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Lambda red- gam- makes a small plaque on P2 lysogens (the partial Spi- phenotype). It has been proposed that inactivation of an additional gene delta, mapping in the recombination region, makes the plaque bigger (the full Spi- phenotype) (Zissler et al., 1917b). The present paper demonstrates that the Chi mutation in lambda (Stahl et al., 1975) confers upon red- gam- phage the full Spi- phenotype and that the deletion of the region of the chromosome attributed to delta does not. It appears unnecessary to invoke a gene delta in the Spi- phenotype. | Chromosome Deletion |
We report a systematic combinatorial exploration of affinity enhancement of antibodies by insertions and deletions (InDels). Transposon-based introduction of InDels via the method TRIAD (transposition-based random insertion and deletion mutagenesis) was used to generate large libraries with random in-frame InDels across the entire single-chain variable fragment gene that were further recombined and screened by ribosome display. Knowledge of potential insertion points from TRIAD libraries formed the basis of exploration of length and sequence diversity of novel insertions by insertional-scanning mutagenesis (InScaM). An overall 256-fold affinity improvement of an anti-IL-13 antibody BAK1 as a result of InDel mutagenesis and combination with known point mutations validates this approach, and suggests that the results of this InDel mutagenesis and conventional exploration of point mutations can synergize to generate antibodies with higher affinity. | Antibody Affinity |
Platelet-rich fibrin (PRF), a second-generation platelet concentrate, has been the focus of intensive research endeavors over the past 2 decades. Over the years, however, numerous reports have inaccurately reported relative centrifugal force (RCF) values, which has caused considerable confusion in the field. Furthermore, the use of trade names such as leukocyte and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) has further confused many readers, since studies have not always used centrifugation parameters with equal rotor sizes, angulation of tubes, and/or tube design. This has led to considerable misperception in the report of relative centrifugal force. Herein is described necessary parameters pivotal for the future report of RCF in studies related to PRF, which include: 1) dimensions of the rotor (radius at the clot and end of the tube); 2) rotor angulation for the tube holder; 3) revolutions per minute (RPM) and time; 4) RCF value calculated at either the RCF-minimum, RCF-clot, or RCF-maximum; 5) composition and size of tubes used to produce PRF; and 6) centrifugation model used. This editorial aims to minimize confusion in the field and create more transparent research reporting RCF values in future studies. | Blood |
Particles released from cobalt-chromium-molybdenum (CoCrMo) alloys are considered common elicitors of chronic inflammatory adverse effects. There is a lack of data demonstrating particle numbers, size distribution and elemental composition of bone marrow resident particles which would allow for implementation of clinically relevant test strategies in bone marrow models at different degrees of exposure. The aim of this study was to investigate metal particle exposure in human periprosthetic bone marrow of three types of arthroplasty implants. Periprosthetic bone marrow sections from eight patients exposed to CoCrMo particles were analyzed via spatially resolved and synchrotron-based nanoscopic X-ray fluorescence imaging. These analyses revealed lognormal particle size distribution patterns predominantly towards the nanoscale. Analyses of particle numbers and normalization to bone marrow volume and bone marrow cell number indicated particle concentrations of up to 1 x 10(11) particles/ml bone marrow or 2 x 10(4) particles/bone marrow cell, respectively. Analyses of elemental ratios of CoCrMo particles showed that particularly the particles' Co content depends on particle size. The obtained data point towards Co release from arthroprosthetic particles in the course of dealloying and degradation processes of larger particles within periprosthetic bone marrow. This is the first study providing data based on metal particle analyses to be used for future in vitro and in vivo studies of possible toxic effects in human bone marrow following exposure to arthroprosthetic CoCrMo particles of different concentration, size, and elemental composition. Graphical abstract. | Vitallium |
4-Aminobutyrate aminotransferase (EC 2.6.1.19, 4 aminobutyrate:2-oxoglutarate aminotransferase) is cleaved by trypsin, yielding an enzymatically active species which can be separated from the split peptides by gel filtration. The shortened enzyme derivative gives one band (Mr = 95,000) on polyacrylamide gradient gel electrophoresis. Changes in protein conformation induced by tryptic digestion were studied by fluorescence spectroscopy. The native enzyme tagged with the chromophore fluorescein yields a rotational relaxation time of 106 ns, whereas the trypsin-digested enzyme gives a rotational relaxation time of 33 ns. The decrease in rotational relaxation time is attributed to flexibility of the polypeptide chain with enhanced rotational freedom of the probe covalently linked to one thiol group. The reactivity of sulfhydryl groups toward 5,5'-dithiobis(2-nitrobenzoic acid) is also affected by trypsin cleavage. More--SH groups (2.6/dimer) become reactive toward 5,5'-dithiobis(2-nitrobenzoic acid) as a result of trypsin digestion. Local conformational fluctuations are induced as a result of tryptic cleavage, but the catalytic sites remain intact. The peptides released from 4-aminobutyrate aminotransferase were characterized by fingerprint analysis and their amino acid composition determined. | Dithionitrobenzoic Acid |
BACKGROUND: Contact endoscopy (CE) was initially described as a method used in the analysis of uterine and vocal folds histology. The first nasal cavity CE studies achieved promising results regarding its use for the differentiation between benign and malignant lesions, considering that biopsy might cause some complications, especially bleeding. This study described and compared the findings of CE on inverted papilloma and nasosinusal squamous cell carcinoma (SCC) and tested the effectiveness of this exam as a noninvasive method for in vivo differentiation between these tumors. METHODS: The patients included in this study were divided into group A, patients diagnosed with inverted papilloma, and group B, patients diagnosed with SCC. CE results were compared among themselves. CE images were presented to examiners not experienced with the method. RESULTS: Twenty-two patients were examined, 13 in group A and 9 in group B. The main relevant differences in CE findings between those two groups were corkscrew vessels, presence of mitoses, keratinization and nuclear pleomorphism in carcinoma, and vacuolated cells in papilloma. The examiners were capable of defining the diagnosis of these nasal tumors only based on CE images. CONCLUSION: CE may be a useful noninvasive exam to be used in the in vivo diagnosis of inverted papilloma and nasosinusal SCC, which may enable better preoperative planning. | Papilloma, Inverted |
Helicobacter pylori outer membrane inflammatory protein A (OipA) was originally named for its role in inducing inflammation in the host, as evidenced by high mucosal IL-8 levels. Expression of OipA is regulated by phase variation of a CT dinucleotide-repeat located in the 5' region of the gene. However, little is known about OipA geographic diversity across isolates. To address this gap, we conducted a large-scale molecular epidemiologic analysis using H. pylori clinical isolates obtained from two geographically distinct populations: Korea and the United States (US). Most Korean isolates (98.7%) possessed two copies of oipA located at two specific loci (A and B) while all US isolates contained only one copy of oipA at locus A. Furthermore, most Korean oipA (94.8%) possessed three or less CT repeats while most US oipA (96.6%) contained five or more CT repeats. Among the two copies, all Korean H. pylori possessed at least one oipA 'on' phase variant while the single copy of oipA in US isolates showed 56.2% 'on' and 43.8% 'off.' Thus, host differences seem to have driven geographic diversification of H. pylori across these populations such that OipA expression in US isolates is still regulated by phase variation with 5 or more CT repeats, while Korean isolates always express OipA; duplication of the oipA combined with a reduction of CT repeats to three or less ensures continued expression. En masse, these findings suggest that diversity in the oipA gene copy number, CT repeats, and phase variation among H. pylori from different populations may confer a benefit in adaptation to particular host populations. | Phase Variation |
Forty-four 50- to 80-year-old Parkinson patients were interviewed about the effects of the disease on their lives. The Q-sort technique was used to analyze the interview data. In addition, the Symptom Checklist 90, the Mini-Mental State, and physician ratings of disease severity were obtained. Four clusters of patients were identified. Cluster I patients were sanguine and engaged; Cluster III patients were depressed and apprehensive about the future; Cluster III patients felt depressed, ashamed, and misunderstood; and Cluster IV patients were passive and resigned. Disease severity, but not demographic or other health variables, discriminated the groups. Patients with a mild to moderate impairment who adjusted effectively to their illness (Cluster I) were distinguished by an ability to put negative thoughts out of mind, by their belief that there are worse fates than having Parkinson's disease, and by efforts to influence certain aspects of their illness. The particular patterns of adaptation of the patients who were depressed and misunderstood (Cluster III) and passive and resigned (Cluster IV) seemed primarily a function of physical condition. This suggest that the degree to which personal attitudes can influence adaptation to somatic disease is limited by specific realities of the disease. | Q-Sort |
The lack of consensus over the transition point for the end of the sigmoid and beginning of the rectum is a problem for the colorectal multidisciplinary team. In this review, we survey the wide number of landmarks for the rectosigmoid junction, and describe the theoretical and evidence-based strengths and weaknesses of each one. Without a reliable definition of the rectum, sigmoid and rectal cancers will be classified inconsistently. As the treatment strategies for sigmoid and rectal cancers are radically different, incorrect tumour localisation has a substantial impact on patient management, leading to under or over treatment. Inconsistent classification will confound investigation of metastatic patterns and treatment outcomes. Now that the rectosigmoid junction has been recognised as a distinct segment of colon by the International Classification of Diseases, further heterogeneity in management and outcomes could result to the detriment of patients and research. We describe a bespoke, anatomical and reliable landmark for the rectosigmoid junction; the sigmoid take-off. | Sigmoid Neoplasms |
Retinitis pigmentosa (RP) is genetically heterogeneous retinopathy caused by photoreceptor cell death and retinal pigment epithelial atrophy that eventually results in blindness in bilateral eyes. Various photoreceptor cell death types and pathological phenotypic changes that have been disclosed in RP demand in-depth research of its pathogenic mechanism that may account for inter-patient heterogeneous responses to mainstream drug treatment. As the primary method for studying the genetic characteristics of RP, molecular biology has been widely used in disease diagnosis and clinical trials. Current technology iterations, such as gene therapy, stem cell therapy, and optogenetics, are advancing towards precise diagnosis and clinical applications. Specifically, technologies, such as effective delivery vectors, CRISPR/Cas9 technology, and iPSC-based cell transplantation, hasten the pace of personalized precision medicine in RP. The combination of conventional therapy and state-of-the-art medication is promising in revolutionizing RP treatment strategies. This article provides an overview of the latest research on the pathogenesis, diagnosis, and treatment of retinitis pigmentosa, aiming for a convenient reference of what has been achieved so far. | Retinitis Pigmentosa |
1,1,1-Trifluoro-3-thenoylacetone was shown to cause complete inhibition of dihydroorotate oxidation in rat liver mitochondria as measured by orotate formation and the rate of dihydro-orotate-dependent reduction of 2,6-dichlorophenol-indophenol or cytochrome c. The inhibition by trifluorothenoylacetone was dose-dependent, and a concentration of 1 mM completely inhibited dihydro-orotate dehydrogenase activity. 1,10-Phenanthroline, another iron-chelating agent, also caused total inhibition of the liver enzyme. Whereas the iron chelators inhibited 100% of dihydro-orotate dehydrogenase activity in liver mitochondria, they inhibited only a maximum of 72% in the case of the brain enzyme. The inhibition by trifluorothenoylacetone was not prevented by addition of phenazine methosulphate or ubiquinone. Dihydro-orotate dehydrogenase-mediated generation of superoxide was abolished when the enzyme was fully inhibited by trifluorothenoylacetone or when the electron-transport system was blocked by antimycin A. These results suggest that the iron component(s) of dihydro-orotate dehydrogenase is of strategic importance for catalytic activity and transfer of reducing equivalents from the primary enzyme to the electron-transport chain. Furthermore, the study indicates that production of superoxide radicals during dihydro-orotate dehydrogenase-catalysed oxidation of dihydro-orotate may be at the cytochrome b-c1 segment of the electron-transport chain (as a consequence of autooxidation of ubisemiquinone) rather than at a site on the primary enzyme. | Dihydroorotate Oxidase |
INTRODUCTION: Colonic urea-nitrogen metabolites have been implicated in the pathogenesis of certain diseases which can be affected by environmental factors. OBJECTIVES: We aimed to explore the influence of ambient humidity on colonic urea-nitrogen metabolism. METHODS: Blood biochemical indexes, metabolites of intestinal tract, and gut microbiota composition of mice (n = 10/group) exposed to high relative humidity (RH, 90 +/- 2%) were analyzed during the 14-day exposure. RESULTS: After 12-h exposure, plasma blood urea nitrogen (BUN) level increased along with a decrease in the activity of erythrocyte Na(+)/K(+) -ATPase. Moreover, abnormal erythrocyte morphologies appeared after 3 days of exposure. The colonic BUN and ammonia levels increased significantly after the 12-h and 24-h exposure, respectively. The colonic level of amino acids, partly synthesized by gut microbiota using ammonia as the nitrogen source, was significantly higher on the 7th day. Furthermore, the level of fecal short-chain fatty acids was significantly higher after 3-day exposure and the level of branched-chain fatty acids increased on the 14th day. Overall, gut microbiota composition was continuously altered during exposure, facilitating the preferential proliferation of urea-nitrogen metabolism bacteria. CONCLUSION: Our findings suggest that short-term high RH exposure influences colonic urea-nitrogen metabolism by increasing the influx of colonic urea and altering gut microbiota, which might further impact the host health outcomes. | Blood Urea Nitrogen |
