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Using rapid assessment and response to operationalise physical activity strategic health communication campaigns in Tonga.
The aim of the present study was to identify stakeholder and program beneficiary needs and wants in relation to a netball communication strategy in Tonga. In addition, the study aimed to more clearly identify audience segments for targeting of communication campaigns and to identify any barriers or benefits to engaging in the physical activity program. A rapid assessment and response (RAR) methodology was used. The elicitation research encompassed qualitative fieldwork approaches, including semistructured interviews with key informants and focus group discussions with program beneficiaries. Desk research of secondary data sources supported in-field findings. A number of potential barriers to behavioural compliance existed, including cultural factors, gender discrimination, socioeconomic factors, stigmatising attitudes, the threat of domestic violence, infrastructure and training issues. Factors contributing to participation in physical activity included the fun and social aspects of the sport, incentives (including career opportunities, highlighting the health benefits of the activity and the provision of religious and cultural sanctions by local leaders towards the increased physical activity of women. The consultative approach of RAR provided a more in-depth understanding of the need for greater levels of physical activity and opportunities for engagement by all stakeholders. The approach facilitated opportunities for the proposed health behaviours to be realised through the communication strategy. Essential insights for the strategy design were identified from key informants, as well as ensuring future engagement of these stakeholders into the strategy. So what? The expanded use of RAR to inform the design of social marketing interventions is a practical approach to data collection for non-communicable diseases and other health issues in developing countries. The approach allows for the rapid mobilisation of scarce resources for the implementation of more strategic, targeted communication campaigns to support behavioural changes. | {
"pile_set_name": "PubMed Abstracts"
} |
Extremely Low Birth Weight Predisposes to Impaired Renal Health: A Pooled Analysis.
A number of studies examined the association between preterm delivery and kidney size and function later in life. However, the number of cases in published cohort studies is low. This study was aimed at performing a multicenter collaboration to pool data to obtain more accurate results to quantify the extent of renal impairment in former extremely low birth weight (ELBW; <1,000 g) children. We performed a subject-level meta-analysis to pool data from Cracow (64 cases/34 controls) and Leuven (93 cases/87 controls). We assessed and analyzed cystatin C, estimated glomerular filtration rate (eGFR), ultrasound kidney length, and blood pressure (BP) in 11-year-old ELBW children compared with controls born at term. The prevalence of hypertension (HT) and prehypertension (preHT) in both groups was also analyzed. The study group comprised 157 former ELBW children (gestational age 23-33 weeks and birth weight 430-1,000 g) and 123 children born at term. Former ELBW children had lower mean eGFR (100.62 ± 16.53 vs. 111.89 ± 15.26 mL/min/1.73 m2; p < 0.001), smaller absolute kidney length (8.56 ± 0.78 vs. 9.008 ± 0.73 cm; <0.001), and higher systolic (111.8 ± 9.8 vs. 107.2 ± 9.07 mm Hg; p = 0.01) and diastolic (68.6 ± 6.8 vs. 66.3 ± 7.7 mm Hg; p = 0.03) BP. Smaller renal size in former ELBW children was positively associated with lower birth weight, shorter gestational age, and severity of perinatal complications (intraventricular hemorrhage, length of stay, mechanical ventilation, and oxygen therapy). ELBW is associated with lower eGFR and a high frequency of preHT and HT. | {
"pile_set_name": "PubMed Abstracts"
} |
Complete structure of a rat RT1 E beta chain: extensive conservation of MHC class II beta chains.
The rat major histocompatibility complex (RT1 complex) encodes two sets of class II molecules, A alpha A beta and E alpha E beta. A cDNA clone encoding a RT1 E beta chain was isolated from a cDNA library prepared from Wistar (RT1 mu) spleen poly(A) RNA by screening with DNA fragments encoding a RT1 A beta chain. The nucleotide sequence of this cDNA insert was determined and was shown to encode a complete RT1 E beta chain. The RT1 E beta chain was highly homologous in terms of sequence identities to H-2 E beta and HLA-DR beta chains. Comparisons of predicted protein sequences of RT1, H-2, and HLA E beta and A beta chains showed that class II beta-chains are highly conserved with 105 out of 278 residues identical in all six beta-chains. The divergences in terms of the number of silent and replacement nucleotide substitutions between class II E beta or A beta sequences showed that the number of replacement substitutions reached a plateau after 10 million yr. Replacement substitutions therefore may be under selective pressure during evolution. The accumulation of silent and replacement substitutions in RT1 and H-2 class II beta-chains was faster than that in HLA beta-chain sequences. Thus, it appears that class II beta chains may be evolving at different rates in different species. | {
"pile_set_name": "PubMed Abstracts"
} |
Involucrin expression in cervical intraepithelial neoplasia: a critical evaluation.
Involucrin is a keratinocyte envelope protein precursor which is synthesized at an early stage of differentiation in normal squamous epithelium. Recent studies suggest that this protein may be a marker for neoplastic epithelium. To address this issue, we analyzed involucrin expression in 105 biopsies containing 119 areas of normal, condylomatous, and neoplastic epithelium. Overall, 88, 75, and 55% of condylomata, well-differentiated CIN, and poorly differentiated CIN (carcinoma in situ) contained positive staining for involucrin. Excluding lesions with severe inflammation, 100, 88, and 55% of these lesions, respectively, were positive. Staining patterns in neoplastic lesions differed from those in the normal epithelium and condylomata; the staining in CIN tended to be focal, and intensity of staining varied widely from cell to cell in all layers of the epithelium. In high grade CIN, staining correlated with increases in cell size and cytoplasmic differentiation. These studies suggest that involucrin will not differentiate between lesions of low versus high risk for progressing to invasive carcinoma. However, the patterns of involucrin expression confirm the marked differences in patterns of cellular differentiation between classical condylomata and CIN. | {
"pile_set_name": "PubMed Abstracts"
} |
Value of a rigid collar in addition to head blocks: a proof of principle study.
All trauma patients with a cervical spinal column injury or with a mechanism of injury with the potential to cause cervical spinal injury should be immobilised until a spinal injury is excluded. Immobilisation of the entire patient with a rigid cervical collar, backboard, head blocks with tape or straps is recommended by the Advanced Trauma Life Support guidelines. However there is insufficient evidence to support these guidelines. To analyse the effects on the range of motion of the addition of a rigid collar to head blocks strapped on a backboard. The active range of motion of the cervical spine was determined by computerised digital dual inclinometry, in 10 healthy volunteers with a rigid collar, head blocks strapped on a padded spine board and a combination of both. Maximal opening of the mouth with all types of immobiliser in place was also measured. The addition of a rigid collar to head blocks strapped on a spine board did not result in extra immobilisation of the cervical spine. Opening of the mouth was significantly reduced in patients with a rigid collar. Based on this proof of principle study and other previous evidence of adverse effects of rigid collars, the addition of a rigid collar to head blocks is considered unnecessary and potentially dangerous. Therefore the use of this combination of cervical spine immobilisers must be reconsidered. | {
"pile_set_name": "PubMed Abstracts"
} |
Prostate biopsy in response to a change in nadir prostate specific antigen of 0.4 ng/ml after treatment with 5α-reductase inhibitors markedly enhances the detection rate of prostate cancer.
We examined the effect of 5α-reductase inhibitor therapy on prostate cancer detection in men with persistently increased or fluctuating prostate specific antigen and prior negative prostate cancer biopsy. A total of 276 men with prostate specific antigen greater than 4 ng/ml (208) or a prostate specific antigen velocity change of 0.75 ng/ml (68) and a normal digital rectal examination who had previously undergone biopsy a minimum of 2 times with prostate cancer not detected were given 5 mg finasteride (154) or dutasteride (122) daily. In phase 1, 97 patients had prostate specific antigen measured at 6 and 12 months with repeat transrectal ultrasonography and biopsy (12 cores) performed at 1 year. In phase 2, 179 patients underwent biopsy triggered by a change in nadir prostate specific antigen of more than 0.4 ng/ml. In phase 1 at 1 year prostate specific antigen had decreased by 2.4 ng/ml (-46.7%), and prostate volume had decreased 7.1 ml (-17.9%). Prostate cancer was detected in 27 of 97 (27.8%) patients and the mean minimum prostate specific antigen velocity from a nadir of 0.4 ng/ml was 0.6 ng/ml. In phase 2, 48 of 179 (26.8%) men underwent repeat biopsy at a mean of 14.6 months. Of these 48 men 26 (54.1%) were found to have prostate cancer. Of the 26 men in whom prostate cancer was detected 20 (76.9%) were found to have Gleason score 7 or greater disease. The magnitude of change in serum prostate specific antigen after 5α-reductase inhibitor therapy may be useful in diagnosing prostate cancer in patients with persistently increased or fluctuating prostate specific antigen and prior negative prostate biopsy. | {
"pile_set_name": "PubMed Abstracts"
} |
In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra dose in 125I permanent prostate implants.
In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions. | {
"pile_set_name": "PubMed Abstracts"
} |
Role of the CLOCK protein in liver detoxification.
Whether and how circadian clock proteins regulate drug detoxification remain elusive. Here we aimed to clarify the impact of CLOCK (a core circadian clock protein) on drug metabolism and detoxification. The regulatory effects of CLOCK protein on drug-metabolizing enzymes were assessed using Clock knockout (Clock-/- ) mice and Hepa-1c1c7/AML-12 cells. The relative mRNA and protein levels were determined by qPCR and Western blotting, respectively. Toxicity and pharmacokinetic experiments were performed with Clock-/- and wild-type mice after intraperitoneal injection of coumarin or cyclophosphamide. Transcriptional gene regulation was investigated using luciferase reporter, mobility shift and chromatin immunoprecipitation (ChIP) assays. Clock ablation disrupted hepatic diurnal expressions of a number of drug-metabolizing enzymes in mice. In particular, CYP2A4/5 expressions were markedly downregulated, whereas CYP2B10 was upregulated. Positive regulation of Cyp2a4/5 and negative regulation of Cyp2b10 by CLOCK were confirmed in Hepa-1c1c7 and AML-12 cells. Based on a combination of luciferase reporter, mobility shift and ChIP assays, we found that CLOCK activated Cyp2a4/5 transcription via specific binding to E-box elements in promoter region, and repressed Cyp2b10 transcription through REV-ERBα/β (two target genes of CLOCK and transcriptional repressors of Cyp2b10). Furthermore, Clock ablation sensitized mice to coumarin toxicity by downregulating CYP2A4/5-mediated metabolism (a detoxification pathway), and to cyclophosphamide toxicity by upregulating CYP2B10-mediated metabolism (generating the toxic metabolite 4-hydroxycyclophosphamide). CLOCK protein regulates CYP metabolism and drug detoxification. Our findings have implications for a deep understanding of the crosstalk between circadian clock and drug detoxification. | {
"pile_set_name": "PubMed Abstracts"
} |
Selection for improved protein stability by phage display.
A library of mutants of a single-chain Fv fragment (scFv) was generated by a combination of directed and random mutagenesis, using oligonucleotides randomized at defined positions and two rounds of DNA shuffling. The library was based on the already well folding and stable scFv fragment 4D5Flu. In order to further improve this framework and test the efficiency of various selection strategies, phage display selection was carried out under different selective pressures for higher thermodynamic stability. Incubation of the display phages at elevated temperatures was compared to exposure of the phages to high concentrations of guanidinium chloride. Temperature stress-guided selection yielded the most stable scFv mutant after two rounds of mutagenesis and selection, due to the irreversibility of the unfolding process. It possessed only two mutations (His(L27d)Asn and Phe(L55)Val) and showed a thermodynamic stability improved by roughly 4 kcal/mol, threefold better expression yields in Escherichia coli as well as a 20-fold better binding constant than the 4D5Flu wild-type. The selection results obtained in this study delineate the advantages, disadvantages and limitations of different stability stress selection methods in phage display. | {
"pile_set_name": "PubMed Abstracts"
} |
Systemic markers of interferon-γ-mediated immune activation and long-term prognosis in patients with stable coronary artery disease.
Interferon γ (IFN-γ) is centrally involved in atherosclerosis-related inflammation, but its activity cannot be reliably assessed by systemic measurements. In activated macrophages, IFN-γ stimulates production of neopterin and conversion of tryptophan to kynurenine. We evaluated the relationships of plasma neopterin and plasma kynurenine:tryptophan ratio (KTR) to long-term prognosis in patients with stable angina pectoris and angiographically verified significant coronary artery disease. Samples were obtained from 2380 patients with a mean age of 63.7 years; 77.3% were men. During a median follow-up of 56 months, 10.8% of patients experienced a major coronary event (MCE), and 9.5% died. For MCE, each SD increment of neopterin and KTR (logarithmically transformed) was associated with multivariable adjusted hazard ratios and 95% CIs of 1.28 (1.10 to 1.48) and 1.28 (1.12 to 1.48), respectively. The corresponding hazard ratios (95% CIs) for all-cause mortality were 1.40 (1.21 to 1.62) (neopterin) and 1.23 (1.06 to 1.43) (KTR). In patients with stable angina pectoris, systemic markers of IFN-γ activity, plasma neopterin, and plasma KTR provide similar risk estimates for MCE and mortality. Our results support experimental data linking IFN-γ to acute atherosclerotic complications. | {
"pile_set_name": "PubMed Abstracts"
} |
Transgenic alternative-splicing reporters reveal tissue-specific expression profiles and regulation mechanisms in vivo.
Alternative splicing of pre-mRNAs allows multicellular organisms to create a huge diversity of proteomes from a finite number of genes. But extensive studies in vitro or in cultured cells have not fully explained the regulation mechanisms of tissue-specific or developmentally regulated alternative splicing in living organisms. Here we report a transgenic reporter system that allows visualization of expression profiles of mutually exclusive exons in Caenorhabditis elegans. Reporters for egl-15 exons 5A and 5B showed tissue-specific profiles, and we isolated mutants defective in the tissue specificity. We identified alternative-splicing defective-1 (asd-1), encoding a new RNA-binding protein of the evolutionarily conserved Fox-1 family, as a regulator of the egl-15 reporter. Furthermore, an asd-1;fox-1 double mutant was defective in the expression of endogenous egl-15 (5A) and phenocopied egl-15 (5A) mutant. This transgenic reporter system can be a powerful experimental tool for the comprehensive study of expression profiles and regulation mechanisms of alternative splicing in metazoans. | {
"pile_set_name": "PubMed Abstracts"
} |
The response of anesthesia trainees to simulated critical incidents.
