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pubmed_828_2397 | CONTEXT
Prospective cohort studies have identified an association between cannabis use and later psychosis-related outcomes, but concerns remain about unmeasured confounding variables. The use of sibling pair analysis reduces the influence of unmeasured residual confounding.
OBJECTIVE
To explore the association between cannabis use and psychosis-related outcomes.
DESIGN
A sibling pair analysis nested within a prospective birth cohort.
SETTING
Births at a Brisbane, Australia, hospital.
PARTICIPANTS
Three thousand eight hundred one young adults born between 1981 and 1984 as part of the Mater-University Study of Pregnancy.
MAIN OUTCOME MEASURES
Cannabis use and 3 psychosis-related outcomes (nonaffective psychosis, hallucinations, and Peters et al Delusions Inventory score) were assessed at the 21-year follow-up. Associations between duration since first cannabis use and psychosis-related outcomes were examined using logistic regression adjusted for sex, age, parental mental illness, and hallucinations at the 14-year follow-up. Within 228 sibling pairs, the association between within-pair differences in duration since first cannabis use and Peters et al Delusions Inventory score was examined with general linear modeling. The potential impact of attrition was examined.
RESULTS
Duration since first cannabis use was associated with all 3 psychosis-related outcomes. For those with duration since first cannabis use of 6 or more years, there was a significantly increased risk of (1) nonaffective psychosis (adjusted odds ratio, 2.2; 95% confidence interval, 1.1-4.5), (2) being in the highest quartile of Peters et al Delusions Inventory score (adjusted odds ratio, 4.2; 95% confidence interval, 4.2-5.8), and (3) hallucinations (adjusted odds ratio, 2.8; 95% confidence interval, 1.9-4.1). Within sibling pairs, duration since first cannabis use and higher scores on the Peters et al Delusions Inventory remained significantly associated.
CONCLUSIONS
Early cannabis use is associated with psychosis-related outcomes in young adults. The use of sibling pairs reduces the likelihood that unmeasured confounding explains these findings. This study provides further support for the hypothesis that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults. | 10.1001/archgenpsychiatry.2010.6 |
pubmed_1082_20210 | The more mature erythroid progenitor assayable in vitro, the colony-forming unit-erythroid (CFU-E), is normally found in the bone marrow (BM) but is virtually absent from peripheral blood (PB), unlike the more immature progenitor, the burst-forming unit-erythroid (BFU-E). We report on the detection of CFU-E in the PB of six of 18 patients during hematopoietic recovery following allogeneic bone marrow transplantation (BMT); three of six patients with PB CFU-E were under treatment with recombinant human erythropoietin (rhEpo) as well as six of 12 who did not present with PB CFU-E. PB CFU-E were found as early as day 14 following BMT, reached a peak on day 28, and were still detectable on day 60. The presence of PB CFU-E was associated with signs of stimulated erythroid engraftment--an accelerated reticulocyte recovery, an increased number of reticulocytes, higher levels of serum transferrin receptor, and a reduction in transfusional requirements were found in these patients compared to those without PB CFU-E. The numbers of PB and BM BFU-E were similar in the two groups, as well as the numbers of PB and BM CFU-granulocyte/macrophage (CFU-GM) and multipotential CFU (CFU-GEMM); on the other hand, the percentage of BM BFU-E in S phase of the cell cycle was higher in the group of patients with PB CFU-E. While there was no difference between the two groups in serum Epo levels assayed on days 14 and 28 after BMT, patients with PB CFU-E had higher Epo levels in serum samples collected before starting the BMT procedure. These data suggest that the appearance of circulating CFU-E early after BMT is characteristic of a group of patients with an accelerated erythroid engraftment, although the mechanisms leading to the circulation of CFU-E after BMT remain unclear. | pubmed_1082_20210 |
pubmed_632_1329 | PURPOSE
To report a retrospective analysis of risk factors for edge restenosis after Viabahn stent-graft treatment of superficial femoral artery (SFA) occlusive disease and determine any protective effect of drug-coated balloons (DCBs) used at the time of stent-graft implantation.
METHODS
Between October 2011 and July 2016, 110 patients (mean age 73.3±7.6 years; 78 men) were treated with the Viabahn stent-graft for long SFA occlusions. Thirty-eight (34.5%) patients had DCB reinforcement at the distal edge of the stent-graft. For analysis, the population was divided into groups of no edge stenosis patients (n=88; mean lesion length 22.4±4.2 cm) and edge stenosis patients (n=22; mean lesion length 23.5±5.7 cm). The clinical outcomes, ankle-brachial indices, computed tomography angiography findings, and patency were compared at a minimum of 12 months. Logistic regression analysis was employed to determine risk factors for edge stenosis; the results are presented as the odds ratio (OR) and 95% confidence interval.
RESULTS
No differences in clinical or procedural characteristics were identified except the higher incidence of diabetes (p=0.008) and greater need for retrograde access (p=0.033) in the edge stenosis group. DCB reinforcement reduced the incidence of edge stenosis (p=0.021) and target lesion revascularization (TLR; p=0.010) and resulted in a significantly higher 1-year primary patency rate (92.1% vs 76.4%, p=0.042). However, multivariate analysis revealed only poor distal runoff (OR 0.31, 95% CI 0.11 to 0.83, p=0.020) as a predictor of edge stenosis.
CONCLUSION
The risk of edge stenosis after Viabahn implantation was higher in patients with poor distal runoff. DCB reinforcement over the distal edge reduced edge stenosis, decreased 1-year TLR, and improved 1-year primary patency. | 10.1177/1526602818771345 |
pubmed_106_15287 | Blue rubber bleb nevus is a rare entity consisting of distinctive angiomas in the skin and gastrointestinal tract, leading to occult or profound gastrointestinal bleeding and chronic anemia. The efficacy has been documented of systemic treatment with corticoids, interferon, vincristine, and, more recently, subcutaneous octreotide in the presence of active lesion proliferation or disseminated intravascular coagulation. A case of blue rubber bleb nevus syndrome with oral hemangiomas in a 24-year-old woman is reported. The surgical specimens were subjected to immunohistochemical study, which showed all of the hemangiomas to be in an inactive phase. | 10.1177/000348940311200713 |
pubmed_885_16128 | BACKGROUND
While several studies have investigated the effects of short-term air pollution on cardiovascular disease, less is known about its effects on cerebrovascular disease, including stroke and transient ischaemic attack (TIA). The aim of the study was to assess the effects of short-term variation in air pollutants on the onset of TIA and minor stroke.
METHODS
We performed secondary analyses of data collected prospectively in the North West of England in a multi-centre study (NORTHSTAR) of patients with recent TIA or minor stroke. A case-crossover study was conducted to determine the association between occurrence of TIA and the concentration of ambient PM10 or gaseous pollutants.
RESULTS
A total of 709 cases were recruited from the Manchester (n = 335) and Liverpool (n = 374) areas. Data for the Manchester cohort showed an association between ambient nitric oxide (NO) and risk of occurrence of TIA and minor stroke with a lag of 3 days (odds ratio 1.06, 95% CI: 1.01 - 1.11), whereas negative association was found for the patients from Liverpool. Effects of similar magnitude, although not statistically significant, were generally observed with other pollutants. In a two pollutant model the effect of NO remained stronger and statistically significant when analysed in combination with CO or SO2, but was marginal in combination with NO2 or ozone and non-significant with PM10. There was evidence of effect modification by age, gender and season.
CONCLUSIONS
Our data suggest an association between NO and occurrence of TIA and minor stroke in Greater Manchester. | 10.1186/1476-069X-11-77 |
pubmed_1071_6058 | The paper represents the Italian Society of Physical " and Rehabilitation Medicine (SIMFER) recommendations to Neck Pain. We searched the principal scientific databases for papers concerning the main approaches to NP, including international guidelines, clinical trials of high methodological value and systematic reviews without any temporal limits. The recommendations were graded on the basis of the National Plan for Guidelines of the Italian Istituto Superiore di Sanità, which includes the level of evidence and strength of the recommendation. The principal sections of the recommendations deal with the Evaluation and Therapy for Neck Pain. The first describes the main evidence concerning the evaluation of patients with NP with or without limb involvement and/or headache: medical history, physical examination, neurological examination, laboratory tests, electrodiagnostics, diagnostic imaging and self-administered questionnaires. The second describes the best evidence synthesis concernig the therapy for Neck Pain: education, exercise, medical therapy, manual therapy, traction, physical therapy, acupuncture, orthoses, multimodal treatment, behavioural treatment. | pubmed_1071_6058 |
pubmed_921_4959 | Vulvovaginal candidiasis (VVC) is a cause of significant morbidity in many women of a childbearing age worldwide. There is a paucity of literature on the prevalence of this condition in postmenopausal women, although it is believed to be uncommon because of the estrogen dependence of VVC. Postmenopausal women who have underlying risk factors for VVC (e.g. hormone replacement therapy, uncontrolled diabetes mellitus, immunosuppression caused by medication or disease) may be at risk of chronic or recurrent VVC. However, as in younger women, it is likely that, even after exhaustive investigations, no cause will be found in a significant number of patients. The investigation and treatment of VVC in older women should be the same as that undertaken in younger women. Both topical and oral preparations are available, but oral regimens are perhaps more acceptable because of the ease of administration and avoidance of potentially messy creams and suppositories. Ketoconazole at a dosage of 400 mg daily for 14 days can be used to achieve clinical remission of symptoms and negative fungal cultures. Induction treatment should be followed by maintenance therapy for 6 months with ketoconazole 100 mg daily, itraconazole 50 to 100 mg daily or fluconazole 100 mg weekly or 150 mg monthly. Short courses of topical therapy, e.g. 500 mg clotrimazole pessaries as a single weekly dose for 6 months or 100mg miconazole pessaries twice weekly for 3 months, followed by once weekly for 3 months may also be used. | 10.2165/00002512-200016050-00003 |
pubmed_827_12093 | As the muscular nature of the heart had been recognized and it had become evident that the heart was nothing but a hollow muscle, it lost its position as the centre of man. This became likewise true for its position within the body studied with anatomical and physiological methods as with the notion of the heart being an organ of sensibility, emotions, intellect, and will revealed in a particular "heart language". The dignity of the heart assigned to it from ancient time was treated with contempt as a but empty phrase. When, however, in the various attempts to study its myocardial architecture its highly sophisticated engeneering became evident, the real marvel of the heart was demonstrated engendering even in men and women of science an "element of aesthetic awe". Thus, in a certain sense, the heart has recovered its dignity. | 10.1016/s0940-9602(04)80112-2 |
pubmed_923_2341 | Medical students on an in-patient service and residents working in an ambulatory care clinic have regularly evaluated their clinical tutors over the 5 years 1985-1989. Both groups of raters reliably and predictably evaluated their tutors and both emphasize between-tutor comparisons more than actual rating values for individual tutors. Tutors active in both contexts regularly receive higher ratings from the medical students than from the residents. Mid-course feedback to tutors in the medical course had no impact on end-of-course ratings. In neither context did tutor ratings improve from one evaluation to the next. Both groups reliably discriminate between the teaching skills and the personality traits of individual tutors. | 10.1111/j.1365-2923.1993.tb00228.x |
pubmed_735_654 | OBJECTIVE
A lack of comprehensive and standardized metrics for measuring park exposure limits park-related research and health promotion efforts. This study aimed to develop and demonstrate an empirically-derived and spatially-represented index of park access (ParkIndex) that would allow researchers, planners, and citizens to evaluate the potential for park use for a given area.
METHODS
Data used for developing ParkIndex were collected in 2010 in Kansas City, Missouri (KCMO). Adult study participants (n=891) reported whether they used a park within the past month, and all parks in KCMO were mapped and audited using ArcGIS 9.3 and the Community Park Audit Tool. Four park summary variables - distance to nearest park, and the number of parks, amount of park space, and average park quality index within 1mile were analyzed in relation to park use using logistic regression. Coefficients for significant park summary variables were used to create a raster surface (ParkIndex) representing the probability of park use for all 100m×100m cells in KCMO.
RESULTS
Two park summary variables were positively associated with park use - the number of parks and the average park quality index within 1 mile. The ParkIndex probability of park use across all cells in KCMO ranged from 17 to 77 out of 100.
CONCLUSION
ParkIndex represents a standardized metric of park access that combines elements of both park availability and quality, which was developed empirically and can be represented spatially. This tool has both practical and conceptual significance for researchers and professionals in diverse disciplines. | 10.1016/j.ypmed.2016.02.012 |
pubmed_362_4334 | Biochars are obtained by biomass pyrolysis, whereas activated carbon is a biochar that has undergone chemical or physical activation. Owing to the large surface area and easy surface modification both solids are widely applied as adsorbents. They are low-costs materials, they could be regenerated and their disposal is not troublesome. Adsorption of heavy metals, dyes, pharmaceuticals on the surface of biochars and activated carbons, from simple systems of adsorbate containing only one compound, are described extensively in the literature. The present paper provides an overview of reports on adsorption of inorganic and organic compounds onto these two types of adsorbents from the mixed adsorbate systems. The described adsorbate systems have been divided into those consisting of: two or more inorganic ions, two or more organic compounds and both of them (inorganic and organic ones). The research of this type is carried out much less frequently due to the more complicated description of interactions in the mixed adsorbate systems. | 10.1016/j.cis.2022.102687 |
pubmed_15_21740 | This study compares 16 different extraction methods for the comprehensive extraction of mouse brain proteome in combination with "shotgun"-based mass spectrometry (MS). Membrane proteins (MPs) are responsible for a large part of the regulatory functions of the cell and are therefore of great interest to extract and analyze. Sixteen protein extraction protocols were evaluated in regards to protein yield and number of identified proteins with emphasis on MPs. The extracted proteins were delipidated, on-filter digested, and analyzed by reversed phase nanoliquid chromatography (RP-nanoLC) in combination with electrospray ionization (ESI) tandem mass spectrometry (MS/MS) using a 7 T hybrid LTQ-FT mass spectrometer. Detergent-based lysis buffers showed higher efficiencies and yields in the extraction of proteins from the brain tissue compared to solubilization with organic solvents or organic acids. The detergent octyl-β-D-glucopyranoside gave the highest number of identified proteins (541) as well as numbers and percentages of identified MPs (29%). Detergent-based protocols are the best sample preparation tools for central nervous system (CNS) tissue and can readily be applied to screen for candidate biomarkers of neurological diseases. | 10.1021/pr201169q |
pubmed_1038_4722 | Protein disulfide isomerase (PDI, EC 5.3.4.1) is a highly unusual multifunctional polypeptide, being identical to the beta subunit of prolyl 4-hydroxylase, a cellular thyroid hormone binding protein and a component of the microsomal triglyceride transfer protein complex, and highly similar to a polypeptide acting in vitro as a glycosylation site binding protein. It has two -Cys-Gly-His-Cys- sequences which, it has been proposed, act as catalytic sites for the isomerase activity, but few data have been available to indicate whether one or both of them do indeed act as catalytic sites and whether the two presumed catalytic sites act independently or cooperatively. We report here on the expression of human PDI in Escherichia coli with three different signal sequences. All three polypeptide variants were secreted into the periplasmic space as fully active enzymes. Oligonucleotide-directed mutagenesis was used to convert either one or both of the -Cys-Gly-His-Cys- sequences to -Ser-Gly-His-Cys-. The PDI activity of both polypeptides containing a single modified sequence was about 50% of that of the wild-type polypeptide, whereas the polypeptide with two modified sequences had no isomerase activity. It is thus concluded that both -Cys-Gly-His-Cys- sequences act as catalytic sites for the isomerase activity, and the two catalytic sites appear to operate independently of one another. | pubmed_1038_4722 |
pubmed_424_10786 | [reaction: see text] Catalytic systems generated in situ from the chiral PNNP ligands with iridium or rhodium hydride complexes exhibited excellent catalytic activity and good enantioselectivity in the asymmetric transfer hydrogenation of aromatic ketones without added base. The best result was obtained in the IrH(CO)(PPh(3))(3)-ligand 2 catalytic system with up to 99% yield and 97% ee. | 10.1021/ol047412n |
pubmed_886_24011 | There is only 1 US Food and Drug Administration-approved drug for acute ischemic stroke: tissue plasminogen activator (tPA). Due to a short time window and fear of intracerebral hemorrhage (ICH), tPA remains underutilized. There is great interest in developing combination drugs to use with tPA to improve the odds of a favorable recovery and to reduce the risk of ICH. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for ICH associated with tPA use. Minocycline is also an anti-inflammatory agent and inhibits poly (ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in the clinical trials conducted to date. | pubmed_886_24011 |
pubmed_517_18564 | BACKGROUND
Cystic fibrosis (CF) lung disease is characterized by perpetuated neutrophilic inflammation with progressive tissue destruction. Neutrophils represent the major cellular fraction in CF airway fluids and are known to form neutrophil extracellular traps (NETs) upon stimulation. Large amounts of extracellular DNA-NETs are present in CF airway fluids. However, the structural contribution of NETs to the matrix composition of CF airway fluid remains poorly understood. We hypothesized that CF airway fluids consist of distinct DNA-NETs that are associated to subcellular structures.
