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pubmed_93_17854
Crucial physiological advances in the phase analysis of cardiac performance with respect to their historical and biographical aspects are elucidated. The described period started from the early measurement of blood pressure (1733) and the first graphical representation of cardiac performance (1861), continued by the progress in recording of cardiac electrical activity and a detailed study of the consecutive events throughout the cardiac cycle (1921) and, finally, reached the recording of changes in the left ventricular dimensions and shape during the phase which precedes the start of blood ejection (1955-2005).
pubmed_93_17854
pubmed_301_4877
Given recent advances in phasing methods, those new to protein crystallography may be forgiven for asking 'what problem?'. As many of those attending the CCP4 meeting come from a biological background, struggling with expression and crystallization, this introductory paper aims to introduce some of the basics that will hopefully make the subsequent papers penetrable. What is the 'phase' in crystallography? What is 'the problem'? How can we overcome the problem? The paper will emphasize that the phase values can only be discovered through some prior knowledge of the structure. The paper will canter through direct methods, isomorphous replacement, anomalous scattering and molecular replacement. As phasing is the most acronymic realm of crystallography, MR, SIR, SIRAS, MIR, MIRAS, MAD and SAD will be expanded and explained in part. Along the way, we will meet some of the heroes of protein crystallography such as Perutz, Kendrew, Crick, Rossmann and Blow who established many of the phasing methods in the UK. It is inevitable that some basic mathematics is encountered, but this will be done as gently as possible.
10.1107/s0907444903017815
pubmed_1080_5732
It was found that [4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate]methanesulfonate (E-3123) inhibits trypsin, thrombin and kallikrein, and its inhibitory activity is most potent toward trypsin. The interactions of these enzymes with E-3123 were studied mainly by using stopped-flow spectrophotometry. E-3123 behaved as a quasi-substrate of the enzymes and the inhibitory property was due to the efficient production of the stable acyl-enzyme. The acylation process with trypsin was exceedingly effective, and the resulting acyl-enzyme was the most stable among the three enzymes tested. This observation affords a rational basis for explaining the action of E-3123, which is a transient inhibitor most active toward trypsin.
10.1248/cpb.37.2855
pubmed_874_6771
INTRODUCTION Primary sclerosing cholangitis (PSC) is a chronic immune-mediated liver disease that results in end-stage liver disease requiring liver transplantation. PSC is closely associated with inflammatory bowel disease (IBD) with 70% of patients with PSC also suffering from IBD. SOURCES OF DATA Data for this review were obtained from PubMed. AREAS OF AGREEMENT Historical and genome-wide association studies have established a strong human leukocyte antigen (HLA) linkage to PSC and defined specific haplotypes associated with enhanced PSC risk. Fifteen non-HLA loci have been defined in PSC. AREAS OF CONTROVERSY The biological role of risk loci in PSC and their place in PSC pathogenesis remain speculative but suggest significant interactions with the host microbiome and therapeutic opportunities. GROWING POINTS Genetics provides a platform to systematically target emerging therapies in PSC. AREAS TIMELY FOR DEVELOPING RESEARCH Linking PSC genotypes with biology and disease phenotypes paves the way for a personalized medicine approach to manage PSC.
10.1093/bmb/ldu008
pubmed_296_417
Extensive stalk elongation in Caulobacter and Asticcacaulis can be obtained in a defined medium by limiting the concentration of phosphate. Caulobacter cells which were initiating stalk formation were labeled with tritiated glucose. After removal of exogenous tritiated material, the cells were subjected to phosphate limitation while stalk elongation occurred. The location of tritiated material in the elongated stalks as detected by radioautographic techniques allowed identification of the site of stalk development. The labeling pattern obtained was consistent with the hypothesis that the materials of the stalk are synthesized at the juncture of the stalk with the cell. Complementary labeling experiments with Caulobacter and Asticcacaulis confirmed this result. In spheroplasts of C. crescentus prepared by treatment with lysozyme, the stalks lost their normal rigid outline after several minutes of exposure to the enzyme, indicating that the rigid layer of the cell wall attacked by lysozyme is present in the stalk. In spheroplasts of growing cells induced with penicillin, the stalks did not appear to be affected, indicating that the stalk wall is a relatively inert, nongrowing structure. The morphogenetic implications of these findings are discussed.
10.1083/jcb.28.3.423
pubmed_681_14012
In Alzheimer's disease (AD) brain the activity of protein phosphatase (PP)-2A is compromised and that of the extracellular signal-regulated protein kinase (ERK1/2) of the mitogen-activated protein kinase (MAPK) family, which can phosphorylate tau, is up-regulated. We investigated whether a decrease in PP-2A activity could underlie the activation of these kinases and the abnormal hyperphosphorylation of tau. Rat brain slices, 400-microm-thick, kept under metabolically active conditions in oxygenated (95% O(2), 5% CO(2)) artificial CSF were treated with 1.0 micromol/L okadaic acid (OA) for 1 hour at 33 degrees C. Under this condition, PP-2A activity was decreased to approximately 35% of the vehicle-treated control slices, and activities of PP-1 and PP-2B were not affected. In the OA-treated slices, we observed a dramatic increase in the phosphorylation/activation of ERK1/2, MEK1/2, and p70 S6 kinase both immunohistochemically and by Western blots using phosphorylation-dependent antibodies against these kinases. Treatment of 6-microm sections of the OA-treated slices with purified PP-2A reversed the phosphorylation/activation of these kinases. Hyperphosphorylation of tau at several abnormal hyperphosphorylation sites was also observed, as seen in AD brain. These results suggest 1) that PP-2A down-regulates ERK1/2, MEK1/2, and p70 S6 kinase activities through dephosphorylation at the serine/threonine residues of these kinases, and 2) that in AD brain the decrease in PP-2A activity could have caused the activation of ERK1/2, MEK1/2, and p70 S6 kinase, and the abnormal hyperphosphorylation of tau both via an increase in its phosphorylation and a decrease in its dephosphorylation.
10.1016/S0002-9440(10)63445-1
pubmed_585_3186
Increasing prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) worldwide is a growing public health concern. MRSA typing is an essential component of an effective surveillance system to describe epidemiological trends and infection control strategies. Current challenges for MRSA typing are focused on selecting the most appropriate technique in terms of efficiency, reliability, ease of performance and cost involved. This review summarises the available information on application, potential and problems of various typing techniques in discriminating the strains and understanding the epidemiology of MRSA strains. The phenotypic methods in general are easier to perform, easier to interpret, cost effective and are widely available, however less discriminatory. The genotypic methods are expensive and technically demanding, however more discriminatory. Newer technologies involving sequencing of various genes are coming up as broadly applicable and high throughput typing systems. Still there is no consensus regarding the single best method for typing of MRSA strains. Phage typing is recommended as first line approach in epidemiological investigation of MRSA strains. PFGE remains the gold standard for characterisation of outbreak strains. DNA sequencing methods including MLST, spa typing, SCCmec typing and toxin gene profile typing are more practical methods for detecting evolutionary changes and transmission events. The choice of typing technique further depends on the purpose of the study, the facilities available and the utility of data generated to answer a desirable research question. A need for harmonisation of typing techniques by following standard protocols is emphasised to establish surveillance networks and facilitate global MRSA control.
10.4103/0255-0857.93015
pubmed_442_22975
INTRODUCTION Transcatheter aortic valve implantation (TAVI) is an effective treatment for high-risk or inoperative patients with severe aortic stenosis. Given the unique characteristics of Asian populations, questions regarding mid-term outcomes in Asians undergoing TAVI have yet to be addressed. We evaluated the two-year clinical outcomes of TAVI in an Asian population using Valve Academic Research Consortium-2 definitions. METHODS This prospective study recruited 59 patients from a major academic medical centre in Singapore. The main outcomes were two-year survival rates, peri-procedural complications, symptom improvement, valvular function and assessment of learning curve. RESULTS Mean age was 76.8 years (61.0% male), mean body surface area 1.6 m2 and mean logistic EuroSCORE 18.7%. Survival was 93.2%, 86.0% and 79.1% at 30 days, one year and two years, respectively. At 30 days post TAVI, the rate of stroke was 1.7%, life-threatening bleeding 5.1%, acute kidney injury 25.0%, major vascular complication 5.1%, and new permanent pacemaker implantation 6.8%. 29.3% of TAVI patients were rehospitalised (47.1% cardiovascular-related) within one year. These composite outcomes were measured: device success (93.2%); early safety (79.7%); clinical efficacy (66.1%); and time-related valve safety (84.7%). Univariate analysis found these predictors of two-year all-cause mortality: logistic EuroSCORE (hazard ratio [HR] 1.07; p < 0.001); baseline estimated glomerular filtration rate (HR 0.97; p = 0.048); and acute kidney injury (HR 5.33; p = 0.022). Multivariate analysis identified non-transfemoral TAVI as a predictor of cardiovascular-related two-year mortality (HR 14.64; p = 0.008). CONCLUSION Despite the unique clinical differences in Asian populations, this registry demonstrated favourable mid-term clinical and safety outcomes in Asians undergoing TAVI.
10.11622/smedj.2016128
pubmed_224_2539
The performing of medical evaluations which result in the awarding or denial of substantial material benefits to claimants in the absence of therapeutic intent creates a situation in which traditional values of medicine cannot operate and raises many difficult ethical questions. The certifying physician is not accountable for the psychosocial consequences to the claimant of denial or direct gratification of basic needs even if these consequences can be determined. With the loss of therapeutic intent, the physician is more likely to be influenced by personal rather than professional values. Because of the adversary nature of these proceedings, the physician is placed in a classic 'double agent' dilemma which may reverberate his own internal conflicts. Since certification determinations often have 'life-and-death' economic consequences for disadvantaged claimants, the 'ethics of reality' may ultimately transcend all other ethical concerns. Perhaps a first step in clarifying these ethical issues would be to make a clear-cut distinction between diagnosing for administrative purposes and diagnosing for therapeutic purposes.
10.1016/0277-9536(83)90122-3
pubmed_436_11325
LEARNING OBJECTIVES Learning objectives of this paper are to review and to summarize the pathogenesis of bowel ischemia and to describe its clinical, pathological, and radiological manifestations. BACKGROUND Bowel ischemia is a common disorder produced by several causes, and it shows various clinical presentations connected with an high mortality. With the increase in average life expectancy, bowel ischemia represents one of the most threatening abdominal conditions in elderly patients. In the last decade, computed tomography has tremendously altered the diagnostic approach to bowel ischemia also influencing the therapeutic approach in the current practice. IMAGING FINDINGS Computed tomographic imaging findings include bowel wall thickening, portal venous gas, intramural pneumatosis, engorgement of mesenteric veins, loss or increase of bowel wall enhancement, and infarction of other abdominal organs. CONCLUSIONS Bowel ischemia shows a broad spectrum of radiological manifestations, and regardless of the primary causes, it produces similar radiological features. Bowel ischemia may simulate cancer or inflammatory conditions; so it is a mandatory tight integration between radiological and clinical signs.
10.1097/RCT.0b013e3180dc8cb1
pubmed_182_20847
OBJECTIVES Gingival recession and alveolar bone loss are common manifestations of periodontitis. Periodontal regeneration is the ideal strategy for rehabilitating periodontal tissue defects and preventing tooth loss. The present study examined whether localized, topical application of gingival overgrowth-inducing drugs, phenytoin, nifedipine or cyclosporine, induces periodontal regeneration. METHODS Polylactic-co-glycolic acid (PLGA) was used as the carrier for preparation of phenytoin, nifedipine or cyclosporine-loaded PLGA microspheres, using an oil-in-water emulsification technique. The drug-loaded microspheres were delivered to periodontal defects created on alveolar ridges mesial to the first maxillary molars of Sprague-Dawley rats. After eight weeks, the operation area in each rat, including the maxillary molars and periodontal tissues, was harvested and evaluated by micro-computed tomography, histochemical and immunohistochemical analyses. RESULTS Physical parameters representative of periodontal regeneration, including the length of new alveolar bone (p < 0.01) and the area of new alveolar bone (p < 0.01) were significantly improved in the phenytoin group. Compared to other groups, the phenytoin group demonstrated increased expression of COL-1, VEGF-A, osteoblast and osteoclast markers (BMP-2, TGF-β1, OCN and TRAP staining), as well as decreased expression of MMP-8. CONCLUSIONS Results of the present study provided new evidence that localized, controlled release of phenytoin confers therapeutic benefits toward gingival recession and alveolar bone loss. Phenytoin appears to be a promising drug that promotes periodontal regeneration.
10.1016/j.archoralbio.2018.10.002
pubmed_840_22979
Aneurysms of the left main coronary artery are exceedingly rare clinical entities, encountered incidentally in approximately 0.1% of patients who undergo routine angiography. Thrombosis within the aneurysm can lead to distal embolization and myocardial infarction. These lesions can extend into adjacent coronary branches and can occur in the presence or absence of obstructive coronary disease. Depending on the severity of coexistent coronary stenoses, patients with left main coronary artery aneurysms can be effectively managed either operatively or medically. We report the cases of 2 patients who were treated medically for large left main coronary aneurysms and concomitant right coronary artery ectasia.
pubmed_840_22979
pubmed_464_10944
Despite the significant prevalence of Major Depressive Disorder in the pediatric population, the pathophysiology of this condition remains unclear, and the treatment outcomes poor. Investigating tools that might aid in diagnosing and treating early-onset depression seems essential in improving the prognosis of the future disease course. Recent studies have focused on searching for biomarkers that constitute biochemical indicators of MDD susceptibility, diagnosis, or treatment outcome. In comparison to increasing evidence of possible biomarkers in adult depression, the studies investigating this subject in the youth population are lacking. This narrative review aims to summarize research on molecular and biochemical biomarkers in child and adolescent depression in order to advocate future directions in the research on this subject. More studies on depression involving the youth population seem vital to comprehend the natural course of the disease and identify features that may underlie commonly observed differences in treatment outcomes between adults and children.
