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Theoretical and numerical analysis of the lattice kinetic scheme for complex-flow simulations. The lattice kinetic scheme (LKS) is a modified version of the classical single relaxation time lattice Boltzmann method. Although used for many applications, especially when large variations in viscosity are involved, a thorough analysis of the scheme has not been provided yet. In the context of this work, the macroscopic behavior of this scheme is evaluated through the Chapman-Enskog analysis. It is shown that the additional degree of freedom provided in the scheme allows for an independent control of higher-order moments. These results are further corroborated by numerical simulations. The behavior of this numerical scheme is studied for selected external and internal flows to clarify the effect of the free parameter on the different moments of the distribution function. It is shown that it is more stable than SRT (single relaxation time) when confronted to fully periodic under-resolved simulations (especially for λ≈1). It can also help minimize the error coming from the viscosity-dependence of the wall position when combined with the bounce-back approach; although still present, viscosity-dependence of the wall position is reduced. Furthermore, as shown through the multiscale analysis, specific choices of the free parameter can cancel out the leading-order error. Overall, the LKS is shown to be a useful and efficient alternative to the SRT method for simulating numerically complex flows.
{ "pile_set_name": "PubMed Abstracts" }
Haematoxylin and eosin staining identifies medium to large bacterial aggregates with a reliable specificity: A comparative analysis of follicular bacterial aggregates in axillary biopsies using peptide nucleic acid-fluorescence in situ hybridization and haematoxylin and eosin staining. Although peptide nucleic acid (PNA), fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy (CLSM) are the reference tools in the study of bacterial aggregates/biofilms, it may also be rather time-consuming. This study aimed to investigate the sensitivity and specificity between bacterial aggregates identified by haematoxylin and eosin (HE) staining vs bacterial aggregates in corresponding PNA-FISH samples. Axillary biopsies were obtained in 24 healthy controls. HE-stained and PNA-FISH samples were investigated using traditional light microscopy and CLSM, respectively. The data demonstrate that HE staining identifies large bacterial aggregates (>10 μm) with a sensitivity of 0.43 and specificity of 1. The methods, however, are not equivalent as demonstrated by a McNemar's test (P=.04). Where bacterial aggregates >10 μm in diameter, HE staining may offer a rapid and practical low-cost tool to evaluate bacterial aggregates.
{ "pile_set_name": "PubMed Abstracts" }
The metabolism of chlorpromazine N-oxide in man and dog. 1. The metabolism of chlorpromazine N-oxide was studied in female dogs and adult male humans after a single oral dose. 2. There was extensive metabolism in both species in that between four and seven metabolites were separately identified in urine and faeces. Apart from chlorpromazine N-oxide, chlorpromazine N,S-dioxide was the only isolated metabolite which retained the N-oxide group. The other identified metabolites were chlorpromazine and its 7-hydroxy, sulphoxide, N-desmethyl, 7-hydroxy-N-desmethyl and N-desmethylsulphoxide derivatives. 3. With dog samples, metabolites were separated by h.p.l.c. and individually collected prior to mass spectrometric analysis. With human samples, metabolites were directly subjected to h.p.l.c.-mass spectrometric determination. With all metabolites their structures were confirmed by direct comparison of their mass spectra and chromatographic behaviours with those of authentic samples. 4. The metabolites identified in urine and faeces were for the most part the same in both species, with the exceptions that chlorpromazine N-oxide was identified in the faeces of dog only and 7-hydroxy-N-desmethylchlorpromazine was identified in the urine of man only. 5. The observation of N-oxide compounds in the excreta of both man and dog contrasted with that for the previously studied rat, where no such compounds were detected.
{ "pile_set_name": "PubMed Abstracts" }
HopAS1 recognition significantly contributes to Arabidopsis nonhost resistance to Pseudomonas syringae pathogens. • Plant immunity is activated by sensing either conserved microbial signatures, called pathogen/microbe-associated molecular patterns (P/MAMPs), or specific effectors secreted by pathogens. However, it is not known why most microbes are nonpathogenic in most plant species. • Nonhost resistance (NHR) consists of multiple layers of innate immunity and protects plants from the vast majority of potentially pathogenic microbes. Effector-triggered immunity (ETI) has been implicated in race-specific disease resistance. However, the role of ETI in NHR is unclear. • Pseudomonas syringae pv. tomato (Pto) T1 is pathogenic in tomato (Solanum lycopersicum) yet nonpathogenic in Arabidopsis. Here, we show that, in addition to the type III secretion system (T3SS)-dependent effector (T3SE) avrRpt2, a second T3SE of Pto T1, hopAS1, triggers ETI in nonhost Arabidopsis. • hopAS1 is broadly present in P. syringae strains, contributes to virulence in tomato, and is quantitatively required for Arabidopsis NHR to Pto T1. Strikingly, all tested P. syringae strains that are pathogenic in Arabidopsis carry truncated hopAS1 variants of forms, demonstrating that HopAS1-triggered immunity plays an important role in Arabidopsis NHR to a broad-range of P. syringae strains.
{ "pile_set_name": "PubMed Abstracts" }
In vivo determination of concentration-effect curves of local anaesthetics in man. In clinical use, the concentrations of local anaesthetics at the site of action are unknown. With the method described here, concentrations of local anaesthetics can be predetermined and kept constant at the site of action. In six volunteers, a blister was raised on the ventral surface of the forearm. After removal of the epithelium, the blister base was rinsed continuously with carbogenated Tyrode's solution with and without increasing concentrations of bupivacaine (Carbostesin) for 15 min each. The effects of bupivacaine were determined by changes in the perception (tactile sensation) of drops falling on the blister base from increasing heights. The minimal height at which the drops were just perceived characterized the threshold of perception. With increasing bupivacaine concentrations, threshold increased until the drops were no longer perceived, at a median concentration of 2.48 mmol litre-1 (range 1.24-3.10 mmol litre-1). After the blister base was rinsed with Tyrode's solution, threshold of perception reached baseline values, which was in accordance with an intact blister base.
{ "pile_set_name": "PubMed Abstracts" }
Certolizumab pegol for the treatment of Crohn's disease. Certolizumab pegol is a polyethylene glycolated FAb' fragment of a humanized anti-TNF-alpha monoclonal antibody. This pegylated molecule binds with circulating TNF-alpha and forms an inactive complex that is then eliminated from the body. The drug has been shown to be better than placebo in the treatment of Crohn's disease and maintaining a clinical response in adult patients with moderate-to-severe active disease who have had an inadequate response to conventional therapy, and the treatment of adults with moderately to severely active rheumatoid arthritis. Comparative trials with an active control group are lacking. The most common adverse reactions include abdominal pain, diarrhea, injection site reactions and infection. All necessary live and attenuated vaccines should be given prior to the initiation of certolizumab pegol therapy, patients should be evaluated for TB risk factors and tested for latent TB prior to initiating therapy, and the initiation of therapy should be avoided if the patient has an active infection. Concomitant use with anakinra is not recommended because of the increased risk of serious infections and neutropenia. Therapy should be discontinued if the patient develops a serious infection during therapy.
{ "pile_set_name": "PubMed Abstracts" }
Orthostatic hypotension: From pathophysiology to clinical applications and therapeutic considerations. Orthostatic hypotension (OH), that is blood pressure fall when standing from the supine to the erect position, is a common cardiovascular disorder, highly prevalent in elderly and frail individuals and in patients with multiple comorbidities. Orthostatic hypotension is considered a manifestation of dysfunction of the autonomic nervous system, caused or facilitated by several neurological or non-neurological diseases and conditions, while its clinical significance is increasingly recognized as a cause of impairment of quality of life and potentially of worse outcomes. Indeed, OH has been extensively studied and numerous prospective cohort studies support its association with adverse events, including coronary artery disease, heart failure, stroke, cognitive dysfunction, and, most importantly, mortality rates. Specific pharmacological and non-pharmacological interventions have been established for the treatment of OH. However, randomized data evaluating the impact of therapeutic interventions on morbidity and mortality outcomes are lacking. Thus, despite that OH seems to have important prognostic implications indicated by several reported associations with adverse events, it remains unclear whether OH treatment could improve prognosis. In the present review, we discuss the clinical applications associated with ΟΗ by outlining the current perspectives on ΟΗ definition, diagnosis, pathophysiology, prognostic role, and treatment.
{ "pile_set_name": "PubMed Abstracts" }
Do missing data influence the accuracy of divergence-time estimation with BEAST? Time-calibrated phylogenies have become essential to evolutionary biology. A recurrent and unresolved question for dating analyses is whether genes with missing data cells should be included or excluded. This issue is particularly unclear for the most widely used dating method, the uncorrelated lognormal approach implemented in BEAST. Here, we test the robustness of this method to missing data. We compare divergence-time estimates from a nearly complete dataset (20 nuclear genes for 32 species of squamate reptiles) to those from subsampled matrices, including those with 5 or 2 complete loci only and those with 5 or 8 incomplete loci added. In general, missing data had little impact on estimated dates (mean error of ∼5Myr per node or less, given an overall age of ∼220Myr in squamates), even when 80% of sampled genes had 75% missing data. Mean errors were somewhat higher when all genes were 75% incomplete (∼17Myr). However, errors increased dramatically when only 2 of 9 fossil calibration points were included (∼40Myr), regardless of missing data. Overall, missing data (and even numbers of genes sampled) may have only minor impacts on the accuracy of divergence dating with BEAST, relative to the dramatic effects of fossil calibrations.
{ "pile_set_name": "PubMed Abstracts" }
Acute effects of nitric oxide and cyclic GMP on human myocardial contractility. Evidence that the activity of nitric oxide synthase and the generation of nitric oxide (NO) within the myocardium are enhanced in several cardiovascular disorders is increasing. Findings whether NO exerts a direct effect on cardiac contractility are contradictory. Therefore, the direct effect of the NO donor sodium nitroprusside (SNP) on isometric force of contraction of human atrial and ventricular myocardium was investigated, and the question was addressed whether the effects of NO on cardiac contractility are mediated via cGMP. Experiments were performed on isolated electrically driven (1 Hz, 37 degrees C) human right atrial trabecula and left ventricular papillary muscle preparations from nonfailing and terminally failing hearts. SNP led to a concentration-dependent decrease of force of contraction (FOC) with a maximum effect at 100 micromol/l. In atrial trabecula, SNP (100 micromol/l) caused an acute decrease in basal FOC as well as in FOC after application of isoprenaline or IBMX by 12.5 +/- 5% (P < .05), 16.6 +/- 3.7% (P < .05) and 18.3 +/- 4.2% (P < .05), respectively. The negative inotropic effects could be attenuated by the guanylyl cyclase inhibitor methylene blue. In papillary muscle preparations, NO release caused a maximum decrease in basal and in isoprenaline-enhanced FOC of 11.0 +/- 1.9% (P < .05) and 23.6 +/- 1.5% (P < .05), respectively. In the presence of isoprenaline, the reduction of FOC was less pronounced in failing than in nonfailing papillary muscles. 8-bromo-cGMP caused a 38.2 +/- 5.2% decrease in atrial trabecula contractility. Both SNP and 8-bromo-cGMP caused a shortening of the contractile twitch with a premature onset of relaxation. As determined by radioimmunoassay, exposure of atrial trabecula to SNP (100 micromol) led to a 6-fold increase in myocardial cGMP concentrations, which could be attenuated by methylene blue. In conclusion, NO exerts a negative inotropic effect on human atrial and ventricular myocardium which seems to be mediated via generation of cGMP. The release of NO within the myocardium in a variety of cardiovascular disorders might explain decreases in cardiac contractility. The control of NO release could be an important target for future therapeutical interventions in these pathological conditions.
{ "pile_set_name": "PubMed Abstracts" }
Computerized tracking to train dexterity after cerebellar tumour: a single-case experimental study. In a child with pure ataxia after tumour removal, does dexterity training at the right elbow improve dexterity at the right elbow? Does improvement in dexterity transfer to improvement in upper limb activity? Single-case experimental study with 2-week baseline, 2-week intervention and 2-week follow-up phases and assessment by a blinded assessor. A 5-year old child 3 years after surgical resection of a low-grade cerebellar tumour underwent to dexterity training. Dexterity was measured using a Finger-to-Nose Test and upper limb activity was measured using the 9-Hole Peg Test. Measures were collected every 2 or 3 days over the 6-week period of the study. Finger-to-Nose Test showed visible but not statistical improvement between baseline and intervention phases in terms of smoothness of movement. On withdrawal of the intervention, visual analysis showed that scores remained at the same level. The 9-Hole Peg Test showed visible but not statistical improvement in terms of speed and smoothness of movement. On withdrawal of the intervention, visual analysis showed that improvement in speed was maintained during follow-up, but smoothness decreased. There is some evidence that dexterity can be trained and that improvement carries over to activity.
