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Dietary supplements are widely used at all levels of sport. Changes in patterns of supplement use are taking place against a background of changes in the regulatory framework that governs the manufacture and distribution of supplements in the major markets. Market regulation is complicated by the increasing popularity of Internet sales. The need for quality control of products to ensure they contain the listed ingredients in the stated amount and to ensure the absence of potentially harmful substances is recognized. This latter category includes compounds prohibited under anti-doping regulations. Several certification programmes now provide testing facilities for manufacturers of both raw ingredients and end products to ensure the absence of prohibited substances. Athletes should carry out a cost-benefit analysis for any supplement they propose to use. For most supplements, the evidence is weak, or even completely absent. A few supplements, including caffeine, creatine, and bicarbonate, are supported by a strong research base. Difficulties arise when new evidence appears to support novel supplements: in recent years, beta-alanine has become popular, and the use of nitrate and arginine is growing. Athletes seldom wait until there is convincing evidence of efficacy or of safety, but caution is necessary to minimize risk. | Dietary Supplements |
This study aimed to assess the prevalence of seven periodontal marker pathogens, before implant placement and 1 yr after loading, in periodontally healthy individuals and to assess the long-term effectiveness of pre-implant reduction of pathogens to below threshold levels. In 93 individuals needing single tooth replacement, pooled subgingival microbiological samples from standard sites were cultured and analyzed before implant treatment and 1 yr after loading. Threshold levels commonly used in periodontology to predict periodontal breakdown were applied. Subjects with levels of pathogens above these thresholds received initial periodontal treatment including systemic antibiotics when indicated. At baseline, 49.5% of periodontally healthy subjects harboured one or more marker pathogens above threshold levels. Periodontal treatment reduced the pathogen levels below threshold values in 78.3% of these initially colonized subjects. In all cases Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were reduced to below threshold. At 1 yr after loading, periodontal pathogens were present above threshold levels in 74.1% of all subjects. It is concluded that in almost half of periodontal healthy individuals the subgingival biofilm harbours periodontal pathogens above threshold values. Long-term effectiveness of pre-implant reduction of the selected marker pathogens appeared limited in our patient population, making pre-implant reduction unpredictive for post-implant levels of these pathogens. Thus, considering the applied microbiological criteria, generalized pre-implant microbiological testing is not contributory in periodontally healthy subjects. | Campylobacter rectus |
The preferred treatment for this lesion should be the total resection of the umbilical polyp with a mini-laparotomy because residual intestinal mucosa at the umbilicus can be confirmed to eliminate the risk of recurrence. | Umbilicus |
OBJECTIVES: (1) Evaluate impact of FCR on provider satisfaction and collaboration. (2) Evaluate impact of FCR on parent satisfaction with provider communication. METHODS: Collaboration and Satisfaction about Care Decisions (CSACD) questionnaire was given to staff on 4 patients 2 days a week for 5 weeks prior to and 6 months after implementation of FCR. Parents received a Parents Stress Scale and Neonatal Instrument of Parent Satisfaction before discharge, prior to and 6 months after starting FCR. RESULTS: 278/288 (97%) staff surveys were completed, 142 pre and 136 post. On the CSACD survey NNPs and fellows showed increased (p < 0.05) collaboration and satisfaction post FCR. No group had decreased satisfaction. Twenty-eight of 45 (62%) parent surveys were completed, 12 pre and 16 post. Parents' satisfaction scores increased (p < 0.01) pre vs. post on survey items regarding communication, meeting with physicians, and obtaining information about their infants. CONCLUSIONS: FCR was associated with enhanced collaboration among team members for NNPs and fellows. Parents' satisfaction scores increased post FCR on survey items regarding communication. Since NNPs and fellows are the primary communicators with parents, the increased satisfaction may reflect improved communication due to FCR. This added opportunity for open dialogue may also contribute to the increased parent satisfaction. | Intensive Care, Neonatal |
Recent studies have highlighted the necessity to thoroughly evaluate medicinal plants due to their therapeutic potential. The current study delves into the phytochemical profile, antioxidant capacity, and hepatoprotective effect of Andrographis paniculata. The investigation specifically targets its effectiveness in mitigating liver dysfunction induced by carbon tetrachloride (CCl(4)) in Wistar albino rats, aiming to uncover its promising role as a natural remedy for liver-related ailments. A. paniculata leaf extract was screened for phytoconstituents and antioxidant and hepatoprotective effects in Wistar albino rats against CCl(4)-induced liver dysfunction. Phytochemical analysis revealed the presence of flavonoids, alkaloids, and phenolic compounds in all extracts. The phenolic concentration ranged from 10.23 to 19.52 mg gallic acid per gram of the sample, while the highest flavonoid concentration was found in the ethanol fraction (8.27 mg rutin equivalents per gram). The antioxidant activity varied from 10.23 to 62.23. GC-MS analysis identified several phytochemicals including octadecanoic acid, stigmasterol, phenanthrenecarboxylic acid, and others. Effects of the ethanol extract of A. paniculata were evaluated in four groups of animals. Biochemical estimations of serum glutamine oxaloacetate transaminase, serum glutamine pyruvate transaminase, and serum bilirubin were significantly higher (p < 0.05) in the CCl(4)-treated group. Treatment with 300 mg/kg b.w. of the ethanol extract of A. paniculata significantly (p < 0.05) decreased these serum enzymes. Lipid peroxidation levels in carbon tetrachloride-treated animals showed a substantial (p < 0.05) rise when compared to untreated animals, while the lipid peroxidation levels were considerably (p < 0.05) reduced after treatment with ethanol extract at 300 mg/kg b.w. Liver biochemical catalase activities were significantly reduced in the carbon tetrachloride-treated animals. The results of this study conclusively demonstrate that A. paniculata extracts are a rich source of phytochemicals and possess significant antioxidant, free radical scavenging, and hepatoprotective properties. | Andrographis paniculata |
Penicillin G acylase (PGA), as a key enzyme, is increasingly used in the commercial production of semi-synthetic beta-lactam antibiotics (SSBAs). With the substitution of conventional chemical synthesis by emerging bioconversion processes, more and more PGAs fermented from different types of strains such as Escherichia coli (E. coli, ATCC 11105), Achromobacter sp. CCM 4824 and Providencia rettgeri (ATCC 31052) have been used in this kind of enzymatic processes. As an intermediate reaction catalyst, PGA protein and its presence in the final products may cause a potential risk of human allergic reaction and bring challenges for both quality and process controls. To achieve qualitative and quantitative analysis of PGAs and their residues in SSBAs, a tryptic digestion coupled with liquid chromatography - tandem mass spectrometry (LC-MS/MS) method was developed and proposed because of advantages like high selectivity and sensitivity. A suitable filter aided sample preparation (FASP) method was also used to remove matrix interference and to enrich the target PGA retained in the ultrafiltration membrane for an efficient enzymatic hydrolysis and subsequent accurate MS detection. Finally, twelve batches of PGAs from eight companies were identified and categorized into two types of strains (E. coli and Achromobacter sp. CCM 4824) using proteomic analysis. In total nine batches of five types of SSBAs (amoxicillin, cephalexin, cefprozil, cefdinir and cefaclor) from eight manufacturers were selected for investigation. Trace levels of PGA residual proteins ranging from 0.01 to 0.44 ppm were detected in six batches of different SSBAs which were far lower than the safety limit of 35 ppm reported by DSM, a manufacturer with expertise in the production of SSBAs by enzymatic processes. The developed FASP with LC-MS/MS method is superior to traditional protein assays in terms of selectivity, sensitivity and accuracy. Moreover, it could provide in-depth analysis of amino acid sequences and signature peptides contributing to assignment of the strain sources of PGAs. This method could become a promising and powerful tool to monitor enzymatic process robustness and reliability of this kind of SSBAs manufacturing. | Penicillin Amidase |
Four species of Prunella L. (Prunella vulgaris L., Prunella laciniata L., Prunella grandiflora L. and Prunella orientalis Bornm.) belong to the family of Lamiaceae and representing popular Western and Chinese herbal medicine were examined for the content of phenolic compounds. Phenolic acids (rosmarinic acid, caffeic acid, ferulic acid, chlorogenic acid, protocatechuic acid), flavonoids (rutin, quercetin) in different quantitative proportions depending on extracts were determined by the rapid, selective and accurate method combining solvent/acid hydrolysis extraction and high performance liquid chromatography-diode array detection (HPLC-DAD). Water, methanol, butanol, acetonitrile, ethyl acetate, hexane and their acidic solutions were used to examine the efficiency of different solvent systems for the extraction of phenolic compounds. Acid hydrolysis extraction was established as the most suitable extraction method for phenolic compounds. | Prunella |
A patient with Ackerman's verrucous carcinoma located on the transitional epithelium of the lower lip is described. No previous cases have been reported with this location. The clinical course was similar to verrucous carcinoma arising on other areas of skin or mucosae. Viral particles were not found on ultrastructural studies. The response to conservative surgical treatment was excellent. | Carcinoma, Papillary |
Linezolid is a novel antibiotic administrable by the intravenous as well as the oral route. It is aimed by its re-imbursement conditions at treating proven beta-lactam- or glycopeptide-resistant staphylococcal and enterococcal infections in the hospital and post-discharge outpatient. It has various indications: pulmonary infections, complicated skin and soft tissue infections, infections in the febrile neutropenic patient, urinary tract infections, intra-abdominal infections, chronic osteitis. Bacteriologic documentation of the infection is required to avoid overconsumption and development of resistance. The oral forms exhibit complete bio-availability. Caution is recommended with regard to linezolid's MAO inhibitory effect and the risk of thrombocytopenia requiring weekly hematologic monitoring. | Acetamides |
There is a growing body of evidence that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. Indeed, large clinical trials have demonstrated a substantial benefit of the blockade of this system for cardiovascular-organ protection. Although several types of angiotensin II type 1 (AT1) receptor blockers (ARBs) are commercially available for the treatment of patients with hypertension, comparisons of the binding affinity to AT1 receptor among them remain to be elucidated. In this study, we examined the dissociation rate of several ARBs from AT1 receptor in vitro. Angiotensin II time-dependently dissociated telmisartan, olmesartan, candesartan, valsartan, losartan and an active metabolite of losartan, EXP3174, from membrane components containing human AT1 receptor The dissociation rate constant of each ARB was 0.003248, 0.004171, 0.005203, 0.009946, 0.01027 and 0.008561 min(-1), with corresponding half-lives of 213, 166, 133, 70, 67 and 81 min, respectively. These results demonstrate that telmisartan has the strongest binding affinity to AT1 receptor among various ARBs examined herein. The rank order of affinity was telmisartan > olmesartan > candesartan > EXP3174 > or = valsartan > or = losartan. The present findings suggest that telmisartan (Micardis) may have long-lasting blood pressure-lowering effects and superior cardioprotective properties in patients with hypertension due to its strongest AT1 receptor antagonistic ability." | Angiotensin II Type 1 Receptor Blockers |
The continued recognition process of dental public health as a specialty of dentistry served as an opportunity for the specialty to rediscover and reevaluate itself. What it found was a discipline that has evolved for 38 years to address the issues of a dynamic society. Dr. Abraham Kobren, ADA past-president has stated that public health dentistry stands as the dental conscience of the nation. The changes in dental public health mirror both changes in society and the technical changes occurring in dentistry. Identifying diseases in children is giving way to identifying diseases in adults. Prevention for adults is taking on as much importance as is prevention in children. Access to dental care for the poor and homeless is as much a problem as is access to care for people with infectious diseases. Infection control, technology transfer, national oral health objectives, and a myriad of new financing mechanisms are some areas of change. What has remained constant is the specialty's goal to improve the oral health of the public, and its commitment to work through organized community efforts" to achieve this goal." | Public Health Dentistry |
PURPOSE: To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats. METHODS: Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days. RESULTS: The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-alpha (TNF-alpha) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, gamma-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. CONCLUSION: PFE could protect the kidney against acute renal toxicity induced by CdCl2. | Pyracantha |
In this paper, I contrast two mathematically equivalent ways of modeling the evolution of altruism, namely the classical inclusive fitness approach and a more recent, direct fitness" approach. Though both are usually considered by evolutionists as mere different ways of representing the same causal process (i.e. that of kin selection), I argue that this consensus is misleading, for there is a fundamental ambiguity concerning the causal interpretation of the DF approach. Drawing on an analogy between the structure of inclusive fitness theory and that of causal decision theory (Stalnaker, 1972), I show that only the inclusive fitness framework can provide us with a proper, and unambiguous causal partition of the relevant variables involved in the evolution of altruism." | Decision Theory |