METHODOLOGY/PRINCIPAL FINDINGS
We employed atomic force microcopy (AFM) and scanning electron microcopy to ultrastructurally characterize the nature of CF sputum and the role of NETs within the extracellular CF sputum matrix. These studies demonstrate that CF sputum is predominantly composed of a high-density meshwork of NETs and NETosis-derived material. Treatment of CF sputum with different DNases degraded CF NETs and efficiently liquefied the mucous-like structure of CF sputum. Quantitative analysis of AFM results showed the presence of three globular fractions within CF sputum and the larger two ones featured characteristics of neutrophil ectosomes.
CONCLUSIONS/SIGNIFICANCE
These studies suggest that excessive NET formation represents the major factor underlying the gel-like structure of CF sputum and provide evidence that CF-NETs contain ectosome-like structures that could represent targets for future therapeutic approaches. | 10.1016/j.jcf.2011.09.008 |
pubmed_212_12803 | A phenomenological theory considering the output characteristics of oxidative phosphorylation has been worked out by adopting the formalism of linear nonequilibrium thermodynamics. The linearity of oxidative phosphorylation in the range of the output forces of practical interest has been experimentally verified. the efficiency of oxidative phosphorylation is zero if either a load with a zero conductance (open-circuited situation) or a load with an infinite conductance (short-circuited situation) is attached to oxidative phosphorylation. In between these extreme conductances there exists a finite load conductance permitting oxidative phosphorylation to operate with optimal efficiency. The necessary and sufficient condition for optimal efficiency was found to be L33/L11 = square root 1 - q2 where L11 is the phenomenological conductance of phosphorylation, L33 the phenomenological conductance of the load and q the degree of coupling of oxidative phosphorylation driven by respiration. This condition was called conductance matching. Under the condition of conductance matching, four output functions of oxidative phosphorylation of practical interest were optimized. A maximal net rate of oxidative phosphorylation occurs at a degree of coupling qf = 0.78. A maximal output power of oxidative phosphorylation, i.e. net rate times established phosphate potential, resuls at qp = 0.91. The maximization of the function net rate times efficiency yielded an economic degree of coupling qfec = 0.95 for maximal ATP flow. Finally, maximization of the function output power times efficiency led to a degree of coupling qpec = 0.97. This last function simultaneously maximized net rate of ATP production, developed phosphate potential and efficiency and reflects therefore the most economic solution to the output problem under the condition of conductance matching. In isolated rat livers perfused in a metabolic resting state, the condition of conductance matching is fulfilled. In addition, the degree of coupling oxidative phosphorylation under these conditions corresponds to the economic degree of coupling qpec. | 10.1111/j.1432-1033.1980.tb04792.x |
pubmed_750_9124 | In adult female, but not male, Sprague Dawley rats, chronic immobilization stress (CIS) increases mossy fiber (MF) Leu-Enkephalin levels and redistributes delta- and mu-opioid receptors (DORs and MORs) in hippocampal CA3 pyramidal cells and GABAergic interneurons to promote excitation and learning processes following subsequent opioid exposure. Here, we demonstrate that CIS females, but not males, acquire conditioned place preference (CPP) to oxycodone and that CIS "primes" the hippocampal opioid system in females for oxycodone-associated learning. In CA3b, oxycodone-injected (Oxy) CIS females relative to saline-injected (Sal) CIS females exhibited an increase in the cytoplasmic and total densities of DORs in pyramidal cell dendrites so that they were similar to Sal- and Oxy-CIS males. Consistent with our earlier studies, Sal- and Oxy-CIS females but not CIS males had elevated DOR densities in MF-CA3 dendritic spines, which we have previously shown are important for opioid-mediated long-term potentiation. In the dentate gyrus, Oxy-CIS females had more DOR-labeled interneurons than Sal-CIS females. Moreover, Sal- and Oxy-CIS females compared to both groups of CIS males had elevated levels of DORs and MORs in GABAergic interneuron dendrites, suggesting capacity for greater synthesis or storage of these receptors in circuits important for opioid-mediated disinhibition. However, more plasmalemmal MORs were on large parvalbumin-containing dendrites of Oxy-CIS males compared to Sal-CIS males, suggesting a limited ability for increased granule cell disinhibition. These results suggest that low levels of DORs in MF-CA3 synapses and hilar GABAergic interneurons may contribute to the attenuation of oxycodone CPP in males exposed to CIS. | 10.1002/syn.22088 |
pubmed_1142_11716 | The International Atomic Energy Agency (IAEA), jointly with the World Health Organization (WHO), has operated a postal dosimetry audit program for radiotherapy centers worldwide since 1969. In 2017 the IAEA introduced a new methodology based on radiophotoluminescent dosimetry (RPLD) for these audits. The detection system consists of a phosphate glass dosimeter inserted in a plastic capsule that is kept in measuring position with a PMMA holder during irradiation. Correction factors for this holder were obtained using experimental methods. In this work these methods are described and the resulting factors are verified by means of Monte Carlo simulation with the general-purpose code PENELOPE for a range of photon beam qualities relevant in radiotherapy. The study relies on a detailed geometrical representation of the experimental setup. Various photon beams were obtained from faithful modeling of the corresponding linacs. Monte Carlo simulation transport parameters are selected to ensure subpercent accuracy. The simulated correction factors fall in the interval 1.005-1.008 (±0.2%), with deviations with respect to experimental values not larger than 0.2(2)%. This study corroborates the validity of the holder correction factors currently used for the IAEA audits. | 10.1016/j.ejmp.2021.04.014 |
pubmed_938_18017 | OBJECTIVES
To determine the symptomatic and urodynamic outcome of elective prostatectomy and to establish whether the outcome is influenced or can be predicted by preoperative urodynamic measurements.
DESIGN
Prospective non-randomised study with follow up at a mean of 11 months after operation. Most men were assessed jointly by a urologist and a general practitioner.
SETTING
Department of urology in a teaching hospital serving a large district population.
PATIENTS
253 Men listed for elective prostatectomy because of symptoms and low urinary flow rates (less than 15 ml/s) and excluding those already on a waiting list or with acute urinary retention, clinically apparent prostatic cancer, and neurological or cerebrovascular disease; 217 (86%) were followed up.
INTERVENTION
Elective prostatectomy.
MAIN OUTCOME MEASURE
Classification on the basis of relief of symptoms assessed by patients and urologist and general practitioner and of symptom scores obtained by questionnaire.
RESULTS
Of the 217 men followed up, 171 (79%) had a satisfactory subjective review and 155 (72%) had a satisfactory review and also low symptom scores. An unsatisfactory outcome was associated with preoperative symptoms of urge incontinence, small prostatic size and resected weight, low voiding pressures, and low urethral resistance. Preoperative maximum urinary flow rates did not predict outcome. Men with poor outcome could be classified into two groups: those with irritative symptoms who were more likely before operation to have had urge incontinence and detrusor instability and men with symptoms of poor urinary flow who were more likely before operation to have had a small prostate, low voiding pressures, and low urethral resistance. In patients in the second group flow rates or voiding pressures improved little after operation. Men with stable detrusors and either low urethral resistance or low voiding pressures were less likely to do well after prostatectomy, but despite these associations preoperative urodynamic measurements were unable to predict outcome accurately.
CONCLUSIONS
Prostatectomy was satisfactory in relieving symptoms and improving urodynamic measurements in most men, but even in those with classic symptoms and low urinary flow rates a substantial minority experienced little improvement afterwards and urodynamic measurements did not accurately predict outcome in individual patients. | 10.1136/bmj.299.6702.762 |
pubmed_170_23623 | OBJECTIVE
To review the efficacy and safety of off-label use of modafinil in the treatment of multiple sclerosis (MS)-related fatigue.
DATA SOURCES
Literature was accessed via MEDLINE (1966-January 2010) and International Pharmaceutical Abstracts (1960-2010), using the medical subject heading terms modafinil, multiple sclerosis, and fatigue.
STUDY SELECTION AND DATA EXTRACTION
All English-language, peer reviewed publications were analyzed for relevance. Studies appropriate to the objective were evaluated, including 3 open-label trials, 1 single-blind trial, and 2 randomized placebo-controlled trials.
DATA SYNTHESIS
Fatigue symptoms, assessed by a variety of self-reported symptom scales, improved in each of the uncontrolled studies reviewed when participants with MS received modafinil 200 mg or less daily for up to 12 weeks. These benefits were not maintained, however, in one uncontrolled study when modafinil was increased to 400 mg daily. Of the 2 randomized, controlled trials, 1 study found that modafinil 200 mg once daily resulted in a reduction in fatigue symptoms measured by the Fatigue Severity Scale at 8 weeks. The other study found no difference in the reduction of fatigue symptoms, measured by the Modified Fatigue Impact Scale at 5 weeks, between the placebo group and patients who received modafinil 100-200 mg twice daily. The most common adverse reactions associated with modafinil use in all studies included gastrointestinal and central nervous system effects.