10.1007/s10578-021-01246-y
pubmed_529_23062
INTRODUCTION An ageing population has become an urgent concern for Asia in recent times. In nursing homes, polypharmacy has also become a compounding issue. Deprescribing practice is an evidence-based strategy to provide a better outcome in this group of patients; however, its implementation in nursing homes is often challenging, and prospective outcome data on deprescribing practice in the elderly is lacking. Our study assesses the implementation of team-care deprescribing to understand the benefits of this practice in geriatric setting and to explore the factors affecting deprescribing practice. METHODS AND ANALYSIS This multicentre prospective study consists of a prestudy interview questionnaire, and a preintervention and postintervention study to be conducted in the nursing home setting on residents at least 65 years old and on five or more medications. We will employ a cluster randomised stepped-wedge interventional design, based on a five-step (reviewing, checking, discussion, communication and documentation) team-care deprescribing practice coupled with the use of a deprescribing guide (consisting of Beers and STOPP criteria, as well as drug interaction checking), to assess the health and pharmacoeconomic outcome in nursing homes' practice. Primary outcome measures of the intervention will consist of fall risks using a fall risk assessment tool. Other outcomes assessed include fall rates, pill burden including number of pills per day, number of doses per day and number of medications prescribed. Cost-related measures will include the use of cost-benefit analysis, which is calculated from the medication cost savings from deprescribing. For the prestudy interview questionnaire, findings will be analysed qualitatively using thematic analysis. ETHICS AND DISSEMINATION This study is approved by the Domain Specific Review Board of National Healthcare Group, Singapore (2016/00422) and Monash University Human Research Ethics Committee (2016-1430-7791). The study findings shall be disseminated in international conferences and peer-reviewed publications. The study is registered with ClinicalTrials.gov (NCT02863341), Pre-results.
10.1136/bmjopen-2016-015293
pubmed_822_23284
Diphosphoric acid (H4P2O7) is the first condensation product of phosphoric acid (H3PO4), the compound with the highest intrinsic proton conductivity in the liquid state. It exists at higher temperature (T > 200 °C) and lower relative humidity (RH ≈ 0.01%) and shows significant ionic conductivity under these conditions. In this work, ab initio molecular dynamics simulations of a pure H4P2O7 model system and NMR spectroscopy on nominal H4P2O7 (which contains significant amounts of ortho- and triphosphoric acid in thermodynamic equilibrium) were performed to reveal the nature and underlying mechanisms of the ionic conductivity. The central oxygen of the molecule is found to be excluded from any hydrogen bonding, which has two interesting consequences: (i) compared to H3PO4, the acidity of H4P2O7 is severely increased, and (ii) the condensation reaction only leads to a minor decrease in hydrogen bond network frustration, which is thought to be one of the features enabling high proton conductivity. A topological analysis of diphosphoric acid's hydrogen bond network shows remarkable similarities to that of phosphonic acid (H3PO3). The hydrogen bonding facilitates protonic polarization fluctuations (Zundel polarization) extending over several molecules (Grotthuss chains), the other important ingredient for efficient structural diffusion of protons. At T = 160 °C, this is estimated to make a conductivity contribution of about 0.1 S/cm, which accounts for half of the total ionic conductivity (σ ≈ 0.2 S/cm). The other half is suggested to result from diffusion of charged phosphate species (vehicle mechanism) that are present in high concentration, resembling conduction in ionic liquids.
10.1021/acs.jpcb.5b09684
pubmed_49_9798
Several recent, large epidemiologic and family studies suggest important temporal changes in the rates of major depression: an increase in the rates in the cohorts born after World War II; a decrease in the age of onset with an increase in the late teenaged and early adult years; an increase between 1960 and 1975 in the rates of depression for all ages; a persistent gender effect, with the risk of depression consistently two to three times higher among women than men across all adult ages; a persistent family effect, with the risk about two to three times higher in first-degree relatives as compared with controls; and the suggestion of a narrowing of the differential risk to men and women due to a greater increase in risk of depression among young men. These trends, drawn from studies using comparable methods and modern diagnostic criteria, are evident in the United States, Sweden, Germany, Canada, and New Zealand, but not in comparable studies conducted in Korea and Puerto Rico and of Mexican-Americans living in the United States. These cohort changes cannot be fully attributed to artifacts of reporting, recall, mortality, or labeling and have implications for understanding the etiology of depression and for clinical practice.
pubmed_49_9798
pubmed_78_69
Autoassociators are a special type of neural networks which, by learning to reproduce a given set of patterns, grasp the underlying concept that is useful for pattern classification. In this paper, we present a novel nonlinear model referred to as kernel autoassociators based on kernel methods. While conventional non-linear autoassociation models emphasize searching for the non-linear representations of input patterns, a kernel autoassociator takes a kernel feature space as the nonlinear manifold, and places emphasis on the reconstruction of input patterns from the kernel feature space. Two methods are proposed to address the reconstruction problem, using linear and multivariate polynomial functions, respectively. We apply the proposed model to novelty detection with or without novelty examples and study it on the promoter detection and sonar target recognition problems. We also apply the model to mclass classification problems including wine recognition, glass recognition, handwritten digit recognition, and face recognition. The experimental results show that, compared with conventional autoassociators and other recognition systems, kernel autoassociators can provide better or comparable performance for concept learning and recognition in various domains.
10.1109/tsmcb.2005.843980
pubmed_847_17374
Metal-organic frameworks (MOFs) are attracting tremendous research interest because of their rich redox sites and high specific area which are beneficial for the energy storage applications. Nevertheless, the poor conductivity, low mechanical strength and unsatisfactory capacity severely hinder their wide application. Hence, it is of practical significance to design highly efficient and facile strategy to solve these issues. Herein, vertically oriented ZnO nanorod arrays are applied as precursor to synthesize laminated scale-like and highly-oriented Ni/Zn-MOF/ZnO nanocomposite. Owing to the desirable conductivity resulting from the doping nickel ions and the interaction between ZnO and its relative MOF, the fabricated 0.3Ni/Zn-MOF/ZnO@CC electrode exhibits an electrochemical capacitance of 1693 mF cm-2 at 1 mA cm-2. Moreover, the electrochemical capacitance retention of 80.7 % after 2500 cycling numbers is obtained under the constant current density of 10 mA cm-2 and the low internal resistance Rs of 0.89 Ω is observed. For practical application, the as-synthesized laminated scale-like Ni/Zn-MOF/ZnO@CC nanocomposite is served as positive electrode to fabricate solid-state asymmetric supercapacitor device. Moreover, a 2.5 V indicator could be powered for 8 min when the prepared supercapacitor units are connected. This work demonstrates the promising potential of the synthesized scale-like Ni/Zn-MOF composites for electrochemical energy storage applications.
10.1016/j.jcis.2022.03.062
pubmed_1073_7538
BACKGROUND Chlorhexidine (CHX) is considered as a gold standard of antimicrobial rinses. Various herbal oral rinses are available in the market. However, little is known of its effectiveness. AIM The aim of this study was to evaluate the clinical changes after the usage of herbal oral rinse and 0.12% CHX. MATERIALS AND METHODS In a randomized clinical trial, 76 patients with dental plaque-induced gingivitis were assigned to Group I (Herbal Oral Rinse - Hiora(®)) and 76 patients with dental plaque-induced gingivitis to Group II (0.12% Chlorhexidine-Peridex(®)). Gingival index and Plaque index scores were recorded at baseline and 21 days after scaling. RESULTS Intragroup comparison in both groups showed that plaque index and gingival index scores were statistically significant after 21 days as compared to baseline. Intergroup comparison showed that plaque index scores and gingival index scores were statistically significant in Group II as compared to Group I. CONCLUSION When herbal oral rinse was compared to 0.12% CHX, 0.12% CHX mouth rinse effectively reduced the clinical symptoms of plaque-induced gingivitis.
10.4103/0972-124X.153478
pubmed_334_10514
Lexical information can bias categorization of an ambiguous phoneme and subsequently evoke a shift in the phonetic boundary. Here, we explored the extent to which this phenomenon is perceptual in nature. Listeners were asked to ignore auditory stimuli presented in a typical oddball sequence in which the standard was an ambiguous sound halfway between /t/ and /p/ embedded in a Dutch word normally ending in /t/ ('vloot', meaning 'fleet') or /p/ ('hoop', meaning 'hope'). As deviant served the non-ambiguous sound /t/ embedded in the same context. The amplitude of the MMN-response, indexing the perceptual difference between the ambiguous sound and unambiguous /t/ was bigger for the p-word 'hoop' than the t-word 'vloot'. This result is taken as an indication that lexical information actually reached down to early perceptual processing stages.
10.1016/j.neulet.2007.04.006
pubmed_324_22195
The human response to uncertainty has been well studied in tasks requiring attention and declarative memory systems. However, uncertainty monitoring and control have not been studied in multi-dimensional, information-integration categorization tasks that rely on non-declarative procedural memory. Three experiments are described that investigated the human uncertainty response in such tasks. Experiment 1 showed that following standard categorization training, uncertainty responding was similar in information-integration tasks and rule-based tasks requiring declarative memory. In Experiment 2, however, uncertainty responding in untrained information-integration tasks impaired the ability of many participants to master those tasks. Finally, Experiment 3 showed that the deficit observed in Experiment 2 was not because of the uncertainty response option per se, but rather because the uncertainty response provided participants a mechanism via which to eliminate stimuli that were inconsistent with a simple declarative response strategy. These results are considered in the light of recent models of category learning and metacognition.
10.3758/s13421-010-0041-4
pubmed_1048_18022
En bloc removal of the coccyx during sacrococcygeal teratoma resection is necessary to decrease the risk of recurrence. However, variable anatomy often makes the border between the coccyx and sacrum difficult to identify. We describe the use of intraoperative lateral pelvic X-ray to localize this border and ensure complete coccygectomy.
10.1007/s00383-016-4025-8
pubmed_157_15911
BACKGROUND Laryngeal cancer is one of the 10 leading causes of cancer in Indian men. The association of laryngeal cancer and tobacco smoking is well-established, but the peculiarities such as wide variation of disease distribution and survival, role of tobacco chewing, indoor air pollution, and dietary factors in laryngeal cancer causation needs to be understood. In this study, we review the descriptive and observational epidemiology of laryngeal cancer in India. MATERIALS AND METHODS MEDLINE and Web of science electronic database was searched from January 1995 to December 2013, using the using keywords "laryngeal cancer, laryngeal cancer outcome, epidemiology, etiological factor and their corresponding Mesh terms were used in combination like OR, AND." Two authors independently selected studies published in English and conducted in India. A total of 15 studies were found to be relevant and eligible for this review. RESULTS In India, laryngeal cancer contributes to approximately 3-6% of all cancers in men. The age-adjusted incidence rate of cancer larynx in males varies widely among registries, highest is 8.18 per 100,000 in Kamprup Urban District and the lowest is 1.26 per 100,000 in Nagaland. The 5-year survival for laryngeal cancer in India is approximately 28%. Indian studies show tobacco, alcohol, long-term exposure to indoor air pollution, spicy food, and nonvegetarian diet as risk factors for laryngeal cancer. CONCLUSION There is wide regional variation in the incidence of laryngeal cancer in India. Survival rates of laryngeal carcinoma are much lower as compared to other Asian countries. Studies conducted in India to identify important risk factors of laryngeal cancer are very limited, especially on diet and indoor air pollution. Hence, more research is required for identifying the etiological factors and development of scientifically sound laryngeal cancer prevention programs.
10.4103/0971-5851.166721
pubmed_912_24498
Reduced graphene oxide (rGO) is a promising material for a variety of thin-film optoelectronic applications. Two main barriers to its widespread use are the lack of (1) fabrication protocols leading to tailored functionalization of the graphene sheet with oxygen-containing chemical groups, and (2) understanding of the impact of such functional groups on the stability and on the optical and electronic properties of rGO. We carry out classical molecular dynamics and density functional theory calculations on a large set of realistic rGO structures to decompose the effects of different functional groups on the stability, work function, and photoluminescence. Our calculations indicate the metastable nature of carbonyl-rich rGO and its favorable transformation to hydroxyl-rich rGO at room temperature via carbonyl-to-hydroxyl conversion reactions near carbon vacancies and holes. We demonstrate a significant tunability in the work function of rGO up to 2.5 eV by altering the composition of oxygen-containing functional groups for a fixed oxygen concentration, and of the photoluminescence emission by modulating the fraction of epoxy and carbonyl groups. Taken together, our results guide the application of tailored rGO structures in devices for optoelectronics and renewable energy.
10.1021/nn305507p
pubmed_1021_8952
Among 68 patients who underwent laparoscopic cholecystectomy for treatment of symptomatic gallstones, serious complications occurred in three cases. One patient developed a stricture of the hepatic duct which probably was caused by electrocautery. In one case uncontrollable bleeding from the hepatic artery resulted in enforced conversion to open operation and one patient had a subphrenic accumulation of bile which could be drained percutaneously. In order to reduce the risk of iatrogenic injury to the bile ducts operative choleangiography should be attempted routinely.
pubmed_1021_8952
pubmed_658_8283
In Spain, any person under the age of 18 is a minor. Generally, minors lack the legal capacity to take legally binding actions because they are deemed incapable of legally binding consent. Spanish civil law recognises, however, that the child, in accordance with the law and being sufficiently mature, may act for himself. It stands, then, that consent, as expressed by the "sufficiently mature" minor, should be legally valid.
10.1136/jme.28.5.326
pubmed_76_16446
A fluorine-containing analogue of the cyclic AMP (cAMP) receptor protein (CRP) from Escherichia coli was prepared by biosynthetic incorporation of 3-fluorophenylalanine (3-F-Phe). 19F n.m.r. studies on this protein have provided direct evidence for cAMP-induced conformational changes not only within the cAMP-binding domain but also within the hinge region connecting the cAMP-binding domain to the DNA-binding headpiece. At 313 K, the 19F n.m.r. spectrum of [3-F-Phe]CRP showed five signals corresponding to the five phenylalanine residues as expected for a symmetrical dimer. Proteolysis of [3-F-Phe]CRP with subtilisin produced a fragment (the alpha-fragment) containing the cAMP-binding domain. The alpha-fragment contains all the phenylalanines except for Phe-136, a residue located in the hinge region. By comparing the 19F spectra of [3-F-Phe]CRP and its alpha-fragment, the signal for Phe-136 was assigned. The chemical shifts of the corresponding signals in the two spectra are similar, indicating that the alpha-fragment retains the structure it has in the intact protein. The largest cAMP-induced shift was observed for the signal from Phe-136 providing direct evidence for a conformational change in the hinge region. However, whereas binding of a single cAMP molecule to a CRP dimer is known to be sufficient to activate the DNA binding, the n.m.r. data indicate that the hinge region does not have the same conformation in both subunits when only one cAMP molecule is bound.