Arylamine N-acetyltransferase (NAT) research has been influenced in recent years by the rapid progress in genomics, proteomics, structural genomics and other cutting-edge disciplines. To keep up with these advancements, the NAT scientific community has fostered collaboration and exchange of know-how between its members. As a specialized event bringing together experts from many different laboratories, the triennial International NAT Workshop has been instrumental in maintaining this culture over the past ten years. The 2007 Workshop took place in Alexandroupolis, Greece, and covered ongoing research on the structure and enzymatic function of human NATs, the prokaryotic and eukaryotic models for NAT, the mechanisms of NAT gene regulation and expression, the frequencies and effects of polymorphisms in the human NAT genes, and the involvement of NATs in multifactorial diseases, including cancer, allergic conditions, endometriosis and endemic nephropathies. Gene nomenclature issues were also addressed and the participants discussed current trends in the field. | Arylamine N-Acetyltransferase |
In 2010, Coxiella burnetii was identified in 75% of northern fur seal placentas from a single rookery in Alaska, but nothing was known about the significance of this organism in the population. Although many infectious organisms cause increased cell death, C. burnetii has been shown to suppress apoptosis of the host macrophages as an intracellular survival mechanism. To determine if infection induces a similar functional change in the placenta, immunohistochemistry for antibodies to cleaved caspase-3 (activated caspase-3) and the (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) technique were used to compare the amount of placental apoptosis in infected and noninfected placentas. There was a statistically significant difference in the frequency of apoptotic cells between infected and uninfected placentas, with more apoptosis identified in the uninfected placentas. This finding suggests that the survival mechanism of C. burnetii in host macrophages to reduce apoptosis may also be utilized in trophoblasts. The significance of decreased trophoblastic apoptosis for the northern fur seal fetus requires further investigation. | In Situ Nick-End Labeling |
In this article, we report on the development of a defined serum-free medium capable of supporting the culture expansion of mesenchymal stromal/stem cells (MSCs) from canine adipose tissue (canine Ad-MSCs). The potential benefits of serum-free media can only be utilized if cells cultured in serum-free media maintain the same functional characteristics as cells cultured in serum-containing media. Therefore, we analyze the characteristics of canine Ad-MSCs cultured in this serum-free medium or in serum-containing medium through evaluation of growth kinetics, clonogenic capacity, senescence, and differentiation capacity. Both, serum-containing medium and our serum-free medium, supported efficient growth and colony formation of canine Ad-MSCs. In addition, canine Ad-MSCs cultured in both media demonstrated similar viability after freeze/thaw, similar cell surface marker expression, and were capable of trilineage differentiation. While canine Ad-MSCs cultured in both media were generally similar, under the conditions of our study, canine Ad-MSCs cultured in serum-free medium demonstrated a shorter lag phase and higher colony-forming capacity, accelerated population doubling, maintained multipotentiality at higher passage numbers, and underwent senescence at higher passage numbers compared to canine Ad-MSCs cultured in conventional serum-containing medium. These results suggest that canine Ad-MSCs cultured in serum-free medium retain the basic characteristics associated with canine Ad-MSCs cultured in serum-containing medium, although some differences in growth kinetics were observed. | Mesenchymal Stem Cells |
Metronidazole, a medicine discovered in the late 1950 s is mainly an antibiotic active against anaerobes and protozoa. There are numerous side effects of metronidazole. Some interactions with other medicines enhance its activity, and some cause the decrease in activity and plasma concentration. A short review of its side effects, mechanisms of action and interactions with other medicines is provided. As resistance towards metronidazole occurred, these mechanisms are described as well. The data presented in the review were selected on the basis of relevancy, citation and age of the used references. | Metronidazole |
This paper presents a robotic flexible drill and its navigation system for total hip arthroplasty (THA). The new robotic system provides an unprecedented and unique capability to perform curved femoral milling under the guidance of a multimodality navigation system. The robotic system consists of three components. Firstly, a flexible drill manipulator comprises multiple rigid segments that act as a sheath to a flexible shaft with a drill/burr attached to the end. The second part of the robotic system is a hybrid tracking system that consists of an optical tracking system and a position tracking system. Optical tracking units are used to track the surgical objects and tools outside the drilling area, while a rotary encoder placed at each joint of the sheath is synchronized to provide the position information for the flexible manipulator with its virtual object. Finally, the flexible drill is integrated into a computer-aided navigation system. The navigation system provides real time guidance to a surgeon during the procedure. The flexible drill system is then able to implement THA by bone milling. The final section of this paper is an evaluation of the flexible and steerable drill and its navigation system for femoral bone milling in sawbones." | Arthroplasty, Replacement, Hip |
Endogenous MPTP-like neurotoxins such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) have been suspected in the etiology of Parkinson's disease (PD). 1BnTIQ was found in a concentration three times higher in cerebrospinal fluid of PD brains than control subjects [J. Neurochem. 65 (6) (1995) 2633]. In the present study, we have evaluated the mechanisms of 1BnTIQ toxicity in human dopaminergic SH-SY5Y cells and tested the neuroprotective action of SKF-38393, a dopamine receptor (D(1)) agonist. 1BnTIQ dose dependently decreased cell viability in dopaminergic SH-SY5Y cells and the extent of cell death was more pronounced when compared to MPP(+). Similar to MPP(+), 1BnTIQ significantly decreased [3H]dopamine uptake. 1BnTIQ significantly increased lipid peroxidation, Bax expression, and active caspase-3 formation. Furthermore, it decreased the expression of Bcl-xL, an anti-apoptotic protein, in these cells. SKF-38393, a dopamine receptor (D(1)) agonist (1 and 10 microM) completely prevented the cell death and significantly increased cell viability. These results strongly suggest that 1BnTIQ induces dopaminergic cell death by apoptosis and dopamine receptor agonists may be useful neuroprotective agents against 1BnTIQ toxicity. | Tumor Cells, Cultured |
This review describes the various types of sebaceous glands, their locations, and where possible their different functions. All sebaceous glands are similar in structure and secrete sebum by a holocrine process. However, the nature of this secretion and the regulation of the secretory process seem to differ among the various types of glands. Methods for measuring sebum secretion and assessing sebaceous gland activity are also described. The area of major interest during the last 20 years has undoubtedly been the mechanisms that control sebaceous gland function. Most studies have focused on the endocrine control and in particular on the role of androgens and pituitary hormones, although evidence suggests that nonendocrine factors may also be important. However, many questions remain and during the next few years attention will certainly be given to the role of retinoids and their mode of action in the treatment of acne. | Sebaceous Glands |
High mobility group AT-hook 2 (HMGA2) has been associated with increased cell proliferation and cell cycle dysregulation, leading to the ontogeny of varied tumor types and their metastatic potentials, a frequently used index of disease prognosis. In this review, we deepen our understanding of HMGA2 pathogenicity by exploring the mechanisms by which HMGA2 misexpression and ectopic expression induces mesenchymal and epithelial tumorigenesis respectively and distinguish the pathogenesis of benign from malignant mesenchymal tumors. Importantly, we highlight the regulatory role of let-7 microRNA family of tumor suppressors in determining HMGA2 misexpression events leading to tumor pathogenesis and focused on possible mechanisms by which HMGA2 could propagate lymphangioleiomyomatosis (LAM), benign mesenchymal tumors of the lungs. Lastly, we discuss potential therapeutic strategies for epithelial and mesenchymal tumorigenesis based on targeting the HMGA2 signaling pathway. | HMGA Proteins |
BACKGROUND: We have previously reported that exposure of embryos to 13-cis-retinoic acid (cRA) results in an abnormal phenotype of the fetal cerebellum. In this study, we analyzed early changes in the cerebellar anlagen (midbrain-hindbrain junction) as well as lesions of the fetal cerebellar vermis after a teratogenic dosing regimen of cRA in the macaque model. METHODS: We examined embryo coronal sections of the midbrain-hindbrain junction immunostained for Pax-2, Engrailed-2 (En-2) and Krox-20. To characterize the cerebellum foliation and fissure formation processes, we analyzed vermal cortical cell layer development and the number and depth of the major fissures on sagittal sections of fetal vermis. We also examined Purkinje cell development in vermal sections immunostained for CD3. RESULTS: Compared with controls, there was a consistent truncation of the midbrain-hindbrain region of early embryos exposed to cRA. The cRA-induced fetal vermis lesions included inhibition in its anteroposterior growth, altered folial patterning, a general loss of prominence of the fissures accompanied by a total loss of sublobular fissures, and changes in cortical cell layer development. CD3(+) Purkinje cells were abnormally dispersed deep into the molecular layer in the vermis. CONCLUSIONS: Our findings indicate that the effects of cRA on the developing cerebellum involve interference with the hierarchy of complex cellular and genetic interactions that lead to the growth and subdivision of the cerebellum into smaller units. The regional vermal defects may be related to early postnatal functional deficits. | Rhombencephalon |
In recent years, a new phenotype of rhinitis has been described; it is characterized by the local production of specific IgE. There isn't any evidence of systemic atopy and it has been called local allergic rhinitis. Understanding the involved physiopathological mechanisms and the behavior of this phenotype translates into the development of strategies and treatments that improve the quality of life of patients with this disease. Below, we present an updated review of the available information regarding this disease and also of the aspects that are yet unresolved. | Rhinitis, Allergic |
human herpesvirus 6 (HHV-6) is the major causative agent of exanthem subitum which is one of popular diseases in infant, and establishes latent infections in adults of more than 90%. Recently, the encephalitis caused by reactivated- HHV-6 has been shown in patients after transplantation. In addition, the relationship HHV-6 and drug-induced hypersensitivity syndrome has also been reported. human herpesvirus 7 (HHV-7) was isolated from the stimulated-peripheral blood lymphocytes of a healthy individual, and also causes exanthema subitum. Both viruses are related viruses which belong to betaherpesvirus subfamily, and replicate and produce progeny viruses in T cells. | Exanthema Subitum |
BACKGROUND: Tibetan hulless barley (Hordeum vulgare var. nudum), adjusting to the harsh environment on Qinghai-Tibet Plateau, is a good subject for analyzing drought tolerance mechanism. Several unannotated differentially expressed genes (DEGs) were identified through our previous RNA-Seq study using two hulless barley accessions with contrasting drought tolerance. One of these DEGs, HVU010048.2, showed up-regulated pattern under dehydration stress in both drought tolerant (DT) and drought susceptible (DS) accessions, while its function in drought resistance remains unknown. This new gene was named as HvLRX (light responsive X), because its expression was induced under high light intensity while suppressed under dark. OBJECTIVE: To provide preliminary bioinformatics prediction, expression pattern, and drought resistance function of this new gene. METHODS: Bioinformatics analysis of HvLRX were conducted by MEGA, PlantCARE, ProtParam, CELLO et al. The expression pattern of HvLRX under different light intensity, dehydration shock, gradual drought stress, NaCl stress, polyethylene glycol (PEG) 6000 stress and abscisic acid (ABA) treatment was investigated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The function of HvLRX was analyzed by virus induced gene silencing (VIGS) in hulless barley and by transgenic method in tobacco. RESULTS: Full cDNAs of HvLRX were cloned and compared in three hulless barley accessions. Homologues of HvLRX protein in other plants were excavated and their phylogenetic relationship was analyzed. Several light responsive elements (ATC-motif, Box 4, G-box, Sp1, and chs-CMA1a) were identified in its promoter region. Its expression can be promoted under high light intensity, dehydration shock, gradual drought stress, PEG 6000, and NaCl stress, but was almost unchanged in ABA treatment. HvLRX-silenced plants had a higher leaf water loss rate (WLR) and a lower survival rate (SR) compared with controls under dehydration stress. The infected leaves of HvLRX-silenced plants lost their water content quickly and became withered at 10 dpi. The SR of HvLRX overexpressed transgenic tobacco plants was significantly higher than that of wild-type plants. These results indicated HvLRX play a role in drought resistance. Besides, retarded vegetative growth was detected in HvLRX-silenced hulless barley plants, which suggested that this gene is important for plant development. CONCLUSIONS: This study provided data of bioinformatics, expression pattern, and function of HvLRX. To our knowledge, this is the first report of this new dehydration and light responsive gene. | Hordeum |
Self-administration of ethanol (E) and nicotine (N) occurs frequently in tandem orders (i.e., N-->E vs. E-->N) and thereby produces differing interoceptive profiles of subjective effects in humans. If the interoceptive stimulus characteristics of N-->E differ from E-->N, it is possible that such differences contribute to their co-dependence. The rationale for the present investigation was to determine whether ethanol, when preceded or followed by nicotine, produces different discriminative stimulus effects in rats. In two experiments, using a one-manipulandum operant drug discrimination procedure, rats were trained to discriminate temporal sequential administrations of ethanol (1.0 g/kg) that was followed or preceded by nicotine (0.3 mg/kg). Sessions alternated between food-reinforcement sessions on a variable interval 30-sec schedule (i.e., S(D)) and non-reinforcement sessions (i.e., S(Delta)). In Experiment 1, administrations of ethanol were followed or preceded by a 10-min interval of nicotine. Training sessions took place 10 min following the second drug injection. Four groups of rats were trained to discriminate only one sequence from sequential administrations of saline, and each drug sequence was counterbalanced across groups for their roles as S(D) or S(Delta). There was robust stimulus control. N-->E and E-->N functioned equally well as S(D) or S(Delta). Experiment 2 used two groups of rats. For one group, the E-->N sequence functioned as the S(D) and the N-->E sequence functioned as the S(Delta). The drug sequences were counterbalanced for the other group. Brief non-reinforcement tests revealed significantly greater responding during the S(D) sequence compared to the S(Delta) sequence for both groups. These results suggest that different drug sequences of ethanol followed or preceded by nicotine established reliable discriminative stimulus control over operant responding, potentially because of characteristic differences in the overlapping pharmacokinetic profiles of the NE compound. The results are discussed in terms of: 1) conditional stimulus control among two interoceptive drug states; and 2) the clinical modulation of human alcohol consumption and tobacco smoking. | Conditioning, Operant |