CONCLUSIONS
Based on the available data, use of modafinil for the treatment of MS-related fatigue has demonstrated benefit in all uncontrolled studies but has conflicting results from 2 controlled studies. Modafinil is a reasonable therapeutic option in this patient population, although larger, long-term, randomized controlled studies are necessary to further elucidate the appropriate dose of modafinil, its effects on MS-related fatigue, and adverse effects associated with its use. | 10.1345/aph.1M705 |
pubmed_1047_3394 | A standardized commercially available immunoassay is not available for detection of IgM antibodies against hepatitis C virus antigens (IgM anti-HCV). Therefore, different "in-house" enzyme immunoassays have been assessed. These assays vary greatly in sensitivity, but specificity seems satisfactory in all of them. A typical IgM antibody response to HCV antigens is usually found in nearly all patients with acute hepatitis C. This antibody response rarely precedes the appearance of IgG anti-HCV, and it persists for a few months at high titer. Low titers of IgM anti-HCV are detectable in 50-80% of cases with chronic hepatitis C. IgM anti-HCV reactivity is typically found during acute exacerbation of chronic hepatitis C. Furthermore, many patients with chronic active hepatitis C without acute exacerbation also have IgM anti-HCV. In these patients a correlation exists between the titer of IgM anti-HCV and the biochemical parameters of liver disease. When alpha interferon therapy induces a sustained remission of liver disease activity, positivity for IgM anti-HCV disappears in more than 70% of cases. In contrast, patients who do not respond to therapy rarely loose IgM anti-HCV. In conclusion, serum IgM antibodies to HCV antigens are reliable markers of active HCV-induced liver disease both in acute and in chronic HCV infection. | 10.1007/978-3-7091-9312-9_21 |
pubmed_1067_6205 | The current-bias (I-V) characteristics at various temperatures, T, of focused-ion-beam (FIB)-deposited Pt contacts on GaN nanowires evolves from low-resistance ohmic (linear I-V) to rectifying as the diameter increases, and both exhibit strongly nonmetallic T-dependence. The small-diameter (66 nm) T-dependent resistance is explained by two-dimensional variable range hopping with a small characteristic energy, ensuring low resistance at 300 K. For large diameters (184 nm), back-to-back Schottky barriers explain the nonlinear I-V at all T values and permit an estimate of doping concentration from the bias-dependent barrier height. Both behaviors can be understood by accounting for the role of FIB-induced amorphization of GaN underneath the contact, as confirmed by cross-sectional transmission electron microscopy. | 10.1021/nl0515697 |
pubmed_93_13757 | Novel 4H structure silver nanowires (4H-AgNWs) have been reported to coexist with the usual face-centered cubic (FCC) ones. Here we report the electrical properties of these polytypic AgNWs for the first time. AgNWs with either 4H or FCC structures in the diameter range of 20-80 nm were measured in situ inside a transmission electron microscope (TEM). Both kinds of AgNW in the diameter range show metallic conductance. The average resistivity of the 4H-AgNWs is 19.9 μΩ cm, comparable to the 11.9 μΩ cm of the FCC-AgNWs. The failure current density can be up to ∼10(8) A cm(-2) for both 4H-and FCC-AgNWs. The maximum stable current density (MSCD) is introduced to estimate the AgNWs' current-carrying ability, which shows diameter-dependence with a peak around 34 nm in diameter. It is attributed to fast annihilation of the current-induced vacancies and the enhanced surface scattering. Our investigations also suggest that the magnetic field of the electromagnetic lens may also introduce some influence on the measurements inside the TEM. | 10.1088/0957-4484/19/8/085711 |
pubmed_1031_3988 | We present 2 cases of sudden death in obese psychiatric patients who had microscopic cardiopulmonary abnormalities. Postmortem analysis of the bloods from both patients detected several kinds of psychiatric drugs, however their levels were below the lethal level. Case 1 was a 33-year-old woman and her heart showed severe fatty infiltration in the atrioventricular (AV) node and left-sided His which was compressed by hypetrophic septal myocardium and hypertensive pulmonary arteriopathy with endocardial thickening of the right atrium and ventricle. Case 2 was a 37-year-old woman and her heart showed mild downward displacement of the tricuspid valve with severe stenosis of the AV node artery. The cause of death in Case 1 was considered to be acute poisoning by three psychiatric drugs through their effect on the preceding cardiopulmonary abnormalities, while that in Case 2 was considered to be the fatal arrhythmia due to occlusion of the AV node artery resulting from the effect of three psychiatric drugs. These 2 cases suggest that microscopic cardiopulmonary abnormalities may be significant findings in obese psychiatric patients and may help in investigations into the manner of death. Further investigation may be needed for exploring the pathological mechanisms of these abnormal findings in obese and/or psychiatric patient. | pubmed_1031_3988 |
pubmed_121_1627 | The groundwater resources of mining areas have been in a challenging condition in terms of metal pollution and human health. Therefore, this study investigated the concentration of cobalt (Co), molybdenum (Mo), selenium (Se), tin (Sn), and antimony (Sb) in groundwater samples (wells, qanats, and springs) in a heavily contaminated mining district, South Khorasan, Eastern Iran. Human health risk of the studied metals to target groups was assessed, and water quality of the studied groundwater was investigated in the study area. A total of 367 sampling sites (279 wells, 74 qanats, and 14 springs) in South Khorasan Province were selected to collect the groundwater samples from June to July 2020. Sampling was performed thrice for each sampling point, and hydrochemical parameters were evaluated using a portable multiparameter. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the metal concentrations. Results showed an order of Se > Mo > Sn > Co > Sb, and hazard index (HI) demonstrated a warning condition for south of South Khorasan (drinking application), southwest of South Khorasan (Irrigation application), and east and center of South Khorasan (drinking-irrigation application). Hydrochemical parameters showed a classification of "Na + K type" and "Mixed Ca-Mg-Cl type" with an overall group of "Na-Cl-HCO3" for sampled waters. Ficklin-Caboi diagram depicted a classification of "near-neutral low metal," and Schoeller diagram classified studied groundwater as "good" for drinking and irrigation consumptions and "Na-Cl" type based on ion balance diagram. Based on the correlation analysis, positive relationships were recorded among EC, TDS, Cl-, Na+, sulfate, Ca2+, salt, total hardness, Mg2+, ammonia, and K+ measured in the water samples. In essence, arid regions of the world greatly rely upon groundwater resources for drinking and irrigation consumptions, and mining districts with a heavy load of active mines can be a serious threat to the groundwater quality and human health. | 10.1007/s11356-022-21494-2 |
pubmed_500_3398 | Some properties of a monoclonal antibody generated against the fibrinogen component of a factor VIII preparation were investigated. The antibody bound with equal affinity in solid phase radioimmunoassays to fibrinogens isolated from both normal patients and patients with von Willebrand disease. It reacted in a sensitive immunoassay of plasma fibrinogen. The specificity of the antibody was confined to the parent molecule with no significant inhibition of fibrinogen binding by the fibrinogen degradation products (FDPs) X, Y, D, or E. The antibody had no significant effect on the activated partial thromboplastin time and prothrombin time of normal plasma. However, it prolonged the thrombin time as determined by the Clauss chronometric fibrinogen method. During fibrinogen lysis by plasmin immunoreactivity of fibrinogen to the antibody was lost at the same rate as the clottable fibrinogen content determined by the Clauss assay. The lack of reactivity of the antibody with FDPs makes it a suitable reagent for investigating plasmin activity as well as studying fibrinogen and fibrin. These findings suggest that the epitope of the antibody lies within the polar protruberance of the carboxy terminal end of the A alpha chain of fibrinogen and is destroyed by plasmin cleavage. | 10.1002/ajh.2830180202 |
pubmed_1050_15088 | Classical clinical findings of multiple evanescent white dot syndrome (MEWDS) include multiple, small white dots scattered throughout the posterior pole, foveal granularity, posterior vitreous cells, and mild optic disc swelling. We describe the case of a 35-year-old man who was admitted to our department with an unusual presentation of MEWDS at the early onset of the disease. A unilateral circumpapillary retinal white spot was observed. Spectral domain optical coherence tomography demonstrated irregularities of the retinal pigment epithelium and disruptions of the outer retinal layers around the optic nerve without other abnormalities. A few days later, the lesion spread centrifugally from the peripapillary region and along the vascular arcades. This distinctive appearance in an early stage of the disease may suggest a disorder other than MEWDS, which can lead to a misdiagnosis and unnecessary treatment. | 10.1159/000509721 |
pubmed_103_9879 | BACKGROUND
Anopheles mosquitoes are the only vectors of human malaria. Anopheles species use standing water as breeding sites. Human activities, like the creation of an artificial lake during the implementation of hydroelectric power plants, lead to changes in environmental characteristics and, therefore, may changes the species richness and composition of Anopheles mosquitoes. The aim of the present study was to verify whether or not there is an association between the artificial flooding resulting from the construction of the Jirau hydroelectric power plant, and the richness and composition of anophelines.
METHODS
Mosquitoes samples were obtained monthly from the Jirau hydroelectric power plant area located at Porto Velho, Rondônia State, using Human Landing Catch (06:00-10:00 PM). Mosquitoes collected were transported to Laboratório de Entomologia Médica FIOCRUZ-RO where they were identified until species using dichotomous key.
RESULTS
A total of 6347 anophelines belonging to eight different species were collected. The anophelines species richness was significantly lower during the first flooding stage. Differences in anophelines species composition were found when comparing the first flooding stage with the other stages. Furthermore, the mean number of Anopheles darlingi, the main vector of malaria in the region, increases during the first and the third flooding stages.
CONCLUSIONS
The continual monitoring of these vectors during the late operational phase may be useful in order to understand how anophelines will behave in this area. | 10.1186/s12936-017-1738-7 |
pubmed_1026_21473 | There is marked sexual dimorphism in the current coronavirus disease 2019 (COVID-19) pandemic. Here we report that estrogen can regulate the expression of angiotensin-converting enzyme 2 (ACE2), a key component for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry, in differentiated airway epithelial cells. Further studies are required to elucidate the mechanisms by which sex steroids regulate SARS-CoV-2 infectivity. | 10.1152/ajplung.00153.2020 |
pubmed_737_11327 | Studies on new antibacterial therapeutics and strategies are currently being conducted in many microbiological, pharmaceutical and biochemical laboratories. The antibacterial activity of plant-derived compounds as well as silver and gold nanoparticles is the subject of this minireview. The application of photodynamic therapy is also discussed. | pubmed_737_11327 |
pubmed_584_21710 | BACKGROUND
Atrial fibrillation (AF) is a recurrent problem that frequently requires repeat cardioversion. Transesophageal echocardiography (TEE) is indicated before cardioversion in patients who are underanticoagulated (warfarin therapy <3 weeks or international normalized ratio [INR] <2.0). It remains uncertain if TEE should be repeated in underanticoagulated patients who had no atrial thrombi detected by previous TEE. Methods and results From January 1996 to June 2001, 76 patients (43 men, 33 women; mean age, 68.8 +/- 10.4 years) who were underanticoagulated and had no atrial thrombi in previous TEE underwent repeat TEE before cardioversion of recurrent AF. The duration of recurrent AF at the time of the second TEE was 5.1 +/- 9.3 months (1 day to 4 years). The underlying diseases included coronary artery disease (n = 30), hypertension (n = 22), valvular heart diseases (n = 8), dilated cardiomyopathy (n = 4), hypertrophic cardiomyopathy (n = 2), and others (n = 10). Eight (10.5%) patients (2 men, 6 women; mean age, 68.6 +/- 6.6 years) were found to have intra-atrial thrombi on the second TEE. Of these 8 patients, 3 had coronary artery disease, 1 had hypertension, 2 had dilated cardiomyopathy, 1 had hypertrophic cardiomyopathy, and 1 had AF of unknown cause. The duration of recurrent AF in patients with and without thrombi was not significantly different (3.6 +/- 4.7 versus 5.3 +/- 9.7 months, P =.22). Of the 8 patients with intra-atrial thrombi on the second TEE, 5 had been taking warfarin for 3 to 4 weeks but had subtherapeutic INR and 3 were taking aspirin only. Compared with patients without intra-atrial thrombi, patients with intra-atrial thrombi had lower ejection fraction (32.5% +/- 18.1% versus 49.9% +/- 14.1%, P =.015), slower left atrial appendage empty velocity (0.22 +/- 0.08 versus 0.41 +/- 0.17 m/s, P <.01), and higher prevalence of spontaneous echo contrast (87.5%) than in patients without intra-atrial thrombi (19.1%, P <.05) but similar left atrial size (49.5 +/- 5.3 versus 47.3 +/- 7.1 mm, P =.15). Cardioversion was cancelled in all patients with atrial thrombi.
CONCLUSIONS
In underanticoagulated patients, repeat TEE is necessary before cardioversion of recurrent AF even if the previous TEE showed no atrial thrombi. | 10.1016/S0002-8703(03)00390-9 |
pubmed_330_15907 | Using only one type of marker to quantify genetic diversity generates results that have been questioned in terms of reliability, when compared to the combined use of different markers. To compare the efficiency of the use of single versus multiple markers, we quantified genetic diversity among 10 S(7) inbred popcorn lines using both RAPD and SSR markers, and we evaluated how well these two types of markers discriminated the popcorn genotypes. These popcorn genotypes: "Yellow Pearl Popcorn" (P1-1 and P1-5), "Zélia" (P1-2 and P1-4), "Curagua" (P1-3), "IAC 112" (P9-1 and P9-2), "Avati Pichinga" (P9-3 and P9-5), and "Pisankalla" (P9-4) have different soil and climate adaptations. Using RAPD marker analysis, each primer yielded bands of variable intensities that were easily detected, as well as non-specific bands, which were discarded from the analysis. The nine primers used yielded 126 bands, of which 104 were classified as polymorphic, giving an average of 11.6 polymorphisms per primer. Using SSR procedures, the number of alleles per locus ranged from two to five, giving a total of 47 alleles for the 14 SSR loci. When comparing the groups formed using SSR and RAPD markers, there were similarities in the combinations of genotypes from the same genealogy. Correlation between genetic distances obtained through RAPD and SSR markers was relatively high (0.5453), indicating that both techniques are efficient for evaluating genetic diversity in the genotypes of popcorn that we evaluated, though RAPDs yielded more polymorphisms. | 10.4238/vol9-1gmr692 |
pubmed_987_8652 | Xylan extraction by alkali is usually a prerequisite for traditional xylooligosaccharide (XOS) production from corncob. In this study, to avoid xylan isolation before XOS production, corncob was delignified by hydrogen peroxide-acetic acid (HPAA), followed by a two-step enzymatic hydrolysis for XOS and monosaccharide production. High lignin removal (55.5%-82.6%) was observed upon pretreatment with 75%-100% HPAA and using 50-100 mM H2SO4 as a catalyst. A high XOS yield of 27.8% was obtained from 75% HPAA-pretreated corncob with 75 mM H2SO4, and the xylose/XOS ratio was only 0.09, indicating that the purity of XOS was relatively high. The highest glucose yield (79.1%) was obtained from 100% HPAA-pretreated corncob with 50 mM H2SO4. Finally, 58.3 g of XOS, 186.9 g of glucose, and 56.4 g of xylose were obtained from 1 kg of corncob. This study provides a promising approach for XOS and monosaccharide production from corncob without xylan isolation. | 10.1016/j.carbpol.2022.119217 |
pubmed_670_8090 | During the mid-1980s, several US communities experienced outbreaks of acute rheumatic fever (ARF), often involving predominantly white, middle-class individuals living in suburban or rural settings. The medical records of all patients diagnosed with ARF in Miami-Dade County, Florida, between 1984 and 1988 were reviewed. Thirty-five cases met the revised Jones criteria and were considered definite; four additional cases were classified as probable. Carditis was present in 54%. Of the 39 patients, 32 (82%) were black. The annual incidence of ARF among black children aged 5-14 years was 12.25 per 100,000 compared to 0.71 for other (non-Hispanic white plus Hispanic) children (P less than .001). ARF was centered in the inner city, where the incidence among black children reached 15.21. Despite the multiethnic, multiracial character of Miami-Dade County and the rapid influx of immigrants, ARF in this community remains primarily a disease of underprivileged, black inner-city children. | 10.1093/infdis/164.4.720 |
pubmed_453_14132 | Skills. Ethics. Attitudes. They are at the core of our professional lives. They are also at the heart of a struggle between younger and older workers. The older and more experienced often express dismay as they try to understand and deal with the modern motivations of their younger colleagues. The resulting friction causes frustration and stress in many organizations. | pubmed_453_14132 |
pubmed_899_17177 | OBJECTIVE
Pinhole single-photon emission computed tomography provides superior trade-off between resolution and detection efficiency as compared with conventional parallel-hole collimators for imaging small objects. This study aims to design and evaluate an optimized adaptive multipinhole (MPH) collimator for improved clinical myocardial perfusion single-photon emission computed tomography imaging (MPI) and preclinical small-animal imaging (SAI) of rats based on a clinical scanner.
METHODS
The target resolution and field of view was set to be 1/20 cm for MPI and 0.15/5 cm for SAI, respectively. We determined the design parameters by maximizing the detection efficiency based on system constraints. Point source simulations using Geant4 Application for Emission Tomography were performed for different collimator-to-center of field of view distances to assess the detection efficiency and resolution trade-off. The XCAT phantom with Tc-99m sestamibi distribution and the four-dimensional mouse whole-body phantom with Tc-99m methylene diphosphonate distribution were used to generate noise-free and noisy projections using a three-dimensional analytical MPH projector. Projections were reconstructed using a three-dimensional MPH ordered-subset expectation maximization algorithm. Noise and bias were assessed on the reconstructed images for different collimators.
RESULTS
The design parameters are (i) 14 pinholes with 3.42 mm aperture size, 14.5 cm collimator-to-detector distance for MPI; (ii) six pinholes with an aperture size of 0.94 mm, 21.2 cm collimator-to-detector distance for SAI. For MPI, the projected full width at half maximum values were 10.68 and 8.19 mm for low energy high resolution (LEHR) and MPH, respectively, whereas MPH had double detection efficiency. For SAI, the projected full width at half maximum values for LEHR and MPH were 4.93 and 1.20 mm, respectively, whereas the detection efficiency of MPH showed 17.5% improvement as compared with LEHR. The noise-bias trade-off improved for MPH as compared with LEHR for both MPI and SAI. The proposed collimator will have adjustable collimator-to-detector distances - that is, 14.5 cm for MPI and 21.2 cm for SAI.
