evaluation Questionnaire. CONCLUSIONS: The 7.5-mg and 15-mg doses of temazepam were equally effective for the treatment of transient insomnia. In keeping with current practice guidelines, initiation of treatment with temazepam for transient insomnia should | Temazepam |
Aggregatibacter actinomycetemcomitans leukotoxin (LtxA) is a major virulence factor that kills leukocytes permitting it's escape from host immune surveillance. A. actinomycetemcomitans strains can produce high or low levels of toxin. Genetic differences reside in the so called JP2" ltxA promoter region. These hyper-leukotoxin producing strains with the 530 bp deletion have been studied in detail. However, regions contained within the 530 bp deletion that could be responsible for modulation of leukotoxin production have not been defined. Here, we report, for the first time, on regions within the 530 bp that are responsible for high-levels of ltxA expression. We constructed a deletion of 530 bps in a primate isolate of A. actinomycetemcomitans, which produced leukotoxin equivalent to the JP2 strain. We then constructed sequential deletions in regions that span the 530 bps. Results indicated that expression of the ltxA transcript was reduced by a potential transcriptional terminator in promoter region 298 to 397 with a DeltaG = -7.9 kcal/mol. We also confirmed previous findings that transcriptional fusion between the orfX region and ltxC increased ltxA expression. In conclusion, we constructed a hyper-leukotoxin producing A. actinomycetemcomitans strain and identified a terminator located in the promoter region extending from 298-397 that alters ltxA expression." | Exotoxins |
Patients requiring extensive restorative care frequently exhibit significant loss of tooth structure. Specific clinical findings in an extremely worn dentition may vary widely and are often confusing. Severe wear can result from a mechanical cause, a chemical cause, or a combination of causes. The location of the wear, the accompanying symptoms and signs, and information gained from the patient interview are essential components in determining the etiology. A diagnostic decision tree facilitates a systematic analysis and diagnosis of dental wear. | Tooth Diseases |
BACKGROUND: Cupping therapy is a common practice in Korean medicine. Despite developments in this clinical and research area, the current knowledge is insufficient to identify the effects of cupping therapy on obesity. We aimed to assess the effects and safety of cupping therapy on obesity by performing a systematic review and meta-analysis of the effects of cupping therapy. METHODS: A systematic search of databases was conducted, including MEDLINE/PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Citation Information by the National Institute of Informatics, KoreaMed, Oriental Medicine Advanced Searching Integrated System, and ScienceON, for full-text randomized controlled trials (RCTs) published through January 14, 2023, with no language restrictions. The experimental groups received cupping therapy combined with traditional Chinese medicine (TCM) and conventional therapy. The control groups received no treatment, conventional therapy, or TCM treatments alone. The experimental and control groups were compared in terms of body weight (BW), body mass index (BMI), hip circumference (HC), waist circumference (WC), waist-hip ratio (WHR), and body fat percentage (BFP). We evaluated the risk of bias using the 7 domains stipulated by the Cochrane Collaboration Group and performed a meta-analysis using Cochrane Collaboration software (Review Manager Software Version 5.3). RESULTS: A total of 21 RCTs were included in this systematic review and meta-analysis. The analysis revealed improvements in BW (P < .001), BMI (P < .001), HC (P = .03), and WC (P < .001). However, there were no clinically significant changes in WHR (P = .65) or BFP (P = .90), both of which had very low certainty of evidence. No adverse events were reported. CONCLUSION: Overall, our results show that cupping therapy can be used to treat obesity in terms of BW, BMI, HC, and WC and is a safe intervention for the treatment of obesity. However, the conclusions of this review should be interpreted with caution in clinical practice because of the uncertain quality of the included studies. | Cupping Therapy |
Selenium is a micronutrient that is essential for the proper functioning of all organisms. Studies on the functions of selenium are rapidly developing. This element is a cofactor of many enzymes, for example, glutathione peroxidase or thioredoxin reductase. Insufficient supplementation of this element results in the increased risk of developing many chronic degenerative diseases. Selenium is important for the protection against oxidative stress, demonstrating the highest activity as a free radical scavenger and anti-cancer agent. In food, it is present in organic forms, as exemplified by selenomethionine and selenocysteine. In dietary supplementation, the inorganic forms of selenium (selenite and selenate) are used. Organic compounds are more easily absorbed by human organisms in comparison with inorganic compounds. Currently, selenium is considered an essential trace element of fundamental importance for human health. Extreme selenium deficiencies are widespread among people all over the world. Therefore, it is essential to supplement the deficiency of this micronutrient with selenium-enriched food or yeast cell biomass in the diet. | Micronutrients |
In the XIX century Claude Bernard discovered the action of the nervous system on the peripheral circulation. In the first half of the XX century Ewald Hering discovered the baro-receptor and the reflex control of the heart rate and blood pressure. Cowley and Guyton demonstrated that sino-aortic denervation induces persistent changes in the blood pressure in the dog. The autonomic nervous system is mainly responsible for the regulation of the circulation and blood pressure in the short term on a beat to beat basis. It controls the vasomotor tone, the heart rate and the cardiac output. With the advent of non invasive methods that measure the blood pressure on a beat to beat basis (Finapres) and with the methods of measurement of the variability of the blood pressure in the frequency domain (spectral analysis) we can currently measure many variables including heart rate, blood pressure, stroke volume, peripheral resistances and the baroreceptor sensitivity and make some inferences about their control mechanisms. These variables can be measured at rest in the supine position, standing up, during rhythmic breathing and during the Valsalva maneuver. In this article we present a review of the neural control of the blood pressure and heart rate. | Pressoreceptors |
The combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) has been successfully used to treat chronic urinary tract infections. Since parenchymal involvement associated with renal insufficiency of varying degree is not infrequent in these patients, it was considered important to study the pharmacokinetics of TMP and SMP in a fixed dose combination. Four groups of patients were studied: 1) 4 patients with endogenous creatinine clearance (CLcR) between 80 and 40 ml/min; 2) 3 patients with CLcR between 40 and 10 ml/min; 3) 3 patients on chronic peritoneal dialysis (CAPD); and 4) 3 patients on haemodialysis. A single oral dose of 250 mg TMP and 200 mg SMP was given to each patient. Multiple samples were collected over 9 days and the following pharmacokinetic parameters were calculated: total area under the plasma level curve, slow disposition rate constant beta and the corresponding t1/2 beta, plasma clearance and the apparent volume of distribution. The results show that the two moieties of the TMP-SMP combination behaved differently in uraemic patients as fas as elimination rate was concerned. TMP was eliminated more slowly both in patients with diminished renal function and in those subjected to haemo- or peritoneal dialysis. The reduction in the rate of elimination of TMP was significantly correlated with the degree of renal impairment. The elimination of SMP, however, was not significantly affected by the reduced renal function; indeed a tendency to increase was noted, at least in dialyzed patients.(ABSTRACT TRUNCATED AT 250 WORDS) | Sulfalene |
A chemical investigation of Cynanchum mongolicum (Maxim.) Kom. identified 8 compounds. On the basis of spectroscopic data, they were determined to be 3 alkaloids and 5 sinapoyl esters, among which were two previously undescribed compounds (1 and 2). The inhibitory effects of the isolated compounds against four human tumor cell lines were evaluated in vitro by MTT assays, which revealed moderate inhibitory effects with IC(50) values < 50 mM, in particularly, three antofine analogues have showed significant antitumor activities with IC(50) values < 0.1 mM, which was obviously better than the 5-fluorouracil and potential to be used as cancer drugs. | Cynanchum |
During the past decade, much progress has been made toward understanding the mechanisms underlying plant hormone activity, from perception to nuclear events. However, the signaling mechanisms for abscisic acid (ABA) have remained largely obscure. Recent breakthroughs identifying FCA, which is an RNA-binding protein, the Mg-chelatase H subunit, and a G protein-coupled receptor as receptors for ABA provide a major leap forward in understanding the initial steps of ABA signaling mechanisms. Recent studies have also revealed the molecular mechanisms of second messenger production, protein modifications such as phosphorylation, and regulatory mechanisms of gene expression in the ABA response. Therefore, the connections between these events are also beginning to be determined. Here, we review recent progress and discuss the overall scheme of the ABA response mechanisms. | Abscisic Acid |
Cloned homobasidiomycete TRP2 genes for Agaricus bisporus and Coprinus bilanatus were sequence-characterised. Both genes encode tri-functional proteins with activity domains for glutamine amidotransferase (GAT; G domain), indole glycerol phosphate synthase (InGP; C domain) and phosphoribosyl anthranilate isomerase (F domain). A conserved intron disrupts the GAT-coding sequence in both genes. Consensus amino acid (aa) signatures were identified for GAT and InGP, but in the latter 15-aa signature, one residue did not fit the previously defined consensus. Protein architecture and parsimony analysis with analogous proteins indicate domain organisation (NH(2)-G-C-F-COOH) was as for other filamentous fungi. The data do not support earlier suggestions that the three activity domains are detached in A. bisporus. | Agaricus |
Auriculo-condylar syndrome (ACS) is characterized by typical ears malformation (so-called question mark" ears), prominent cheeks, microstomia, and abnormality of the temporomandibular joint and condyle of the mandible. In this report we describe a new simplex case and a previously unreported family with affected individuals in three generations documenting clinical variability. Linkage study for markers located in candidate region for ACS1 (1p21.1-q23.3) was excluded in our familial case, reinforcing the hypothesis of genetic heterogeneity for this condition. A review of the literature focusing diagnostic criteria and features of ACS was performed." | Microstomia |