Medical treatments of coronary myocardial bridging (CMB) generally include beta-blockers and calcium channel blockers. Nitrates are avoided because symptoms may worsen. Nicorandil is a hybrid of a nitrate and a potassium channel opener. However, the effect of nicorandil on CMB is unknown. We analyzed nicorandil reactivity at the site with CMB in 51 patients. Maximal and minimal diameters of CMB were measured by quantitative angiography at baseline and at 60 seconds after intracoronary administration of 200 mg nicorandil. The maximal diameter during diastole increased from 2.15 + 0.42 mm to 2.34 + 0.44 mm after administration of nicorandil (P < .001), and the minimal diameter during systole increased from 1.24 + 0.63 mm to 1.67 + 0.64 mm (P < .001). Thus, nicorandil reduced the percentage vessel narrowing from 44.0 + 26.1% to 30.3 + 21.2% (P < .001). In 22 patients, we also evaluated the effect of nitroglycerin. The maximal diameter during diastole increased from 2.25 + 0.47 mm to 2.51 + 0.44 mm after administration of nitroglycerin (P < .019), and the minimal diameter during systole decreased from 1.28 + 0.64 mm to 1.14 + 0.60 mm (P = .276). Thus, nitroglycerin augmented the percentage vessel narrowing from 44.9% + 25.0% to 56.0% + 23.5% (P = .023). These results indicate that intracoronary administration of nicorandil could dilate coronary arteries during diastole as well as systole in patients with CMB during coronary angiography. | Myocardial Bridging |
Tea from the leaves of guayusa (Ilex guayusa) has a long history of consumption by Ecuadorian natives in regions where the plant is indigenous. The tea contains the methylxanthines caffeine and theobromine as well as chlorogenic acids, flavonoids, and sugars. Various studies were performed to evaluate the general and genetic toxicology of a standardized liquid concentrate of guayusa (GC). Guayusa concentrate was found to be negative in in vitro genotoxicity tests including the Ames test and a chromosome aberration study in human lymphocytes. The oral median lethal dose (LD50) of GC was >5,000 mg/kg for female rats. Guayusa concentrate was administered to male and female rats in a 90-day subchronic study at 1,200, 2,500, and 5,000 mg/kg/d of GC and a caffeine-positive control at 150 mg/kg/d corresponding to the amount of caffeine in the high-dose GC group. Effects observed in the GC-treated groups were comparable to those in the caffeine control group and included reductions in body weights, food efficiency, triglycerides values, and fat pad weights and increases in blood chemistry values for serum aspartate aminotransferase, serum alanine aminotransferase, and cholesterol and adaptive salivary gland hypertrophy. No signs of incremental toxicity due to any other components of guayusa were observed. The studies indicate no harmful effects of GC in these test systems. | Ilex guayusa |
The role of the interventional radiologist in the care of patients requiring placement of central venous access devices is rapidly evolving. With experience gained from diagnosing and treating central venous catheter-related complications, interventional radiologists are assuming an increasing role in the placement of these devices. With imaging guidance, catheter and guidewire skills, and a commitment to providing a clinical service that includes management of catheter malfunctions and complications, central venous access by the interventional radiologist has proven a safe and effective alternative to standard surgical techniques. | Radiography, Interventional |
The ability of bacteria to recognize kin provides a means to form social groups. In turn these groups can lead to cooperative behaviors that surpass the ability of the individual. Kin recognition involves specific biochemical interactions between a receptor(s) and an identification molecule(s). Recognition specificity, ensuring that nonkin are excluded and kin are included, is critical and depends on the number of loci and polymorphisms involved. After recognition and biochemical perception, the common ensuing cooperative behaviors include biofilm formation, quorum responses, development, and swarming motility. Although kin recognition is a fundamental mechanism through which cells might interact, microbiologists are only beginning to explore the topic. This review considers both molecular and theoretical aspects of bacterial kin recognition. Consideration is also given to bacterial diversity, genetic relatedness, kin selection theory, and mechanisms of recognition. | Bacterial Proteins |
OBJECTIVE: To characterise the functional morphology of the nasal microcirculation in humans in comparison with reindeer as a means of testing the hypothesis that the luminous red nose of Rudolph, one of the most well known reindeer pulling Santa Claus's sleigh, is due to the presence of a highly dense and rich nasal microcirculation. DESIGN: Observational study. SETTING: Tromso, Norway (near the North Pole), and Amsterdam, the Netherlands. PARTICIPANTS: Five healthy human volunteers, two adult reindeer, and a patient with grade 3 nasal polyposis. MAIN OUTCOME MEASURES: Architecture of the microvasculature of the nasal septal mucosa and head of the inferior turbinates, kinetics of red blood cells, and real time reactivity of the microcirculation to topical medicines. RESULTS: Similarities between human and reindeer nasal microcirculation were uncovered. Hairpin-like capillaries in the reindeers' nasal septal mucosa were rich in red blood cells, with a perfused vessel density of 20 (SD 0.7) mm/mm(2). Scattered crypt or gland-like structures surrounded by capillaries containing flowing red blood cells were found in human and reindeer noses. In a healthy volunteer, nasal microvascular reactivity was demonstrated by the application of a local anaesthetic with vasoconstrictor activity, which resulted in direct cessation of capillary blood flow. Abnormal microvasculature was observed in the patient with nasal polyposis. CONCLUSIONS: The nasal microcirculation of reindeer is richly vascularised, with a vascular density 25% higher than that in humans. These results highlight the intrinsic physiological properties of Rudolph's legendary luminous red nose, which help to protect it from freezing during sleigh rides and to regulate the temperature of the reindeer's brain, factors essential for flying reindeer pulling Santa Claus's sleigh under extreme temperatures. | Reindeer |
A reliable and efficient protocol for the synthesis of 2 '-([1,2,3]triazol-1-yl)-2 '-deoxyadenosine derivatives from vidarabine is presented. Vidarabine was converted to 2'-azido-2'-deoxy-3',5-O-(tetraisopropyldisiloxane-1,3-diyl)-adenosine. This azide was used as the starting material for the Cu(I)-catalyzed parallel synthesis of 1,2,3-triazoles using a variety of alkynes. The reactions proceeded in good yield and gave almost exclusively the 1,4-disubstituted 1,2,3-triazoles. | Deoxyadenosines |
Elderberry and chokeberry food supplements may be 'functional food' in patients with metabolic syndrome or influenza but, for this, adequate amounts of co-active ingredients must be consumed in the daily dose. This study aimed to quantify the anthocyanin content in three elderberry and six chokeberry products to assess their usefulness as functional food. Analyses were carried out using an established HPLC procedure. The minimum anthocyanin doses for the treatment of metabolic syndrome disorders were estimated as 110 mg per day and 3.5 g per day for influenza. Three products were inappropriate for clinical use. The lowest liquid supplies were achieved with a proprietary elderberry concentrate (11 mL) and a proprietary chokeberry mother juice (100 mL). Clinical studies are now required to prove the effectiveness and adapt the doses according to the clinical symptoms. | Photinia |
1. Measurements were made of the relative fractions of diffuse and specular reflexions in the fovea and periphery of the human fundus oculi.2. All the light emerging from the eye is scattered or reflected behind the receptors as bleaching the retina affects both fractions equally.3. Bruch's membrane is the most likely surface at which specular reflexion occurs whereas the choroid and sclera are probably involved in scattering.4. Both diffuse and specular components show marked directional effects that vary with wave-length. | Fundus Oculi |
Viruses can cause a severe lymphopenia early in infection and a subsequent, lasting loss of pre-existing CD8(+) memory T cells. We therefore questioned how well virus Ag-specific memory CD8(+) T cells could reconstitute mice rendered lymphopenic as a consequence of genetics, irradiation, or viral or poly(I:C)-induced cytokines. In each case, reconstitution of the CD8(+) compartment was associated with limited division of virus-specific memory T cells and a reduction in their proportion. This indicates that foreign Ag-experienced CD44(high)CD8(+) memory T cells may respond differently to homeostatic signals than other CD44(high)CD8(+) cells, and that events inducing lymphopenia may lead to a permanent reduction in T cell memory. | Pichinde virus |
There is considerable concern regarding the biological plausibility of the response of certain chemicals in the in vitro photoclastogenicity assay, suggesting that this assay is oversensitive and lacks specificity. To explore this further, four coded compounds (aminotriazole, propantheline bromide, cycloheximide and disulfoton) were evaluated for their potential response in a photoclastogenicity assay in cultured Chinese hamster ovary (CHO) cells. None of the four compounds were shown to absorb ultraviolet radiation (UVR) or visible light in the 290- to 700-nm region of the electromagnetic spectrum. A fifth coded compound, tetracycline, which absorbs UVR, was also tested as this has previously been shown to be phototoxic in vitro (3T3-NRU assay) and is cytotoxic, but not genotoxic, at high concentrations in standard 'dark' genotoxicity assays in mammalian cells. The results showed that cycloheximide, disulfoton and tetracycline were clastogenic in CHO cells following UVR exposure (solar-simulated light at 700 mJ/cm(2)) but not in the absence of UVR. Aminotriazole and propantheline were negative in the presence and absence of UVR exposure. Follow-up testing showed that neither cycloheximide nor disulfoton was positive in the 3T3-NRU assay, the standard in vitro regulatory test for phototoxicity, a result consistent with their inability to absorb UVR. These data suggest that both cycloheximide and disulfoton are pseudophotoclastogens, like zinc oxide. Together, these data question the specificity of the in vitro photoclastogencity assay in CHO cells and raises further concern regarding its use for the assessment of chemical photosafety for regulatory purposes. At the very least, a review of the current guidance documents for the photosafety evaluation of pharmaceuticals and cosmetics should be undertaken urgently. | Propantheline |
Local cultivars of comfrey (Symphytum spp.) have been used to cover protein and mineral requirements of farm animals in low-input systems. Due to its known health-promoting (e.g. allantoin), but also anti-nutritive ingredients (e.g. pyrrolizidine alkaloids), multidisciplinary approaches are essential in order to quantify the nutritional value and the potential of its use in poultry and farm animals in terms of meeting animal needs, using local resources as well as remediating over-fertilized soils. Focusing on animal effects, here one-day old sexed Cobb500 broiler chickens were subjected to either a standard control diet or a standard diet supplemented with 4% dried comfrey leaves for 32 days. Performance traits indicate good acceptance of supplementation with comfrey leaves. Parameters for liver function, mineral homeostasis, bone mineral density as well as intestinal microanatomy revealed no signs of impairment. Quantified pyrrolizidine alkaloids were below the detection limit in liver and breast muscle (<5 mug/kg tissue). Comfrey supplemented male broiler chickens showed higher ash content in breast muscle and revealed altered gene expression profiles for metabolic pathways in blood cells. In healthy broiler chickens, the transcriptome analyses revealed no aberrations in the immune-related pathways due to comfrey supplementation. The results imply that the use of comfrey leaves in a high-performance broiler line seems feasible and offers the potential for closed nutrient cycles in site-adapted local agricultural systems. Further analyses need to focus on possible growth-promoting and health-improving components of comfrey and the safe use of chicken products for human consumption. | Comfrey |
The authors have developed a prompt and informative method for assessment of the depth and reversibility of the morphofunctional changes in the common bile duct (CBD) wall with the use of staining by hematoxylin basic, fuchsin-picric acid. Four types of the morphologic changes in CBD wall, which characterize the different degree of reversibility, were established. Depending of presence of these types, the corresponding surgical tactics is recommended. | Cholangitis |
The gtf gene coding for glucosyltransferase (GTF), which produces a water-soluble glucan, was cloned from Streptococcus sobrinus OMZ176 (serotype d) into plasmid vector pBR322. This gene was expressed in Escherichia coli, and the product was purified to near homogeneity. The antigenicity of recombinant GTF (rGTF) was examined with the antisera raised against purified GTF P1, P2, P3, and P4 obtained from S. sobrinus AHT (serotype g). The rGTF reacted only with anti-GTF P1 serum in a Western blot (immunoblot) analysis. The rGTF closely resembled GTF P1 in its molecular mass, Km value for sucrose, optimal pH, primer dependency, and immunological properties. The high-molecular-weight, water-soluble glucan produced by the rGTF also resembled that of GTF P1, which is the most efficient primer donor for primer-dependent, water-insoluble glucan synthesis. Properties of the rGTF were also compared with those of rGTFS, which was purified from E. coli carrying the gtfS gene isolated from Streptococcus downei (previously S. sobrinus serotype h) MFe28. Both rGTF and rGTFS synthesized water-soluble glucan from sucrose without primer dextran, but their characteristics in Km values for sucrose, optimal pHs, and polymer sizes of the glucan were different. Furthermore, the gtf gene did not hybridize with the gtfS gene in a Southern blot analysis. These results showed that rGTF is similar to S. sobrinus AHT GTF P1 but distinct from rGTFS that has been previously purified from E. coli carrying the gtfS gene. | Glucosyltransferases |