CONCLUSION
The new collimator yields substantial improvement in image quality as compared with current MPI using LEHR with extra capability for SAI, bridging the clinical and preclinical imaging based on the same platform. | 10.1097/MNM.0000000000000429 |
pubmed_229_12028 | OBJECTIVE
To improve the quality and specificity of written evaluations by faculty attendings of internal medicine residents during inpatient rotations.
DESIGN
Prospective randomized controlled trial.
SETTING
Four hospitals: tertiary care university hospital, Veterans' Administration hospital, and two community hospitals.
PARTICIPANTS
Eighty-eight faculty and 157 residents from categorical and primary-care internal medicine residency training programs rotating on inpatient general medicine teams.
INTERVENTION
Focused 20-minute educational session on evaluation and feedback, accompanied by 3 by 5 reminder card and diary, given to faculty at the start of their attending month.
MEASUREMENTS AND MAIN RESULTS
PRIMARY OUTCOMES
1) number of written comments from faculty specific to unique, preselected dimensions of competence; 2) number of written comments from faculty describing a specific resident behavior or providing a recommendation; and 3) resident Likert-scale ratings of the quantity and effect of feedback received from faculty. Faculty in the intervention group provided more written comments specific to defined dimensions of competence, a median of three comments per evaluation form versus two in the control group, but when adjusted for clustering by faculty, the difference was not statistically significant (P =.09). Regarding feedback, residents in the intervention group rated the quantity significantly higher (P =.04) and were significantly more likely to make changes in clinical management of patients than residents in the control group (P =.04).
CONCLUSIONS
A brief, focused educational intervention delivered to faculty prior to the start of a ward rotation appears to have a modest effect on faculty behavior for written evaluations and promoted higher quality feedback given to house staff. | 10.1046/j.1525-1497.2001.016007427.x |
pubmed_261_19552 | This paper estimates the impact of travel distance on the decision to attend for screening for gestational diabetes mellitus (GDM), controlling for a range of personal, clinical and lifestyle characteristics. The results suggest that women who live further away from a screening site are less likely to attend for screening. In particular, the probability of attending for screening is reduced by 1.8% [95% CI: 1.2% to 2.4%] for every additional 10 kms of travel. This is consistent wth previous research that shows geographic inequalities in access to GDM screening in Ireland. We also find that older women, those with a family history of diabetes, and those who are obese are more likely to accept the screening offer, suggesting that certain higher-risk groups may be either self-selecting into the screening programme or are being targeted by health care professionals through specific initiatives. | pubmed_261_19552 |
pubmed_830_8736 | The aquaporin 2 (AQP2) water channel, expressed in kidney collecting ducts, contributes critically to water homeostasis in mammals. Animals lacking or having significantly reduced levels of AQP2, however, have not only urinary concentrating abnormalities but also renal tubular defects that lead to neonatal mortality from renal failure. Here, we show that AQP2 is not only a water channel but also an integrin-binding membrane protein that promotes cell migration and epithelial morphogenesis. AQP2 expression modulates the trafficking and internalization of integrin β1, facilitating its turnover at focal adhesions. In vitro, disturbing the interaction between AQP2 and integrin β1 by mutating the RGD motif led to reduced endocytosis, retention of integrin β1 at the cell surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2-null mice exhibited significant retention of integrin β1 at the basolateral membrane and had tubular abnormalities. In summary, these data suggest that the water channel AQP2 interacts with integrins to promote renal epithelial cell migration, contributing to the structural and functional integrity of the mammalian kidney. | 10.1681/ASN.2012010079 |
pubmed_191_581 | Pediatric reference ranges for osteocalcin measured by a new, fully automated, chemiluminescent immunometric assay on the Immulite immunoanalyzer are presented. Samples from 627 children, ranging from newborns to 18 years of age, were measured. Osteocalcin values are generally higher in children than in adults, highest levels being reached during the puberty growth spurt at about 12 years in girls and 14 years in boys, thereafter rapidly declining towards adult levels. | 10.1515/CCLM.2001.159 |
pubmed_749_2109 | There is evidence that Thai patients receiving standard doses of ritonavir (RTV)-boosted atazanavir (ATV/r) have high exposure to atazanavir (ATV) leading to a higher risk of toxicity. A lower dose of ATV/r may provide adequate exposure in this population. However, pharmacokinetic data on ATV/r in Thai patients required for dose adjustment are limited. This study aimed to develop a population pharmacokinetic model of ATV/r and to determine the influence of patient characteristics on ATV pharmacokinetics. Monte Carlo simulations were performed to estimate the proportion of patients achieving target ATV trough concentration (Ctrough) with the standard ATV/r dose of 300/100 mg and a low dose of 200/100 mg once daily (OD). A total of 127 Thai HIV-infected patients were included in this study. One random blood sample was collected to determine ATV and RTV concentrations at each clinic visit from 100 patients. Intensive data from 27 patients enrolled in previous studies were also included. Data were analysed using the non-linear mixed-effects modelling approach. A one-compartment model with first-order absorption and elimination and absorption lag time best described the data. The population mean clearance of ATV/r was 4.93 L/h in female patients and was 28.7% higher in male patients. Simulation results showed a higher proportion of patients achieving ATV Ctrough within the target range with ATV/r 200/100 mg compared with 300/100 mg. The 200/100 mg OD dose of ATV/r provides adequate ATV exposure in Thai HIV-infected patients. Therefore, a lower dose of ATV/r should be considered for Thai and Asian populations. | 10.1016/j.ijantimicag.2016.11.019 |
pubmed_798_8058 | The atherothrombotic conditions, coronary artery disease, cerebrovascular disease and peripheral arterial disease (PAD), together account for almost one-half of all deaths in Europe each year; however, perception of the specific risks associated with PAD is generally poor compared with its related conditions. PAD is not just a localised disease--it has serious systemic effects, and affected individuals have a higher risk of serious cardiovascular sequelae or death within 1 year of diagnosis compared with those with coronary artery or cerebrovascular disease. PAD, which currently affects approximately 16% of the general population aged over 55 years, is increasing because of the population aging and the continuing rise in cardiovascular risk factors. The management of PAD is a multi-disciplinary approach, and while this can have its advantages, it can also mean that responsibility for patient care is unclear. Globally, almost one-third of all patients with PAD are under internist care. Internists are ideally placed to identify patients at risk of PAD and initiate prompt risk factor management because of their role in the continued care of elderly patients and those with diabetes, hypertension, dyslipidaemia, and chronic renal disease. Multi-disciplinary guidelines for the clinical management of PAD, based on consensus among international specialists in a number of fields, have been developed to create an informed, unified and proactive approach to the treatment of PAD. They stress the continuity of care, the use of office-based ankle-brachial index testing to aid early diagnosis, and prompt and aggressive risk factor management. | 10.1016/j.ejim.2008.09.013 |
pubmed_1071_10661 | Obesity has become more prevalent in most developed countries over the past few decades, and is increasingly recognized as a major risk factor for several common types of cancer. As the worldwide obesity epidemic has shown no signs of abating, better understanding of the mechanisms underlying obesity-associated cancer is urgently needed. Although several events were proposed to be involved in obesity-associated cancer, the exact molecular mechanisms that integrate these events have remained largely unclear. Here we show that senescence-associated secretory phenotype (SASP) has crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of deoxycholic acid (DCA), a gut bacterial metabolite known to cause DNA damage. The enterohepatic circulation of DCA provokes SASP phenotype in hepatic stellate cells (HSCs), which in turn secretes various inflammatory and tumour-promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Notably, blocking DCA production or reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer or depleted of senescent HSCs, indicating that the DCA-SASP axis in HSCs has key roles in obesity-associated HCC development. Moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with non-alcoholic steatohepatitis, indicating that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer and open up new possibilities for its control. | 10.1038/nature12347 |
pubmed_631_3405 | Ubiquitination is one of the most ubiquitous posttranslational modifications in eukaryotes and is involved in various cellular events such as proteasomal degradation and DNA repair. The overwhelming majority of studies aiming to understand ubiquitination and deubiquitination have employed unanchored ubiquitin chains and mono-ubiquitinated proteins. To shed light on these processes at the molecular level, it is crucial to have facile access to ubiquitin chains linked to protein substrates. Such conjugates are highly difficult to prepare homogenously and in workable quantities using the enzymatic machinery. To address this formidable challenge we developed new chemical approaches to covalently attach ubiquitin chains to a protein substrate through its Cys residue. A key aspect of this approach is the installation of acyl hydrazide functionality at the C-terminus of the proximal Ub, which allows, after ubiquitin chain assembly, the introduction of various reactive electrophiles for protein conjugation. Employing α-globin as a model substrate, we demonstrate the facile conjugation to K48-linked ubiquitin chains, bearing up to four ubiquitins, through disulfide and thioether linkages. These bioconjugates were examined for their behavior with the USP2 enzyme, which was found to cleave the ubiquitin chain in a similar manner to unanchored ones. Furthermore, proteasomal degradation study showed that di-ubiquitinated α-globin is rapidly degraded in contrast to the mono-ubiquitinated counterpart, highlighting the importance of the chain lengths on proteasomal degradation. The present work opens unprecedented opportunities in studying the ubiquitin signal by enabling access to site-specifically polyubiquitinated proteins with an increased size and complexity. | 10.1021/ja412594d |
pubmed_659_14298 | Due to the spread of the new coronavirus (COVID-19), the tourism industry has been experiencing a worldwide crisis. However, the effects of the virus differ widely across regions and countries, and the current situation varies considerably. In this study, I will discuss the difficulties faced by the tourism industry regarding the new coronavirus by comparing Japan and Sweden, focusing on discrimination in the tourism industry. In Japan, discrimination based on place of residence has been observed, while in Sweden, race-based discrimination has been confirmed. Considering the current situation, we will examine how information and communication technology (ICT) can be used to salvage the tourism industry in each country. Specifically, we propose a method to increase the sense of security of guests and hosts in the tourism industry through many types of location-based games, such as Pokémon Go and various contact tracing apps. This study is expected to foster trust in the tourism and service industries and bring about business innovation. | 10.1007/s12626-021-00072-x |
pubmed_1005_17058 | BACKGROUND
Laptop computers are used in various places and situations. The number of laptop users experiencing musculoskeletal disorders (MSDs) has increased drastically due to, in part, inappropriate workstations.
OBJECTIVE
To investigate the neck and shoulder postures, and muscle activity relative to perceived pain when using the laptop at a low-height table, sofa, and bed.
METHODS
Twenty male participants aged 18-25 years were randomly assigned to perform laptop computer operation at 3 workstations for 10 minutes during which neck and shoulder angles, muscle activity, and pain were recorded by using an Electrogoniometer, Electromyography (EMG), and visual analog scale (VAS), respectively.
RESULTS
Neck flexions when working at the sofa (18.6°±12.2°) and bed (17.2°±10.5°) were significantly (p < 0.05) greater than that at the low-height table (7.8°±6.5°). However, shoulder flexion when working at the low-height table (28.2°±13.0°) was significantly (p < 0.05) greater than that at the sofa (13.8°±8.6°) and bed (10.91°±7.8°). Working at the low-height table caused the shoulder flexor muscle activity to be significantly (p < 0.05) higher than working at the sofa and bed. Neck pain was reported during laptop computer use at the sofa and bed, and upper back pain when working at the low-height table.