INTRODUCTION: The efficacy of Nigella sativa supplementation for asthma control remains controversial. We conduct a systematic review and meta-analysis to explore the influence of Nigella sativa supplementation on asthma control. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of Nigella sativa supplementation for asthma control. This meta-analysis is performed using the random-effect model. RESULTS: Four RCTs are included in the meta-analysis. Overall, compared with control group for asthma, Nigella sativa supplementation is associated with increased ACT scores (Std. MD = 0.50; 95% CI = 0.11 to 0.88; P = 0.01), FEV1 (Std. MD = 1.84; 95% CI = 0.07 to 3.60; P = 0.04), but demonstrates no obvious impact on PEF (Std. MD = 3.11; 95% CI = -1.30 to 7.52; P = 0.17), IL-4 (Std. MD = -0.31; 95% CI = -1.21 to 0.59; P = 0.50), or IFN-gamma (Std. MD = 1.11; 95% CI = -0.44 to 2.67; P = 0.16). CONCLUSIONS: Nigella sativa supplementation may provide additional benefits for the treatment of asthma. | Nigella |
During the last 10 years, gene therapy has certainly risen to the forefront of basic science and clinical medicine. Designing more efficient gene delivery systems is currently the holy grail" of genetic therapeutics, because even the most efficient viral vectors do not transfect all cells at the treatment site, which leads to local recurrence in the case of most brain tumors. The use of oncolytic viruses that propagate through tumors may have the best potential for treating skull base lesions in the future. Because many skull base tumors are histologically benign, gene therapy approaches for these tumors may be an excellent first step, as partial killing leading to local control with minimal morbidity and mortality may soon be possible. The accessibility of these tumors by endovascular approaches is also currently feasible, which could lead to high vector concentrations within the tumor bed, although limiting vector administration and gene expression in the adjacent brain. With advances in vector development, limiting gene expression to tumor cells with transcriptional or transductional targeting, and the application of more toxic gene therapy paradigms, the treatment of many skull base tumors may soon be possible." | Skull Base Neoplasms |
Childhood exanthems are a common cause of skin disease in children. Several new aspects of exanthems are reviewed. Two conditions, unilateral laterothoracic exanthem and asymmetric periflexural exanthem, may be variations of the same disease and could potentially represent a cutaneous reaction to several infectious agents. An eruption that has been called papular-purpuric gloves and socks syndrome is usually, but not invariably, caused by parvovirus B19 infection. Another unusual exanthem, eruptive pseudoangiomatosis, is also discussed. Finally, several new developments in the etiology and disease spectrum of exanthem subitum are emphasized. | Roseolovirus Infections |
The diagnosis of constrictive pericarditis remains a challenge because it is often mimicked by restrictive cardiomyopathy. The last few years have seen numerous advances in our ability to differentiate between these two conditions which often have similar physical findings and hemodynamics. This review begins with a brief history of constrictive pericarditis; this is followed by an extensive discussion of newer etiologies, and then the classical clinical history and physical examination findings are described. Radiologic, electrocardiographic, and angiographic findings are discussed. The hemodynamics of constrictive pericarditis are reviewed. Recent results of echocardiographic and echo-Doppler investigations are presented. Emphasis is placed upon the limitations of M-mode echocardiography in the diagnosis of constrictive pericarditis. The value of echocardiographic Doppler studies of mitral and tricuspid flow velocity patterns, as well as of those in the pulmonary veins and hepatic veins, is described. Nuclear ventriculograms and angiocardiograms tend to show more rapid ventricular filling in constrictive pericarditis than in restrictive cardiomyopathy. Although only a small number of patients has been studied, these evaluations seem to have merit in separating restrictive cardiomyopathy from constrictive pericarditis. The role of computed tomography scanning and magnetic resonance imaging studies of pericardial thickness in confirming the presence of constrictive pericarditis is discussed. Abnormal pericardial thickening (> 3 mm) confirms the diagnosis of constrictive pericarditis, but only if the characteristic hemodynamic pattern is present. The usefulness of endomyocardial biopsy in recognizing specific varieties of restrictive cardiomyopathy is presented.(ABSTRACT TRUNCATED AT 250 WORDS) | Pericarditis, Constrictive |
OBJECTIVE: The aim of this study was to investigate the rate of herpes simplex virus (HSV) shedding from the oral cavity, because recent studies suggest that shedding is more frequent than originally reported. Factors that could influence the rate and duration of shedding from the oral cavity were examined. METHODS: Existing epidemiologic data from 22 reports of HSV shedding from more than 3,500 individuals were analyzed with regard to demographics, frequency of sampling, and methodologic assays. RESULTS: HSV-1 was more likely to be detected than HSV-2 in the oral cavity of asymptomatic persons (7.5 odds ratio, 95% confidence interval 4.4-12.8; P < .0001). The rate of shedding was highly variable among individuals, ranging from none to 92% of days tested, and occurred in seropositive and seronegative individuals. In cell culture studies, the rate of detection on a single day was 6.3%. Polymerase chain reaction studies provided a different picture. HSV-1 DNA was present in 97 of 180 patients (53.9%) at multiple visits, with a rate of daily detection of 33.3%. The mean duration of shedding was between 1 and 3 days, but more than 3 days in about 10% of patients. CONCLUSIONS: At least 70% of the population shed HSV-1 asymptomatically at least once a month, and many individuals appear to shed HSV-1 more than 6 times per month. Shedding of HSV-1 is present at many intraoral sites, for brief periods, at copy numbers sufficient to be transmitted, and even in seronegative individuals. The dental implications of these findings are discussed. | Virus Shedding |
OBJECTIVE: To determine whether treatment with patient-controlled analgesia (PCA) alone or in combination with nonsteroidal anti-inflammatory drugs can prevent postoperative pulmonary complications after cardiac surgery, when compared with conventional nurse-controlled analgesia. DESIGN: Randomized controlled trial. SETTING: University Medical Center. PATIENTS: A total of 120 patients undergoing elective coronary artery bypass grafting. INTERVENTIONS: After extubation of the trachea, 120 patients were randomly allocated to three different methods of postoperative pain relief for 72 hrs. In group 1, patients received PCA with a bolus of 1.5 mg piritramide combined with a 10-min lockout interval. Group 2 patients were treated with a combination of PCA and administration of nonsteroidal anti-inflammatory drugs prescribed three times per day. Patients of group 3 received conventional nurse-controlled analgesia. Postoperative assessment included daily visual analog pain scoring (VAS) and chest radiographs. All chest radiographs were graded for the extent of atelectasis by a radiologist blinded as to treatment using a scale from 0 to 9 for each of the three lung fields of the right and left lungs. MEASUREMENTS AND MAIN RESULTS: Chest radiograph atelectasis scores and VAS values were similar among the three groups on the first and second days. On the third day, the chest radiograph atelectasis scores of the left lower and the right middle lung field were significantly better in the groups treated with PCA alone (4.7 +/- 3.0; 0.3 +/- 1.0) and in combination with nonsteroidal anti-inflammatory drugs (3.9 +/- 1.1; 0.4 +/- 1.2) than in the control group (5.5 +/- 3.1; 0.8 +/- 1.8). Furthermore, on the third day, the VAS values for maximum pain were higher in the control group (42.6 +/- 19.7) compared with the VAS values in the two groups with PCA (32.2 +/- 17.9 and 34.5 +/- 21.0). CONCLUSIONS: PCA significantly decreases postoperative pulmonary atelectasis in patients after coronary artery bypass grafting when compared with nurse-controlled analgesia. In addition, patients treated with PCA experienced a higher quality of analgesia. We therefore conclude that treatment with PCA may reduce respiratory complications after coronary artery bypass grafting. | Pirinitramide |
The most important recent developments concerning chancroid have been in its epidemiology (a tremendous increase in the incidence of the disease in the United States over the past several years), diagnosis (better culture media), and treatment (several newer and older drugs that have been shown to be effective against chancroid in recent studies). | Chancroid |
Cellular accumulation of galactitol has been suggested to cause the apparent dietary-independent, long-term complications in classic galactosemia. Experimental animals rendered hypergalactosemic by galactose feeding accumulate tissue galactitol, as well as millimolar quantities of galactose, and manifest biochemical, physiological and pathological abnormalities which are generally eliminated or curtailed by the concomitant administration of an aldose reductase inhibitor. This includes reduced cellular content of the cyclic polyol, myo-inositol, which like galactitol may function as an alternate intracellular osmolyte. However, the abnormalities detected in experimental galactosemic animals are more compatible with findings in experimental diabetes mellitus than in human galactosemia. Because patients with galactokinase deficiency fail to manifest the CNS and ovarian complications which characterize classic galactosemia, yet during long-term lactose restriction excrete comparable urinary quantities of galactitol, this polyol alone is not likely to play an important role during postnatal life in the pathogenesis of long-term complications. Notwithstanding, a role for either galactitol or myo-inositol in an intrauterine toxicity cannot be dismissed. | Galactitol |
The consultants agreed that dermatofibrosarcoma protuberans is characterized by its persistent growth and locally aggressive behavior. However, they did not all agree on the mode of treatment. Drs. Schuller and Snyderman favored surgical resection of the involved areas including the right cheek, lower eyelid, and any necessary portions of the nasal ala and upper lip. They encouraged the use of Moh's chemosurgery to detect microscopic disease. They were also in agreement regarding reconstruction, suggesting a cervical-facial or bi-lobed flap for the cheek. A full-thickness skin graft was recommended for the lower eyelid with primary closure planned for the lip defect. They disagreed on the use of postoperative radiation therapy. Dr. Schuller elected not to irradiate; Dr. Snyderman favored 60 to 65 Gy post-operatively. Dr. Quivey expressed concern regarding the morbidity from such a large resection and extensive reconstruction and suggested primary radiation therapy with external beam. All three consultants felt that good follow-up would include thorough head and neck examinations with MRI and/or CT scans if there were any concern about tumor recurrence. | Facial Neoplasms |
The Sez6 family consists of Sez6, Sez6L, and Sez6L2. Its members are expressed throughout the brain and have been shown to influence synapse numbers and dendritic morphology. They are also linked to various neurological and psychiatric disorders. All Sez6 family members contain 2-3 CUB domains and 5 complement control protein (CCP) domains, suggesting that they may be involved in complement regulation. We show that Sez6 family members inhibit C3b/iC3b opsonization by the classical and alternative pathways with varying degrees of efficacy. For the classical pathway, Sez6 is a strong inhibitor, Sez6L2 is a moderate inhibitor, and Sez6L is a weak inhibitor. For the alternative pathway, the complement inhibitory activity of Sez6, Sez6L, and Sez6L2 all equaled or exceeded the activity of the known complement regulator MCP. Using Sez6L2 as the representative family member, we show that it specifically accelerates the dissociation of C3 convertases. Sez6L2 also functions as a cofactor for Factor I to facilitate the cleavage of C3b; however, Sez6L2 has no cofactor activity toward C4b. In summary, the Sez6 family are novel complement regulators that inhibit C3 convertases and promote C3b degradation. | Complement C3-C5 Convertases |
This study investigates the influence of the controlled release of bone morphogenetic protein 7 (BMP-7) from cross-linked chitosan microparticles on pre-osteoblasts (OB-6) in vitro. BMP-7 was incorporated into microparticles by encapsulation during the particle preparation and coating after particle preparation. Chitosan microparticles had an average diameter of 700 microm containing approximately 10-15 ng of BMP-7. The release study profile indicates that nearly 98% of the BMP-7 coated on the microparticles was released in a period of 18 days while only 36% of the BMP-7 encapsulated in the microparticles was released in the same time period. Cell attachment study indicated that the BMP-7 coated microparticles have many cells adhered on the microparticles in comparison with microparticles without growth factors on day 10. DNA assay indicated a statistical significant increase (p < 0.05) in the amount of DNA obtained from BMP-7 encapsulated and coated microparticles in comparison with microparticles without any growth factors. A real-time RT-PCR experiment was performed to determine the expression of a few osteoblast specific genes-Dlx5, runx2, osterix, osteopontin, osteocalcin, and bone sialoprotein. The results thus suggest that chitosan microparticles obtained by coacervation method are biocompatible and helps in improving the encapsulation efficiency of BMP-7. Also BMP-7 incorporated in the microparticles is being released in a controlled fashion to support attachment, proliferation and differentiation of pre-osteoblasts, thus acting as a good scaffold for bone tissue regeneration. | Bone Morphogenetic Protein 7 |