The KCNQ family (KCNQ1-KCNQ5) of voltage-gated potassium channels plays critical roles in many physiological and pathological processes. It is known that the channel opening of all KCNQs relies on the signaling lipid molecule phosphatidylinositol 4,5-bisphosphate (PIP2). However, the molecular mechanism of PIP2 in modulating the opening of the four neuronal KCNQ channels (KCNQ2-KCNQ5), which are essential for regulating neuronal excitability, remains largely elusive. Here, we report the cryoelectron microscopy (cryo-EM) structures of human KCNQ4 determined in complex with the activator ML213 in the absence or presence of PIP2. Two PIP2 molecules are identified in the open-state structure of KCNQ4, which act as a bridge to couple the voltage-sensing domain (VSD) and pore domain (PD) of KCNQ4 leading to the channel opening. Our findings reveal the binding sites and activation mechanisms of ML213 and PIP2 for neuronal KCNQ channels, providing a framework for therapeutic intervention targeting on these important channels. | KCNQ Potassium Channels |
Mulberry leaf tea reduces atherosclerotic lesions and its main component is Deoxynojirimycin (DNJ). We aimed to explore the effects of Mulberry leaf DNJ (MLD) on atherosclerotic lesions in the patients with coronary heart disease (CHD). MLD and serum DNJ was detected by high-performance liquid chromatography (HPLC). The CHD patients with low-density lipoprotein cholesterol >140 mg/dl were assigned into the EG (MLD treatment) and the CG (placebo treatment) groups. Serum biochemical indices, the cerebrovascular and cardiovascular events and carotid intima-media thickness (IMT) were measured before and after a 1-year intervention. Pearson Correlation Coefficient test was used to explore the relationship between serum levels of DNJ and IMT values. Serum DNJ was 70 +/- 50 ng/ml in the EG group but no serum DNJ was detected in the CG group. The incidence of cerebrovascular and cardiovascular events in the EG was lower than that in the CG group (p < .05). MLD therapy improved antioxidant and anti-inflammatory properties and serum lipid profile (p < .05). The IMT values in the EG group were lower than those in the CG group (p < .05). Serum levels of DNJ had a strong negative relationship with IMT values. MLD treatment attenuates atherosclerotic lesions possibly via DNJ. PRACTICAL APPLICATIONS: Mulberry leaves Deoxynojirimycin (MLD) treatment improved antioxidant and anti-inflammatory properties and serum lipid profile in heart disease patients. MLD reduce carotid intima-media thickness (IMT) and serum levels of DNJ (the main ingredient of mulberry leaf) had a strong relationship with IMT values. MLD is an amazing treat used for reducing the incidence of cerebrovascular and cardiovascular events in heart disease patients. | 1-Deoxynojirimycin |
OBJECTIVE: To clone, express and characterize the capsid protein of human Norwalk virus Guangzhou strain NVgz01. METHODS: On the basis of successful construction of full-genome clones and sequence analysis of human norovirus Guangzhou strain NVgz01, the full capsid gene was ligated into pET28a (+) for expression. After IPTG induction, the recombinant protein was purified through metal (Ni(2+)) chelating affinity chromatography. Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to determine the antigenicity of the recombinant protein. RESULTS: The recombinant capsid gene was overexpressed in E.coli, yielding the recombinant protein with relative molecular mass of 62x10(3) that was highly purified through metal (Ni(2+)) chelating affinity chromatography. IDEIA Norovirus Kit and immunoassay showed that the recombinant protein had good antigenicity. CONCLUSION: The capsid gene of norovirus Guangzhou strain has been cloned and expressed, which can be useful for developing diagnostic reagents or vaccine of norovirus. | Norwalk virus |
Ultra high pressure homogenisation (UHPH) is an emerging technology to obtain fine and stable soymilk emulsions. Very little information is available about the stability of this kind of product during storage. Changes of isoflavone profile, protein digestibility and lysine availability in pasteurised-UHPH soymilks were studied for 21 days at 4 degrees C in comparison to heat-pasteurised soymilks. Neither heat nor UHPH treatments affected the isoflavone profile, as the percentage of each chemical form, in comparison with unprocessed-soymilk. During storage, there was a conversion of isoflavone forms to aglycones, being higher in heat-processed samples. In addition, UHPH samples showed a lesser percentage of blocked lysine during storage. No differences were observed in the evolution of protein digestibility among samples. Therefore, UHPH treatment seems to produce a better product, due to lower amounts of aglycones, and higher protein nutritional quality than heat treatment. | Isoflavones |
The autoimmune exocrinopathy Sjogren's syndrome (SS) is characterized by mononuclear cell (MNC) infiltrates of exocrine glands and overactivity of B lymphocytes. Although T cells have long been perceived as the prime effectors, increasing evidence indicates that the key role is rather served by B cells. Among related abnormalities are rheumatoid factor (RF), anti-SSA/Ro, and anti-SSB/La antibodies (Ab). Also, supporting this view is our finding of an increase in the number of circulating naive mature B (Bm) cells, with a reciprocal decrease in that of memory B cells. Furthermore, a ratio of Bm2-plus-Bm2' cells to early Bm5-plus-late Bm5 above 5 is diagnostic. This variation partly reflects the migration of active memory B cells into the exocrine glands of the patients, as well as into their skin. More recently, the B-cell-activating factor of the TNF family (BAFF) has been endorsed with a pivotal role in B-cell survival and hence implicated in the pathogenesis of autoimmunity. In practice, B cells have turned quite attractive as a target for biotherapy. For example, treatment with anti-CD20 Ab has afforded some benefits in this disease, while BAFF blockers are still on the way, but should expand our armamentarium for treating SS. With such B-cell-directed biotherapies in mind, we delineate herein the distinguishing traits of B lymphocytes in SS. | B-Lymphocyte Subsets |
We previously proposed that three metacognitive processes - meta-awareness, disidentification from internal experience, and reduced reactivity to thought content - together constitute decentering. We review emerging methods to study these metacognitive processes and the novel insights they provide regarding the nature and salutary function(s) of decentering. Specifically, we review novel psychometric studies of self-report scales of decentering, as well as studies using intensive experience sampling, novel behavioral assessments, and experimental micro-interventions designed to target the metacognitive processes. Findings support the theorized inter-relations of the metacognitive processes, help to elucidate the pathways through which they may contribute to mental health, and provide preliminary evidence of their salutary roles as mechanisms of action in mindfulness-based interventions. | Metacognition |
The mortality associated with invasive candidiasis remains unacceptably high. The T2 magnetic resonance (T2MR) assay is a novel US FDA-approved molecular diagnostic assay for the diagnosis of candidemia that can rapidly detect the five most commonly isolated Candida spp. In clinical trials, T2MR has exhibited good clinical sensitivity and specificity. Potential benefits from the adoption of T2MR technology in the diagnostic and therapeutic algorithms for invasive candidiasis can arise from timely diagnosis of disease, increased case detection, tailored therapy and decrease in empiric antifungal treatment. As everyday clinical experience with the assay is evolving, we discuss the utility of T2MR in invasive candidiasis with and without candidemia based on the currently available evidence regarding its performance. | Candidiasis, Invasive |
Recent discussions of French army reform before the Revolution have revived interest in the more general topic of military culture in the ancien regime. One account of this period speaks of an evolution in criteria for military merit, one in which professional efficiency came to overshadow traditional martial virtues, such as fidelity and courage. But a review of the evidence, both archival and published, from the Maison militaire du Roi reveals that here, at least, old virtues continued to be central until the end, serving as expressions of a relationship with the king in which royal graces were their natural complement. Viewed historically, this conception of service continued a feudal tradition. The milieu of the Maison was distinctive in the encouragement it gave to such traditions, but the function of the institution as a pepiniere of officers for the army gave it a potentially wide influence in balancing the tendencies towards professionalism. | Social Conditions |
Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, are a relatively recently described entity. Most exhibit a mutated tyrosine kinase receptor gene and in some capacity are treated by tyrosine kinase inhibitors. GISTs can occur across the age spectrum but are more common in patients older than 40 years. They exhibit a wide range of clinical presentations and imaging characteristics. All patterns of enhancement on contrast enhanced computed tomography (CECT) can be seen with GISTs, including hypoenhancing, isoenhancing, and hyperenhancing tumors. They can be large or small, endoluminal or exophytic. Clinical presentations include asymptomatic patients, nonspecific symptoms, obstruction, and bleeding. Bleeding can take the form of slow, intraluminal GI bleeding or massive intraperitoneal bleeding secondary to rupture and can be seen regardless of the enhancement pattern. Some can cavitate, ulcerate, rupture or cause fistulae. The radiologist's knowledge of the variety of combinations of presentations can narrow the differential diagnosis and ultimately lead to faster diagnosis and treatment." | Gastrointestinal Stromal Tumors |
PURPOSE: To evaluate the risk of active choroidal neovascularization (CNV) in presence of deep irregular vascular network (IVN) in eyes with angioid streaks (AS). METHODS: Observational case series including three treatment-naive eyes with angioid streaks and IVN, without CNV. Patients were followed-up during 18 months with multimodal imaging including structural optical coherence tomography (OCT) and OCT Angiography (OCT-A) to detect possible neovascular complication. RESULTS: On OCT-A, IVN was detected as a peripapillary and/or macular high-flow lesion, filling the spaces between the angioid streaks in the outer retina slab. Repeated OCT-A could detect an active CNV emerging from the IVN, as a high-flow rich anastomotic vascular network with a perilesional dark halo. Patient was treated with intravitreal injections of Bevacizumab on a Pro Re Nata regimen, with a decreased CNV area and lower vascular density on control OCT-A. CONCLUSION: OCT-A shown to be helpful in detecting the presence of IVN in asymptomatic eyes with AS during a routine examination. In our series, the IVN seems to be predictor of active CNV, needing a close surveillance and frequent follow-up to allow early treatment upon CNV activation. | Angioid Streaks |
The treatment of skin diseases with ultraviolet radiation represents an important therapeutic modality in clinical dermatology, and the number of skin diseases that improve under the phototherapeutic modalities of today is still growing. While clinical phototherapy was originally based on empirical observations, our present understanding of the underlying mechanisms has improved substantially due to important progress in photobiological science. The better understanding of this scientific basis of treatment allows to both choose the correct phototherapeutic modality and determine the most effective treatment regimen. The aim of this article is to discuss the appropriate indications for phototherapy as well as its safe and effective employment, providing practical help in daily clinical phototherapeutic practice. | Phototherapy |
Decreased ability to maintain tissue integrity is critically involved in aging and degenerative diseases. Fatty acid (FA) metabolism has a profound impact on animal development and tissue maintenance, but our understanding of the underlying mechanisms is limited. We investigated whether and how FA abundance affects muscle integrity using Caenorhabditis elegans. We show that reducing the overall FA level by blocking FA biosynthesis or inhibiting protein myristoylation leads to disorganization of sarcomere structure and adult-onset paralysis. Further analysis indicates that myristoylation of two ARF guanosine triphosphatases (GTPases) critically mediates the effect of FA deficiency on sarcomere integrity through inducing endoplasmic reticulum (ER) stress and ER unfolded protein response (UPR(ER)), which in turn leads to reduction of the level of sarcomere component PINCH and myosin disorganization. We thus present a mechanism that links FA signal, protein myristoylation, and ER homeostasis with muscle integrity, which provides valuable insights into the regulatory role of nutrients and ER homeostasis in muscle maintenance. | Myristic Acid |
DNA-protein interactions are central to fundamental cellular processes, yet widely implemented technologies for measuring these interactions on a genome scale in bacteria are laborious and capture only a snapshot of binding events. We devised a facile method for mapping DNA-protein interaction sites in vivo using the double-stranded DNA-specific cytosine deaminase toxin DddA. In 3D-seq (DddA-sequencing), strains containing DddA fused to a DNA-binding protein of interest accumulate characteristic mutations in DNA sequence adjacent to sites occupied by the DNA-bound fusion protein. High-depth sequencing enables detection of sites of increased mutation frequency in these strains, yielding genome-wide maps of DNA-protein interaction sites. We validated 3D-seq for four transcription regulators in two bacterial species, Pseudomonas aeruginosa and Escherichia coli. We show that 3D-seq offers ease of implementation, the ability to record binding event signatures over time and the capacity for single-cell resolution. | Cytosine Deaminase |
In this paper we review some recent results on the evolution of probability measures under cellular automata acting on a fullshift. In particular we discuss the crucial role of the attractiveness of maximal measures. We enlarge the context of the results of a previous study of topological Markov chains that are Abelian groups; the shift map is an automorphism of this group. This is carried out by studying the dynamics of Markov measures by a particular additive cellular automata. Many of these topics were within the focus of Francisco Varela's mathematical interests. | Markov Chains |
1,4-Dioxane is a highly mobile and persistent groundwater pollutant that often forms large dilute plumes. Because of this, utilizing aggressive pump-and-treat and ex-situ technologies such as advanced oxidation can be prohibitively expensive. In this study, we bioaugmented the poplar rhizosphere with dioxane-degrading bacteria Mycobacterium dioxanotrophicus PH-06 or Pseudonocardia dioxanivorans CB1190 to enhance treatment of 1,4-dioxane in bench-scale experiments. All treatments tested removed 10 mg/L dioxane to near health advisory levels (<4 mug/L). However, PH-06-bioaugmented poplar significantly outperformed all other treatments, reaching <4 mug/L in only 13 days. Growth curve experiments confirmed that PH-06 could not utilize root extract as an auxiliary carbon source for growth. Despite this limitation, our findings suggest that PH-06 is a strong bioaugmentation candidate to enhance the treatment of dioxane by phytoremediation. In addition, we confirmed that CB1190 could utilize both 1,4-dioxane and root extract as substrates. Finally, we demonstrated the large-scale production of these two strains for use in the field. Overall, this study shows that combining phytoremediation and bioaugmentation is an attractive strategy to treat dioxane-contaminated groundwater to low risk-based concentrations (~1 mug/L). | Pseudonocardia |