CONCLUSIONS
High neck flexion and pain were found while working at sofa and bed, whereas high muscle activity at shoulder and upper back pain were found while working at the low-height table. | 10.3233/WOR-192942 |
pubmed_383_2239 | Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in most developed countries and even more in developing countries. Dyslipidemia is a well known main risk factor for ASCVD. Lipid-lowering treatment, particularly lowering LDL-cholesterol (LDL-C), can decrease the risk for ASCVD. New data and guidelines based upon them suggest that we should go with LDL-C levels as low as we can. Therefore, conventional lipid lowering agents (statins and statins+ezetimibe) are not enough mainly because of poor compliance and statin intolerance which is in the real world mostly pseudo-intolerance. PCSK9 inhibitors provided a new hope to further decrease LDL-C but are still expensive, they have to be injected subcutaneously twice a month and their long-lasting adverse effects are not known. Therefore, there is a constant need to develop novel, more potent, more safe, less expensive, more user friendly regimens of hypolipemic agents (bempedoic acid, selective PPAR alpha receptor modulators etc). One of the ways to overcome poor compliance and increase the potency of therapy with less adverse effects are fixed combinations of established drugs (statin+ezetimibe). The future of hypolipemic agents is based on antisense therapy, ie. the use of specific oligonucleotide sequences blocking the translation of the selected protein (targeting apolipoprotein CIII, lipoprotein (a), apolipoprotein B) or RNA silencing technique (PCSK9 mRNA) and are in various stages of clinical trials. Some of them are almost ready to use in everyday clinical practice. High risk and very high risk patients (eg. familial hypercholesterolemia, familial severe chylomicronemia syndrome) will benefit most. The aim of this review is to inform about novel hypolipemic agents - potent and safe drugs for dyslipidemia which should reduce the risk of ASCVD. | 10.2147/JEP.S267376 |
pubmed_518_2226 | The membrane integrity of a cell is a well-accepted criterion for characterizing viable (active or inactive) cells and distinguishing them from damaged and membrane-compromised cells. This information is of major importance in studies of the function of microbial assemblages in natural environments, in order to assign bulk activities measured by various methods to the very active cells that are effectively responsible for the observations. To achieve this task for bacteria in freshwater and marine waters, we propose a nucleic acid double-staining assay based on analytical flow cytometry, which allows us to distinguish viable from damaged and membrane-compromised bacteria and to sort out noise and detritus. This method is derived from the work of S. Barbesti et al. (Cytometry 40:214-218, 2000) which was conducted on cultured bacteria. The principle of this approach is to use simultaneously a permeant (SYBR Green; Molecular Probes) and an impermeant (propidium iodide) probe and to take advantage of the energy transfer which occurs between them when both probes are staining nucleic acids. A full quenching of the permeant probe fluorescence by the impermeant probe will point to cells with a compromised membrane, a partial quenching will indicate cells with a slightly damaged membrane, and a lack of quenching will characterize intact membrane cells identified as viable. In the present study, this approach has been adapted to bacteria in freshwater and marine waters of the Mediterranean region. It is fast and easy to use and shows that a large fraction of bacteria with low DNA content can be composed of viable cells. Admittedly, limitations stem from the unknown behavior of unidentified species present in natural environments which may depart from the established permeability properties with respect to the fluorescing dyes. | 10.1128/AEM.67.10.4662-4670.2001 |
pubmed_530_1711 | Waste disposal on land and the consequent transport of bacterial and viral pathogens in soils and aquifers are of major concern worldwide. Pathogen transport can be enhanced in the presence of organic matter due to occupation of attachment sites in the aquifer materials thus preventing pathogen attachment leading to their faster transport for longer distances. Laboratory column studies were carried out to investigate the effect of organic matter, in the form of dissolved organic carbon (DOC), on the transport of Escherichia coli and MS2 phage in saturated clean silica sand. Transport rates of these microbial tracers were also studied in a contaminated field site. Laboratory column studies showed that low concentrations (0.17 mg L(-1)) of DOC had little effect on E. coli J6-2 removal and slightly reduced the attachment of MS2 phage. After progressive conditioning of the column with DOC (1.7 mg L(-1) and 17 mg L(-1)), neither E. coli J6-2 nor MS2 phage showed any attachment and recovery rates increased dramatically (up to 100%). The results suggest that DOC can affect the transport rates of microbial contaminants. For E. coli J6-2 the predominant effect appeared to be an increase in the secondary energy minimum leading to an increase in E. coli attachment initially. However, after 17 mg L(-1) DOC conditioning of the silica sand no attachment of E. coli was observed as the DOC took up attachment sites in the porous media. MS2 phage appeared to be affected predominantly by out-competition of binding sites in the clean silica sand and a steady reduction in attachment was observed as the DOC conditioning increased. Field study showed a high removal of both E. coli and MS2 phage, although E. coli was removed at a lower rate than MS2 phage. In the field it is likely that a combination of effects are seen as the aquifer material will be heterogeneous in its surface nanoscale properties, demonstrated by the differing removal of E. coli and MS2 phage compared to the laboratory scale experiments. This research demonstrates the importance of combining laboratory scale and field scale studies to fully understand removal of microbes in groundwater aquifers affected by organic matter (DOC). | pubmed_530_1711 |
pubmed_16_5892 | This study investigated the relationships between walking speed and heart rate (HR) variability (HRV) in eleven subjects during a 24-h race. It was hypothesized that the nycthemeral rhythm on HR is preserved during the race. RR intervals and walking speed were measured. Fast Fourier transform was applied to samples of 1,024 successive RR intervals collected every hour from a HR monitor. Walking speed was averaged every hour and decreased (first lap: 8.8 +/- 0.3 vs. last lap: 7.3 +/- 0.8 km h(-1), P < 0.001) with HR also decreasing (max at 19:00 h: 143 +/- 9 vs. min at 7:00 h: 117 +/- 14 beats min(-1), P < 0.001) following a third order polynomial shape. HRV power spectral components followed distribution patterns similar to the mean RR during the race with a minimum in the early evening (19:00-20:00 h) and a maximum in the morning (5:00-8:00 h). Thus, as for mean RR, spectral components over time are also fitted to a third order polynomial regression. LF/HF ratio increased linearly (min = 0.5 +/- 0.3, max = 2.8 +/- 5.3, P = 0.02). Although mean HF peak did not decrease significantly over time, it was positively correlated with walking speed. In conclusion, this study showed that despite a constant decrease in walking speed, HR circadian rhythm is preserved during a continuous 24-h walking race. The short-term HRV components remain linked to HR whereas the LF/HF ratio increases linearly until the end of the race whatever HR is. | 10.1007/s00421-006-0341-3 |
pubmed_187_16263 | Few scientific data are available on the effectiveness of commonly used modalities for reducing pressure at the site of neuropathic ulcers in persons with diabetes mellitus. The authors' aim was to compare the effectiveness of total contact casts, half-shoes, rigid-soled postoperative shoes, accommodative dressings made of felt and polyethylene foam, and removable walking casts in reducing peak plantar foot pressures at the site of neuropathic ulcerations in diabetics. Using an in-shoe pressure-measurement system, data from 32 midgait steps were collected for each treatment. There was a consistent pattern in the devices' effectiveness in reducing foot pressures at ulcer sites under the great toe and ball of the foot. Removable walking casts were as effective as or more effective than total contact casts. Half-shoes were consistently the third most effective modality, followed by accommodative dressings and rigid-soled postoperative shoes. | 10.7547/87507315-87-10-466 |
pubmed_545_12179 | BACKGROUND
Epistaxis is a disease well known to general practitioners and ENT specialists in the outpatient sector as well as in hospitals. The aim of this study was to analyze data of patients that were treated as inpatients at the ENT university hospital Freiburg between 2014-2018.
MATERIALS AND METHODS
This retrospective study analyzes data of admitted patients with epistaxis regarding age, medication, bleeding site, underlying health conditions, radiological imaging and treatment. Risk factors for longer inpatient length of stay and readmission were identified.
RESULTS
Median length of stay was 3.5 days. 55 % of the patients suffered from posterior epistaxis. 72.3 % of patients were treated with anticoagulants at the time of admission. The most prevalent medical conditions were hypertension (66 %) and arrhythmia due to atrial fibrillation (36.1 %). 63.5 % of the patients were treated by nasal packing. 97 patients (14.6 %) had to be treated surgically. Surgical treatment, transfusion, posterior epistaxis and anticoagulant treatment were risk factors for longer length of inpatient stay. Preexisting hypertension, posterior bleeding and single anticoagulant treatment increased the risk of readmission.
CONCLUSIONS
Determination and consideration of risk factors allow identification of patients at risk of longer inpatient length of stay and readmission. Adequate management accounting for risk profiles of patients could help reduce morbidity. | 10.1055/a-1342-0090 |
pubmed_241_11643 | OBJECTIVE
To evaluate the distribution and affecting factors of blood glucose in normal rats for the criterion of hyperglycemia in animal model.
METHODS
The data of fast blood glucose (FBG) and 120 min postprandial blood glucose (PBG) of nearly 500 Wistar and SD rats from different experiment in our laboratory were collected and analyzed by multi-variable analysis and optimal scaling regression for the distribution and key affecting factors of blood glucose. Comparing the blood glucose determined by different method (glucose oxidase method or glucose monitor with strips), different duration (fasting for 5 h or 11 h), different blood source (from abdominal aorta or tail), and different time for separating serum after sampling (at once or till 120 min) was conducted in another 40-100 Wistar rats. A mathematical model for the contribution of different components was evaluated and combined by parameters of half width and range.
RESULTS
The average FBG and PBG of normal Wistar rats was (3.95 +/- 1.31) mmol/L and (5.65 +/- 1.63) mmol/L, and the 95% upper limit was 6.2 mmol/L and 7.9 mmol/L respectively. The differences of fasting duration, sample source, time before separating serum and testing methods, excepting for rat species, were significant (P < 0.05). The results showed that the blood glucose tested by glucose monitor method was not comparable with GOD method while the range of blood glucose was out of 7-11 mmol/L. The difference of blood glucose between fasting for 5h and 11 h was 0.8 mmol/L. Blood glucose from abdominal aorta was 40% higher than that from tail. The reduction of blood glucose was 8% in 60 min and over 50% in 120 min after blood being sampled. After the test requirement being regulated, the upper limit for FBG and PBG was expanded to 7.5 mmol/L and 10.4 mmol/L, respectively.
CONCLUSION
The onset of diabetics in rat is judged as blood glucose being higher than the expanded normal upper level. The criteria for rats are close to that for human. | pubmed_241_11643 |
pubmed_433_16466 | An artificial alanine-based amino acid {(S)-2-amino-3-[4-propyl-3-(thiophen-2-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoic acid, here named TioxAla}, bearing a substituted triazolyl-thione group on the side chain and able to bind RNA biomedical targets, was here chosen as a valuable scaffold for the synthesis of new platinum complexes with potential dual action owing to the concomitant presence of the metal centre and the amino acid moiety. Three new platinum complexes, obtained from the reaction of TioxAla with K2PtCl4, were characterized by mass spectrometry, nuclear magnetic resonance and UV-vis spectroscopy: one compound (Pt1, bis-{(S)-2-amino-3-[4-propyl-3-(thiophen-2-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoate-O,S} platinum(II)) consisted of two amino acid units coordinating the Pt(II) ion; the other two, Pt2 [potassium dichloro-{(S)-2-amino-3-[4-propyl-3-(thiophen-2-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoate (O,S)} platinum(II)] and Pt3 [potassium dichloro-{(S)-2-amino-3-[4-propyl-3-(thiophen-2-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoate (O,N)} platinum(II)], were isomers bearing one TioxAla unit, and two chlorides as Pt-ligands. Pt coordination involved preferentially the amino, carboxylic and thione functions of TioxAla. By preliminary antiproliferative assays, a moderate cytotoxic activity on cancer cells was observed only for Pt2 and Pt3, while no anticancer activity was found for both the chloride-free complex (Pt1) and TioxAla. This cytotoxicity, however lower than that of cisplatin, well correlated with the marked ability, here found only for Pt2 and Pt3 complexes, to bind DNA sequences either in random coil or in structured forms (duplex and G-quadruplex), as verified by spectroscopic and spectrometric analysis. | 10.1016/j.jinorgbio.2019.110868 |
pubmed_60_13186 | BACKGROUND
Primary immunodeficiencies are potentially life-threatening diseases. Over the last years, the clinical phenotype and the molecular basis of an increasing number of immunological defects have been characterized. However, in daily practice primary immunodeficiencies are still often diagnosed too late. Considering that an early diagnosis may reduce morbidity and mortality of affected patients, an interdisciplinary guideline for the diagnosis of primary immunodeficiencies was developed on behalf of the Arbeitsgemeinschaft Pädiatrische Immunologie (API) and the Deutsche Gesellschaft für Immunologie (DGfI).
METHODS
The guideline is based on expert opinion and on knowledge from other guidelines and recommendations from Germany and other countries, supplemented by data from studies that support the postulated key messages (level of evidence III). With the contribution of 20 representatives, belonging to 14 different medical societies and associations, a consensus-based guideline with a representative group of developers and a structured consensus process was created (S2k). Under the moderation of a representative of the Association of the Scientific Medical Societies in Germany (AWMF) the nominal group process took place in April 2011.
RESULTS
The postulated key messages were discussed and voted on following a structured consensus procedure. In particular, modified warning signs for primary immunodeficiencies were formulated and immunological emergency situations were defined. | 10.1055/s-0031-1287835 |
pubmed_471_78 | BACKGROUND
Early management of unilateral coronal synostosis (UCS) aims to treat the cranial abnormality with the hope of improving middle and lower facial morphology. This study analyzed osseous volume and 3-dimensional distances in the midface and mandible of patients with UCS to assess changes in facial symmetry following a cranial vault procedure.
METHODS
Patients who underwent fronto-orbital advancement for UCS repair between 1981 and 2012 with follow-up of at least 3 years were included. Computed tomography-based 3-dimensional reconstructions of the mandible and LeFort III midface were divided by 3 midline osseous landmarks and measured for volume. Distances between 11 osseous landmarks were measured in the midface and mandible. Ratios between the measurements on synostotic and nonsynostotic sides were calculated. Presurgical to postsurgical changes were evaluated with paired samples t tests. The study was powered to detect differences between preoperative and postoperative ratios of at least 3%.
RESULTS
Eleven patients were included. Mean age at initial imaging was 4.7 ± 3.2 months (range, 0.4-9.2 months) with postoperative follow-up of 9.0 ± 5.3 years (range, 3.3-17.0 years). Midfacial symmetry of osseous volume improved following surgery (synostotic to nonsynostotic ratio, 94.1% vs 98.9%, P = 0.044). The width (P < 0.001), height (P = 0.039), and anterior-posterior depth of the midface (P = 0.011) also became more symmetric. In the mandible, however, volumetric and linear symmetry did not improve.
CONCLUSIONS
Symmetry of the midface, but not the mandible, improves significantly following the cranial procedure in patients with UCS. | 10.1097/SCS.0000000000004877 |
pubmed_39_16471 | BACKGROUND
Prostate cancer is a major concern of public health. Microvascular density (MVD) is one of the prognostic markers for various solid cancers. Matrix metalloproteinase 11 (MMP11) plays an important role in angiogenesis and changes in its expression level are known to be associated with tumor progression and clinical outcome.
AIM
To investigate the relationship between MVD and MMP11 expression in prostatic adenocarcinoma tissues.
MATERIALS AND METHODS
The expression levels of MMP11 and MVD were analyzed immunohistochemically for 50 specimens of prostatic adenocarcinoma.
RESULTS
MMP11 was mainly expressed in stromal cells but rarely seen in epithelial cells. Mean MVD was 36/mm2, and it was correlated significantly only with bone metastases. MVD was also significantly correlated with MMP11 expression (r=0.29, p=0.044).
CONCLUSIONS
MMP11 may alter the stromal microenvironment of prostate cancer to stimulate tumor angiogenesis. | 10.7314/apjcp.2015.16.15.6639 |
pubmed_888_17449 | PURPOSE
For almost 3 years, Radiologists and Physicists from Padova and Ferrara Universities have collaborated together, with the aim of collecting and comparing experimental data useful to define the most significant parameters for quality controls in digital mammography. Successively, radiologists and physicists working in other sites where a digital mammography unit was installed joined the work-group.
MATERIALS AND METHODS
In this study we report the results obtained from measurements of linearity, uniformity, short- and long-term reproducibility, AEC stability performed on 5 digital equipment by using a simple test object. X-ray beam quality and tube yield were preliminarily checked in such a way that possible uncertainties of digital system responses could be separated from those due to differences among X-ray tubes.
RESULTS
Results showed that the equipment considered, comparable in terms of both beam quality (HVL) and tube yield, always displayed linear response and reproducibility errors lower than 5%. Uniformity was very good and the grey level compensation as a function of exposure parameters remained within 5%. Differences in choice of parameters by exposure control system (AOP) were emphasised, especially for crossing between track/filter combinations (from Mo/Mo to Mo/Rh and from Mo/Rh to Rh/Rh); those differences were attributed to the +/-2 mm tolerance of breast thickness measurement (mechanically obtained) greater than the AOP tolerance (+/-1 mm).