Transposons are mobile genetic elements that can relocate from one genomic location to another. As well as modulating gene expression and contributing to genome plasticity and evolution, transposons are remarkably diverse molecular tools for both whole-genome and single-gene studies in bacteria, yeast, and other microorganisms. Efficient but simple in vitro transposition reactions now allow the mutational analysis of previously recalcitrant microorganisms. Transposon-based signature-tagged mutagenesis and genetic footprinting strategies have pinpointed essential genes and genes that are crucial for the infectivity of a variety of human and other pathogens. Individual proteins and protein complexes can be dissected by transposon-mediated scanning linker mutagenesis. These and other transposon-based approaches have reaffirmed the usefulness of these elements as simple yet highly effective mutagens for both functional genomic and proteomic studies of microorganisms. | DNA Footprinting |
According to the literature and the authors' data in patients who died of dysentery Shigellae are found seldom because of postmortem shedding of superficial colonic epithelium infected by them. Shigella adhesion and invasion into the colonocytes are regularly found in the colon biopsies. As shown recently in experiments, Shigella outer membrane proteins forming contact haemolysin" ("virulence plasmid" product) are responsible for their invasion. In the small intestine this cytotoxin is destroyed by trypsin, therefore Shigella invasion takes place in the large intestine where it also lyses vacuole membranes around the bacteria in colonocytes. Widespread cytopathic alterations of the epithelium with a damage to ribosome and protein synthesis, disturbance of vascular permeability and fluid hypersecretion in the small intestine result from Shiga-like enterotoxin-cytotoxin. Extent of the inflammatory leukocyte response depends on the degree of Shigella invasion and multiplication and the destruction of the epithelium. Damages to the endothelium and blood coagulation system resulting occasionally in the infectious-toxic shock, are associated with Shigella destruction by leukocytes and absorption of lipopolysaccharide endotoxin released by them. Interepithelial lymphocytes especially those containing lysosome-like granules (similar to the blood "natural killers") play an important role in the response to Shigella." | Shigella boydii |
Epstein-Barr virus-associated gastric cancer (EBVaGC) accounts for nearly 10% of gastric cancer. Cyclooxygenase-2 (COX-2) plays a crucial role in cancer progression. However, there is no experimental study on the regulation mechanism of EBV on COX-2 in EBVaGC. To understand more about the tumorigenic mechanism of EBVaGC, the study investigated the role of EBV encode latent membrane protein LMP1 and LMP2A in the regulation of COX-2. The expression of COX-2 was examined in EBVaGC and EBV negative gastric cancer (EBVnGC) cell lines. The plasmids were transfected in SGC7901 to overexpress LMP1/2A. Small interfering RNA (si-RNA) targeting LMP1/2A in GT38 and targeting TRAF2 in SGC7901 were used to detect the expression of COX-2. Furthermore, si-ERK1/2 and the MEK inhibitor PD0325901 were used to investigate whether p-ERK participate in the regulation of COX-2 in SGC7901. The overexpression of LMP1 or LMP2A in SGC7901 down-regulates both COX-2 and TRAF2 expression, and knockdown of LMP1 or LMP2A in GT38 resulted in a certain recovery of COX-2 and TRAF2 expression. Moreover, si-TRAF2 indicated that a sharp down-regulation of COX-2. And the decrease of p-ERK also mediates the inhibitory effect of LMP1 on COX-2. In summary, overexpression of LMP1 and LMP2A inhibits COX-2, which is mediated by a decrease of TRAF2, and p-ERK is involved in the inhibition of COX-2 by LMP1 in gastric cancer." | TNF Receptor-Associated Factor 2 |
Tuberculosis (TB) is known for its varied presentation and complications, the most dreaded complication being central nervous system (CNS) TB which includes tuberculoma. We present a case report of an asymptomatic recurrent case of CNS tuberculoma requiring multiple surgeries and prolonged critical care management." | Central Nervous System Bacterial Infections |
A rapid HPLC assay was developed for monitoring the activity of the two proprotein convertases, PACE-4 and furin. Six novel peptide substrates were synthesized containing the minimal PC recognition sequence (Arg-X-X-Arg), as well as tryptophan residue(s) for easy detection. Four of the peptides were cleaved by both PCs and their kinetic parameters determined. Two peptides were not cleaved but were shown to be good negative controls although not inhibitors of either PC. In addition, inhibition curves were plotted and IC(50) values calculated for PACE-4 and furin in the presence of two polyarginine peptides, hexa and deca-D-arginine. | Proprotein Convertases |
The plasminogen activating enzyme system has been exploited and harnessed for therapeutic, mainly thrombolytic benefit for many years. While plasminogen activator-based thrombolysis turned out to be a resounding success, it has become apparent that the plasminogen activating system" per se is not only designed to simply remove fibrin and some other matrix proteins. Indeed, the plasminogen activators and the plasminogen activator inhibitors have important effects on cell signalling through both proteolytic and non-proteolytic means and can promote unwanted side effects, particularly in the brain. Tissue type plasminogen activator (t-PA) was heralded as a fibrin-selective plasminogen activator and subjected to clinical development in the early 1980's initially for the treatment of patients with myocardial infarction. t-PA was given FDA approval in the mid 1990's for use in ischaemic stroke patients, but it could only be administered within a short 3h window post- stroke as later use was associated with an increased risk of intracerebral haemorrhage. Hence only a small percentage of these patients were eligible for thrombolysis to restore blood flow to the brain. Since t-PA-mediated plasmin generation is not only impacting on the cerebral blood clot, extending the therapeutic time window for thrombolysis is not a simple task. The ultimate success will depend on how well the future generation of thrombolytic agents promote efficacious removal of a fibrin clot without promoting collateral damage particularly in the brain." | Carboxypeptidase B2 |
OBJECTIVE: To determine if passive leg raising (PLR) significantly increases cardiac output in a cohort of healthy pregnant women during the third trimester. STUDY DESIGN: Using a noninvasive monitor, baseline hemodynamic measurements for arterial blood pressure, systolic and diastolic blood pressure, heart rate, cardiac output, cardiac index, stroke volume, and systemic vascular resistances were obtained with patients in the semirecumbent position. Measurements were repeated after a 3-minute PLR maneuver in supine, right lateral decubitus, and left lateral decubitus positions. RESULTS: After 10 minutes of bed rest, the cohort's mean baseline heart rate was 80 +/- 12 beats/minute. Baseline stroke volume was 98 +/- 14 mL, mean cardiac output was 7.8 +/- 1.2 L/min, and mean cardiac index was 4.32 +/- 0.63 L/min. The baseline systemic vascular resistance value was 893 +/- 160 dynes/sec/cm(5). Baseline mean arterial blood pressure was 84 +/- 11 mm Hg. Following a PLR maneuver in the supine position, heart rate decreased significantly. No difference was noted in other measurements. Findings were similar with PLR in the left lateral decubitus. PLR in the right lateral decubitus resulted in significantly decreased heart rate, cardiac output, and cardiac index. CONCLUSIONS: PLR did not result in cardiac output recruitment in a cohort of healthy pregnant women during the third trimester. | Pregnancy Trimester, Third |
Cysteine-rich intestinal protein (CRIP) is a zinc-binding protein where the binding domain is in the so-called LIM double zinc finger motif. Methods are described for the preparation of CRIP from rat small intestine. Gel-filtration and ion-exchange chromatography and preparative PAGE gave homogeneous CRIP, based upon analytical PAGE, mass spectrometry and microsequencing. Initial localization of CRIP during chromatography was based on binding of 65Zn radioisotope introduced into the intestine. The stoichiometry of binding by CRIP is less than 2 atoms of zinc per molecule. The metal-binding affinity in vitro is zinc > cadmium > copper > iron, at low metal concentrations. Zinc is the predominant metal bound when these metals are taken up from the intestinal lumen. Zinc binding was not influenced by pH between values of 4.5 to 7.5. Metallothionein has a much greater zinc-binding affinity than CRIP. The tissue concentration of CRIP is of the order of 15-20 micrograms/g of mucosal tissue, suggesting that the protein is more abundant than zinc-finger-containing transcription factors. The metal-binding properties of CRIP are consistent with proposed zinc-related functions for this cytoplasmic protein, which is expressed in the small intestine during the postnatal period. | Zinc Radioisotopes |
The use of personal protective equipment, including a safety harness, is one of the basic methods of protection against falls from a height. The presented studies, using an anthropomorphic dummy, identified the effect on the human body of the dangerous phenomena accompanying safety harness performance during fall arrest. The displacement of the dummy in the safety harness, the mutual displacement of the adjustment buckles and the webbing of the harness, the tightening of the straps on the dummy and the impacts exerted on the head of the dummy by the harness elements were considered. The correlation between the design of the safety harness and the parameters and phenomena in question has been demonstrated. It has been shown that for the purposes of assessment of novel harness designs it is necessary to carry out studies utilizing an anthropomorphic dummy in addition to resistance tests. | Protective Devices |
Clostridium perfringens isolated from sheep and goat with enterotoxaemia at necropsy and from healthy animals at slaughter were typed using specific PCR assays for the detection of the alpha-, beta- and epsilon-toxin genes. Clostridium perfringens isolated from all 52 animals with pathological signs of enterotoxaemia showed the presence of the alpha- and epsilon-toxin genes but were devoid of the beta-toxin gene. These strains could therefore be identified as type D, characteristic for clostridial enterotoxaemia of sheep, lambs and goats. In contrast, Cl. perfringens isolated from 11 of 13 healthy animals only contained the alpha-toxin gene which is typical for type A. Two of the healthy animals contained Cl. perfringens with the alpha- and epsilon-toxin genes. However, when several individual Cl. perfringens colonies were analysed from each of these two animals, only a small percentage was found to contain the epsilon-toxin gene, whereas the majority of the colonies were of type A with the alpha-toxin gene only. This is in contrast to the findings from the diseased animals which contained practically only type D Cl. perfringens. The beta-toxin gene was not found in any Cl. perfringens isolate from goat and sheep. Comparison of the PCR data with results obtained by the classical biological toxin assay using the mouse model showed a good correlation. | Enterotoxemia |
This study examined the associations between the two main kinds of food rejection, neophobia and pickiness, and executive functions in young children. Caregivers of children (n = 240) aged 3-6 years completed measures of their children's food neophobia and pickiness. A battery of tests measured children's executive functions and world knowledge. Children with higher levels of neophobia and pickiness had lower cognitive flexibility scores than children with lower levels of food rejection. Moreover, the association between food neophobia and cognitive flexibility was stronger than the association between food pickiness and cognitive flexibility. Working memory, inhibition, and world knowledge were not related to children's food rejection. These findings unraveled for the first time the negative relationship between cognitive flexibility and the main psychological barriers to dietary variety. These results contribute to a better understanding of the set of cognitive factors that are associated with food rejection in young children." | Avoidant Restrictive Food Intake Disorder |
The non-random distribution of degenerate code words in Bacteriophage MS2 RNA can be explained partially by considerations of the stability of the codon-anticodon complex in prokaryotic systems. Supporting this hypothesis we note that wobble codons are positively selected in codons having G and/or C in the first two positions. In contrast, wobble codons are statistically less likely in codons composed of A and U in the first two positions. Analyses of nucleotides adjacent to 5' and 3' ends of codons indicate a nonrandom distribution as well. It is thus likely that some elements of RNA evolution are independent of the structural needs of the RNA itself and of the translated protein product. | Genetic Code |
4-META and new phosphate-methacrylate resins adhere strongly to dental alloys. However, for strengthening the water durability of the adhesive interface, the oxidation of the alloy surface is indispensable. A new oxidation method using ion-sputtering was developed, and the effectiveness of this surface treatment on two dental alloys--a type IV gold alloy and Ni-Cr-Be alloy--was investigated. As an endurance test, thermocycling for a maximum of 100,000 cycles was adopted, and the tensile adhesive bond strength was then measured. Ion-coating the surface of the alloys resulted in strong bonds with adhesive resins, and after 100,000 thermocycles, a bond strength of above 20 MPa was maintained. | Dental Alloys |
Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub-Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE-binding glycans recognized up to 2008 were considered to be classical" cross-reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE-binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose-alpha-1,3-galactose (alpha-gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha-gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross-reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub-Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed." | Cross Reactions |