Few naturally-occurring plasmids are maintained in mammalian cells. Among these are genomes of gamma-herpesviruses, including Epstein-Barr virus (EBV) and Kaposi's Sarcoma-associated herpesvirus (KSHV), which cause multiple human malignancies (1-3). These two genomes are replicated in a licensed manner, each using a single viral protein and cellular replication machinery, and are passed to daughter cells during cell division despite their lacking traditional centromeres (4-8). Much work has been done to characterize the replications of these plasmid genomes using methods such as Southern blotting and fluorescence in situ hybridization (FISH). These methods are limited, though. Quantitative PCR and Southern blots provide information about the average number of plasmids per cell in a population of cells. FISH is a single-cell assay that reveals both the average number and the distribution of plasmids per cell in the population of cells but is static, allowing no information about the parent or progeny of the examined cell. Here, we describe a method for visualizing plasmids in live cells. This method is based on the binding of a fluorescently tagged lactose repressor protein to multiple sites in the plasmid of interest (9). The DNA of interest is engineered to include approximately 250 tandem repeats of the lactose operator (LacO) sequence. LacO is specifically bound by the lactose repressor protein (LacI), which can be fused to a fluorescent protein. The fusion protein can either be expressed from the engineered plasmid or introduced by a retroviral vector. In this way, the DNA molecules are fluorescently tagged and therefore become visible via fluorescence microscopy. The fusion protein is blocked from binding the plasmid DNA by culturing cells in the presence of IPTG until the plasmids are ready to be viewed. This system allows the plasmids to be monitored in living cells through several generations, revealing properties of their synthesis and partitioning to daughter cells. Ideal cells are adherent, easily transfected, and have large nuclei. This technique has been used to determine that 84% of EBV-derived plasmids are synthesized each generation and 88% of the newly synthesized plasmids partition faithfully to daughter cells in HeLa cells. Pairs of these EBV plasmids were seen to be tethered to or associated with sister chromatids after their synthesis in S-phase until they were seen to separate as the sister chromatids separated in Anaphase(10). The method is currently being used to study replication of KSHV genomes in HeLa cells and SLK cells. HeLa cells are immortalized human epithelial cells, and SLK cells are immortalized human endothelial cells. Though SLK cells were originally derived from a KSHV lesion, neither the HeLa nor SLK cell line naturally harbors KSHV genomes(11). In addition to studying viral replication, this visualization technique can be used to investigate the effects of the addition, removal, or mutation of various DNA sequence elements on synthesis, localization, and partitioning of other recombinant plasmid DNAs. | Plasmids |
OBJECTIVE: Inhalation of noble and other gases after cardiac arrest (CA) might improve neurological and cardiac outcomes. This article discusses up-to-date information on this novel therapeutic intervention. DATA SOURCES: CENTRAL, MEDLINE, online published abstracts from conference proceedings, clinical trial registry clinicaltrials.gov, and reference lists of relevant papers were systematically searched from January 1960 till March 2019. STUDY SELECTION: Preclinical and clinical studies, irrespective of their types or described outcomes, were included. DATA EXTRACTION: Abstract screening, study selection, and data extraction were performed by two independent authors. Due to the paucity of human trials, risk of bias assessment was not performed DATA SYNTHESIS: After screening 281 interventional studies, we included an overall of 27. Only, xenon, helium, hydrogen, and nitric oxide have been or are being studied on humans. Xenon, nitric oxide, and hydrogen show both neuroprotective and cardiotonic features, while argon and hydrogen sulfide seem neuroprotective, but not cardiotonic. Most gases have elicited neurohistological protection in preclinical studies; however, only hydrogen and hydrogen sulfide appeared to preserve CA1 sector of hippocampus, the most vulnerable area in the brain for hypoxia. CONCLUSION: Inhalation of certain gases after CPR appears promising in mitigating neurological and cardiac damage and may become the next successful neuroprotective and cardiotonic interventions. | Noble Gases |
We examined the possibility to improve the effectiveness of the in vitro transcription system using T7 RNA polymerase by coexistence with organic bases. The effect of the additives was evaluated by measuring the amount of RNA products in comparison with that of the control system (without additive). We found that four commercial bases and a series of ethylated polyamine analogues newly designed were active enhancers in the following activation order, 1,8-bis(ethylamino)octane > 1,8-octanediamine > 1,5-bis(ethylamino)pentane > cadaverine > 1,8-bis(ethylamino)-4-azaoctane > spermidine 1,18-bis(ethylamino)-5,14-diazaoctadecane > agmatine. It was shown that RNA products were corresponding, only in the presence of active enhancers, to the full length size of the template DNA, and that sequencing signals were enhanced by the presence of active enhancers with high fidelity so that the transcriptional sequencing was further refined to be a highly sensitive sequencing method from a small amount of linear dsDNA. These results suggest that T7 RNA polymerase was activated by the specific binding of the polyamine additive to produce RNA transcripts with fidelity to the template DNA. Therefore, it is expected that the transcriptional sequencing in the presence of active enhancers might be a powerful and sensitive method, in place of the prevalent DNA amplification method, for genomic science projects and clinical and practical gene diagnoses. | Polyamines |
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially fatal condition. Despite existing treatments, recurrence rates and complications remain high. Understanding the pathophysiology of thrombus formation is crucial for developing effective therapies. This narrative review provides an overview of the critical elements of acute and chronic DVT, presents a theoretical framework for understanding thrombus formation, and discusses potential implications for therapeutic interventions. In addition, a hypothesis of thrombus formation is formulated, encompassing all elements described in this work. | Embolism and Thrombosis |
BACKGROUND: The arterial switch operation (ASO) is the preferred procedure for children with dextrotransposition of the great arteries or Taussig-Bing anomaly. Short- as well as long-term outcome of ASO are excellent, but coronary artery stenoses are reported as a common long-term complication. It has been hypothesized that these might result in sudden cardiac death late after ASO. METHODS: A systematic search of PubMed and EMBASE was conducted to evaluate sudden cardiac death because of coronary complications late after ASO. Data on patients surviving >/= 5 years post-ASO were collected from selected studies, corrected for duplicate data, and analyzed. RESULTS: After duplicate data correction 52 studies remained for data analysis. Among the 8798 survivors with follow-up, 27 patients died >/= 5 years post-ASO (0.3%). Of these patients, 10 were known with relevant residual lesions. Five late deaths were sudden, possibly from a cardiac cause. None of the late sudden deaths were confirmed to be coronary-related. CONCLUSIONS: Sudden cardiac death in asymptomatic patients as a result of coronary artery stenosis or occlusion is extremely rare, with 5 possible cases and no proven cases of coronary artery-related sudden cardiac death in 8798 patients with 66,450 patient follow-up years. Therefore, routine coronary imaging of asymptomatic, single-stage ASO patients is not justified. | Arterial Switch Operation |
Due to ethical and legal aspects involved in the handling of cadavers and animals the synthetic simulators are an alternative for learning how to suture technique plus the practice of various procedures such as incision and surgical flap. In this context, this paper describes and propose the use of a synthetic model manufactured from plates of ethylene-vinyl acetate (EVA) to teach primary surgical skills in medical students with no previous exposure to surgery. The model that provides the convenience of being easily reproducible, allowing the students in training can thus improve their skills before applying the technique in clinical practice. | Wound Closure Techniques |
Antifertility effects of an aqueous leaf extract of Oldenlandia affinis on male rats were investigated. The extract was administered intraperitoneally in sexually mature male rats at a dose of 24 mg/rat (n=8) for a total of eight injections over a 4 week period. There was a decrease in testis weights but all other accessory sex organs and vital organ weights were not affected by treatment with O. affinis extract. Testis histology revealed fewer spermatozoa or azoospermic seminiferous tubules in treated animals compared to controls with no change in neither tubule thickness nor Sertoli cell structure. O. affinis treatment caused a 17% decrease in sperm motility but there was no change in cauda epididymal sperm counts. However, serum testosterone levels decreased significantly (P<0.05) in the experimental group (602.4 +/- 57 ng/dL) compared to controls (808.9 +/- 55 ng/dL). These preliminary results show that the aqueous leaf extract of O. affinis suppresses fertility parameters in male rats. | Oldenlandia |
Post-thrombotic syndrome (PTS) can be debilitating to patients and have a major economic impact on health-care services. It arises after deep venous thrombosis (DVT) due to residual venous obstruction or valvular reflux, leading to increased venous pressure in the microcirculation. While the inflammatory process at the time of DVT may aid thrombus resolution, it may also promote destruction of venous valves. The diagnosis of PTS is principally clinical and patients typically complain of leg heaviness, swelling, pain, itching, cramps, ulcer and signs of lipodermatosclerosis. Several clinical scales or classifications have been used but it is recommended that Villalta scale is the most suitable. Risk factors for PTS include a proximal DVT and recurrent thrombosis as well as obesity and prior varicose veins. Poor quality of anticoagulation control may also be a factor. Established PTS is usually managed along the same lines as chronic venous hypertension with compression therapy and leg elevation. Surgery has only a limited role but may benefit some patients. Further trials are desperately needed to define the role of acute thrombolysis and mechanical thrombectomy, which seem to be promising treatments in the studies to date. For patients who have had a DVT more attention should be given to prescribing and using compression hosiery. | Postphlebitic Syndrome |
Ease of transfusion and high long-term survival rate were obtained when whole blood was administered via the corpus cavernosum of the penis and removed from the orbital sinus of male C57Bl mice. When 2 volumes of blood are replaced approximately 14% of pre-transfusion red cells remain after hematocrit corrections are made. The post-transfusion hematocrit levels dropped 19%, probably the result of leakage, which is difficult to avoid." | Exchange Transfusion, Whole Blood |
Edwardsiellosis is one of the most important bacterial diseases in eels. Edwardsiella tarda (E. tarda) isolates (n=94) from diseased eels were screened against the eight most commonly used antimicrobial agents in aquaculture in Taiwan. These isolates were highly susceptible to ampicillin, amoxicillin, florfenicol, oxolinic acid and flumequine. In total, 20 of the 94 (21.3 per cent) isolates tested were resistant to oxytetracycline (OTC). Among the 20 tetracycline-resistant E. tarda isolates, tet(A) was the predominant resistance determinant and was detected in 100 per cent of the isolates, whereas 90 per cent of these isolates carried the tet(M) determinant. The efflux pump inhibitor omeprazole reduced the minimum inhibitory concentrations (MICs) of OTC for these isolates by twofold to eightfold, suggesting that an intact efflux pump, presumably encoded by tet(A), is required for high-level tetracycline resistance. Real-time PCR experiments showed that increased expression levels of tet(A) and tet(R) could contribute to OTC resistance. Southern blot hybridisation also confirmed that the 20 OTC-resistant E. tarda isolates all carried the TetA determinant on a plasmid that is approximately 50 or 70 kb in size, and restriction fragment length polymorphisms (RFLP) showed that the tet(A) gene was located on an 8-10 kb EcoRI fragment in all of these plasmids. The same plasmid type and RFLP patterns were detected across different farms in the same region, but differences in their pulsed-field gel electrophoresis (PFGE) patterns were observed. This suggests a possible role for horizontal spreading and local transmission of the plasmid in the OTC-resistant E. tarda population of eels from two different geographic origins. | Tetracycline Resistance |
To search for efficient agricultural antifungal lead compounds, 39 Chimonanthus praecox derivatives were designed, synthesized, and evaluated for their antifungal activities. The structures of target compounds were fully characterized by (1)H NMR, (13)C NMR, and MS spectra. The preliminary bioassays revealed that some compounds exhibited excellent antifungal activities in vitro. For example, the minimum inhibitory concentration (MIC) of compound b15 against Phytophthora infestans was 1.95 microg mL(-1), and the minimum inhibitory concentration (MIC) of compound b17 against Sclerotinia sclerotiorum was 1.95 microg mL(-1). Therefore, compounds b15 and b17 were identified as the most promising candidates for further study. | Calycanthaceae |
While research in previous decades demonstrated a link between the pulvinar nucleus of the thalamus and visual selective attention, the pulvinar's specific functional role has remained elusive. However, methodological advances in electrophysiological recordings in non-human primates, including simultaneous recordings in multiple brain regions, have recently begun to reveal the pulvinar's functional contributions to selective attention. These new findings suggest that the pulvinar is critical for the efficient transmission of sensory information within and between cortical regions, both synchronizing cortical activity across brain regions and controlling cortical excitability. These new findings further suggest that the pulvinar's influence on cortical processing is embedded in a dynamic selection process that balances sensory and motor functions within the large-scale network that directs selective attention. | Pulvinar |
An improved separation procedure is described for isolating five leghemoglobin components from the nodules of soybean plants. After a preliminary oxidation with ferricyanide, and separation from endogenous nicotinate at pH 9.2, the ferrileghemoglobins are separated by DEAE-cellulose chromatography using gradient elution with acetate buffer (pH 5.2). The components have been characterized by their acetate and nicotinate binding affinities, gel electrophoretic, visible, and circular dichroic spectra in the ultraviolet, Soret and visible regions. Two formerly unresolved components of leghemoglobin c have indistinguishable circular dichroic, electrophoretic, and ligand binding properties, but differ in their spin states as judged by their visible spectra, their amino acid analyses, and their tryptic maps. | Leghemoglobin |