DISCUSSION AND CONCLUSIONS
Obtained results can be useful, as comparison and reference values, for users employing a digital mammography unit of the same kind reported in this paper. Moreover, the same results could be used as "orientation" also by other users having different digital mammography technologies, whose operation should be nevertheless specifically studied and understood in order to find the most useful parameters for quality controls. The acquired experience clearly showed us that years of investigations will be necessary in order to be able to write reliable protocols. This should induce people to contemplate the necessity of not improvising "theoretical" protocols, that are unreliable and dangerous for their negative clinical implications. | pubmed_888_17449 |
pubmed_81_11398 | Amorphous drugs have a higher kinetic solubility and dissolution rate than their crystalline counterparts. However, this advantage is lost if the amorphous form converts to the stable crystalline form during the dissolution as the dissolution rate will gradually change to that of the crystalline form. The purpose of this study was to use in situ Raman spectroscopy in combination with either partial least squares discriminant analysis (PLS-DA) or partial least squares (PLS) regression analysis to monitor as well as quantify the solid-phase transitions that take place during the dissolution of two amorphous drugs, indomethacin (IMC) and carbamazepine (CBZ). The dissolution rate was higher from amorphous IMC compared to the crystalline alpha- and gamma-forms. However, the dissolution rate started to slow down during the experiment. In situ Raman analysis verified that at that time point the sample started to crystallize to the alpha-form. Amorphous CBZ instantly started to crystallize upon contact with the dissolution medium. The transition from the amorphous form to CBZ dihydrate appears to go through the anhydrate form I. Based on the PLS analysis the amount of form I formed in the sample during the dissolution affected the dissolution rate. Raman spectroscopy combined with PLS-DA was also more sensitive to the solid-state changes than X-ray powder diffraction (XRPD) and was able to detect changes in the solid-state that could not be detected with XRPD. | 10.1016/j.ejpb.2008.06.001 |
pubmed_380_1610 | The effects of iron (Fe) deficiency on fruit yield and quality were measured in two peach cultivars, Carson (yellow-skin fruit) and Babygold (red-skin fruit). In both cultivars, Fe deficiency caused major decreases in fruit fresh weight per tree and number of fruits per tree. Fruits from Fe-deficient peach trees had a smaller size, resulting in a large decrease in the percentage of commercially acceptable fruits, whereas fruit firmness was unaffected. In cv. Babygold, Fe deficiency greatly decreased the red color of the fruit skin. Part of these results was likely associated with a delay in fruit ripening. When fruits with similar appearance were compared, taking into account fruit size, color, and firmness, Fe deficiency generally led to higher concentrations of organic anions (especially succinate and quinate), vitamin C, and phenolic compounds and to lower total sugar/total organic acid ratios. This could lead to decreased fruit eating quality and to a slight improvement in fruit nutritional value. | 10.1021/jf034402c |
pubmed_730_10819 | The synthesis of new 1 beta-methylcarbapenems (1a-l) having a proline reverse amide moiety at the C-2 position and their in vitro antibacterial activities are described. The compounds were evaluated by the Mueller-Hinton agar dilution method and compared with meropenem as control. Aliphatic amides (1a-h) are found to show greater antibacterial activity than aromatic amides (1i-l). Moreover, C-2 free amino compound (1m) reveals greater activity than any other amide compounds (1a-l). | 10.1002/(sici)1521-4184(199804)331:4<139::aid-ardp139>3.0.co;2-u |
pubmed_702_7718 | Fournier's gangrene is a potentially fatal necrotizing fasciitis affecting the perineum and genital area. The usual treatment includes prompt surgical debridement and, in many cases, a diverting colostomy. We present two cases of Fournier's gangrene that were treated with extensive local debridement and rectal diversion with a new device for faecal matter management, avoiding the need for a colostomy. | 10.1007/s10151-009-0474-6 |
pubmed_387_8761 | Increased expression of major histocompatibility complex (MHC) antigens may occur following liver transplantation. The mechanism by which this occurs is unclear. Postoperative complications may result in cholestasis. We have investigated the possibility that cholestasis may cause increased expression of MHC antigens in the liver. Cholestasis was induced in rat livers by bile duct ligation and transection. Total serum bilirubin rose markedly postoperatively and remained elevated over a period of 21 days. Samples of bile taken from rats were shown to remain sterile during the study period and there was no evidence of viral infection. Liver tissue taken 1, 3, 7, and 21 days postobstruction showed a marked increase in the expression of rat class I MHC antigens but not class II antigens. We suggest that cholestasis itself can induce increased MHC class I antigens in the liver. Therefore, if cholestasis occurs postoperatively in the human liver transplant recipient this might lead to increased expression of human class I MHC antigens and add to the overall cellular immune activity in a rejection reaction, although cholestasis probably cannot initiate rejection. | 10.1097/00007890-198804000-00017 |
pubmed_505_21266 | UNLABELLED
This study compared the results of neurodevelopmental examination at 6 months' corrected age of premature infants with neonatal seizures and/or intracranial hemorrhage and normal premature infants. There was a statistically significant correlation (p=0.000007) between intracranial hemorrhage and seizures in the group of 68 premature infants seen in the neurodevelopmental outpatient service at Hospital de Clínicas de Porto Alegre, Brazil. Intracranial hemorrhage was significantly associated with multiparity (p=0.02). The neurodevelopmental examination at 6 months' corrected age revealed that patients who suffered neonatal intracranial hemorrhage and/or seizures had inappropriate muscle tone, strength and reflexes, as well as delay in head control.
CONCLUSION
We compared the results of neurodevelopmental examinations of two groups of premature infants at 6 months' corrected age. The difference in neurological development at 6 months' corrected age was statistically significant when comparison was corrected for premature infants who had neonatal seizures and periventricular hemorrhage. | 10.1590/s0004-282x2003000600002 |
pubmed_946_1863 | Plasma renin substrate concentration, renin activity, serum sex hormone binding globulin and total protein concentration were measured sequentially in 10 women after elective caesarean section. Plasma renin substrate concentration decreased from 5406 +/- 000 micrograms AI/l (mean +/- SD) at term to 2369 +/- 726 micrograms AI/l 6 days post partum. Plasma renin activity decreased from 6.2 +/- 3.3 micrograms AI/l/h at term to 4.2 +/- 4.0 micrograms AI/l/h 6 days after delivery. Serum sex hormone binding globulin decreased more slowly than plasma renin substrate concentration. Clearance of plasma renin substrate based on plasma renin activity was calculated. This consumption by renin could explain only 12% of the decrement in plasma renin substrate concentration at the steepest part of the plasma renin substrate disappearance curve. It is concluded that metabolic clearance of plasma renin substrate may be much greater than that calculated from plasma renin activity. | pubmed_946_1863 |
pubmed_178_7246 | The humoral immune response of human volunteers vaccinated with highly purified type II-or type III-specific polysaccharide of group B streptococci was evaluated using an enzyme-linked immunosorbent assay standardized with quantitative precipitin analysis, a method which permits calculation of the micrograms of specific antibody protein per milliliter of serum, rather than expression of the data as titers. By inhibition studies, the assays were shown to be specific for antibody to the undegraded type II or III polysaccharide antigen. Purity of the antigens and the specificity of the immune response to them were evidenced by an increase in level of antibody only to the type-specific antigen used for immunization. The isotype of the antibody raised in the sera of immunized volunteers was primarily IgG, thus confirming the potential utility of vaccination against group B streptococci using polysaccharide vaccines to induce antibodies which will cross the human placenta. | 10.1093/infdis/147.5.847 |
pubmed_658_8724 | This article compares four Dutch environmental certification schemes for agricultural food crops, analysing their methodology and the completeness of their criteria on five aspects: pesticide use, nutrient use, water management, energy and materials consumption, and habitat management. The least stringent of the labels, the MBT ('Environmentally Aware Cultivation') certificate, serves mainly to increase farmers' awareness of nutrient and pesticide use. With regard to both administrative obligations and actual management practices, the MBT label largely mirrors the terms of standing Dutch legislation. The CC ('Controlled Cultivation') and AMK ('Agro-Environmental') labels comprise more and more stringent criteria. With their restrictions on nutrient and pesticide use, these two labels serve as the two principal labels in the field of integrated agriculture. There is little difference between the two and it is recommended that they be merged, on the basis of a standardised definition of integrated agriculture. The EKO ('Organic Agriculture') label proceeds from different principles, but as a minimum should also comply with Dutch legislation without exception. For both integrated and organic agriculture, in addition to criteria on pesticide and nutrient use, criteria should also be developed for water management, energy and materials use and habitat management. The relationship between the criteria and their respective thresholds and Dutch legislation is also addressed. Existing criteria are frequently specified in such a way that the environmental benefits cannot be ascertained. This is a serious drawback for the parties further down the chain: auctioneers, retailers and consumers. It is recommended to develop qualitative guidelines for an Agricultural Stewardship Council at international level, like the Forest Stewardship Council, and a separate label for integrated agriculture per country comprising quantitative criteria for all relevant aspects of farming operations. | 10.1006/jema.2002.0548 |
pubmed_325_23742 | Determination of left-right asymmetry in mouse embryos is established by a leftward fluid flow that is generated by clockwise rotation of node cilia. How node cilia achieve stable unidirectional rotation has remained unknown, however. Here we show that brief exposure to the microtubule-stabilizing drug paclitaxel (Taxol) induces randomly directed rotation and changes the ultrastructure of node cilia. In vivo observations and a computer simulation revealed that a regular 9+0 arrangement of doublet microtubules is essential for stable unidirectional rotation of node cilia. The 9+2 motile cilia of the airway, which manifest planar beating, are resistant to Taxol treatment. However, the airway cilia of mice lacking the radial spoke head protein Rsph4a undergo rotational movement instead of planar beating, are prone to microtubule rearrangement, and are sensitive to Taxol. Our results suggest that the absence of radial spokes allows node cilia to rotate unidirectionally but, as a trade-off, renders them ultrastructurally fragile. | pubmed_325_23742 |
pubmed_834_15568 | It has been possible to follow-up 74 (54%) of the 137 patients who were treated for orbital floor fractures in our clinic between 1988 and 1992. The minimum observation time was 12 months. The results of the orbital reconstruction were analysed on the basis of the postoperative findings and the advantages of access via a central lower lid incision and the use of allogenic dura mater, were evaluated on the basis of the functional results. The biocompatibility, stability and ready availability of allogenic dura mater all support its use in orbital floor restoration. Nevertheless, the potential problems of CJD transmission are discussed. | 10.1016/s1010-5182(05)80251-3 |
pubmed_621_19840 | Ion Beam Aperture Array Lithography was applied to top-down fabrication of large dense (10(8)-10(9) particles/cm(2)) arrays of uniform micron-scale particles at rates hundreds of times faster than electron beam lithography. In this process, a large array of helium ion beamlets is formed when a stencil mask containing an array of circular openings is illuminated by a broad beam of energetic (5-8 keV) ions, and is used to write arrays of specific repetitive patterns. A commercial 5-micrometer metal mesh was used as a stencil mask; the mesh size was adjusted by shrinking the stencil openings using conformal sputter-deposition of copper. Thermal evaporation from multiple sources was utilized to form magnetic particles of varied size and thickness, including alternating layers of gold and permalloy. Evaporation of permalloy layers in the presence of a magnetic field allowed creation of particles with uniform magnetic properties and pre-determined magnetization direction. The magnetic properties of the resulting particles were characterized by Vibrating Sample Magnetometry. Since the orientation of the particles on the substrate before release into suspension is known, the orientation-dependent magnetic properties of the particles could be determined. | 10.1371/journal.pone.0037440 |
pubmed_223_21890 | The emergence of PET probes for amyloid plaques and neurofibrillary tangles, hallmarks of Alzheimer disease (AD), enables monitoring of pathology in AD mouse models. However, small-animal PET imaging is limited by coarse spatial resolution. We have installed a custom-fabricated PET insert into our small-animal MRI instrument and used PET/MRI hybrid imaging to define regions of amyloid vulnerability in 5xFAD mice. We compared fluorine-18 [18F]-Florbetapir uptake in the 5xFAD brain by dedicated small-animal PET/MRI and PET/CT to validate the quantitative measurement of PET/MRI. Next, we used PET/MRI to define uptake in six brain regions. As expected, uptake was comparable to wild-type in the cerebellum and elevated in the cortex and hippocampus, regions implicated in AD. Interestingly, uptake was highest in the thalamus, a region often overlooked in AD studies. Development of small-animal PET/MRI enables tracking of brain region-specific pathology in mouse models, which may prove invaluable to understanding AD progression and therapeutic development. | 10.1038/s41598-020-67284-z |
pubmed_217_13788 | INTRODUCTION
Duodenal Crohn's disease is a rare clinical entity that occurs in 0.5-4.0% of patients with Crohn's disease. A unique case of Crohn's disease of the upper gastrointestinal tract characterized by multiple strictures within the duodenum and jejunum is described in our review.
PRESENTATION OF CASE
A 41-year-old male presented with a 2-month history of intermittent, crampy abdominal pain accompanied by nausea, bilious emesis, early satiety, anorexia and weight loss. Physical examination revealed fullness in the epigastric region. Imaging demonstrated strictures in the proximal and distal duodenum with dilatation of the intervening segments. There was also gross dilatation of the proximal jejunum, which was followed by a 9cm strictured segment. There was no evidence of acute Crohn's disease. Although a Whipple's resection was initially considered as a form of operative intervention given the extent of disease within the duodenum, the discovery of unexpected disease intra-operatively presented a surgical dilemma. In this case, strictureplasty, surgical resection and bypass were used to treat the patient.
DISCUSSION
Diffuse stricturing of the proximal gastrointestinal tract is a rare manifestation of Crohn's disease. Although imaging can aid in surgical planning, intra-operative decision-making to deal with unexpected findings will remain an important aspect of the management of this entity.