Despite a mistake during the preparation of technetium-99m (Tc)-nanocolloid rhenium sulphide (Nanocis) because of lack of heating, the apparent radiochemical purity (RCP) of this product was correct. The objectives of this study were to evaluate the impact of absence of heating on the RCP of Tc-nanocolloid rhenium sulphide and the effect of heating on particle size. Five Tc-Nanocis were prepared according to the manufacturer's instructions and five others were realized without any heating step. Quality controls were performed for each preparation. To evaluate the effect of heating on particle size, preparations were filtered through a 0.22 microm sterilizing membrane filter before and after 30 min of heating. The radioactivity was measured before and after the filtration. The results showed that absence of heating does not influence the apparent RCP of Tc-nanocolloid of rhenium sulphide. In terms of the particle size, 72% of particles had a diameter less than 0.22 microm before heating, as opposed to 21% after heating. To conclude, this study underlines a problem of quality control of the Tc-nanocolloid rhenium sulphide preparation, which cannot detect a lack of heating and can lead to the release of preparations that would not be suitable for scintigraphy. | Rhenium |
Aromatase inhibitors (AIs) are used for treatment of estrogen receptor alpha (ER)-positive breast cancer; however, resistance is a major obstacle for optimal outcome. This preclinical study aimed at identifying potential new treatment targets in AI-resistant breast cancer cells. Parental MCF-7 breast cancer cells and four newly established cell lines, resistant to the AIs exemestane or letrozole, were used for a functional kinase inhibitor screen. A library comprising 195 different compounds was tested for preferential growth inhibition of AI-resistant cell lines. Selected targets were validated by analysis of cell growth, cell cycle phase distribution, protein expression, and subcellular localization. We identified 24 compounds, including several inhibitors of Aurora kinases e.g., JNJ-7706621 and barasertib. Protein expression of Aurora kinase A and B was found upregulated in AI-resistant cells compared with MCF-7, and knockdown studies showed that Aurora kinase A was essential for AI-resistant cell growth. In AI-resistant cell lines, the clinically relevant Aurora kinase inhibitors alisertib and danusertib blocked cell cycle progression at the G2/M phase, interfered with chromosome alignment and spindle pole formation, and resulted in preferential growth inhibition compared with parental MCF-7 cells. Even further growth inhibition was obtained when combining the Aurora kinase inhibitors with the antiestrogen fulvestrant. Our study is the first to demonstrate that Aurora kinase A and B may be treatment targets in AI-resistant cells, and our data suggest that therapy targeting both ER and Aurora kinases may be a potent treatment strategy for overcoming AI resistance in breast cancer. | Aurora Kinase B |
The aim of this study was to investigate the protective effect of vitamin C towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay. None of the vitamin C concentrations tested (1-10 microM) in presence or absence of formamidopyrimidine-DNA glycosylase (Fpg enzyme) caused DNA damage per se. HepG2 cells simultaneously treated with vitamin C and N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosodibutylamine (NDBA) or N-nitrosopiperidine (NPIP) reduced the genotoxic effects of the N-nitrosamines in a dose-dependent manner. At concentrations of 1-5 microM vitamin C, the protective effect was higher towards NPYR-induced oxidative DNA damage (78-79%) than against NDMA (39-55%), NDBA (12-14%) and NPIP (3-55%), in presence of Fpg enzyme. However, a concentration of 10 microM vitamin C led to a maximum reduction in NDBA (94%), NPYR (81%), NPIP (80%) and NDMA (61%)-induced oxidative DNA damage, in presence of Fpg enzyme. The greatest protective effect of vitamin C (10 microM) was higher towards NDBA-induced oxidative DNA damage. One feasible mechanism by which vitamin C exerted its protective effect is that may interact with the enzyme systems catalyzing the metabolic activation of the N-nitrosamines, blocking the production of genotoxic intermediates. Vitamin C (10 microM) strongly reduced the coumarin hydroxylase (82%) activity. However, the p-nitrophenol hydroxylase and the ethoxyresorufine O-deethylation activities were slightly and weakly reduced (32-19%), respectively. | N-Nitrosopyrrolidine |
This chapter discusses the use of ratiometric fluorescent probes for measuring intracellular pH (pHi) and Cai(2+) concentration at the single cell level. The development of sensitive and stable probes for monitoring pHi and Cai(2+) in living cells has provided the scientists with invaluable tools for studying a multitude of cellular processes. These probes afford a noninvasive and semiquantitative assessment of pHi and Cai(2+), eliminating the need to impale cells with microelectrodes. The development and availability of membrane permeant Cai(2+)- and pH-specific fluorescent probes coupled to major advances in the technology and design of low-light-level charge-coupled devices geared toward biological applications, and improved microscope optics, have made it possible to visualize a two-dimensional fluorescence signal that is related to Cai(2+) and pHi. The chapter describes the basis for using dual excitation ratio imaging and tries to provide a framework for understanding and developing the technique for investigating the roles of Cai(2+) and pHi in cellular processes. The technique of quantitative ratio imaging for the measurement of pHi and Cai(2+) has revolutionized the field of cell physiology. Using the proper equipment and choosing the right dyes for the experimental needs should provide reliable and reproducible results. More importantly, the amount of data produced from each experiment, when analyzing pHi and Cai(2+) on an individual cell basis, yields valuable information on the heterogeneity of cellular responses. | Fura-2 |
A total of 101 local rice varieties, composted of 85 glutinous and 16 non-glutinous varieties grown in wet season 2016, were analyzed for tocopherols (TOC), tocotrienols (T3) and gamma-oryzanol (Orz). Two popular varieties, RD6 and KDML105, were used as standard checks for glutinous and non-glutinous varieties, respectively. gamma-TOC was found in all glutinous varieties (0.47-9.78 mg/kg), which were higher than RD6 (0.16 mg/kg). alpha-TOC was found in 40 varieties (1.02-6.29 mg/kg), only 6 varities were higher than RD6 (3.95 mg/kg). delta-T3 was found in 81 varieties (0.57-7.00 mg/kg), mostly varities were higher than RD6 (0.67 mg/kg). gamma-T3 was found in all glutinous varieties (8.00-22.1 mg/kg), while RD6 contained 13.3 mg/kg. For alpha-T3, it was found in 39 glutinous varieties (1.52-9.94 mg/kg), mostly varities were higher than RD6 (2.62 mg/kg). Orz was found in all glutinous rice varieties (276-638 mg/kg), while RD6 contained 423 mg/kg. gamma-TOC was found in all non-glutinous varieties (0.67-5.21 mg/kg), which were higher than KDML105. alpha-TOC was found in only 5 varieties (1.92-2.83 mg/kg), while KDML105 contained 2.23 mg/kg. delta-T3 was found in all non-glutinous varieties (1.64-8.87 mg/kg), which were higher than KDML105 (0.71 mg/kg). gamma-T3 was also found in all non-glutinous varieties (8.80-17.58 mg/kg), while KDML105 contained 15.8 mg/kg. alpha-T3 was found in 9 non-glutinous varieties (4.56-8.93 mg/kg),while KDML105 contained only 0.86 mg/kg. Orz was also found in all those non-glutinous varieties (272-469 mg/kg), while KDML105 contained 469 mg/kg. These results indicate that gamma-T3 was the highest vitamin E isomer present in all rice samples, while gamma-TOC, alpha-TOC, delta-T3 and alpha-T3 were present in trace amounts. Orz was found in all local rice varieties. | Tocopherols |
Janus kinase 1 (JAK 1) plays a critical role in initiating responses to cytokines by the JAK-signal transducer and activator of transcription (JAK-STAT). This controls survival, proliferation and differentiation of a variety of cells. Docking, 3D quantitative structure activity relationship (3D-QSAR) and molecular dynamics (MD) studies were performed on a series of Imidazo-pyrrolopyridine derivatives reported as JAK 1 inhibitors. QSAR model was generated using 30 molecules in the training set; developed model showed good statistical reliability, which is evident from r(2)(ncv) and r(2)(loo) values. The predictive ability of this model was determined using a test set of 13 molecules that gave acceptable predictive correlation (r(2)(Pred)) values. Finally, molecular dynamics simulation was performed to validate docking results and MM/GBSA calculations. This facilitated us to compare binding free energies of cocrystal ligand and newly designed molecule R1. The good concordance between the docking results and CoMFA/CoMSIA contour maps afforded obliging clues for the rational modification of molecules to design more potent JAK 1 inhibitors. | Janus Kinase 1 |
Atmospheric and climate change will expose tropical forests to conditions they have not experienced in millions of years. To better understand the consequences of this change, we studied photosynthetic acclimation of the neotropical tree species Tabebuia rosea to combined 4 degrees C warming and twice-ambient (800 ppm) CO(2) . We measured temperature responses of the maximum rates of ribulose 1,5-bisphosphate carboxylation (V(CMax) ), photosynthetic electron transport (J(Max) ), net photosynthesis (P(Net) ), and stomatal conductance (g(s) ), and fitted the data using a probabilistic Bayesian approach. To evaluate short-term acclimation plants were then switched between treatment and control conditions and re-measured after 1-2 weeks. Consistent with acclimation, the optimum temperatures (T(Opt) ) for V(CMax) , J(Max) and P(Net) were 1-5 degrees C higher in treatment than in control plants, while photosynthetic capacity (V(CMax) , J(Max) , and P(Net) at T(Opt) ) was 8-25% lower. Likewise, moving control plants to treatment conditions moderately increased temperature optima and decreased photosynthetic capacity. Stomatal density and sensitivity to leaf-to-air vapour pressure deficit were not affected by growth conditions, and treatment plants did not exhibit stronger stomatal limitations. Collectively, these results illustrate the strong photosynthetic plasticity of this tropical tree species as even fully developed leaves of saplings transferred to extreme conditions partially acclimated. | Tabebuia |
Agricultural pesticides are extensively used for weed- and pest control, resulting in residues of these compounds in food. The general population is mainly exposed through dietary intake. Exposure to certain pesticides has been associated with adverse human health outcomes. Our aim was to assess urinary concentrations and temporal trends in the biomarkers of commonly used pesticides. Samples were collected from adolescents (n = 1060) in Scania, Sweden, from 2000 to 2017. Concentrations of 14 pesticide biomarkers were analyzed in urine using LC-MS/MS. Temporal trends in biomarker concentrations (ln-transformed) were evaluated using linear regression. Biomarkers of pyrethroids (3-PBA and DCCA), chlorpyrifos (TCPy), chlormequat (CCC), thiabendazole (OH-TBZ), and mancozeb (ETU) were detected in >90% of the population all sampling years. The biomarkers CCC and TCPy had the highest median concentrations (>0.8 microg/L), whereas the biomarkers of cyfluthrin (4F-3-PBA) and two pyrethroids (CFCA) had the lowest median concentrations (<0.02 microg/L). Increasing temporal trends were found for the biomarkers 3-PBA (3.7%/year), TCPy (1.7%/year) and biomarkers of pyrimethanil (11.9%/year) and tebuconazole (12.2%/year). Decreasing trends were found for CCC (-5.5%/year), OH-TBZ (-5.5%/year), and ETU (-3.9%/year). Our results suggest that Swedish adolescents are commonly exposed to pesticides in low concentrations (median concentrations <3.88 microg/L). | Ethylenebis(dithiocarbamates) |
Since 1985, our knowledge of the biology of acute leukemias has been greatly enhanced by new investigative tools and techniques. This new information in turn has produced improved diagnostic criteria, new classifications, and tailored therapeutic approaches for the acute leukemias. The intent of the following article is to present the clinical and laboratory features that facilitate a diagnosis of AML and provide insight into the biologic basis and treatment of these disorders. | Leukemia, Myeloid, Acute |