The authors presented and discussed the results of the use of the natural and instrumental physical methods for therapy, prevention and rehabilitation of 280 patients with coronary heart disease (CHD) and 300 patients with arterial hypertension (AH). The efficacy of the optimized use of a number of physical factors (precardial and segmental massage, low frequency magnetic field) was shown in the CHD and AH patients by the short- and long-term follow-up results. The authors substantiated the appropriateness of expanding the concept nonpharmacological" methods proceeding from its practical meaning at the present-day stage of CHD and AH control." | Physical Therapy Modalities |
The promoters of many genes whose expression is rapidly and transiently increased upon growth factor or mitogen stimulation of susceptible cells harbor a common regulatory element, the serum response element (SRE). The transcription factors that interact with the SRE of these immediate-early genes are being intensively studied so as to elucidate the signal transduction cascades that link cell surface receptors to the SRE, and to determine the mechanisms by which signal-dependent phosphorylation events modulate their function. | ets-Domain Protein Elk-4 |
BACKGROUND: Clinical Competency Committees (CCCs) are charged with making summative assessment decisions about residents. OBJECTIVE: We explored how review processes CCC members utilize influence their decisions regarding residents' milestone levels and supervisory roles. METHODS: We conducted a multisite longitudinal prospective observational cohort study at 14 pediatrics residency programs during academic year 2015-2016. Individual CCC members biannually reported characteristics of their review process and Accreditation Council for Graduate Medical Education milestone levels and recommended supervisory role categorizations assigned to residents. Relationships among characteristics of CCC member reviews, mean milestone levels, and supervisory role categorizations were analyzed using mixed-effects linear regression, reported as mean differences with 95% confidence intervals (CIs), and Bayesian mixed-effects ordinal regression, reported as odds ratios (ORs) and 95% credible intervals (CrIs). RESULTS: A total of 155 CCC members participated. Members who provided milestones or other professional development feedback after CCC meetings assigned significantly lower mean milestone levels (mean 1.4 points; CI -2.2 to -0.6; P < .001) and were significantly less likely to recommend supervisory responsibility in any setting (OR = 0.23, CrI 0.05-0.83) compared with CCC members who did not. Members recommended less supervisory responsibility when they reviewed more residents (OR = 0.96, 95% CrI 0.94-0.99) and participated in more review cycles (OR = 0.22, 95% CrI 0.07-0.63). CONCLUSIONS: This study explored the association between characteristics of individual CCC member reviews and their summative assessment decisions about residents. Further study is needed to gain deeper understanding of factors influencing CCC members' summative assessment decisions. | Committee Membership |
GTP has been found to markedly enhance the formation of CDPdiacylglycerol in rat liver microsomes. The magnitude of the GTP stimulatory effect was influenced by the fatty acid composition of the phosphatidic acid substrate. Heat or proteolytic treatment of microsomal membranes prevented GTP from stimulating liponucleotide formation. Treatment of microsomes with low levels of detergent reduced the stimulatory action of the GTP. The increased synthesis of CDPdiacylglycerol obtained by the addition of GTP to the incubation medium is due to an increase in CTP:phosphatidate cytidylyltransferase activity, rather than to a reduction in the breakdown of either the substrates or product of the reaction. The results suggest that some other protein or enzyme mediates the effect of GTP upon CTP:phosphatidate cytidylyltransferase activity." | Cytidine Diphosphate Diglycerides |
Drug-induced cholestasis has a wide range of clinical presentations, and in a small number of patients, it can progress to severe ductopenia. A 63-year-old woman was referred to our department with progressive cholestasis and hyperbilirubinaemia following a course of flucloxacillin. Despite the comprehensive laboratory, imaging and genetic investigations, no other cause for the cholestasis was demonstrated. Sequential liver biopsies confirmed the development of vanishing bile duct syndrome. She developed significant cachexia and pruritus that did not respond to medical therapy, and hence she was listed for liver transplantation. She underwent liver transplantation 6 months after the initial drug-induced injury. She has remained well with good graft function at 1-year follow-up. The case highlights an extreme form of drug-induced ductopenia and underscores the need for meticulous hepatology input and consideration of liver transplantation in some patients. | Floxacillin |
Acinic cell carcinoma is a tumor that occurs most commonly in the parotid glands. We have experienced a rare case of acinic cell carcinoma of the left maxillary sinus. The patient was a 71-year-old female. She noticed her left nasal congestion and epiphora from left eye in April 1994. She had a history of left maxillary sinus surgery in February, 1972. Antrotomy was performed and histopathological examination of specimen from the maxillary sinus proved acinic cell carcinoma. The tumor was considered to be the recurrence 22 years after initial surgery, because it coincided with the surgical specimen of previous surgery. Radical resection of maxilla was performed for complete resection of tumor with palate reconstruction by left scapula and latissimus dorsi myocutaneous flap. No recurrence is observed for more than 4 years after surgery. Although this tumor is of low grade malignancy, complete resection with adequate surgical margin is advisable due to high incidence of this tumor to recur after long periods of time. | Carcinoma, Acinar Cell |
Leishmania donovani, the causative agent of visceral leishmaniases, is an intracellular pathogen which proliferates within the host macrophages. Analysis of the thiol composition of L. donovani by means of the thiol-specific reagent, 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin, indicated that this organism produces substantial amounts of ovothiol A. This observation was further substantiated by HPLC of extracts of L. donovani after derivatization with bromobimane. L. donovani extracts contained a thiol, the bimane derivative of which had identical retention time and fluorescence quenching to a thiol from Crithidia fasciculata, which had previously been identified as ovothiol A. By comparison, the intracellular bacterial pathogen, Mycobacterium bovis, contained only one major low-molecular-mass thiol, which was assigned the trivial name mycothiol. The structure of the bimane derivative of mycothiol was solved by a combination of one- and two-dimensional 1H and 13C NMR spectroscopy. Spatial relationships in the molecule were further refined by NOE experiments and allowed identification of mycothiol as 1-D-myo-inositol-2-(N-acetyl-L-cysteinyl)amino-2-deoxy-alpha-D-glucopyra noside. This assignment was confirmed by positive-ion fast-atom-bombardment mass spectrometry which gave m/z = 677.6 Da and a sodiated species at 699.6 Da. Analysis of the dansylated hydrolysis products of performic-acid-oxidized mycothiol indicated the presence of 0.85 mol glucosamine and 1.02 mol cysteic acid/mol sulfhydryl groups. Crude extracts of M. bovis contained an enzyme which catalysed the NAD(P)H2-dependent reduction of mycothiol disulfide to the free thiol. Analysis of perchloric acid extracts of Mycobacterium tuberculosis H37RV indicated the presence of a thiol which comigrated with mycothiol, both as the free thiol and as the 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin and bimane derivatives, on reverse-phase HPLC. The significance of these findings in terms of the evasion of the host defense mechanisms by leishmania parasites and mycobacteria is considered. | Methylhistidines |
BACKGROUND: Few terms and concepts have been so extensively debated in dentistry as the words 'centric relation' (CR). Debates involve its biological, diagnostic and therapeutic usefulness. METHODS: A review of the literature on the current concepts on CR as a diagnostic or therapeutic aid in dentistry was provided. Clinical trials assessing the superiority of one CR recording method over the others to identify patients with temporomandibular disorders (diagnostic use) or to manage patients with prosthodontic or orthodontic needs (therapeutic use) were tentatively included. RESULTS: Due to the absence of literature addressing either of the above targets, a comprehensive overview was provided. The diagnostic use of CR as a reference position to identify the correct position of the temporomandibular joint condyle within the glenoid fossa is not supported and lacks anatomical support. From a therapeutic standpoint, the use of CR can be pragmatically useful in prosthodontics as a maxillo-mandibular reference position when occlusal re-organization is warranted and/or when the position of maximum intercuspation is no longer available. CONCLUSIONS: The derived occlusal goals from a diagnostic misuse of CR are generally the result of circular reasoning, that is a technique is based on the recording of a certain condylar position that is believed to be 'ideal' and the treatment is considered successful when such position is shown by the specific instrument that was manufactured for that purpose. The term 'Centric Relation' might be replaced with the term 'Maxillo-Mandibular Utility Position'. | Centric Relation |
PURPOSE: To determine the incidence and clinical characteristics of angiographic subtypes of polypoidal choroidal vasculopathy (PCV). METHODS: It is a prospective, multicenter, cross-sectional study. Patients with newly diagnosed exudative macular degeneration are classified into PCV, age-related macular degeneration (AMD), and retinal angiomatous proliferation. Polypoidal choroidal vasculopathy is further classified into two subtypes depending on the presence (Type 1: polypoidal choroidal neovascularization) or absence (Type 2: typical PCV) of feeder vessels on indocyanine green angiography. RESULTS: We enrolled 169 patients: 76 (45%) with PCV, 75 (44.4%) with AMD, and 14 (8.3%) with retinal angiomatous proliferation. Of the patients with PCV, 20 (26%) were classified as Type 1 PCV and 56 (74%) were classified as Type 2 PCV. The Type 1 PCV had a similar mean age compared to the AMD group (73.1 +/- 9.6 vs. 75.6 +/- 8.8 years, P = 0.281) and the Type 2 PCV (68.8 +/- 9.6 years) was younger than the AMD group (P < 0.001). Type 1 PCV presented with worse visual acuity compared with the AMD. Both PCV subtypes had a higher incidence of hemorrhagic complications (85% and 75% respectively). CONCLUSION: Type 2 PCV is more common than Type 1 PCV in Taiwan. Our results support the hypothesis that polypoidal choroidal neovascularization and typical PCV may be distinct entities. | Choroid Diseases |
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder that accounts for approximately 30 % of adult leukemias and 25 % of Non-Hodgkin lymphomas (NHL). It is the most common form of leukemia in the western world (incidence 3-5/100 000). Elderly people are mainly affected, median age at diagnosis is around 70 years and there is a slight predominance in men. The etiology of the disease is unknown. The initial symptoms are nonspecific. Cervical lymphadenopathy and splenomegaly followed by general fatigue are seen most commonly. Other possible symptoms include night sweats, fever, loss of weight (so-called B symptoms) and frequent infections. Several patients develop autoimmune complications as autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia (ITP). To confirm the diagnosis more than 5000 B-lymphocytes/microl need to be present. The expression of the typical surface markers CD5, CD19, and CD23 has to be confirmed by flow cytometry. Imaging studies as X-ray of the chest, ultrasound of the abdomen, or CT scan are used to assess the degree of lymphadenopathy or organomegaly. A bone marrow biopsy is not mandatory for the diagnosis. According to the European Binet staging system, CLL is divided into 3 stages (A, B and C). Patients in Binet stage A have 0 to 2 areas of node or organ enlargement with normal levels of hemoglobin and platelets. Binet stage B patients have 3 to 5 areas of node or organ enlargement and normal or slightly decreased levels of hemoglobin and platelets. Binet stage C patients have anemia (hemoglobin < 10 g/dl) and/or thrombocytopenia (platelet counts < 100 000/microl), with or without lymphadenopathy or organomegaly. As there is no survival benefit associated with early intervention, asymptomatic patients with early stage CLL (Binet stage A and B) are usually not treated but are followed on a "watch and wait" principle. Treatment indications include stage Binet C or signs of an active disease as rapidly progressive lymphadenopathy or organomegaly together with physical limitation, B symptoms that cannot be tolerated, rapidly deteriorating blood values, or rapidly increasing leukocyte counts. The patient's physical condition has major impact on the treatment decision. Currently immunochemotherapy with fludarabine, cyclophosphamide and the CD20-antibody rituximab (FCR) is the standard of care in previously untreated and physically fit CLL-patients. An alternative regimen is the combination of bendamustine and rituximab (BR). Physically compromised patients can be treated with the oral drug chlorambucil or with bendamustine with or without rituximab. Due to high morbidity and mortality, allogeneic stem cell transplantation is limited to a small group of patients and should be discussed in a high-risk situation, such as 17p deletion, lack of response to standard therapy or early relapse." | Leukemia, Lymphocytic, Chronic, B-Cell |
46 postmenopausal women with estrogen receptor positive breast cancer entered a phase II study with a novel antiestrogen, toremifene. Patients had either recurrent or primarily inoperable advanced disease. No prior or concurrent cytostatic or hormonal treatment was allowed. Eight patients (17%) achieved complete response (CR), 17 (37%) partial response (PR) and 13 (28%) had stabilization of their disease at least for three months. The mean durations of responses were 52 +, 53 + and 27 + weeks, respectively, with 5 patients in CR, 6 in PR and 1 with no change (NC) still continuing the treatment. No significant differences could be seen in response rates according to the concentration of estrogen receptors or presence of progesteron receptors in this group of patients. Toxicity was not a problem, in general, the treatment was well tolerated. Two side effects (sweating and vertigo) were classified as severe and one patient after achieving PR interrupted the treatment because of tremor. | Toremifene |
Bovine viral diarrhea virus (BVDV) is one of the most important pathogens to the cattle industry, causing a significant economic loss throughout the world. Despite the wide use of various control measures for BVDV, the disease remains prevalent. In this study, we achieved an efficient inhibition of NADL strain replication by plasmid-mediated shRNA targeting conserved regions of the viral genome. To further enhance the inhibiting efficiency, a dual shRNA expression plasmid, which could simultaneously express two different shRNA, was established and showed stronger inhibitory effects on virus replication. Moreover, the antiviral activity induced by the dual shRNA expression system was also evident on other BVDV-1 subgenotypes (BVDV-1a, BVDV-1b and BVDV-1c). Therefore, the dual shRNA system provides a more powerful strategy for inhibiting BVDV replication in a cross-resistance manner." | Diarrhea Virus 1, Bovine Viral |