10.1042/bj2870627
pubmed_75_17953
Technetium99 Methylene Diphosphate bone scanning has been considered an early valuable tool to diagnose necrotizing progressive "malignant" external otitis. However, to our knowledge, no formal studies have actually compared bone scans of otherwise young, healthy patients with severe external otitis to scans of patients with clinical presentation of malignant external otitis. Twelve patients with only severe external otitis were studied with Technetium99 Diphosphate and were compared to known cases of malignant otitis. All scans were evaluated by two neuroradiologists with no prior knowledge of the clinical status of the patients. Nine of the 12 patients had positive bone scans with many scans resembling those reported with "malignant" external otitis. Interestingly, there was no consistent correlation between the severity of clinical presentation and the amount of Technetium uptake. These findings suggest that a positive bone scan alone should not be interpreted as indicative of "malignant" external otitis.
10.1002/lary.1986.96.11.1193
pubmed_463_6799
BACKGROUND Metastatic cancer infrequently involves the pancreas. When the pancreas hosts a metastatic tumor, cytopathological evaluation of fine-needle aspirate material is a crucial part of the diagnostic process. In this study, we show two institutions' experience with cytopathological diagnosis of pancreatic metastasis. METHODS Databases of institutional experience at The Johns Hopkins Hospital and Ohio State University Medical Center were queried for cases of metastatic tumors in the pancreas that underwent fine-needle aspiration. Demographic and pathological features were compiled and the cytomorphology was reviewed. RESULTS Forty-two cases of tumor metastasis to the pancreas were found. Over the time of this review, 5,495 aspirates were performed, and 43% (2,389/5,495) had malignant cytological findings. Thus, the 42 cases of metastatic disease to the pancreas comprised 0.8% of all pancreas aspirates and 1.8% of the malignant ones. Renal cell carcinoma was the most common metastasis, followed by melanoma and non-small cell lung carcinoma. Among the other tumors in this series, 2 cases each of rare metastases such as the fibrolamellar variant of hepatocellular carcinoma and solitary fibrous tumor were also seen. CONCLUSION The pancreas is rarely involved with metastatic disease, but when it is involved the most common tumor is renal cell carcinoma followed by melanoma and non-small cell lung cancer. Clinical history and awareness of the primary pancreatic mimickers are necessary for arriving at the correct diagnosis. As conventional pancreatic adenocarcinoma is uncommon in children and young adults, history of other tumors - even ones that usually follow an indolent course - is essential.
10.1159/000352006
pubmed_289_24680
Adverse antenatal maternal environments during pregnancy influence fetal development that consequently increases risks of mental health problems including psychiatric disorders in offspring. Therefore, behavioral and brain alterations caused by adverse prenatal environmental conditions are generally considered as deficits. In this article, we propose a novel hypothesis, along with summarizing a body of literatures supporting it, that fetal neurodevelopmental alterations, particularly synaptic network changes occurring in the prefrontal cortex, associated with adverse prenatal environmental conditions may be adaptation to cope with expected severe postnatal environments, and therefore, psychiatric disorders may be able to be understood as adaptive strategies against severe environmental conditions through evolution. It is hoped that the hypothesis presented in this article stimulates and opens a new venue on research toward understanding of biological mechanisms and therapeutic treatments of psychiatric disorders.
pubmed_289_24680
pubmed_1028_2761
In the rat, intravenous injection of BCG induced an increase in complement activity, oxidative activity towards paraphenylenediamine and serum haptoglobin level. A strong correlation was shown between oxidative activity and haptoglobin level. These increases were inhibited by glucocorticoids (cortisone, dexamethasone, methylprednisolone) but not by two non-steroidal anti-inflammatory drugs (indometacin, phenylbutazone). It is suggested that these BCG effects are related to the release of macrophage constituents and that this is inhibited by glucocorticoids.
pubmed_1028_2761
pubmed_716_15333
BACKGROUND AND AIM This retrospective, multicenter study aims to assess the efficacy and safety in Wilson disease (WD) patients treated with trientine tetrahydrochloride (TETA 4HCl) after switch from trientine dihydrochloride (TETA 2HCl). METHODS In total, 68 WD patients with stable copper metabolism were identified to receive TETA 4HCl (Cuprior™) after previous treatment with TETA 2HCl. We analyzed biochemical markers such as urinary copper, serum copper, non-coeruloplasmin bound copper (NCC), and transaminases as well as clinical scores (APRI; FIB-4 score) at baseline with a follow-up (FU) of 12 months. Safety of TETA 4HCl treatment was based on reported adverse events (AEs). RESULTS The study cohort reflects a common WD cohort with a mean age of 20.3 years at diagnosis and 38.3 years at baseline. There are no significant differences concerning serum copper, NCC, transaminases, APRI, and FIB-4 score in the 3-month FU. Six-month FU revealed a decreased AST (P = 0.008), APRI (P = 0.042), and FIB-4 score (P = 0.039). GGT varied only borderline significantly in the 3-month, but not in the 6-month FU. Comparison of urinary copper within the subsets did not reveal a difference to baseline in all FUs, suggesting stable control of copper metabolism. Few AEs during TETA 4HCl treatment were reported, most commonly gastrointestinal discomfort. Only three treatments with TETA 4HCl were discontinued. CONCLUSION Copper parameters and liver function were stable after treatment switch to TETA 4HCl. Treatment with TETA 4HCl was generally well tolerated. This study indicates that the switch from TETA 2HCl to TETA 4HCl is safe and viable.
10.1111/jgh.16050
pubmed_415_21363
This issue of Methods of Information in Medicine celebrates the journal's first 50 years. As the oldest journal in biomedical and health informatics and, being broader in its scope, as the journal dealing with the methodology and scientific fundamentals of organizing, representing and analysing data, information and knowledge in biomedicine and health care, the journal publications during the last five decades also reflect the formation of a scientific field that deals with information in biomedicine and health care. Five papers that arose from a scientific symposium on "biomedical informatics: confluence of multiple disciplines" held in Heidelberg, Germany, in June 2011 are included in this volume. The papers reflect not only the broad interdisciplinary scope of the journal, but also the broad and evolving scope of the field itself. We can also recognise that there is an ongoing need for original and relevant research. As a discipline that has an impact on many other fields and is also influenced by them, scientific exchange and collaborative research continues to be needed.
pubmed_415_21363
pubmed_751_3877
It is unfortunate that we cannot report, in the area of coagulation, advances that have been seen in related fields such as thrombolytic therapy. The reported progress (Gold et al, 1984; Van de Werf et al, 1984) with human recombinant tissue plasminogen activator (Pennica et al, 1983) augers well for the application of recombinant technology to the problems faced by patients with coagulation defects. While plasminogen activator is being assessed in an acute therapeutic setting, its use signals a beginning of the application of the technology to abnormalities of the haemostatic mechanism. Chronic administration of coagulation factors for prophylaxis and replacement therapy would appear to be just one more step down the pathway illuminated by the biochemists, microbiologists and cell biologists who have preceded the clinicians in this promising area. There is no record of the use of genetically engineered materials in the treatment of coagulation defects, primarily because the body of knowledge and refined techniques have only recently been acquired. For this reason we have had to project developments in other areas onto the problems that exist for the haemostatically compromised patient. In describing the potential usefulness of these technologies, it is difficult to ascertain where the logical projection, from a fully investigated model system, diverges from flights of imaginative fancy. Cloning projects considered overly ambitious and grandiose at the beginning of this decade are already accomplished feats. The feasibility of gene therapy in the mammalian system has been demonstrated, and trade publications now discuss governmental approval for investigative use of this procedure in 1985. Panels of physicians, scientists and even politicians now seriously contemplate and promulgate views and regulations pertaining to the efficacy and ethics of the use of genetic engineering in the treatment of human disease. The haemophilias will certainly be among the first genetic diseases to be approached with the techniques of recombinant DNA technology. Diagnostic testing, using cloned DNA, is already underway and therapeutic trials are predicted for the near future. Every observer of this rapidly growing field has to define for himself when the future is. For the potential carrier of haemophilia B, the future is now. For the physician managing the patient with a haemophilic inhibitor, the future can't come soon enough. And, for those who are concerned with man's tampering with the gene pools of living things, from viruses to humans, the future comes too quickly to be dealt with in a rational and understanding way.
pubmed_751_3877
pubmed_74_18241
Primary salivary gland-like tumors of the sella are rare and often challenging to diagnose. They reportedly derive from serous and mucinous glands that remain trapped in the infundibulum during embryogenesis. We report a 68-year-old man who presented with partial left third cranial nerve palsy, visual loss in the left eye without visual field defects, headache, weight loss and reduced muscle bulk. Neuroimaging studies demonstrated a solid and cystic, avidly enhancing lesion expanding the pituitary fossa and extending to the left cavernous sinus. The patient underwent craniotomy and the tissue removed showed features of epithelial-myoepithelial carcinoma similar to the salivary gland, skin and breast counterpart. No primary tumor was found outside the sella. The lesion behaved aggressively despite radio-chemotherapy and the patient died 22 months from the onset. The tumor showed a novel TP53 in-frame deletion (Gly154del) while no variants were found in H-RAS hotspot regions (codons 12, 13 and 61). Our report expands the spectrum of salivary gland-like tumors primarily occurring in the sella and emphasizes the need for specialist review of rare, non-neuroendocrine tumors of the pituitary and sella regions.
10.1111/neup.12628
pubmed_383_1647
During 450 million years of diversification on land, plants and microbes have evolved together. This is reflected in today's continuum of associations, ranging from parasitism to mutualism. Through phylogenetics, cell biology, and reverse genetics extending beyond flowering plants into bryophytes, scientists have started to unravel the genetic basis and evolutionary trajectories of plant-microbe associations. Protection against pathogens and support of beneficial, symbiotic, microorganisms are sustained by a blend of conserved and clade-specific plant mechanisms evolving at different speeds. We propose that symbiosis consistently emerges from the co-option of protection mechanisms and general cell biology principles. Exploring and harnessing the diversity of molecular mechanisms used in nonflowering plant-microbe interactions may extend the possibilities for engineering symbiosis-competent and pathogen-resilient crops.
10.1126/science.aba6605
pubmed_783_19620
The highly coordinated, dynamic nature of growth requires plants to perceive and react to various environmental signals in an interactive manner. Elaborate signaling networks mediate this plasticity in growth and the ability to adapt to changing environmental conditions. The fluctuations of stress-responsive hormones help alter the cellular dynamics and hence play a central role in coordinately regulating the growth responses under stress. Recent experimental data unequivocally demonstrated that interactions among various phytohormones are the rule rather than exception in integrating the diverse input signals and readjusting growth as well as acquiring stress tolerance. The presence of multiple and often redundant signaling intermediates for each phytohormone appears to help in such crosstalk. Furthermore, there are several examples of similar developmental changes occurring in response to distinct abiotic stress signals, which can be explained by the crosstalk in phytohormone signaling. Therefore, in this brief review, we have highlighted the major phytohormone crosstalks with a focus on the response of plants to abiotic stresses. The recent findings have made it increasingly apparent that such crosstalk will also explain the extreme pleiotropic responses elicited by various phytohormones. Indeed, it would not be presumptuous to expect that in the coming years this paradigm will take a central role in explaining developmental regulation.
10.1007/s00299-013-1461-y
pubmed_548_20978
DATA SOURCES Cochrane Oral Health Groups Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, key international orthodontic and dental journals and the World Health Organization (WHO) International Clinical Trials Registry Platform. STUDY SELECTION Randomised controlled trials comparing surgical anchorage with conventional anchorage in orthodontic patients. Trials comparing two types of surgical anchorage were also included. DATA EXTRACTION AND SYNTHESIS Data extraction was performed independently and in duplicate by three review authors and the Cochrane risk of bias tool was used to assess bias. Random-effects meta-analysis was used for more than three studies when pooling of the data was clinically and statistically appropriate. Fixed-effect analysis was undertaken with two or three studies. RESULTS Fifteen studies, involving 543 analysed participants, were included. Five ongoing studies were identified. Eight studies were assessed to be at high overall risk of bias, six at unclear risk and one study at low risk of bias. Ten studies (407 randomised and 390 analysed patients) compared surgical anchorage with conventional anchorage for the primary outcome. A random-effects meta-analysis of seven studies for the primary outcome found strong evidence of an effect of surgical anchorage. Compared with conventional anchorage, surgical anchorage was more effective in the reinforcement of anchorage by 1.68 mm (95% CI -2.27 mm to -1.09 mm) (moderate quality evidence). This result should be interpreted with some caution, however, as there was a substantial degree of heterogeneity for this comparison. There was no evidence of a difference in overall duration of treatment between surgical and conventional anchorage (low quality of evidence).Information on patient-reported outcomes such as pain and acceptability was limited and inconclusive. When direct comparisons were made between two types of surgical anchorage, there was a lack of evidence to suggest that any one technique was better than another. CONCLUSIONS There is moderate quality evidence that reinforcement of anchorage is more effective with surgical anchorage than conventional anchorage, and that results from mini-screw implants are particularly promising. While surgical anchorage is not associated with the inherent risks and compliance issues related to extra-oral headgear, none of the included studies reported on harms of surgical or conventional anchorage.