In selected circumstances, especially those associated with pain and mechanical instability, early surgical therapy is indicated for patients with rheumatoid arthritis. Close consultation between the rheumatologist and surgeon enables identification of focused goals attainable by synovectomy, ligament or tendon reconstruction, joint replacement, or arthrodesis. If these goals are met, the result can be a gratifying return of function and independence. This article describes some of the more common deformities of the hand, wrist, and elbow in patients with rheumatoid arthritis. Current surgical therapy, along with outcome and complications, is also discussed. Emphasis is placed on decisions and indications for surgical evaluation. | Synovectomy |
OBJECTIVE: Although peer difficulties and sluggish cognitive tempo (SCT) are related, studies have yet to examine environmental factors that may advance further understanding of this association. The current study tested whether peer difficulties, specifically social competence and peer victimization, interacted with school support, a component of school climate, in relation to adolescents' SCT symptoms. Further, we explored whether these relations would be differentially associated with SCT in adolescents with and without attention-deficit/hyperactivity disorder (ADHD). METHOD: Adolescents (N = 288; M(age) = 14.08, 45% female, 82.6% White; 52% with ADHD) completed measures of social competence, peer victimization, school climate support, and SCT and ADHD inattentive (IN) symptoms. Parents also reported on adolescents' social competence, SCT, and ADHD-IN symptoms. RESULTS: Results indicated that adolescent and parent ratings of lower social competence were both associated with higher adolescent-reported SCT symptoms in the context of low, but not high, school support. Relational and nonphysical victimization were associated with higher self-reported SCT symptoms in the context of low school support. Lower adolescent- and parent-reported social competence were also related to higher parent-reported SCT symptoms, with these associations not moderated by school support. These results remained after controlling for demographics and ADHD-IN symptoms and were similar across adolescents with and without ADHD. CONCLUSIONS: Findings from the current study are the first to provide evidence that peer difficulties and school climate are jointly related to adolescents' self-reported SCT and underscore the importance of continued research investigating social adversity and environmental factors in relation to SCT. | Sluggish Cognitive Tempo |
Cytotoxicity of arabinofuranosylcytosine (ara-C) has been related in vitro to the inhibition of the DNA polymerase activities by arabinosylcytosine triphosphate (ara-CTP) and the incorporation of ara-C into the DNA where, acting as a chain terminator, it slows the chain elongation. Induced in vitro cellular resistance to ara-C was shown to be secondary to altered deoxycytidine (dCyd) kinase activity, dCyd deaminase activity, or deoxynucleotides triphosphates (dNTP) pools. Recent studies reported no differences of ara-C metabolism in cells obtained from leukemic patients at diagnosis and at relapse after ara-C therapy, suggesting that unknown cellular biochemical determinants may be involved in acquisition of ara-C resistance. Using dialysed crude extracts of leukemic cells obtained from patients at diagnosis, we observed variable inhibition of their DNA polymerase activities by arabinosylcytosine monophosphate (ara-CMP) at 2 mmol/L (0% to 50% inhibition). In similar conditions, ara-CMP reduced the polymerase activities of human thymus extract by 35% and 55% in extract of HL-60 cells (cultured human promyelocytic cells). The ara-CMP factor responsible for inhibition of DNA polymerase activity was nondialysable, heat labile, proteinase K sensitive, and has an estimated molecular mass of 30 kilodalton by gel filtration. After partial purification, this protein had no DNA polymerase RNA polymerase activities. In presence of the regulator and ara-CMP at 2 mmol/L, we observed no inhibition of the HL-60 3'----5' and 5'----3' exonucleases activities, suggesting the regulator interaction being mainly with the DNA polymerases in presence of ara-CMP. The relevance of the presence or absence of this protein regarding the cell sensitivity to ara-C is under investigation. | Cytidine Monophosphate |
This presents four new cases of pertussoid eosinophilic pneumonia in young infants. The 19 previously reported cases have been young infants with bilateral intersitial infiltrates and eosinophilia. The cause of this syndrome is unknown. Cultures from the four patients were negative; however, studies of immunoglobulin levels suggest that the disease has an infectious etiology. The cause of the eosinophilia is also unknown; however, it appears to be associated with a favorable prognosis in young infants with severe bilateral pneumonitis. | Pulmonary Eosinophilia |
Semliki Forest virus (SFV) is an enveloped alphavirus that is transmitted in the wild by mosquito vectors. In tissue culture cells, SFV requires cholesterol in the cell membrane both for virus membrane fusion and for the efficient exit of progeny virus from the cell. A previously isolated SFV mutant, srf-3, is strikingly less cholesterol-dependent for virus fusion, exit, and growth due to a single amino acid change in the E1 spike protein subunit, proline 226 to serine. Here we show that when mosquitoes were infected by intrathoracic injection at a range of virus multiplicities, the growth of srf-3 was significantly more rapid than that of wild-type virus, particularly at low multiplicity infection. The differential cholesterol requirements for wild-type and srf-3 infection were maintained during virus passage through mosquitoes. The presence or absence of cholesterol in the srf-3 virus membrane did not affect its infection properties in mosquitoes. Thus the srf-3 mutation causes a growth advantage in the tissues of the mosquito host. | Semliki forest virus |
Severe progressive fatal neurological degeneration occurs in fucosidosis, a storage disease. Bone marrow transplantation into affected dogs has shown that haematopoietic stem cells can provide enzyme producing daughter cells to the central nervous system, altering disease course. This makes canine fucosidosis an ideal large animal model for gene therapy. Fucosidosis affected allogeneic or autologous canine marrow was transduced ex vivo by cocultivation, then transplanted into fucosidosis affected dogs conditioned with total lymphoid irradiation. The vectors were Moloney murine leukaemia virus based. Transduction efficiency was increased with multiple cytokines in short term marrow culture. Despite high levels of transduction, proviral sequence was detected 2 months post transplant in only one dog. Early or total graft failure occurred in all transplants. We believe lack of engraftment could be caused by differentiation or change of repopulating ability of marrow cells occurring with multiple cytokine mixes in culture media. | Fucosidosis |
Chronic infection with a vaccine strain of mumps virus (MV) was produced and studied in human cell cultures L-41 and HEp-2. The establishment and course of the infection was not accompanied by cytopathic changes. Among probable protective factors (mechanisms) interferon (IFN) was detected in L-41 culture and defective interfering particles in either cell culture. Their role in the establishment and maintenance of chronic infection was not confirmed, however. | Rubulavirus |
We present the case of a patient with an intracerebral hemorrhage as complication of an infectious endocarditis (EI) produced by Neisseria sicca on a prosthetic mitral valve. The patient was anticoagulated previously with Acenocumarol as prophylaxis of thrombosis of the prosthetic valve. He was diagnosed as having IE and later he presented neurological symptoms as consequence of several intracerebral hemorrhagic foci. We decided to continue the anticoagulation with sodium heparin followed of Bemiparina and no new hemorrhagic complications nor thrombosis of the valve were observed after three months of the event. We have not found in the literature any case where low molecular weight heparin has been used as method of anticoagulation in these cases beyond two weeks. | Neisseria sicca |
Yeast species provide excellent models for fundamental biological research. In this review, I will describe characteristics of the two most common laboratory systems: the fission yeast Schizosaccharomyces pombe, and the budding yeast Saccharomyces cerevisiae. They have substantial similarities that make them powerful as research tools, and also striking biological differences that make them complementary experimental models. Each provides unique tools for understanding environmental effects on cellular systems. | Schizosaccharomyces |
The core of the decision to commit to either oogenesis or spermatogenesis lies in the timing of meiotic entry. Primordial germ cells within the fetal ovary become committed to the female pathway prior to birth and enter meiosis during embryonic development. In the fetal testis, however, the germ cells are protected from this signal before birth and instead receive this trigger postnatally. There is a growing body of evidence to indicate that RA is the meiosis-inducing factor in both sexes, with the gender-specific timing of meiotic entry controlled via degradation of this molecule only within the fetal testis. This chapter will review our current understanding of how RA controls germ cell fate in both the embryonic ovary and postnatal testis, highlighting the key studies that have led to the hypothesis that RA can drive the commitment to meiosis in both sexes and discussing the current debate over whether RA truly is the meiosis-inducing factor in the fetal ovary. | Gametogenesis |
We explore the temporal attention function in a non-clinical sample of adolescents varying in impulsivity, as assessed with the Barratt Impulsiveness Scale. In a Rapid Serial Visual Presentation task, in which two targets (T(1) and T(2)) were presented in close temporal proximity among distractors, participants tried to identify T(1) and detect T(2) in one (dual-task) experiment and only to detect T(2) in a second, control (single-task) experiment. The sensitivity of T(2) detection was analyzed using signal detection theory. The attentional blink -- the impairment in T(2) detection following the identification of T(1) -- was increased in magnitude and protracted in adolescents with high impulsivity, compared with those with low impulsivity. Moreover, a few more participants with high impulsivity appeared to have a blink temporally weighing toward a later time, an observation also made in children with attention deficit hyperactivity disorder (ADHD) in an earlier study. Taken together, these findings suggest impairment in temporal attention in adolescents with high impulsivity. As in ADHD children, a gating deficit may play a central role in this attention impairment. | Blinking |
The role of inflammation in the development of aortic aneurysms is emerging, along with the potential diagnostic and therapeutical potential of this correlation. Abdominal aorta aneurysms have a strong inflammatory substrate since atherosclerosis, which is undoubtedly linked to inflammation, is also a predisposing factor to their formation. Yet, data have emerged that the development of thoracic aorta aneurysms involves several inflammatory pathways, although they were previously referred to as a non-inflammatory disease. Since aortic aneurysms are mainly asymptomatic during their clinical course until their complications-which may be lethal-serum biomarkers for their early diagnosis are a necessity. Studies highlight that inflammation molecules may have a critical role in that direction. In addition, imaging techniques that trace aortic wall inflammation are developed in order to predict aneurysm growth rates and sites vulnerable of rupture. Several anti-inflammatory agents have been also studied in animal models and clinical trials for the treatment of aortic aneurysms. This review highlights the role of inflammation in pathogenesis, diagnosis and treatment of aortic aneurysms. | Aortic Aneurysm |