PURPOSE: Anaplastic thyroid cancer (ATC) is a rare and lethal malignant cancer. In recent years, the application of molecular-driven targeted therapy and immunotherapy has markedly improved the prognosis of ATC. This study aimed to identify characteristic genes for ATC diagnosis and revealed the role of ATC characteristic genes in drug sensitivity and immune cell infiltration. METHODS: We downloaded ATC RNA-sequencing data from the GEO database. Following the combination and normalization of the dataset, we first divided the combined datasets into the training cohort and the validation cohort. We identified differentially expressed genes (DEGs) in ATC by differential expression analysis in the training cohort. We used two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) to identify ATC characteristic genes. The CIBERSORT algorithm was performed to calculate the abundance of various immune cells in ATC. Finally, we validated the expression of ATC characteristic genes by quantitative RT-PCR (RT-qPCR) in ATC cell lines and immunohistochemistry (IHC). RESULTS: A total of 425 DEGs were identified in the training cohort, including 240 upregulated genes and 185 downregulated genes. Four ATC characteristic genes (ADM, PXDN, MMP1, and TFF3) were identified, and their diagnostic value was validated in the validation cohort (AUC in ROC analysis > 0.75). We established a practical gene expression-based nomogram to accurately predict the probability of ATC. We also found that ATC characteristic biomarkers are associated with the tumor immune microenvironment and drug sensitivity. CONCLUSION: ADM, PXDN, MMP1, and TFF3 might serve as potential ATC diagnostic biomarkers and may be helpful for ATC molecular targeted therapy and immunotherapy. | Thyroid Carcinoma, Anaplastic |
Fetal brain tumors are rare. This report describes a giant posterior fossa capillary hemangioma treated with 3 mg/kg/day of propranolol for 6 months. Total regression was confirmed at 1 year, and no additional tumors were observed during the subsequent 2 years. No side effects relating to the use of this drug were detected; thus, the authors believe that propranolol may be useful for treating all intracranial capillary hemangiomas. | Hemangioma, Capillary |
PURPOSE: This study aims to determine the relationship of frozen section (FS) to final histology and determine how incorporating FS may change preoperative malignancy risk estimates based on preoperative fine needle aspiration cytology (FNAC). The secondary aim is to determine if FS is useful in influencing intraoperative decision-making. METHODS: Retrospective review of 426 intraoperative FS for parotidectomies performed for primary parotid lesions. RESULTS: Risk of malignancy with a benign FS was 2.5%, with indeterminate 36.1%, and with malignant 100%. Incorporating FS to fine needle aspiration for cytology helped to stratify malignancy risk especially in the Milan categories of atypia of undetermined significance, neoplasm of uncertain malignant potential and non-diagnostic categories, where a malignant FS increased malignancy risk significantly. FS was only able to identify 11% of high-risk histological subtypes for which a neck dissection would be recommended. CONCLUSIONS: FS may be used to stratify malignancy risk intraoperatively but has limited utility in clinical decision-making to perform a neck dissection and more extensive parotid resection in high-risk histological subtypes. | Parotid Neoplasms |
An account is given of 30 Nigerian patients of the Igbo ethnic group whose biopsies showed tuberculous peritonitis. The maximum incidence occurred in the 20-39 year age group and the female: male ratio was 2:1. The commonest clinical findings were abdominal pain and swelling and ascites. An increase in the mean age was found in Igbos suffering from tuberculous peritonitis compared with those who had tuberculous peripheral lymphadenitis. | Peritonitis, Tuberculous |
An apparently healthy 46-year-old woman was admitted because of progressive shortness of breath that had begun 2 months before her admission. Physical examination revealed a patient with respiratory distress, tachycardia, and mild jugular venous distention; otherwise, results were unremarkable. Our investigation revealed hypoxia and severe pulmonary hypertension with signs of right heart dysfunction, but no primary cause was found. The patient died 5 days after admission. Autopsy revealed pulmonary lymphangitis carcinomatosis caused by papillary carcinoma. No primary tumor was found. | Lymphangitis |
Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells. A wealth of literature shows that these individual cellular networks are complex, robust and evolvable. To some extent, they are able to monitor their own performance, and display sufficient autonomy to be termed selfish". Their robustness is linked to quality control mechanisms which are embedded in and act upon the individual networks, thereby providing a basis for selection during gametogenesis. These selective processes are equally likely to affect cellular functions that are not gamete-specific, and the evolution of the most complex organisms, including man, is therefore likely to occur via two pathways: essential housekeeping functions would be regulated and evolve during gametogenesis within the parents before being transmitted to their progeny, while classical selection would operate on other traits of the organisms that shape their fitness with respect to the environment." | Antibody Diversity |
The ionic currents of the nodal membrane were measured under voltage clamp conditions. The membrane being +40 mv. The replacing of the external Na+-ions to K+- and NH4+-ions have showed that the relative pearmeabilities of the veratrine-modified channels calculated from the constant field theory are arranged in the following row: PNa:PK:PNH4 = 1:0.29:0.61, which differs from the same row for the normal channels. The decreasing of the slope of current-voltage relations of the modified channels with the replacing of Na+-ions to K+- and NH4+-ions is the evidence of a more strong binding of these ions to external mouth of the modified channel compared to the binding of Na+-ions. | Veratrine |
Amino acids contribute to the taste of foods. Previous studies on the taste of amino acids focused mainly on alpha-amino acids, and therefore, the taste characteristics of amino acid derivatives remain unclear. In the present study, we targeted 6 different amino acid derivatives, beta-alanine, citrulline, creatine, gamma-aminobutyric acid, taurine, and ornithine, and evaluated their taste characteristics in a human sensory study. All tested amino acid derivatives showed multiple taste qualities; no derivatives had only a single taste quality. However, their taste intensities were relatively weak even at high concentrations. Given that the interactions between amino acid derivatives and nucleotide result in taste enhancements, we investigated the effect of inosine 5'-monophosphate (IMP) on the taste characteristics and found that the taste intensity of ornithine increased in the presence of IMP. This finding will be useful for understanding the role of amino acid derivatives as taste substances in daily foods. | Inosine Monophosphate |
BACKGROUND: The aim of this study is to provide a quantitative evaluation of the blood-aqueous barrier (BAB) in patients with ocular blunt trauma and evaluate its association with intraocular pressure (IOP) elevation. METHODS: This is a prospective case-control study, and the following 3 groups were included: elevated IOP (45 patients with an elevated IOP secondary to ocular blunt trauma), normal IOP (27 patients with a normal IOP after ocular blunt trauma), and healthy controls. The main outcome measures were IOP and BAB function evaluated using a laser flare-cell meter (LFCM). RESULTS: Patients had significantly higher flare intensities and cell counts than the normal controls (both p < 0.001), and the elevated-IOP group displayed even higher LFCM readings than the normal-IOP group. Aqueous flare and cell readings were positively correlated with IOP (r = 0.529 and 0.590, respectively, p < 0.001). LFCM readings in the elevated-IOP group were still significantly high even on postraumatic day 120 following anti-inflammatory treatment. CONCLUSION: BAB dysfunction occurred following ocular blunt trauma. Eyes with an elevated IOP displayed a more seriously disturbed BAB and a longer recovery course. Examination with a LFCM provides insight into the pathophysiology of IOP elevation and assists in making decisions concerning anti-inflammatory treatment during follow-up. | Blood-Aqueous Barrier |
A mixed MEKC method for the analysis of budesonide and its related substances is presented. The micelles were formed from sodium cholate (CHOL) and 3-(N,N-dimethylmyristylammonio)propanesulfonate (MAPS). A multivariate optimisation was carried out with the aim of obtaining a baseline separation of all compounds. The influence of voltage, borate concentration, cholate concentration, MAPS concentration and pH was evaluated on the responses, corresponding to critical resolution values. Problems with the investigated experimental design were encountered due to the complexity of the separation process. As a consequence, a first design was not sufficient to reach the optimal conditions, but was needed in order to obtain the necessary information to successfully plan a second in-depth study by means of response surface methodology. The optimal conditions were as follows: capillary total and effective lengths of 48.5 and 40.0 cm, respectively, with 50 microm id; 70 mM borate buffer (pH 8.8) containing 65 mM CHOL and 10 mM MAPS; temperature 20 degrees C and voltage 16 kV. Separation of all the compounds, including R- and S-epimers of budesonide, was obtained in a reasonable time. Validation of the method was performed for both drug substances and drug product. | Cholates |
TRP cation channels are conserved throughout animal phylogeny and include many members that function in sensory physiology. The founding TRP is required for Drosophila phototransduction and has served as a paradigm for unravelling the roles and macromolecular organizations of TRP channels in native tissues. Two other TRPC channels, TRPL and TRPgamma, are expressed in photoreceptor cells and form heteromultimers with TRP and with each other. TRP is a member of a supramolecular signalling complex, the signalplex, which includes the PDZ scaffold protein, INAD, and two other core members that remain bound and depend on INAD for localization. Other INAD binding proteins are proposed to interact dynamically with INAD, one of which, TRPL, undergoes light-dependent translocation in photoreceptor cells. Surprisingly, TRP has non-channel functions, including an anchoring role necessary for retaining INAD in the rhabdomeres. Loss of TRP function or constitutive TRP activity results in retinal degeneration, which can be suppressed by disruption or overexpression of the Na+/Ca2+ exchanger, CalX, respectively. Given that hypoxia-induced constitutive activity of some mammalian TRPs leads to neuronal cell death, interventions that increase Na+/Ca2+ exchanger or decrease TRP function have the potential to reduce the severity of cell death due to ischaemia." | Photoreceptor Cells, Invertebrate |
Mitochondrial translation is of high significance for cellular energy homeostasis. Aminoacyl-tRNA synthetases (aaRSs) are crucial translational components. Mitochondrial aaRS variants cause various human diseases. However, the pathogenesis of the vast majority of these diseases remains unknown. Here, we identified two novel SARS2 (encoding mitochondrial seryl-tRNA synthetase) variants that cause a multisystem disorder. c.654-14T > A mutation induced mRNA mis-splicing, generating a peptide insertion in the active site; c.1519dupC swapped a critical tRNA-binding motif in the C-terminus due to stop codon readthrough. Both mutants exhibited severely diminished tRNA binding and aminoacylation capacities. A marked reduction in mitochondrial tRNASer(AGY) was observed due to RNA degradation in patient-derived induced pluripotent stem cells (iPSCs), causing impaired translation and comprehensive mitochondrial function deficiencies. These impairments were efficiently rescued by wild-type SARS2 overexpression. Either mutation caused early embryonic fatality in mice. Heterozygous mice displayed reduced muscle tissue-specific levels of tRNASers. Our findings elucidated the biochemical and cellular consequences of impaired translation mediated by SARS2, suggesting that reduced abundance of tRNASer(AGY) is a key determinant for development of SARS2-related diseases. | Aminoacylation |
Nearly 3% of the population has hyperhidrosis. Quality of life is affected, impacting on social relationships and professional activity, and social anxiety disorder can sometime develop. We review the definition and causes of hyperhidrosis and the clinical evaluation of patients. After describing the different clinical aspects of the condition, we discuss the medical and surgical treatments. Of such treatments currently available, particular mention is made of the use of botulinum toxin in some forms of hyperhidrosis as an intermediate option between the traditional treatments and surgery. We also draw attention to the use of minimal access surgical techniques (videothoracoscopy), which, over the past decade, have become established as an effective, safe, and permanent approach for the treatment of hyperhidrosis when indicated. | Antiperspirants |
Cell migration requires a complex array of molecular events to promote protrusion at the front of motile cells. The scaffold protein LL5beta interacts with the scaffold ERC1, and recruits it at plasma membrane-associated platforms that form at the front of migrating tumor cells. LL5 and ERC1 proteins support protrusion during migration as shown by the finding that depletion of either endogenous protein impairs tumor cell motility and invasion. In this study we have tested the hypothesis that interfering with the interaction between LL5beta and ERC1 may be used to interfere with the function of the endogenous proteins to inhibit tumor cell migration. For this, we identified ERC1(270-370) and LL5beta(381-510) as minimal fragments required for the direct interaction between the two proteins. The biochemical characterization demonstrated that the specific regions of the two proteins, including predicted intrinsically disordered regions, are implicated in a reversible, high affinity direct heterotypic interaction. NMR spectroscopy further confirmed the disordered nature of the two fragments and also support the occurrence of interaction between them. We tested if the LL5beta protein fragment interferes with the formation of the complex between the two full-length proteins. Coimmunoprecipitation experiments showed that LL5beta(381-510) hampers the formation of the complex in cells. Moreover, expression of either fragment is able to specifically delocalize endogenous ERC1 from the edge of migrating MDA-MB-231 tumor cells. Coimmunoprecipitation experiments show that the ERC1-binding fragment of LL5beta interacts with endogenous ERC1 and interferes with the binding of endogenous ERC1 to full length LL5beta. Expression of LL5beta(381-510) affects tumor cell motility with a reduction in the density of invadopodia and inhibits transwell invasion. These results provide a proof of principle that interfering with heterotypic intermolecular interactions between components of plasma membrane-associated platforms forming at the front of tumor cells may represent a new approach to inhibit cell invasion. | MDA-MB-231 Cells |