{ "pile_set_name": "PubMed Abstracts" }
Mercury speciation in sea food by flow injection cold vapor atomic absorption spectrometry using selective solid phase extraction. An on-line inorganic and organomercury species separation, preconcentration and determination system consisting of cold vapor atomic absorption spectrometry (CV-AAS or CV-ETAAS) coupled to a flow injection (FI) method was studied. The inorganic mercury species was retained on a column (i.d., 3 mm; length 3 cm) packed to a height of 0.7 cm with a chelating resin aminopropyl-controlled pore glass (550 A) functionalized with [1,5-bis (2 pyridyl)-3-sulphophenyl methylene thiocarbonohydrazyde] placed in the injection valve of a simple flow manifold. Methylmercury is not directly determined. Previous oxidation of the organomercurial species permitted the determination of total mercury. The separation of mercury species was obtained by the selective retention of inorganic mercury on the chelating resin. The difference between total and inorganic mercury determined the organomercury content in the sample. The inorganic mercury was removed on-line from the microcolumn with 6% (m/v) thiourea. The mercury cold vapor generation was performed on-line with 0.2% (m/v) sodium tethrahydroborate and 0.05% (m/v) sodium hydroxide as reducing solution. The determination was performed using CV-AAS and CV-ETAAS, both approaches have been used and compared for the speciation of mercury in sea food. A detection limit of 10 and 6 ng l(-1) was achieved for CV-AAS and CV-ETAAS, respectively. The precision for 10 replicate determinations at the 1 microg l(-1) Hg level was 3.5% relative standard deviation (R.S.D.), calculated from the peak heights obtained. Both approaches were validated with the use of two certified reference materials and by spiking experiments. By analyzing the two biological certified materials, it was evident that the difference between the total mercury and inorganic mercury corresponds to methylmercury. The concentrations obtained by both techniques were in agreement with the certified values or with differences of the certified values for total Hg(2+) and CH(3)Hg(+), according to the t-test for a 95% confidence level. It is amazing how this very simple method is able to provide very important information on mercury speciation.
{ "pile_set_name": "PubMed Abstracts" }
M1 is a major subtype of muscarinic acetylcholine receptors on mouse colonic epithelial cells. Muscarinic acetylcholine receptors (mAChRs) are major regulators of gut epithelial functions. However, the precise subtype composition has not been clarified. We characterized the pharmacological profile of mAChRs on mouse colonic crypts, employing [(3)H]-N-methyl scopolamine chloride as a radioligand and several subtype-selective chemicals, and the functional aspect by measuring short-circuit current (I sc) in Ussing chambers and by evaluating MAP kinase phosphorylation in mouse colonic mucosal sheets. The mAChRs were detected on the crypts (K d = 163.2 ± 32.3 pM, B max = 47.3 ± 2.6 fmol/mg of total cell protein). Muscarinic toxin 7 (MT-7, M1 subtype selective) gave a displacement curve with high affinity, but there was a part insensitive to MT-7 (18.8 ± 0.4 % of the total specific binding). The MT-7-insensitive component was displaced completely by darifenacin (M3 selective) with high affinity. ACh induced an increase in I sc, which was significantly enhanced by MT-7 but was completely inhibited by darifenacin or atropine. Colitis induction resulted in a significant decrease in the density of mAChRs, which occurred mainly in the MT-7-sensitive component (M1 subtype). Immunological experiments exhibited a reduction of M1 but not of M3 signal after colitis induction. Muscarinic stimulation induced an increase in MAP kinase phosphorylation, which was completely suppressed by MT-7 and was attenuated by inflammation, in mouse colonic epithelium. These results suggest that mAChRs in mouse colonic epithelial cells consist of two subtypes, M1 (80 %) and M3 (20 %). The major M1 subtype was likely to regulate epithelial chloride secretion negatively and was susceptible to inflammation and may be relevant to inflammatory gut dysfunction.
{ "pile_set_name": "PubMed Abstracts" }
Oritavancin--an investigational glycopeptide antibiotic. Antibiotics save countless lives each year; however, increasing rates of drug-resistant bacteria have limited antibiotic selection. Currently, there are few available options for treating resistant Gram-positive organisms. Oritavancin, a novel glycopeptide antibiotic with bactericidal activity, has been developed and recently completed the first round of Phase III clinical trials for the treatment of complicated skin and skin structure infections. Investigations into oritavancin's efficacy will be explored in catheter-related bacteraemia and nosocomial pneumonia. Oritavancin demonstrates similar activity to vancomycin but possesses extended activity against vancomycin-resistant Staphylococcus and Enterococcus. The pharmacokinetics and pharmacodynamics of oritavancin appear to be favourable and once-daily dosing is likely. The incidence of multi-drug resistant bacteria is increasing and explorations into additional treatment options are essential. Further development of oritavancin is necessary to determine clinical efficacy.
{ "pile_set_name": "PubMed Abstracts" }
[Study on prevention of paraplegia during occlusion blockade of the thoracic aorta--examination of the evoked potential in the motor nerve induced by stimulation of the motor area of cerebral cortex]. In an attempt to trace the motor neurons in the descending tract of the motor system of the spinal cord and anterior horn, we have succeeded in inducing a potential in the peripheral motor nerve (evoked motor nerve action potential: EMNAP) by stimulating the motor area of the cerebral cortex in dogs, we have examined the characteristics of this potential. Besides the EMNAP, we have induced the conventional somatosensory evoked potential (SSEP) and evoked spinal cord potential (ESCP) during spinal ischemia. These are compared with each other, with theoretical predictions and with pathological findings. EMNAP possessed a biphasic negative potential (N1, N2) and subsequent multiphasic potential (N3+n) during the latency 10-18 msec. The stimulation threshold of EMNAP in the lower limbs was the lowest near the longitudinal fissure in the anterior part of the cerebral crucial groove. The amplitude of N2 and N3+n of EMNAP decreased under the condition of frequent stimulation. N2 and N3+n did not disappear after the dorsal root was severed. When the three potentials of EMNAP, SSEP, and ESCP were simultaneously induced, the left subclavian artery was occluded, the descending aorta was partially occluded immediately under the bifurcation of this artery, and the pressure of the partially occluded periphery was gradually reduced, EMNAP alone disappeared at 45.2 +/- 6.2 mmHg. Although ESCP and SSEP did not disappear even when partial occluding was continued for 90 minutes under this condition, histopathological findings obtained by formalin perfusion fixation showed ischemic disorder of the anterior horn cells when compared with the normal group fixed in the same way. EMNAP was considered to be induced through the alpha-motoneuron in the anterior horn of the spinal cord, and disappeared under the critical ischemia in which ESCP and SSEP do not disappear. Disorder of the anterior horn cells were also observed histopathologically. Direct monitoring of the alpha-motoneuron in the anterior horn, which is most susceptible to disorders, seems appropriate as a method for preventing paraplegia. EMNAP may be useful for monitoring motor function of the spinal cord not only during chest surgery but also for other types of diagnosis and treatment.
{ "pile_set_name": "PubMed Abstracts" }
Overdentures: an alternative implant methodology for edentulous patients. Two groups of elderly edentulous patients with implant-supported mandibular overdentures were compared. There were 25 patients with an average age of 62.2 years and 34 patients with an average age of 68.9 years treated in Toronto and in Bern, respectively. A high incidence of compromised general health was found in both groups. All patients had been treated in the years 1984 through early 1987 and had worn their implant-supported overdentures for the previous 5 years. Regular monitoring of the patients was done by two investigators using periodontal and radiographic parameters. Two different implant systems were used: Brånemark fixtures in Toronto and ITI implants in Bern. Most overdentures were retained by only two implants in both groups. The 5-year longitudinal data show a similar high success rate (> 90%) for both patient groups.
{ "pile_set_name": "PubMed Abstracts" }
[Epithelial surface of trachea in adult male albino rats (author's transl)]. The epithelial surface of trachea in adult male albino rats is studied by reflection scanning electron microscopy (REM). Surface morphology of the tracheal epithelium shows extensive individual and regional variability. Identical surface morphology may result by different causal factors. Regional morphology is presented by a mapping of the epithelial surface. Special attention is given to the structure of the cilia. Furthermore the morphology and distribution of possible receptor cell terminals is shown. The validity of reflection scanning electron microscopic studies for identifying the patho-histogenetic action of air pollutants is discussed.
{ "pile_set_name": "PubMed Abstracts" }
Subunit Protein Vaccine Delivery System for Tuberculosis Based on Hepatitis B Virus Core VLP (HBc-VLP) Particles. Despite the development of modern medicine, tuberculosis (TB), caused by the pathogenic bacterium, Mycobacterium tuberculosis (Mtb), remains one of the deadliest diseases. This bacterium can lay dormant in individuals and get activated when immunity goes down and has also shown considerable prowess in mutating into drug resistant forms. The global emergence of such drug resistant Mtb and the lack of efficacy of Bacille Calmette Guérin (BCG), the only vaccine available so far, have resulted in a situation which cries out for a safe and effective tuberculosis vaccine.Number of different strategies has been used for developing new anti-TB vaccines and several protective antigens have been identified so far. One strategy, the use of protein subunits, has the potential to develop into a powerful tuberculosis vaccine, not only because of its efficacy and safety, but also because they are economical. The proper delivery of protein subunit vaccines with adjuvants or novel delivery systems is necessary for inducing protective immune responses. The available adjuvants or delivery systems are inadequate for generating such a response. In the present method, we have constructed a vaccine delivery system for tuberculosis based on Virus-Like Particles (VLPs). Hepatitis B Virus core antigen gene was recombinantly modified using Overlap Extension PCR (OEPCR). The final construct was designed to express HBc-VLP carrying external antigen (fusion VLP). Mycobacterium tuberculosis antigen CFP-10 was used for the construction of fusion VLP. The recombinant gene for the construct was cloned into a pET expression system and transformed into E. coli BL21(DE3) and induced with IPTG to express the protein. The fusion protein was purified using the Histidine tag and allowed to form VLPs. The preformed VLPs were purified by sucrose density gradient centrifugation. The VLPs were characterized using Transmission Electron Microscopy (TEM).
{ "pile_set_name": "PubMed Abstracts" }
Consumption of vegetables, fruit, and antioxidants during pregnancy and wheeze and eczema in infants. Two previous cohort studies showed inverse relationships between maternal vitamin E and zinc intake during pregnancy and the risk of wheeze and/or asthma in the offspring. We investigated the association between maternal intake of vegetables, fruit, and selected antioxidants during pregnancy and the risk of wheeze and eczema in the offspring aged 16-24 months. Subjects were 763 Japanese mother-child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Data on symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood. Higher maternal intake of green and yellow vegetables, citrus fruit, and beta-carotene during pregnancy was significantly associated with a reduced risk of eczema, but not wheeze, in the offspring {adjusted odds ratios (ORs) between extreme quartiles [95% confidence intervals (CIs)] = 0.41 (0.24-0.71), 0.53 (0.30-0.93), and 0.52 (0.30-0.89), respectively}. Maternal vitamin E consumption during pregnancy was significantly inversely related to the risk of infantile wheeze, but not eczema [adjusted OR (95% CI) = 0.54 (0.32-0.90)]. No statistically significant exposure-response associations were observed between maternal intake of total vegetables, vegetables other than green and yellow vegetables, total fruit, apples, alpha-carotene, vitamin C, or zinc and the risk of wheeze or eczema in the children. Higher maternal consumption of green and yellow vegetables, citrus fruit, and beta-carotene during pregnancy may be protective against the development of eczema in the offspring. Higher maternal vitamin E intake during pregnancy may reduce the risk of infantile wheeze.