Streptomyces venezuelae ISP5230 was grown in the presence of phenylalanine analogues to observe whether they could be incorporated into novel jadomycin structures. It was found that the bacteria successfully produced jadomycins incorporating 4-aminophenylalanine enantiomers. Upon isolation and characterization of jadomycin 4-amino-l-phenylalanine (1), it was synthetically derivatized, using activated succinimidyl esters, to yield a small jadomycin amide library. These are the first examples of oxazolone-ring-containing jadomycins that have incorporated an amino functionality subsequently used for derivatization. | Oxazolone |
Plant-based repellents have been used for generations in traditional practice as a personal protection measure against host-seeking mosquitoes. Knowledge on traditional repellent plants obtained through ethnobotanical studies is a valuable resource for the development of new natural products. Recently, commercial repellent products containing plant-based ingredients have gained increasing popularity among consumers, as these are commonly perceived as safe" in comparison to long-established synthetic repellents although this is sometimes a misconception. To date insufficient studies have followed standard WHO Pesticide Evaluation Scheme guidelines for repellent testing. There is a need for further standardized studies in order to better evaluate repellent compounds and develop new products that offer high repellency as well as good consumer safety. This paper presents a summary of recent information on testing, efficacy and safety of plant-based repellents as well as promising new developments in the field." | Insect Repellents |
BACKGROUND: Acid reflux is a common problem, and is thought to occur in 4% to 10% of patients presenting to ENT clinics. A recent study of reflux and voice disorders suggests that up to 55% of patients with hoarseness (dysphonia) have laryngopharyngeal reflux. Anti-reflux therapy is often used empirically in treating patients with hoarseness, where no other cause has been identified by examination. OBJECTIVES: The aim of the review was to assess the effectiveness of anti-reflux therapy for patients with hoarseness, in the absence of other identifiable causes, whether or not a definitive diagnosis of laryngopharyngeal and gastro-oesophageal reflux has been made. This was assessed by evaluation of prospective randomised controlled studies that were identified by a systematic review of the literature. Both medical and surgical treatments were evaluated. SEARCH STRATEGY: The Cochrane ENT Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 3, 2005), MEDLINE (1966 to 2005), EMBASE (1974 to 2005) and conference proceedings were searched with prespecified terms. The date of the last search was September 2005. SELECTION CRITERIA: Randomised controlled trials recruiting patients with hoarseness in the absence of other identifiable causes, such as malignancy, cord palsy or nodules, whether or not a definitive diagnosis of laryngopharyngeal and gastro-oesophageal reflux has been made. DATA COLLECTION AND ANALYSIS: Three reviewers examined the search results and identified studies before deciding which would be included in the review. MAIN RESULTS: 302 potential studies were identified by the search strategy. No trials were identified which met our inclusion criteria. Six randomised controlled trials were identified in which some, but not all patients presented with hoarseness, and were treated with proton pump inhibition. As we could not determine with certainty whether all these patients had hoarseness among the other laryngeal symptoms, these were excluded. However, these studies suggest a significant placebo response, which is comparable to the benefit derived from anti-reflux therapy in some studies. As no trials met our criteria, we are unable to reach any firm conclusions regarding the effectiveness of anti-reflux treatment for hoarseness. AUTHORS' CONCLUSIONS: There is a need for high quality randomised controlled trials to evaluate the effectiveness of anti-reflux therapy for patients with hoarseness which may be due to laryngopharyngeal and gastro-oesophageal reflux. | Hoarseness |
OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. However, there is a gap in how often providers counsel patients about SUDEP. One potential solution is to electronically prompt clinicians to provide counseling via automated detection of risk factors in electronic medical records (EMRs). We evaluated (1) the feasibility and generalizability of using regular expressions to identify risk factors in EMRs and (2) barriers to generalizability. METHODS: Data included physician notes for 3000 patients from one medical center (home) and 1000 from five additional centers (away). Through chart review, we identified three SUDEP risk factors: (1) generalized tonic-clonic seizures, (2) refractory epilepsy, and (3) epilepsy surgery candidacy. Regular expressions of risk factors were manually created with home training data, and performance was evaluated with home test and away test data. Performance was evaluated by sensitivity, positive predictive value, and F-measure. Generalizability was defined as an absolute decrease in performance by <0.10 for away versus home test data. To evaluate underlying barriers to generalizability, we identified causes of errors seen more often in away data than home data. To demonstrate how small revisions can improve generalizability, we removed three "boilerplate" standard text phrases from away notes and repeated performance. RESULTS: We observed high performance in home test data (F-measure range = 0.86-0.90), and low to high performance in away test data (F-measure range = 0.53-0.81). After removing three boilerplate phrases, away performance improved (F-measure range = 0.79-0.89) and generalizability was achieved for nearly all measures. The only significant barrier to generalizability was use of boilerplate phrases, causing 104 of 171 errors (61%) in away data. SIGNIFICANCE: Regular expressions are a feasible and probably a generalizable method to identify variables related to SUDEP risk. Our methods may be implemented to create large patient cohorts for research and to generate electronic prompts for SUDEP counseling." | Sudden Unexpected Death in Epilepsy |
Bioluminescence resonance energy transfer (BRET) has gained impetus to monitor protein interactions in proximity. BRET involves the energy transfer from a bioluminescent donor (luciferases) to a fluorescent acceptor. Since bioluminescence is an intrinsic phenomenon, BRET excludes the need for external illumination and serves as a powerful alternative to fluorescence-based systems. However, BRET has not been widely adopted for single-cell imaging applications, mainly due to the low signal output resulting in poor signal-to-noise ratio. In this chapter, we describe a protocol to optimize spatiotemporal BRET imaging by adopting fluorescent HaloTag acceptors, adapting cell culture conditions and microscopic setup. | Energy Transfer |
Cancer has been viewed as one of the deadliest diseases worldwide. Among various types of cancer, breast cancer is the most common type of cancer in women. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a promising druggable target and is overexpressed in cancerous cells, like, breast cancer. We conducted structure-based modeling on the allosteric site of the enzyme. Targeting the allosteric site avoids the problem of drug resistance. Pharmacophore modeling, molecular docking, HYDE assessment, drug-likeness, ADMET predictions, simulations, and free-energy calculations were performed. The RMSD, RMSF, RoG, SASA, and Hydrogen-bonding studies showed that seven candidates displayed stable behaviour. As per the literature, average superimposed simulated structures revealed a similar protein conformational change in the alphaE'-betaf' loop, causing its displacement away from the allosteric site. The MM-PBSA showed tight binding of six compounds with the allosteric pocket. The effect of inhibitors interacting in the allosteric site causes a decrease in the binding energy of J49 (active-site inhibitor), suggesting the effect of allosteric binding. The PCA and FEL analysis revealed the significance of the docked compounds in the stable behaviour of the complexes. The outcome can contribute to the development of potential natural products with drug-like properties that can inhibit the MTHFD2 enzyme." | Methylenetetrahydrofolate Dehydrogenase (NADP) |
The definition of unnecessary surgery" has never been made very precise. A useful definition might be provided by the economist's notion of patient costs and benefits as they would be calculated by a fully informed patient-consumer. Combining both clinical information and consumer preferences, it is impossible to demonstrate unnecessary surgery for most diagnoses. Conclusions in recent Congressional reports on unnecessary surgery are not supported by evidence likely to benefit either individual physicians or patients." | Insurance, Surgical |
OBJECTIVE: To assess image quality and radiation dose associated with ultra-low dose CT protocol for patients with benign paranasal sinus diseases undergoing functional endoscopic surgery (FESS). METHODS: We scanned the head portion of Alderson RANDO phantom on a second generation, dual-source, multidetector-row CT scanner (Siemens Definition Flash) using standard-dose and five low-dose protocols. Two radiologists assessed the image quality for each protocol to determine best ultra-low-dose protocols for imaging patients with benign paranasal sinus diseases undergoing FESS. The ultra-low-dose CT protocols were then used for scanning. Thereafter, 40 adult patients (age range 18-54 years, M:F 23:17) were scanned with the four low dose scanning protocols (10 patients per protocol). On both transverse and coronal reformatted CT images, two radiologists assessed visibility of key anatomic landmarks for FESS on a 2-point scale (1 = clear and complete visualization; 2 = suboptimal visualization). Data were analyzed with descriptive statistics and Cohen's kappa coefficient for interobserver agreement. RESULTS: In phantom study, the lowest dose scan protocol (CTDI(vol) 2.1 mGy, 70 kV, 75 mAs) was unacceptable due to poor image quality. For patient studies, both radiologists gave acceptable image quality scores for ultra-low-dose scan protocol with axial scan mode, automatic tube potential selection and tube current modulation (CTDI(vol) 2.2 mGy; DLP 22.9 mGy.cm) with up to 60% lower dose compared to prior standard-dose CT (CTDI(vol) 5.3 mGy; DLP 73.5 mGy.cm). CONCLUSIONS: Ultra-low-dose CT protocol provides sufficient image quality for scanning patients undergoing functional endoscopic surgery for benign paranasal sinus diseases. | Paranasal Sinuses |
The aim of this study was to evaluate the relationship between the protamine ratio (P1/P2), DNA fragmentation of spermatozoa and protamine deficiency. Patients were grouped into fertile (G1; n = 151) and sub-fertile (G2; n = 121). DNA fragmentation in spermatozoa was analysed by a TUNEL assay (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling), and the protamination was determined by CMA3 staining, while Western blot was used to measure protamine P1 and P2. While sperm DNA fragmentation (SDF) and protamine ratio were significantly elevated in G2 compared with G1 (12.31 +/- 7.01% vs. 17.5 +/- 9.5%; p = .001) and (0.91 +/- 0.43 vs. 0.75 +/- 0.42; p = .003); respectively, the CMA3 positive showed no difference at all between G1 and G2. In G1, the CMA3 positive correlated negatively with the P1/P2 ratio and SDF (r = -.586, r = -.297; p = .001 respectively). In contrast, the protamine ratio correlated positively with SDF (r = .356; p = .001). In G2, no correlation was observed between CMA3 positive, SDF and the P1/P2 ratio but the P1/P2 ratio showed a positive correlation with SDF (r = .479; p = .001). In conclusion, the spermatozoa DNA deterioration was closely associated with abnormal protamination but showed an association with the protamine ratio, more than with CMA3 positive. Therefore, for the evaluation of DNA damage in spermatozoa, the P1/P2 ratio might act as an additional biomarker. | Protamines |