CONCLUSION
The fundamental goal of the surgical management of strictures secondary to Crohn's disease is to relieve obstruction while maximizing bowel conservation. A variety of operative techniques are currently described for the management of duodenal Crohn's disease and are reviewed in this case report. | 10.1016/j.ijscr.2012.03.012 |
pubmed_399_4577 | Flavone acetic acid represents a novel chemical structure currently undergoing clinical investigation. Broad spectrum activity has been observed in preclinical animal screens, but at doses close to toxic in mice. Phase I clinical trials have established that equivalent plasma drug levels can be achieved in humans, but to date Phase II trials have not demonstrated significant activity in a range of tumor types. Little is known about the drug's biotransformation, although metabolites have been implicated in proposed mechanisms of action. In this paper, we have purified the two major human metabolites present in urine (also the only two metabolites detected in plasma) and characterized their structure, chemical properties, activity, and pharmacokinetics. Metabolite 1 (M1) was a glucuronide conjugated to the 8-acetic acid grouping (Mr 456), was chemically labile, and showed a strong tendency to undergo chemical rearrangement at mildly alkaline pH. Metabolite 2 (M2) was also a glucuronide (Mr 456) but appeared to be an unusual isomer of M1. Both were noncytotoxic. In patients, biotransformation represented the predominant mechanism of drug clearance with as much as 80% of a low dose (0.5 g/m2) recovered in urine as M1 and M2 after only 6 h. At high dose (4.8 to 8.6 g/m2, 1- to 6-h infusion) the appearance of peak concentrations of metabolites in plasma and urine was delayed, apparently due to saturation of glucuronidation pathways. This resulted in an overall reduction in drug clearance by 3- to 4-fold. Mice cleared flavone acetic acid much more slowly than patients (289 ml/h/m2 after 600 mg/m2 i.p. versus 2.3 liters/h/m2 after 4.8 g/m2-1-h i.v. infusion) without producing M1 or M2. A different metabolite, exhibiting characteristics of a conjugate, was detected at low concentrations in plasma, tissues, and tumor. Extensive metabolism to inactive products followed by their rapid clearance may contribute to the lack of activity so far seen in humans. | pubmed_399_4577 |
pubmed_1136_16902 | Sufentanil is a potent synthetic opioid. Like other opioids, sufentanil creates a stable hemodynamic environment in cardiovascularly compromised pediatric patients. Clearance, expressed as per kilogram, is increased in children compared to adults. The P450 CYP3A4 enzyme is responsible for the major metabolic N-dealkylation pathway. Enzyme activity is reduced in neonates but the maturation of sufentanil clearance is not described. The free active fraction is affected by age because of the reduced α(1) -acid glycoprotein plasma concentrations in neonates. Intranasal administration of sufentanil is a possible option for premedication, procedural sedation and analgesia in children, as this option has been found to be safe and effective. Studies concerning the pharmacokinetics and dynamics of sufentanil administered as a bolus or continuous infusion in children are few. | 10.1111/j.1460-9592.2010.03411.x |
pubmed_1076_22761 | OBJECTIVE
To provide an overview on the increase of forensic psychiatric hospitalizations in Saxony, and present findings on criminal conviction and recidivism rates of 277 criminal offenders ordered to a forensic psychiatric facility caring for addictive disorders between 1996 and 2001.
METHODS
Cluster- and regression-analytic procedures identified predictive variables for declaring the forensic psychiatric hospitalization as useless, and for relevant criminal offences after discharge.
RESULTS
About 85 % of the study sample showed more than four offences and more than 1.5 years of imprisonment before admission to the index-treatment episode. About half of the patients was successfully treated as indicated by being released on licence. Socialization in institutions, social disintegration before admission, and absconding during the index-treatment episode are important factors increasing the probability of declaring the hospitalization as useless. In the 2-year observation period, the criminal recidivism rate was 40.0 %.
CONCLUSIONS
Social reintegration of this group of mentally disordered criminal offenders is as difficult as important. Findings on recidivism rates indicate a need for extending the number of specialized forensic outpatient departments and a need to focus on primary prevention. | 10.1055/s-2006-952006 |
pubmed_573_22247 | OBJECTIVES
The aim of this study was to investigate the presence of PER-1-type ESBLs in drug resistant Pseudomonas aeruginosa isolates.
MATERIALS AND METHODS
During one-year period (2008-2009), following isolation and identification of 56 P. aeruginosa, the E-test method was performed for determination of minimal inhibitory concentration of ceftazidim. The isolates that they had MIC≥16 µg/ml against ceftazidim were used for determination of ESBL-producing by combined disk test (CDT) and double disk synergy test (DDST) methods. Bla PER-1 gene was investigated by PCR. P. aeruginosa KOAS was used as positive control.
RESULTS
Twenty-nine (51.78%) out of fifty six isolates had MIC≥16 µg/ml to ceftazidime, twenty two (75.86%) of them were ESBL producers. Some isolates (27.5%) contained bla PER-1 gene.
CONCLUSION
PER-1-type ESBLs producing P.aeruginosa has not been reported previously in but there has been a rather high prevalence of it. | pubmed_573_22247 |
pubmed_465_2677 | In order to demonstrate an alternative way to correct diaphyseal defects allogenic cortical bone prepared as "osteogenin containing gelatine (OCG)" was used in sheep. Animals without any implants served as controls. Healing was assessed by radiological examination after 3, 6, 9 and 12 weeks and histological examination after 12 weeks. In the control group there was no bridging of the defect in all of the four animals. Out of the six animals of the OCG-group one animal suffered from a postoperative infection and one animal failed because of a breakdown of the osteosynthesis. The other four animals exhibited a complete reconstruction of the former defect roentgenologically after 9 weeks. Histologically a new formed spongious bone could be demonstrated in the former defective site. The OCG-implants were completely resorbed after 12 weeks. | 10.1055/s-2008-1045078 |
pubmed_801_2979 | BACKGROUND
Few data are available on access to contraception following a natural disaster. The current study extends the literature by examining access to various types of birth control in a large sample of women from diverse backgrounds following Hurricane Ike, which made landfall on September 13, 2008, on the upper Texas Gulf Coast.
METHODS
We examined Hurricane Ike's influence on access to contraceptives through survey results from 975 white, black, and Hispanic women 16-24 years of age receiving care at one of five publicly funded reproductive health clinics in the Texas Gulf Coast region between August 2008 and July 2010.
RESULTS
Overall, 13% of women reported difficulties accessing contraception. Black women had more difficulty than their white (p<0.001) and Hispanic (p=0.019) counterparts. Using multivariate analysis, we found that although family planning clinics in the area were open, black women (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.37-3.73; p=0.001] and hurricane evacuees (OR 2.17, 95% CI 1.27-3.72; p=0.005) reported greater difficulty in accessing birth control. Last, we found that a lack of access to birth control was related to having a higher frequency of unprotected sex for women of all races (p=0.001).
CONCLUSIONS
Access to resources is critical in differentiating the level of impact of disasters on various groups of people. We suggest a community-based disaster preparedness and response model that takes women's reproductive needs into account. | 10.1089/jwh.2010.2613 |
pubmed_929_14441 | The non-modified nanocarriers-based therapies for the treatment of cancer and other infectious diseases enhanced the chemical stability of therapeutically active agents, protected them from enzymatic degradation and extended their blood circulation time. However, the lack of specificity and off-target effects limit their applications. Mannose receptors overexpressed on antigen presenting cells such as dendritic cells and macrophages are one of the most desirable targets for treating cancer and other infectious diseases. Therefore, the development of mannosylated nanocarrier formulation is one of the most extensively explored approaches for targeting these mannose receptors. The present manuscript gives readers the background information on C-type lectin receptors followed by the roles, expression, and distribution of the mannose receptors. It further provides a detailed account of different mannosylated nanocarrier formulations. It also gives the tabular information on most relevant and recently granted patents on mannosylated systems. The overview of mannosylated nanocarrier formulations depicted site-specific targeting, enhanced pharmacokinetic/pharmacodynamic profiles, and improved transfection efficiency of the therapeutically active agents. This suggests the bright future ahead for mannosylated nanocarriers in the treatment of cancer and other infectious diseases. Nevertheless, the mechanism behind the enhanced immune response by mannosylated nanocarriers and their thorough clinical and preclinical evaluation need to explore further. | 10.1016/j.jconrel.2020.01.046 |
pubmed_1089_12638 | Nonselective vitamin D receptor activators (VDRA), such as calcitriol and alfacalcidol, have been successfully used in the treatment of secondary hyperparathyroidism (SHPT) in hemodialysis. Despite their beneficial effects on the control of serum PTH levels, their use has been limited by intolerance (development of hypercalcemia and hyperphosphatemia with consecutive cardiovascular toxicity). Apart from becoming intolerant, in 20-30 % of patients who use nonselective VDRA, serum PTH levels do not decrease appropriately despite increasing doses of these agents. These patients are considered calcitriol-resistant patients. Thus, calcitriol resistance and intolerance are two sides of the same coin: active vitamin D failure. Despite the clinical relevance of active vitamin D failure, definitions of resistance and intolerance are imprecise and have varied over time. More selective VDRA claim to produce less hypercalcemia and hyperphosphatemia and could help clinicians to overcome intolerance. Also, some studies have also shown that paricalcitol can be even useful in resistant patients. Significant limitations of iPTH as a reliable and useful clinical biomarker have been increasingly appreciated. There is evidence that intact PTH concentration must differ by 72 % between any two measurements before it can be considered a significant change. VDR polymorphisms could be involved in the development of SHPT in CKD patients. Interestingly, a higher incidence of the b allele of the VDR BsmI gene variant has been shown to be present in SHPT. The BsmI genotype can also affect the response of hemodialysis to IV calcitriol. A challenge for the future will be to establish biomarkers such as laboratory determinations or ultrasound findings that can help us to early identify those patients who will not respond appropriately to calcitriol or exhibit intolerable side effects . | 10.1007/s11255-013-0637-2 |
pubmed_1036_14458 | The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion inhibits the sustained expression of lipogenic enzymes FAS, ACL, and SCD1. As a result, mammary tissue has reduced lipid content and the milk produced has altered lipid composition, resulting in attenuated pup growth. Consistent with PERK-dependent regulation of the lipogenic pathway, loss of PERK inhibits expression of FAS, ACL, and SCD1 in immortalized murine embryonic fibroblasts when cultured under conditions favoring adipocyte differentiation. These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway. | 10.1073/pnas.0808517105 |
pubmed_642_3068 | Oilseed rape (Brassica napus L.) is an oleoproteaginous crop characterized by low N use efficiency (NUE) that is mainly related to a weak Nitrogen Remobilization Efficiency (NRE) during the sequential leaf senescence of the vegetative stages. Based on the hypothesis that proteolysis efficiency is crucial for the improvement of leafNRE, our objective was to characterize key senescence-associated proteolytic mechanisms of two genotypes (Ténor and Samouraï) previously identified with contrasting NREs. To reach this goal, biochemical changes, protease activities and phytohormone patterns were studied in mature leaves undergoing senescence in two genotypes with contrasting NRE cultivated in a greenhouse under limiting or ample nitrate supply. The genotype with the higher NRE (Ténor) possessed enhanced senescence processes in response to nitrate limitation, and this led to greater degradation of soluble proteins compared to the other genotype (Samouraï). This efficient proteolysis is associated with (i) an increase in serine and cysteine protease (CP) activities and (ii) the appearance of new CP activities (RD21-like, SAG12-like, RD19-like, cathepsin-B, XBCP3-like and aleurain-like proteases) during senescence induced by N limitation. Compared to Samouraï, Ténor has a higher hormonal ratio ([salicylic acid] + [abscisic acid])/([cytokinins]) that promotes senescence, particularly under low N conditions, and this is correlated with the stronger protein degradation and serine/CP activities observed during senescence. Short statement: The improvement in N recycling during leaf senescence in a genotype of Brassica napus L. characterized by a high nitrogen remobilization efficiency is related to a high phytohormonal ratio ([salicylic acid] + [abscisic acid])/([cytokinins]) that promotes leaf senescence and is correlated with an increase or the induction of specific serine and cysteine protease activities. | 10.3389/fpls.2019.00046 |
pubmed_465_5123 | In a 21-year-old woman with McCune-Albright syndrome, acromegaly and hyperprolactinemia with hypopituitarism developed secondary to a large pituitary tumor. Bromocriptine suppressed the secretion of growth hormone and prolactin, with a reduction in tumor size. However, at the age of 8, she already showed evidence of biochemical acromegaly, with a paradoxical rise of growth hormone levels during two glucose tolerance tests, in the presence of a radiologically normal pituitary fossa. These data support the hypothesis that long-standing hypothalamic stimulation may have been responsible for the later development of a pituitary tumor. | 10.1001/archpedi.1983.02140280032008 |
pubmed_131_5336 | Eleven newly diagnosed insulin dependent patients were studied before and during the first 16 h after start of insulin treatment. All the patients were found to have significant amounts of C-peptide in plasma indicating residual insulin secretion. The fall in blood glucose after start of insulin therapy was followed by a parallel decrease in C-peptide (R = 0.99, P < 0.01) suggesting that the beta-cells may respond to variation in blood glucose. Eight of the patients were studied 1, 4, 7, 14, 90 and 180 days after start of insulin therapy. During the first 90 days of treatment an increasing maximal C-peptide concentration was found after a standard breakfast test meal. Two thirds of this improvement i beta-cell function was found after the initial 14 days with an average increase in maximal C-peptide of 260 per cent. The sensitivity to glucose improved. | 10.1530/acta.0.0950359 |
pubmed_259_5426 | Prostaglandin E(2) (PGE(2)) has been implicated as an inducer of angiogenesis in human colon cancer. Here, we demonstrate that PGE(2) exposure induces the expression of vascular endothelial growth factor (VEGF) mRNA in HCT116 human colon carcinoma cells that is mediated by the transcriptional activator hypoxia-inducible factor 1 (HIF-1). PGE(2) exposure induces the phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. Pharmacologic inhibition of ERK phosphorylation blocks the induction of VEGF mRNA and HIF-1alpha protein expression in response to PGE(2) stimulation. Inhibition of C-SRC tyrosine kinase activity also blocks PGE(2)-induced HIF-1alpha protein and VEGF mRNA expression without blocking ERK phosphorylation. In contrast, phosphorylation of AKT is dependent on ERK and C-SRC activity. Thus, the activity of multiple signal transduction pathways is required for the HIF-1-mediated induction of VEGF expression in colon cancer cells exposed to PGE(2). | pubmed_259_5426 |
pubmed_558_13764 | BACKGROUND
Since 1990, most schoolchildren in the United States have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. Elimination of endemic rubella virus circulation in the United States was declared in 2004. The objective of the current study was to evaluate the short- and long-term rubella immunogenicity of MMR2.
METHODS
At enrollment in 1994-1995, children (n = 307) in a rural Wisconsin health maintenance organization received MMR2 at age 4-6 years. A comparison group of older children (n = 306) was vaccinated at age 9-11 years. Serum specimens were collected during a 12-year period. Rubella antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 1:10).
RESULTS
Before administration of MMR2 in the kindergarten group, 9% of subjects were seronegative, 60% had the lowest detectable titer, and the geometric mean titer (GMT) was 1:13. One month after administration of MMR2, 1% were seronegative, 6% had the lowest detectable titer, and the GMT was 1:42. Four-fold boosts occurred in 62% of subjects, but only 0.3% were immunoglobulin M positive. Twelve years after MMR2 administration, 10% were seronegative, 43% had the lowest detectable titer, and the GMT was 1:17. The middle-school group showed similar patterns.
CONCLUSIONS
Rubella antibody response to MMR2 was vigorous, but titers decreased to pre-MMR2 levels after 12 years. Because rubella is a highly epidemic disease, vigilance will be required to assure continued elimination. | 10.1086/605410 |
pubmed_559_12383 | BACKGROUND
Seeking to identify where litigious claims against otolaryngologists are targeted (i.e. areas of highest risk) within the NHS and private sector would have positive implications in risk management and limiting the amount of litigation against otolaryngologists.
METHOD
The National Health Service Litigation Authority (NHSLA) and Medical Defence Union (MDU) were contacted and anonymous data obtained on claims within ENT.