{ "pile_set_name": "PubMed Abstracts" }
[An initial exploration of the application of transanal endoscopic microsurgery in rectal cancer patients with clinical complete response after neoadjuvant chemoradiotherapy]. Objective: To preliminarily explore the value of transanal endoscopic microsurgery (TEM) in rectal cancer patients with clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: Using descriptive case series method, Clinical data of 13 patients who met the criteria of nCRT and were considered to be cCR after MRI or CT scanning, digital rectal examination and colonoscopic biopsy, as well as no lymph node or distant metastasis were found, then underwent TEM from 2013 to 2016 at the Department of General Surgery of Peking Union Medical College Hospital were collected retrospectively. A 3-course combination of capecitabine and oxaliplatin (XELOX) was used for chemotherapy. Besides, a 6MV-X ray radiation was used as radiotherapy simultaneously. Six to eight weeks after completion of radiotherapy, a preoperative assessment was carried out with intrarectal ultrasound, MRI, or pelvic abdominal CT examination. TEM was performed afterwards with informed consent. Postoperative pathological findings and follow-up results were used to evaluate the value of diagnosis and treatment of TEM on those patients. Results: There were 8 males and 5 females with a median age of 63 (27-80) years. Preoperative examination showed that the lesions were located in the anterior wall in 3 cases, the posterior wall in 3 cases, the left side wall in 4 cases, and the right side wall in 3 cases. Before nCRT, the distance between tumor and anal margin was (4.8±1.1) (2.0-7.5) cm; after nCRT, this distance was (5.2±1.3) (3.0-7.5) cm. All the 13 patients underwent extended local resection of rectal cancer via TEM with the placement of urethral catheter. The average operative time was (52.2±3.7) (42-70) minutes, and the average intraoperative blood loss was (19.2±2.8) (5-30) ml. All the patients could engage in daily activities on postoperative day 1, and could cater themselves orally on postoperative day 2. The main discomfort was postoperative anal pain and foreign body sensation (n=5), which could be alleviated by non-steroidal anti-inflammatory drugs. One case had postoperative lung infection and was cured by antibiotic treatment. One case had urinary retention after removing urine catheter, and then a urine catheter was re-inserted. Average postoperative hospital stay was (2.8±2.4) (2-12) days. All specimens were completely resected via TEM. Histopathological examination confirmed that 7 specimens had achieved pathologic complete response (pCR) and the other 6 specimens had obtained partial tumor response of CAP grade 2. Seven patients with pCR received a median follow-up of 24 (8-48) months and no local recurrence or distant metastasis was reported during follow-up period. Among these 7 cases, one developed defecation dysfunction after discharge, mainly for defecation pain and even dare to defecate, who returned to normal defecation within 2 months after surgery; One developed severe anal pain within six months after surgery and the pain disappeared after symptomatic pain relief. The other 6 patients with CAP grade 2 refused to undergo further radical operation because of their strong desire in preserving anus, and received remedial adjuvant chemotherapy instead. Conclusion: For rectal cancer patients with cCR after nCRT, TEM does have certain application values if the patient has a strong desire to preserve anus.
{ "pile_set_name": "PubMed Abstracts" }
Association of macronutrient consumption with arterial aging in adults without clinically overt cardiovascular disease: a 5-year prospective cohort study. There is limited and inconsistent evidence regarding longitudinal effects of macronutrients on blood pressure (BP) haemodynamics and arterial aging in populations without cardiovascular disease (CVD). We aimed to prospectively investigate potential association of dietary macronutrients with long-term changes in peripheral and central haemodynamics and arterial stiffness. One hundred and fifteen subjects (46.7 ± 8.73 years, 70 women), free of clinically overt CVD were consecutively recruited. Dietary macronutrient intake was evaluated using 3-day food records at baseline. Aortic stiffness and arterial wave reflections were assessed at baseline and in one follow-up visit 5 years later by pulse wave velocity (PWV) and augmentation index (AI), respectively. Individuals with the highest consumption of saturated fatty acids (SFA) presented the highest rate of progression in PWV, AI and aortic diastolic BP (p < 0.05 for all) after adjustment for age, gender, smoking, body mass index, hyperlipidemia, insulin resistance, changes in systolic BP and treatment with antihypertensive and hypolipidemic drugs. After similar multivariable adjustments, high consumption of carbohydrates was associated with higher progression of AI, whereas high consumption of monounsaturated fatty acids (MUFA) and fibre with lower progression in aortic and peripheral systolic and diastolic BP (p < 0.05 for all). In subjects without CVD, high consumption of SFA is related to accelerated arterial stiffening, while high consumption of MUFA and fibre and low intake of carbohydrates is associated with attenuated progression in blood pressure and arterial wave reflections, respectively. These findings expand current knowledge on the association of macronutrient consumption with arterial aging in the general population.
{ "pile_set_name": "PubMed Abstracts" }
A development of conceptual framework for structured data entry in procedure. This study was performed to provide the well-designed conceptual framework of clinical contents in procedures that enables clinicians to execute structured data entry at the point of care. The conceptual framework was developed through applying the ISO's conceptual framework for clinical contents modeling, semantic structuring, and using the Entity-Attribute-Value (EAV) model for data representation. We provided the conceptual framework in procedures, including twenty-one attributes and structured clinical data sets for operation records that are six diseases based on the conceptual framework.
{ "pile_set_name": "PubMed Abstracts" }
Probability of a false-negative HIV antibody test result during the window period: a tool for pre- and post-test counselling. Failure to understand the risk of false-negative HIV test results during the window period results in anxiety. Patients typically want accurate test results as soon as possible while clinicians prefer to wait until the probability of a false-negative is virtually nil. This review summarizes the median window periods for third-generation antibody and fourth-generation HIV tests and provides the probability of a false-negative result for various days post-exposure. Data were extracted from published seroconversion panels. A 10-day eclipse period was used to estimate days from infection to first detection of HIV RNA. Median (interquartile range) days to seroconversion were calculated and probabilities of a false-negative result at various time periods post-exposure are reported. The median (interquartile range) window period for third-generation tests was 22 days (19-25) and 18 days (16-24) for fourth-generation tests. The probability of a false-negative result is 0.01 at 80 days' post-exposure for third-generation tests and at 42 days for fourth-generation tests. The table of probabilities of falsely-negative HIV test results may be useful during pre- and post-test HIV counselling to inform co-decision making regarding the ideal time to test for HIV.
{ "pile_set_name": "PubMed Abstracts" }
A histological study of the hph-1 mouse mutant: an animal model of phenylketonuria and infantile hypertrophic pyloric stenosis. To quantify the chronological sequence of changes in the morphology and immunoreactivity for neurotransmitters in the pylorus of an animal model of infantile hypertrophic pyloric stenosis and phenylketonuria. Thirty specimens of pylorus from hph-1 mice and age/sex matched controls (age range: 10-180 days) were examined using conventional histology and immunohistochemistry for a variety of antigens: protein gene product 9.5, a pan neuronal marker; vasoactive intestinal polypeptide; nitric oxide synthase two antigens coalesced to the same inhibitory neurons in humans; substance P, a potent excitatory neurotransmitter; and calcitonin gene related peptide, a neurotransmitter implicated in the somatic afferent innervation of the stomach. The changes in the morphology of the muscle layers were quantified and statistically analysed for each age group (10, 20, 40, 90 and 180 days). Between 10 and 90 days of age, all muscle layers of the hph-1 mice were hypertrophied, for example, 10 days, hph-1 longitudinal muscle mean diameter = 3.4, control = 1.8; hph-1 circular muscle width = 11.5, control = 4.7. The hph-1 mice were significantly smaller during this period (40 days, hph-1 weight = 10 g, control = 25 g). There was no change in the pattern of expression of the antigens examined within the hph-1 mice compared with the controls. Hph-1 mice develop a transient smooth muscle hypertrophy of the pylorus attended by gastric distension and failure to gain weight. These changes resolve as the pyloric muscle hypertrophy resolves.
{ "pile_set_name": "PubMed Abstracts" }
Screening for abdominal aortic aneurysm reduces overall mortality in men. A meta-analysis of the mid- and long-term effects of screening for abdominal aortic aneurysms. Four randomised controlled trials of screening older men for abdominal aortic aneurysms (AAA) have been completed. A meta-analysis was performed to examine the pooled effects of screening on both mid- and long-term AAA-related and total mortality, and operations for AAA. Pooled mid-term (3(1/2)-5 years) and long term (7-15 years) effects were calculated as odds-ratios (ORs) with 95% confidence intervals in fixed effect models. Long-term data from the West Australian trial were limited to all-caurse deaths. Heterogeneity between the studies was assessed by the chi(2)-test. In cases of heterogeneity, random effect models were used. The pooled mid-term analysis showed the offer of screening caused a significant reduction in AAA related mortality (OR=0.56, 95% C.I. 0.44,0.72), and emergency operations (OR=0.55, 95% C.I.: 0.39; 0.76), while the number of elective operations increased significantly (OR=3.27, 95% C.I.: 2.14; 5.00). Overall mortality was reduced, but not significantly (OR=0.94, 95% C.I.: 0.86; 1.02). The long-term results also showed a significant reduction in AAA-related mortality (OR=0.47, 95% C.I.: 0.25; 0.90), overall mortality (OR=0.94, 95% C.I.: 0.92; 0.97) and emergency operations (OR=0.48, 95% C.I.: 0.28; 0.83), while the number of elective operations increased significantly (OR=2.81, 95% C.I.: 2.40; 3.30). Population screening for AAA reduces AAA-related and overall mortality, however local differences may exits which could influence cost effectiveness of screening.
{ "pile_set_name": "PubMed Abstracts" }
Cadmium binding to a histidine-rich glycoprotein from marine mussel blood plasma: potentiometric titration and equilibrium speciation modeling. Cadmium-binding parameters (conditional stability constants and carrying capacities) of Mytilus edulis blood plasma histidine-rich glycoprotein (HRG) were investigated by potentiometric titrations using a Cd ion-specific electrode. Titration data were applied to a single-component complexation model and expressed as Scatchard plots that were analyzed using the graphical curve peeling method and the algebraic statistical mechanical method. These sets of binding parameters, derived for the purified HRG, were subsequently entered into the geochemical speciation model MINTEQA2 and then used to simulate the experimental titration, thereby determining which set of log K and CL values best represented the titration data. The Cd binding to HRG was best described by a two-class model with log K values of 7.65 +/- 0.10 and 5.41 +/- 0.06 M-1 and carrying capacities of 6.0 +/- 1.2 and 9.5 +/- 0.4 sites/molecule, respectively. At concentration of total Cd measured in the blood plasma of field-collected mussels (< or = 2 x 10(-7) M), plasma Cd speciation would be dominated by the strong affinity sites of HRG (> 93.5% of total Cd binds to HRG), whereas HRG itself would only be 0.05% saturated with Cd, indicating a high-capacity, apparently nonsaturable Cd transport system.
{ "pile_set_name": "PubMed Abstracts" }
Ethylene biosynthesis and perception during ripening of loquat fruit (Eriobotrya japonica Lindl.). In order to gain insights into the controversial ripening behavior of loquat fruits, in the present study we have analyzed the expression of three genes related to ethylene biosynthesis (ACS1, ACO1 and ACO2), two ethylene receptors (ERS1a and ERS1b), one signal transduction component (CTR1) and one transcription factor (EIL1) in peel and pulp of loquat fruit during natural ripening and also in fruits treated with ethylene (10μLL-1) and 1-MCP (10μLL-1), an ethylene action inhibitor. In fruits attached to or detached from the tree, a slight increase in ethylene production was detected at the yellow stage, but the respiration rate declined progressively during ripening. Accumulation of transcripts of ethylene biosynthetic genes did not correlate with changes in ethylene production, since the maximum accumulation of ACS1 and ACO1 mRNA was detected in fully coloured fruits. Expression of ethylene receptor and signaling genes followed a different pattern in peel and pulp tissues. After fruit detachment and incubation at 20°C for up to 6days, ACS1 mRNA slightly increased, ACO1 experienced a substantial increment and ACO2 declined. In the peel, these changes were advanced by exogenous ethylene and partially inhibited by 1-MCP. In the pulp, 1-MCP repressed most of the changes in the expression of biosynthetic genes, while ethylene had almost no effects. Expression of ethylene perception and signaling genes was barely affected by ethylene or 1-MCP. Collectively, a differential transcriptional regulation of ethylene biosynthetic genes operates in peel and pulp, and support the notion of non-climacteric ripening in loquat fruits. Ethylene action, however, appears to be required to sustain or maintain the expression of specific genes.
{ "pile_set_name": "PubMed Abstracts" }
Biological vs. conventional combination treatment and work loss in early rheumatoid arthritis: a randomized trial. The introduction of biological tumor necrosis factor inhibitors has improved the treatment of rheumatoid arthritis (RA) but at a substantial cost. These drugs have been shown to lead to superior radiological outcomes compared with a combination of conventional disease-modifying antirheumatic drugs over 2 years. To investigate whether radiological superiority translates into better work loss outcomes. Multicenter, 2-arm, parallel, randomized, active-controlled, open-label trial. Patients with early RA (symptom duration <1 year) were recruited from 15 rheumatology clinics in Sweden from October 1, 2002, through December 31, 2005. The study population was restricted to working-age patients (aged <63 years). Patients who did not achieve low disease activity after 3 to 4 months of methotrexate therapy were randomized to receive additional biological treatment with infliximab or conventional combination treatment with sulfasalazine plus hydroxychloroquine. Monthly sick leave and disability pension days 21 months after randomization retrieved from the nationwide Swedish Social Insurance Office register. Main analyses were by intention to treat, including all patients, and adjusted for baseline sick leave and disability pension. Of 204 eligible patients, 105 were randomized to biological and 99 to conventional treatment. Seven patients in the biological and 4 in the conventional treatment group never received the study drug, and 72 and 52 patients, respectively, followed the study per protocol for 21 months. The baseline mean (SD) work loss was 17 (13) d/mo (median, 16 d/mo) in both groups (mean difference, 0.6 d/mo; 95% CI, -3.0 to 3.9). The mean changes in work loss at 21 months were -4.9 d/mo in the biological and -6.2 d/mo in the conventional treatment group (adjusted mean difference, 1.6 d/mo; 95% CI, -1.2 to 4.4). Including only patients receiving at least 1 dose of assigned treatment, the adjusted mean difference was 1.5 d/mo (95% CI, -1.5 to 4.4), and in per-protocol analysis the adjusted mean difference was 0.3 d/mo (95% CI, -2.8 to 3.8). The radiological superiority of biological compared with conventional combination therapy did not translate into better work loss outcomes in patients with early RA who had experienced an insufficient response to methotrexate. clinicaltrials.gov Identifier: NCT00764725.