Spermine is a constituent of all vertebrate cells. Nevertheless, it exerts toxic effects if it accumulates in cells. Spermine is a natural substrate of the FAD-dependent polyamine oxidase, a constitutive enzyme of many cell types. It has been reported that the toxicity of spermine was enhanced if polyamine oxidase was inhibited. We were interested to examine spermine toxicity to human colon carcinoma-derived CaCo-2 cells because, in contrast to most tumor cell lines, CaCo-2 cells undergo differentiation, which is paralleled by changes in polyamine metabolism. CaCo-2 cells were remarkably resistant to spermine accumulation, presumably because spermine is degraded by polyamine oxidase at a rate sufficient to provide spermidine for the maintenance of growth. Inactivation of polyamine oxidase increased the sensitivity to spermine. A major reason for the enhanced spermine cytotoxicity at low polyamine oxidase activity is presumably the profound depletion of spermidine, and the consequent occupation of spermidine binding sites by spermine. Hydrogen peroxide and the aldehydes 3-aminopropanal and 3-acetamidopropanal, the products of polyamine oxidase-catalyzed splitting of spermine and N1-acetylspermine, contribute little to spermine cytotoxicity. Activation of caspase by spermine was insignificant, and the formation of DNA ladders, another indicator of apoptotic cell death, could not be observed. Thus it appears that cell death due to excessive accumulation of spermine in CaCo-2 cells was mainly nonapoptotic. The content of brush border membranes did not change between days 6 and 8 after seeding, and it was not affected by exposure of the cells to spermine. However, the activities of alkaline phosphatase, sucrase, and aminopeptidase in nontreated cells were considerably enhanced during this period, but remained low if cells were exposed to spermine. These changes appear to indicate that differentiation is prevented by intoxication with spermine, although other explanations cannot be excluded. | Caco-2 Cells |
BACKGROUND: Fetal imaging for congenital anomalies increases pregnancy terminations late in gestation. OBJECTIVES: We assessed whether late-pregnancy terminations can accidentally result in live births, and how these births impact infant mortality rates over time. METHODS: We carried out a population-level analysis of 12,141 infant deaths in Quebec, Canada from 1986 to 2012. We calculated the proportion of infants born alive who died following pregnancy termination. The exposure was pregnancy termination with or without congenital anomaly recorded on death certificates. The main outcome was mortality on the first day of life by the hour. RESULTS: Pregnancy termination was the cause of 19.4 infant deaths per 100,000 in 2000-2012, compared with 1.0 per 100,000 in 1986-1999. Most deaths after termination occurred in the first 3 h of life among infants with anomalies who weighed <500 g. In 2000-2012, infants who died following pregnancy termination led to an excess of 0.2 deaths per 1,000 on the first day of life, i.e. an 8.6% increase in the infant mortality rate (p value = 0.002). CONCLUSIONS: Pregnancy termination in mid-gestation carries the risk of accidental live birth. These neonates increasingly affect infant mortality rates. Better recording is needed, including data on the prevention and management of accidental live births after pregnancy termination. | Infant Mortality |
Mannose binding lectin (MBL) is a serum protein with structure and functions similar to those of complement factor C1q, and is a key molecule in innate immunity. Interestingly, absence or extremely low concentration of serum MBL (MBL deficiency) seems to be a risk factor for occurrence of autoimmune diseases, in particular systemic lupus erythematosus. In addition, individuals with MBL deficiency are at risk of infection when in immunocompromised conditions. The concentration of serum MBL is greatly influenced by relatively common single nucleotide polymorphisms of the MBL gene. Therefore, typing of the MBL gene, or measurement of serum MBL may be valuable for determining the risk of infections in patients with systemic autoimmune diseases, who frequently undergo immunosuppressive therapies. MBL deficiency may also be a risk factor for atherosclerosis and arterial thrombosis, both being common complications of autoimmune diseases. On the other hand, MBL may be pathological in tissue injuries, and the precise roles of MBL in autoimmune diseases, and the value of MBL gene typing or serum MBL measurement in a clinical setting are yet to be clarified. Recently, presence of anti-MBL autoantibodies in sera of SLE patients has been reported. The significance of this autoantibody remains to be elucidated. | Mannose-Binding Lectins |
Poly(2-aminoadenylic acid) forms both double and triple helices with poly(uridylic acid) [poly(U)]. The 2-amino group forms a third hydrogen bond, elevating the 2 leads to 1 transition temperature by 33 degrees C. The third strand, however, has about the same stability as poly(A)-2poly(U), as measured by Tm 3 leads to 2. This selective stabilization of the two-stranded helix results in a much greater resolution of the differnt thermal transitions than that observed in analogous polynucleotide systems. In contrast to other A, U systems 3 leads to 1 and 2 leads to 3 transitions are not observed under any conditions, and the triple helix always undergoes a 3 leads to 2 transition even at very high ionic strength. A 1:1 mixture of poly(2NH2A) and poly(U) exhibits no transient formation of 1:2 complex, unlike similar mixtures of poly(A) with poly(U) and poly(T). This difference is evidently due to a more rapid displacement reaction: [poly(2NH2A) + poly(2NH2A)-2poly(U) leads to 2 poly(2NH2A)-poly(U)] With poly(2NH2A) than with poly(A). We describe a method for establishing the combining ratios of polynucleotide complexes which used a computer to calculate the angles of intersection of mixing curves as explicit and continuous functions of the wavelength. The wavelength dispersions of the angles of intersection determine optimum wavelengths for establishing stoichiometry and can also provide reliable negative evidence that presumably plausible complexes are not formed. Analogous computer procedures have been developed to determine wavelengths which are selective for the formation of both 1:1 and 1:2 complexes. Infrared spectra of the 1:1 and 1:2 complexes resemble those of other A, U homoribopolynucleotide helices in having two and three strong bands, respectively, in the region of carbonyl stretching vibrations. CD spectra of the two complexes are unusual in having negative first extrema of moderate intensity. We attribute these extrema to intrastrand interactions of strong, well-resolved transitions at 278 nm (B2u) of the 2-aminoadenine residues. The CD spectra are correlated with those of other polynucleotide helices. | Polyribonucleotides |
Brucks (Anim Cogn 25(2):473-491, 2021) have published an intriguing paper on the differing abilities of various species of parrots to succeed in a delay of gratification task. I find their interspecies comparisons of considerable interest but take exception to their misrepresentation of prior research on delayed gratification from our laboratory in Koepke (J Comp Psychol 129:339-346, 2015). Contrary to their claims, our subject was never trained on the task; rather, one might argue instead that all their subjects received considerable training or at least forms of pre-exposure that could affect their overall claims. I also briefly discuss other design features that may have affected their results. | Parrots |
Factors that directly impact horizontal transmission of the microsporidium Amblyospora albifasciati to its intermediate copepod host, Mesocyclops annulatus were examined in laboratory bioassays. Results were evaluated in relation to life history strategies that facilitate persistence of the parasite in natural populations of its definitive mosquito host, Ochlerotatus albifasciatus. A moderately high quantity of meiospores from mosquito larvae was required to infect adult female copepods; the IC50 was estimated at 3.6 x 10(4) meiospores/ml. Meiospore infectivity following storage at 25 degrees C was detected up to 30 days, while meiospores stored at 4 degrees C remained infectious to copepods for 17 months with virtually no decline in infectivity. Uninfected female M. annulatus are long-lived; no appreciable mortality was observed in field-collected individuals for 26 days, with a few individuals surviving up to 70 days. The pathological impact of A. albifasciati infection on M. annulatus resulted in a 30% reduction in survivorship after 7 days followed by gradual progressive mortality with no infected individuals surviving more than 40 days. This moderate level of pathogenicity allows for a steady continual release of spores into the environment where they may be ingested by mosquito larvae. Infected female copepods survived in sediment under conditions of desiccation up to 30 days, thus demonstrating their capacity to function as a link for maintaining A. albifasciati between mosquito generations following periods of desiccation. The susceptibility of late stage copepodid M. annulatus to meiospores of A. albifasciati and subsequent transstadial transmission of infection to adult females was established. | Amblyospora |
Transanal endoscopic surgery (TES) consists of a series of anorectal surgical procedures using different devices that are introduced into the anal canal. TES has been developed significantly since it was first used in the 1980s. The key point for the success of these techniques is how accurately patients are selected. The main indication was the resection of endoscopically unresectable adenomas. In recent years, these techniques have become more widespread which has allowed them to be applied in conservative rectal procedures for both benign diseases and selected cases of rectal cancer. For more advanced rectal cancers it should be considered palliative or, in some controlled trials, experimental. The role of newer endoscopic techniques available has not yet been defined. TES may allow for new strategies in the treatment of rectal pathology, like transanal natural orifice transluminal endoscopic surgery or total mesorectal excision. | Transanal Endoscopic Surgery |
This study reviewed some new aspects of the modular proteoglycan perlecan, a colossal proteoglycan with a 467â¯kDa core protein and five distinct functional domains. Perlecan is a heparan sulphate proteoglycan that transiently displays native CS sulphation motifs 4-C-3 and 7-D-4 during tissue morphogenesis these are expressed by progenitor cell populations during tissue development. Perlecan is susceptible to fragmentation by proteases during tissue development and in pathological tissues particularly in domains IV and V. The fragmentation pattern of domain IV has been suggested as a means of grading prostate cancer. Domain V of perlecan is of interest due to its interactive properties with integrin alpha5beta1 that promotes pericyte migration enhancing PDGF-BB-induced phosphorylation of PDGFRbeta, Src homology region 2 domain-containing phosphatase-2, and focal adhesion kinase supporting the repair of the blood brain barrier following ischaemic stroke. Fragments of domain V can also interact with alpha2beta1 integrin disrupting tube formation by endothelial cells. LG1-LG2, LG3 fragments can antagonise VEGFR2, and alpha2beta1 integrin interactions preventing angiogenesis by endothelial cells. These domain V fragments are of interest as potential anti-tumour agents. Perlecan attached to the luminal surfaces of endothelial cells in blood vessels acts as a flow sensor that signals back to endothelial and smooth muscle cells to regulate vascular tone and blood pressure. Perlecan also acts as a flow sensor in the lacuno-canalicular space regulating osteocytes and bone homeostasis. Along with its biomechanical regulatory properties in cartilaginous tissues this further extends the functional repertoire of this amazingly diverse functional proteoglycan. | Integrin alpha2beta1 |
PURPOSE OF REVIEW: Sinonasal tumors are rare and heterogeneous diseases which pose challenges in diagnosis and treatment. Despite significant progress made in surgical, oncological, and radiotherapy fields, their prognosis still remains poor. Therefore, alternative strategies should be studied in order to refine diagnosis and improve patient care. RECENT FINDINGS: In recent years, in-depth molecular studies have identified new biological markers, such as genetic abnormalities and epigenetic variations, which have allowed to refine diagnosis and predict prognosis. As a consequence, new histological entities have been described and specific subgroup stratifications within the well-known histotypes have been made possible. These discoveries have expanded indications for immunotherapy and targeted therapies in order to reduce tumor spread, thus representing a valuable implementation of standard treatments. Recent findings in molecular biology have paved the way for better understanding and managing such rare and aggressive tumors. Although further efforts need to be made in this direction, expectations are promising. | Paranasal Sinus Neoplasms |
The aim of the present experimental animal study was to investigate the efficacy of bovine lactoferrin (LF) on wound healing in an animal model of nasal septum perforation (NSP).Twenty-two, 8 to 10 weeks of age, male Sprague-Dawley rats were separated into two groups. Nasal septum perforation was created in each rat. The saline (control) and 0.05 mg LF (study) groups were delivered locally for 14 days. On the 14th day of the study, after the sacrifice, the cartilage nasal septa of the animals were excised. The degeneration and regeneration observed in the nasal septum epithelium and cartilage, the number of acute inflammatory cells, the number of eosinophils, the amount of new vessel formation, the amount of granulation, and the collagen density were examined microscopically. The microscopic parameters and macroscopic healing of NSPs were analyzed. The epithelium regeneration, the fibroblast number, the granulation tissue formation, the collagen density, and the macroscopic healing were significantly higher in the LF group (p < 0.05). Besides, the acute inflammatory cell count was lower in the LF group (p = 0.034). In conclusion, the topically delivered LF can improve wound healing in an experimental rat model of NSP. | Nasal Septal Perforation |
The optical purity of N-acetyl-L-cysteine was tested by capillary electrophoresis. The D-enantiomer can be found down to a ratio of 0.4:99.6 within 4 min without the use of the D-form or the racemate as a standard. The efficiency was optimized during method development up to a theoretical plate number, N, of several hundred thousand. The migration order and the separation mechanism was explained. The assumed structure of the formed isoindole S-[2-(1-carboxy-2-methylpropyl)isoindole-1-yl]-N-acetylcysteine diastereomers was confirmed and its stability was examined. | Acetylcysteine |