RESULTS
887 claims were notified - 457 NHSLA and 430 MDU. The commonest claim in both groups was failure or delay in diagnosis (12 per cent NHSLA, 23 per cent MDU). The other commonest claims were all related to complications (nerve damage 10 per cent, deafness 8 per cent and dental damage 5 per cent). Dissatisfaction with results was 8 per cent total and, within the private sector, was almost exclusively in rhinology.
CONCLUSIONS
This study once again emphasizes the need for thorough clinical assessment, record keeping and good communication with patients. Recognising these areas of highest risk may limit future claims. | 10.1017/S0022215106001812 |
pubmed_1047_5428 | We studied the excitatory motor evoked potentials (MEPs) and the inhibitory (silent period) responses to focal transcranial magnetic stimulation (TMS) in the abductor pollicis brevis (APB) of 5 normal subjects to learn whether the scalp topography of the two responses differed. At the scalp location where stimulation produced the highest-amplitude MEP in the voluntarily activated APB, stimulus intensities below the MEP threshold produced silent periods with little or no preceding facilitation. The silent periods had a mean duration of 26.8 +/- 6.8 msec and a mean onset latency of 27.6 +/- 3.6 msec, which was 7.2 +/- 2.3 msec longer than the latency of MEPs produced in the APB by higher stimulus intensities. A period of excitation, with an onset latency of 50-80 msec, often followed the silent period. On averaged trials, a stimulus intensity just above the threshold of the MEP at its optimal position produced MEPs followed by silent periods at a cluster of scalp locations 1 cm apart on the central scalp (medial area) and silent periods with very slight or no preceding facilitation in 3-9 locations lateral to the MEP area (lateral area). This finding was confirmed in 3 subjects with maps constructed from statistical analysis of multiple trials. These maps also showed that MEPs produced from the medial area occurred 4-6 msec earlier than those produced from the lateral area. The integral of the silent period tended to be larger in the lateral area. The motor representation of APB, as defined by TMS, is not homogeneous but rather contains at least two components that differ physiologically and topographically. | 10.1016/0168-5597(93)90116-7 |
pubmed_265_14219 | Anatomical structures of shoulder joints of five adult cheetahs were examined by dissection, corrosion casts and radiography. The bones, capsules and auxiliary synovial devices were described, as well as ligaments and adjacent muscles. The cheetah shoulder has many similarities with the shoulder joint of the domestic cat, but also considerable differences. Proper osteological features were the large supraglenoid tubercle, the caudally directed coracoid process and the extension of the articular surface of the scapula to the lateral area of the supraglenoid tubercle. On the proximal end of the humerus the width of the head of humerus, the facet of infraspinatus muscle as a shallow cavity with the insertion of the infraspinatus muscle around it and two raised roughnesses on the proximal end of the tricipital line for the insertions of the lateral glenohumeral ligament and the teres minor muscle were noticeable. The insertion of the joint capsule was mainly on the glenoid labrum, only in part of the articular surface on the lateral area of the supraglenoid tubercle laterally on the scapula. The joint capsule formed a supra- and infraspinatus recess laterally, an intertubercular tendon sheet for the biceps brachii muscle cranially, and a bipartited subscapular recess medially. An extracapsular transverse ligament passing the intertubercular groove, a laterally capsular strengthening--called lateral glenohumeral ligament--and an intracapsular medial glenohumeral ligament could be found. The latter one was joined to the capsule by a mesoligament, dividing the subscapular recess into two pouches. | 10.1111/j.1439-0264.1998.tb00166.x |
pubmed_1132_16148 | INTRODUCTION
Genetic aberrancies within epidermal growth factor receptor (EGFR) pathway are associated with therapeutic outcomes of EGFR-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, the impact of chemotherapy on EGFR-related genes alterations has not been defined in NSCLC. Our study aims to investigate the impact of neoadjuvant chemotherapy (Neoadj-Chemo) on EGFR activating mutations and associated EGFR-TKIs resistance-related genes.
PATIENTS AND METHODS
Matched tumor samples were obtained retrospectively from 66 NSCLC patients (stages IIb-IIIb) corresponding to pre- and post- Neoadj-Chemo. EGFR mutations were detected by denaturing high performance liquid chromatography (DHPLC) and confirmed by Amplification Refractory Mutation System technology (ARMS), KRAS mutations, T790M mutation and c-MET amplification were identified using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), ARMS, and real-time PCR, respectively.
RESULTS
Before Neoadj-Chemo, EGFR mutations were identified in 33.3% (22/66) of NSCLC patients. Only 18.2% (12/66) of patients carried EGFR mutations after Neoadj-Chemo (p = 0.013). The median peak value of EGFR 19 exon mutations decreased non-significantly after Neoadj-Chemo. KRAS mutation rate decreased from 4.6% (3/66) to 3.0% (2/66) with Neoadj-Chemo. Although the overall percentage of patients exhibiting c-MET amplifications (6.1% [4/66]) did not change with Neoadj-Chemo, two patients transitioned from negative to positive c-MET amplification, and two patients reversed these changes post-Neoadj-Chemo. T790M mutations were absent from all samples.
CONCLUSION
Neoadjuvant chemotherapy tends to decrease the mutation frequency of EGFR mutation and downstream genes, which suggests that real-time samples analysis for genetic aberrancies within EGFR pathways have important value to delineate specific patient populations and facilitate individualized treatment. | 10.1371/journal.pone.0051021 |
pubmed_953_21956 | The inflammatory response induced by Vipera lebetina venom (VLV) in the mice hind paw was evaluated by paw edema value and vascular permeability changes. The edema was produced in a dose- and time-dependent manner. This response was maximal within 2 h and disappeared after 24 h The minimum edema-forming dose was estimated at 0.8 μg/20 g body weight. Microscopic examination confirmed that VLV also induces skin structure alterations with collagen fiber dissociation and polynuclear infiltration, which is characteristic of edema formation. The induced edema with VLV (1 μg/paw) could be due to the release of pharmacological active substances at the site of injection. Histamine, serotonine, and arachidonate metabolites may play important roles in the vasoactive and edematic effect of VLV since pretreatment of mice with cromoglycate, cyproheptadine, ibuprofen, loratidine, and indomethacin significantly reduced the edema formation (77, 63, 57, 45, and 43 %, respectively). The obtained results demonstrate that the induced edema and vasodilatation by this venom may be triggered and maintained by different pharmacological mechanisms, since cromoglycate and cyproheptadine were the most active inhibitors of the edema. The relationships between histamine and serotonin release from mast cells and arachidonate metabolites activation could be the main step in edema-forming and the induced vasodilatation by the venom. | 10.1007/s10753-012-9563-1 |
pubmed_789_4104 | Sexual debut represents a developmental transition that holds possibility for growth and for risk. Family and neighborhood may impact timing of debut. This qualitative study examined family strategies (e.g., moving, parental monitoring), perceptions of neighborhood, and attitudes about sex and sexual debut among sexually experienced and inexperienced African American adolescent females living in disadvantaged urban neighborhoods. Findings show that more familial strategies were reported by sexually inexperienced females, suggesting that strategies may delay sexual debut. Furthermore, experiences with neighborhood violence related to attitudes about sex and sexual debut, suggesting a linkage between death anxiety and sexual debut among female youth. | 10.1080/15427609.2012.654430 |
pubmed_265_8321 | The association of bone loss with age, sex, and several prevalent and modifiable potential risk factors for osteoporosis was studied in 1,856 men and 2,452 women aged 55 years and over from the Rotterdam Study, a population-based cohort study in the Netherlands. The rate of change in femoral neck bone mineral density was estimated longitudinally between 1990 and 1995, after 2 years of follow-up on average. These rates, adjusted for age and body mass index, were -0.0025 (95% confidence interval -0.0038 to -0.0012) in men and -0.0045 (95% confidence interval -0.0056 to -0.0034) g/cm2/year in women (p=0.03). Bone loss accelerated with age, as seen more clearly in men than in women. Lower body mass index and cigarette smoking were associated with increased bone loss in both men and women. In men, higher calcium intake was associated with lower rates, and disability was associated with borderline significantly higher rates of bone loss (p=0.07). In women, a nonsignificant relation was observed with disability, but not with dietary calcium intake. Alcohol intake was not consistently related to the rate of bone loss in either sex. It is concluded that in elderly people the rate of bone loss is higher in women, progresses with age, and is further determined by several modifiable risk factors, particularly in men. | 10.1093/oxfordjournals.aje.a009541 |
pubmed_446_18149 | For the first time, the adsorption of xyloglucan (XG) on chitin nanocrystals (ChiNC) surface was proved using quartz crystal microbalance with dissipation (QCM-D) and by successfully building up spin-coated assisted layer-by-layer (LbL) structures on solid substrates. Several parameters in the adsorption process, such as ChiNC concentrations (0.5-3.0 g L(-1)), number of layers, or the outmost layer material (ChiNC or XG), were investigated to better understand the fabrication process of multilayer films. The thickness of the homogeneous film increased linearly with the number of bilayers, with an average thickness per bilayer of 12.3 nm. Additionally surface morphology was studied by atomic force microscopy (AFM), which revealed an almost completely covered surface after the adsorption of ChiNC. The final structures were found to have semireflective properties capable of being tuned by adjusting the ChiNC dispersion parameters. | 10.1021/bm401474c |
pubmed_286_21340 | INTRODUCTION
Basal insulin is among the second line treatment options for Type 2 Diabetes Mellitus (T2DM). Efficacy and safety of basal insulin in patients of T2DM, uncontrolled with Oral Antidiabetic Agents (OAAs) remains understudied in the Indian setting.
AIM
To assess the efficacy and safety of insulin glargine in patients with T2DM who have uncontrolled glycaemic levels despite single or two OAAs therapy.
MATERIALS AND METHODS
In this prospective, open label study, T2DM patients above 40 years of age, having inadequate glycaemic control [Glycosylated Haemoglobin (HbA1c) above 8% and/or fasting glucose level of 140 mg/dl and above] with single or two OAAs over three consecutive months were included. Dosing of insulin glargine was adjusted as per Fasting Blood Glucose (FBG) and Post Prandial Blood Glucose (PPBG) levels. Patients were followed for 12 weeks and data was analysed by comparing 12th week findings to baseline values.
RESULTS
In 40 cases included in final analysis, mean age was 56.35 ± 6.77 years, 52.5% were females and mean body mass index was 26.96 ± 4.59 kg/m2. Compared to baseline, significant reduction in HbA1c, FBG and PPBG blood glucose (all p<0.05) was seen. HbA1c goal of < 7% was achieved in 37.5% cases. Systolic (p>0.05) and diastolic (p<0.05) blood pressures reduced at 12 weeks as compared to baseline. Increase in weight was modest with mean increase of 1.06 kg (p>0.05). Overall, 14 symptomatic hypoglycaemia events were observed with none being severe.
CONCLUSION
Short term administration of insulin glargine is effective in reducing glycaemia and is safe with lower rates of severe hypoglycaemia. It can be considered in patients with uncontrolled T2DM on mono- or two- OAAs treatment. | 10.7860/JCDR/2017/27649.10214 |
pubmed_1136_15922 | To estimate the effect of breastfeeding initiation and duration on child development outcomes. 3,271 children and their mothers participating in the Child Development Supplement of the Panel Study of Income Dynamics provide data for these analyses. Main outcomes include Woodcock Johnson Psycho-Educational Battery-Revised (WJ-R) test score (letter word, passage comprehension, applied problem, and broad reading), and Wechsler Intelligence Scale for Children-Revised (WISC-R) test score at the 2002 survey. Controlled variables include family, maternal, and child characteristics, many of which can be traced back to the year the child was born. The analytic technique is propensity score matching with multiple imputations. After using propensity scores to adjust for confounding factors, breastfeeding initiation showed statistically significant effects but the practical scale remains small. Breastfeeding duration showed a non-linear effect on those outcomes and most of the effects are not significant. The effects of breastfeeding on child's cognitive outcomes are modest in practical terms. The non-linear effects suggest that selection into breastfeeding may account for the increased score of children who are breastfed. | 10.1007/s10995-010-0677-5 |
pubmed_612_23841 | INTRODUCTION
Chronic hepatitis B is an important public health concern. Introduction of oral nucleos(t)ide analogs (NAs), inhibitors of hepatitis B virus (HBV) polymerase, was a milestone that lowered the high viral loads associated with an increased risk of liver-related complications.
AREAS COVERED
Although the currently available NAs are effective in suppressing viral replication, anti-HBV treatment in principle requires lifelong drug administration, and some patients have limitations such as the incidence of liver cancer and the likelihood of toxicities following long-term treatment despite viral suppression. Besifovir dipivoxil maleate (BSV), an oral nucleotide analog, is a prodrug that is metabolized to its active form. It has consistent and well-characterized pharmacokinetics in animals and human. In clinical studies, BSV exhibits significant and potent viral suppression of HBV replication with maintenance of antiviral efficacy for over 192 weeks without resistance, or renal and bone toxicities. Herein, the authors discuss the data of BSV and provide the reader with their expert opinion.
EXPERT OPINION
BSV is a newly developed antiviral agent against HBV. This new agent has strong antiviral activity with low toxicity and a high barrier to resistance. Because there is concern that patients treated with a high dose of BSV require carnitine supplementation, BSV with carnitine supplementation is recommended during antiviral therapy. | 10.1080/14656566.2021.1967321 |
pubmed_810_14553 | The immune milieu in malignant tumors can influence the prognosis of patients. However, little is known about the effect the antitumoral therapy has on the inflammatory infiltrate. In head and neck squamous cell carcinoma we found evidence that a neoadjuvant radiochemotherapy could modulate the composition of the intratumoral inflammation into an anti-tumoral pattern. | 10.4161/onci.20200 |
pubmed_168_3388 | Core-shell nanostructures consisting of FePt magnetic nanoparticles as the core and semiconducting chalcogenides as the shell were synthesized by a series of reactions in a one-pot procedure. Adding Cd(acac)2 as the cadmium precursor to a reaction mixture containing FePt nanoparticles afforded FePt@CdO core-shell intermediates. The subsequent addition of chalcogens yielded FePt@CdX core-shell nanocrystals (where X was S or Se). The reverse sequence of addition, i.e., adding X before Cd, resulted in spongelike nanostructures because the chalcogens readily formed nanowires in the solution. Transmission electron microscopy, energy-dispersive X-ray spectrometry, selected area electron diffraction, fluorescence spectroscopy, and SQUID were used to characterize the nanostructures. These core-shell nanostructures displayed superparamagnetism at room temperature and exhibited fluorescence with quantum yields of 2.3-9.7%. The flexibility in the sequence of addition of reagents, combined with the compatibility of the lattices of the different materials, provides a powerful yet convenient strategy for generating sophisticated, multifunctional nanostructures. | 10.1021/ja0731017 |
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