{ "pile_set_name": "PubMed Abstracts" }
Inhibition by lysosomotropic amines of dog thyroid secretion in vitro. The lysosomotropic amines are well-known inhibitors of lysosomal protein degradation. These drugs were used in dog thyroid slices to ascertain the role of the lysosome in thyroglobulin hydrolysis and in hormone secretion. NH4Cl (1-20 mM) and chloroquine (5-500 microM) inhibited, in a concentration-dependent manner, the TSH-stimulated secretion. The high concentrations of these compounds also inhibited the basal secretion. The inhibition was not toxic since 1) the nonbutanol extractable iodine, an index of follicle disruption, was not increased, except slightly by 20 mM NH4Cl; 2) the compounds did not inhibit the TSH-induced stimulation of protein iodination; 3) the inhibition of secretion caused by these compounds was reversible; 4) the ultrastructural changes induced by NH4Cl were reversed after its withdrawal. The inhibition of secretion was presumably related to the lysosomal trapping of the drugs because: 1) the time lag for the fall in secretion rate after drug addition was shorter than for the inhibition of secretion at the level of pseudopod formation by carbamylcholine and cytochalasin B; 2) for NH4Cl this delay and the degree of inhibition were modulated by the [H+] gradient between the medium and the lysosome; 3) 20 min after NH4Cl addition, 92% of the lysosomes were vacuolated and swollen (median section area, 126 mu2 vs. 50 mu2 for the controls) and 8% of the lysosomes were swollen and still dense (median, 206 mu2); 20 min after chloroquine addition, 90% of the lysosomes remained dense and had a significantly higher section area (median, 79 mu2) than the controls (P less than 0.001), whereas 10% of the lysosomes were vacuolated and large (median area, 438 mu2). The number of pseudopods measured by scanning electron microscopy significantly decreased only after 1 h (P less than 0.001). This late decrease could not account for the early block of secretion and suggested a lack of membrane recycling. In conclusion, lysosomotropic amines interfere with a post phagocytotic, presumably lysosomal, step in secretion by dog thyroid. These data constitute the first biochemical evidence in the intact cell of the role of lysosomes in TSH-induced thyroglobulin hydrolysis and thyroid hormone secretion.
{ "pile_set_name": "PubMed Abstracts" }
Zollinger-Ellison syndrome associated with parathyroid adenomas and ectopic gastric tissue in the lower esophageal mucosa. A rare case of the Zollinger-Ellison syndrome associated with hyperparathyroidism and ectopic gastric tissue in the lower esophageal mucosa is reported. Preoperatively the patient, a 53-year-old woman, had hyperchlorhydria and her fasting serum gastrin concentration was mildly elevated. There was a considerable increase in the gastric acid output and concentration of serum calcium after secretin infusion. At operation the patient had a gastric ulcer 10 cm in diameter, an islet cell tumour of the pancreas 14 cm in diameter, and ectopic gastric mucosa in the distal third of the esophagus. A gastrectomy was perfomed, the pancreatic tumour excised and part of the distal esophagus removed through a left thoracotomy. Four months after the operation the gastrin concentration had returned to low normal, but the serum calcium values remained high. One month later two parathyroid adenomas were removed which effectively cured the hypercalcemia.
{ "pile_set_name": "PubMed Abstracts" }
[Assessment and application for the results of global intercalibration study of typical perfluoroalkyl substances in foods and human matrices]. To analyze the result of global intercalibration study of typical perfluoroalkyl substances( PFASs) and their typical isomers in foods, human milk and serum from 2010 to 2017 and discuss the application of the result in quality assurance and control. Z-scores were employed to assess the result of PFASs and their typical isomers from global intercalibration study. Combined with the concentrations of the samples, we have also analyzed the key point of the method. The absolute values of the Z-scores of most PFASs and their typical isomers were less than 1, indicating that the concentrations determined by our laboratory were satisfactory. The problems in the method could be found in time by participating in the global intercalibration study. Therefore we can improve the method to ensure the accuracy of the data and provide the effective technical support for determining the levels of PFASs and their typical isomers in foods, human milk and serum in China.
{ "pile_set_name": "PubMed Abstracts" }
[The effect of steroid therapy on post adenotonsillectomy recovery]. Previous studies on dexamethasone's antiemetic and antinflammatory potential in patients undergoing adenotonsillectomy have produced conflicting results. To determine the effect of intraoperative I.V. single dose dexamethasone on recovery and complications after adenotonsillitis while anesthesia techniques, surgical techniques and perioperative treatment are standardized. Prospective randomized, controlled study. A total of 230 patients aged 2-16 years undergoing elective adenotonsillectomy enrolled in the study. Patients were randomly assigned to receive i.v. dexamethasone 0.5 mg/kg (study group), or no treatment (control group). Pain score, emesis, oral intake and bleeding were assessed on the first and tenth postoperative day. Overall, 204 completed the study, 101 in the study group, 103 in the control group. It was found that intraoperative single I.V. dexamethasone significantly reduces emesis during the first postoperative day (P < 0.0001), significantly reduces pain score on the first (P < 0.0001), and tenth postoperative day (P = 0.053), significantly increases the number of patients returning to soft diet on the first postoperative day (P = 0.0002) and normal diet on the tenth postoperative day (P < 0.0001). No significant difference in bleeding tendency between the two groups was noted (P = 0.7202). Intraoperative injection of I.V. dexamethasone 0.5 mg/kg effectively reduced post adenotonsillectomy morbidity.
{ "pile_set_name": "PubMed Abstracts" }
Local control after the use of adjuvant electron beam intraoperative radiotherapy in patients with high-risk head and neck cancer: the UCSF experience. We assess the effect of electron beam intraoperative radiotherapy (EB-IORT) on local-regional control and any associated complications in patients with locally advanced or recurrent head and neck cancer. The records of 30 patients with head and neck cancer who received EB-IORT from March 1991 to December 1994 were retrospectively reviewed. The indications for EB-IORT in 25 patients were recurrent or persistent disease despite previous treatment with full-course external-beam radiotherapy and/or one or more resections. In five other cases the indication was extensive primary disease with multiple high-risk factors for local recurrence, including extension into the base of the skull, advanced extensive disease, and perineural or bony invasion. All patients had a Karnofsky performance score > or = 70 prior to EB-IORT. Median age was 65 years. Final pathology revealed positive or close surgical margins in all patients. The areas treated were generally inaccessible to catheter placement for brachytherapy. The most common histology was squamous cell carcinoma. EB-IORT was given as a single fraction of 1500 cGy to the 90% isodose with 6 or 9 Mev electrons using cone sizes ranging from 2.5 to 7 cm in diameter. Data were analyzed to determine the local-regional control rate, survival, and complications after EB-IORT. With a median follow-up time of 30 months, nine patients (27%) had only local recurrence. Of these, only one recurrence was inside the EB-IORT field and eight were outside the EB-IORT field. Two patients (7%) developed distant metastases only and one patient (3%) had both local recurrence and distant metastasis. Seven patients died, five with disease. Twenty-two patients are known to be alive, 15 (68%) of whom have no evidence of disease. One patient was lost to follow-up after 12 months; when last examined he was free of disease. Five patients (16%) have had mild-to-moderate transient complications probably related to EB-IORT. The 3-year actuarial local-regional control rate was 60%. Our data suggest that EB-IORT may play an important role in decreasing local recurrence in patients with multiple high-risk factors. Despite previous full-course external beam radiotherapy and extensive resections, EB-IORT did not confer significant additional long-term morbidity. Although results are encouraging, randomized studies are required to definitively establish the role of EB-IORT in the management of advanced or recurrent head and neck cancer.
{ "pile_set_name": "PubMed Abstracts" }
A detailed and fast model of extracellular recordings. We present a novel method to generate realistic simulations of extracellular recordings. The simulations were obtained by superimposing the activity of neurons placed randomly in a cube of brain tissue. Detailed models of individual neurons were used to reproduce the extracellular action potentials of close-by neurons. To reduce the computational load, the contributions of neurons further away were simulated using previously recorded spikes with their amplitude normalized by the distance to the recording electrode. For making the simulations more realistic, we also considered a model of a finite-size electrode by averaging the potential along the electrode surface and modeling the electrode-tissue interface with a capacitive filter. This model allowed studying the effect of the electrode diameter on the quality of the recordings and how it affects the number of identified neurons after spike sorting. Given that not all neurons are active at a time, we also generated simulations with different ratios of active neurons and estimated the ratio that matches the signal-to-noise values observed in real data. Finally, we used the model to simulate tetrode recordings.
{ "pile_set_name": "PubMed Abstracts" }
Regulation by RNA. In recent years, noncoding RNAs (ncRNAs) have been shown to constitute key elements implicated in a number of regulatory mechanisms in the cell. They are present in bacteria and eukaryotes. The ncRNAs are involved in regulation of expression at both transcriptional and posttranscriptional levels, by mediating chromatin modifications, modulating transcription factor activity, and influencing mRNA stability, processing, and translation. Noncoding RNAs play a key role in genetic imprinting, dosage compensation of X-chromosome-linked genes, and many processes of differentiation and development.
{ "pile_set_name": "PubMed Abstracts" }
Rehabilitation needs in oncological patients: the On-rehab project results on patients operated for musculoskeletal tumors. Rehabilitation plays an important role in improving functional outcome in patients operated on musculoskeletal tumors. Literature in the field is scarce and the specific needs for rehabilitation of these patients are still unknown. To analyze the rehabilitation needs of patients with primary malignant musculoskeletal tumors. Observational, longitudinal study on both inpatient and outpatient operated on musculoskeletal tumors. Rehabilitation needs of oncological patients were explored by means of questionnaires administered by a physician. Demographic, oncological, psychological domains were also assessed. Twenty-nine patients were evaluated in the immediate post-operative period, 25 patients had a follow up at 6 months, and 11 patients at 12 months. Rehabilitation needs concerned essentially the neuromotor function and the improvement of independence at home/outside home. At first admission, support for occupational rehabilitation was also relevant, while its importance was reduced over the follow-up. Pain control need was greater at first admission (VAS over the follow-up 3.3, 0.52, and 1.09, respectively) and required treatment with painkillers. Quality of life (EORTC) increased over the three assessments (respectively 48.80; 71.42; 82.14). The Psychological Distress Inventory (PDI) scores were 26.23, 21.75, 23.6, and the Caregiver Needs Assessment (CNA) scores were 32.69, 27.95, and 31.7 respectively at the three follow up. The relevant domains in which rehabilitation needs emerged in up to 1 year follow up were the neuromotor area in order to gain independence at home and outside the home, pain control, particularly after surgery, nursing, psychological support of patients and caregivers, and occupational activities (personal, work, school, social). The findings of the present study suggest that: short and midterm clinical rehabilitation programs should be made available for patients operated on musculoskeletal tumors. Physical function recovery is only one aspect of rehabilitation, and psychosocial functioning must be taken into account and coordinated by a comprehensive team of specialists. Appropriate assessment tools should be used, and a continuum of care from the hospital to the patient's home should be promoted.
{ "pile_set_name": "PubMed Abstracts" }
Interactions of food and dietary supplements with drug metabolising cytochrome P450 enzymes. Drug side effects and toxicity and often the drug efficacy are highly dependent on drug metabolism determining the activation and/or elimination of the respective compound. In humans, cytochromes P450 are the most important drug metabolizing enzymes of the first phase of drug biotransformation. Their activity can vary due to interindividual genetic differences, but it can be changed also by inhibition or induction of the enzymes by their substrates or other compounds that are not only drugs themselves and/or drugs taken concomitantly. Often, influence on drug metabolism by compounds that occur in the environment, most remarkably in the food, is forgotten. Some commonly used herbs, fruits as well as e.g. alcohol may cause failure of the therapy up to serious alterations of the patient's health. This review presents a brief overview of potentially dangerous nutrition factors including herbs (incl. teas, infusions) that should be considered when indicating individual drug therapy. Examples include primarily grapefruits, pomelo, star fruit, pomegranates and some other fruits, St John's Wort (Hypericum perforatum), caffeine, as well as alcohol and cigarette smoking.