PURPOSE: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication. METHODS: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated. RESULTS: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82). CONCLUSIONS: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI. | Angioedema |
Machine learning (ML) models were applied to pharmacovigilance (PV) data in a two-component proof-of-concept study. PV data were partitioned into Training, Validation, and Holdout datasets for model training and selection. During the first component ML models were challenged to identify factors in individual case safety reports (ICSRs) involving spinosad and neurological and ocular clinical signs. The target feature for the models were these clinical signs that were disproportionately reported for spinosad. The endpoints were normalized coefficient values representing the relationship between the target feature and ICSR free text fields. The deployed model accurately identified the risk factors demodectic," "demodicosis," and "ivomec." In the second component, the ML models were trained to identify high quality and complete ICSRs free of confounders. The deployed model was presented with an external Test dataset of six ICSRs, one that was complete, of high quality, and devoid of confounders, and five that were not. The endpoints were model-generated probabilities for the ICSRs. The deployed ML model accurately identified the ICSR of interest with a greater than 10-fold higher probability score. Although narrow in scope, the study supports further investigation and potential application of ML models to animal health PV data." | Pharmacovigilance |
The biosynthesis of geosmin (1) and (1(10)E,5E)-germacradien-11-ol (2), two volatile terpenoid compounds emitted by the myxobacteria Myxococcus xanthus and Stigmatella aurantiaca, was investigated in feeding experiments with different labeled precursors. In these experiments, the volatiles released by the cell cultures grown on agar plates were collected with a closed-loop stripping apparatus (CLSA) and analyzed by GC-MS. [(2)H(10)]Leucine and [4,4,4,5,5,5-(2)H(6)]dimethylacrylate were fed to wild-type strains and bkd mutant strains, which are impaired in the degradation of leucine to isovaleryl-CoA. [(2)H(10)]Leucine was incorporated into 1 and 2 only by the wild-type strains via the biosynthetic pathway that involves leucine degradation and branching into the mevalonate pathway. Dimethylacrylyl-CoA (DMA-CoA) is an intermediate in the leucine degradation and in the recently discovered pathway from HMG-CoA to isovaleryl-CoA. The corresponding free acid, [4,4,4,5,5,5-(2)H(6)]dimethylacrylic acid, was incorporated into 1 and 2 only by the mutants impaired in leucine degradation. [4,4,6,6,6-(2)H(5)]Mevalonic acid lactone (12) was synthesized and fed to M. xanthus and S. aurantiaca wild-type strains and a double mutant strain of M. xanthus. This strain does not degrade leucine and is impaired in the reduction of 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid. The mass spectral analysis of labeled 1 and 2 obtained in these feeding experiments led to a biosynthetic scheme to 1 with intermediate 2. This pathway differs from that observed in the liverwort Fossombronia pusilla and thus suggests microbial geosmin biosynthesis following a route different from that in liverworts. Our results are supported by a 1,2-hydride shift of the tertiary hydrogen atom at C-4a into the ring opposite to that in F. pusilla. | Stigmatella |
Conserved and multifunctional Geminivirus Replication-associated Protein (Rep) specifically recognizes the replication origin and initiates viral DNA replication. We report the X-ray crystallography-based structures of two complexes containing the N-terminal domain (5-117aa) of Tomato yellow leaf curl virus (TYLCV) Rep: the catalytically-dead Rep in complex with nonanucleotide ssDNA (Rep(5-117) Y101F-ssDNA) as well as the catalytically-active phosphotyrosine covalent adduct (Rep(5-117)-ssDNA). These structures provide functional insight into the role of Rep in viral replication. Metal ions stabilize the DNA conformation by interacting with the phosphate group of adenine and thus promote formation of the catalytic center. Furthermore, we identified a compound that inhibits the binding of Rep to ssDNA and dsDNA and found that the addition of metal ions compromises the inhibitory effectiveness of this compound. This study demonstrates the mechanism of DNA recognition and cleavage process of viral Rep, emphasizing the role of metal ions. | Begomovirus |
Epidemiological data, family history, clinical data, and HLA typing were studied in three groups of patients with Behcet's syndrome: six Israeli Ashkenazi Jews, 29 non-Ashkenazi Jews, and three Israeli Arabs. HLA-B51 and B52 were present in 24/38 (63%) and 8/38 (21%), respectively, of the patients compared with 13/151 (9%) of the control group for both cases, a relative risk of 18.2 and 2.8 respectively. The syndrome was found in six of the 34 families. Ninety five per cent of the affected family members were either B51 or B52 positive. Eleven of the 14 families (79%) chosen for study contained a close relative of the proband who had recurrent oral ulcers. All the relatives with ulcers, except for one, were B51 or B52 carriers. Recurrent oral ulcers in the patients with Behcet's syndrome began a few years before other manifestations of the syndrome occurred. Our findings suggest that (a) HLA-B51 and HLA-B52 are primarily associated with Behcet's disease of Israeli patients; (b) the familial occurrence of this syndrome is high and occurs predominantly in the B5 positive group; (c) recurrent oral ulcers may be the first symptom of Behcet's syndrome, appearing early in life; HLA analysis can provide the clue for a correct diagnosis; (d) ulcer recurrence is common among members of a family containing a patient with Behcet's syndrome. | HLA-B52 Antigen |
Macrophage activation is intimately linked to metabolic reprogramming. Inflammatory (M1) macrophages are able to sustain inflammatory responses and to kill pathogens, mostly by relying on aerobic glycolysis and fatty acid biosynthesis. Glycolysis is a fast way of producing ATP, and fatty acids serve as precursors for the synthesis of inflammatory mediators. On the opposite side, anti-inflammatory (M2) macrophages mediate the resolution of inflammation and tissue repair, switching their metabolism to fatty acid oxidation and oxidative phosphorylation. Over the years, this classical view has been challenged by recent discoveries pointing to a more complex metabolic network during macrophage activation. Lipid metabolism plays a critical role in the activation of both M1 and M2 macrophages. Recent evidence shows that fatty acid oxidation is also essential for inflammasome activation in M1 macrophages, and glycolysis is now known to fuel fatty acid oxidation in M2 macrophages. Ultimately, targeting lipid metabolism in macrophages can improve the outcome of metabolic diseases. Here, we review the main aspects of macrophage immunometabolism from the perspective of the metabolism of lipids. Building a reliable metabolic network during macrophage activation will bring us closer to targeting macrophages for improving human health. | Macrophage Activation |
To explore a noncontact drive solution for linear piezoelectric actuators, a novel type of noncontact linear piezoelectric actuator modulated by the electromagnetic field is proposed. The proposed actuator employs electromagnetic force to modulate and transfer the locomotion between the stator and the runner. The drive scheme reduces the wear and friction between the stator and the runner and can control the coupling force by the electric system. Here, the design pattern and working principles are described. The amplification ratio equation of the flexible amplification mechanism is established, and the calculation method of the dynamic electromagnetic force is illustrated. For assessing the validity and measure the output characteristics of the proposed actuator, a prototype is fabricated to measure the output speeds, the stepping distances, and the output forces. The experimental results show the actuator with the driving frequency of 1 Hz, the electromagnetic modulation voltage of 4 V, and the piezoelectric driving voltage of 100 V can continuously output a stall load force of about 0.15 N and speed of 0.33 mm/s. | Magnetic Phenomena |
Vagus nerve injury may complicate carotid endarterectomy (CEA). The recurrent laryngeal nerve (RLN) branches from the vagus nerve, innervating the ipsilateral vocal cord. Vagus nerve injury can cause vocal cord dysfunction. Intraoperative vocal cord monitoring can detect vagus nerve injury during CEA. A patient with distorted neck anatomy from radiotherapy to treat oropharyngeal cancer and resultant right vocal cord paralysis required left CEA. Anticipating difficult neck dissection risking vagus nerve damage with associate RLN malfunction, we added vocal cord electromyography (EMG) to routine CEA electroencephalography (EEG). We recommend vocal cord EMG in anatomically complex CEA to avoid vagus nerve injury. | Vagus Nerve Injuries |
The Japanese isolates of Palyam serogroup viruses isolated from 1985 to 2001 were investigated for the genome sequence of segments 2 and 7 and were phylogenetically analyzed in comparison with Australian and African isolates of the same serogroup. The nucleotide sequences of segment 7 were highly conserved within Japanese isolates (95.1 to 100%) and between Japanese and Taiwanese isolates (96.0 to 100%), whereas the identities between Japanese and Taiwanese isolates and Australian and African isolates were fairly conserved (84.2 to 92.0%). Phylogenetic analysis based on segment 7 revealed three clusters according to geographical origin. As a result of the nucleotide sequence analysis of segment 2, which encodes a serotype-specific antigen, Japanese isolates were classified into two groups by genome length and nucleotide identities. Four of the nine Japanese isolates were categorized into the same group as prototype strain K-47 of the Chuzan virus, and the remaining isolates were categorized into the same group as the D'Aguilar virus and Nyabira virus. Phylogenetic analysis based on segment 2 revealed two clusters, the cluster containing Chuzan virus and the cluster containing the D'Aguilar and Nyabira viruses. To examine the antigenic relationship among viruses categorized in different clusters, we conducted a cross-neutralization test. KSB-29/E/01, isolated in 2001 in Japan, was neutralized by antiserum not only to strain B8112 of D'Aguilar virus but also to Chuzan virus. These results indicated that genetically and antigenically unique characteristics of KSB-29/E/01 were attributed to genetic reassortment of segment 2 between Chuzan virus and D'Aguilar virus. | Palyam Virus |
Studies in eukaryotic ribosome biogenesis have largely been performed in yeast, where they have described a highly complex process involving numerous protein and RNA components. Due to the complexity and crucial nature of this process, a number of checkpoints are necessary to ensure that only properly assembled ribosomes are released into the cytoplasm. Assembly of the 5S ribonucleoprotein (RNP) complex is one of these checkpoints for late-stage 60S subunit maturation. Studies in Saccharomyces cerevisiae have identified the 5S rRNA and four proteins, L5, L11, Rpf2, and Rrs1, as comprising the ribosome-associated 5S RNP. Work from our laboratory has shown that in the eukaryotic pathogen Trypanosoma brucei, the 5S RNP includes trypanosome-specific proteins P34/P37, as well as homologues of L5, Rpf2, and 5S rRNA. In this study, we examine a homologue of Rrs1 and identify it as an additional member of the T. brucei 5S RNP. Using RNA interference, we show that TbRrs1 is essential for the survival of T. brucei and has an important role in ribosome subunit formation and, together with TbRpf2, plays a role in 25/28S and 5.8S rRNA processing. We further show that TbRrs1 is a member of the T. brucei 5S RNP through the identification of novel direct interactions with P34/P37 and 5S rRNA as well as with TbL5 and TbRpf2. These unique characteristics of TbRrs1 highlight the importance of studying ribosome biogenesis in the context of diverse organisms and identify interactions that could be targeted for future drug development.IMPORTANCETrypanosoma brucei is a parasite responsible for human and animal African trypanosomiasis. Current treatments for these diseases have numerous problems, and the development of novel chemotherapeutics can be achieved by identifying targets that are parasite specific and part of essential processes. Ribosome biogenesis is the process of generating translation-competent ribosomes and is critical for survival in all organisms. Work from our laboratory has shown that the formation of the 5S RNP, a crucial checkpoint in ribosome biogenesis, requires trypanosome-specific proteins P34/P37 and homologues of Rpf2 and L5 which possess parasite-specific characteristics. In this study, we characterize TbRrs1, an additional member of the T. brucei 5S RNP, and show that it is essential for parasite survival and has unique interactions with P34/P37 and 5S rRNA. This expands our understanding of the 5S RNP in T. brucei and identifies new targets for future drug development. | RNA, Ribosomal, 5S |
Five patients with atopy who had chronic dermatophytosis manifested an immediate and strong trichophytin skin reaction but no delayed reaction. This phenomenon may be caused by the neutralization of injected antigen by serum antibodies during the immediate reaction. When we injected a second dose of trichophytin into the wheal of the immediate reaction, 20 minutes after the first injection, a strong delayed reaction was elicited, demonstrating cell-mediated immune responses in these patients. | Trichophytin |
Assembly of the SNARE proteins syntaxin1, SNAP25, and synaptobrevin into a SNARE complex is essential for exocytosis in neurons. For efficient assembly, SNAREs interact with additional proteins but neither the nature of the intermediates nor the sequence of protein assembly is known. Here, we have characterized a ternary complex between syntaxin1, SNAP25, and the SM protein Munc18-1 as a possible acceptor complex for the R-SNARE synaptobrevin. The ternary complex binds synaptobrevin with fast kinetics, resulting in the rapid formation of a fully zippered SNARE complex to which Munc18-1 remains tethered by the N-terminal domain of syntaxin1. Intriguingly, only one of the synaptobrevin truncation mutants (Syb1-65) was able to bind to the syntaxin1:SNAP25:Munc18-1 complex, suggesting either a cooperative zippering mechanism that proceeds bidirectionally or the progressive R-SNARE binding via an SM template. Moreover, the complex is resistant to disassembly by NSF Based on these findings, we consider the ternary complex as a strong candidate for a physiological intermediate in SNARE assembly. | R-SNARE Proteins |