Using a comprehensive anesthesia simulation environment (CASE 1.2) we studied the response of anesthesia trainees (10 first-year residents and 9 second-year residents) to five simulated critical incidents: 1) endobronchial intubation; 2) kinked IV; 3) atrial fibrillation with hypotension; 4) breathing circuit disconnection; 5) cardiac arrest. Simulations were videotaped, and the response times for detecting and initiating correction of the problems were measured. Different problems had significantly different response characteristics. Breathing circuit disconnection and cardiac arrest were quickly detected (21 +/- 17 seconds; 7 +/- 5 seconds), and correction was begun quickly, although major errors in managing the cardiac arrest occurred in 58% of cases. Endobronchial intubation and atrial fibrillation took longer than the other problems to detect (105 +/- 142 seconds; 111 +/- 158 seconds) and to correct (555 +/- 358 seconds; 365 +/- 121 seconds). Intravenous kink was detected more slowly (238 +/- 269 seconds) but once discovered was quickly corrected. The response of different individuals was highly variable; experience level was a significant factor for correction (P = 0.03) but not for detection of problems overall. Because of high individual variation, experience was not a significant factor in correcting any signal problem. The data suggest that some types of problems are harder to handle than others and that individuals vary widely in their problem-handling abilities. Experience is a beneficial factor in anesthesia problem solving but not in a simple fashion. Vigilant detection of problems is only the first step in a complex response pathway that might be strengthened by improved protocols and repeated practice. | {
"pile_set_name": "PubMed Abstracts"
} |
Analysis of a correlation-based model for the development of orientation-selective receptive fields in the visual cortex.
We analyse a model for the development of orientation-selective receptive fields of simple cells in a locally connected network of cortical neurons. The Hebbian learning rule that underlies the development is described by a linear differential equation. The structure of the emerging cortical map can be predicted by deriving the eigenfunctions corresponding to the leading eigenvalues of the associated matrix. We show that the receptive fields have the typical form of a wavelet. Mathematically, receptive fields are given by a Hermitian polynomial with Gaussian cut-off and a phase factor. Both the phase of the wavelet and the orientation are changing periodically along the surface of the cortical map as suggested by previous simulation studies and as also found in experiments. In order to get orientation-selective receptive fields, the spatial correlation function of the inputs that drive the development must have a zero crossing. | {
"pile_set_name": "PubMed Abstracts"
} |
A colorimetric and near-infrared fluorescent probe for detection of hydrogen sulfide and its real multiple applications.
A novel colorimetric and near-infrared fluorescent probe (L) with D-π-A structure derived from 4-diethylaminosalicylaldehyde and 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene)malononitrile has been developed. Probe L displays highly selective and sensitive recognition for H2S over various anions with a large Stokes shift (96 nm) in DMF/H2O (3/7, v/v, PBS-HCl 10 mM, pH = 7.4). A naked-eye observable color change of L solution from colorless to bluish-purple occurred on treatment with H2S. The potential applications of probe L were evaluated and the results show that probe L can detect H2S vapor and H2S in real water, red wine and living cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Assessing the implications of implementing the NICE guideline 95 for evaluation of stable chest pain of recent onset: a single centre experience.
Prompt and accurate assessment of patients with chest pain likely of cardiac origin (of recent onset) is important and requires excellent coordination between the specialist cardiology services with general/emergency medicine and primary care physicians. The presence of clear guidelines helps streamline this process for all stakeholders, to meet the requirements set out in with the National Service Framework for managing coronary artery disease (CAD). However, the new guidance offered by NICE guideline 95 (March 2010)(1) for evaluation of patients in England and Wales with chest pain of recent onset, represent several major changes to its former guideline (NICE TA 73), and the Scottish Intercollegiate Guidelines Network (SIGN) guideline 96 (2007, which is based on recommendations from European Society of Cardiology(2)) currently guiding the management of such patient in Scotland. This is likely to cause confusion and lack of uniformity in assessing patients across the United Kingdom. We evaluated what change of practices and services that may be necessary, if the recommendations of this NICE guideline 95 were accommodated or adopted by SIGN, in a Rapid Access Chest Pain Clinic (RACPC) setting in a medium sized teaching hospital in Scotland, United Kingdom. All patients (n = 96) evaluated with chest pain of recent onset in the RACPC at Ninewells Hospital for two consecutive calendar months (January, February 2010, i.e. immediately prior to issue of the NICE guideline 95) were included in this analysis. The study design was retrospective review of case notes. The investigations currently offered and their outcomes were recorded and contrasted with outcomes if the new NICE guidelines were adopted, based on the NICE guidance to calculate Pre-test likelihood of presence of significant coronary artery disease. If the NICE guidance on chest pain of recent onset had been implemented in our study population, a significant change in the offer of specialist cardiac investigations may have been required at the initial clinical assessment. This includes a 42.7% increase in offer of invasive coronary angiography, 24.0% increase in functional imaging, 8.3% increase in CT calcium scoring as the initial test of choice, in lieu of a 74.1% reduction of offer of exercise tolerance tests. If the NICE guidance on chest pain of recent onset had been implemented in our study population, the need for change of the offer of specific first line tests (as discussed above) means that, a major re-organisation in both the services in RACPCs and the current process of referral to these specialists cardiac services from the primary care physicians will be required. Whilst acknowledging that regional variations may exist in the proportions of tests needed (depending on the incidence and prevalence of CAD and risk factors), these figures from our study represent a much higher level of need of these specialist tests for patients attending RACPCs than initially suggested by contemporary reviews. We therefore conclude that data from larger studies in many regions may be useful for understanding the degree of regional and national changes required for organising the structure and referrals to specialist cardiac services in Scotland, if an equitable service based on NICE guidance 95 is rolled out throughout United Kingdom in future. | {
"pile_set_name": "PubMed Abstracts"
} |
Removal of a migrated fully covered metal biliary stent by cholangioscope-assisted inversion technique.
| {
"pile_set_name": "PubMed Abstracts"
} |
Vogt-Koyanagi-Harada syndrome in patients of Vietnamese ancestry.
Vogt-Koyanagi-Harada syndrome (VKH), is an idiopathic, multisystem inflammatory disorder primarily involving the eye. HLA typing has shown a strong association between the HLA-DR4 antigen and people of Japanese, Han Chinese and Hispanic ancestry with VKH. This study reviewed the clinical features and HLA typing of Vietnamese patients with VKH. A retrospective review of four unrelated Vietnamese patients with VKH seen in private practice and hospital clinic. The American Uveitis Society (1978) criteria for VKH diagnosis were satisfied. Standard microcytotoxic assays for Class I antigens and HLA-DNA typing of Class II DR antigens (DRB1 genotyping) by the PCR-SSO method were performed. The clinical features of VKH in Vietnamese were comparable to those seen in other Asian races. HLA-DR4 was present in three of the four VKH patients. Two of these patients also expressed the allele DRB1*0405. The strong association between HLA-DR4 and the DRB1*0405 allele and VKH seen in Japanese people, may well also exist in Vietnamese people. The HLA association suggests an immunogenetic predisposition to VKH. | {
"pile_set_name": "PubMed Abstracts"
} |
Exploiting genetic alterations to design novel therapies for cancer.
In the 3 decades since the signing of the National Cancer Act, there has been tremendous progress in the elucidation of the molecular underpinnings of cancer. Molecular genetic studies have been particularly insightful, revealing genetic rearrangements, such as chromosomal translocations, which may be the seminal event leading to deregulated cell growth for many childhood and adult cancers. These findings have led to new diagnostic and prognostic tools but have been slow to be translated into new therapeutic modalities. This article reviews a variety of methods now under development to exploit genetic changes in cancer to develop specific anticancer agents using gene therapy, viral therapy, and immunotherapy approaches. As many of these strategies inevitably enter the clinic, it will be imperative for health care professionals to be familiar with these novel approaches as they help patients navigate the likely broad array of treatment options. | {
"pile_set_name": "PubMed Abstracts"
} |
Obesity and sedentarism in children and adolescents: what should be bone?
Paediatric overweight continues to be a public health problem, and the etiology of obesity is multifactorial and complex. Dietary patterns, physical activity (PA) and sedentary behaviors are acknowledged as major behavioural determinants of obesity. New technologies and electronic based activities have produced a decrease in PA levels, and an increase in sedentary activities in children and adolescents. Potential mechanisms that explain the association between TV viewing and childhood obesity are: displacement of PA, unhealthy food preferences produced by food advertisements, a higher energy intake by automatic eating and overconsumption caused by distraction. Interventions aimed to reduce time in sedentary behaviours are in children generally positive. However, their benefits on adiposity markers are small. Thus, if global and macro-level obesogenic factors are not changed substantially, the interventions oriented to prevent obesity will produce small benefits. | {
"pile_set_name": "PubMed Abstracts"
} |
What makes therapy work? A multifaceted question.
The question "what makes therapy work?" has many facets. For instance, if there is evidence for a certain form of psychotherapy, one must question whether the positive effects are due to its methods or rather to "common factors" that may be shared with a number of other procedures. Second, because all evidence-based forms of psychotherapy represent treatment packages that involve a large number of components, there is the issue of the relative importance of these various treatment components. A third issue involves mechanisms of change: by what kind of mechanisms do the active treatment components obtain their effects? Finally, a fourth issue concerns the concepts used in these descriptions and analyses: are these concepts sufficiently well defined to formulate good hypotheses about what makes therapy work? In this article, these questions are discussed briefly, while relating them to the eight articles that comprise this special issue. | {
"pile_set_name": "PubMed Abstracts"
} |
Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients.
Transfusion has long been identified as a risk factor for acute lung injury (ALI)/ARDS. No study has formally evaluated the transfusion of specific blood products as a risk factor for ALI/ARDS in critically ill medical patients. In this single-center retrospective cohort study, 841 consecutive critically ill patients were studied for the development of ALI/ARDS. Patients who received blood product transfusions were compared with those who did not, in univariate and multivariate propensity analyses. Two hundred ninety-eight patients (35%) received blood transfusions. Transfused patients were older (mean [+/- SD] age, 67 +/- 17 years vs 62 +/- 19 years; p < 0.001) and had higher acute physiologic and chronic health evaluation (APACHE) III scores (74 +/- 32 vs 58 +/- 23; p < 0.001) than those who had not received transfusions. ALI/ARDS developed more commonly (25% vs 18%; p = 0.025) in patients exposed to transfusion. Seventeen patients received massive RBC transfusions (ie, > 10 U of blood transfused within 24 h), of whom 13 also received fresh-frozen plasma (FFP) and 11 received platelet transfusions. When adjusted for the probability of transfusion and other ALI/ARDS risk factors, any transfusion was associated with the development of ALI/ARDS (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.24 to 3.75). Among those patients receiving individual blood products, ALI/ARDS was more likely to develop in patients who received FFP transfusions (OR, 2.48; 95% CI, 1.29 to 4.74) and platelet transfusions (OR, 3.89; 95% CI, 1.36 to 11.52) than in those who received only RBC transfusions (OR, 1.39; 95% CI, 0.79 to 2.43). Transfusion is associated with an increased risk of the development of ALI/ARDS in critically ill medical patients. The risk is higher with transfusions of plasma-rich blood products, FFP, and platelets, than with RBCs. | {
"pile_set_name": "PubMed Abstracts"
} |
Glass ionomers and discoloration: a comparative study of the effects of tea and coffee on three brands of glass ionomer dental cement.
This study was undertaken to compare the in vitro discoloration of 3 brands of glass ionomer dental cement, Chemfil, Fuji Type II, and Ketac-Fil. Forty-eight specimens of each brand were prepared. Sixteen specimens of each brand were placed in tea, coffee and, as a control, water. Discoloration was evaluated by means of reflection spectrophotometry at 2, 4, 8, and 16 wk. Analysis of the data indicated that most discoloration occurred during the first 2 wk of immersion in the staining media and a little further discoloration took place between 2 and 16 wk (p less than 0.05). Tea discoloured glass ionomer more than did coffee (p less than 0.05) and Fuji Type II discoloured the most, Ketac-Fil the least whilst the discoloration of Chemfil lay between these two (p less than 0.05). | {
"pile_set_name": "PubMed Abstracts"
} |
[Selection of high avermectins producing strain and identification of avermectin B1].
Three types of colony, powdery gray, white and bald, were isolated from Streptomyces avermitilis ATCC31272. Among them, only the powdery grey one produces avermectins. Sa-76 strain was selected from the powdery grey strain by mutation with high energy electric flow, and its avermectins titer attainde 100 micrograms/mL in shaking flask. Avermectin B1 was extracted and purified from the mycelia of Sa-76, and identified by UV, IR, 1H-NMR, 13C-NMR and mass spectra. After Sa-76 strain was treated twice with NTG, a strain named Sa-76-8 was selected with avermectins titer over 2000 micrograms/mL. The Sa-76-8 strain was treated with NTG once again, and a high avermectins producing strain named as Sa-76-9 with avermectins titer up to 3500-4000 micrograms/mL was selected. | {
"pile_set_name": "PubMed Abstracts"
} |
Ultrasound-assisted emulsification microextraction based on solidification of floating organic droplet combined with HPLC-UV for the analysis of antidepressant drugs in biological samples.
Ultrasound-assisted emulsification microextraction based on the solidification of floating organic droplet combined with high-performance liquid chromatography-ultra violet (HPLC-UV) detection was applied for the extraction and determination of fluoxetine, citalopram, and venlafaxine as antidepressants drugs in biological samples. In total, 30 μL of undecanol was injected slowly into a glass-centrifuge tube containing 5 mL alkaline sample solution that was located inside the ultrasonic water bath. The formed emulsion was centrifuged and the fine droplets of solvent were floated at the top of the test tube. The test tube was then cooled in an ice bath and the solidified solvent transferred into a conical vial; it melted quickly at room temperature. Then the analysis of the extracts was carried out by high-performance liquid chromatography. Under optimal conditions, the preconcentration factors were between 174 and 316. Detection limits (LODs) of 3 μg/L were obtained and the calibration graphs were linear within the range of 10-1000 μg/L. Finally, the feasibility of the proposed method was successfully confirmed by extraction and determination of the antidepressant drugs in human urine and plasma samples in the range of microgram per liter and suitable results were obtained. | {
"pile_set_name": "PubMed Abstracts"
} |
The structure of past and future lives in depression.