10.1038/sj.ebd.6401060
pubmed_24_20396
In circular smooth muscle bundles isolated from the guinea-pig stomach antrum, the effects of quinidine, Ni2+, flufenamic acid, niflumic acid, La3+, SKF-96365 and 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) on acetylcholine (ACh)-induced depolarization were investigated. Recording membrane potentials from smooth muscle cells with intracellular microelectrodes revealed that ACh (1 microM) depolarized the membrane by 5-8 mV and increased the amplitude and frequency of slow potentials. These effects were inhibited by atropine. Quinidine (10 microM) increased the amplitude of ACh-induced depolarization, with no alteration to the properties of slow potentials. Ni2+ (50 microM) transiently (5-10 min) depolarized the membrane by about 5 mV, with an associated increase in frequency and amplitude of slow potentials. In the stabilized condition with Ni2+, the amplitude of ACh-induced depolarization remained unchanged. Flufenamic acid (10 microM) inhibited the generation of slow potentials, with no change in either the amplitude of ACh-induced depolarization or of the amplitude and frequency of slow potentials generated during ACh stimulation. A high concentration of flufenamic acid (100 microM) depolarized the membrane and increased the amplitude of ACh-induced depolarization. Niflumic acid (10 microM) hyperpolarized the membrane and increased the amplitude and frequency of slow potentials and also the amplitude of ACh-induced depolarization. DIDS (100 microM) hyperpolarized the membrane and inhibited the amplitude and frequency of slow potentials, with no alteration to the amplitude of ACh-induced depolarization. SKF-96365 (3-50 microM) depolarized the membrane in a concentration-dependent manner, but did not change the level of ACh-induced depolarization. La3+ (50 microM) did not alter the properties of the slow potentials or the ACh-induced responses. These results provide evidence that ACh-induced depolarization is not inhibited by chemicals known to inhibit non-selective cation channels. We suggest that muscarinic receptor-mediated signal transduction may be different in smooth muscle and interstitial cells.
10.1540/jsmr.41.313
pubmed_442_21159
Two planarized analogues of the prototypical Blatter radical (1), peri-annulated 1S and 1O , are demonstrated and provide a new platform for molecular and supramolecular engineering, and for tuning electronic and magnetic properties of the radical. Planarization of 1 results in bathochromic shift to the near-IR region, greater spin delocalization, and anodic shift of the reduction potential only for 1S . Magnetization studies revealed nearly ideal paramagnetic behavior at high temperatures for both radicals 1S and 1O with one-dimensional ferromagnetic interaction in the former (2J=14.4 cm(-1) ) and antiferromagnetic interactions in 1O at low temperatures.
10.1002/anie.201605612
pubmed_217_16094
OBJECTIVE To report our experience in the selection of newborns candidate to therapeutic hypothermia. METHODS Retrospective study involving 47 newborns suffering from perinatal asphyxia from January 2008 to September 2011. RESULTS Thirty-five of 47 newborns admitted to our hospital fulfilled metabolic and neurological criteria for recruitment and were cooled. aEEG was carried out in 26 of them and resulted always abnormal. In three of the 12 newborns with only metabolic criteria, aEEG was moderately abnormal. They were cooled and their outcome (evaluated by General Movements and Griffiths Mental Development Scales for children aged 0-2 years) is good. Three additional newborns who only met the metabolic criterion reached our hospital after the therapeutic window for hypothermia and exhibited seizures; their outcome is poor. CONCLUSIONS In our experience, the inclusion of aEEG in the entry criteria would not have precluded newborns with neurological criteria from cooling. On the contrary, without an early aEEG, we would have excluded from hypothermia infants with moderate hypoxic-ischemic encephalopathy without precocious neurological signs who exhibited only the metabolic criterion, but with abnormal aEEG. If further studies will confirm that early aEEG might identify newborns suitable for cooling even in the absence of clinical signs, a revision of the entry criteria should be considered.
10.3109/14767058.2012.683896
pubmed_471_10043
Parents' cognitive schemas about parenting, personal vulnerabilities, and personal resources may affect their risk of engaging in parent-child aggression (PCA). This longitudinal study examined predictors of change in mothers' and fathers' PCA risk across the transition to parenthood, comparing trajectories of parents evidencing high versus low sociodemographic risk. Potential predictors involved parenting-relevant schemas (consistent with Social Information Processing theory, including approval of PCA, negative attributions of child behavior, and knowledge of nonphysical discipline options), personal vulnerabilities (psychopathology, intimate partner violence, substance use issues), and resources (problem-focused coping, emotion regulation, social support, and partner satisfaction). Results indicated that increases in PCA approval, negative child behavior attributions, and symptoms of psychopathology, as well as decreases in problem-focused coping skills, emotion regulation ability, and partner satisfaction, all significantly predicted changes in mothers' and fathers' PCA risk over time-regardless of risk group status. Notably, increases in intimate partner violence victimization and decreases in social support satisfaction predicted mothers' but not fathers' PCA risk change; moreover, increases in knowledge of nonphysical discipline alternatives or in substance use issues did not predict change in PCA risk for either mothers or fathers. Risk groups differed in PCA risk across all predictors with minimal evidence of differential trajectories. Overall, these findings have important implications for child abuse prevention programs involving both universal and secondary abuse prevention efforts.
10.1016/j.chiabu.2018.09.008
pubmed_949_14716
BACKGROUND The study of the sensitivity of screening assays is greatly facilitated by testing the sequential changes in seroconverting individuals. The aim of this study was to investigate the early immunologic response after hepatitis C virus (HCV) infection and to evaluate whether HCV envelope (E2) recombinant antigen would provide a significant increase in sensitivity for detection of anti-HCV. STUDY DESIGN AND METHODS Twenty hemodialysis patients who were seroconverting to anti-HCV were included in this study. They were followed up for a mean period (+/- SD) of 10.5 +/- 3.3 months, in which 13 to 46 serum samples per case were collected. Each sample was tested for anti-HCV by second- and third-generation enzyme immunoassay (EIA-2 and EIA-3) and recombinant immunoblot assay (RIBA-3). E2 antibodies were tested by a prototype EIA in which E2 was expressed as a recombinant antigen in Chinese hamster ovary cells. RESULTS Alanine aminotransferase elevation was observed in 18 of 20 cases. Reactivity against c100, c33c, c22, NS5, and E2 was detected in 15 (75%), 19 (95%), 15 (75%), 2 (10%), and 17 (85%) patients, respectively; c33c was the most immunogenic antigen, followed in descending order by E2, c22, c100, and NS5. E2 antibody reactivity resolved the two RIBA-3-indeterminate cases. However, there was no case in which E2 reactivity preceded all other HCV antigens. Anti-E2 was found to react in all patients of genotypes 1a, 1b, and 3a but in only 2 of 4 patients of genotype 4a. CONCLUSION In this group of seroconverting individuals, E2 antigen was shown to be highly immunoreactive and did resolve some RIBA-3-indeterminate samples as being positive, on the basis of reactivity to multiple antigens, but it did not improve early detection of seroconversion.
10.1046/j.1537-2995.1997.37897424411.x
pubmed_143_6207
The diverse reactivity of N-heterocyclic carbenes (NHCs) in organocatalysis is due to the possibility of different modes of action. Although NHC-bound enolates and dienolates are known, the related NHC-bound cross-conjugated aza-trienolates remain elusive. Herein, we demonstrate the NHC-catalyzed formal [6+2] annulation of nitrogen-containing heterocyclic aldehydes with α,α,α-trifluoroacetophenones leading to the formation of versatile pyrrolooxazolones (29 examples). The catalytically generated cross-conjugated aza-trienolates (aza-fulvene type) underwent smooth [6+2] annulation with electrophilic ketones to afford the product in moderate to good yields under mild conditions. Preliminary DFT studies on the mechanism are also provided.
10.1002/chem.201905177
pubmed_808_16107
Protein interactions (PI) underlie complex biological processes. Protein interaction partners include DNA, RNA, ions, small chemical compounds, and proteins (protein-protein interactions; PPI). Analysis of sequence variants within regions corresponding to experimentally validated PI sites presents novel opportunities for understanding of complex diseases. Such information has not been systematically collected due to the fact that datasets are dispersed throughout databases and publications. Sequence variants and PI regions were obtained from the UniProt database. The location of the variants was compared to start and end positions of each PPI. Associations of sequence variants with phenotype were obtained from databases including COSMIC, GAD, PharmGKB, and dbSNP. We developed a catalogue of 603 sequence variants located within regions corresponding to experimentally validated PI sites, mostly PPI regions. These sequence variants were previously associated with risk for cancer, reproduction, ageing, renal, and immune system diseases. The developed catalogue connects information from different research papers and databases, represents a new layer of information and enables designing new hypotheses. It provides a baseline for prioritization of sequence variants, which may affect protein function and binding sites. The study contributes to the development of the proteogenomics field and provides new insights for understanding molecular mechanisms underlying disease development.
10.1002/minf.201700017
pubmed_653_20484
OBJECTIVES Pulmonary artery sling is frequently associated with tracheal and/or bronchial stenosis. A number of patients receive only re-implantation or relocation of the left pulmonary artery (LPA) while other patients may require tracheoplasty for stenosis of the airway. This study used computer tomography (CT) scans for the evaluation of airways and to evaluate the trachea diameter and the clinical outcomes with or without tracheoplasty. METHODS A total of 15 patients with PA sling who received CT scans were included in this study. We reviewed the clinical outcomes and the severity of trachea stenosis, and evaluated various surgical strategies. RESULTS Among the 15 patients, one received only conservative treatment, 14 (93%) patients received LPA re-implantation, and eight (53%) received tracheoplasty. For the eight patients that received LPA reimplantation and tracheoplasty, five received slide tracheoplasty and all survived, two patients had pericardial patch augmentation and both died, and one patient received a resection and end-to-end anastomosis and survived. The diameter of the trachea in survivors without tracheoplasty was significantly larger than those who died or received tracheoplasty (3.2 ± 0.3 mm vs. 2.2 ± 0.4 mm, P = 0.003). Establishing 3.0 mm as the threshold, the positive predictive value for tracheoplasty or mortality was 89% and the negative predictive value was 83%. CONCLUSIONS In this study cohort, approximately 60% of the patients with PA sling received tracheoplasty. A diameter of the trachea <3 mm is associated with the use of tracheoplasty or poor outcomes. Slide tracheoplasty provided acceptable good results.
10.1002/ppul.22516
pubmed_744_18304
The information provided by functional images may be used to guide radiotherapy planning by identifying regions that require higher radiation dose. In this work we investigate the dosimetric feasibility of delivering dose to lung tumors in proportion to the fluorine-18-fluorodeoxyglucose activity distribution from positron emission tomography (FDG-PET). The rationale for delivering dose in proportion to the tumor FDG-PET activity distribution is based on studies showing that FDG uptake is correlated to tumor cell proliferation rate, which is shown to imply that this dose delivery strategy is theoretically capable of providing the same duration of local control at all voxels in tumor. Target dose delivery was constrained by single photon emission computed tomography (SPECT) maps of normal lung perfusion, which restricted irradiation of highly perfused lung and imposed dose-function constraints. Dose-volume constraints were imposed on all other critical structures. All dose-volume/function constraints were considered to be soft, i.e., critical structure doses corresponding to volume/function constraint levels were minimized while satisfying the target prescription, thus permitting critical structure doses to minimally exceed dose constraint levels. An intensity modulation optimization methodology was developed to deliver this radiation, and applied to two lung cancer patients. Dosimetric feasibility was assessed by comparing spatially normalized dose-volume histograms from the nonuniform dose prescription (FDG-PET proportional) to those from a uniform dose prescription with equivalent tumor integral dose. In both patients, the optimization was capable of delivering the nonuniform target prescription with the same ease as the uniform target prescription, despite SPECT restrictions that effectively diverted dose from high to low perfused normal lung. In one patient, both prescriptions incurred similar critical structure dosages, below dose-volume/function limits. However, in the other patient, critical structure dosage from the nonuniform dose prescription exceeded dose-volume/function limits, and greatly exceeded that from the uniform dose prescription. Strict compliance to dose-volume/ function limits would entail reducing dose proportionality to the FDG-PET activity distribution, thereby theoretically reducing the duration of local control. Thus, even though it appears feasible to tailor lung tumor dose to the FDG-PET activity distribution, despite SPECT restrictions, strict adherence to dose-volume/function limits could compromise the effectiveness of functional image guided radiotherapy.
10.1118/1.1750991
pubmed_439_7151
Chitooligosaccharide (COS)-polyphenol (PPN) conjugates prepared using different PPNs, including gallic, caffeic, and ferulic acids, epigallocatechin gallate, and catechin, at various concentrations were characterized via UV-visible, FTIR, and 1H-NMR spectra and tested for antioxidant, antidiabetic, and antimicrobial activities. Grafting of PPNs with COS was achieved. The highest conjugation efficiency was noticed for COS-catechin (COS-CAT), which was identified to have the highest total phenolic content (TPC) out of all the conjugates (p &lt; 0.05). For antioxidant activities, DPPH and ABTS radical scavenging activities (DPPH-RSA and ABTS-RSA, respectively), oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), and metal chelating activity (MCA) of all the samples were positively correlated with the TPC incorporated. COS-CAT had higher DPPH-RSA, ABTS-RSA, ORAC, and FRAP than COS and all other COS-PPN conjugates (p &lt; 0.05). In addition, COS-CAT also showed the highest antidiabetic activity of the conjugates, as determined by inhibitory activity toward α-amylase, α-glucosidase, and pancreatic lipase (p &lt; 0.05). COS-CAT also had the highest antimicrobial activity against all tested Gram-negative and Gram-positive bacteria (p &lt; 0.05). Overall, grafting of PPNs, especially CAT on COS, significantly enhanced bioactivities, including antioxidant and antimicrobial, which could be used to retard spoilage and enhance shelf-life of various food systems. Moreover, the ability of COS-CAT to inhibit digestive enzymes reflects its preventive effect on diabetes mellitus and its complications.
10.3390/foods11070920
pubmed_176_18946
The HeartMate II LVAD has provided a bridge to heart transplantation or a permanent fixture for destination therapy for patients with heart failure. LVAD infections are associated with significant morbidity even when treated with explantation, device exchange, or a salvage procedure. We present an unusual complication following the placement of the HeartMate II device in an adolescent, whereby a pocket infection resulted in a large soft tissue defect overlying and surrounding the device. The novel use of a VRAM flap was successfully used to repair the defect and salvage the device.