{ "pile_set_name": "PubMed Abstracts" }
Cutaneous adenocarcinoma of sebaceous gland in a captive male jaguar Panthera onca: a case report. High incidence of neoplasia in captive jaguar (Panthera onca) has been recorded but there have been no reports of cutaneous adenocarcinoma of the sebaceous gland. A high incidence of neoplasia has been detected in captive jaguars, possibly associated with longevity and husbandry practices in captivity. Neoplasm is a major cause of mortality in jaguar. Tumours of sebaceous gland are common in older domestic felids. A case of cutaneous adenocarcinoma of the sebaceous gland was diagnosed in a male captive jaguar in the Zoological Garden, Alipore, Kolkata, India and was managed successfully. The tumour was observed as a superficial, ulcerated, multilobulated intradermal mass. After preoperative haematological evaluation the tumour was excised through routine surgical procedure under chemical immobilisation. Post-operative management was uneventful. Local tumour recurrence was not noticed till one year after post-operation.
{ "pile_set_name": "PubMed Abstracts" }
Liposomal bupivacaine and novel local anesthetic formulations. Novel preparations allowing for the extended duration of action of local anesthetics have many clinically relevant benefits. With regard to this, the development of liposomal bupivacaine has the potential to significantly impact patient care by improving perioperative pain control. The unique liposomal bilayer that encapsulates bupivacaine allows for a sustained release of local anesthetic for up to 72 h after a single use and can significantly decrease postoperative opioid consumption. SABER-bupivacaine is another depot formulation that helps in sustained release of bupivacaine from an encapsulated bupivacaine in a biodegradable sucrose acetate isobutyrate biolayer. HTX-011 is an investigational extended-release local anesthetic formulation currently undergoing Phase 3 clinical trials. HTX-011 is composed of a bioerodible polymer with bupivacaine and low-dose meloxicam in which the polymer undergoes hydrolysis and allows for sustained release of bupivacaine and meloxicam for 3 days. The present investigation reviews pharmacologic considerations related to the formulation of liposomal bupivacaine, current FDA-approved indications for its use, and future extended-release local anesthetic formulations currently under investigation.
{ "pile_set_name": "PubMed Abstracts" }
A career mobility program for skilled nursing facilities. This article reports the results of a 3-year demonstration project in career mobility for nursing personnel in skilled nursing facilities. The goal of the project was to demonstrate the effectiveness of a career mobility program in addressing service delivery challenges such as recruitment, retention, and satisfaction of nursing personnel in skilled nursing facilities. The project was a joint effort between an educational department of a large university and a major long-term care corporation. The project evaluation addressed the effectiveness of this career mobility program in attracting and retaining nursing personnel, the satisfaction of nursing personnel with their jobs, and whether the additional training affected the quality of care. Five pilot and three comparison sites were designated in Southern California. Survey, self-report, and interview data were collected at yearly intervals and at the completion of the project. Descriptive statistics and analysis of variance formed the basis for data analysis and interpretation. Overall, the findings suggested that the career mobility program has the potential to retain staff who benefit from a career development program. The career mobility program was a valuable strategy, but its success was only as good as the management team's authority to support the program and emphasize its goals.
{ "pile_set_name": "PubMed Abstracts" }
Severe reversible thrombocytopenia resulting from butoconazole cream. A 54-year-old woman with a 19-year history of rheumatoid arthritis developed life-threatening thrombocytopenia one week after beginning butoconazole therapy for a vaginal yeast infection. This was complicated by upper gastrointestinal hemorrhage that probably resulted from ibuprofen and methotrexate therapy. Sepsis, myelophthisic anemias, and other potential etiologies were ruled out. Once stabilized, the patient was rechallenged with other medications without incident. These findings indicate that a potentially serious thrombocytopenia may result from the administration of butoconazole vaginal cream or in combination with methotrexate and/or ibuprofen.
{ "pile_set_name": "PubMed Abstracts" }
Obstetric simulation for medical student, resident, and fellow education. Simulation for training new providers is no longer the wave of the future, but the reality of the present. It provides significant activation and allows for both the integration of concepts with actual application and the ability to practice a wide range of procedural skills at an earlier stage of training than would otherwise be possible. It is also an optimal method to sharpen teamwork and communication skills that are critical to patient safety. These concepts are especially relevant in the field of obstetrics, where even routine deliveries may become life-threatening emergencies and the health of the mother and child are dependent on correct and timely interventions and teamwork. Almost all of the skills needed, even for advanced invasive procedures, in obstetrics can be taught with currently available simulators. In this report we will discuss the use of medical simulation for training obstetric providers from medical school through subspecialty level training.
{ "pile_set_name": "PubMed Abstracts" }
[Radiologic determination of the length of the distal end of the radius and ulna]. The influence of inaccurate positioning of the hand and forearm upon the relative lengths of the ulna and radius is investigated systematically in anatomical specimens and living persons. Increased or decreased ulnar lengths could be produced by moving up and down, by tilting or by pronation of the forearm. Extension of the elbow also influences the ulnar variance measurement.
{ "pile_set_name": "PubMed Abstracts" }
Bone marrow aspiration in resource poor environment: our experience in Kenya. Bone marrow aspiration examination is performed mainly to evaluate haematological disorders. Several bone marrow aspiration needles are available that include the Salah, Klima, Jamshidi and Islam. However, cost is an issue in our local environment as most of our patients are not medically insured. We describe our experience of bone marrow aspiration using an 18-gauge lumbar puncture needle at the posterior superior iliac spine. The technique is safe and cost effective and the site is easily accessible, even in obese patients. The crush preparations provide good morphology, therefore avoiding repeats. Additional training is not required for the procedural technique. We recommend this technique for use in resource challenged settings.
{ "pile_set_name": "PubMed Abstracts" }
Aragusterol C: a novel halogenated marine steroid from an Okinawan sponge, Xestospongia sp., possessing potent antitumor activity. A novel chlorinated steroid, aragusterol C, was isolated from an Okinawan marine sponge of the genus Xestospongia. The compound strongly inhibited the proliferation of KB cells in vitro, and also showed potent in vivo antitumor activity against L1210 cells in mice. The complete structure of aragusterol C was determined by spectroscopic analysis and X-ray crystallographic analysis.
{ "pile_set_name": "PubMed Abstracts" }
Relationship between time related serum albumin concentration, optic nerve sheath diameter, cerebrospinal fluid pressure, and neurological prognosis in cardiac arrest survivors. The optimal time to measure serum albumin concentration (SAC) to predict prognosis in cardiac arrest (CA) survivors has not been elucidated. We aimed to compare the relationships between time-related SAC, optic nerve sheath diameter (ONSD), intracranial pressure (ICP), and neurological prognosis in CA survivors. We undertook a retrospective study examining CA patients treated with target temperature management (TTM). ICP was measured using cerebrospinal fluid (CSF) pressure and ONSD was obtained before TTM. SAC was measured repeatedly at 4-6 h intervals from the hospital arrival time. We analysed CSF pressure, ONSD, and minimum SAC (MSAC) separately, or in combination, to predict poor neurological outcome. Of 83 patients enrolled, the good outcome group comprised 25 (34%) patients. MSAC at 24 h (MSAC24) had a higher area under the receiver operating characteristic curve (AUC) (0.687; 95% confidence interval (CI), 0.668-0.926) than other time points. CSF pressure showed a higher AUC (0.973; 95% CI, 0.911-0.996) than MSAC24 and ONSD (0.677; 95% CI, 0.565-0.776). In contrast to using MSAC24 and ONSD separately, the combination of both modalities resulted in a better AUC, thus improving the prediction of the neurological outcome (0.734; 95% CI, 0.626-0.825) and ICP (0.758; 95% CI, 0.651-0.845) after return of spontaneous circulation (ROSC) from CA. A higher ICP was strongly associated with and seemed predictive of poor outcome. Furthermore, the MSAC24/ONSD combination may be a useful predictor of high ICP and poor neurological outcome. Prospective studies should be conducted to confirm these results.
{ "pile_set_name": "PubMed Abstracts" }
Fibroblast remodeling activity at two- and three-dimensional collagen-glycosaminoglycan interfaces. Previously we demonstrated that high throughput gene expression experiments can yield novel information about how cells respond to a collagen-glycosaminoglycan (GAG) three-dimensional culture environment. The goal of the current study was to determine which of these differences result from culture in a three-dimensional construct versus those caused simply by the presence of the collagen-GAG biomaterial. To make this distinction, cells were cultured both in collagen-GAG scaffolds fabricated using a phase separation method and on thin two-dimensional coatings of the same material. Control cells were grown on standard tissue culture polystyrene (TCPS). Cell response was measured using histology and microarray analysis and select results were verified with real time polymerase chain reaction (RT-PCR) assays. Genes involved in matrix remodeling (matrix components, matrix metalloproteinases and growth factors) and angiogenesis (VEGF, HGF and HMOX) were shown to be differentially expressed between the treatment conditions. Several matrix metalloproteinases (MMPs) were up regulated in mesh grown cell while some of their inhibitors (TIMPs) were down regulated. These results suggest that the three-dimensional presentation of the collagen-GAG material to the cells is required to stimulate the observed increase in fibroblast remodeling behavior.
{ "pile_set_name": "PubMed Abstracts" }
Pelvic pain from a giant presacral Tarlov cyst successfully obliterated using aneurysm clips in a patient with Marfan syndrome. Patients with Marfan syndrome used to succumb early in life from cardiovascular complications. With the current rapid advance in medical and surgical care, such patients may now have near-normal longevities. Consequently, rare late-life complications are emerging in these patients and represent challenges to clinicians for their diagnoses and treatments. The authors report a rare case of pelvic pain and genital prolapse from a giant presacral Tarlov cyst in a 67-year-old patient with Marfan syndrome. This 67-year-old Caucasian female presented with progressively severe pelvic pain, intermittent explosive diarrhea, and dysuria. Physical and bimanual examination demonstrated genital prolapse and a nontender, cyst-like mass fixed in the midline. She underwent ultrasound, CT, and eventually MRI evaluations that led to the diagnosis of a giant (6.7 × 6.4 × 6.6 cm) Tarlov cyst originating from the right S-2 nerve root sleeve/sacral foramen with intrapelvic extension. She underwent S1-S2 and S2-S3 laminectomy with obliteration of the Tarlov cyst using aneurysm clips. Postoperatively, her pelvic pain and bowel symptoms resolved and the bladder symptoms improved. The 3-month follow-up CT of abdomen/pelvis demonstrated resolution of the cyst. The present case illustrates that clinicians caring for elderly patients with Marfan syndrome need to increasingly recognize such unusual late-life complications. Also, these large Tarlov cysts can be simply and effectively obliterated with aneurysm clips.
{ "pile_set_name": "PubMed Abstracts" }
Indirect upstream effects of dams: consequences of migratory consumer extirpation in Puerto Rico. Large dams degrade the integrity of a wide variety of ecosystems, yet direct downstream effects of dams have received the most attention from ecosystem managers and researchers. We investigated indirect upstream effects of dams resulting from decimation of migratory freshwater shrimp and fish populations in Puerto Rico, USA, in both high- and low-gradient streams. In high-gradient streams above large dams, native shrimps and fishes were extremely rare, whereas similar sites without large dams had high abundances of native consumers. Losses of native fauna above dams dramatically altered their basal food resources and assemblages of invertebrate competitors and prey. Compared to pools in high-gradient streams with no large dams, pool epilithon above dams had nine times more algal biomass, 20 times more fine benthic organic matter (FBOM), 65 times more fine benthic inorganic matter (FBIM), 28 times more carbon, 19 times more nitrogen, and four times more non-decapod invertebrate biomass. High-gradient riffles upstream from large dams had five times more FBIM than did undammed riffles but showed no difference in algal abundance, FBOM, or non-decapod invertebrate biomass. For epilithon of low-gradient streams, differences in basal resources between pools above large dams vs. without large dams were considerably smaller in magnitude than those observed for pools in high-gradient sites. These results match previous stream experiments in which the strength of native shrimp and fish effects increased with stream gradient. Our results demonstrate that dams can indirectly affect upstream free-flowing reaches by eliminating strong top-down effects of consumers. Migratory omnivorous shrimps and fishes occur throughout the tropics, and the consequences of their declines upstream from many tropical dams are likely to be similar to those in Puerto Rico. Thus, ecological effects of migratory fauna loss upstream from dams encompass a wider variety of species interactions and biomes than the bottom-up effects (i.e., elimination of salmonid nutrient subsidies) recognized for northern temperate systems.