Within a survey of coma scales we distinguish scales of clinical findings (Glasgow Coma Scale [GCS], Glasgow Liege Scale [GLS], Innsbruck Coma Scale [ICS], Comprehensive Level of Consciousness Scale [CLOCS]), grading tests (Vigilance Scale [VS], Funktionspsychose-Skala-B [FPBS-B]) and level-scales (Reaction-Level-Scale [RLS-85], Munich Coma Scale [MCS]). With regard to the purpose we differentiate a classification of depth, the prediction of prognosis and the monitoring of changes. For the purpose of classification of depth, the RLS-85 because of its superior objectivity is preferable, but the GCS is of comparable validity and more widely used. The GLS differentiates the deeper states of coma better than either of these because brainstem-reflexes in cranio-caudal order are added. Within the prediction of prognosis all coma-scales have only limited validity and for the purpose of resource economy require additional criteria in the individual case. For the purpose of monitoring changes the level-scales primarily do not fit, the GCS is not sensitive enough. The Glasgow-Cologne-List is better suited; it is more than one-dimensional, but can be expressed through the GCS numbers for comparative purposes. The ICS is not widely used and the prognostic validity has not been proven to the same extent. The Glasgow-Cologne-List could be amplified for the less severe disturbances of consciousness according to Price (32,33), and for the lower levels according to the GLS (2,3,4). In both cases the expense is slightly higher.(ABSTRACT TRUNCATED AT 250 WORDS) | Consciousness Disorders |
Many neuronal circuits driving coordinated locomotion are composed of chains of half-center oscillators (HCOs) of various lengths. The HCO is a common motif in central pattern generating circuits (CPGs); an HCO consists of two neurons, or two neuronal populations, connected by reciprocal inhibition. To maintain appropriate motor coordination for effective locomotion over a broad range of frequencies, chains of CPGs must produce approximately constant phase-differences in a robust manner. In this article, we study phase-locking in chains of nearest-neighbor coupled HCOs and examine how the circuit architecture can promote phase-constancy, i.e., inter-HCO phase-differences that are frequency-invariant. We use two models with different levels of abstraction: (1) a conductance-based model in which each neuron is modeled by the Morris-Lecar equations (the ML-HCO model); and (2) a coupled phase model in which the state of each HCO is captured by its phase (the phase-HCO model). We show that one of four phase-waves with inter-HCO phase-differences at approximately 0, 25, 50 or 75 % arises robustly as a result of the inter-HCO connection topology, and its robust existence is not affected by the number of HCOs in the chain, the difference in strength between the ascending and descending nearest-neighbor connections, or the number of nearest-neighbor connections. Our results show that the internal anti-phase structure of the HCO and an appropriate inter-HCO connection topology together can provide a mechanism for robust (i.e., frequency-independent) limb coordination in segmented animals, such as the 50 % interlimb phase-differences in the tripod gate of stick insects and cockroaches, and the 25 % interlimb phase-differences in crayfish and other long-tailed crustaceans during forward swimming. | Locomotion |
BACKGROUND: Borderline Personality Disorder (BPD) is a complex and debilitating disorder, characterized by deficits in metacognition and emotion dysregulation. The gold standard" treatment for this disorder is psychotherapy with pharmacotherapy as an adjunctive treatment to target state symptoms. The present randomized clinical trial aims to assess the clinical and neurobiological changes following Metacognitive Interpersonal Therapy (MIT) compared with Structured Clinical Management (SCM) derived from specific recommendations in APA (American Psychiatric Association) guidelines for BPD. METHODS: The study design is a randomized parallel controlled clinical trial and will include 80 BPD outpatients, aged 18-45 enrolled at 2 recruitment centers. Primary outcome will be the clinical change in emotion regulation capacities assessed with the Difficulties in Emotion Regulation Scale (DERS). We will also investigated the effect of psychotherapy on metacognitive abilities and several clinical features such as BPD symptomatology, general psychopathology, depression, personal functioning, and trait dimensions (anger, impulsivity, alexithymia). We will evaluate changes in brain connectivity patterns and during the view of emotional pictures. A multidimensional assessment will be performed at the baseline, at 6, 12, 18 months. We will obtain structural and functional Magnetic Resonance Images (MRIs) in MIT-Treated BPD (N = 30) and SCM-treated BPD (N = 30) at baseline and after treatment, as well as in a group of 30 healthy and unrelated volunteers that will be scanned once for comparison. DISCUSSION: The present study could contribute to elucidate the neurobiological mechanisms underlying psychotherapy efficacy. The inclusion of a multidisciplinary study protocol will allow to study BPD considering different features that can affect the treatment response and their reciprocal relationships. TRIAL REGISTRATION: NCT02370316 . Registered 02/24/2015." | Interpersonal Psychotherapy |
Transactive response DNA-binding protein of 43 kDa (TDP-43), an RNA and DNA binding protein involved in transcriptional repression, RNA splicing and RNA metabolism during the stress response, is the major component of neuronal inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions, now referred to as FTLD-TDP. While initially thought to be relatively specific to ALS and FTLD-TDP, TDP-43 pathology has now been detected in a number of other neurodegenerative diseases, many associated with tau pathology, including Guam Parkinson dementia complex and Alzheimer's disease (AD). TDP-43 pathology is detected in 25% to 50% of AD cases, especially those with more severe clinical phenotype and greater Alzheimer type pathology, as well as AD cases with hippocampal sclerosis (HS). HS is characterized by selective neuronal loss affecting CA1 sector of the hippocampus, and most cases of HS, with or without AD, have TDP-43 pathology. Whether TDP-43 pathology is merely an incidental finding in AD or actually contributing to the more severe clinical phenotype remains unresolved. Presence of TDP-43 in normal elderly, who are at increased risk for AD, would strengthen the argument that it is not merely a secondary or incidental finding in end stage AD. Limited studies suggest that TDP-43 pathology is infrequent in neurologically normal elderly (3% or less). We provide an overview of what is known about TDP-43 in AD, normal aging and in other disorders and suggest that TDP-43 proteinopathies be considered in two classes - primary and secondary. | TDP-43 Proteinopathies |
Monitoring the effectiveness of tsetse fly control interventions that aim to reduce transmission of African trypanosomiasis requires highly efficient sampling tools that can catch flies at low densities. The sticky small target (StS-target) has previously been shown to be more effective in sampling Glossina fuscipes fuscipes compared to the biconical trap. However, its efficiency in terms of the proportion of flies it catches out of those that visit it has not been reported. Furthermore, there are no reports on whether tsetse samples caught using the StS-target can be used for subsequent processes such as molecular tests. In this study, we evaluated the efficiency of the biconical trap and targets for sampling G. f. fuscipes. All targets were tiny (0.25 x 0.50 m) but varied in their capture system. We used targets with sticky surface (StS-targets) and those with an electrified surface (ES-targets). We also assessed the suitability of flies caught on the StS-target for molecular tests by amplifying DNA of bacterial communities. Randomized block design experiments were undertaken in Mbita area and Manga Island on Lake Victoria of western Kenya. Fly catches of each sampling tool were compared to those of the sampling tool flanked by electric (E) nets and analyzed using a negative binomial regression. The total catch for each sampling tool alone was divided by the total catch of the sampling tool flanked by two E-nets to obtain its efficiency expressed as a percentage. A proportion of flies caught on the StS-target was preserved for molecular tests. Overall, the efficiencies of the biconical trap, ES-target and StS-target were 7.7%, 13.3% and 27.0%, respectively. A higher proportion of females (69 to 79%) than males approached all the sampling tools, but the trap efficiency was greater for male G. f. fuscipes than females. Furthermore, sequencing the 16S rRNA gene from fly samples caught on the StS-target revealed the presence of Spiroplasma. Our results indicate that the SS-target is the most efficient trap to monitor G. f. fuscipes population during interventions, with the biconical trap being the least efficient, and samples collected from StS-targets are suitable for molecular studies. | Glossinidae |
Infrared neuromodulation (INM) is a branch of photobiomodulation that offers direct or indirect control of cellular activity through elevation of temperature in a spatially confined region of the target tissue. Research on INM started about 15 ago and is gradually attracting the attention of the neuroscience community, as numerous experimental studies have provided firm evidence on the safe and reproducible excitation and inhibition of neuronal firing in both in vitro and in vivo conditions. However, its biophysical mechanism is not fully understood and several engineered interfaces have been created to investigate infrared stimulation in both the peripheral and central nervous system. In this review, recent applications and present knowledge on the effects of INM on cellular activity are summarized, and an overview of the technical approaches to deliver infrared light to cells and to interrogate the optically evoked response is provided. The micro- and nanoengineered interfaces used to investigate the influence of INM are described in detail. | Infrared Rays |
In the present study the therapeutic efficacy and the side effects of two antiretroviral compounds used in human acquired immunodeficiency syndrome (AIDS) research, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine, Retrovir) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), were investigated in the treatment of cats naturally infected with feline immunodeficiency virus (FIV) and cats naturally infected with feline leukemia virus (FeLV). AZT was administered subcutaneously at a dose of 5 mg kg-1 body weight every 12 h and PMEA was administered subcutaneously at a dose of 2.5 mg kg-1 body weight every 12 h during a 3 week hospitalization. The therapeutic efficacy of both compounds was investigated. There was a stronger potency of PMEA than of AZT on the regression of stomatitis in FIV and in FeLV infected cats. In addition, in FIV infection PMEA had a stronger effect on the improvement of the general clinical status. Both antiretroviral compounds were potent agents to improve the immunologic status of FIV infected cats by raising the CD4/CD8 ratio. In FeLV infection PMEA and AZT appeared to reduce antigenemia. The hematological side effects caused by PMEA were severe and stronger than those of AZT. Therefore the advantage of PMEA in clinical and immunologic improvement was diminished by the hematologic disorders, which do not allow long term treatment with this drug in the dose used. | Leukemia, Feline |