10.1111/j.1399-3046.2011.01474.x
pubmed_835_24410
A 31-year-old man presented to our hospital's Emergency Department with sudden epigastric pain and vomiting. He had undergone endoscopic resection via the retroperitoneal route for a retroperitoneal tumor located in the left diaphragmatic crus of the esophageal hiatus at another hospital 8 months previously. Radiography and computed tomography showed inversion of the stomach beyond the diaphragm into the thoracic cavity, with the gastroesophageal junction serving as the fulcrum point. This finding led to a diagnosis of postoperative diaphragmatic hernia accompanied by an upside-down stomach (UDS). The prolapsed stomach in the thoracic cavity was reduced to the abdominal cavity using laparoscopic surgery. The postoperative course was favorable, and the patient was discharged from the hospital on postoperative day 7. No recurrence has been observed in the past 5 years. The pathological condition of a UDS observed in esophageal hiatal hernias may be found in postoperative diaphragmatic hernias. Laparoscopic surgery for a postoperative diaphragmatic hernia with a UDS is considered a useful surgical procedure. Laparoscopic surgery can simultaneously confirm the viability of the herniated organs, reduce the organs to the abdominal cavity, and close and reinforce the diaphragm.
10.1177/03000605221115158
pubmed_322_21316
BACKGROUND There is inconsistent evidence suggesting the clinical relevance of the early detection of future needs of preterm patent ductus arteriosus (PDA) surgery. We tested the hypothesis that echocardiographic indices at 3 days of age predict the future need for PDA surgery. METHODS We analyzed a database including the clinical and echocardiographic data of 710 preterm infants with gestational ages between 23 and 29 weeks in 34 Japanese neonatal intensive care units, and prospectively collected data over 14 months. The predictive or discriminative ability of each echocardiographic index at 3 days of age for future PDA surgical closure was evaluated using multivariable logistic regression analyses with adjustment for gestational age, sex, and small-for-gestational-age status, according to the areas under the receiver-operating characteristic curves (AUCs) of the models. RESULTS A total of 688 eligible patients (median gestational age: 26 weeks, body weight at birth: 843 g) were analyzed, of whom 77 (11%) underwent PDA surgery (median age: 21 days) after full consideration of clinical conditions. The AUC of PDA diameter (PDAd) was the largest, followed by that of the left pulmonary artery end-diastolic velocity (LPAedv). Compared with the ratio of left atrial-to-aorta diameter (AUC 0.76), PDAd (AUC 0.84, p < 0.001) and LPAedv (AUC 0.82, p = 0.003) were significantly better predictors of future PDA surgery. CONCLUSION Echocardiographic indices at 3 days of age, especially PDAd and LPAedv, may predict the future need for surgical closure of PDA in preterm infants.
10.1016/j.jjcc.2021.08.007
pubmed_173_11133
CD26 is a T cell activation marker consisting in a type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. It has been described that DPPIV inhibition delays the onset of type 1 diabetes and reverses the disease in non-obese diabetic (NOD) mice. The aim of the present study was to assess the effect of MK626, a DPPIV inhibitor, in type 1 diabetes incidence and in T lymphocyte subsets at central and peripheral compartments. Pre-diabetic NOD mice were treated with MK626. Diabetes incidence, insulitis score, and phenotyping of T lymphocytes in the thymus, spleen and pancreatic lymph nodes were determined after 4 and 6 weeks of treatment, as well as alterations in the expression of genes encoding β-cell autoantigens in the islets. The effect of MK626 was also assessed in two in vitro assays to determine proliferative and immunosuppressive effects. Results show that MK626 treatment reduces type 1 diabetes incidence and after 6 weeks of treatment reduces insulitis. No differences were observed in the percentage of T lymphocyte subsets from central and peripheral compartments between treated and control mice. MK626 increased the expression of CD26 in CD8+ T effector memory (TEM) from spleen and pancreatic lymph nodes and in CD8+ T cells from islet infiltration. CD8+TEM cells showed an increased proliferation rate and cytokine secretion in the presence of MK626. Moreover, the combination of CD8+ TEM cells and MK626 induces an immunosuppressive response. In conclusion, treatment with the DPPIV inhibitor MK626 prevents experimental type 1 diabetes in association to increase expression of CD26 in the CD8+ TEM lymphocyte subset. In vitro assays suggest an immunoregulatory role of CD8+ TEM cells that may be involved in the protection against autoimmunity to β pancreatic islets associated to DPPIV inhibitor treatment.
10.1371/journal.pone.0142186
pubmed_591_9616
A homogeneous Pd-catalyzed stereodivergent reduction of alkynes to Z and E alkenes by using H2 O as the H2 source is presented. Mediated by a diboron reagent, the transfer hydrogenation has been accomplished to yield the desired geometrical isomer by rational ligand selection. The switchable stereoselectivity achieved using simple phosphine ligands is generally excellent. D2 O has also been used as a D2 source for synthesizing the corresponding deuterated olefins. Supported by a gram-scale synthesis, the reaction can easily be scaled up making it an efficient way to prepare alkenes commercially as well. Mechanistic studies suggest formation of H-PdL2 -OAc as the crucial step leading to the presence of two pathways involving H-Pd-B(OR)2 and molecular H2 as active intermediates.
10.1002/chem.201803147
pubmed_1121_15648
We present a mathematical model and a statistical framework to estimate uncertainty in the number of SARS-CoV-2 genome copies deposited in the respiratory tract of a susceptible person, , over time in a well mixed indoor space. By relating the predicted median for a reference scenario to other locations, a Relative Exposure Index (REI) is established that reduces the need to understand the infection dose probability but is nevertheless a function of space volume, viral emission rate, exposure time, occupant respiratory activity, and room ventilation. A 7  h day in a UK school classroom is used as a reference scenario because its geometry, building services, and occupancy have uniformity and are regulated. The REI is used to highlight types of indoor space, respiratory activity, ventilation provision and other factors that increase the likelihood of far field (  m) exposure. The classroom reference scenario and an 8  h day in a 20 person office both have an and so are a suitable for comparison with other scenarios. A poorly ventilated classroom (1.2 l s-1 per person) has suggesting that ventilation should be monitored in classrooms to minimise far field aerosol exposure risk. Scenarios involving high aerobic activities or singing have ; a 1  h gym visit has a median , and the Skagit Choir superspreading event has . Spaces with occupancy activities and exposure times comparable to those of the reference scenario must preserve the reference scenario volume flow rate as a minimum rate to achieve , irrespective of the number of occupants present.
10.1016/j.buildenv.2021.107617
pubmed_340_1846
Shengmai San (SMS) is a traditional Chinese medicine (TCM) comprising three different herbal components, Panax ginseng, Ohiopogon japonicus and Fructus schisandrae and has been used for treating coronary heart diseases (Bensky and Barolet, 1990). It was shown that SMS effectively prevented cerebral oxidative injury in rats when it administered into the duodenum before cerebral ischemia-reperfusion. In the present study, we examined whether post-ischemic administration of SMS can ameliorate cerebral ischemia-reperfusion injury in rats as well. Results showed that SMS injected immediately after ischemia also prevented the ischemia-reperfusion injury, when the effect was evaluated by the formation of protein carbonyl and thiobarbituric acid reactive substance (TBARS), and the loss of glutathione peroxidase (GPX). The preventative potential of SMS was decreased rapidly dependent on the time lag until SMS was injected after ischemia. However, it was noted that intravenously administered SMS protected the oxidative injury approximately 30% even after 60 min of reperfusion in terms of protein carbonyl formation. It is thus suggested that SMS injection might be useful for preventing the progression of injury in cerebral infarction after stroke.
10.1142/S0192415X06004120
pubmed_426_5615
A low power carbon dioxide laser was used to perform 212 end-to-end laser-assisted microvascular anastomoses (LAMA) of femoral arteries (mean diameter, 1.2 mm) in Sprague-Dawley rats. Eighty-two conventional microvascular suture anastomoses (CMSA) utilizing 10-0 monofilament interrupted sutures were done for comparison of techniques and wound healing. The mean duration of each anastomosis procedure was 16 minutes for the LAMA repairs, compared to an average of 27 minutes for the CMSA repairs (P less than 0.05). All anastomoses were patent at the completion of the procedure. Each laser-assisted anastomosis required an average of seven intermittent laser exposures of 0.1 to 0.3 seconds each with approximately 80 mW of CO2 (wavelength = 10.6 micron) radiation at a spot size of 150 micron. A patency rate of 95% was obtained on the LAMA vessels (202 of 212) compared to 96% for the CMSA repairs (79 of 82). A total of 14 aneurysms were noted in the LAMA group (7%) compared to 11 in the CMSA (13%). All aneurysms were in patent vessels. Histological analysis indicates that the progression of wound healing of LAMA and CMSA anastomoses follows similar paths chronologically and morphologically with increased scar tissue formation around the suture. Scanning electron microscopy confirms the comparable luminal healing of the LAMA and CMSA vessels, with complete reendothelialization occurring by 3 weeks postoperatively. The tensile strength of the LAMA repair, although low immediately after operation, is comparable to that of the intact artery at 21 days. These findings suggest that a low energy carbon dioxide microsurgical laser has potential beneficial clinical application for anastomosis of small vessels.
10.1227/00006123-198612000-00006
pubmed_314_10203
The purpose of this paper is to review the epidemiologic evidence for the effects of tobacco use and tobacco use cessation on a variety of oral diseases and conditions. Exposures considered include cigarette and bidi smoking, pipe and cigar smoking, and smokeless tobacco use. Oral diseases and disorders considered include oral cancer and precancer, periodontal disease, caries and tooth loss, gingival recession and other benign mucosal disorders as well as implant failure. Particular attention is given to the impact of tobacco use cessation on oral health outcomes. We conclude that robust epidemiologic evidence exists for adverse oral health effects of tobacco smoking and other types of tobacco use. In addition, there is compelling evidence to support significant benefits of tobacco use cessation with regard to various oral health outcomes. Substantial oral health benefits can be expected from abstention and successful smoking cessation in a variety of populations across all ages.
pubmed_314_10203
pubmed_692_6403
Lantana camara, a native plant from tropical America, is considered one of the most harmful invasive species worldwide. Several studies have identified potentially invasible areas under scenarios of global change, on the assumption that niche is conserved during the invasion process. Recent studies, however, suggest that many invasive plants do not conserve their niches. Using Principal Components Analyses (PCA), we tested the hypothesis of niche conservatism for L. camara by comparing its native niche in South America with its expressed niche in Africa, Australia and India. Using MaxEnt, the estimated niche for the native region was projected onto each invaded region to generate potential distributions there. Our results demonstrate that while L. camara occupied subsets of its original native niche in Africa and Australia, in India its niche shifted significantly. There, 34% of the occurrences were detected in warmer habitats nonexistent in its native range. The estimated niche for India was also projected onto Africa and Australia to identify other vulnerable areas predicted from the observed niche shift detected in India. As a result, new potentially invasible areas were identified in central Africa and southern Australia. Our findings do not support the hypothesis of niche conservatism for the invasion of L. camara. The mechanisms that allow this species to expand its niche need to be investigated in order to improve our capacity to predict long-term geographic changes in the face of global climatic changes.
10.1371/journal.pone.0111468
pubmed_632_7092
The aim of this study was to develop surface-enhanced Raman spectroscopy (SERS) methods in combination with novel gold nanomaterial-based substrates for rapid measurement and quantification of pesticides extracted from lemon, carrot, and mango juice. Facile synthesis of a sensitive and robust SERS substrate was achieved by assembling gold nanorods (AuNRs) into vertically aligned arrays on silicon slides. The nanorod arrays were orderly aligned and can induce vigorous electromagnetic field for SERS measurement. The synthesized SERS substrate was utilized for detection and quantification of thiabendazole in juice samples using partial least squares analysis with R values of 0.99, 0.98, and 0.99 for lemon, carrot, and mango juice, respectively. The detection limits of thiabendazole were 149, 216, and 179 μg/L in lemon, carrot, and mango juice, respectively. These results demonstrate that SERS combined with AuNR substrates is a quick, convenient, and highly sensitive technique for detection of thiabendazole residues in fruits juice.
10.1016/j.foodchem.2018.03.105
pubmed_532_9289
The human copper chaperone Atox1 plays a central role in the transport of copper in cells. It has been reported that the conserved residue Lys60 contributes to the heterocomplex stability of Atox1 with its target protein ATPase, and that the K60A mutation could diminish the copper transfer. In this work, we carried out the structure determination and dynamic analysis of Atox1 with the K60A mutation in order to elucidate the role of the conserved residue Lys60 in the copper transport. Results show that the K60A mutation results in crucial secondary structure rearrangements and side-chain orientation alteration of the metal-binding residues in Atox1. Protein dynamic studies reveal that the K60A mutation leads to increased overall flexibility, and a significant difference in dynamic properties of the metal-binding sites. The structure and dynamic changes cause a decrease in the copper-binding stability of the K60A mutant. In addition, Cu(i)-mediated hetero-protein interactions with ATP7A are present in the metal transfer of both Atox1 variants, although copper transfer is accompanied with smaller structural alteration in the K60A mutant. These results indicate that Lys60 is crucial in maintaining the structure and dynamic properties of Atox1.
10.1039/c3mt00190c
pubmed_313_953
Sensing environmental temperature is crucial for animal life. The model animal, Drosophila melanogaster, can be investigated with a large number of genetic tools, which have greatly facilitated studies of the cellular and molecular mechanisms of thermal sensing. At the molecular level, a group of proteins, including Transient Receptor Potential channels and ionotropic receptors, have been characterized as potential thermal sensors in both larval and adult Drosophila. At the cellular and circuit levels, peripheral and central thermosensory neurons have been identified. More interestingly, thermal information has been found to be specifically encoded by specific central neurons. In this short review, we mainly survey the progress in understanding the molecular mechanisms of thermosensation and the neuronal mechanisms of thermal information processing in the brain of Drosophila. Other recent temperature-related findings such as its impact on neurosecretion and thermotactic behavior in Drosophila are also introduced.
10.1007/s12264-016-0087-9
pubmed_699_7366
Tricho-hepato-enteric syndrome (THES) (OMIM #222,470) is a rare autosomal recessive syndromic enteropathy whose primary manifestations are dysmorphism, intractable diarrhea, failure to thrive, hair abnormalities, liver disease, and immunodeficiency with low serum IgG concentrations. THES is caused by mutations of either Tetratricopeptide Repeat Domain 37 (TTC37) or Ski2 like RNA Helicase (SKIV2L), genes that encode two components of the human SKI complex. Here, we report a patient with a TTC37 homozygous mutation phenotypically typical for tricho-hepato-enteric syndrome in whom extremely elevated IgM with low IgG was present at the time of diagnosis. These manifestations were not previously described in THES patients and this raised our index of suspicion towards "atypical" hyper IgM syndrome. Although the pathogenesis of immunoglobulin production dysfunction in THES is still elusive, this disorder should be considered in the differential diagnosis in patients with elevated IgM and syndromic features.