BACKGROUND: Frozen shoulder is not an uncommon disorder, and steroid injection into the glenohumeral (GH) joint is one of the most well-known approaches for the frozen shoulder. However, their results have been varied with beneficial effects or no additional advantage. With the understanding about the pathological changes taking place in frozen shoulder and the biomechanics involved, we wanted to evaluate the short- and long-term efficacy of steroid injection by a novel three-site (NTS) injection technique and compare it with the single-site injection (SSI). MATERIAL AND METHODS: This was a prospective study with 85 patients including all stages and randomized into two groups. SSI group received steroid injection through posterior approach. NTS group received the same dose of steroid in diluted doses at three sites (posterior capsule, subacromial and subcoracoid). Second sitting was repeated after 3 weeks. Both groups had received the same physiotherapy. The patients were evaluated by CONSTANT score at initial, 3 week, 6 week and 6 month. RESULTS: NTS group patients had significant pain relief and early improvement in activities of daily living ( p < 0.005). Both groups had improvement in shoulder movements but with NTS group, early near-normal scores were attained and sustained after 6 months. About 43% in SSI group could not attain near-normal levels and had relapses. CONCLUSION: The three-site approach to steroid instillation in frozen shoulder is a safe method and provides early recovery and better improvement in shoulder function with less relapses. | Methylprednisolone Acetate |
The feasibility of using normalized cumulative difference attenuation (NCDA) map for tracking the spatial and temporal evolution of temperature during microwave hyperthermia experiment on in-vitro phantoms is explored in this study. The NCDA maps were estimated from the beamformed ultrasound radio frequency (RF) data using a regularized log spectral difference (RLSD) technique. The NCDA maps were estimated at different time instants for the entire period of the experiment. The contour maps of the NCDA and the ground truth temperature map, obtained using an infra-red(IR) thermal camera corresponding to the ultrasound imaging plane, showed that NCDA was able to locate the axial and lateral co-ordinates of the hotspot with the error of <; 1.5 mm axially and <; 0.1 mm laterally. The error in the estimated hotspot area was less than 8 %. This preliminary in-vitro study suggests that NCDA maps estimated using RLSD may have potential in evaluating the spatio-temporal evolution of temperature and may help in the development of ultrasound-based image-guided temperature monitoring system for microwave hyperthermia. | Electromagnetic Radiation |
The toxic diatom genus Pseudo-nitzschia is a growing presence in the Gulf of Maine (GOM), where regionally unprecedented levels of domoic acid (DA) in 2016 led to the first Amnesic Shellfish Poisoning closures in the region. However, factors driving GOM Pseudo-nitzschia dynamics, DA concentrations, and the 2016 event are unclear. Water samples were collected at the surface and at depth in offshore transects in summer 2012, 2014, and 2015, and fall 2016, and a weekly time series of surface water samples was collected in 2013. Temperature and salinity data were obtained from NERACOOS buoys and measurements during sample collection. Samples were processed for particulate DA (pDA), dissolved nutrients (nitrate, ammonium, silicic acid, and phosphate), and cellular abundance. Species composition was estimated via Automated Ribosomal Intergenic Spacer Analysis (ARISA), a semi-quantitative DNA finger-printing tool. Pseudo-nitzschia biogeography was consistent in the years 2012, 2014, and 2015, with greater Pseudo-nitzschia cell abundance and P. plurisecta dominance in low-salinity inshore samples, and lower Pseudo-nitzschia cell abundance and P. delicatissima and P. seriata dominance in high-salinity offshore samples. During the 2016 event, pDA concentrations were an order of magnitude higher than in previous years, and inshore-offshore contrasts in biogeography were weak, with P. australis present in every sample. Patterns in temporal and spatial variability confirm that pDA increases with the abundance and the cellular DA of Pseudo-nitzschia species, but was not correlated with any one environmental factor. The greater pDA in 2016 was caused by P. australis - the observation of which is unprecedented in the region - and may have been exacerbated by low residual silicic acid. The novel presence of P. australis may be due to local growth conditions, the introduction of a population with an anomalous water mass, or both factors. A definitive cause of the 2016 bloom remains unknown, and continued DA monitoring in the GOM is warranted. | Shellfish Poisoning |
The management of Human Immunodeficiency Virus type 1 (HIV-1) infection requires life-long treatment that is associated with chronic toxicity and possible selection of drug-resistant strains. A new opportunity for drug intervention is offered by antivirals that act as allosteric inhibitors targeting two viral functions (dual inhibitors). In this work, we investigated the effects of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) derivatives on both HIV-1 Integrase (IN) and Reverse Transcriptase associated Ribonuclease H (RNase H) activities. Among the tested compounds, the dihydroxyindole-carboxamide 5 was able to inhibit in the low micromolar range (1-18 muM) multiple functions of IN, including functional IN-IN interactions, IN-LEDGF/p75 binding and IN catalytic activity. Docking and site-directed mutagenesis studies have suggested that compound 5 binds to a previously described HIV-1 IN allosteric pocket. These observations indicate that 5 is structurally and mechanistically distinct from the published allosteric HIV-1 IN inhibitors. Moreover, compound 5 also inhibited HIV-1 RNase H function, classifying this molecule as a dual HIV-1 IN and RNase H inhibitor able to impair the HIV-1 virus replication in cell culture. Overall, we identified a new scaffold as a suitable platform for the development of novel dual HIV-1 inhibitors." | Ribonuclease H, Human Immunodeficiency Virus |
L-Citrulline is a non-essential but still important amino acid that is released from enterocytes. Because plasma levels are reduced in case of impaired intestinal function, it has become a biomarker to monitor intestinal integrity. Moreover, oxidative stress induces protein citrullination, and antibodies against anti-citrullinated proteins are useful to monitor rheumatoid diseases. Citrullinated histones, however, may even predict a worse outcome in cancer patients. Supplementation of citrulline is better tolerated compared to arginine and might be useful to slightly improve muscle strength or protein balance. The following article shall provide an overview of L-citrulline properties and functions, as well as the current evidence for its use as a biomarker or as a therapeutic supplement. | Proteostasis |
The role of the lower urinary tract (LUT) is to act as a reservoir for urine at low pressures and to empty at appropriate times. In health the bladder becomes gradually filled during the storage phase, and afferent pathways convey signals of bladder fullness. When deemed to be a socially appropriate time and place, there is a switch from the storage phase to the voiding phase. Voiding, which involves co-ordinated activity between detrusor contraction and urethral sphincter relaxation occurs until the bladder is empty. The level of co-ordinated activity is complex, requiring both voluntary and autonomic control. In health, the control of LUT activity is achieved at several levels involving the peripheral nerves, spinal cord and cerebral cortex. The pathway becomes damaged following neurological disease resulting in LUT dysfunction. This chapter outlines the neural organization and control of micturition and the consequences of neurological disease. | Urination |
INTRODUCTION: Laminectomy/laminoplasty either free or vascularized pedicle flap is currently performed with a variety of expensive instruments. Use of Tudor Edwards rib shears to perform above procedure is described. MATERIALS AND METHODS: Tudor Edwards rib shear was used to cut lamina in 18 cases for a variety of spinal lesions. Depending upon the size of lesion, laminectomy/laminoplasty was required for 2 to 8 levels. Vascularized pedicle laminoplasty or free flap laminoplasty was done with Tudor Edwards rib shears. Ligamentum flavum and interspinous and supraspinous ligaments were preserved in cases of vascularized pedicled laminoplasty, which was carried out in 12 cases. Free flap laminoplasty was carried out in 6 cases. RESULTS: In all our cases, laminectomy was successfully achieved with rib shears without any injury to the dura or its underlying structures. It was possible to perform vascularized pedicle laminoplasty or free flap laminoplasty in all cases. Laminectomy was easier to perform in the cervical region and dorsal region, while it was difficult in the lumbar region due to the wider, thick lamina and its angulation, especially in adults. CONCLUSION: Laminectomy/laminoplasty with Tudor Edwards rib shears is quick, safe, and easy. Beveled cut edges with minimal bony loss prevents sinking of laminoplasty, thereby facilitates lamina fixation. This is an alternative method of performing laminectomy/laminoplasty, especially for those not having accessibility to expensive equipment. | Laminoplasty |
Spatial organization of chromosome territories and interactions between interphase chromosomes themselves, as well as with the nuclear periphery, play important roles in epigenetic regulation of the genome function. However, the interplay between inter-chromosomal contacts and chromosome-nuclear envelope attachments in an organism's development is not well-understood. To address this question, we conducted microscopic analyses of the three-dimensional chromosome organization in malaria mosquitoes. We employed multi-colored oligonucleotide painting probes, spaced 1 Mb apart along the euchromatin, to quantitatively study chromosome territories in larval salivary gland cells and adult ovarian nurse cells of Anopheles gambiae, An. coluzzii, and An. merus. We found that the X chromosome territory has a significantly smaller volume and is more compact than the autosomal arm territories. The number of inter-chromosomal, and the percentage of the chromosome-nuclear envelope, contacts were conserved among the species within the same cell type. However, the percentage of chromosome regions located at the nuclear periphery was typically higher, while the number of inter-chromosomal contacts was lower, in salivary gland cells than in ovarian nurse cells. The inverse correlation was considerably stronger for the autosomes. Consistent with previous theoretical arguments, our data indicate that, at the genome-wide level, there is an inverse relationship between chromosome-nuclear envelope attachments and chromosome-chromosome interactions, which is a key feature of the cell type-specific nuclear architecture. | Polytene Chromosomes |
Twenty six propargylamine mycophenolate analogues were designed and synthesized from mycophenolic acid 1 employing a key step A(3)-coupling reaction. Their cytotoxic activity was examined against six cancer cell lines. Compounds 6a, 6j, 6t, 6u, and 6z exhibited selective cytotoxicity towards neuroblastoma (SH-SY5Y) cancer cells and were less toxic to normal cells in comparison to the lead compound, MPA 1 and a standard drug, ellipticine. Molecular docking results suggested that compound 6a is fit well in the key amino acid of three proteins (CDK9, EGFR, and VEGFR-2) as targets in cancer therapy. The propargylamine mycophenolate scaffold might be a valuable starting point for development of new neuroblastoma anticancer drugs. | Pargyline |
The spectrophotometric method for the determination of carboxyhemoglobin (HbCO) in blood reported by Fretwurst and Meinecke was modified so as to give the same values of percentage HbCO (HbCO%) as those determined by the oxygen electrode method. Values of HbCO% of nine practical samples determined by both the oxygen electrode method and the present method were nearly identical regardless of the presence of methemoglobin (Met-Hb) in blood. The present method is suitable for forensic practice. | Methemoglobin |
BACKGROUND: Different systems contributing to copper homeostasis in bacteria have been described in recent years involving periplasmic and transport proteins that provide resistance via metal efflux to the extracellular media (CopA/Cue, Cus, Cut, and Pco). The participation of these proteins in the assembly of membrane, periplasmic and secreted cuproproteins has also been postulated. The integration and interrelation of these systems and their apparent redundancies are less clear since they have been studied in alternative systems. Based on the idea that cellular copper is not free but rather it is transferred via protein-protein interactions, we hypothesized that systems would coevolve and be constituted by set numbers of essential components. RESULTS: By the use of a phylogenomic approach we identified the distribution of 14 proteins previously characterized as members of homeostasis systems in the genomes of 268 gamma proteobacteria. Only 3% of the genomes presented the complete systems and 5% of them, all intracellular parasites, lacked the 14 genes. Surprisingly, copper homeostatic pathways did not behave as evolutionary units with particular species assembling different combinations of basic functions. The most frequent functions, and probably because of its distribution the most vital, were copper extrusion from the cytoplasm to the periplasm performed by CopA and copper export from the cytoplasm to the extracellular space performed by CusC, which along with the remaining 12 proteins, assemble in nine different functional repertoires. CONCLUSIONS: These observations suggest complex evolutionary dynamics and still unexplored interactions to achieve copper homeostasis, challenging some of the molecular transport mechanism proposed for these systems. | Periplasmic Proteins |
BACKGROUND AND OBJECTIVES: To update and review the application of dexmedetomidine in anesthesia and intensive care. This study is a comprehensive review of clinical uses, pharmacology, pharmacokinetics, mechanism of action and adverse effects of dexmedetomidine. CONTENT: The effective use of sedative-hypnotic agents and analgesics is an integral part of comfort and safety of patients. Dexmedetomidine is a potent and highly selective alpha-2 adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties, which has been described as a useful and safe adjunct in many clinical applications. It provides a unique conscious sedation", analgesia, without respiratory depression. The current reviewed uses include sedation at Intensive Care Unit-ICU (both adult and pediatric), emergency department, regional and general anesthesia, neurosurgery, sedation for pediatric procedures, awake fiber-optic intubation, cardiac surgery and bariatric surgery. CONCLUSIONS: Dexmedetomidine offers a unique ability of providing both sedation and analgesia without respiratory depression. It is a new agent with a wide safety margin, excellent sedative capacity and moderate analgesic properties. Although its wide use is currently in patients of surgical and non-surgical intensive care units, dexmedetomidine seems to have promising future applications in neuroprotection, cardioprotection and renoprotection. More detailed studies are required to define its role as sedative in critical, neurosurgical and pediatric patients, as anesthesia adjunct and sedative during procedures." | Hypnotics and Sedatives |