A new simplified procedure for the purification of chorismate mutase/prephenate dehydratase, based on affinity chromatography on Sepharosyl-phenylalanine, has been developed. The method utilizes the effect of NaCl on the binding properties of the enzyme. NaCl inhibits both the mutase and dehydratase activities of the enzyme. In each case this inhibition is cooperative indicating homotropic interactions between NaCl binding sites on the enzyme. In addition NaCl induces homotropic cooperative effects between chorismate binding sites and between prephenate binding sites. NaCl also increases the sensitivity of the enzyme to inhibition by phenylalanine. | Prephenate Dehydratase |
Dust deposition in the lung tissue of 10 cases with pathologically diagnosed stage I CWP was determined. The left lung tissue was digested by 37% hydrochloric acid, and its organic composition was removed by chloroform and 50% ethanol. Results showed total dust content averaged 8.64 grams per left lung, with a standard deviation of 5.54 grams. Dust content varied in different parts of the lung, measured the highest in lymph nodes, the upper lobe and pleura the next and the lowest in the lower lobe, with a very significant difference by ANOVA (F = 44.76, P < 0.001). Dust less than 5 microns in diameter accounted for 94.0% of the total content, and that equal to or more than 10 microns only 0.8%. A certain amount of fibrous dust could be found in the lung. Dust deposited in the lung accounted only for 0.64% of that exposed to. | Anthracosilicosis |
The evolution of interactions in the bovine serum albumin (BSA) protein solution on addition of mono and multivalent (di, tri and tetra) counterions has been studied using small-angle neutron scattering (SANS), dynamic light scattering (DLS) and zeta-potential measurements. It is found that in the presence of mono and divalent counterions, protein behavior can be well explained by DLVO theory, combining the contributions of screened Coulomb repulsion with the van der Waals attraction. The addition of mono or divalent salts in protein solution reduces the repulsive barrier and hence the overall interaction becomes attractive, but the system remains in one-phase for the entire concentration range of the salts, added in the system. However, contrary to DLVO theory, the protein solution undergoes a reentrant phase transition from one-phase to a two-phase system and then back to the one-phase system in the presence of tri and tetravalent counterions. The results show that tri and tetravalent (unlike mono and divalent) counterions induce short-range attraction between the protein molecules, leading to the transformation from one-phase to two-phase system. The two-phase is characterized by the fractal structure of protein aggregates. The excess condensation of these higher-valent counterions in the double layer around the BSA causes the reversal of charge of the protein molecules resulting into reentrant of the one-phase, at higher salt concentrations. The complete phase behavior with mono and multivalent ions has been explained in terms of the interplay of electrostatic repulsion and ion-induced short-range attraction between the protein molecules. | Aluminum Chloride |
METTL3 (methyltransferase-like 3) mediates the N(6)-methyladenosine (m(6)A) methylation of mRNA, which affects the stability of mRNA and its translation into protein(1). METTL3 also binds chromatin(2-4), but the role of METTL3 and m(6)A methylation in chromatin is not fully understood. Here we show that METTL3 regulates mouse embryonic stem-cell heterochromatin, the integrity of which is critical for silencing retroviral elements and for mammalian development(5). METTL3 predominantly localizes to the intracisternal A particle (IAP)-type family of endogenous retroviruses. Knockout of Mettl3 impairs the deposition of multiple heterochromatin marks onto METTL3-targeted IAPs, and upregulates IAP transcription, suggesting that METTL3 is important for the integrity of IAP heterochromatin. We provide further evidence that RNA transcripts derived from METTL3-bound IAPs are associated with chromatin and are m(6)A-methylated. These m(6)A-marked transcripts are bound by the m(6)A reader YTHDC1, which interacts with METTL3 and in turn promotes the association of METTL3 with chromatin. METTL3 also interacts physically with the histone 3 lysine 9 (H3K9) tri-methyltransferase SETDB1 and its cofactor TRIM28, and is important for their localization to IAPs. Our findings demonstrate that METTL3-catalysed m(6)A modification of RNA is important for the integrity of IAP heterochromatin in mouse embryonic stem cells, revealing a mechanism of heterochromatin regulation in mammals." | Genes, Intracisternal A-Particle |
Dentin bonding relies on complete resin impregnation throughout the demineralised hydrophilic collagen mesh. Chondroitin sulphate-glycosaminoglycans are claimed to regulate the three-dimensional arrangement of the dentin organic matrix and its hydrophilicity. The aim of this study was to investigate bond strength of two etch-and-rinse adhesives to chondroitinase ABC treated dentin. Human extracted molars were treated with chondroitinase ABC and a double labeling immunohistochemical technique was applied to reveal type I collagen and chondroitin 4/6 sulphate distribution under field emission in-lens scanning electron microscope. The immunohistochemical technique confirmed the effective removal of chondroitin 4/6 sulphate after the enzymatic treatment. Dentin surfaces exposed to chondroitinase ABC and untreated specimens prepared on untreated acid-etched dentin were bonded with Adper Scotchbond Multi-Purpose or Prime and Bond NT. Bonded specimens were submitted to microtensile testing and nanoleakage interfacial analysis under transmission electron microscope. Increased mean values of microtensile bond strength and reduced nanoleakage expression were found for both adhesives after chondroitinase ABC treatment of the dentin surface. Adper Scotchbond Multi-Purpose increased its bond strength about 28%, while bonding made with Prime and Bond NT almost doubled (92% increase) compared to untreated specimens. This study supports the hypothesis that adhesion can be enhanced by removal of chondroitin 4/6 sulphate and dermatan sulphate, probably due to a reduced amount of water content and enlarged interfibrillar spaces. Further studies should validate this hypothesis investigating the stability of chondroitin 4/6 and dermatan sulphate-depleted dentin bonded interface over time. | Chondroitin ABC Lyase |
Cytoplasmic extracts of primary rabbit kidney cells inoculated with fibroma virus revealed 2 peaks of DNA complexes (120S and greater than or equal to 410S) in a linear sucrose gradient. Pulse-chase experiments demonstrated a shift in the gradient profile of lighter complexes toward heavier complexes. Synthesis of DNA complexes was inhibited by adding puromycin or actinomycin D. The DNA from virus-infected cultures hybridized 7 to 9 times greater with fibroma virus DNA than did the DNA from noninfected cultuures. The DNA complexes became increasingly resistant to deoxyribonuclease digestion as a function of time during viral growth cycle and produced tumors in rabbits. | Fibroma Virus, Rabbit |
Through a study of 68 patients, presenting 84 supernumerary teeth all together and, after a thorough survey of the literature, we can now state accurately about the frequency, location, surgery, X-Ray and heredity involved. After recalling and discussing the various pathological theories already set up, a theory has been put forward, more specifically intent on the explanation of frequent supernumerary teeth in the upper front teeth area. Nevertheless, the theories of extra growth and the overgrowth of the external layer remain worth while to explain some other locations." | Stomatognathic System Abnormalities |
INTRODUCTION: White bryony, Bryonia alba L., is a relatively little known plant in the history of folk medicine and folk botany in eastern and northern Europe. The main aim of this article is to bring together data about Bryonia alba and to summarise its cultural history and folk botanical importance in eastern and northern Europe. Nowadays, this species is considered at best as an ornamental plant, and at worst as a noxious weed. However, ethnographic and historical sources show that it used to be of magical, medicinal and ritual importance in our part of Europe. METHODS: A diachronic perspective was chosen in order to outline and analyse the devolution and changes in the use of B. alba, in the course of which we take into account the social, ecological and chemical aspects of the usage of this plant. We have therefore traced down and analysed published sources such as ethnographical descriptions, floras, linguistic records and topographical descriptions from northern and central-eastern Europe, particularly Scandinavia, Baltic States, Germany, Poland, Belarus, Ukraine and the Balkan Peninsula. The analysed material is presented and discussed within the biocultural domains that developed in the interaction between human societies and Bryonia alba. RESULTS AND DISCUSSION: Bryonia alba has many folk names in northern and central-eastern parts of Europe: some of them refer to its medicinal properties, life form, odour, or toxicity; others to its possession by the devil. As we learn, Bryonia alba was an inexpensive surrogate for mandrake (Mandragora officinarum L.) and sold as such in the discussed parts of Europe. The folklore and medicinal properties ascribed to mandrake were passed on to white bryony due to an apparent resemblance of the roots. In ethnographic descriptions, we find a mixture of booklore, i.e. written traditions, and oral traditions concerning this species. Some of this folklore must have been an alternative stories spread by swindlers who wished to sell fake mandrake roots to people. CONCLUSIONS: Plant monographs and reviews of particular species tend to concentrate on the botanicals, which might have great useful potential. White bryony presents a precisely opposite example, being a plant that used to be of medicinal relevance and was furnished with symbolical meaning, and has nowadays preserved only its ornamental value among some urban and rural dwellers of northern Europe. Nonetheless, it might be considered as a part of the biocultural heritage in old, well-preserved gardens. It is still used as a medicine in some parts of the Balkan Peninsula. | Bryonia |
PURPOSE OF REVIEW: With the advent of highly active antiretroviral therapy, the epidemiology of AIDS-lymphoma has changed, and prognosis has improved. Paradigms of therapy have changed. Although the incidence of AIDS-lymphoma has decreased, the incidence of HIV-associated Hodgkin's lymphoma has increased; mechanisms for these changes in epidemiology will be discussed. RECENT FINDINGS: Use of highly active antiretroviral therapy, either concomitantly or immediately after completion of chemotherapy, has resulted in rates of complete remission and survival that are similar to those in HIV-negative patients. The use of rituximab, while initially controversial because of reports of increased risk of infectious death, is associated with improved outcome; the increased risk of infectious death has not been confirmed. The infusional etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin regimen is associated with excellent results. High-dose chemotherapy with autologous stem cell transplant is associated with long-term, disease-free survival in approximately 50-80% of patients with relapsed/refractory AIDS-lymphoma. SUMMARY: Highly active antiretroviral therapy should be used with chemotherapy. Addition of rituximab is associated with improved response rates, without an increase in infections. Infusional etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin is associated with excellent results among patients with either diffuse large B cell lymphoma or Burkitt's lymphoma. Optimal therapy for patients with HIV-Hodgkin's lymphoma has not yet been defined. | Lymphoma, AIDS-Related |