10.1007/s12026-022-09305-9
pubmed_74_15385
Brain growth and development occur at peak rates in early childhood through adolescence, and for some children, this must happen in conjunction with chronic kidney disease (CKD), associated medical conditions, and their treatment(s). This review provides an overview of key findings to date on the topic of the brain in pediatric CKD. Here, we specifically address the topics of neuroimaging and cognition in pediatric CKD with consideration to biomarkers of disease progression that may impact cognition. Current cognitive data suggest that most children with mild to moderate CKD do not exhibit significant cognitive impairments, but, rather, the presence of somewhat lower intellectual abilities and subtle deficits in selected executive functions. Although promising, modern neuroimaging data remain inconclusive in linking cognitive findings to neuroimaging correlates in the pediatric CKD population. Certainly, it is important to note that even subtle cognitive concerns can present barriers to learning, social functioning, and overall quality of life if not appropriately recognized or addressed. Further longitudinal research utilizing concurrent and targeted cognitive and neuroimaging evaluations is warranted to better understand the impact of CKD progression on brain development and associated neurocognitive outcomes.
10.1007/s00467-019-04417-1
pubmed_556_19890
Infection with the virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) stimulates an immune response which can serve as a marker for current or past exposure to this pathogen, and possibly for resistance to re-infection. This response to COVID-19 can be monitored based on the production of antibodies, and thus, serologic tests have become available for diagnostic purposes. Despite progress in this area, concerns have been raised that too many of the commercially available serologic detection systems are not completely reliable. To address this issue, Western blots should be considered for confirming a positive or borderline-positive result from a screening test, such as an ELISA. An additional benefit of Western blots would be to identify antigens that could form the basis for developing a vaccine. Little is known about the cell-mediated immune response against COVID-19. One way to address this would be to use skin testing to measure the delayed-type hypersensitivity response in patients recovering from COVID-19.
10.1016/j.diagmicrobio.2020.115148
pubmed_874_20386
OBJECTIVE To separate and identify the surface proteins and secreted proteins of Toxoplasma gondii tachyzoites of RH strain. METHODS T. gondii tachyzoites were cultured in Vero cells, and purified by filtration and Percoll cell separation solution. The biotin-labeled tachyzoites were lysed, and the surface and secreted proteins were separated by NeutrAvidin agarose beads. After condensation and SDS-PAGE, the protein were collected, digested and identified by LC/MS-MS. RESULTS A total of 785 T. gondii proteins were identified, 81 (10.3%) of which were originally annotated as the surface or secreted proteins. Among the highly-expressed (PSM>10) 65 proteins, 43 (66%) were originally annotated as surface or secreted proteins, while the others were predicted unknown proteins. CONCLUSION The surface and secreted proteins of T. gondii are separated by biotin labeling and avidin chromatography, among which some potential new surface or secreted proteins of T. gondii are identified.
pubmed_874_20386
pubmed_1142_25151
As an anthracycline antibiotic, doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents for treating various types of tumors. Unfortunately, the clinical application of this drug results in severe side effects, particularly dose-dependent cardiotoxicity. There are multiple mechanisms involved with the cardiotoxicity caused by DOX, among which intracellular iron homeostasis plays an essential role based on a recent discovery. In this mini-review, we summarize the clinical features and symptoms of DOX-dependent cardiotoxicity, discuss the correlation between iron and cardiotoxicity, and highlight the involvement of iron-dependent ferroptotic cell death therein. Recent advances in this topic will aid the development of novel DOX delivery systems with reduced adverse effects, and expand the clinical application of anthracycline.
10.1039/d1tb00551k
pubmed_539_20053
We studied the diagnostic and prognostic value of diffusion- and perfusion-weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and follow-up monitoring of patients with stroke that had ensued less than 6 hours previously. Further, we examined the role of vessel patency or occlusion and subsequent recanalization or persistent occlusion for further clinical and morphological stroke progression so as to define categories of patients and facilitate treatment decisions. Fifty-one patients underwent stroke magnetic resonance imaging (DWI, PWI, magnetic resonance angiography, and T2-weighted imaging) within 3.3 +/- 1.29 hours, and, of those, 41 underwent follow-up magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and 90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients exhibited recanalization on day 2. Vessel occlusion was associated with a PWI-DWI mismatch on the initial magnetic resonance imaging, vessel patency with a PWI-DWI match (p < 0.0001). Outcome scores and lesion volumes differed significantly between patients experiencing recanalization and those who did not (all p < 0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical scores and only modestly with outcome scores. We have concluded on the basis of this study that early recanalization saves tissue at risk of ischemic infarction and results in significantly smaller infarcts and a significantly better clinical outcome. Patients with proximal vessel occlusions have a larger amount of tissue at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization seems to be of utmost importance for these patients.
pubmed_539_20053
pubmed_501_2843
A total of 210 male Charles River CD rats, 45 days old, were subjected to a fracturing of the right radius and ulna by digital pressure while under ether anesthesia. These animals were then assigned randomly to dose groups (1, 2 or 4 mg/kg/day of indomethacin and 100, 200, or 300 mg/kg/day of aspirin) and were dosed for 21 days. Dose levels were chosen to provide approximately equipotent levels of the test compounds with the highest dose approaching toxicity. Radiographs were taken of control-rat fractures on days 8, 14, and 21. Three rats at 4 mg/kg/day of indomethacin died of interstinal perforation prior to scheduled sacrifice. On day 22, all remaining rats were sacrificed by exsanguination under anesthesia. Histologic secretions of the radius and ulna were examined in random sequence without knowledge of the treatment regimen. A histologic grade based on the morphologic stage of fracture healing was given. There was a drug- and dose-related retardation of fracture healing, which was statistically significant at all dose levels of indomethacin and the highest level of aspirin, as compared to controls. Decreased mean grades in the groups given 100 and 200 mg/kg/day of aspirin, though not statistically significant, suggest a retarding effect on fracture healing at these levels also. No statistically significant changes in numbers of pseudoarthroses were found.
10.3109/17453678008990848
pubmed_1086_3907
BACKGROUND New antiviral drugs can rapidly improve the symptoms of influenza, but some patients still have prolonged fever and complications. The cause of the prolonged symptoms despite antiviral therapy remains unclear. Recent studies have shown a synergistic effect between influenza viruses and bacteria. This study investigated the frequency of bacterial infection in such patients and its effects on the clinical course to determine the need for antibiotics. METHODS In two seasons (December 2001 through March 2002, and December 2002 through March 2003), throat cultures were obtained from 387 patients with influenza being treated with oseltamivir, and clinical courses were observed. Control throat cultures were obtained from 109 healthy children. RESULTS The detection rate of pathogens was higher in patients with influenza (54.3%) than in control (23.9%, p<0.001). The most common pathogen was Streptococcus pneumoniae (49.7%) in patients with influenza and was Haemophilus influenzae (69.2%) in controls. Of the patients with normal flora, 4.1% had fever for 4 or more days and showed pathogens in throat cultures on day 4. Of the patients with pathogen-positive cultures who did not receive antibiotics, 40.3% had fever for 4 or more days. CONCLUSION Throat cultures obtained on the first or fourth day of treatment with oseltamivir were positive for pathogenic bacteria in all patients with fevers for 4 or more days. Our observations suggest that patients with influenza and prolonged fever despite receiving oseltamivir should be given antibiotics.
10.1272/jnms.73.122
pubmed_520_14461
BACKGROUND As climate variability and extreme weather events associated with climate change become more prevalent, public health authorities can expect to face an expanding spectrum of vector-borne diseases with increasing incidence and geographical spread. Common interventions include the use of larvicides and adulticides, as well as targeted communications to increase public awareness regarding the need for personal protective measures, such as mosquito repellant, protective clothing, and mosquito nets. Here, we propose a simplified compartmental model of mosquito-borne disease dynamics that incorporates the use of personal protection against mosquito bites influenced by two key individual-level behavioral drivers-concern for being bitten by mosquitos as a nuisance and concern for mosquito-borne disease transmission. METHODS We propose a modified compartmental model that describes the dynamics of vector-borne disease spread in a naïve population while considering the public demand for community-level control and, importantly, the effects of personal-level protection on population-level outbreak dynamics. We consider scenarios at low, medium, and high levels of community-level vector control, and at each level, we consider combinations of low, medium, and high levels of motivation to use personal protection, namely concern for disease transmission and concern for being bitten in general. RESULTS When there is very little community-level vector control, nearly the entire population is quickly infected, regardless of personal protection use. When vector control is at an intermediate level, both concerns that motivate the use of personal protection play an important role in reducing disease burden. When authorities have the capacity for high-level community vector control through pesticide use, the motivation to use personal protection to reduce disease transmission has little additional effect on the outbreak. CONCLUSIONS While results show that personal-level protection alone is not enough to significantly impact an outbreak, personal protective measures can significantly reduce the severity of an outbreak in conjunction with community-level control. Furthermore, the model provides insight for targeting public health messaging to increase the use of personal protection based on concerns related to being bitten by mosquitos or vector-borne disease transmission.
10.1186/s13071-022-05481-7
pubmed_779_10776
BACKGROUND Endoscopic screening and adherence to a healthy lifestyle are major avenues for colorectal cancer (CRC) prevention. We investigated changes in lifestyles after endoscopic screening. METHODS We drew data from 76,303 pairs of time- and age-matched individuals who had and had not, respectively, reported first time endoscopic screening, in the 3 cohorts (Nurses' Health Study I and II and the Health Professionals Follow-up Study). Detailed information was collected every 2-4 years on endoscopy screening, 12 lifestyle factors (including smoking, physical activity, regular use of aspirin/nonsteroidal anti-inflammatory drugs, body weight, and 8 dietary factors), and adherence to a healthy lifestyle based on a score defined by 5 major lifestyle factors (smoking, alcohol, body weight, physical activity, and diet). We assessed changes in lifestyle from pre- to post-screening periods for the matched pairs. We also conducted subgroup analysis according to screening findings (negative, low- and high-risk polyps, and CRC). RESULTS Endoscopic screening was associated with higher prevalence of adherence to a healthy lifestyle (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.16). The association strengthened with the severity of the screening findings, with an OR of 1.09 (95% CI, 1.03-1.15) for negative screening, 1.19 (95% CI, 1.07-1.33) for low-risk polyps, 1.42 (95% CI, 1.14-1.77) for high-risk polyps, and 1.55 (95% CI, 1.17-2.05) for CRC. The individual lifestyle factors and diet showed modest change. CONCLUSIONS Endoscopic screening was associated with a modest improvement in healthy lifestyles, particularly in individuals with more severe endoscopic findings. Further efforts of integrating lifestyle medicine into the screening setting are needed, to better leverage the teachable moment in improving CRC prevention.
10.1016/j.cgh.2021.07.014
pubmed_17_15327
The aim of the present work was to identify and quantify the phenolic compounds and fatty acids in acorns from Quercus ilex, Quercus rotundifolia, and Quercus suber. The concentration of oleic acid was >63% of total fatty acids in all cases, followed by palmitic and linoleic acids at similar concentrations (12-20%). The concentrations of alpha-tocopherol in Q. rotundifolia, Q. ilex, and Q. suber were 19, 31, and 38 mg/kg of dry matter (DM), respectively, whereas the concentrations of gamma-tocopherol were 113, 66, and 74 mg/kg of DM, respectively. Thirty-two different phenolic compounds were distinguished. All of them were gallic acid derivatives, in the form of either galloyl esters of glucose, combinations of galloyl and hexahydroxydiphenoyl esters of glucose, tergallic O- or C-glucosides, or ellagic acid derivatives. Several tergallic acid C-glucosides were also present in the extracts obtained from Q. suber. Acorns from Q. ilex and Q. rotundifolia showed similar polyphenol patterns mainly with gallic acid-like spectra. Chromatograms of Q. suber showed mainly polyphenols with ellagic acid-like spectra. Valoneic acid dilactone was especially abundant in Q. suber skin. The contribution of skin to the total phenolics of the acorn was relatively small in Q. rotundifolia and Q. ilex but relatively high in Q. suber. Skin extracts from Q. suber, Q. rotundifolia, and Q. ilex showed 1.3, 1.4, and 1.0 antioxidant efficiencies, respectively (compared to that of butylhydroxyanisole). Endosperm extracts showed lower capacity to prevent lipid peroxidation than skin extracts.
10.1021/jf030216v
pubmed_248_10436
Nowadays, about 6-8% of the German population suffers from diabetes mellitus mostly type 2 but in patients with angiopathies about 30% have known diabetes and a further 30% have newly diagnosed diabetes or impaired glucose tolerance. Therefore diagnosis and therapy of glucose impairment play a central role for management of these patients. The antidiabetic therapy for secondary prevention of cardiovascular disease has to be embedded in a multifactorial concept with management of hypertension, hyperlipidemia and hypercoagulability. The management of diabetes following guidelines is a stepwise therapy with lifestyle interventions (diet, exercise) and oral drugs or insulin. Metformin has shown favorable outcome in overweight patients if aware of side effects; insulin is a safe drug in multimorbid patients and with planned interventions or operations. We are awaiting the results of multiple endpoint studies with newer antidiabetic drugs which may change our current concept of management of diabetes mellitus in these patients in the near future.
10.1007/s00392-005-1408-6
pubmed_783_13109
The ultrastructural characterization of neuronal compartments in intact tissue labeled with green fluorescent protein (GFP) remains a frequently encountered challenge, despite work establishing photooxidation of GFP in cultured cells. However, most applications require the detection of GFP or GFP fusion proteins expressed in intact tissue. Here, we report that illumination of GFP variants in oxygen-enriched environment reliably generated electron-dense 3,3'-diaminobenzidine (DAB) precipitates in slices from rat brain. The method is applicable to GFP variants tagged to presynaptic proteins as well as to soluble GFP in various brain regions. Serial section scanning electron microscopy was used to examine genetically labeled presynaptic terminals at high resolution and to generate three-dimensional representations of the synapses. Thus, we introduce a generally applicable correlative approach for the identification of presynaptic terminals genetically labeled with green fluorescent proteins in tissue slices and their ultrastructural characterization.