This study assessed the organization of past autobiographical knowledge in individuals with either current major depressive disorder (MDD), MDD in remission, or no history of MDD (the control group). Participants generated personal lists of "life chapters," dividing both their past and potential future into subjectively meaningful episodes or themes (e.g., "married life"). They were then given a list of potentially chapter-descriptive positive or negative attributes and sorted them according to the different chapters. Results revealed that, relative to the control group, MDD participants selected more negative attributes overall, showed greater redundancy for negative attributes (i.e., using the same ones repeatedly across chapters) and reduced redundancy for positive attributes, and exhibited greater compartmentalization (i.e., the negative and positive attributes were clustered separately across different chapters). A similar pattern emerged for the remitted MDD group relative to controls, with the exception of negative redundancy, which was not elevated. For future chapters, there were no group differences. Finally, a greater number of past depressive episodes was associated with increasingly reduced positive redundancy. These data reveal a "depressogenic" structuring of past (but not future) knowledge in MDD that is also evident in a remitted MDD group, with the exception of negative redundancy, which appears to be a marker of the acute state. These findings shed light on important aspects of the organization of past knowledge that are likely to be linked to maladaptive processing biases in those with a depression history. | {
"pile_set_name": "PubMed Abstracts"
} |
[Reactivation Performance of Nitrosation Flocculent Sludge After Long-term Storage].
In order to explore the nitrogen removal performance of nitrosation flocculent sludge subject to long-term storage, nitrosation flocculent sludge which had been stored at 4℃ for ten months was inoculated in a continuous stirred tank reactor (CSTR) to investigate its activity recovery performance. MiSeq high throughput sequencing technology was also employed to analyze the structure of the microbial community before and after reactivation. Results showed that, under DO control of DO 0.4-0.8 mg·L-1, pH value of about 8 and temperature of (30±1)℃, the sludge could be reactivated in 15 days. Both the removal efficiency of ammonia nitrogen and the accumulation ratio of nitrite nitrogen were higher than 90%. The color of the sludge quickly changed from grey at early inoculation to brown, while the sludge volume index (SVI) quickly decreased and both mixed liquor volatile suspended solids (MLVSS)/mixed liquor suspended solids (MLSS) and extracellular polymer substances (EPS) significantly increased. With the recovery of nitrosation performance, anaerobic and heterotrophic bacteria were washed out, the relative abundance of ammomia-oxidizing bacteria such as Nitrosomonas significantly increased, while the growth of nitrite-oxidizing bacteria such as Nitrospria was selectively inhibited. Nitrosation flocculent sludge could be inoculated after long-term storage to achieve rapid start-up of partial nitrification and allow practical application of partial nitrification processes. | {
"pile_set_name": "PubMed Abstracts"
} |
Major vascular resections in retroperitoneal sarcoma.
Retroperitoneal sarcomas (RPS) frequently involve major vessels, which either originate from them or secondarily encase or invade them. In this field, major vascular resections result in increased morbidity. However, survival does not seem to be affected by the need for vascular resection or by this higher morbidity. This paper aims to provide descriptions of the surgical strategy and outcomes for retroperitoneal sarcomas involving major vessels. | {
"pile_set_name": "PubMed Abstracts"
} |
Quantitation of HBeAG and anti-HBe by RIA in sera of chronic HBsAG carriers and individuals with type B hepatitis.
This paper gives the results for HBeAg and anti-HBe titers in chronic HBsAg carriers and patients with type B hepatitis using a "solid-phase" radioimmunoassay. In tumor and hemodialysis patients the HBeAg titers are statistically significant higher compared to the group of HBsAg positive CAH or CPH. High anti-HBe titers are a characteristic finding in "healthy" HBsAg carriers. On the other hand, there is a subgroup of HBsAg positive CAH with anti-HBe; although there are signs of an ongoing virus B replication these cases of CAH proceed sometimes to cirrhosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Cell response endpoints enhance sensitivity of the immature mouse uterotropic assay.
Outbred immature CD-1 mice were subcutaneously (s.c.) injected once on postnatal day 17 or on postnatal days 17, 18, and 19 with 17beta-estradiol, diethylstilbestrol, tamoxifen, 4-hydroxytamoxifen, methoxychlor, the methoxychlor metabolite HPTE, nonylphenol, o,p'-DDT, endosulfan, or kepone over a wide dose range (0.1 to 1,000,000 microg/kg). On the day following the last injection, uterine weight/body weight ratios were determined and uterine tissues processed for histologic examination. All compounds except endosulfan and kepone increased uterine wet weight compared to vehicle controls; however, the dose response curve and magnitude of response varied depending on the compound. Choosing the maximum wet weight dose for each compound, uterine tissue was evaluated for epithelial cell height, epithelial and stromal cell proliferation, endometrial gland number, and induction of estrogen-inducible proteins lactoferrin and complement C3. All compounds elicited estrogen-responsive changes in these endpoints that were individually more sensitive than uterine weight alone. We conclude that these endpoints enhance the sensitivity of the uterotropic bioassay. | {
"pile_set_name": "PubMed Abstracts"
} |
Variant late infantile neuronal ceroid-lipofuscinosis: pathology and biochemistry.
The neuronal ceroid-lipofuscinoses (NCL) are among the most common inherited neurodegenerative disorders of childhood. The genomic defect causing a variant late infantile neuronal ceroid-lipofuscinosis (vLINCL, also called CLN-5 or variant Jansky-Bielschowsky disease) has recently been localized to chromosome 13q22, thus delineating this disease as a separate entity. This particular form of NCL is clinically well defined, but lacks pathomorphological and biochemical description. The present analyses indicate that subunit c of the mitochondrial ATP synthase is the major protein in vLINCL brain storage cytosomes. These cytosomes also contain minor amounts of sphingolipid activator proteins (SAPs). The immunohistological distribution of subunit c and SAPs in the central nervous system (CNS) and visceral tissues closely resembles that of classical LINCL. Thus, despite clinical differences and the fact that various forms of NCL are caused by different genetic defects, variant and classical LINCL as well as juvenile NCL are all characterized by pronounced lysosomal accumulation of the same hydrophobic protein, subunit c of the mitochondrial ATP synthase. | {
"pile_set_name": "PubMed Abstracts"
} |
A curative treatment strategy using tumor debulking surgery combined with immune checkpoint inhibitors for advanced pediatric solid tumors: An in vivo study using a murine model of osteosarcoma.
This study aimed to assess the significance of tumor debulking surgery by using immune checkpoint inhibitors for advanced pediatric solid tumors in a murine model of advanced osteosarcoma. In C3H mice, 5 × 106 LM8 (osteosarcoma cell line with a high metastatic potential in the lungs originating from the C3H mouse) cells were transplanted subcutaneously. Thereafter, the mice were divided into 4 groups as follows: the control group received no intervention (CG, n = 5), the surgery group underwent subcutaneous tumor resection (tumor debulking surgery) 11 days after transplantation (SG, n = 10), the immunotherapy group received a cocktail consisting of 200 μg each of three antibodies (anti-Tim-3, anti-PD-L1, and anti-OX-86) intraperitoneally on posttransplantation days 11, 14, 18, and 21 (IG, n = 10), and the combination therapy group, tumor debulking surgery on day 11 and the cocktail intraperitoneally on days 11, 14, 18, and 21 (COMBG, n = 10). Survival curves were plotted by using the Kaplan-Meier method and compared with those plotted using the log-rank test. Next, the lungs of mice in the 4 groups were pathologically evaluated. The COMBG showed significantly longer survival than the other three groups (P ≤ 0.002), whereas the SG and IG revealed no difference in survival rate compared to CG. Pathological evaluations revealed no lung metastasis 16 weeks after tumor transplantation in the survivors of COMBG. The results of this study suggest that tumor debulking surgery combined with immune checkpoint inhibitors could be a curative treatment for advanced pediatric solid tumors. | {
"pile_set_name": "PubMed Abstracts"
} |
A P2X7 receptor antagonist attenuates experimental autoimmune myocarditis via suppressed myocardial CD4+ T and macrophage infiltration and NADPH oxidase 2/4 expression in mice.
Myocarditis is a clinically serious disease; however, no effective treatment has been elucidated. The P2X7 receptor is related to the pathophysiology of inflammation in many cardiovascular diseases. The P2X7 receptor antagonist is promising as an immunosuppressive treatment; however, its role in myocarditis is still to be established. To clarify the role of the P2X7 receptor, we used a murine experimental autoimmune myocarditis (EAM) model. Mice were immunized on day 0 and 7 with synthetic cardiac myosin peptide to establish EAM. The mice with induced EAM were treated with A740003, the P2X7 receptor antagonist (n = 10), or not treated (n = 11); hearts were harvested on day 21. The P2X7 receptor antagonist improved myocardial contraction of the EAM hearts via suppressed infiltration of CD4+ T cells and macrophages. Similarly, mRNA expression of interleukin 1 beta, the P2X7 receptor and NADPH oxidase 2/4 was lower in the heart of the P2X7 receptor antagonist-treated group compared to the non-treat group. The P2X7 receptor antagonist suppressed EAM development; thus, this inhibition is promising for treating clinical myocarditis. | {
"pile_set_name": "PubMed Abstracts"
} |
Ectopic High Expression of E2-EPF Ubiquitin Carrier Protein Indicates a More Unfavorable Prognosis in Brain Glioma.
Ubiquitination of proteins meant for elimination is a primary method of eukaryotic cellular protein degradation. The ubiquitin carrier protein E2-EPF is a key degradation enzyme that is highly expressed in many tumors. However, its expression and prognostic significance in brain glioma are still unclear. The aim of this study was to reveal how the level of E2-EPF relates to prognosis in brain glioma. Thirty low-grade and 30 high-grade brain glioma samples were divided into two tissue microarrays each. Levels of E2-EPF protein were examined by immunohistochemistry and immunofluorescence. Quantitative real-time polymerase chain reaction was used to analyze the level of E2-EPF in 60 glioma and 3 normal brain tissue samples. The relationship between E2-EPF levels and prognosis was analyzed by Kaplan-Meier survival curves. E2-EPF levels were low in normal brain tissue samples but high in glioma nuclei. E2-EPF levels gradually increased as glioma grade increased (p < 0.05). Ectopic E2-EPF levels in high-grade glioma were significantly higher than in low-grade glioma (p < 0.01). The 5-year survival rate of glioma patients with high E2-EPF levels was shorter than in patients with low expression (p < 0.05). Furthermore, the 5-year survival rate of patients with ectopic E2-EPF was significantly shorter than patients with only nuclear E2-EPF (p < 0.01). These results suggest that higher E2-EPF levels, especially ectopic, are associated with higher grade glioma and shorter survival. E2-EPF levels may play a key role in predicting the prognosis for patients with brain glioma. | {
"pile_set_name": "PubMed Abstracts"
} |
Identification of interactive loci linked to insulin and leptin in mice with genetic insulin resistance.
Mice double heterozygous (DH) for deletion of insulin receptor and insulin receptor substrate-1 are lean, insulin resistant, and have a phenotype that strongly depends on the genetic background of the mouse. On the C57BL/6 (B6) background, DH mice develop marked hyperinsulinemia and diabetes, whereas on the 129S6 background, DH mice exhibit only mild elevations of insulin and remain free of diabetes. F2 male mice created by an intercross between these two strains exhibit a 60% incidence of diabetes and a bell-shaped distribution of insulin levels as related to glucose, reminiscent of that in humans with type 2 diabetes. These mice also exhibit a wide range of leptin levels as related to body weight. A genome-wide scan of F2 mice reveals a quantitative trait locus (QTL) related to hyperinsulinemia on chromosome 14 (D14Mit55) with a peak logarithm of odds (LOD) score of 5.6, accounting for up to 69% of this trait. A QTL with a LOD score of 3.7 related to hyperleptinemia is present on chromosome 7 at D12Mit38 (a marker previously assigned to chromosome 12) in the area of the uncoupling protein 2/3 gene cluster. This locus also interacts synergistically with D14Mit55 in development of hyperinsulinemia and with a QTL on chromosome 12 (D12Mit231) related to hyperglycemia. These data demonstrate how multiple genetic modifiers can interact and influence the development of diabetes and the phenotype of animals with genetically programmed insulin resistance and provide evidence as to the location and nature of these genes. | {
"pile_set_name": "PubMed Abstracts"
} |
A Retrospective Analysis of the Contribution of Reported Factors in Cochlear Implantation on Hearing Preservation Outcomes.
Preservation of residual hearing is essential to perceive acoustic stimulation from hybrid cochlear implants (CI). Preservation is a good marker of atraumatic surgery and residual hearing may be exploited further or enhanced in future therapies, making complete hearing preservation a desirable goal for all current CI surgeries. There is large variability in the amount of hearing preserved and the timeframe over which it is lost after CI. The increase in numbers of patients with high levels of residual hearing at implantation means that understanding the variables affecting its preservation is more important than ever. An English search term with generic and specific items concerning hearing preservation and cochlear implantation was searched on the Web of Science service. The search timeframe was limited to 2000 to 2014, with no language limitations on results. Hearing preservation, retrospective CI outcome studies which reported pre- and post-surgical pure-tone audiometry (PTA) were identified and selected. PTA thresholds were extracted from audiograms or tables and converted into a low-frequency hearing preservation (LFHP) score. Data for 21 factors associated with hearing preservation were collected from studies. Factors were included in a hearing preservation model if they had both a significant bivariate correlation with LFHP and a significant Kruskal-Wallis H test result (for ordinal data) or a significant multiple regression analysis result (for scale data). Seven factors were found to have a significant effect on hearing preservation: insertion site, progressive versus stable hearing loss, insertion angle of electrode, use of intraoperative topical steroids, use of steroids (via any route/timing), hearing etiology, and electrode array type. The best hearing preservation options are given. | {
"pile_set_name": "PubMed Abstracts"
} |
Influence of repetitive UVA stimulation on skin protection capacity and antioxidant efficacy.
Topically applied antioxidants (AOs) are widely used in cosmetic products - especially in day and sun care - to help reduce oxidative stress caused by exogenous influences such as ultraviolet (UV) radiation. Despite several advances in recent years, little is known about the duration of protective effects by application of topical AOs, AO protection capacity (APC) or the activation of an endogenous protection capacity (EPC). By measuring oxidative-stress-induced photon emission of human skin in vivo with the ICL-S method (induced chemiluminescence of human skin), the protective effect of daily AO treatment for 2 weeks was examined on 4 consecutive days after treatment. UVA-dose-independent effects were investigated by decay curve intersection point analysis. In addition, chemiluminescence signal integration was used to investigate the influence of different UVA doses for stimulation on the determined APC as well as the modulation of the EPC by repetitive UVA stimulation both forming the skin protection capacity (SPC). The SPC showed a strong dependency on the UVA dose used for stimulation. AO pretreatment was more effective against lower UVA doses. Over the course of 4 days, the AO-induced SPC did not change significantly for a given UVA dose. Analyzing the decay curve intersection point for 2 different UVA doses, however, revealed a decrease in SPC with time. In addition, we found that a repetitive UVA irradiation of 1 J/cm(2) caused a statistically significant protective effect against UVA irradiation by stimulation of endogenous mechanisms. Topically supplemented AOs provide a protective effect against oxidative stress for at least 3 days, supporting their widespread use in cosmetic products. Especially their interaction with cutaneous protective mechanisms should be investigated in more detail for maximal protection, as endogenous defense mechanisms are already triggered by 2 low-dose UVA irradiations within 24 h. In summary, the in vivo measurement of UVA-induced cutaneous chemiluminescence permits the UVA-dose-independent determination of the AO efficacy for better comparability of the results while also taking endogenous defense mechanisms into account. | {
"pile_set_name": "PubMed Abstracts"
} |
[Automatic implantable cardioverter-defibrillator (AICD) and antitachycardia pacemaker (Tachylog 651) in the treatment of ventricular tachyarrhythmias].