{ "pile_set_name": "PubMed Abstracts" }
Psychopathology and resilience following traumatic injury: a latent growth mixture model analysis. To investigate trajectories of PTSD and depression following traumatic injury using latent class growth curve modeling. A longitudinal study of 330 injured trauma survivors was conducted and participants were assessed during hospitalization, and at 1, 3, and 6 months follow-up. Acute Stress Disorder (ASD) was assessed during hospitalization using the Acute Stress Disorder Interview (ASD-I), PTSD was measured at all follow-up with the Post-Traumatic Stress Diagnostic Scale (PDS) and depression was measured at hospitalization with the (BSI) and at follow-up with the Center for Epidemiologic Studies Depression Scale (CESDS). Covariates were explored, including coping self-efficacy, anger, education level, and mechanism of injury. Four latent classes were identified for PTSD and Depression symptoms: chronic distress, delayed distress, recovered, and resilience. When compared to the resilient group, individuals with chronic distress were more likely to have been assaulted, had higher levels of anger, and had less coping self-efficacy. The delayed distress group had lower education levels, higher levels of coping self-efficacy, and higher levels of anger. Individuals in the recovered group had fewer years of education, and higher levels of anger. The majority of the injured trauma sample demonstrated resiliency, with those exhibiting distress doing so as a delayed, chronic, or recovered trajectory. Coping self efficacy, education, assaultive trauma type, and anger were important covariates of depression and PTSD trajectories. These results are similar to studies of individuals who experienced a major health threat and with survivors from the World Trade Center attacks in the U.S.
{ "pile_set_name": "PubMed Abstracts" }
Gamma-radiation induces apoptosis via sarcoplasmatic reticulum in guinea pig ileum smooth muscle cells. We investigated the effects of gamma-radiation on cells isolated from the longitudinal smooth muscle layer of the guinea pig ileum, a relatively radioresistant tissue. Single doses (up to 50 Gy) reduced the amount of sarcoplasmatic reticulum and condensed the myofibrils, as shown by electron microscopy 3 days post-irradiation. After that, contractility of smooth muscle strips was reduced. Ca(2+) handling was altered after irradiation, as shown in fura-2 loaded cells, with elevated basal intracellular Ca(2+), reduced amount of intrareticular Ca(2+), and reduced capacitive Ca(2+) entry. Radiation also induced apoptosis, judged from flow cytometry of cells loaded with proprium iodide. Electron microscopy showed that radiation caused condensation of chromatin in dense masses around the nuclear envelope, the presence of apoptotic bodies, fragmentation of the nucleus, detachment of cells from their neighbors, and reductions in cell volume. Radiation also caused activation of caspase 12. Apoptosis was reduced by the administration of the caspase inhibitor Z-Val-Ala-Asp-fluoromethyl-ketone methyl ester (Z-VAD-FMK) during the 3 day period after irradiation, and by the chelator of intracellular Ca(2+), 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA), from 1 h before until 2 h after irradiation. BAPTA also reduced the effects of radiation on contractility, basal intracellular Ca(2+), amount of intrareticular Ca(2+), capacitative Ca(2+) entry, and apoptosis. In conclusion, the effects of gamma radiation on contractility, Ca(2+) handling, and apoptosis appear due to a toxic action of intracellular Ca(2+). Ca(2+)-induced damage to the sarcoplasmatic reticulum seems a key event in impaired Ca(2+) handling and apoptosis induced by gamma-radiation.
{ "pile_set_name": "PubMed Abstracts" }
Direct Determination of Dynamic Properties of Coulomb and Yukawa Classical One-Component Plasmas. Dynamic characteristics of strongly coupled classical one-component Coulomb and Yukawa plasmas are obtained within the nonperturbative model-free moment approach without any data input from simulations so that the dynamic structure factor (DSF) satisfies the first three nonvanishing sum rules automatically. The DSF, dispersion, decay, sound speed, and other characteristics of the collective modes are determined using exclusively the static structure factor calculated from various theoretical approaches including the hypernetted chain approximation. A good quantitative agreement with molecular dynamics simulation data is achieved.
{ "pile_set_name": "PubMed Abstracts" }
Chronic urticaria sera increase basophil CD203c expression. Approximately 40% of patients with chronic idiopathic urticaria have antibodies to the alpha subunit of the high-affinity IgE receptor. CD203c is a basophil activation marker known to be upregulated by cross-linking of the FcepsilonRIalpha receptor and may serve as a useful marker to identify these patients. The primary objective was to assess the affect of sera from patients with chronic idiopathic urticaria on basophil CD203c expression. Secondary objectives were to correlate CD203c expression with basophil histamine release and size of the autologous serum skin test and to determine whether the mechanism is mediated by an IgG antibody. Sera were obtained from patients with chronic idiopathic urticaria and positive autologous serum skin test or negative autologous serum skin test and normal controls. Sera were incubated with donor whole blood. Activated basophils from whole blood were identified by flow cytometry on the basis of the presence of CD203c on high-expressing IgE positive cells. Incubation of donor basophils with sera from patients with chronic idiopathic urticaria and positive autologous serum skin test demonstrated significant upregulation of CD203c. IgG depletion of representative sera from patients with chronic idiopathic urticaria resulted in significant decrease in CD203c expression on donor basophils. CD203c expression correlated with basophil histamine release and the size of the autologous serum skin test. Sera from patients with chronic idiopathic urticaria and positive autologous serum skin test significantly upregulate basophil CD203c and correlate with basophil histamine release. This article describes an activation marker on basophils whose expression is increased by sera from patients with chronic idiopathic urticaria.
{ "pile_set_name": "PubMed Abstracts" }
Ameloblastoma of the upper jaw. A clinical study was made of three cases of Ameloblastoma (Adamantinoma) of the maxilla. One case presented with oro-antral fistula following extraction of a molar tooth. Extensive bone destruction and involvement of ethmoidal air sinuses and nasal cavity was seen in one of the patients. At times histological diagnosis can be difficult; therefore, accurate diagnosis should be obtained by an experienced histopathologist. Partial maxillectomy with a wide margin of healthy bone should be the choice of treatment in the majority of cases. There tumours are sensitive to deep-X-ray to a varying degree. One should consider radiotherapy post-operatively if growth has been excised inadequately. Radiotherapy may be helpful when surgery is contraindicated.
{ "pile_set_name": "PubMed Abstracts" }
Proteomic workflow for analysis of archival formalin-fixed and paraffin-embedded clinical samples to a depth of 10 000 proteins. Archival formalin-fixed and paraffin-embedded clinical samples represent a very diverse source of material for proteomic investigation of diseases, often with follow-up patient information. Here, we describe an analytical workflow for analysis of laser-capture microdissected formalin-fixed and paraffin-embedded samples that allows studying proteomes to a depth of 10 000 proteins per sample. The workflow involves lysis of tissue in SDS-containing buffer, detergent removal, and consecutive digestion of the proteins with two enzymes by the multienzyme digestion filter-aided sample preparation method. Resulting peptides are fractionated by pipette-tip based strong anion exchange into six fractions and analyzed by LC-MS/MS on a bench top quadrupole Orbitrap mass spectrometer. Analysis of the data using the MaxQuant software resulted in the identification of 9502 ± 28 protein groups per a 110 nL sample of microdissected cells from human colonic adenoma. This depth of proteome analysis enables systemic insights into the organization of the adenoma cells and an estimation of the abundances of known biomarkers. It also allows the identification of proteins expressed from tumor suppressors, oncogenes, and other key players in the development and progression of the colorectal cancer. Our proteomic platform can be used for quantitative comparisons between samples representing different stages of diseases and thus can be applied to the discovery of biomarkers or drug targets.
{ "pile_set_name": "PubMed Abstracts" }
Synthesis and biological evaluation of novel fluconazole analogues bearing 1,3,4-oxadiazole moiety as potent antifungal agents. A novel series of fluconazole based mimics incorporating 1,3,4-oxadiazole moiety were designed and synthesized. All the title compounds were characterized by (1)H-NMR, (13)C-NMR, and Q-TOF-MS. Preliminary results revealed that most of analogues exhibited significant antifungal activity against seven pathogenic fungi. Compounds 9g and 9k (MIC80 ≤ 0.125 μg/mL, respectively) were found more potent than the positive controls itraconazole and fluconazole as broad-spectrum antifungal agents. The observed docking results showed that the 1,3,4-oxadiazole moiety enhanced the affinity binding to the cytochrome P450 14α-demethylase (CYP51).
{ "pile_set_name": "PubMed Abstracts" }
Glomerular changes in microscopic haematuria, studied by quantitative immunoelectron microscopy and in situ zymography. Haematuria of glomerular origin, even if mild, implies the development of defects in the glomerular basement membrane (GBM). In diseases where there is no infiltration of leukocytes into the glomerulus-such as thin basement membrane disease (TBMD) and histologically mild cases of IgA nephropathy (IgAN)-the mechanism by which such defects form is unclear. Frozen renal tissue from 18 cases of TBMD, 18 of mild IgAN and 18 cases with no detectable abnormality were studied: (i) by quantitative in situ zymography, to estimate the activity of glomerular collagenases; and (ii) by quantitative immunoelectron microscopy to estimate the amount of major basement membrane proteins per unit length and per unit area of glomerular basement membrane. Cases of IgAN showed considerably more glomerular collagenase activity than normal (P=0.001). Thin basement membrane disease showed no difference in collagenase activity. A count of LCA-positive cells in glomeruli confirmed that the IgAN cases did not show glomerular leukocyte infiltration. Conversely, cases of IgAN showed no difference in GBM composition from normal, nor was any difference in GBM thickness detected in this group. However, cases of TBMD showed considerably less laminin (P=0.0008), fibronectin (P=0.002) and type VI collagen (P=0.0005) per unit length of basement membrane. Collagen IV showed a smaller reduction per unit length (P=0.01), but unlike the other protein studies it appeared to be present in higher concentration per unit area (P=0.03), suggesting that it is more 'compact' in TBMD disease. Two distinct mechanisms of haematuria seem to be involved in these two conditions. In IgAN there is increased activity of enzymes that can degrade GBM, probably reflecting mesangial cell activation. In TBMD an abnormal composition of the thinned GBM is confirmed. When considered with published reports of genetic abnormalities in TBMD, these results raise the possibility of an abnormal interaction between collagen IV and laminin.
{ "pile_set_name": "PubMed Abstracts" }
Pericardial cysts in children: surgical or conservative approach? The authors present a case of an 11-year-old boy with a history of mild asthma and cough who underwent radiographic examination of the chest. The radiograph showed a round, discrete mass in the right cardiophrenic angle. The patient underwent thoracoscopic excision, and histologic examination found a unilocular, pericardial cyst. The possible causes of mediastinal masses and an argument for their surgical removal is presented.
{ "pile_set_name": "PubMed Abstracts" }
Outcome of cardiovascular surgery and pregnancy: a systematic review of the period 1984-1996. The outcomes of cardiovascular operations during pregnancy, at delivery, and post partum were reviewed from published material in the period 1984-1996. Surgery during pregnancy resulted in fetal-neonatal morbidity and mortality of 9% and 30%, respectively, and in maternal morbidity and mortality of 24% and 6%, respectively. Duration of pregnancy at surgery and duration and temperature of cardiopulmonary bypass did not influence fetal-neonatal outcome. Maternal complications and mortality of surgery immediately after delivery were 29% and 12%, respectively, and for surgery performed with a postpartum interval the respective rates were 38% and 14%. Hospitalization after week 27 of gestation and extreme emergency contributed significantly to poor maternal outcome. Maternal deaths were reported in 9% of valvular procedures and in 22% of aortic or arterial dissection repairs and pulmonary embolectomies. Fetal-neonatal risks of maternal surgery during pregnancy are high and unpredictable. Maternal risks of cardiovascular procedures during pregnancy are moderate, significantly increase if an operation is performed at or after delivery, and, overall, should be considered as higher than those in nonpregnant cardiovascular surgical patients.
{ "pile_set_name": "PubMed Abstracts" }
Lithium maintenance: 2. Effects of personality and attitude on health information acquisition and compliance. During a controlled education programme, the medication compliance of 60 attenders at a lithium clinic was tested using reported tablet omissions and intra-erythrocytic lithium levels. Both measures improved, along with patients' knowledge and attitude. These effects were examined and related to aspects of obsessional trait and health locus of control.