10.1371/journal.pone.0064764
pubmed_1081_10162
INTRODUCTION Prostate cancer has become an important clinical issue within deceased organ donors. There is still a considerable number of undiagnosed cancers, especially in early stage, despite frozen section analysis. The aim of the study was to evaluate outcomes of orthotopic liver transplants (OLTx) with organs from donors with prostate cancer. MATERIAL AND METHODS A retrospective analysis was performed in deceased liver donors whose prostate glands were harvested for histologic examinations because of prostate cancer suspicion. The study group consisted of 72 men reported as potential liver donors between 2011 and November 2017. Prostate glands were primarily assessed by frozen sections and afterward in routine examination. Generally cancer diagnosed in frozen specimen was not considered for OLTx. Recipients who received an organ from the donor with prostate cancer were actively surveilled. RESULTS There were 19 cases (26.40%) of prostate cancer diagnosed among the study group. In 12 cases diagnosis was made by frozen section assessment, of which 11 organs were disqualified from OLTx and 1 was transplanted. In 7 cases prostate cancer was diagnosed after OLTx in final routine histologic examination. Finally, 8 recipients (5 men and 3 women) received a new organ. Only 1 died during the perioperative period. In the remaining 7 patients the perioperative period was uneventful and no disease transmission was observed during follow-up. CONCLUSIONS Diagnosis of prostate cancer in donors should not be treated as a contraindication for OLTx because the risk of disease transmission is low. Potential recipients must be fully informed and kept under oncological surveillance.
10.1016/j.transproceed.2018.02.129
pubmed_346_6888
Neurologic infections in children are frequently accompanied by cutaneous findings that may direct the physician toward the correct diagnosis. In some instances, the appearance of an eruption (such as erythema chronicum migrans and Lyme disease) is specific or a rapid bedside diagnostic test (Tzanck preparation for herpes simplex) is extremely helpful in sorting out the differential diagnosis of a child's illness. In this article, cutaneous clues to some of the more important childhood infections will be reviewed.
pubmed_346_6888
pubmed_98_15345
PURPOSE This study examined the mediational role of household chaos in the link between family resources and child sleep outcomes during the transition to kindergarten. PROCEDURES Participants included 230 families of children entering kindergarten (50% female) who participated in an 8-day measurement burst at pre-kindergarten (July-August), early kindergarten (September/October), and mid-kindergarten (November/December). At pre-kindergarten, mothers completFed the Family Resources Scale-Revised (FRS-R), while at pre- and early-kindergarten, trained observers assessed household chaos using the Descriptive In-Home Survey of Chaos-Observer ReporteD (DISCORD). To better understand perturbations in child sleep during this transition, actiwatches (AW Spectrum Plus, Philips/Respironics, Murrysville, PA) were used to measure both child sleep duration and proportion of recommended sleep duration (9+ hours per night) at early- and mid-kindergarten. MAIN FINDINGS Results found that family resources were more clearly predictive of child sleep outcomes than household income. Controlling for quality of coparenting and maternal depressive symptoms, household chaos mediated the link between family resources and child sleep duration at both early and mid-kindergarten, the link between family resources and the proportion of recommended sleep duration in mid-kindergarten, and the change in proportion of recommended sleep from pre-kindergarten to early-kindergarten. CONCLUSIONS Findings highlight household chaos as a mechanism by which family resources, a metric of socioeconomic risk, influences child sleep during the transition to kindergarten.
10.1016/j.sleh.2021.10.005
pubmed_251_9392
T lymphocytes can kill antigen-presenting cells (APC) in the presence of antigen or lectin. The subject of this study was to investigate whether the state of activation or phenotype of monocytes, influence their susceptibility to killing by T cells activated with pokeweed mitogen (PWM) or anti-CD3 monoclonal antibody. The data are presented which show that monocytes activation with cytokines (IFN-gamma, IL-4, or IL-2), PPD, phorbol ester or phagocytic stimulus, have no influence on monocyte susceptibility to killing by T lymphocytes. Furthermore, flow cytometry data suggest that monocytes eliminated from culture have no characteristic phenotype. In conclusion, our data indicate that elimination of monocytes by activated T lymphocytes does not depend on the state of activation of monocytes.
pubmed_251_9392
pubmed_453_3779
Over the past 10 years, I have been privileged to conduct educational forums for audiences containing many recovering alcoholics or otherwise chemically dependent persons. In these forums about the addictive diseases and their treatment and research possibilities, significant interaction with the audience members occurs. During these interactions, certain anecdotal phenomena seem to predominate.
pubmed_453_3779
pubmed_1066_11225
Electrocardiogram is fundamental to diagnose ST-segment elevation myocardial infarction in patients with chest pain, other consistent symptoms, and/or echocardiographic abnormalities. Nevertheless, physicians should remember that other conditions can cause an ST-segment elevation myocardial infarction-like electrocardiogram. We exemplify this warning describing the case of an electrocardiogram mimicking ST-segment elevation myocardial infarction caused by severe dysionia. (Level of Difficulty: Beginner.).
10.1016/j.jaccas.2020.11.019
pubmed_1123_22094
BACKGROUND Few studies looked at the association between gait variability and executive subdomains (ESD). The aim of this study was to examine the association between ESD (i.e., information updating and monitoring) and stride time variability among healthy older adults. METHODS Seventy-eight healthy older adults (mean age 69.9 ± 0.9 years, 59% women) were divided into 3 groups according to stride time variability (STV) tertiles while steady state walking. Coefficient of variation of stride time was used as a marker of STV. Scores on cognitive tests evaluating information updating and monitoring (Digit Span test), mental shifting (Trail Making Test part A and part B) and cognitive inhibition (Stroop Color Word test) were used as measures of ESD. RESULTS The full adjusted and the stepwise backward logistic regression models showed that the highest tertile (i.e., the worst performance) of STV was only associated with lower Digit Span performance (Odds ratio = 0.78 with P = 0.020 and Odds ratio = 0.81 with P = 0.019). CONCLUSIONS Information updating and monitoring are associated with STV in the sample of studied participants, suggesting that walking may be a complex motor task depending specifically of this subdomain of executive functions.
10.1186/1743-0003-9-12
pubmed_498_582
Wastewater (sewage) treatment plants generate a high volume of sludge that, although it is classified as class II-A (not inert) non-hazardous waste, is commonly disposed of in sanitary landfills. Hence the environmental urge to assess its valorization possibilities. The present study describes the use of a sewage sludge as raw material in the production of red ceramic bricks by extrusion, focusing on the technological changes brought about by the presence of the sludge during the plastic forming process, in terms of the plasticity of the mixture and its subsequent extrudability. To quantitatively identify the best moisture conditions for the extrusion of high-quality products, shear strain amplitude sweep (torsional) tests were conducted on green (moist) prismatic samples produced with different moisture and sludge contents. For sewage sludge contents up to 10 wt%, the optimal moisture content was identified at 31-33 wt%. Higher water demand was identified for 15 wt% of sludge, for which optimal extrusion results required 35 wt% moisture. The total linear shrinkage after drying and firing, as well as the water absorption, were within the limits required for ceramic bricks for all the sludge contents. The results for compressive strength of the fired bricks also demonstrate that the incorporation of up to 15 wt% sewage sludge into the clay mixture is highly feasible for the production of extruded ceramic bricks.
10.1016/j.jenvman.2021.113238
pubmed_295_2869
The rheology of polymer crystallization is an old problem that often defies explanation due to the complex interrelationships between crystallization and flow properties. Although separate measurements of rheology and crystallinity can give some information on their relationship, it is only through simultaneous measurements that ideas on the rheology of polymer crystallization can be tested and developed. This Perspective details recent experimental developments in simultaneous crystallinity and rheology measurements as well as continuum modeling efforts for the case of quiescent and isothermal crystallization. Experimental results reveal that the rheology is dominated initially by growth of individual spherulites that evolve into spherulitic superstructures that eventually span the measurement geometry. A generalized effective medium model based on this concept of percolation can explain both the growth of the viscoelastic modulus during crystallization and the changes in the relaxation spectrum of the crystallizing polymer, including a critical gel response at percolation. The success of the combined measurement techniques and percolation concepts motivate research to extend the semicrystalline polymer materials space where these methods are applied as well as further develop novel techniques to gain additional insight into the evolution of structure and relaxation dynamics during crystallization.
10.1002/pcr2.10162
pubmed_51_22895
In ulcerative colitis, mucosal healing has clearly been incorporated in the assessment of treatment efficacy. In Crohn's disease, this concept has only emerged in recent clinical trials with biological therapies. Systemic steroids don't reliably induce mucosal healing in Crohn's disease, but purine analogues and anti-TNF agents have a potential to heal mucosal ulcerations. Evidence for mucosal healing has now been provided for the anti-TNF agents infliximab, adalimumab and certolizumab pegol. For infliximab in Crohn's disease, mucosal healing has been associated with a reduction in clinical relapses, disease-related hospitalizations and surgeries. On the contrary, the benefit of treating asymptomatic patients with IBD more intensively until they achieve mucosal healing has not been proven. In clinical practice, assessing mucosal healing should be considered in patients with persistent symptoms despite adequate therapy as well as in patients where treatment discontinuation is being considered.
10.2174/138945012802429679
pubmed_703_20247
OBJECTIVE Learn about the perception of public health students in Mexico and Colombia regarding the management of the influenza A (H1N1) epidemic to determine which curriculum contents in epidemiological education can be improved. METHODS Survey administered to graduate students during the epidemic, from June to August 2009. The 30 epidemiological competencies for "intermediate epidemiologists" of the Council of State and Territorial Epidemiologists were evaluated. The results were described through stratification by covariables, and the less developed competencies were identified through exploratory factor analysis. RESULTS A total of 154 students participated, 55.8% of whom were in Mexico. Significant differences in the student profile from each country were observed, which partially explains the perception of response to the epidemic. The first factor, which explains 21.5% of the variance, had lower scores in the factor analysis. This factor was associated with competencies related to the links between health personnel and the community, in which knowledge of the social sciences and communication skills are relevant. CONCLUSIONS The students perceived that the response to the epidemic could have been better. It is suggested that public health human resources education include subjects related to the impact of culture on behavior and thinking, recognition of the prejudices of experts, effective community-level communication, and the ability to adapt to new situations. The "natural experiment" of the epidemic facilitated the identification of areas of opportunity to improve the teaching of epidemiology to health personnel.
pubmed_703_20247
pubmed_333_6327
1. ATP-D-hexose-6-phosphotransferase activity was measured in red blood cells of man, rabbit, pig and cow. Mean values ranged from 0.60 to 1.06 units/g haemoglobin and no significant difference was obtained with different glucose concentrations. 2. The characteristics of glucose phosphorylating activities in red blood cells of the species studied were similar. 3. Chromatography on DEAE column revealed two different glucose phosphorylating activities in red cells of man, rabbit and pig, and only one in cow red cells. 4. The first hexokinase activity is the predominant form and is saturated with low glucose concentrations; the second is noticeably marked at high glucose concentrations.
10.1016/0305-0491(78)90108-6
pubmed_895_23220
BACKGROUND Berries are associated with health benefits. Little is known about the effect of baseline metabolome on the overall metabolic responses to berry intake. OBJECTIVE We studied the effects of berries on serum metabolome. DESIGN Eighty overweight women completed this randomized crossover study. During the interventions of 30 d, subjects consumed dried sea buckthorn berries (SBs), sea buckthorn oil (SBo), sea buckthorn phenolics ethanol extract mixed with maltodextrin (SBe+MD) (1:1), or frozen bilberries. Metabolic profiles were quantified from serum samples by using (1)H nuclear magnetic resonance spectroscopy. RESULTS All interventions induced a significant (P < 0.001-0.003) effect on the overall metabolic profiles. The effect was observed both in participants who had a metabolic profile that reflected higher cardiometabolic risk at baseline (group B: P = 0.001-0.008) and in participants who had a lower-risk profile (group A: P < 0.001-0.009). Although most of the changes in individual metabolites were not statistically significant after correction for multiplicity, clear trends were observed. SB-induced effects were mainly on serum triglycerides and very-low-density lipoprotein (VLDL) and its subclasses, which decreased in metabolic group B. SBo induced a decreasing trend in serum total, intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) cholesterol and subfractions of IDL and LDL in group B. During the SBe+MD treatment, VLDL fractions and serum triglycerides increased. Bilberries caused beneficial changes in serum lipids and lipoproteins in group B, whereas the opposite was true in group A. CONCLUSION Berry intake has overall metabolic effects, which depend on the cardiometabolic risk profile at baseline. This trial was registered at clinicaltrials.gov as NCT01860547.
10.3945/ajcn.113.060590
pubmed_530_11308
BACKGROUND Secondary rhytidectomy procedures present an additional level of complexity in comparison with primary procedures. Patients may seek secondary rhytidectomy, in part, as a result of complications stemming from the initial procedure, because of the natural process of aging, or a combination of the two. The aim of this literature review was to examine the difference in patient characteristics, techniques, and challenges specific to secondary face lifts. METHODS A literature search was performed on secondary face-lift procedures using MEDLINE, PubMed, and Cochrane databases. Using the keywords "facelift," "face lift," "rhytidoplasty," and "rhytidectomy" combined with "secondary," "reoperation," "revision," and "multiple," an initial search was performed. Then, all abstracts were evaluated for relevance. RESULTS The search yielded 291 articles with these key terms. The articles were reviewed for relevance and, in total, 13 were identified specific to secondary rhytidectomy procedures. Six were retrospective studies and the rest were expert special topic articles. CONCLUSIONS Although there are limited data specific to secondary rhytidectomy procedures, several important principles were evident from these retrospective reviews and editorial articles. It is important to assess whether the patient is exhibiting stigmata of the primary rhytidectomy procedure or natural signs of aging, such as volumetric deflation and recurring ptosis of previously lifted tissues. Accurate and systematic preoperative analysis is key for successful planning and execution of secondary rhytidectomy procedures.