For the electrotherapy of refractory ventricular tachycardia the automatic implantable cardioverter-defibrillator (AICD) and antitachycardia pacemaker are available. The long-term use of antitachycardia pacing is still limited by the potential risk of acceleration to ventricular fibrillation. To combine the advantages of antitachycardia pacing with back-up defibrillation, we evaluated the use of an antitachycardia pacemaker with the automatic defibrillator. The AICD was implanted in 13 patients with a mean age of 62 years (from 46 to 75 years); six of them with recurrent ventricular tachycardia (170 +/- 16 per minute) which could reliably be terminated by overdrive pacing, received also an antitachycardia pacemaker (Tachylog 651). The underlying cardiac disease was coronary heart disease in 11 patients and cardiomyopathy in 2 cases. All patients had survived 1 to 6 cardiac arrests and had not responded to 6 +/- 1.5 antiarrhythmic drugs. For antitachycardia pacing we used burst stimulation with 4 to 6 stimuli and coupling intervals from 260 to 300 ms. During the follow-up period of 12 +/- 2 months, 83% of 744 tachycardias could be terminated by burst stimulation, according to the diagnostic data of the pulse generator. If the pacemaker failed to terminate or in case of acceleration (three patients), the automatic countershock of the AICD (5-42 per patient) restored sinus rhythm. In seven patients with high rate tachycardia, 2 to 69 AICD discharges occurred. No patient died suddenly, but three died due to underlying disease and one because of a pneumonia postoperatively. Future antitachycardia devices should be flexible with regard to detection and termination modes, combining antitachycardia pacing with back-up defibrillation. | {
"pile_set_name": "PubMed Abstracts"
} |
Primary squamous cell carcinoma of the endometrium.
A rare case of primary squamous cell carcinoma of the endometrium, probably originating from adenomyosis, is presented. A 58-year-old Japanese woman was referred to Kitasato Institution Medical Center Hospital to explore the cause of her postmenopausal bleeding. The endometrial cytology specimen obtained with the Endocyte (an device for endometrial check up) showed cells suggesting well differentiated squamous cell carcinoma. The patient underwent modified radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy, followed by postoperative radiation therapy. The dissected uterus revealed keratinizing-type squamous cell carcinoma localized in the fundal portion of the uterine body and invading deeply into the myometrium, coexistent with a large area of adenomyosis with a transitional area to carcinoma. The residual endometrium was atrophic. There was no atypical finding in the cervix. Human papilloma virus DNA was not detected. The carcinoma recurred 26 months after the surgery, and the patient died of the disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Designer coordination polymers: dimensional crossover architectures and proton conduction.
Coordination polymers (CPs) have large degrees of freedom in framework compositions and in the structures and environment of the inner pores. This review focuses on the recent significant progress achieved by controlling these degrees of freedom. Two breakthroughs are reviewed for constructing sophisticated structures of CP frameworks, especially in dimensional crossover regions. The first is the synthesis of quasi one-dimensional halogen-bridged coordinative tubes by applying state-of-the-art techniques of coordination chemistry. The electronic state of the coordinative tube was studied by structural, spectroscopic and theoretical methods and found to be distinct from conventional one-dimensional systems. The second breakthrough is the achievement of a quasi-two-dimensional architecture by combining Langmuir-Blodgett and layer-by-layer methods. Two-dimensional LB CP films were prepared on liquid; the films were stacked layer by layer, and a crystalline quasi-two-dimensional structure was constructed. This review also covers the design of the environment of the inner pore, where hydrogen bond networks with various acidic sites were modified. By appropriate design of the hydrogen bond network, proton-conductive CPs are invented, which are summarized in this review. Types of proton donor sites are discussed and classified, and superprotonic conductive CPs were achieved in these investigations. These results will provide new strategies for constructing functional materials for smart devices. | {
"pile_set_name": "PubMed Abstracts"
} |
Elevated sympathetic nervous system activity in patients with recently diagnosed rheumatoid arthritis with active disease.
To investigate sympathetic (SNS) and parasympathetic (PNS) nervous system activity in patients with recently diagnosed rheumatoid arthritis (RA), and to analyze the association between activity of these systems and disease activity, and complaints that frequently occur in RA, viz., pain, fatigue, negative mood, and stiffness. To assess sympathetic and parasympathetic nervous activity, the Pre-Ejection-Period (PEP) and Respiratory Sinus arrhythmia (RSA) were measured on two consecutive nights in a real-life environment in 25 patients with RA [19 female (f), 6 male (m), mean age 55.2 years) and 28 healthy controls (20f, 8m, mean age 55.8 years]. Patients showed a significantly shorter PEP (reflecting elevated SNS activity) compared to healthy controls, an effect that was most pronounced in those with active disease. RSA and the heart period did not differ between patients and healthy controls. The heart period was significantly associated with stiffness, but neither PEP nor RSA were associated with pain, fatigue, mood, or stiffness. Our study showed that cardiac sympathetic nervous system activity is elevated in RA, whereas cardiac parasympathetic activity remains at a normal level. Our results suggest that inflammatory stress rather than the common symptoms of RA challenge the SNS. | {
"pile_set_name": "PubMed Abstracts"
} |
[Aggregatibacter segnis endocarditis mimicking antineutrophil cytoplasmic antibody-associated vasculitis presenting with cerebral hemorrhage: a case report].
A 56-year-old man who underwent a tooth extraction in the previous year presented with weakness of the right upper extremity. Brain CT and MRI scans showed subcortical hemorrhage in the left frontal lobe. His body temperature was 37.5°C. Blood examination revealed anemia, elevated levels of C-reactive protein, and a positive result for PR3-ANCA. Aggregatibacter segnis was identified in the incubated blood cultures, and transesophageal echocardiograms showed infectious growth in the anterior mitral leaflet. He was diagnosed with infectious endocarditis. After treatment with ceftriaxione, the clinical symptoms were improved. We concluded that infectious endocarditis caused cerebral hemorrhage and that the positive result for PR3-ANCA was a false positive. Infectious endocarditis can mimic ANCA-associated vasculitis. When ANCA-associated vasculitis is suspected, infectious endocarditis must be ruled out. | {
"pile_set_name": "PubMed Abstracts"
} |
[Pancreatic echo-endoscopy and preoperative localization of insulinomas].
Preoperative localization of insulinomas often fails because of the small size of these tumors. The aim of this study was to analyse the value of endoscopic ultrasonography of the pancreas in comparison with them to those of conventional localization procedures. From 1983 to 1997, 32 patients, operated with a preoperative diagnosis of insulinoma, underwent one or more localization procedures: ultrasonography (US) (n = 31), computed tomography (CT) (n = 31), magnetic resonance imaging (MRI) (n = 10), angiography (ANG) (n = 6), transhepatic portal venous samplings (THPVS) (n = 3), and/or endoscopic ultrasonography (EUS) (n = 25). More recently, 4 patients had scintigraphy with labelled octreotide. During surgery, intraoperative palpation and ultrasonography of the pancreas, performed in all but one cases (laparoscopy), allowed the localization of 29 solitary tumors and 2 multiple tumors (one of which in a case of a MEN II). A malignant tumor was found in 6 patients. The sensitivity of the localization procedures was as follows: US = 19%, CT = 39%, IRM = 30%, ANG = 33%, THPVS = 0%, EUS = 96%. Labelled octreotide scintigraphy was positive in 3/4 cases. Surgical procedures included: 15 enucleations or partial resections, 14 left pancreatectomies (5 of which with splenectomy), 3 duodenopancreatectomies. In one case the tumor was resected laparoscopically (distal pancreatectomy). EUS was the best preoperative localization procedure in this study. It may avoid the need for other imaging procedures. Combined with intraoperative ultrasonography, EUS could allow laparoscopic resections in selected cases. | {
"pile_set_name": "PubMed Abstracts"
} |
Symmetrical excessive pectus excavatum in children.
The indications for repair of pectus excavatum are controversial. We present our surgical results in children with severe pectus excavatum. 27 children aged 6-15-years were included in the study. Pulmonary function tests and chest measurements were performed pre- and postoperatively. Deformed cartilages were resected subperichondrially, and a Kirchner wire was used to support the chest cage; it was removed 5 days after the operation. Fourteen children with restricted pulmonary function were considered to have excessive pectus excavatum. 3 patients had asthma-like symptoms that resolved postoperatively. None suffered chest pain postoperatively. Postoperative hospital stay was 7.1 days. Only minor complications occurred postoperatively. The mean pectus severity index was 0.27 ± 0.2 preoperatively and 0.41 ± 0.1 postoperatively (p < 0.05). For children with restricted pulmonary function, it was 0.17 ± 0.3 preoperatively and 0.38 ± 0.2 postoperatively (p < 0.05). Mean percentage of predicted forced expiratory volume in 1 s changed significantly from 79.2% ± 17.8% preoperatively to 83.6% ± 12.2% by the 3rd postoperative month. For children with a pectus severity index <0.2, it changed from 68.5% ± 13.2% preoperatively to 82.3% ± 13.4%. Pulmonary restriction correlated with a worse pectus severity index (r = 0.8). After 6 and 13 months, a minor decrease in pulmonary function was noted. Significant increases in right and left ventricular function occurred in cases of severe deformity. Surgery is recommended not only for cosmetic reasons but also to increase cardiorespiratory functional capacity and alleviate symptoms. Kirchner wires can be used safely. | {
"pile_set_name": "PubMed Abstracts"
} |
Heterogeneity of the human CD4+ T-cell population: two distinct CD4+ T-cell subsets characterized by coexpression of CD45RA and CD45RO isoforms.
Activation of unprimed CD4+CD45RA+/RO- T cells results in a gradual loss of CD45RA expression concomitant with the acquisition of CD45RO. It has been suggested that this conversion occurs in vivo through a CD45RAbright/RObright stage. Next to this small CD45RAbright/RObright subset (Dbright), a larger subpopulation that expresses both RA and RO isoforms at low levels (Ddull) can be found in the circulating CD4+ T-cell population of all donors. The properties of the latter population are largely undefined. Here, we show that Ddull cells have an intermediate phenotype for antigens such as CD31, CD621, CD58, and CD95 that are differentially expressed on unprimed versus primed T cells. In addition, they are able to provide help for B-cell differentiation and contain substantial numbers of tetanus toxoid (TT)-specific precursor cells. Remarkably, both intracellular cytokine staining and analysis of T-cell clones showed that Ddull cells and CD45RO+ T cells produce comparable high amounts of both interferon (IFN)-gamma and interleukin (IL)-4, which clearly distinguishes them from CD45RA+ and Dbright T cells. Finally, prolonged culture of sorted Ddull cells in a mixture of IL-2, IL-6, and tumor necrosis factor (TNF)-alpha showed that about half of the population retained the Ddull phenotype. Part of the cells upregulated the CD45RA isoform, whereas only a minority switched to single CD45RO expression. Our findings indicate that the Ddull population contains primed T cells, some of which may reacquire an "unprimed" phenotype in the absence of antigenic stimulation. | {
"pile_set_name": "PubMed Abstracts"
} |
Mutation burden profile in familial Alzheimer's disease cases from India.
This study attempts to identify coding risk variants in genes previously implicated in Alzheimer's disease (AD) pathways, through whole-exome sequencing of subjects (N = 17) with AD, with a positive family history of dementia (familial AD). We attempted to evaluate the mutation burden in genes encoding amyloid precursor protein metabolism and previously linked to risk of dementias. Novel variants were identified in genes involved in amyloid precursor protein metabolism such as PSEN1 (chr 14:73653575, W161C, tgg > tgT), PLAT (chr 8:42039530,G272R), and SORL1 (chr11:121414373,G601D). The mutation burden assessment of dementia-related genes for all 17 cases revealed 45 variants, which were either shared across subjects, or were present in just the 1 patient. The study shows that the clinical characteristics, and genetic correlates, obtained in this sample are broadly comparable to the other studies that have investigated familial forms of AD. Our study identifies rare deleterious genetic variations, in the coding region of genes involved in amyloid signaling, and other dementia-associated pathways. | {
"pile_set_name": "PubMed Abstracts"
} |
Influence of androgens on the genital tract of cyclic heifers.
Cyclic heifers were implanted with the synthetic androgen trenbolone acetate (TBA = 17 beta-hydroxy-19-norandrosta-4, 9, 11-trien-3-on-17 beta-acetate, C2OH2403) (for formulas see Fig. 1). The influence of this androgen on the macroscopic and microscopic morphology of the genital tract was studied. The most striking result was the induction of polycystic ovaries. The clitoris was markedly enlarged and the cervix showed an increased amount of mucus. Microscopically, extensive folding of the cervical epithelium, consisting of tall swollen columnar cells with basal nuclei was seen. The vagina showed an increase of PAS-positive granules in the superficial layer of the epithelium, while there was no increase in the height of the epithelium. These effects are due to androgenic influence on the female genital tract and are in no case specific to one particular product. They could be of help in the detection of the illegal use of agents with androgenic activity. | {
"pile_set_name": "PubMed Abstracts"
} |
[Studies of the expectancy wave (CNV) in patients with interruption of the thalamo-prefrontal interconnnection pathways caused by psychosurgical prefrontal lobotomy operations].
Frontal and vertex CNVs were studied in 8 selected nonschizophrenic patients subjected to unilateral or bilateral extensive prefrontal lobotomy. The dorsomedial thalamo-frontal pathways had been severed and their regeneration must be considered impossible. Standard CNV task (S1-S2-R) was followed in order to elicit CNVs from the frontal areas anterior to the line of sections and at Cz. In 7 out of 8 patients it was quite easy to evoke CNV with almost normal features and equal latencies in each case from all the cortical areas explored. These results show that CNV formation is not grossly altered in the prefrontal areas which have been irreversibly deprived of normal bi-directional mediothalamic-frontocortical connnections. This suggests that the role of the dorsomedial thalamo-frontal pathways are not essential in the genesis of the frontal CNV in humans. These findings would suggest that the CNV is a diffuse electrical event essentially related to a unitary cerebral process mediated fundamentally by nonspecific ascending meso-diencephalic reticular systems. The differences in morphology and polarity of the CNVs detectable in various brain structures are presumably related to their intrinsic anatomo-functional characteristics and to the method commonly utilized in recording the CNV. | {
"pile_set_name": "PubMed Abstracts"
} |
Anti-leukemia selectivity in actinomycin analogues.