BACKGROUND: It was shown recently on the level of gene expression that UGT8, coding UDP-galactose:ceramide galactosyltransferase, is one of six genes whose elevated expression correlated with a significantly increased the risk of lung metastases in breast cancer patients. In this study primary tumours and their lung metastases as well as breast cancer cell lines were analysed for UGT8 expression at the protein level. METHODS: Expression of UGT8 in breast cancer tissue specimens and breast cancer cell lines was analysed using IHC, real-time PCR and Western blotting. RESULTS: Comparison of the average values of the reaction intensities (IRS scale) showed a significant difference in UGT8 expression between (1) primary and metastatic tumours (Mann-Whitney U, P<0.05), (2) tumours of malignancy grades G3 and G2 (Mann-Whitney U, P<0.01) as well as G3 and G1 (Mann-Whitney U, P<0.001) and (3) node-positive and node-negative tumours (Mann-Whitney U, P<0.001). The predictive ability of increased expression of UGT8 was validated at the mRNA level in three independent cohorts of breast cancer patients (721). Similarly, breast cancer cell lines with the 'luminal epithelial-like' phenotype did not express or weakly expressed UGT8, in contrast to malignant, 'mesenchymal-like,' cells forming metastases in nude mice. CONCLUSION: Our data suggest that UGT8 is a significant index of tumour aggressiveness and a potential marker for the prognostic evaluation of lung metastases in breast cancer." | Ganglioside Galactosyltransferase |
Two hundred and fifty-five patients from Mazandaran Province, Iran, all presenting with hypochromic and microcytic anemia, were selected for alpha-thalassemia (alpha-thal) mutation screening. We detected a total of 274 alpha-globin mutations in 227 (89%) of these patients. Among the 21 different alpha-globin alleles found, the -alpha(3.7) (44.9%), polyadenylation signal 2 (poly A2) (AATAAA>AATGAA) (18.2%), -alpha(4.2) (9.1%), alpha(IVS-I(-5 nt)) (6.5%), - -(MED) (4.3%), and alpha(codon 19 (-G)) (4%) were the most frequent. The other 15 mutations included variants that had not yet been observed in Iran, such as Hb Bleuland [alpha108(G15)ThrAsn, ACC>AAC (alpha2)], as well as a novel mutation on the alpha2 gene, also not described to date [3 ' untranslated region (3 'UTR) nucleotide (nt) 46 (C>A)]. These comprehensive new data are useful for establishing a screening strategy for the effective control of alpha-thal in Mazandaran Province. | alpha-Globins |
The current U.S. Environmental Protection Agency (EPA) and other national/international guidelines specify the use of two species and two sexes rodents (usually the rat and the mouse) for carcinogenicity testing of chemicals. In view of the enormous number of chemicals to be tested, the high cost of testing, and the large number of animals used in the present protocol, many academic, industrial, and government authorities are examining the possibility of using a reduced protocol (less than two species and two sexes of rodents) for carcinogenicity testing of chemicals. The use of a reduced protocol offers many advantages as well as some disadvantages. To pursue further the potential implications and impacts of using a reduced protocol for carcinogenicity testing on the processes of hazard identification and risk assessment, a workshop entitled Evaluation of Reduced Protocols for Carcinogenicity Testing of Chemicals" was held at the Embassy Suites Hotel in Alexandria, Virginia on September 22 and 23, 1992. It was cosponsored by EPA's Office of Prevention, Pesticides and Toxic Substances (OPPTS) and the National Toxicology Program of the National Institutes of Environmental Health Sciences (NTP/NIEHS) and attended by more than 60 participants from government, industry, academia, and the general public. The Expert Consensus Panel and most of the participants supported the use of reduced protocols in carcinogenicity testing. However, it was recognized that reduced protocols may not be appropriate for the testing of all chemicals and that additional analyses/data may be needed for selection of the most appropriate reduced protocol for certain chemicals/chemical classes." | Carcinogenicity Tests |
The taxonomical classification among fungi kingdom in the last decades was evolved. In this work the targeted metabolomics study based on (1)H NMR spectroscopy combined with chemometrics tools was reported to be useful for differentiation of three model of fungal strains, which represent various genus of Ascomycota (Aspergillus pallidofulvus, Fusarium oxysporum, Geotrichum candidum) were selected in order to perform metabolomics studies. Each tested species, revealed specific metabolic profile of primary endo-metabolites. The species of A. pallidofulvus is represented by the highest concentration of glycerol, glucitol and Unk5. While, F. oxysporum species is characterised by increased level of propylene glycol, ethanol, 4-aminobutyrate, succinate, xylose, Unk1 and Unk4. In G. candidum, 3-methyl-2-oxovalerate, glutamate, pyruvate, glutamine and citrate were elevated. Additionally, a detailed analysis of metabolic changes among A. pallidofulvus, F. oxysporum and G. candidum showed that A. pallidofulvus seems to be the most pathogenic fungi. The obtained results demonstrated that targeted metabolomics analysis could be utilized in the future as a supporting taxonomical tool for currently methods. | Fungi |
We examined whether galantamine (GAL), a cholinesterase inhibitor and allosteric potentiating ligand for alpha7 nicotinic acetylcholine receptor (nAChR), had an impact on emotional abnormalities in forebrain-specific cholecystokinin receptor-2 overexpressed transgenic mice. Treatment with GAL (1 mg/kg, s.c.) attenuated the decrease of social interaction time, but failed to attenuate anxiety-like behavior in the elevated plus-maze test. The effect of GAL was blocked by an alpha7 nAChR antagonist, methyllycaconitine (3 mg/kg, i.p.). These results suggest that GAL improved social interaction impairments via alpha7 nAChR and could be useful to treat sociability-related emotional abnormalities. | Receptor, Cholecystokinin B |
A 6-year-old child presented with generalized hyperkeratosis, most marked over the flexures; windswept deformity of the legs; and limping since 3 years. On the basis of the clinical, histopathologic and biochemical findings, he was diagnosed as a case of epidermolytic hyperkeratosis with rickets. He was treated with parenteral vitamin D3 and calcium supplements orally. Nutritional rickets has been reported in children with various types of ichthyosis like lamellar and X-linked types. We report this case of epidermolytic hyperkeratosis with rickets for its rarity. | Hyperkeratosis, Epidermolytic |
It is now well established that peptides that were first identified on the basis of their ability to inhibit growth of bacteria and fungi are multifunctional and so are more informatively described as host-defense peptides. In some cases, their role in protecting the organism against pathogenic microorganisms, although of importance, may be secondary. A previous article in the journal (Peptides 2014; 57:67-77) assessed the potential of peptides present in the skin secretions of frogs for development into anticancer, antiviral, immunomodulatory and antidiabetic drugs. This review aims to extend the scope of this earlier article by focusing upon therapeutic applications of host-defense peptides present in skin secretions and/or skin extracts of species belonging to other vertebrate classes (Agnatha, Elasmobranchii, Teleostei, Reptilia, and Mammalia as represented by the human) that supplement their potential role as anti-infectives for use against multidrug-resistant microorganisms. | Hyperotreti |
Modern microbial systematics requires a range of methodologies for the comprehensive characterization, classification and identification of microorganisms. While whole-genome sequences provide the ultimate reference for defining microbial phylogeny and taxonomy, selected biomarker-based strategies continue to provide the means for the bulk of microbial systematic studies. Proteomics, the study of the expression of genes, as well as the structure and function of the resulting proteins, offers indirect measures of genome sequence data. Recent developments in applications of proteomics for analyzing microorganisms have paralleled the growing microbial genome sequence database, as well as the evolution of mass spectrometry (MS) instrumentation and bioinformatics. MALDI-TOF MS, which generates proteomic mass patterns for 'fingerprint'-based characterizations, has provided a marked breakthrough for microbial identification. However, MALDI-TOF MS is limited in the number of targets that can be detected for strain characterization. Advanced methods of tandem mass spectrometry, in which proteins and peptides generated from proteins, are characterized and identified, using LC-MS/MS, provide the ability to detect hundreds or thousands of expressed microbial strain markers for high-resolution characterizations and identifications. Model studies demonstrate the application of proteomics-based analyses for bacterial species- and strain-level detection and identification and for characterization of environmentally relevant, metabolically diverse bacteria. Proteomics-based approaches represent an emerging complement to traditional methods of characterizing microorganisms, enabling the elucidation of the expressed biomarkers of genome sequence information, which can be applied to 'proteotyping' applications of microorganisms at all taxonomic levels. | Proteome |
Nightmares, far from being unsuccessful dreams or exceptions to rules about dreams, can be considered paradigms for all dreaming. They allow us to follow exactly how a disturbance or perturbation is handled by the processing systems in our minds. The data considered here consists of dream series in the weeks and months immediately following trauma in adults--in other words, nightmares and dreams occurring as the trauma resolves. It appears the traumatized person may dream first about the actual trauma (though not always), then, very quickly, the dreams appear to deal with the dominant emotion. Dreams of being overwhelmed by a tidal wave or being swept up by a whirlwind are common after almost any trauma. Clearly, such dreams are not about the sensory input from the actual trauma. Rather, the dreams are about the dominant emotion. The dreams contextualize (find a picture context for) the emotional concern. After trauma, the dominant emotion is usually first terror and fear, then often followed by guilt (such as survivor guilt). This too is pictured in the dream series. The same pattern of contextualizing an emotional concern can be seen in stressful situations, in pregnancy, or in patients whose lives are dominated by one emotion. This pattern is paradigmatic for all dreams, but it may be difficult to detect in ordinary" dreams, because there may be a number of other relatively smaller emotional concerns present, as opposed to the one clear-cut dominant one (as after trauma). A theory of dreaming is sketched out based on these data which suggests that overall dreaming makes connections more broadly than waking in the nets of the mind, and that the connections are not made randomly but guided by the dreamer's emotional concerns. It is also suggested that the making of connections may be functional for the organism in the sense of "weaving in," or integrating, new material." | Dreams |
OBJECTIVE: To describe the feasibility and outcomes of endovascular repair of distal aortic arch aneurysms using a patient-specific stent graft with a pre-loaded single retrograde left subclavian artery (LSA) branch stent graft. METHODS: We reviewed the clinical data and outcomes of consecutive patients enrolled in an ongoing prospective, non-randomized physician-sponsored investigational device exemption study to evaluate the outcomes of endovascular aortic arch repair using patient-specific arch branch stent grafts (William Cook Europe, Bjaeverskov, Denmark) between 2019 and 2022. All patients received a design with triple-wide scallop and a single retrograde LSA branch with a pre-loaded catheter. RESULTS: There were five male patients with median age of 77 years old (72-80) treated using the single LSA branch stent graft. Technical success was achieved in all patients. Median operating time, fluoroscopy time, and total radiation dose area product were 103 (78-134) minutes, 26 (19-39) minutes, and 123 (71-270) mGy.cm(2), respectively. There were no 30-day or in-hospital mortality, neurological or other major adverse events (MAEs). During median follow-up of 21 (20-27) months, all patients were alive with patent LSA branches, except for one who died of COVID-19 complications. There was no branch instability or secondary interventions. CONCLUSION: This early feasibility study demonstrates successful endovascular repair of distal aortic arch aneurysms using a patient-specific stent graft with single retrograde LSA branch without technical failures, mortality or neurological events. Larger clinical experience and longer follow-up are needed to determined effectiveness of this approach in patients who need endovascular repair with proximal extension into Zone 2. | Aneurysm, Aortic Arch |
Dyskeratosis congenita (DC) is a rare bone marrow failure syndrome that displays marked clinical and genetic heterogeneity. The identification of dyskeratosis congenita gene 1 (DKC1) mutations in X-linked recessive patients initially suggested that DC is a defective pseudouridylation disorder. The subsequent identification of mutations in the telomerase RNA component (TERC) of autosomal dominant DC patients together with the discovery that both TERC and the DKC1-encoded protein, dyskerin, are closely associated in the telomerase complex have suggested that the pathophysiology of DC predominantly relates to defective telomere maintenance. Recent discoveries have shown that autosomal dominant DC exhibits disease anticipation and that this is associated with progressive telomere shortening owing to the haplo-insufficiency of TERC. | Dyskeratosis Congenita |