10.1097/PRS.0b013e31826d9eea
pubmed_135_16340
One new taraxastane-type triterpenoid, three new grayanane-type diterpenoids (2 - 4), and 12 known compounds (5 - 16) were isolated from the leaves of Craiobiodendron yunnanens W. W. Smith. The structures of these compounds were elucidated on the basis of their spectroscopic data and chemical evidence. Compounds 1 and 8 exhibited partly anti-inflammatory activity based on the inhibition of NF-κB activity in SW480 cells at 10 μM with inhibition ratios of 60.53 and 59.20%, respectively. Compounds 10 and 13 showed excellent cytotoxicity against human leukemia cell (MV4-11) at 10 μM with inhibition ratios of 43.02 and 49.11%, respectively.
10.1080/10286020.2022.2132482
pubmed_834_19701
Previous studies have shown that the majority of C1q-binding IgG in patients with systemic lupus erythematosus (SLE) is composed of autoantibodies to the collagen-like region of C1q. Mice of the MRL/l strain are considered as a murine model of human SLE and possess autoantibodies to nuclear antigens as well as IgM and IgG rheumatoid factors (RF). This study was undertaken to characterize the C1q-binding IgG in MRL/l mice. In contrast to human SLE, C1q-binding IgG in MRL/l mice showed immunochemical characteristics of immune complexes rather than those of autoantibodies to C1q. Namely, C1q-binding IgG in MRL/l mice was large-sized upon HPLC gel filtration and abolished by digestion with pepsin or by high salt concentration, and bound to the globular region of C1q. The C1q-binding activity in MRL/l mice was absorbed by double-stranded DNA- or single-stranded DNA-cellulose. The medium-sized immune complexes containing RF have been well documented in MRL/l mice. In this study, however, mouse IgG-Sepharose failed to absorb fully C1q-binding IgG. We conclude that the majority of C1q-binding IgG in MRL/l mice consists of large-sized immune complexes containing antibodies to DNA.
10.1006/clin.1995.1063
pubmed_533_5067
After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.
10.15430/JCP.2017.22.4.203
pubmed_177_6768
Hypoxia is a common feature of solid tumors that is closely associated with radiotherapy and chemotherapy resistance, metastasis and tumors prognosis. Thus, it is important to assess hypoxia in tumors for estimating prognosis and selecting appropriate treatment procedures. 18F-Fluoromisonidazole positron emission tomography (18F-FMISO PET) has been widely used to visualize tumor hypoxia in a comprehensive and noninvasive way, both in the clinical and preclinical settings. Here we review the concept, mechanisms and detection methods of tumor hypoxia. Furthermore, we discuss the correlation between 18F-FMISO PET and other detection methods, current applications of 18F-FMISO PET and the development prospects of this imaging technology.
10.18632/oncotarget.21662
pubmed_969_13330
A hybridoma (3B2-F7) has been established which secretes a monoclonal antibody (Mab) directed against a peptide determinant of human seminal plasma glycoprotein (HSP-gP). The deglycosylation of HSP-gP was performed chemically with TFMS hydrolysis and enzymatically in the presence of detergent and further treated with periodic acid after fixing deglycosylated HSP on plastic wells. The Mab 3B2-F7 (IgM, kappa) exhibited sperm immobilization activity (256 units of SI50) and inhibited sperm binding to human zona pellucida. Human epididymis, pancreatic islets of Langerhan's and distal tubulus of kidney were strongly labelled whilst other tissues were essentially negative by avidin-biotin complex tissue staining with this Mab. The antigen epitope to the Mab was in the 36 kDa molecule of human HSP-gP. The antigenic determinant recognized by Mab 3B2-F7 was destroyed by six different proteases, but was resistant to N-glycanase and other carbohydrate splitting enzymes. This epitope is therefore likely to be composed of a polypeptide chain. Peptide fragments after proteolysis of the HSP molecule with Staph. aureus V8 protease and trypsin retained antigenicity, hence the epitope corresponding to the Mab may be a peptide chain and not dependent on the conformational structure of the polypeptide.
10.1016/0165-0378(90)90035-5
pubmed_197_20701
INTRODUCTION The aim of this study was to evaluate the effects of different curing units and 2 luting cements on the push-out bond strength of a translucent fiber post. METHODS Thirty maxillary incisor roots were endodontically treated. Post spaces were prepared, and the smear layers were removed. Posts (FRC Postec Plus) were luted with either a self-etch cement (Panavia F 2.0) or a self-adhesive cement (Maxcem). Luting agents were then light-activated with a quartz-tungsten-halogen, a blue light-emitting diode, or a plasma-arc curing unit. Roots/cemented posts were transversally sectioned from coronal to apical. Push-out tests were performed, and data were analyzed by using three-way analysis of variance and Tukey tests. RESULTS Push-out bond strengths were significantly affected by the type of luting agent (P < .05) and root region (P < .05). The type of light source used in curing did not affect push-out bond strengths (P > .05). CONCLUSIONS Self-adhesive resin cement provided higher bond strength than the self-etch cement when smear layer was removed before the post cementation. The push-out bond strength in the apical portion of the root was significantly lower than in the coronal region. The use of different curing units in the photoirradiation of dual-cured resin cement did not affect the retention of the fiber post as a result of the limited light transmission capability of this post.
10.1016/j.joen.2010.04.026
pubmed_300_3729
In enzymatic saccharification of lignocellulosics, the access of the enzymes to exposed cellulose surfaces is a key initial step in triggering hydrolysis. However, knowledge of the structure-hydrolyzability relationship of the pretreated biomass is still limited. Here we used fluorescent-labeled recombinant carbohydrate-binding modules (CBMs) from Clostridium josui as specific markers for crystalline cellulose (CjCBM3) and non-crystalline cellulose (CjCBM28) to analyze the complex surfaces of wood tissues pretreated with NaOH, NaOH-Na(2)S (kraft pulping), hydrothermolysis, ball-milling, and organosolvolysis. Japanese cedar wood, one of the most recalcitrant softwood species was selected for the analysis. The binding analysis clarified the linear dependency of the exposure of crystalline and non-crystalline cellulose surfaces for enzymatic saccharification yield by the organosolv and kraft delignification processes. Ball-milling for 5-30 min increased saccharification yield up to 77%, but adsorption by the CjCBM-cyan fluorescent proteins (CFPs) was below 5%. Adsorption of CjCBM-CFPs on the hydrothermolysis pulp were less than half of those for organosolvolysis pulp, in coincidence with low saccharification yields. For all the pretreated wood, crystallinity index was not directly correlated with the overall saccharification yield. Fluorescent microscopy revealed that CjCBM3-CFP and CjCBM28-CFP were site-specifically adsorbed on external fibrous structures and ruptured or distorted fiber surfaces. The assay system with CBM-CFPs is a powerful measure to estimate the initiation sites of hydrolysis and saccharification yields from chemically delignified wood pulps.
10.1002/bit.22550
pubmed_330_2477
We quantified episcleral drug clearance of sodium fluorescein (NaFl) in rats to examine the hypothesis that there is rapid clearance of episcleral water soluble drugs, and that this rapid clearance may limit the amount of drug that is able to reach the posterior segment from an episcleral location. 2 mm implants containing either 12 or 22 microg of NaFl were manufactured and in vitro release rates were determined. Implants were placed in the sub-Tenon's space and the amount of drug remaining in the conjunctiva/sclera/choroid complex (CSCC) at various time points was quantified following tissue solubilization and fluorescence quantification using a spectrofluorometer. Kinetics of NaFl clearance was determined in live animals, following euthanasia and in animals in which choroidal non-perfusion had been achieved with indocyanine green-enhanced 810 nm diode laser thrombosis of the choroidal vasculature. Choroidal non-perfusion in these laser-treated rats was verified with Concavalin-A staining of choroidal flatmounts. In vitro, >99% of drug was released by 25 min for the low dose implants, and by 60 min for the high dose implants. In vivo, both implant doses were >99% cleared from the episcleral tissue by 3 h. By 7 h, an average of only 0.14 +/- 0.131 ng of NaFl per mg of wet tissue weight (mean +/- SD) remained in the CSCC with the low dose implant, and 0.29 +/- 0.428 ng of NaFl per mg of wet tissue weight remained in animals with the high dose implant. By comparison, in euthanized animals at 7 h following sub-Tenon's implantation, 432.0 +/- 181.40 ng of NaFl per mg of wet tissue weight was in the episcleral tissue of animals with the low dose implant, and of 787.8 +/- 409.89 ng of NaFl per mg of wet tissue weight remained in the animals with the high dose implant. In live animals with selective thrombosis of the choroidal vasculature, the difference in the amount of drug remaining in the episcleral tissue as compared to control live animals was not significant at all time points for both implant doses. In conclusion, there is rapid clearance of episcleral NaFl delivered from a bioerodible sub-tenon's implant. The clearance mechanisms are dramatically reduced following euthanasia, suggesting that elimination is occurring via active physiologic mechanisms, rather than by passive diffusion clearance (CL(diff)) (Pfister et al., 2003). Interestingly, the choroid does not appear to play a prominent role as clearance of episcleral NaFl was not affected by elimination of choroidal blood flow. Further work is needed to delineate the pathways of episcleral drug clearance.
10.1016/j.exer.2010.01.001
pubmed_1064_20196
This paper describes the results of an investigation of the difference in performance, posture used, strain on forearm musculature, and subjective ratings of three handy scanners (models A, B and C). Both models A and B were scanners on the market. Model C was developed for validation. The gripping posture of the three models is distinct both in the anatomical and functional sense. Work with model A requires a thumb-forefinger side grip which induces an ulnar deviation angle; work with model B requires a thumb-finger grip; work with model C requires a thumb-finger-palmar grip. Performance evaluation of scanner models A, B and C on different scanning tasks (with and without stitch) using different resolution modes (100 and 400 dpi), indicated that using the proposed model C resulted in a 13% higher success rate, a 14% shorter completion time, the smallest self-selected working area, least strain on the forearm muscles, and highest subjective ratings among the three. Model C appeared to provide the greatest opportunity for delicate adjustments of posture in response to the activity of the skin receptors, justifying the ergonomic input into the design.
10.1016/0003-6870(95)00070-4
pubmed_973_3810
This study aimed to investigate the effects of hydrofluoric acid (HF) treatment of grit-blasted Ti implants on osseointegration in ovariectomized (OVX) rats. After blasting with aluminium oxide particles, half implants were treated with 0.2 vol.% HF, and the other half were kept non-modified as control. The topographical and chemical changes of implant surface were determined by Scanning Electron Microscope, Atomic Force Microscope, and X-ray Photoemission Spectroscopy. 12 Weeks after bilateral ovariectomy, each rat accepted two implants in distal femora, with the control implant on the left and the fluoride-modified on the right. As a result, fluoride modification induced markedly changed surface topography and chemical composition. 12 Weeks after implant insertion, the fluoride-modified implants showed improved osseointegration compared to control, with the bone area ratio and bone-to-implant contact increased by 0.9- and 1.4-fold in histomorphometry, the bone volume ratio and percent osseointegration by 0.8- and 1.3-fold in micro-CT evaluation, and the maximal push-out force and ultimate shear strength by 1.2- and 2.0-fold in biomechanical test. These promising results indicated that HF treatment of Ti surface improved implant osseointegration in OVX rats, and suggested the feasibility of using fluoride modification to improve Ti implant osseointegration in osteoporotic bone.
10.1016/j.biomaterials.2010.01.028
pubmed_88_9632
The growth and multiplication of cells are regulated, in part, by polypeptide growth factors that bind to high-affinity receptors typically found on the plasma membrane. One such receptor is human epidermal growth factor receptor 2 (HER2). In around a quarter of all primary breast cancers, cells possess abnormally high numbers of (overexpress) HER2. [symbol: see text] Trastuzumab (pronounced tra-stoo-zoo-mab; Herceptin-Roche), a recombinant humanised mouse monoclonal antibody directed against HER2, is available as a treatment for certain patients with metastatic breast cancer. It is licensed as a first-line treatment in combination with [symbol: see text] paclitaxel for those whose cancer cells overexpress HER2 and for whom an anthracycline is unsuitable, and as a third-line treatment used alone when treatment with (where appropriate) an anthracycline, a taxane and hormonal therapy has failed. The National Institute for Clinical Excellence (NICE) has recommended trastuzumab as a treatment option for metastatic breast cancer in accordance with the licensed indications. What does trastuzumab offer?
pubmed_88_9632
pubmed_290_1835
BACKGROUND Various studies reported changes in grey matter volumes and modifications in functional connectivity of cortical and subcortical structures in patients suffering from trigeminal neuralgia (TN) and trigeminal neuropathic pain (TNP). This study meta-analyzed the concordant structural and functional changes in foci and provide further understanding of the anatomy and biology of TN/TNP. METHODS Relevant articles on magnetic resonance imaging (MRI) and functional MRI in TN/TNP, published before August 2018, were searched for on PubMed and Embase. Following exclusion of unsuitable studies, a meta-analysis was performed using activation likelihood estimation (ALE). RESULTS In total, 322 paper were identified, 11 of which could be included based on the predefined inclusion and exclusion criteria. Eight papers, totaling 279 subjects, discussing structural changes and four papers, totaling 102 subjects, discussing functional changes were included (i.e., one paper investigated both structural and functional alterations). ALE analysis showed that in TN/TNP, grey matter decreases are found in the thalamus, (anterior) cingulate gyrus, bilateral striatum, the superior-, middle- and transverse temporal gyrus, subcallosal gyrus, the bilateral insular cortex, the pre- and postcental gyrus, the middle frontal gyrus bilaterally and the anterior cerebellar lobe. Grey matter increases were seen in the periaqueductal grey (PAG). Increased resting state functional organization was found within the bilateral middle- and superior frontal gyri, the (posterior) cingulate cortex and the thalamus/pulvinar. CONCLUSIONS Structural and functional changes meta-analyzed in this paper may contribute to elucidating the central pathophysiological mechanisms involved in TN/TNP. These results may be used as biomarkers to predict the response to medication and, ideally, in the future to offer personalized treatments.
10.1016/j.nicl.2019.102039