Santos, GAd, Numata-Filho, ES, Rosa, TdS, Passos Neves, RV, Simoes, HG, and Moreira, SR. Anaerobic threshold determination in cycle ergometer from rating of perceived exertion. J Strength Cond Res 36(5): 1277-1281, 2022-The objective of the study was to investigate the validity of the rating of perceived exertion threshold (TRPE) for anaerobic threshold (AT) estimation during an incremental test (IT) on a cycle ergometer. Nineteen physically active and healthy men performed an IT on a cycle ergometer. The intensity corresponding to the AT was considered as the point immediately before the abrupt increase in blood lactate concentration ([La]) in the IT. TRPE was determined in the last intensity corresponding to perceptual response previous the 15 arbitrary units (AU) in the 15-point RPE scale. The heart rate (HR), [La], and RPE were obtained at the end of each stage of the IT. There was no significant difference between workload obtained from the AT (150 [120-150] watts) and TRPE (150 [120-150] watts) (p > 0.05). In addition, there were no differences between HR (AT, 139.5 +/- 12.7 b.min-1 vs. TRPE, 141.9 +/- 14.6 b.min-1, p > 0.05) and [La] (AT, 3.1 [2.8-3.2] mM vs. TRPE, 3.1 [2.9-3.7] mM, p > 0.05). There was a strong correlation between the intensities in AT and TRPE during the IT (r = 0.88). A substantial reliability (intraclass correlation coefficient = 0.84 [0.64-0.94 confidence interval 95%]) was evidenced, as well as a substantial agreement between the AT and TRPE intensities (Pc = 0.84), as confirmed by the Bland-Altman plot (-4.7 [-34.2/24.7]). TRPE was a predictor of the AT (beta = 1.146, R = 0.770, SEE = 15.070, p < 0.01). It can be concluded that TRPE is valid for AT estimation during an IT on a cycle ergometer. | Ergometry |
BACKGROUND: Hospitalized children generate up to 152 alarms per patient per day outside of the intensive care unit. In that setting, as few as 1% of alarms are clinically important. How nurses make decisions about responding to alarms, given an alarm's low specificity for detecting clinical deterioration, remains unclear. OBJECTIVE: Our objective was to describe how bedside nurses think about and act upon monitor alarms for hospitalized children. DESIGN, SETTING, PARTICIPANTS: This was a qualitative study that involved the direct observation of nurses working on a general pediatric unit at a large children's hospital. MEASUREMENTS: We used a structured tool that included predetermined categories to assess nurse responses to monitor alarms. Data on alarm frequency and type were pulled from bedside monitors. RESULTS: We conducted 61.3 patient-hours of observation with nine nurses, in which we documented 207 nurse responses to patient alarms. For 67% of alarms heard outside of the room, the nurse decided not to respond without further assessment. Nurses most commonly cited reassuring clinical context (eg, medical team in room), as the rationale for alarm nonresponse. The nurse deemed clinical intervention necessary in only 14 (7%) of the observed responses. CONCLUSION: Nurses rely on clinical and contextual details to determine how to respond to alarms. Few of the alarm responses in our study resulted in a clinical intervention. These findings suggest that multiple system-level and educational interventions may be necessary to improve the efficacy and safety of continuous monitoring. | Clinical Alarms |
Public services are increasingly operating through network governance, requiring those at all levels of the system to build collaborations and adapt their practice. Agent-focused implementation theories, such as 'street-level bureaucracy', tend to focus on decision-making and the potential of actors to subvert national policy at a local level. While it is acknowledged that network leaders need to be adaptable and to build trust, much less consideration has been given to the requirement for skills of 'diplomacy' needed by those at the front line of delivering public services. In this article, drawing on theoretical insights from international relations about the principles of 'multi-track diplomacy', we propose the concept of street level diplomacy, offer illustrative empirical evidence to support it in the context of the implementation of public health (preventative) policies within primary care (a traditionally responsive and curative service) in the English NHS and discuss the contribution and potential limitations of the new concept. The article draws on qualitative data from interviews conducted with those implementing case finding programmes for cardiovascular disease in the West Midlands. The importance of communication and adaptation in the everyday work of professionals, health workers and service managers emerged from the data. Using abductive reasoning, the theory of multi-track diplomacy was used to aid interpretation of the 'street-level' work that was being accomplished. | Diplomacy |
BACKGROUND: Oral health research in children has focused both on identifying the risk factors for dental caries and on the impact the disease has on children's life. AIM: Identifying studies that used the salutogenic theory to investigate positive aspects to promote a healthy condition in preschool children. DESIGN: A literature scoping review was conducted to answer the question: 'What has been produced in scientific literature about children's oral health with a salutogenic theoretical reference?' The checklist preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) was applied. The research was conducted on the databases PubMed, Scopus, and Web of Science with no language, design, country or date restrictions. Three independent reviewers selected the studies to be included in the research, extracted data, and assessed the studies' contribution to the review. RESULTS: Among the 38 studies retained, 10 were included, those were published between 2009 and 2018: five in Brazil, two in the United States of America, and one in Canada, China and India, respectively. All articles were published in English language. Nine studies investigated the relation between the parents'/caretakers' sense of coherence and aspects related to the children's oral health condition. One study investigated health factors among the parents of caries-free children. CONCLUSION: Salutogenic orientation must be included in oral health research, so that salutary and risk factors may coexist, contributing to a new perspective for oral health promotion among children. | Sense of Coherence |
The penicillin tolerance of amino acid-deprived relA+ Escherichia coli is attributed to the stringent response; i.e., relaxation of the stringent response suppresses penicillin tolerance. The beta-lactam-induced lysis of amino acid-deprived bacteria resulting from relaxation of the stringent response was inhibited by cerulenin, or by glycerol deprivation in the case of a gpsA mutant (defective in the biosynthetic sn-glycerol 3-phosphate dehydrogenase). Therefore, beta-lactam-induced lysis of amino acid-deprived cells was dependent on phospholipid synthesis. The lysis process during amino acid deprivation can be experimentally dissociated into two stages designated the priming stage (during which the interaction between the beta-lactam and the penicillin-binding proteins occurs) and the beta-lactam-independent lysis induction stage. Both stages were shown to require phospholipid synthesis. It has been known for some time that the inhibition of phospholipid synthesis is among the plethora of physiological changes resulting from the stringent response. These results indicate that the inhibition of peptidoglycan synthesis and the penicillin tolerance associated with the stringent response are both secondary consequences of the inhibition of phospholipid synthesis. | Bacteriolysis |
Three new alkylated chalcones, villosins A - C (1 - 3), five known analogues, together with ten known coumarins, were isolated from Fatoua villosa. The structures of the new compounds were elucidated by extensive spectroscopic analysis, including 1D-, 2D-NMR, and MS data. Compounds 1 - 3 showed cytotoxicity against five kinds of human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC(50) values ranging from 1.4 +/- 0.1 to 5.7 +/- 0.3 mum. | Digitaria |
Amanitin-induced apoptosis is proposed to have a significant effect on the pathogenesis of liver damage. However, few reports have focused on proteome changes induced by alpha-amanitin (alpha-AMA). Here, we evaluated changes in mitochondrial proteins of hepatocytes in response to 2â¯muM alpha-AMA, a concentration at which alpha-AMA-induced cell damage could be rescued at cellular level by common clinical drugs. We found 56 proteins were differentially expressed in an alpha-AMA-treated group. Among them, 38 proteins were downregulated and 18 were upregulated. Downregulated functional proteins included importer TOMM40, respiratory chain component cytochrome C, and metabolic enzymes of citrate acid cycle such as malate dehydrogenase, which localize on the mitochondrial outer membrane, inner membrane and matrix respectively. Immunoblot analysis showed that alpha-AMA decreased mitochondrial import receptor subunit TOMM40 and cytochrome c accompanied by an increase in the cytosol although their total protein levels were not affected significantly. The mitochondrial membrane potential was also destroyed by alpha-AMA and was restored by the clinical drug silibinin. Immunofluorescence suggested that mitochondrial morphology did not change. Taken together, our results provide further insights into the toxic mechanism of alpha-AMA on hepatocytes. | Alpha-Amanitin |
The crosstalk between cells is important for differentiation of cells. Murine-derived feeder cells, SNL76/7 feeder cells (SNLs) or mouse primary embryonic fibroblast feeder cells (MEFs) are widely used for culturing undifferentiated human induced pluripotent stem cells (hiPSCs). It is still unclear whether different culture conditions affect the induction efficiency of definitive endoderm (DE) differentiation from hiPSCs. Here we show that the efficiency of DE differentiation from hiPSCs cultured on MEFs was higher than that of hiPSCs cultured on SNLs. The qPCR, immunofluorescent and flow cytometry analyses revealed that the expression levels of mRNA and/or proteins of the DE marker genes, SOX17, FOXA2 and CXCR4, in DE cells differentiated from hiPSCs cultured on MEFs were significantly higher than those cultured on SNLs. Comprehensive RNA sequencing and molecular network analyses showed the alteration of the gene expression and the signal transduction of hiPSCs cultured on SNLs and MEFs. Interestingly, the expression of non-coding hXIST exon 4 was up-regulated in hiPSCs cultured on MEFs, in comparison to that in hiPSCs cultured on SNLs. By qPCR analysis, the mRNA expression of undifferentiated stem cell markers KLF4, KLF5, OCT3/4, SOX2, NANOG, UTF1, and GRB7 were lower, while that of hXIST exon 4, LEFTY1, and LEFTY2 was higher in hiPSCs cultured on MEFs than in those cultured on SNLs. Taken together, our finding indicated that differences in murine-feeder cells used for maintenance of the undifferentiated state alter the expression of pluripotency-related genes in hiPSCs by the signaling pathways and affect DE differentiation from hiPSCs, suggesting that the feeder cells can potentiate hiPSCs for DE differentiation. | Feeder Cells |
The aim of the present study was to investigate in vitro toxicological effects of PM2.5 suspensions, their water-soluble fraction and solvent-extractable organics from dust storm on the viability and DNA of rat alveolar macrophages and in vivo toxicological effects of PM2.5 suspensions on DNA of lung cells of rats. PM2.5 samples from dust storm and normal weather were collected in Baotou city, Inner Mongolia Autonomous Region, and Wuwei city, Gansu Province, China, in March, 2004. DNA damage was detected with single cell gel electrophoresis technique and cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The results showed that: (1) In vitro, PM2.5 suspensions, their water-soluble fraction and solvent-extractable organics from both dust storm and normal weather caused a decrease of the cell viability and an increase of DNA damage of rat alveolar macrophages in a dose-response manner; for both Baotou city and Wuwei city, the samples of normal weather showed higher DNA damage than those of dust storm at the highest treated dosage; for both normal weather PM2.5 and dust storm PM2.5, their solvent-extractable organics showed higher DNA damage than the water-soluble fraction. (2) In vivo, PM2.5 from both dust storm and normal weather caused an increase of DNA damage of rat lung cells in a dose-response manner. (3) Baotou city is one of the heavy industrial cities, while Wuwei is one of agricultural cities in Northwest region of China. The effects induced by normal weather samples in Baotou city slightly higher than those in Wuwei city on DNA damage, though there was no significant difference was found between two cities. These results lead to conclusions that dust storm PM2.5 as well as normal weather PM2.5 could lead to DNA damage and the organic compounds and the insoluble particle-core might be the main contributors to DNA damage. Our results suggest that the risk of health effects may be greater during dust storms because dust storm PM2.5 whose airborne mass were much higher. Further studies are needed to determine the components of dust storm particles that may contribute to the particle toxicity. | Macrophages, Alveolar |
INTRODUCTION: Wolf-Hirschhorn syndrome (WHS) is a chromosome pathology produced by a deletion in the distal region of the short arm of chromosome 4. It is characterised by the presence of a peculiar phenotype, delayed growth, delayed psychomotor development and epilepsy. AIMS: To describe the characteristics of a series of children with WHS, including the mean amount of time spent on reaching the diagnosis, and to evaluate the opinion of the families about the diagnostic process. PATIENTS AND METHODS: The researchers contacted the National WHS Association and, through them, contact was established with 29 families affected by the condition. Information was collected about the clinical features of the child and the opinion about the diagnostic process, and the families were asked to present medical reports that confirmed the information they had given. Once a database of information about the patients had been created, it was submitted to a statistical analysis. RESULTS: Information was obtained on 27 families. The mean age of the patients is currently 6.94 +/- 6.37 years. The mean age of diagnosis was 14.34 months. Delayed intrauterine growth exists in 92.6% of the pregnancies. Epilepsy is present in 92.6% of patients, 44.4% of them in monotherapy. Delayed psychomotor/cognitive development exists in all the patients. Thirty-three per cent of them can walk unaided. The parents rated the treatment offered by physicians with a mean score of 7.25 +/- 2.17 and the information they were provided with was given a score of 6.29 +/- 2.11. CONCLUSIONS: No references have been found regarding the mean age of diagnosis for WHS. In our sample there are important variations in this respect, possibly influenced by the phenotype of the case and the doctor's own experience. The clinical characteristics are similar to the ones that were expected. The estimated degree of dependence is high and, in contrast, the quality of the information received by the family is low. | Wolf-Hirschhorn Syndrome |
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