The capacity of morphine to suppress natural and precipitated withdrawal was compared in morphine-dependent rhesus monkeys. A similar severity of withdrawal was induced by 14-hr deprivation or precipitated by naloxone, naltrexone, cyclazocine, Win 44,441 or MR 2266. Regardless of the procedure used to induce withdrawal, behavioral signs were completely suppressed by a cumulative dose of 17.5 mg/kg morphine. Thus, an equivalent level of withdrawal induced by reversible antagonists is as sensitive to subsequent morphine administration as is deprivation-induced abstinence. This is in accordance with the theory that vacancy of opiate receptors normally occupied by morphine is related to the level of abstinence observed. In contrast to Win 44,441, however, an equivalent level of withdrawal precipitated by buprenorphine required 175 mg/kg morphine for complete suppression. This is more informative than comparing duration of action; when given as 24-h pretreatments, a high dose of Win 44,441 (10 mg/kg) was only slightly less effective than buprenorphine (3.2 mg/kg) in antagonizing morphine-induced stupor in normal monkeys. Comparison of the ability of morphine to suppress precipitated withdrawal provides evidence of the relative reversibility of antagonists in vivo and demonstrates the extraordinarily stable nature by which buprenorphine acts at opiate receptors. | Morphine Dependence |
The stimulative effect of Carbadox, Nitrovin and Glypondin substances was tested on juvenile rats. A stimulative effect relative to physical weight was proved only with Carbadox at a dose of 2 mg kg-1 and Nitrovin (only in males) in doses of 10 and 50 mg kg-1 p. o. An overdosing of Carbadox revealed rather a negative effect, because already a dose ten times higher had a negative effect on physical growth and a dose fifty times higher caused obvious toxical symptoms. Glypondin was ineffective in each of the tested doses. The consumption of food per unit of weight increase was reduced after supplying carbadox dosed at 2 mg kg-1 by 25.6% in males and by 10.8% in females. After Nitrovin the intake of food was reduced most after a dose of 10 mg kg-1 in both sexes (8.6 and 8.4% respectively). The most frequent effect on the change of physical weight was the relative reduction in weight of the thyroid gland. For the screening of stimulators laboratory rats are not very suitable. | Nitrovin |
Magnetic circular dichroism (MCD) spectroscopy has been utilized to characterize the change in coordination structure in native ferric sperm whale myoglobin upon cyanogen bromide-modification. Comparison of the MCD properties of the ferric high-spin state of cyanogen bromide-modified myoglobin (BrCN-Mb) with those of native ferric horseradish peroxidase and Aplysia myoglobin suggests that ferric BrCN-Mb is a potential MCD model for the pentacoordinate state of ferric high-spin histidine-ligated heme proteins. These five-coordinate heme proteins afford a relatively weak and unsymmetric signal in the Soret region of the MCD spectrum. In contrast, native ferric myoglobin and the benzohydroxamic acid adduct of ferric horseradish peroxidase show a strong and symmetric derivative-shaped Soret MCD signal which is indicative of hexacoordination with water and histidine axial ligands. Therefore it seems that MCD spectroscopy could be used to probe the presence of water ligated to the distal side of ferric high-spin heme proteins. The MCD spectra of the ferric-azide, ferrous-deoxy and ferrous-CO forms of BrCN-Mb have also been measured and compared to those of analogous native myoglobin complexes. The present MCD study has been extended to include new ligands, NO, thiocyanate and cyanate, which bind to ferric BrCN-Mb. With exogenous ligands such as CO, NO and thiocyanate, the coordination structures of the BrCN-Mb complexes are similar to those of the respective native myoglobin adducts. In the case of ferrous-deoxy and ferric-cyanate BrCN-Mb, however, the altered MCD spectra (and EPR for the latter) reveal changes in electronic structure which likely correlate with alterations of the coordination environment of these BrCN-Mb derivatives. Data are also presented which support the proposed tetrazole-bound structure for azide-treated BrCN-Mb (Hori, H., Fujii, M., Shiro, Y., Iizuka, T., Adachi, S. and Morishima, I. (1989) J. Biol. Chem. 264, 5715-5719) and the inability of the distal histidine of BrCN-Mb to stabilize the ferric ligand-bound state. | Myoglobin |
A unified synthesis of the C1-C19 building blocks 8-10 of halichondrins A-C was developed from the common synthetic intermediates 26a,b. Acetylenic ketones 26a,b were in turn synthesized via selective activation/coupling of polyhalogenated nucleophiles 23a,b with aldehyde 11 in a (Ni)/Cr-mediated coupling reaction. Compared with Ni/Cr-mediated couplings of vinyl iodides and aldehydes, this (Ni)/Cr-mediated coupling exhibited two unique features. First, the coupling was found to proceed with a trace amount or no added Ni-catalyst. Second, TES-Cl, a dissociating agent to regenerate the Cr-catalyst, was found to give a better yield than Zr(Cp)2Cl2. An adjustment of the oxidation state was required to transform acetylenic ketones 26a,b into C1-C19 building blocks 8 and 9 of halichondrins A and B, respectively. In the halichondrin B series, a hydroxyl-directed (Me)4NBH(OAc)3 reduction of E- and Z-beta-alkoxy-enones 30 was found cleanly to achieve the required transformation, whereas a DMDO oxidation of E-vinylogous ester 27 allowed to introduce the C13 hydroxyl group with a high stereoselectivity in the halichondrin A series. In the halichondrin C series, Hf(OTf)4 was used to convert the double oxy-Michael product 28 into C1-C19 building block 10. | Ethers, Cyclic |
Pure human skin fibroblast procollagenase has been utilized in this study as a model system in which to examine the pathways of organomercurial and trypsin activation. Three organomercurials, p-(hydroxymercuri) benzoate, mersalyl, and p-aminophenylmercuric acetate, were able to fully activate human skin procollagenase with no accompanying loss of molecular weight. Lower molecular weight species were subsequently produced, particularly with a fourth organomercurial, phenylmercuric chloride. The activation process was dependent upon the concentration of the organomercurial compound and the time of incubation, but not on enzyme protein concentration. No evidence of a role for free sulfhydryls was found. Trypsin produced an initial cleavage product of procollagenase which was collagenolytically inactive yet underwent a concentration independent autocatalysis. Thus, procollagenase appeared to have an autocatalytic property which was enhanced by treatment with a variety of agents, all of which may function by perturbation of the zymogen conformation. | Phenylmercury Compounds |
Use of a neodymium:yttrium-aluminum-garnet laser to remove exuberant granulation tissue from the esophagus of a horse A 4-year-old Quarter Horse mare was evaluated because of recurrent esophageal obstruction. Endoscopic examination revealed a proliferative mass in the esophagus approximately 55 cm aborad to the nares. Histologic examination of biopsy specimens revealed diffuse suppurative esophagitis and granulation tissue with no evidence of neoplasia. The mass was excisedand ablated transendoscopically with a neodymium:yttrium-aluminum-garnet laser. During a follow-up examination 2 weeks after the final laser procedure, the mass was no longer apparent, and the esophagus appeared healed. Six months after the final examination, there had been no recurrence of the mass. In this horse, transendoscopic laser excision was efficacious and avoided problems associated with an esophagotomy. | Laser Therapy |
Chemistry, once king of fluorescence microscopy, was usurped by the field of fluorescent proteins. The increased demands of modern microscopy techniques on the photon budget" require better and brighter fluorophores, causing a renewed interest in synthetic dyes. Here, we review the recent advances in biochemistry, protein engineering, and organic synthesis that have allowed a triumphant return of chemical fluorophores to modern biological imaging." | Luminescent Proteins |
BACKGROUND: Morulas with delayed growth sometimes coexist with blastocysts. There is still limited evidence regarding the optimal disposal of surplus morulas. With the advancement of vitrification, the freezing-thawing technique has been widely applied to zygotes with 2 pronuclei, as well as embryos at the cleavage and blastocyst stages. The freezing of morulas, however, has rarely been discussed. The purpose of this study was to investigate whether these poor-quality and slow-growing morulas are worthy of cryopreservation. METHODS: This is a retrospective, observational, proof-of-concept study. A total of 1033 day 5/6 surplus morulas were cryopreserved from January 2015 to December 2018. The study included 167 women undergoing 180 frozen embryo transfer cycles. After the morulas underwent freezing-thawing procedures, their development was monitored for an additional day. The primary outcome was the blastocyst formation rate. Secondary outcomes were clinical pregnancy rate, live birth rate and abortion rate. RESULTS: A total of 347 surplus morulas were thawed. All studied morulas showed delayed compaction (day 5, n = 329; day 6, n = 18) and were graded as having low (M1, n = 54), medium (M2, n = 138) or high (M3, n = 155) fragmentation. The post-thaw survival rate was 79.3%. After 1 day in extended culture, the blastocyst formation rate was 66.6%, and the top-quality blastocyst formation rate was 23.6%. The day 5 morulas graded as M1, M2, and M3 had blastocyst formation rates of 88.9, 74.0, and 52.8% (p < 0.001), respectively, and the top-quality blastocyst formation rates were 64.8, 25.2, and 9.0% (p < 0.001), respectively. The clinical pregnancy rate was 33.6%. CONCLUSIONS: The post-thaw blastocyst formation rate was satisfactory, with approximately one-half of heavily fragmented morulas (M3) developing into blastocysts. Most of the poor-quality morulas were worth to freeze, with the reasonable goal of obtaining pregnancy and live birth. This alternative strategy may be a feasible approach for coping with poor-quality surplus morulas in non-PGS (preimplantation genetic screening) cycles. | Morula |
Rab27a, a Rab family small GTPase, is involved in the exocytosis of secretory granules in melanocytes and cytotoxic T-cells. Rab27a mutations cause type 2 Griscelli syndrome, which is characterized by immunodeficiency, including uncontrolled macrophage activation known as hemophagocytic syndrome. However, the role of Rab27a in phagocytosis remains elusive. Here, using macrophage-like differentiated HL-60 cells and C3bi-opsonized zymosan as a pathogen-phagocyte model, we show that Rab27a negatively regulates complement-mediated phagocytic activity in association with F-actin remodeling. We found that transfection of Rab27a shRNA into HL-60 cells enhances complement-mediated phagocytosis. To clarify the mechanisms underlying the elevated phagocytosis in Rab27a knockdown cells, we analyzed the process of phagosome formation focusing on F-actin dynamics: F-actin assembly, followed by F-actin extension around the particles and the subsequent degradation of F-actin, leading to internalization of the particles enclosed in phagosomes. Microscopic analysis revealed that these actin-related processes, including F-actin coating and F-actin degradation, proceed more rapidly in Rab27a knockdown cells than in control HL-60 cells. Both elevated phagocytosis and accelerated F-actin remodeling were restored by expression of rescue-Rab27a and Rab27a-Q78L (GTP-bound form), but not by Rab27a-T23N (GDP-bound form). Furthermore, an increased accumulation of Coronin 1A surrounding F-actin coats was observed in Rab27a knockdown cells, suggesting that the function of Coronin 1A is related to the regulation of the F-actin coating. Our findings demonstrate that Rab27a plays a direct regulatory role in the nascent process of phagocytosis by prolongation of the stage of actin coating via suppression of Coronin 1A. This study may contribute to an explanation of the underlying mechanisms of excessive phagocytosis observed in Griscelli syndrome. | Piebaldism |