An excellent anti-leukemia activity has been found in a group of actinomycin D analogues derivatized at the 2,2'- or 5,5'-position of the depsipeptides. On the basis of the water solubilities, the DNA binding affinities, the RNA synthesis inhibitory activities, the anticancer activities of actinomycin D (AMD), and the crystal structures of DNA-AMD complexes, it becomes clear that AMD is extremely well designed as an effective poison produced by micro-organisms. The anticancer activity of AMD is mainly due to its selective inhibition of RNA synthesis. We have hypothesized that a modification on the AMD structure at a site not involved in DNA interaction can either increase or decrease the diffusion rate of the analogue into certain cancer cells. Since the i-propyl groups of the D-valine residues at the 2,2'-positions and N-methyl-L-valine residues at the 5,5'-positions in the depsipeptides do not participate in interaction with DNA, these amino acid residues were replaced with other D-amino acid residues and N-methyl-L-amino acid residues, respectively. The cancer screen tests have indicated that AMD analogues 2,2'-D-PheAMD, 2,2'-D-OmeAMD, 5,5'-L-TyrAMD, 5,5'-D-ValAMD, 5,5'-D-TyrAMD, 5,5'-D-PheAMD, and 5,5'-D-OmeAMD, inhibit selectively the growth of leukemia cell lines at about 100- to 500-fold lower drug concentrations than those required to inhibit other cancer cell lines. | {
"pile_set_name": "PubMed Abstracts"
} |
In situ cyanogen bromide cleavage of N-terminally blocked proteins in a gas-phase sequencer.
Herein we describe a procedure for the in situ cyanogen bromide cleavage of N-terminally blocked proteins which have been immobilised onto the glass fiber sample disk of the gas-phase sequencer. In this manner, new amino terminii suitable for automated Edman degradation can be generated. Cytochrome C was cleaved using this method on the carboxyl side of methionine residues 65 and 80. This allowed sequence analysis to begin simultaneously at residues 66 and 81 (Table 1). This procedure offers an alternative sequencing tactic for methionine-containing proteins which are N-terminally blocked. | {
"pile_set_name": "PubMed Abstracts"
} |
Influence of diabetes control on synthesis of protein and basement membrane collagen in isolated glomeruli of diabetic rats.
Diabetic rats were treated with insulin at various dosages and for various periods of time. The influence of metabolic control on the synthesis of protein and basement membrane collagen of isolated glomeruli was investigated. The protein and basement membrane collagen synthesis was increased in the untreated diabetic rats compared to non-diabetic controls. The synthesis was not affected by high doses of insulin with brief normalization of the blood sugar. Insulin treatment from the beginning of diabetes only led to a normalization of protein synthesis in moderate metabolic control. On the other hand, a rise of the basement membrane collagen synthesis could only be prevented by a strict metabolic control of the rats. The results show that basement membrane collagen synthesis reacts very sensitively to the diabetic metabolic situation. Insulin deficiency itself does not appear to be alone responsible for alterations of basement membrane synthesis in diabetes. | {
"pile_set_name": "PubMed Abstracts"
} |
Characterization of monoclonal antibodies against human tissue plasminogen activator (tPA): quantitation of free tPA in human cell cultures by an ELISA.
Seven murine monoclonal antibodies produced against tissue plasminogen activator (tPA) were evaluated by means of enzyme-linked immunosorbent assays (ELISAs), and their effects on the enzymatic activities of tPA towards a synthetic substrate (S-2288) and plasminogen were investigated. One of the antibodies, TPA1-70, strongly inhibited the enzymatic activity of tPA in a fibrin agarose plate assay, while it did not affect the enzymatic activity towards the synthetic substrate or plasminogen. The antibody is directed to an epitope on the B-chain of tPA, which is necessary for the formation of a ternary complex of tPA, fibrin and plasminogen, but probably not to the active site. Another antibody, TPA2-14, partially inhibited the enzymatic activities of tPA towards the synthetic substrate and plasminogen, but it was not able to bind to the inactive tPA complexed with plasminogen activator inhibitor-1 (PAI-1). The antibody is directed to an epitope on the second kringle region, which is probably one of the PAI-1 binding sites. This property of the antibody enabled us to develop an ELISA for selective quantitation of free tPA in culture media conditioned with several human cell lines. The results indicate that tPA in these media exists either partially or almost entirely in a complex with PAI-1. | {
"pile_set_name": "PubMed Abstracts"
} |
Using Client's Routine Urinalysis Records From Multiple Treatment Systems to Model Five-Year Opioid Substitution Treatment Outcomes.
At global, national, and local level, the need for ongoing, timely and cost efficient, comprehensive drug treatment monitoring, and evaluation systems have clearly been well recognized. To test the feasibility of linking laboratory data and client intake data and its usefulness for modeling retrospectively, for the first time, 5-year longitudinal drug treatment outcomes in an Irish opiate treatment setting. A multisite, retrospective, longitudinal cohort study was implemented to evaluate outcomes for opiate users based on 1.7 million routine urinalysis results collected from 4,518 individuals presenting for opioid substitution treatment in Ireland from January 2006 to December 2010. Analysis of opiates, cocaine, benzodiazepine, and cannabis use at treatment intake, 6 months and at 1-5 year follow-ups revealed differences in urinalysis protocols; significant differences in age of first drug use between those using and not using opiates at 5 years; significant decreases in opiate use; increases in benzodiazepine use and significant increasing effects of concurrent cocaine and benzodiazepine use on the odds of using opiates. Time series analysis of weekly proportions opiate positive predicted 16% (95% confidence interval: 7%-25%) of clients would be opiate positive 5 years postinitial intake. CONCLUSIONS IMPORTANCE: Underutilized urinalysis data can be used to address the need for cost effective, efficient evidence of drug-treatment outcomes across time, place, and systems. Linking and matching the cross-sectional data across sites and times also revealed where improvements in electronic records could be made. | {
"pile_set_name": "PubMed Abstracts"
} |
Transobturator vaginal tape for treatment of urinary incontinence in spayed bitches.
This study investigated the long-term effectiveness and safety of a variant of the transobturator vaginal tape inside-out technique for acquired urinary incontinence. Twelve spayed female dogs were operated over a 2 yr period. No intraoperative complications were encountered. Transient dysuria was the most common postoperative complication (7 out of 12 dogs). On the 12th day postoperatively, incontinence was completely cured in 11 out of 12 dogs (92%). At the time of the second evaluation (median follow-up time was 21 mo), patients classified as "cured," "greatly improved," or "improved" were 25, 50, and 25% of the total, respectively. At the time of either the fourth evaluation or at the time of death (median follow-up time was 52 mo), 50% of the bitches (6 out of 12) had the same results as previously but the other 50% had leakage that reappeared sporadically. A fistula appeared on the path of the tape in two bitches at 28 and 32 mo postsurgically. The technique presented is effective and more cost effective than the standard technique and could constitute an attractive alternative; however, it could be associated with an immediate postoperative dysuria, delayed fistula formation, and a partial recurrence of clinical signs. | {
"pile_set_name": "PubMed Abstracts"
} |
Spiro-cyclopropanation from oxoallylsilanes.
A novel highly stereoselective spiro-cyclopropanation reaction from oxoallylsilanes is described. Oxoallylsilanes are readily obtained by silylcupration of allene followed by conjugate addition to enones. The former oxoallylsilanes undergo a tandem cyclization-cyclopropanation reaction when treated with CH2I2/Me3Al, leading to hydroxylated polycyclic systems bearing the spiro-cyclopropane moiety. The scope of the process is studied, and a feasible pathway is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
The relationship between metabolic syndrome, its components, and the whole-body atherosclerotic disease burden as measured by computed tomography angiography.
Quantify the whole-body atherosclerotic disease in asymptomatic subjects with and without metabolic syndrome (MetS) and to assess the contribution of the syndrome and its components to the atherosclerotic burden. Sixty-five subjects with and 51 without ATPIII-defined MetS underwent a 64-slice computed tomography angiography (CTA). Plaques causing >0% stenosis in coronary or extra-coronary arteries were classified as positive. The prevalence of plaques in coronary, carotid and peripheral arteries as well as their severity did not differ between groups. Conversely, it was seen an almost 3-fold increased likelihood (OR=2.70; 95% CI 1.30-5.57; P<0.001) of atherosclerosis in any district across categories of MetS components (0-1 vs. 2-3 vs. 4-5). Hypertriglyceridemia (P<0.05) and high blood glucose (P<0.05) were independent predictors of the atherosclerotic burden. Atherosclerotic burden as revealed by 64-TCA appears to be more strongly associated with the number of MetS-related factors than to the clinical diagnosis of MetS itself. | {
"pile_set_name": "PubMed Abstracts"
} |
Role of the JNK-interacting protein 1/islet brain 1 in cell degeneration in Alzheimer disease and diabetes.
Numerous epidemiological studies and some pharmacological clinical trials show the close connection between Alzheimer disease (AD) and type 2 diabetes (T2D) and thereby, shed more light into the existence of possible similar pathogenic mechanisms between these two diseases. Diabetes increases the risk of developing AD and sensitizers of insulin currently used as diabetes drugs can efficiently slow cognitive decline of the neurological disorder. Deposits of amyloid aggregate and hyperphosphorylation of tau, which are hallmarks of AD, have been also found in degenerating pancreatic islets beta-cells of patients with T2D. These events may have a causal role in the pathogenesis of the two diseases. Increased c-Jun NH(2)-terminal kinase (JNK) activity is found in neurofibrillary tangles (NFT) of AD and promotes programmed cell death of beta-cells exposed to a diabetic environment. The JNK-interacting protein 1 (JIP-1), also called islet brain 1 (IB1) because it is mostly expressed in the brain and islets, is a key regulator of the JNK pathway in neuronal and beta-cells. JNK, hyperphosphorylated tau and IB1/JIP-1 all co-localize with amyloids deposits in NFT and islets of AD and patients with T2D. This review discusses the role of the IB1/JIP-1 and the JNK pathway in the molecular pathogenesis of AD and T2D. | {
"pile_set_name": "PubMed Abstracts"
} |
Evolution of the bacterial community during granules formation in denitrifying reactors followed by molecular, culture-independent techniques.
The microbial community in two acetate-fed denitrifying reactors, inoculated with methanogenic sludge, was monitored by 16S rDNA-based methods (SSCP and FISH). Both reactors converged to similar, stable communities. The predominant organisms belonged to the genera Thauera, Paracoccus and Denitrobacter, detected both by molecular and culture-based methods. | {
"pile_set_name": "PubMed Abstracts"
} |
[Epidemiological research of the nutrition men of Kabardino-Balkaria: social-economic and medical aspects, national peculiarities].
The epidemiological research of the nutrition status and the prevalance of the main risk factors of cardiovascular deseases among men aged 35-60 was held in Kabardino-Balkaria. The comporative analyse of consumption of the main groups of foods in the families of the men with different level of income and treatment of nutrients, energy and micronutrients. The results showd the connection between the studied parameters and economical status of the examined men. The necessity of development of nutrition support in low-income people and teaching the whole population principles of healthy nutrition with the consideration of regional and national peculiarities of KBR was shown. | {
"pile_set_name": "PubMed Abstracts"
} |
Multimodality Imaging Assessment of Fabry Disease.
Fabry disease is a lysosomal storage disease with a variety of cardiac manifestations. Although not specific for a diagnosis of Fabry disease, certain cardiac imaging findings may be highly suggestive of the diagnosis of Fabry disease in previously undiagnosed patients or cardiac involvement for patients with a known diagnosis of Fabry disease. In this review, we explore the current applications of multimodality cardiac imaging in the diagnosis and monitoring of patients with Fabry disease. Additionally, data regarding tissue characterization by cardiac magnetic resonance imaging and novel nuclear imaging techniques and their role in evaluating phenotype development is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Cytogenetic studies of esophageal squamous cell carcinomas in the northern Chinese population by comparative genomic hybridization.
Esophageal cancer is the fourth most prevalent malignancy in China. So far, the genetic events involved in esophageal cancer remain largely unknown. To identify chromosomal alterations in this disease, comparative genomic hybridization was performed on 25 primary tumors of esophageal squamous cell carcinomas. Results exhibited nonrandom copy number changes in chromosome DNA, with higher incidence in gain than in loss. The average gains and losses per patient were 7.76 and 4, respectively. The most common gains were 3q (20/25), 1q (15/25), 8q (15/25), 20p (12/25), 20q (11/25), 5p (10/25), 15q (8/25), and 9q (8/25) with two minimal amplification loci mapped to chromosomal regions of 8q24 (2 cases) and 11q13 (7 cases). High-level amplification was observed at 3q (8 cases), 5p (4 cases), and 8q (4 cases). Losses at 3p (10/25), 13q (8/25), 18q (7/25), Xp (7/25), 4 (6/25), 9p (6/25), 14q (6/25), 18p (6/25), and 21q (6/25) were identified. Remarkably, ten cases showed both loss of the entire 3p and overrepresentation of almost the whole 3q. No significant differences in stage or grade of tumor were found for DNA copy number changes. The results provided candidate regions for potential oncogenes and tumor suppressor genes related to Chinese esophageal cancer, to which further molecular studies should be addressed. | {
"pile_set_name": "PubMed Abstracts"
} |
Pancreatic islet transplantation in type 1 diabetes mellitus: an update on recent developments.
Type 1 diabetes mellitus is an autoimmune disease that is characterized by the destruction of the islets of Langerhans cells which produce insulin. The current gold standard treatment is exogenous insulin injection, but this is onerous for the patients, and can lead to severe complications. Another approach involves transplanting pancreatic islet cells in order to restore endogenous insulin production under physiologic regulation. Although there has been some success with this treatment plan, there have been several hurdles. The largest hurdle is improving the 5 year survival of the graft, which is currently at 10%. In order to do so, there has been research into better locations for the graft, better isolation techniques, alternate immune suppression regimens, and novel transplantation methodologies utilizing encapsulated grafts. Another hurdle for pancreatic islet transplantation is that current methodologies require islets from several pancreata in order to create one successful graft, which leads to difficulties since there is a limited supply. However, there has been research looking into single donor transplants and porcine xenografts to increase the supply and address this problem. In this article, we review the current state of research regarding pancreatic islet transplantation. | {
"pile_set_name": "PubMed Abstracts"
} |
Aberrant single-minded homolog 1 methylation as a potential biomarker for cervical cancer.