{ "pile_set_name": "PubMed Abstracts" }
Endothelial-specific deficiency of Junctional Adhesion Molecule-C promotes vessel normalisation in proliferative retinopathy. In proliferative retinopathies, like proliferative diabetic retinopathy and retinopathy of prematurity (ROP), the hypoxia response is sustained by the failure of the retina to revascularise its ischaemic areas. Non-resolving retina ischaemia/hypoxia results in upregulation of pro-angiogenic factors and pathologic neovascularisation with ectopic, fragile neovessels. Promoting revascularisation of the retinal avascular area could interfere with this vicious cycle and lead to vessel normalisation. Here, we examined the function of endothelial junctional adhesion molecule-C (JAM-C) in the context of ROP. Endothelial-specific JAM-C-deficient (EC-JAM-C KO) mice and littermate JAM-C-proficient (EC-JAM-C WT) mice were subjected to the ROP model. An increase in total retinal vascularisation was found at p17 owing to endothelial JAM-C deficiency, which was the result of enhanced revascularisation and vessel normalisation, thereby leading to significantly reduced avascular area in EC-JAM-C KO mice. In contrast, pathologic neovessel formation was not affected by endothelial JAM-C deficiency. Consistent with improved vessel normalisation, tip cell formation at the interface between vascular and avascular area was higher in EC-JAM-C KO mice, as compared to their littermate controls. Consistently, JAM-C inactivation in endothelial cells resulted in increased spreading on fibronectin and enhanced sprouting in vitro in a manner dependent on β1-integrin and on the activation of the small GTPase RAP1. Together, endothelial deletion of JAM-C promoted endothelial cell sprouting, and consequently vessel normalisation and revascularisation of the hypoxic retina without altering pathologic neovascularisation. Thus, targeting endothelial JAM-C may provide a novel therapeutic strategy for promoting revascularisation and vessel normalisation in the treatment of proliferative retinopathies.
{ "pile_set_name": "PubMed Abstracts" }
The Liebau phenomenon: a translational approach to new paradigms of CSF circulation and related flow disturbances. The aim of the study is to provide a comparison between Liebau's effect, underlying the working principles of impedance pumps, and the cerebrospinal fluid (CSF) circulation. Gerhard Liebau was a cardiologist with a specific interest in severe aortic regurgitation. Such interest drew his scientific attention to the flow-driven efficiency of valveless pumps. During one of his experiments, he assembled two rubber tubes of different sizes and documented how water could be aspirated against gravity when the tube of larger diameter underwent rhythmic compression. He subsequently tested an elastic tube connected to glass pipes of the same size on both ends, immersed in a water bucket. When the elastic tube was periodically pumped with a finger, a net flow could be observed in both directions; depending on the pumping site on the elastic tube, the flow was directed towards the most closely connected glass tube. The principles of a hydraulic system of different elasticity and compliance were also recently applied to the physiology and fluid dynamics of embryonic hearts. Impedance pumps and the CSF dynamics model are both valveless systems and can both be activated by the effects of the cardiac cycle. The novel hydraulic model of impedance pumps was the foundation for the development of modern valveless micropumps and contributes to explain how the embryonic valveless tubular heart is capable of generating blood flow. Liebau's effect and the mechanism of impedance pumps can enlighten some of the aspects of CSF dynamics and related flow disturbances.
{ "pile_set_name": "PubMed Abstracts" }
Embryonic pig pancreatic tissue for the treatment of diabetes: potential role of immune suppression with "off-the-shelf" third-party regulatory T cells. Xenogeneic embryonic pancreatic tissue can provide an attractive alternative for organ replacement therapy. However, immunological rejection represents a major obstacle. This study examines the potential of regulatory T cells (Tregs) in the prevention of E42 pancreas rejection. To develop new approaches to combat rejection, we evaluated engraftment, growth, and development of E42 pig pancreatic tissue in mice treated with ex vivo expanded Tregs in combination with T-cell debulking and the conventional immunosuppressive drugs, rapamycin and FTY720. Transplantation of E42 pig pancreas into C57BL/6 mice immunosuppressed by this protocol resulted in complete rejection within less than 6 weeks. In contrast, additional treatment with a single infusion of ex vivo expanded third-party Tregs markedly delayed the onset of graft rejection to 10 weeks. The infusion of Tregs was associated with a significant reduction in CD4 and CD8 expansion in the lymph nodes and other peripheral organs at the priming stages after implantation. Freezing and thawing of the Tregs did not affect their efficacy, indicating the potential of Tregs banking. Considering the technical difficulties encountered in the generation of Tregs from patients or from specific donors, our results demonstrate the feasibility of using "off-the-shelf" fresh or frozen third-party Tregs to control rejection in organ transplantation.
{ "pile_set_name": "PubMed Abstracts" }
Ontogeny of gonadotropin releasing hormone-containing neurons in the teleost brain. We investigated changes in two gonadotropin releasing hormone (GnRH)-containing neuronal populations during juvenile development in the African teleost, Haplochromis burtoni. Juveniles were sampled at weekly intervals and GnRHir neurons were identified through immunocytochemistry (ICC), then counted and measured on computer-captured video images. Soma size of GnRH neurons in the preoptic area (POA), which regulate gonadotropin release from the pituitary, is socially modulated in adults. Here we show that in juveniles the soma size of these neurons increases as a linear function of body weight. Terminal nerve (TN) GnRHir neurons, in contrast, are not involved in pituitary regulation and their soma size is not socially modulated in adults. In juveniles, soma size of these neurons is a quadratic function of body size and the covariance of soma size and body size is much less than in the POA GnRHir neurons. In both populations, GnRHir neuronal number covaries with body size or age only in the earliest juvenile stages. Analysis of the development of these two distinct GnRHir neuronal populations provides insight into their functional differentiation in adults.
{ "pile_set_name": "PubMed Abstracts" }
MicroRNAs as novel targets and tools in cancer therapy. MicroRNAs (miRNAs) are currently experiencing a renewed peak of attention not only as diagnostics but also especially as highly promising novel targets or tools for clinical therapy in several different malignant diseases. Moreover, the recent discovery of competing endogenous RNAs (ceRNAs) as novel miRNA-regulators has contributed exciting insights in this regard. Therefore, this review summarizes and discusses the latest findings on (1) how miRNAs have become therapeutic targets of diverse synthetic antagonists, (2) how novel endogenous regulators of miRNAs such as ceRNAs or pseudogenes could emerge as therapeutics scavenging oncogenic miRNAs and (3) how miRNAs themselves are already, and will increasingly be, used as therapeutics. Recent advances on the importance of miRNA-target affinity and the subcellular localization of miRNAs are also discussed. The potential of these developments in different tumor entities and particular hallmarks of cancer such as metastasis, disease progression, interactions with the tumor microenvironment, or cancer stem cells are equally highlighted.
{ "pile_set_name": "PubMed Abstracts" }
[The component composition of the body in children with progressive obesity]. The aim of the investigation was to determine the major components of body mass in obese children. Two hundred and thirty-four children aged 8-16 years, including 181 healthy children and 53 obese children, were examined. The components of body mass in obese children were comparatively analyzed, by taking into account gender, age, and the disease seventy, which Indicated that the adipose tissue was the major component of the body, greatly dominating over muscular and bony components with its increase in progressive disease (up to 280 and 448% of the normal values in second- and third-degree obesity, respectively). The absolute content of fat as the body's major component in overweight children has no great gender differences. In children, obesity progression is accompanied by a statistically significant reduction in absolute body mass and in the proportion of an osseal component in younger age (8-10 years) groups.
{ "pile_set_name": "PubMed Abstracts" }
Insulin inhibits Na+/H+ exchange in vascular smooth muscle and endothelial cells in situ: involvement of H2O2 and tyrosine phosphatase SHP-2. Insulin signals through several intracellular pathways. Here, we tested the hypothesis that insulin modulates Na+/H+ exchange (NHE) activity in vascular cells through H2O2-mediated inhibition of tyrosine phosphatase Src homology 2 domain containing tyrosine phosphatase 2 (SHP-2). We measured intracellular pH (pHi) in isolated mouse mesenteric arteries using fluorescence confocal and wide-field microscopy. In the absence of CO(2)/HCO(3)(-), removal of bath Na(+) produced endothelial acidification (DeltapHi = -0.71 +/- 0.12) inhibited by cariporide. Cariporide reduced endothelial steady-state pHi (DeltapHi=-0.28 +/- 0.08). Insulin and H2O2 acidified endothelial cells 0.2-0.3 pH units and reduced the acidification upon Na+ removal by approximately 65%. Cariporide abolished the effect of insulin and H2O2. In vascular smooth muscle cells, H2O2 produced intracellular acidification (DeltapHi = -0.48 +/- 0.06) as did high concentrations of insulin (DeltapHi = -0.03 +/- 0.01). NHE activity after an NH4+ prepulse was approximately 80% attenuated by H2O2 and approximately 40% by high insulin concentrations. H2O2 had no effect on Na+-HCO3- cotransport activity. NHE1 (slc9a1) was the only plasma membrane NHE isoform detected in mouse mesenteric arteries by RT-PCR analyses. In both cell types, polyethylene glycol catalase abolished the effect of insulin on pHi. Exposure to insulin increased the intracellular concentration of reactive oxygen species estimated with the fluorophore 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein. The SHP-2 selective inhibitor NSC-87877 and protein tyrosine phosphatase (PTP) inhibitor IV reduced steady-state pHi up to 0.3 pH units and inhibited NHE activity 60-80%; when applied in combination with insulin or H2O2, no further effect was obtained. We conclude that NHE contributes to pHi regulation in arterial endothelial and smooth muscle cells in situ and is inhibited by insulin and H2O2. We propose that insulin signaling involves H2O2 and inhibition of PTP SHP-2.
{ "pile_set_name": "PubMed Abstracts" }
Nuclear imaging in three dimensions: a unique tool in cancer research. Tumorigenesis includes alterations in the three-dimensional (3D) nuclear organization of the genome. The combination of sensitive quantitative fluorescent in situ hybridization (Q-FISH) and three-dimensional (3D) microscopy have evolved as powerful tools in studying the dynamic 3D organization of telomeres and chromosomes in the interphase nucleus of individual normal and tumor cells. Tumor-specific alterations in 3D telomere architecture, particularly the appearance of telomeric aggregates, are early events in tumorigenesis and have diagnostic and prognostic value. Novel tools in the 3D nuclear imaging arsenal now include high-throughput scanning capabilities and new 3D nano-resolution microscopy of tissues and cells. In this review, we summarize our current understanding of the biology of telomeres in the context of tumorigenesis and elucidate the important integrating function of advanced 3D imaging technologies in translating new discoveries in basic cancer research into new diagnostic tools for clinical oncologists to improve patient care.
{ "pile_set_name": "PubMed Abstracts" }
Brevican distinctively assembles extracellular components at the large diameter nodes of Ranvier in the CNS. Brevican is known to be an abundant extracellular matrix component in the adult brain and a structural constituent of perineuronal nets. We herein show that brevican, tenascin-R (TN-R) and phosphacan are present at the nodes of Ranvier on myelinated axons with a particularly large diameter in the central nervous system. A brevican deficiency resulted in a reorganization of the nodal matrices, which was characterized by the shift of TN-R, and concomitantly phosphacan, from an axonal diameter-dependent association with nodes to an axonal diameter independent association. Supported by the co-immunoprecipitation results, these observations indicate that the presence of TN-R and phosphacan at nodes is normally brevican-dependent, while in the absence of brevican these molecules can also be recruited by versican V2. The versican V2 and Bral1 distribution was not affected, thus indicating a brevican-independent role of these two molecules for establishing hyaluronan-binding matrices at the nodes. Our results revealed that brevican plays a crucial role in determining the specialization of the hyaluronan-binding nodal matrix assemblies in large diameter nodes.
{ "pile_set_name": "PubMed Abstracts" }
Chronic T2 Lesions in Multiple Sclerosis are Heterogeneous Regarding Phase MR Imaging. Phase imaging provides additional information on multiple sclerosis (MS) lesions and may in combination with mean diffusivity (MD) and magnetization transfer ratio (MTR) help differentiating heterogeneity of MS lesion pathology. Magnetic resonance imaging (MRI) was performed in 23 MS patients including diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and SWI. Mean values (MTR, MD, and homodyne filtered phase) from 138 chronic MS lesions and normal appearing white matter (NAWM) were obtained and correlations examined. For explorative analysis, a divisive hierarchical clustering algorithm was applied. Phase characteristics were an independent characteristic of chronic T2 lesions, as MTR and MD were not correlated with phase values (R = - 0.23, R = - 0.18). Dependent on MTR, MD, and phase, cluster analysis led to five lesion groups. Of the two groups with phase values close to NAWM, one presented with highest MD and most severe MTR decrease (p = 0.01), the other with slight MD increase and MTR decrease. Two lesion groups with highest phase values (p = 0.01) displayed slightly increased MD and moderate decrease in MTR. Clinical data including EDSS, disease duration, and age did not differ significantly between groups. Increased phase is predominantly detectable in lesions with clear MTR decrease but only moderate MD increase. Phase images seem to represent an independent parameter for MS lesion characterization and may provide additional information on MS lesion heterogeneity.