Cancer patients mount T-lymphocyte responses against antigens expressed selectively by their malignancy, but these responses often fail to control their disease, because tumors select mechanisms that allow them to resist immune destruction. Among the numerous resistance mechanisms that have been proposed, metabolic inhibition of T cells by tryptophan catabolism deserves particular attention, because of the frequent expression of tryptophan-degrading enzymes in human tumors, and because in vitro and in vivo studies have shown that their enzymatic activity can be readily blocked by pharmacologic inhibitors, thereby restoring T-cell-mediated tumor cell killing and paving the way to targeted therapeutic intervention. In view of recent observations, and taking into account the differences between human and mouse data that differ in several aspects, in this Cancer Immunology at the Crossroads article, we discuss the role of the three enzymes that have been proposed to control tryptophan catabolism in tumoral immune resistance: indoleamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3-dioxygenase (TDO), and indoleamine 2,3-dioxygenase 2 (IDO2). | Tryptophan Oxygenase |
Phenol, as a very toxic pollutant, exists widely in rivers in China. To explore the effect of bacterial augmentation on phytoremediation of phenol by Acorus calamus L., some plant growth and physiological parameters and percent removal of phenol were determined in hydroponics containing phenol with addition of Bacillus thuringiensis A1. The A. calamus L. and B. thuringiensis A1 consortium increased the growth rate of plant height, chlorophyll content, the activity of superoxide dismutase (SOD) and peroxidase (POD) in A. calamus L. 10.00-36.54%, 0.62 - 22.15%, 3.94 - 11.25% and 1.37-10.50% respectively compared with single plant treatments at same phenol concentrations. However, the addition of B. thuringiensis A1 decreased the content of malondialdehyde (MDA) and relative electrical conductivity (REC) in A. calamus L. 12.99-23.66% and 8.38-29.98% respectively compared with single plant treatments. The removal efficiency of phenol (increased from 1.56% to 13.78%) by the A. calamus L. and B. thuringiensis A1 consortium was higher than the removal efficiency of phenol of the independent A. calamus L. system. In conclusion, the addition of B. thuringiensis A1 alleviated phenol stress to A. calamus L and enhanced phenol removal due to phenol removal by bacterial augmentation.Novelty statementThe addition of B. thuringiensis A1 alleviated phenol stress to A. calamus L. and enhanced phenol removal due to phenol removal by bacterial augmentation. | Acoraceae |
BACKGROUND: Augmented reality neuronavigation (ARN) systems can overlay three-dimensional anatomy and disease without the need for a two-dimensional external monitor. Accuracy is crucial for their clinical applicability. We performed a systematic review regarding the reported accuracy of ARN systems and compared them with the accuracy of conventional infrared neuronavigation (CIN). METHODS: PubMed and Embase were searched for ARN and CIN systems. For ARN, type of system, method of patient-to-image registration, accuracy method, and accuracy of the system were noted. For CIN, navigation accuracy, expressed as target registration error (TRE), was noted. A meta-analysis was performed comparing the TRE of ARN and CIN systems. RESULTS: Thirty-five studies were included, 12 for ARN and 23 for CIN. ARN systems could be divided into head-mounted display and heads-up display. In ARN, 4 methods were encountered for patient-to-image registration, of which point-pair matching was the one most frequently used. Five methods for assessing accuracy were described. Ninety-four TRE measurements of ARN systems were compared with 9058 TRE measurements of CIN systems. Mean TRE was 2.5 mm (95% confidence interval, 0.7-4.4) for ARN systems and 2.6 mm (95% confidence interval, 2.1-3.1) for CIN systems. CONCLUSIONS: In ARN, there seems to be lack of agreement regarding the best method to assess accuracy. Nevertheless, ARN systems seem able to achieve an accuracy comparable to CIN systems. Future studies should be prospective and compare TREs, which should be measured in a standardized fashion. | Neuronavigation |
Crimean-Congo hemorrhagic fever (CCHF) is a viral infection associated with a high mortality rate. Ribavirin is the only drug used in the treatment of this disease. Studies investigating the effectiveness of ribavirin in CCHF have been retrospective and to date have included only a small number of cases. In recent years, due to climate changes, the number of cases of CCHF in Turkey has increased, and experience in the treatment of CCHF has improved. Several studies have evaluated the efficacy of ribavirin in Turkey, including one randomized controlled trial and two studies with a large number of cases. In these studies, ribavirin therapy was not shown to decrease mortality rates; the mortality rate was 2-9% in patients treated with ribavirin and 5.6-11% in those who were not treated with this drug. These findings suggest that patients with CCHF should be followed with supportive care only until randomized controlled trials with larger groups have been conducted. | Hemorrhagic Fever, Crimean |
Nanopores have emerged as a prominent single-molecule analytic tool with particular promise for genomic applications. In this review, we discuss two potential applications of the nanopore sensors: First, we present a nanopore-based single-molecule DNA sequencing method that utilizes optical detection for massively parallel throughput. Second, we describe a method by which nanopores can be used as single-molecule genotyping tools. For DNA sequencing, the distinction among the four types of DNA nucleobases is achieved by employing a biochemical procedure for DNA expansion. In this approach, each nucleobase in each DNA strand is converted into one of four predefined unique 16-mers in a process that preserves the nucleobase sequence. The resulting converted strands are then hybridized to a library of four molecular beacons, each carrying a unique fluorophore tag, that are perfect complements to the 16-mers used for conversion. Solid-state nanopores are then used to sequentially remove these beacons, one after the other, leading to a series of photon bursts in four colors that can be optically detected. Single-molecule genotyping is achieved by tagging the DNA fragments with gamma-modified synthetic peptide nucleic acid probes coupled to an electronic characterization of the complexes using solid-state nanopores. This method can be used to identify and differentiate genes with a high level of sequence similarity at the single-molecule level, but different pathology or response to treatment. We will illustrate this method by differentiating the pol gene for two highly similar human immunodeficiency virus subtypes, paving the way for a novel diagnostics platform for viral classification. | Genes, pol |
OBJECTIVES: This study investigates the levels of participation and the relative association of economic and noneconomic factors on primary care physician participation in the Medicare program. METHODS: Demographic information, participation in Medicare, and attitudes toward both the Medicare program and Medicare patients were collected in a written survey mailed to half the primary care physicians in Iowa. Ordinary least squares and logistic regression analyses were conducted to determine factors associated with the percentage of Medicare patients in a practice and the acceptance of all new Medicare patients, respectively. RESULTS: Two thirds of physicians were accepting all new Medicare patients, whereas 16% were accepting no new Medicare patients. Factors associated with having a higher percentage of Medicare patients in a practice were as follows: (1) a larger proportion of Medicare recipients in the county, (2) practice as a general internal medicine physician, (3) more years in practice at the current location, (4) greater enjoyment treating elderly patients, (5) less concern about having too many Medicare patients, and (6) a stronger belief that the Medicare program respects their professional judgment. Physicians less concerned about having too many Medicare patients in their practice and physicians in counties with a higher percentage of Medicare patients were significantly more likely to accept all new Medicare patients. CONCLUSIONS: These results suggest that as Medicare reforms are discussed, careful consideration of the impact of these reforms on noneconomic issues is important to ensure adequate physician participation and access for elderly patients through the Medicare program. | Medicare Assignment |
Enrico Mugnaini has devoted part of his long and fruitful neuroscientific career to investigating the structural similarities between the cerebellar cortex and one of the first relay stations of the mammalian auditory pathway: the dorsal cochlear nucleus. The hypothesis of the cerebellar-like nature of the superficial layers of the dorsal cochlear nucleus received definitive support with the discovery and extensive characterization in his laboratory of unipolar brush cells, a neuron type unique to certain regions of the cerebellar cortex and to the granule cell domains of the cochlear nuclei. Paradoxically, a different line of research carried out in his laboratory revealed that, unlike the mammalian cerebellar cortex, the dorsal cochlear nucleus receives direct projections from the cerebral cortex, a fact that constitutes one of the main differences between the cerebellum and the dorsal cochlear nucleus. In an article published in 1995, Mugnaini's group described in detail the novel direct projections from the rat auditory neocortex to various subcollicular auditory centers, including the nucleus sagulum, the paralemniscal regions, the superior olivary complex, and the cochlear nuclei (Feliciano et al., Auditory Neuroscience 1995; 1:287-308). This review gives Enrico Mugnaini credit for his seminal contribution to the knowledge of auditory corticosubcollicular projections and summarizes how this growing field has evolved in the last 20 years. | Myelencephalon |
Elderly and young hypertensive patients differ with regard to clinical and pathophysiologic profiles. In the elderly, hypertension is generally characterized by elevated peripheral vascular resistance and decreased cardiac output. To establish an individualized or patient-specific approach to their treatment, antihypertensive agents must be evaluated specifically in this subpopulation. Labetalol, an alpha- and beta-blocking agent, has been shown to lower blood pressure in young and elderly hypertensive patients primarily by reducing peripheral vascular resistance without compromising cardiac output. Examination of recent reports on the pharmacokinetics and pharmacodynamic effects, and on the efficacy and safety of labetalol in elderly persons with hypertension, leads us to conclude that the drug appears to be well suited for use in these patients. | Labetalol |
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