The aim of this study is to evaluate the possibility of using the methylation status of single-minded homolog 1 (SIM1) as a diagnostic biomarker for cervical cancer. All the patient and normal specimens including the normal cervix (n = 10), cervical cancer tissues (n = 45), blood (n = 45), and cervical brush specimens (n = 110) were retrospectively obtained. Quantitative methylation-specific PCR was performed to detect SIM1 methylation in primary tumors, cervical brush specimens, and plasma circulating cell-free DNA (ccfDNA). SIM1 expression was detected by western blot analysis. We found that SIM1 was highly methylated in the majority of the cervical cancer tissues that we tested, but not in any of the normal tissues. Hypermethylation of SIM1 led to a pronounced reduction in SIM1 expression in cervical cancer tissues compared with normal cervix. SIM1 methylation status on cervical brush specimens also distinguished cervical cancer from normal, cervical intraepithelial neoplasia (CIN) 1 and 2. The degree of SIM1 methylation was significantly associated with the severity of the disease (Ptrend < .0001). We also investigated the possibility of detecting methylated SIM1 in plasma ccfDNA from cervical cancer patients. Methylated SIM1 was detected in 36.6% (15/41) of ccfDNA samples, and concordance rate with the matched cancer tissues was 41.5% (17/41) with sensitivity 38.5% and specificity 100%. This study has shown that SIM1 is frequently hypermethylated in cervical cancer, compared with normal cervix tissue, CIN1 and 2 samples, suggesting that the methylation status of SIM1 could be a potential diagnostic biomarker for cervical cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
ATP and calcium modulation of nonselective cation channels in IMCD cells.
The mIMCD-3 cell line, developed from simian virus 40 transformed mice, was grown on coverslips for single-channel analysis of the apical membrane. An amiloride-sensitive nonselective cation channel (NCATP) was demonstrated that occurred predominantly in excised patches. The selectivity sequence for NCATP was NH4+ = Na+ = K+ = Li+ = Rb+ > Cl-. The single-channel conductance was 24 pS and nonrectifying in 140 mM KCl or NaCl solutions. NCATP was not permeable to barium from the extracellular side. NCATP was not voltage gated but was activated spontaneously upon patch excision or after applying negative pressure (20-40 mmHg) to an excised patch in bath solutions containing 1 microM Ca2+ [mean number of open channels (NPl) = 1.45]. NCATP was not activated when excised into a bath solution in which Ca2+ was reduced to 100 nM. The open probability of NCATP was reduced by 68% when 2 mM ATP was added to the intracellular side of an excised patch but was unaffected when 0.1 mM 8-bromoguanosine 3',5'-cyclic monophosphate was added to the intracellular side. In cell-attached patches, NCATP was activated upon response to a hyposmotic (210 mosmol/kgH2O) bathing solution containing 0.5 mM Ca2+ (NPo = 0.35). These results show that the mIMCD-3 cell line contains a volume-sensitive nonselective cation channel that is modulated by ATP and calcium but not guanosine 3',5'-cyclic monophosphate. It is postulated that NCATP may act to initiate the volume regulatory response in IMCD cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Coupling of proton flow to ATP synthesis in Rhodobacter capsulatus: F(0)F(1)-ATP synthase is absent from about half of chromatophores.
F(0)F(1)-ATP synthase (H(+)-ATP synthase, F(0)F(1)) utilizes the transmembrane protonmotive force to catalyze the formation of ATP from ADP and inorganic phosphate (P(i)). Structurally the enzyme consists of a membrane-embedded proton-translocating F(0) portion and a protruding hydrophilic F(1) part that catalyzes the synthesis of ATP. In photosynthetic purple bacteria a single turnover of the photosynthetic reaction centers (driven by a short saturating flash of light) generates protonmotive force that is sufficiently large to drive ATP synthesis. Using isolated chromatophore vesicles of Rhodobacter capsulatus, we monitored the flash induced ATP synthesis (by chemoluminescence of luciferin/luciferase) in parallel to the transmembrane charge transfer through F(0)F(1) (by following the decay of electrochromic bandshifts of intrinsic carotenoids). With the help of specific inhibitors of F(1) (efrapeptin) and of F(0) (venturicidin), we decomposed the kinetics of the total proton flow through F(0)F(1) into (i) those coupled to the ATP synthesis and (ii) the de-coupled proton escape through F(0). Taking the coupled proton flow, we calculated the H(+)/ATP ratio; it was found to be 3.3+/-0.6 at a large driving force (after one saturating flash of light) but to increase up to 5.1+/-0.9 at a smaller driving force (after a half-saturating flash). From the results obtained, we conclude that our routine chromatophore preparations contained three subsets of chromatophore vesicles. Chromatophores with coupled F(0)F(1) dominated in fresh material. Freezing/thawing or pre-illumination in the absence of ADP and P(i) led to an increase in the fraction of chromatophores with at least one de-coupled F(0)(F(1)). The disclosed fraction of chromatophores that lacked proton-conducting F(0)(F(1)) (approx. 40% of the total amount) remained constant upon these treatments. | {
"pile_set_name": "PubMed Abstracts"
} |
Cimetidine-theophylline complex formation.
Cimetidine forms a complex with theophylline in vitro in both pH 7.4 buffer and human plasma. The increase in the amount of theophylline in solution is about 20% in the buffer system and about 36% in plasma. It is hypothesized that this complex formation may contribute to and be part of the mechanism of the clinically observed decreased theophylline clearance in man in presence of cimetidine. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluating the effects of rater and subject factors on measures of association.
Large-scale agreement studies are becoming increasingly common in medical settings to gain better insight into discrepancies often observed between experts' classifications. Ordered categorical scales are routinely used to classify subjects' disease and health conditions. Summary measures such as Cohen's weighted kappa are popular approaches for reporting levels of association for pairs of raters' ordinal classifications. However, in large-scale studies with many raters, assessing levels of association can be challenging due to dependencies between many raters each grading the same sample of subjects' results and the ordinal nature of the ratings. Further complexities arise when the focus of a study is to examine the impact of rater and subject characteristics on levels of association. In this paper, we describe a flexible approach based upon the class of generalized linear mixed models to assess the influence of rater and subject factors on association between many raters' ordinal classifications. We propose novel model-based measures for large-scale studies to provide simple summaries of association similar to Cohen's weighted kappa while avoiding prevalence and marginal distribution issues that Cohen's weighted kappa is susceptible to. The proposed summary measures can be used to compare association between subgroups of subjects or raters. We demonstrate the use of hypothesis tests to formally determine if rater and subject factors have a significant influence on association, and describe approaches for evaluating the goodness-of-fit of the proposed model. The performance of the proposed approach is explored through extensive simulation studies and is applied to a recent large-scale cancer breast cancer screening study. | {
"pile_set_name": "PubMed Abstracts"
} |
Computational model of the fluid dynamics of a cannula inserted in a vessel: incidence of the presence of side holes in blood flow.
Vascular access methods, performed by the insertion of cannulae into vessels, may disturb the physiological flow of blood, giving rise to non-physiological pressure variations and shear stresses. To date, the hydrodynamic behaviour of the cannulae has been evaluated comparing their pressure loss-flow rate relationships, as obtained from in vitro experiments using a monodimensional approach; this methodology neither furnish information about the local fluid dynamics nor the established flow field in specific clinical work conditions. Since the shear stress is a critical factor in the design of artificial circulatory devices, more knowledge should be necessary about the local values assumed by the haemodynamic parameters during cannulation. An alternative way to investigate the fluid dynamic as accurately as possible is given by numeric studies. A 3D model of cannula concentrically placed in a rigid wall vessel is presented, with the finite element methodology used to numerically simulate the steady-state flow field in two different venous cannulation case studies, with two cannulae having a central hole and two or four side holes, respectively, with the same boundary conditions. Lower velocity and shear stress peak values have been computed for the model with four side holes upstream of the central hole, in the region of the cannula where the inlet flows meet and towards cannula's outlet, due to the increased flow symmetry and inlet area with respect to the model with two side holes. Starting from the investigation of different cannula designs, numerically assessing the local fluid dynamics, indications can be drawn to support both the design phase and the device optimal clinical use, in order to limit risks of biomechanical origin. Thus the presence of four side holes implied, as a consequence of the greater inlet area and of the increased symmetry, a less disturbed blood flow, together with reduced shear stress values. Furthermore, results show that the numerical simulations furnished useful informations on the interaction between vessel and cannula, e.g. on the fluid dynamics establishing in the free luminal space left, in the vessel, by the inserted cannula. | {
"pile_set_name": "PubMed Abstracts"
} |
[Association analysis between polymorphism of dopamine transporter variable number tandem repeat and breast cancer with abnormal Hilit].
To explore the association between polymorphism of dopamine 1 transporter variable number tandem repeat (DAT1 VNTR) and breast cancer with abnormal Hilit in Chinese Han population from Xinjiang. The breast caner patients were divided into four body fluids according to Uighur medicine theory. And polymerase chain reaction and VNTR polymorphism technique were employed to detect genotypic and allelic frequencies of a 40 bp VNTR polymorphism situated in 3' untranslated region of DAT1 gene in 144 breast cancer patients with abnormal Hilit and 104 normal control subjects in Han population of Xinjiang province. In our sample, the repeat numbers of 40 bp were 7 and 9 - 11 (PCR product length of 360 bp and 440 bp to 520 bp) and 10-repeat allele (480 bp) detected was the dominant allele of DAT1 gene polymorphisms with an allelic frequency of 90.9%; Seven kinds of genotype were detected and genotype 10/10 was the most common genotype with a genotypic frequency of 83.1%. The frequency of 10-repeats allele and 10/10 genotype was significantly higher in breast caner patients with abnormal balgham Hilit than in controls (OR = 0.127, 95%CI 0.016 - 0.988, P = 0.026; OR = 0.134, 95%CI 0.018 - 1.016, P = 0.020) and breast caner patients with abnormal Sapra Hilit (OR = 0.132, 95%CI 0.016 - 1.075, P = 0.049; OR = 0.132, 95%CI 0.017 - 1.042, P = 0.033). The 10-repeats allele and 10/10 genotype of 40 bp VNTR polymorphism of DAT1 may increase the risk of breast cancer with Uighur medicine abnormal Hilit in Chinese Han population from Xinjiang province and it is not correlated with the susceptibility to breast cancer with Uighur medicine abnormal Sapra Hilit. | {
"pile_set_name": "PubMed Abstracts"
} |
Improved Utility of Photolabile Solid Phase Synthesis Supports for the Synthesis of Oligonucleotides Containing 3'-Hydroxyl Termini.
Oligonucleotides are synthesized on, and cleaved from, a solid phase support (6) using the o-nitrobenzyl intramolecular photochemical redox reaction. The yields of isolated oligonucleotides relative to yields obtained using conventional hydrolytic cleavage vary between 67% and 82.5%. Synthesis of oligonucleotides using phosphoramidites that do not contain N-benzoyl protecting groups enables one to photolytically cleave the biopolymers in good yields using a commonly available UV irradiation source. Tritium labeling indicates that less than 3% thymidine.thymidine photodimers are formed during photolytic cleavage of polythymidylates from 6 using a transilluminator. No UV-induced damage is detected via HPLC analysis of enzymatically digested oligonucleotides that were obtained following photolytic cleavage from 6. | {
"pile_set_name": "PubMed Abstracts"
} |
Temporal bone fractures: evaluation of 77 patients and a management algorithm.
We aimed to evaluate the etiologies, otolaryngological features, radiological findings, management strategies, and outcomes of temporal bone fractures. Seventy-seven temporal bone fracture cases were retrospectively evaluated for age and gender distribution, side of the fracture, etiology of injuries, the presence of blood otorrhea, tympanic membrane perforation, cerebrospinal fluid otorrhea, hearing loss, hemotympanum, and facial or other cranial nerve palsies, and computerized tomography reports. Nearly 55% of the cases were caused by traffic accidents and were predominantly male (76.6%). Otolaryngological presentations in order to frequency were early conductive hearing loss (65.8%), blood otorrhea (61.2%), hemotympanum (58.5%), tympanic membrane perforation (25.6%), facial nerve paralysis (12.3%), cerebrospinal fluid otorrhea (8.5%), and sensorineural hearing loss (5.4%). Most of the fractures were petrous (65.8%) and longitudinal type (51.2%). In this research, otolaryngological findings in order of frequency and treatment approaches were compared with literature findings and discussed in 77 temporal bone fracture cases. We formed a management algorithm for the systematic evaluation and treatment of temporal fractures. | {
"pile_set_name": "PubMed Abstracts"
} |
[Clinical trial updates for malignant brain tumors].
Gliomas account for approximately 40% of all brain tumors and are thus the most common primary tumors of the central nervous system (CNS). High-grade (WHO grades III and IV) malignant gliomas that include anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic oligoastrocytoma (AOA), and glioblastoma multiforme (GBM) are often resistant to treatment; especially, GBM, the most common glioma in adults, kills patients within a median time span of a year after diagnosis despite treatment with aggressive surgical resection, chemotherapy, and radiotherapy. In 2006, Temozolomide (TMZ) was certified as the treatment agent for malignant gliomas in Japan, and it is now used as the first-line therapy. However, its clinical outcomes depend on the O(6)-methylguanine-DNA methyltransferase (MGMT) status, and MGMT modification is one of the key factors to obtain greater clinical benefits. Previously, we demonstrated that Interferon-β (IFN-β) markedly enhanced chemosensitivity to TMZ in an in vitro study of human glioma cells; this finding suggested that one of the major mechanisms by which IFN-β enhances chemosensitivity is the downregulation of MGMT transcription via p53 induction. Previously, we tried clinical trial of gene therapy by means of IFN-β gene in order to evaluate the safety, feasibility, and preliminary clinical effectiveness, and reasonable results could be obtained. As a next step, we are conducting a clinical trial study, namely, genomic therapy using with siRNA-MGMT. We hope that these new regimen will be safe and well tolerated, and may prolong survival in patients with GBM. | {
"pile_set_name": "PubMed Abstracts"
} |
Human type II hyperlipoproteinemia enhances platelet-collagen adhesion in flowing nonanticoagulated blood.