PURPOSE: To provide a method for determining the vector that, when added to the preoperative astigmatism, results in no prediction error (PE) and to specify statistical methods for evaluating astigmatism and determining the 95% confidence convex polygon. SETTING: Baylor College of Medicine, Houston, Texas, and University of Southern California, Los Angeles, California. DESIGN: Retrospective consecutive case series. METHODS: An analysis of 3 clinical trials involving toric intraocular lenses was performed. 3 formulas were evaluated (generic vergence formula with zero surgically induced astigmatism, the Barrett toric formula, and the Holladay toric formula). Scalar and vector analyses were performed on each dataset with each formula and the results compared. Since the PE was not a Gaussian distribution, a 95% convex polygon was used to determine the spread of the data. RESULTS: The mean values for the vector absolute astigmatism PEs were not different for the 3 formulas and 3 datasets. The Barrett and Holladay toric calculators were statistically superior to the zero formula for 3 intervals (0.75, 1.0, and 1.25) in the high astigmatism dataset. CONCLUSIONS: Residual astigmatism and vector absolute astigmatism PE mean values and SDs are useful but require extremely large datasets to demonstrate a statistical difference, whereas examining percentages in 0.25 diopters (D) steps from 0.25 to 2.0 D reveals differences with far fewer cases using the McNemar test for a P value. Double-angle plots are especially useful to visualize astigmatic vector PEs, and a 95% confidence convex polygon should be used when distributions are not Gaussian. | Astigmatism |
Osmium tetraoxide, in the presence of ligands such as pyridine and bipyridine, adds across the etheno bridge of 1,N6-etheno-9-methyladenine and poly-1,N6-ethenoadenylic acid. The Os:P ratio in the labeled polynucleotide was approximately equal to 1 when bipyridine was used as the stabilizing ligand. A similar study with polycytidylic acid, which had been partially modified with chloroacetaldehyde so that some bases were converted to 3,N4-ethenocytosine, gave an OS:P ratio of approximately equal to 1.3. Calf-thymus DNA, in which the adenine and cytosine bases were modified by chloroacetaldehyde, gave an Os:P ratio of approximately equal to 1 after 24 h. These results suggest that 3,N4-ethenocytosine will add two Os labels. | Osmium Compounds |
Tracheobronchial obstruction resulting from esophageal carcinoma is uncommon. Patients with advanced esophageal carcinoma with tracheobronchial obstruction usually present with severe dyspnea or hemoptysis or both and may die of suffocation. The Lahey Clinic experience using laser bronchoscopy for the palliation of symptoms of airway obstruction in patients with esophageal carcinoma is presented. From 1982 to 1990, nine patients were treated in 13 procedures using the neodymium: yttrium-aluminum-garnet laser. Of the patients, seven had undergone previous treatment of the primary tumor. Tumors were located in the trachea in seven patients and in the main stem bronchi in three patients. Improvement of the airway caliber was achieved in all patients with relief of the dyspnea. The mean hospital stay was 2 days. One patient lived 4 years after laser treatment with no recurrence of tumor, and one patient died 1 week after treatment as a result of his poor general condition. The rest of the patients lived 3 to 41 weeks, with a median survival of 35 weeks. No complications were related to the procedures, and in particular, no tracheoesophageal fistulas developed. Our experience indicates that bronchoscopic application of this laser in conjunction with other treatment modalities can improve the quality and duration of life in selected patients with esophageal carcinoma that invades and obstructs the trachea. | Light Coagulation |
The intracellular localization of two neurotropic drugs, flunitrazepam (benzodiazepine) and triflupromazine (phenothiazine), was studied by secondary ion mass spectrometry microscopy (SIMS) in three varieties of cells. The images of the intracellular distributions of the two drugs are easily obtained by selecting the fluorine atom of the molecules. These images show that the drug from the benzodiazepine group is mainly located in the nuclei, whereas the phenothiazine is exclusively located inside the cytoplasm. | Triflupromazine |
Kimura disease (KD) is a rare, idiopathic chronic inflammatory disorder that usually presents as unilateral painless lymphadenopathy or soft tissue swelling of the head and neck region in young Asian males. The disease lacks pathognomonic clinical and cytomorphological features and can be mistaken for many reactive and malignant conditions. We report three cases of KD presenting as bilateral swelling of the head and neck region, and describe the cytomorphological features of each. In the correct clinical setting, a polymorphous lymphoid aspirate with eosinophils and Warthin-Finkeldey giant cells should raise a suspicion of KD and prompt further work up. | Kimura Disease |
BACKGROUND: The risk factors of paraplegia and paraparesis (P/P) after surgical repair of descending thoracic aortic aneurysm (TAA) are controversial. PATIENTS AND METHODS: Seventy five patients underwent surgical repair of descending TAA from 2001 through 2002. The mean age was 64.2+/-5.2 years old (range; 26-81) and 58 patients (77.3%) are male. There were 47 patients (62.7%) with nondissecting aortic aneurysm and 28 patients (37.3%) with chronic dissecting aortic aneurysm. Emergent operation was performed in 13 cases (17.3%). Retrospective analysis based on data of these 75 patients was performed to determine the risk factors of P/P. RESULTS: 30-days hospital mortality was 2.7%. The overall incidence of P/P was 12.0% (9/75) overall (immediate paraplegia; 4 (5.3%), delayed paraplegia; 1 (1.3%), immediate paraparesis; 3 (4.0%), delayed paraparesis; 1 (1.3%)). Logistic regression analysis revealed that predictive factors of the development of P/P were; cases in which the distal part (below Th9) of the descending thoracic aorta was included in the extent of graft replacement (P=0.020; odds ratio (OR), 7.981) and nondissecting aneurysm (P=0.029; OR, 12.109). CONCLUSION: There was an increased risk of P/P after descending TAA repair in cases in which the extent of graft replacement included below the Th9 or in cases with nondissecting aortic aneurysm. | Paraparesis |
Agrin plays a crucial role in the maintenance of the neuromuscular junction. However, it is expressed in other tissues as well, including T lymphocytes, where cell activation induces its expression. Agrin from activated T cells has the capacity to induce aggregation of key receptors and to regulate signalling. Interestingly, T cells isolated from patients with systemic lupus erythematosus over-express Agrin and its co-stimulation with the T cell receptor enhances production of pathogenic cytokines. These early studies point to an important function for Agrin in T cell biology and make the case for a more thorough and systematic investigation into its role in the immune system. | Agrin |
We describe the history and features of the Ladder of Life Detection, a tool intended to guide the design of investigations to detect microbial life within the practical constraints of robotic space missions. To build the Ladder, we have drawn from lessons learned from previous attempts at detecting life and derived criteria for a measurement (or suite of measurements) to constitute convincing evidence for indigenous life. We summarize features of life as we know it, how specific they are to life, and how they can be measured, and sort these features in a general sense based on their likelihood of indicating life. Because indigenous life is the hypothesis of last resort in interpreting life-detection measurements, we propose a small but expandable set of decision rules determining whether the abiotic hypothesis is disproved. In light of these rules, we evaluate past and upcoming attempts at life detection. The Ladder of Life Detection is not intended to endorse specific biosignatures or instruments for life-detection measurements, and is by no means a definitive, final product. It is intended as a starting point to stimulate discussion, debate, and further research on the characteristics of life, what constitutes a biosignature, and the means to measure them. | Mars |
The historical but questionable size-distance invariance hypothesis (SDIH) features computation over geometric, oculomotor, and binocular cues and the coupling of percepts-perceived size, S', is mediated by perceived distance, D'. A contemporary non-mediational hypothesis holds that S' and D' are specific to distinct optical variables. We report two experiments with an optical tunnel, an arrangement of alternating black and white concentric rings, that allows systematic manipulation of the optic array at a point of observation while controlling a variety of size and depth cues. Participants viewed targets of different sizes at different distances monocularly, reporting S' and D' via magnitude production. In Experiment 1, the target was either placed in a continuous tunnel (extending 164cm) or in a tunnel that truncated at the target's location. Experiment 2 included a third tunnel, one that was truncated with a flat depiction of the posterior surface structure that would have been visible in the continuous tunnel. In both experiments, S' decreased with D but D' was unaffected by S. Partial correlation analyses showed that the relationship between S' and D' was not significant when the contributions of other variables were removed. Importantly, S' and D' were affected differently by manipulations of the optical tunnel's continuity while computationally obvious visual cues were controlled. These outcomes suggest that D' is not a mediator of S'. Rather S' and D' are independently determined with correlated but different optical bases, results that support the direct model. | Size Perception |
The LHMDS-promoted in situ generation of difluoroenolates from readily available 1-aryl and 1-alkyl 2,2,4,4,4-pentafluorobutan-1,3-dione hydrates has been used to produce a series of pentafluorinated beta-hydroxy ketones in up to 95% yield. The reaction proceeds under mild conditions, tolerates a wide range of functional groups, and is complete within 10 min. Reduction toward the corresponding 1,3-diol with DIBAL gives quantitative amounts and favors the formation of the syn-isomer. | Ketones |
PURPOSE: This in vitro study was to compare the flexural properties, fracture toughness and hardness of three machinable composite materials. METHODS: Three kinds of resin composite ceramic Upcera Hyramic, 3M Lava Ultimate, Vita Enamic and a glass ceramic Vitablocs Mark II were chosen for the study. Bar-shaped specimens (16 mmx4 mmx1 mm, 2 mm) were prepared for flexural strength experiment; specimens (17 mmx4 mmx3 mm) were prepared for fracture toughness experiment and specimens of 4 mm thickness were prepared for hardness test. Flexural test and fracture toughness experiment were performed with an universal testing machine at a cross-head speed of 0.5 mm/min. Hardness test was performed with an micro hardness tester.Scanning electron microscope was used to observe the roughness of fracture surface. One-way variance analysis was used to determine the statistical differences with SPSS 17.0 software package. RESULTS: The mean flexural strength of the tested blocks at 1 mm thickness was Hyramicï¼Â207.7515+/-13.12ï¼ÂMPaï¼ÂVita Enamicï¼Â182.0286+/-15.18ï¼ÂMPaï¼ÂLava Ultimateï¼Â145.8469+/-8.98ï¼ÂMPaï¼ÂVitablocs MarkâÂ
¡ï¼Â103.0542+/-18.19ï¼ÂMPa. The mean flexural modulus were Vitablocs MarkâÂ
¡ï¼Â49.49+/-5.50ï¼ÂGPaï¼ÂVita Enamicï¼Â40.65+/-3.80ï¼ÂGPaï¼ÂHyramicï¼Â14.89+/-2.38ï¼ÂGPaï¼ÂLava Ultimateï¼Â7.09+/-1.24ï¼ÂGPa. The mean flexural strength of the tested blocks at 2 mm thickness was Hyramicï¼Â208.1986+/-25.07ï¼ÂMPaï¼ÂLava Ultimateï¼Â172.9297+/-12.73ï¼ÂMPaï¼ÂVitablocs MarkâÂ
¡ï¼Â158.6587+/-15.37ï¼ MPaï¼ÂVita Enamicï¼Â155.3670+/-13.77ï¼ÂMPa. The mean flexural modulus were Vitablocs MarkâÂ
¡ï¼Â24.07+/-1.86ï¼ÂGPaï¼ÂVita Enamicï¼Â19.64+/-0.98ï¼ÂGPaï¼ÂHyramicï¼Â10.35+/-0.87ï¼ÂGPaï¼ÂLava Ultimateï¼Â8.68+/-0.86ï¼ÂGPa. The mean fracture toughness was Vita Enamicï¼Â1.6357+/-0.16ï¼ÂMPa.m(1/2)ï¼ÂLava Ultimateï¼Â1.4286+/-0.11ï¼ÂMPa.m(1/2)>Vitablocs MarkIIï¼Â1.3233+/-0.10ï¼ÂMPa.m(1/2)>Hyramicï¼Â1.0614+/-0.09ï¼ÂMPa.m(1/2). The hardness of the experimental group was significantly lower than that of the control group. CONCLUSIONS: According to ISO 6872/2008, three kinds of machinable resin ceramic composites meet the needs of clinical strength.Hyramic showed higher flexural strength at different thickness, it is an ideal material for dental restoration. Vita Enamic has not only higher flexural strength at the thickness of 1 mm, but also good toughness, it is suitable for repair of patients that have limited occlusal space and great bite force, named occlusal veneer. | Pliability |
The prevalence rate of overactive bladder symptoms is 16% for men and 16.9% for women. Currently, m-anticholinergics are the first line of therapy. The selective and non-selective antimuscarinic drugs are available in Russian Federation. Some patients refuse long-term use of -anticholinergics due to either side effects, or insufficient efficacy. This situation prompted world scientific community to search of alternative treatment methods. Mirabegron is a selective 3-adrenoreceptors agonist, which represent a new approach to the treatment of patients with overactive bladder. In this article the studying of adrenoreceptors, properties of mirabegron and the possibilities for its applications are reviewed." | Adrenergic beta-3 Receptor Agonists |
Chitinases, a category of pathogenesis-related proteins, are responsible for catalyzing the hydrolysis of chitin into the N-acetyl-d-glucosamine. Therefore, chitinases are believed to function as a guardian against chitin-containing pathogens. Here, we examined the role of the Brassica rapa chitinase family genes in clubroot disease. A total of 33 chitinase genes were identified and grouped into five classes based on their conserved domain. They were distributed unevenly across eight chromosomes in B. rapa, and 31 of them contained few introns (</=2). In addition, the expression of these genes was organ-specific, and 14 genes were expressed differentially in response to Plasmodiophora brassicae challenge of clubroot-susceptible (CS NIL) and resistant (CR NIL) lines. Furthermore, reduced pathogen DNA content and clubroot symptoms were observed in the CS NILs after their treatment with chitin oligosaccharides 24â¯h prior to inoculation with P. brassicae. The findings indicate that chitinases play a crucial role in pathogen resistance of the host plants. The results offer an insight into the role of chitinase in B. rapa-P. brassicae interaction. | Plasmodiophorida |
Diphtheria antitoxin content in sera were determined automatically in Vero cell assay by spectrophotometric determination of the equivalence point between toxin and antitoxin followed by computer analysis of absorption values. The method was more accurate than visual reading and made handling of many samples easy. | Diphtheria Antitoxin |
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