We investigated the effects of high plasma lipid levels on platelet adhesion and platelet thrombus formation in nonanticoagulated human blood on collagen fibrils at an arterial wall shear rate of 2600 seconds-1. Nonanticoagulated blood was drawn directly at a flow rate of 10 mL/min for 3 minutes from an antecubital vein of patients with type IIa (n = 5) and type IIb (n = 4) hyperlipoproteinemia over purified human type III collagen fibrils that were positioned on a plastic coverslip in a parallel-plate perfusion chamber. Results were compared with those obtained in healthy individuals with normal lipid plasma levels (n = 9). Blood-collagen interactions were quantified by morphometry as platelet-collagen adhesion, thrombus volume, and fibrin deposition. Platelet-collagen adhesion in the two groups of patients was significantly higher than in healthy individuals (70.7 [61.2 to 82.0] and 70.3 [66.4 to 81.0] in types IIa and IIb patients, respectively, versus 51.2 [44.5 to 68.6] in control subjects; P < .05. All values are percent median [range]). In contrast, the thrombus volume was similar in the three groups (11.3 [8.0 to 13.0], 9.6 [6.4 to 15.3], and 10.2 [6.8 to 16.1] microns3/microns2 [range], respectively). Differences in fibrin deposition were not observed. Thus, it appears that platelet-collagen adhesion is augmented in patients with type IIa and IIb hyperlipoproteinemia, indicating that the process of thrombogenesis is hastened in these patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Fetal heart modelling based on a pressure-volume relationship.
Study of the cardiovascular system of the human fetus is based on non-invasive measurement methods such as Doppler echography systems. The circulation conditions in fetal vessels are usually evaluated by resistance indices, giving limited physiological information on distal territories such as the placenta or the brain. To enhance the understanding of human fetal haemodynamics, a numerical model of the fetal heart has been developed, using the hydraulic-electric analogy. The model is based on a mechanical hypothesis of parallel functioning of the right and left ventricles, considered to have analogue elastance properties. Their behaviour is equivalent to that of a single ventricle ejecting an equivalent blood volume of 7 ml in the aorta. The characterisation of the equivalent ventricle is based on the determination of a set of four parameters (Emax, Vo, kv and Po) representing the maximum ventricle contractility, a reference volume, and volume and pressure constants, respectively. The model proposed is validated by studying the effects of preload and afterload variations on the fetal heart work, and by comparing the numerical results with literature and measured data. The model constitutes the first step towards a global model of the cardiovascular system of the human fetus. | {
"pile_set_name": "PubMed Abstracts"
} |
Explaining the abundance of ants in lowland tropical rainforest canopies.
The extraordinary abundance of ants in tropical rainforest canopies has led to speculation that numerous arboreal ant taxa feed principally as "herbivores" of plant and insect exudates. Based on nitrogen (N) isotope ratios of plants, known herbivores, arthropod predators, and ants from Amazonia and Borneo, we find that many arboreal ant species obtain little N through predation and scavenging. Microsymbionts of ants and their hemipteran trophobionts might play key roles in the nutrition of taxa specializing on N-poor exudates. For plants, the combined costs of biotic defenses and herbivory by ants and tended Hemiptera are substantial, and forest losses to insect herbivores vastly exceed current estimates. | {
"pile_set_name": "PubMed Abstracts"
} |
Successful Implementation of an Automated Sedation Vacation Process in Intensive Care Units.
This quality improvement initiative sought to develop a sedation vacation (SV) protocol to increase SV performance and ensure sustainability. A standardized, nurse-driven SV protocol within the electronic medical record was implemented in adult intensive care units (ICUs) at Boston Medical Center. For 6 months, data were collected on the number of assessments performed, SV completion, SV eligibility, and reason for exclusion. Secondary outcomes included ICU length of stay (LOS) and ventilator LOS. Of 1730 patient-days during this 6-month period, SV assessments were performed 70% (n = 1211) of the time. SVs were conducted on 60.0% (n = 726) during days in which an assessment occurred. There was no significant change in ICU LOS or ventilator LOS during the study period. This SV protocol attained a 70% adherence rate, which was sustained over the 6-month period. There were no significant changes in secondary outcomes. | {
"pile_set_name": "PubMed Abstracts"
} |
Aggressive natural killer cell leukemia presenting with hemophagocytic lymphohistiocytosis.
Aggressive natural killer cell leukemia (ANKL) is a very rare condition and when reported occurs almost exclusively in adults. We report a pediatric case of ANKL that presented with hemophagocytic syndrome, preceding the onset of leukemia by 12 weeks. Clinical and laboratory findings are discussed, along with morphology, immunophenotyping and cytogenetics, as well as the association with Epstein-Barr virus (EBV). This case is noteworthy for the expression of CD8 on the malignant cells, the cytogenetic findings that include abnormalities of chromosomes 6 and 7, as well as the age of the patient. | {
"pile_set_name": "PubMed Abstracts"
} |
Evolution of X-degenerate Y chromosome genes in greater apes: conservation of gene content in human and gorilla, but not chimpanzee.
Compared with the X chromosome, the mammalian Y chromosome is considerably diminished in size and has lost most of its ancestral genes during evolution. Interestingly, for the X-degenerate region on the Y chromosome, human has retained all 16 genes, while chimpanzee has lost 4 of the 16 genes since the divergence of the two species. To uncover the evolutionary forces governing ape Y chromosome degeneration, we determined the complete sequences of the coding exons and splice sites for 16 gorilla Y chromosome genes of the X-degenerate region. We discovered that all studied reading frames and splice sites were intact, and thus, this genomic region experienced no gene loss in the gorilla lineage. Higher nucleotide divergence was observed in the chimpanzee than the human lineage, particularly for genes with disruptive mutations, suggesting a lack of functional constraints for these genes in chimpanzee. Surprisingly, our results indicate that the human and gorilla orthologues of the genes disrupted in chimpanzee evolve under relaxed functional constraints and might not be essential. Taking mating patterns and effective population sizes of ape species into account, we conclude that genetic hitchhiking associated with positive selection due to sperm competition might explain the rapid decline in the Y chromosome gene number in chimpanzee. As we found no evidence of positive selection acting on the X-degenerate genes, such selection likely targets other genes on the chimpanzee Y chromosome. | {
"pile_set_name": "PubMed Abstracts"
} |
Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age.
The mean wall thickness (MWT) of packets of trabecular bone was measured in undecalcified iliac crest bone samples of 36 normal subjects (14 female and 22 male) under polarized light. The mean wall thickness was 49.7 +/- 8.7 microns at a mean age of 50.9 years. There existed a significant decrease of MWT with advancing age. With an appositional rate of 0.72 micron/day, the mean formation time of iliac trabecular bone packets is 69 days. The decrease of MWT with age corresponds to a decrease in bone formation at the basic multicellular unit (BMU) level with aging and can partly explain the physiological senile osteopenia. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis and biological activity of lipophilic analogs of the cationic antimicrobial active peptide anoplin.
Anoplin is a short natural cationic antimicrobial peptide which is derived from the venom sac of the solitary wasp, Anoplius samariensis. Due to its short sequence G1 LLKR5 IKT8 LL-NH2 , it is ideal for research tests. In this study, novel analogs of anoplin were prepared and examined for their antimicrobial, hemolytic activity, and proteolytic stability. Specific substitutions were introduced in amino acids Gly1 , Arg5 , and Thr8 and lipophilic groups with different lengths in the N-terminus in order to investigate how these modifications affect their antimicrobial activity. These cationic analogs exhibited higher antimicrobial activity than the native peptide; they are also nontoxic at their minimum inhibitory concentration (MIC) values and resistant to enzymatic degradation. The substituted peptide GLLKF5 IKK8 LL-NH2 exhibited high activity against Gram-negative bacterium Zymomonas mobilis (MIC = 7 µg/ml), and the insertion of octanoic, decanoic, and dodecanoic acid residues in its N-terminus increased the antimicrobial activity against Gram-positive and Gram-negative bacteria (MIC = 5 µg/ml). The conformational characteristics of the peptide analogs were studied by circular dichroism. Structure activity studies revealed that the substitution of specific amino acids and the incorporation of lipophilic groups enhanced the amphipathic α-helical conformation inducing better antimicrobial effects. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors that influence femoral neck length. Analysis of 1543 patients with advanced osteoarthritis of the hip.
There is little known about the relationship between patient characteristic and the variance in geometrical properties of the femoral neck. The length of the femoral neck is relevant when considering a femoral neck preserving hip replacement. Based on surgical experience we hypothesised that femoral neck length (FNL) decreased with age. We investigated whether certain patient characteristics were related to FNL and the femoral head diameter/FNL ratio. The femoral neck length of 1543 patients with osteoarthritis grade 3 and 4 was measured on calibrated pelvic radiographs. Increasing age and height were associated positively, while increasing CCD angle and femoral head diameter were associated negatively with femoral neck length. Female gender and height were associated negatively and CCD angle positively with the femoral head diameter/FNL ratio. The FNL in 10 year older individuals was on average 0.2 mm (1%) longer. Moreover, every 10 extra degrees in CCD coincided with a neck length decrease of 1.5 mm (8%) in our population. It seems justified to conclude that age is not a clinical relevant factor in the indication for femoral neck preserving hip arthroplasty. In this respect, CCD angle seems the most clinical relevant factor. Severe valgus angled hips are not a very suitable indication for femoral neck preserving prosthesis. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effect of Coeloglossum. viride var. bracteatum extract on oxidation injury in sub-acute senescent model mice].
To study the anti-aging effects of Coeloglossum. viride (L) Hartm. var. bracteatum (Willd) Richter extract (CE) on senescent model mice induced by D-galactose and sodium nitrite. After one week of accommodation, 60 female NIH mice were divided into six groups with 10 mice in each group: normal control group, aging model group, Piracetam (positive control) group [300 mg/ (kg x d)], and CE reatment groups [2.5, 5, and 10 mg/ (kg x d)]. Mice in aging model group, Piracetam group, and CE treatment group were consecutively intraperitoneally injected with D-galactose [120 mg/ (kg x d)] and sodium nitrite [90 mg/ (kg x d)] for 60 days. From day 47, mice in Piracetam group and CE treatment group were po given Piracetam 300 mg/ (kg x d) or CE 2.5, 5, and 10 mg/ (kg x d). Mice in normal control group and aging model group were po given saline. The drug administration lasted for 14 days. Water maze test was performed to evaluate the learning and memory function in the mice. The activity of superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the activities of adenosinetriphosphatase (ATPase), and monoamine-oxidase (MAO) in brain tissue were measured. The latencies in water maze test in aging model group mice were significantly longer than in normal control group (P < 0.01, P < 0.05), and the number of errors increased (P < 0.05). In aging model group mice, the activities of SOD, Na+K(+)-ATPase, and Ca2+Mg(2+)-ATPase decreased (P < 0.01, P < 0.05), while the content of MDA and the activities of MAO-A and MAO-B increased (P < 0.01). Piracetam [300 mg/ (kg x d), po] and CE [2.5, 5, 10 mg/ (kg x d), po] ameliorated the above changes in aging model mice. CE may improve the memory dysfunction induced by consecutive injection of D-galactose and sodium nitrite,and has nootropic and antiaging effects. | {
"pile_set_name": "PubMed Abstracts"
} |
A canine model for comparative study of respiratory and systemic immunologic reactions.
A canine model for the comparative study of lower respiratory and systemic immunologic reactions is described. The techniques of bronchopulmonary lavage and percutaneous splenic aspiration were employed to obtain serial samples of pulmonary and systemic lymphocytes. The morphologic features and the yield of cells obtained by these procedures were characterized. The presence of lymphocytes and plasma cells among the cell populations obtained by pulmonary lavage was confirmed by electron microscopy. The effect of serial bronchopulmonary lavage per se on the yield, composition, and functional properties of bronchoalveolar lymphocytes and macrophages was found to be minor. By contrast, the effect of immununization on these parameters was marked and easily detected. Evidence is presented that at least 2 anatomically and functionally different populatons of immunocytes subserve the lower respiratory tract, namely, the hilar lymph node cells and the bronchoalveolar lymphocytes. It is concluded that the canine model is well suited for the investigation of respiratory and systemic immunity and is useful for the study of bronchoalveolar lymphocyte and alveolar macrophage function, either independently or in concert with the study of pulmonary host defense and the pathogenesis of lung disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Specific pattern of early white-matter changes in pure hereditary spastic paraplegia.
Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. Most MR studies on HSP include very heterogeneous samples of patients, and findings were inconsistent. Here, we examined six patients with pure HSP and SPG4 mutations by clinical evaluation, detailed neuropsychological testing, and neuroimaging analyses, including conventional MRI, diffusion tensor imaging (DTI), and brain volumetry. Differences of voxel-wise statistics and ROI-based analysis of DTI data between patients and 32 healthy volunteers were evaluated. Although conventional MRI and brain volumetry were normal, DTI revealed widespread disturbance of white matter (WM) integrity (P < 0.001), mainly affecting the corticospinal tract. With longer disease duration, frontal regions were also involved. The WM changes were also present in subclinical subjects harbouring the pathogenic mutation. These subtle WM abnormalities have functional relevance because they correlated with clinical symptoms. Thus, early alterations of nerve fibres, which can be detected by DTI, might serve as a biological marker in HSP, in particular with respect to future longitudinal studies. | {
"pile_set_name": "PubMed Abstracts"
} |
Structure-based exploration and pharmacological evaluation of N-substituted piperidin-4-yl-methanamine CXCR4 chemokine receptor antagonists.
Using the available structural information of the chemokine receptor CXCR4, we present hit finding and hit exploration studies that make use of virtual fragment screening, design, synthesis and structure-activity relationship (SAR) studies. Fragment 2 was identified as virtual screening hit and used as a starting point for the exploration of 31 N-substituted piperidin-4-yl-methanamine derivatives to investigate and improve the interactions with the CXCR4 binding site. Additionally, subtle structural ligand changes lead to distinct interactions with CXCR4 resulting in a full to partial displacement of CXCL12 binding and competitive and/or non-competitive antagonism. Three-dimensional quantitative structure-activity relationship (3D-QSAR) and binding model studies were used to identify important hydrophobic interactions that determine binding affinity and indicate key ligand-receptor interactions. | {
"pile_set_name": "PubMed Abstracts"
} |
Joint experimental and theoretical study of vibrationally inelastic electron scattering on propane.
Vibrational electron energy loss spectra were measured for propane at incident energies of 3, 6, 10, 15, 20, and 25 eV at scattering angles of 40 degrees, 55 degrees, 70 degrees, 85 degrees, and 100 degrees . The spectra are compared with the results of ab initio calculations using a recently developed two-channel discrete momentum representation method. Good agreement between theory and experiment was found for large scattering angles and energies above the resonant region. | {
"pile_set_name": "PubMed Abstracts"
} |
Diskitis in children.
Thirty-six patients diagnosed with diskitis from 1978 to 1988 and followed for an average of 29.2 months were reviewed. The study included 23 boys and 13 girls with an average age of 5.3 years. The initial symptoms varied, but distinct clinical patterns emerged and were identifiable in different age groups. Both the leukocyte count and sedimentation rate were elevated. Routine roentgenograms were positive for intervertebral disk space narrowing in 82% of cases, technetium bone scans positive in 72%, and magnetic resonance imaging positive in all recent cases. Treatment consisted of bed rest for all patients, plaster casts for 50%, antibiotics for 40%, and traction for 23%. Regardless of the treatment combination, the course of the disease in most children is benign. At the completion of the study, all patients were asymptomatic including three children who had recurrences. In spite of being asymptomatic, 74% had persistent roentgenographic changes. The administration of antibiotics appears to be appropriate when indicated, i.e., failure to respond to immobilization. Disk space aspiration or biopsy should be reserved for those cases that are refractory to immobilization and antibiotics. | {
"pile_set_name": "PubMed Abstracts"
} |
[Telbivudine treatment on cirrhosis resulting from chronic hepatitis B].
To study the therapeutic efficacy of 48-week telbivudine treatment on cirrhosis resulting from chronic hepatitis B. 80 patients were equally divided into two groups, and treated with telbivudine 600 mg or lamivudine 100mg once daily for 48 weeks, respectively. The changes of virological and biochemical markers, PTA, Child-Pugh score, and viral resistance were observed at the different time points after antiviral treatment. The mean of serum HBV DNA level in telbivudine group before treatment was (6.52+/-1.33) log10 copies/ml, and the mean reduction of serum HBV DNA was (2.09+/-1.30), (2.83+/-1.22), (3.23+/-1.27), (3.42+/-1.32), (3.65+/-1.30), (3.67+/-1.43) log10 copies/ml at 2, 4, 8, 12, 24, 48 weeks, respectively. The proportion of patients with serum HBV DNA undetectable was 92.5% (37/40) at 24, 48 weeks. At week 24 and 48, the rates of HBeAg/anti-HBe seroconversion were 30.0% (6/20), 35.0% (7/20), respectively. ALT, AST, albumin, total bilirubin, PTA, and Child-Pugh score were improved (P less than 0.05). Mutation of YMDD observed in telbivudine group was 5.0%. The mean reduction of serum HBV-DNA and the proportion of patients with undetectable serum HBV-DNA were greater in telbivudine group than in lamivudine group (P less than 0.05). Telbivudine can rapidly and effectively inhibit the replication of HBV in patients with cirrhosis resulting from chronic hepatitis B, and the resistance mutation rate was low. In addition, telbivudine treatment can improve the liver function. | {
"pile_set_name": "PubMed Abstracts"
} |
Blunt trauma to the abdomen.
There is general agreement that physical examination alone is inadequate for abdominal evaluation in the multiply injured blunt trauma patient; but controversy exists regarding the preferred method of detecting intraabdominal injuries requiring celiotomy. Both peritoneal lavage and the newer computed tomography imaging techniques have advantages and disadvantages. Direct comparisons of the two techniques have not determined a preferred method. When used as complementary rather than competitive studies, diagnostic peritoneal lavage and computed tomography imaging provide more information than either test alone. | {
"pile_set_name": "PubMed Abstracts"
} |
Heterogeneity in the liver mitochondria of the tadpole, Rana catesbeiana.
1. The heterogeneity of liver mitochondria of the tadpoles, Rana catesbeiana, undergoing metamorphosis was investigated by a combination of pulse-chase labeling of mitochondria with [methyl-3H]thymidine and centrifugation of mitochondria on a density gradient of metrizamide. 2. The liver mitochondria of tadpole at premetamorphic stage are separated into two populations with mean densities of 1.128 (M2) and 1.112 (M3). 3. At metamorphic stage a population with mean densities of 1.174 (M1) appears additionally. 4. The activity of mitochondria to take up [methyl-3H]thymidine in vivo is 2-3 times higher at metamorphic stage than at premetamorphic stage. 5. The M1 population has a prominently high activity to take up L-[4.5-3H]leucine in vitro and also a high specific activity of cytochrome c oxidase. 6. These findings suggest that the mitochondrial populations found are of alternate stages in the mitochondrial maturation. | {
"pile_set_name": "PubMed Abstracts"
} |
Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes.
Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS2-12, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59% increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50%. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-gamma2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis, characterization, and properties of organically templated lanthanide oxalatophosphates with a three-dimensional honeycomb structure: (H4APPIP)[Ln3(C2O4)(5.5)(H2PO4)2].5H2O (Ln = Er-Lu, APPIP = 1,4-bis(3-aminopropyl)piperazine).
Four isostructural organically templated lanthanide oxalatophosphates, (H(4)APPIP)[Ln(3)(C(2)O(4))(5.5)(H(2)PO(4))(2)].5H(2)O (Ln = Er-Lu and APPIP = 1,4-bis(3-aminopropyl)piperazine), have been synthesized under hydrothermal conditions and characterized by single-crystal and powder X-ray diffraction. Their structures contain LnO(8) trigonal dodecahedra linked by three bis-bidentate oxalates to form layers in the (102) plane, which are connected by dihydrogen phosphate and bis-monodentate oxalate ligands to form a 3D framework. The charge-compensating tetraprotonated 1,4-bis(3-aminopropyl)piperazinium cations and lattice water molecules are located in the 12-membered ring straight channels. They are the first examples of organically templated lanthanide oxalatophosphates. The thermal stability, guest desorption-sorption properties, variable-temperature in situ powder X-ray diffraction, magnetic susceptibility, and photoluminescence spectrum of the Er compound and catalytic activity of the Yb compound for the Biginelli reaction have also been studied. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical and Histologic Effects of Fractional Microneedling Radiofrequency Treatment on Rosacea.
Fractional microneedling radiofrequency (FMR) is an emerging treatment modality, but its effect on rosacea has not been studied yet. To investigate the potential impact of FMR treatment on clinical improvement and histologic changes in rosacea patients. A 12-week, prospective, randomized, split-face clinical trial was conducted. Two sessions of FMR were performed on one side of the cheeks with 4-week interval and the other side remained untreated. Erythema index from DermaSpectrometer and a* value from Spectrophotometer CM-2002 were measured at each visit for the objective measurement of erythema. Histologic analysis of skin samples was also carried out. Clinical evaluation and photometric measurement revealed the reduction of redness in the treated side compared with untreated side and baseline. Erythema index decreased 13.6% and a* value decreased 6.8% at Week 12 compared with baseline. Reduced expression of markers related to inflammation, innate immunity, and angiogenesis was observed in immunohistochemical staining of tissue obtained after FMR treatment. Fractional microneedling radiofrequency treatment showed modest clinical and histologic improvement of rosacea, and it might be used as an alternative or in combination with other treatment methods. | {
"pile_set_name": "PubMed Abstracts"
} |
[The changes in alpha-granule membrane protein (GMP-140) on plasma membrane of platelets during cardiopulmonary bypass].
The degree of activation and damage of platelets during various stages of cardiopulmonary bypass (CPB) was studied with monoclonal antibody SZ-51 specific for an alpha-granule membrane protein (GMP-140) on the surface of activated platelets. The number of platelets fell significantly at the commencement of CPB and reached the minimum at the end of CPB; GMP-140 molecules on the platelet surface increased significantly after the commencement of CPB and reached the peak between the ending of bypass and administration of protamine and returned to normal level at 2 hours postoperatively, however, the concentration of GMP-140 in plasma began increasing at the end of CPB and reached the peak at 2 hours postoperatively and became normal at 24 to 48 hours after operation. The results indicate that platelet activation and damaging occur during CPB. | {
"pile_set_name": "PubMed Abstracts"
} |
Analysis of hybrid statistical textural and intensity features to discriminate retinal abnormalities through classifiers.
Retinal image analysis relies on the effectiveness of computational techniques to discriminate various abnormalities in the eye like diabetic retinopathy, macular degeneration and glaucoma. The onset of the disease is often unnoticed in case of glaucoma, the effect of which is felt only at a later stage. Diagnosis of such degenerative diseases warrants early diagnosis and treatment. In this work, performance of statistical and textural features in retinal vessel segmentation is evaluated through classifiers like extreme learning machine, support vector machine and Random Forest. The fundus images are initially preprocessed for any noise reduction, image enhancement and contrast adjustment. The two-dimensional Gabor Wavelets and Partition Clustering is employed on the preprocessed image to extract the blood vessels. Finally, the combined hybrid features comprising statistical textural, intensity and vessel morphological features, extracted from the image, are used to detect glaucomatous abnormality through the classifiers. A crisp decision can be taken depending on the classifying rates of the classifiers. Public databases RIM-ONE and high-resolution fundus and local datasets are used for evaluation with threefold cross validation. The evaluation is based on performance metrics through accuracy, sensitivity and specificity. The evaluation of hybrid features obtained an overall accuracy of 97% when tested using classifiers. The support vector machine classifier is able to achieve an accuracy of 93.33% on high-resolution fundus, 93.8% on RIM-ONE dataset and 95.3% on local dataset. For extreme learning machine classifier, the accuracy is 95.1% on high-resolution fundus, 97.8% on RIM-ONE and 96.8% on local dataset. An accuracy of 94.5% on high-resolution fundus 92.5% on RIM-ONE and 94.2% on local dataset is obtained for the random forest classifier. Validation of the experiment results indicate that the hybrid features can be deployed in supervised classifiers to discriminate retinal abnormalities effectively. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of deferoxamine methanesulfonate on Trichophyton mentagrophytes.
Deferoxamine methanesulfonate (Desferal), an iron chelator, inhibited germ tube formation and growth of Trichophyton mentagrophytes in a microculture assay. A 50% reduction of germ tube formation required Desferal at 5 mg/ml and a 50% reduction of growth required 1.5 mg/ml. Growth was almost completely inhibited with 50 and 100 mg/ml. Also, Desferal at 100 mg/ml inhibited further elongation when added to short hyphae (II and 21 micrometer), but showed less inhibitory effects when added to long hyphae (64 micrometer). Iron (133 microgram/ml) reversed the inhibition of growth produced by incubating spores with Desferal at 5 mg/ml, providing iron was added before 72 h incubation. Desferal at 100 mg/ml decreased viability of activated spores incubated for 3 days at 30 degrees C, but did not decrease viability of spores incubated for 3 days at 4 degrees C. The growth inhibitory effect of Desferal and transferrin were compared. Transferrin was inhibitory at low molarities (0.001 to 1.0 mM), while Desferal was inhibitory only at higher molarities (greater than 1 mM). Desferal (0.05 mM) also reversed the inhibition expected with 0.05 mM transferrin. These findings indicate that Desferal and transferrin deprive T. mentagrophytes of nutritional iron and thus inhibit growth of the fungus. Low concentrations of Desferal can also promote growth in the presence of transferrin. | {
"pile_set_name": "PubMed Abstracts"
} |
Loss of motivation for speaking with bilateral lacunes in the anterior limb of the internal capsule.
A 76-year-old man suddenly presented with loss of motivation for speaking. He had no aphasia, depression or dementia, but he did not want to speak with other people. CT scan showed hypodensities, presumably lacunes, mainly in the anterior limb of the two internal capsules. Global behavioral changes with loss of self psychic activation have been reported, but in our patient the disturbance was restricted to oral language. The role of activating cortico-subcortical loops is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Supporting rehabilitation training of COPD patients through multivariate sensor-based monitoring and autonomous control using a Bayesian network: prototype and results of a feasibility study.
Repeated endurance training - supervised by an expert - is one of the most effective rehabilitation methods for patients with chronic obstructive pulmonary disease (COPD) to improve physical function. Monitoring of vital signs in combination with an automatic intelligent training control and emergency detection facilitates supervised training without the physical presence of an expert as well as training optimisation through individualisation. The aim of this study is the development of a suitable analysis and control method for this purpose. Healthy volunteers and patients with COPD were equipped with body sensors during ergometer training to enable measuring their vital signs continuously. Depending on these values, the exercise load of the ergometer was controlled automatically using a Bayesian network. The network, trained with expert knowledge and training data, is embedded in our system by using Java application programming interface. Extensive tests in a laboratory setting have proved safe usage of our prototype. In a case study, evaluation during training sessions with patients with COPD took place. Due to the automatic control the patients' vital signs ranged inside the predefined optimal thresholds for at least 95% of the time. Furthermore, our results suggest an increase of the training efficiency compared with the conventional method (constant exercise load). | {
"pile_set_name": "PubMed Abstracts"
} |
High frequency source localization in a shallow ocean sound channel using frequency difference matched field processing.
Matched field processing (MFP) is an established technique for source localization in known multipath acoustic environments. Unfortunately, in many situations, particularly those involving high frequency signals, imperfect knowledge of the actual propagation environment prevents accurate propagation modeling and source localization via MFP fails. For beamforming applications, this actual-to-model mismatch problem was mitigated through a frequency downshift, made possible by a nonlinear array-signal-processing technique called frequency difference beamforming [Abadi, Song, and Dowling (2012). J. Acoust. Soc. Am. 132, 3018-3029]. Here, this technique is extended to conventional (Bartlett) MFP using simulations and measurements from the 2011 Kauai Acoustic Communications MURI experiment (KAM11) to produce ambiguity surfaces at frequencies well below the signal bandwidth where the detrimental effects of mismatch are reduced. Both the simulation and experimental results suggest that frequency difference MFP can be more robust against environmental mismatch than conventional MFP. In particular, signals of frequency 11.2 kHz-32.8 kHz were broadcast 3 km through a 106-m-deep shallow ocean sound channel to a sparse 16-element vertical receiving array. Frequency difference MFP unambiguously localized the source in several experimental data sets with average peak-to-side-lobe ratio of 0.9 dB, average absolute-value range error of 170 m, and average absolute-value depth error of 10 m. | {
"pile_set_name": "PubMed Abstracts"
} |
[Age-related and seasonal variations in the ATPase system of mitochondria of skeletal muscles in rabbit].
Seasoned variations in the activity of Mg++-ATPase and Mg++-DNP-ATPase have been revealed in studies on ATPase system of mitochondria of skeletal muscles of newborn, 7-, 10-day and adult rabbits. The degree of activation of ATPase by 2-4-DNP did not depend on the age of animals and the season of year. Absolute values for DHPATPhase were lower in young animals in spring. The activity of Mg++- and Mg++-DNP-ATPases and the extent of activation of the enzymes by Mg++ increased with the increase in the age of animals. | {
"pile_set_name": "PubMed Abstracts"
} |
[Correlation between the species radiosensitivity of animals and concentration of AT-rich sequences in DNA].
The authors have revealed a positive and statistically significant correlation between the sum of T-"pure" and T-rich pyrimidine DNA clusters and radiosensitivity of animals of different species. It was demonstrated that the share of a DNA fraction rich in AT-pairs and denaturing within the temperature range from 55 to 75 degrees increases with increasing specific radiosensitivity of animals. | {
"pile_set_name": "PubMed Abstracts"
} |
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