{ "pile_set_name": "PubMed Abstracts" }
Taste response variability and temporal coding in the nucleus of the solitary tract of the rat. Theories of taste coding in the brain stem have been based on the idea that taste responses are integrated over time without regard to the temporal structure of the taste-evoked spike train. In the present experiment, the reliability of response rate across stimulus repetitions and the potential contribution of temporal coding to the discrimination of taste stimuli was examined. Taste stimuli representing the four basic taste qualities were presented repeatedly, and electrophysiological responses were recorded from single cells in the nucleus of the solitary tract (NTS) of anesthetized rats. Blocks of the four tastants were repeated for as long as the cell remained isolated. Nineteen cells were recorded with between 8 and 27 repetitions of each stimulus. Response magnitude to a given tastant varied widely within some NTS cells. This impacted the determination of both the breadth of tuning and best stimulus for a given cell. The contribution of spike timing and the pattern of interspike intervals to discrimination of taste stimuli was evaluated by an information-theoretic approach based on two families of metrics. Spike timing significantly contributed to the discrimination of taste qualities in 10 of 19 (53%) cells. This contribution was especially notable during the initial 2 s of the response. Those cells that showed the most variable firing rates in response to repetition of taste stimuli tended to show the largest contribution of temporal coding. These results suggest that, in addition to response rate, the temporal parameters of responses may convey information about taste stimuli in the NTS.
{ "pile_set_name": "PubMed Abstracts" }
Proteomic insights into the maturation and capacitation of mammalian spermatozoa. Spermatozoa represent the epitome of terminally differentiated, highly specialized cells. They are transcriptionally and translationally silent and yet manage to undergo a complete functional transformation after they leave the testes, entirely fuelled by post-translational modifications occurring during epididymal maturation and capacitation. The latter have been recognized as biological processes for more than half a century. However, the biochemical mechanisms that drive these events have remained elusive, as have the pathological mechanisms that lead to defective sperm function and infertility. In the past decade the combined power of advanced proteomics, biochemistry, and functional genomics has permitted an unprecedented improvement in our understanding of sperm cell biology. We can also predict that a systems-biology approach, in concert with the new tools provided by the 'omics' revolution, will lead to dramatic gains in our understanding in the near future. As a result of such advances, insights will be generated that should ultimately lead to significant improvements in our capacity to diagnose and treat the infertile male.
{ "pile_set_name": "PubMed Abstracts" }
Diffuse fasciitis with eosinophilia. The recently described syndrome of diffuse fasciitis with eosinophilia consists of scleroderma-like cutaneous changes in the absence of Raynaud's phenomenon and without visceral involvement. Peripheral blood eosinophilia and hypergammaglobulinemia occur in the majority of patients. The biopsy specimen is characteristic and shows a diffusely thickened fascia with a noticeable inflammatory infiltrate. The etiology and pathogenesis of the entity are unknown. The majority of the cases have been reported to respond to corticosteroids. Pulmonary function abnormalities and rheumatoid factor elevation in one of our patients suggests that this syndrome may be a variant scleroderma or may have previously unrecognized systemic manifestations. The patients' objective responses to corticosteroids were minimal.
{ "pile_set_name": "PubMed Abstracts" }
Dextrous and shared interaction with medical data: stereoscopic vision is more important than hand-image collocation. The current experiment was carried out to extend our knowledge about the relative importance of stereoscopic display and hand-image collocation for dextrous interaction. We devised a new task, the Volumetric Dexterity Test (VDT), which quite accurately duplicates the way professional personnel such as surgeons and radiologists interact with detailed medical data in a VR environment. Our results were surprising. Stereo vision was very important to both accuracy and speed of task completion, as we found previously. But the presence of hand-image collocation did not improve accuracy, despite the fact that this was a truly three-dimensional task. If this finding is borne out it has important implications for the volumetric presentation of medical data to individual practitioners and in group settings.
{ "pile_set_name": "PubMed Abstracts" }
The protective effects of nutritional antioxidant therapy on Ehrlich solid tumor-bearing mice depend on the type of antioxidant therapy chosen: histology, genotoxicity and hematology evaluations. Strong evidence indicates that reactive oxygen species (ROS) play an important role in the initiation as well as the promotion phase of carcinogenesis. Studies support the role of ROS in cancer, in part, by showing that dietary antioxidants act as cancer-preventive agents. Although results are promising, the research on this topic is still controversial. Thus, the aim of this study was to investigate whether vitamins C, E and pequi oil can, individually, provide prevention and/or be used afterward as an adjuvant in cancer therapy. Ehrlich solid tumor-bearing mice received antioxidant as follows: before tumor inoculation, before and after tumor inoculation (continuous administration), and after tumor inoculation; morphometric analyses of tumor, genotoxicity and hematology were then carried out. Antioxidant administrations before tumor inoculation effectively inhibited its growth in the three experimental protocols, but administrations after the tumor's appearance accelerated tumor growth and favored metastases. Continuous administration of pequi oil inhibited the tumor's growth, while the same protocol with vitamins E and C accelerated it, favoring metastasis and increasing oxidative stress on erythrocytes. Except for continuous administration with vitamin E, the development of ascites tumor metastases was linked with increased inflammation. Results suggest that the efficiency and applicability of antioxidants in the medical clinic can depend not only on the nature of the antioxidant, the type and stage of cancer being treated and the prevailing oxygen partial pressure in the tissues, but also on the type of antioxidant therapy chosen.
{ "pile_set_name": "PubMed Abstracts" }
[Instability of the cervical spine caused by arthrosis. An unusual form of degenerative spondylolisthesis]. A case of a patient with spondylolisthesis between C4 and C5 is reported. There were neurological signs of spinal cord involvement and the lesions were essentially those of a posterior degenerative arthrosis with disc degeneration at other levels. This severe instability was cured by an anterior interbody fusion.
{ "pile_set_name": "PubMed Abstracts" }
[The patterns of admission for patients with suspected acute myocardial infarction]. The patterns of admission to hospital for 161 patients with suspected acute myocardial infarction during the period 1.2.1988-30.9.1988 were investigated. This revealed that 59% called their doctor, 20% called the ambulance directly, 11% arrived at the doctor's office or casualty department and 7% were admitted with cardiac arrest. The durations of delay were investigated. The median duration of delay by the doctor was 15 minutes but only 7% of the cases were escorted to hospital by the doctor. In 53% of the cases, the doctors waited for the ambulance without escorting the patient. In 40% of the cases, the doctors did not wait for the ambulance. 44% of the patients with acute myocardial infarction referred to hospital by doctors who did not accompany them were in poor condition on arrival (one patient died in the ambulance). 33% of these patients died in hospital. The ambulances were staffed by three persons with paramedical training in only 5% of the cases when the patient first called the doctor and in 41% of the cases when the ambulance was called as an emergency. The study reveals that prehospital treatment of cardiac patients should be improved.
{ "pile_set_name": "PubMed Abstracts" }
Clinical usefulness of serum carboxyterminal propeptide of procollagen I and tartrate-resistant acid phosphatase determinations to evaluate bone turnover in patients with chronic renal failure. We have studied the levels of the biochemical markers of bone formation total serum alkaline phosphatase, osteocalcin (BGP) and carboxyterminal propeptide of type I procollagen (PICP), the levels of the biochemical marker of bone resorption serum tartrate-resistant acid phosphatase (TRAP) and those of intact immunoreactive PTH (iPTH) in 30 patients at different stages of chronic renal failure (CRF), all of them without verifiable hepatopathy, and in 9 patients in hemodialysis with hepatopathy measured by the Knodell index. Sixteen control subjects were also studied. In the group of patients with CRF with or without hepatopathy, the levels of biochemical markers of bone turnover were significantly elevated with respect to those of control patients. We did not find any significant difference in the levels of these parameters between the groups with and without liver damage, in spite of the fact that TRAP and PICP are cleared mainly by the liver. Levels of TRAP and PICP correlated significantly with the other biochemical markers of bone turnover studied. The good relation observed between PICP, TRAP and the biochemical indexes of bone activity and iPTH levels suggests the clinical value of these markers in the follow-up of bone involvement in patients with CRF. On the other hand, the frequent hepatopathy found in patients with CRF does not seem to affect to a significant extent the diagnostic value of PICP and TRAP in this pathology.
{ "pile_set_name": "PubMed Abstracts" }
Lipoxygenase from baker's yeast: purification and properties. Lipoxygenase activity was extracted from the mitochondrial fraction of baker's yeast and was purified by affinity chromatography on a linoleyl aminoethyl sepharose column. Two lipoxygenases were eluted from the affinity column. The second enzyme eluted was characterized as a true lipoxygenase. The lipoxygenase eluted showed maximum activity at pH 6.5 with a Km of 2.68 X 10(-4) M on linoleate. The reaction products of the second lipoxygenase with linoleate were characterized by u.v., i.r., NMR spectra and mass spectrometry and were found to be: 9-hydroperoxy-octadeca-trans-10,cis-12-dienoic acid and 13-hydroperoxy-octadeca-cis-9,trans-11-dienoic acid.
{ "pile_set_name": "PubMed Abstracts" }
Occurrence of gastrointestinal parasites in horses in metropolitan Perth, Western Australia. To assess the occurrence of gastrointestinal parasites in horses in Perth. To apply polymerase chain reaction (PCR) for the identification of some species of encysted larval cyathostomes. Between February and September of 2000, the gastrointestinal tracts of 29 horses submitted to a local knackery and Murdoch University Veterinary hospital in Perth were examined post mortem for the presence of gastrointestinal parasites. The gastrointestinal tract was divided into six sections, which were screened for the presence of parasites such as Gasterophilus sp, Anoplocephala sp and Parascaris equorum. Samples of contents were taken for worm counts. Cyathostomes were found in 28 of the 29 horses. Eighteen species of gastrointestinal helminths were identified. Twelve of these were cyathostomes, with the four most common species being Cyathostomum catinatum, Cylicocyclus nassatus, Cylicostephanus longibursatus and Cylicostephanus goldi. The large strongyle, Triodontophorus serratus, was found in three of the horses but species of Strongylus were not found. In contrast to a study conducted on horses from this region in 1985, cyathostomes were the most common gastrointestinal parasites found. The four most common cyathostome species found in the present study correlated well with findings of studies in other locations. The high number of cyathostomes may be due to the increase in resistance to anthelmintics among the species, and to improper anthelmintic use. The apparent reduction in number of large strongyles may be due to the widespread use of ivermectin, which is very effective against these parasites, and also possibly because some larvae may not have been detected.
{ "pile_set_name": "PubMed Abstracts" }
The effect of 1,25-dihydroxyvitamin D3 on insulin binding, insulin receptor mRNA levels, and isotype RNA pattern in U-937 human promonocytic cells. We have studied the effect of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on insulin binding, insulin receptor gene expression, and isotype mRNA pattern in U-937 human promonocytic cells. Binding assays indicated that 1,25-(OH)2D3 increased total receptor number without altering receptor affinity, while the dissociation rate of the hormone bound to its receptor remained unchanged. RNA blot assays indicated that 1,25-(OH)2D3 increased the levels of the two major insulin receptor mRNAs (11 and 8.5 kb) present in these cells. Experiments with the RNA synthesis inhibitor actinomycin D suggested that 1,25-(OH)2D3 did not alter the stability of total insulin receptor mRNA. Experiments with the protein synthesis inhibitor cycloheximide indicated that the increase in the amounts of this mRNA occurs as a direct response to the action of the hormone. Finally, polymerase chain reaction assays revealed that the insulin receptor mRNA isotype lacking the exon 11 (A isotype) was the only one present in both untreated and 1,25-(OH)2D3-treated U-937 cells. This indicates that 1,25-(OH)2D3 does not alter the splicing of the primary insulin receptor transcript in this cell line.
{ "pile_set_name": "PubMed Abstracts" }
Induction of somatostatin by kainic acid in pyramidal and granule cells of the rat hippocampus. Seizures were induced in rats by systemic administration of kainic acid and, 1.5-12 h after, expression of preprosomatostatin and c-fos mRNAs in 9 hippocampal areas and in the cerebral perirhinal cortex was investigated using in situ hybridization histochemistry. Immunohistochemistry was also performed to study somatostatin peptide. In the control animals preprosomatostatin mRNA was expressed in some cells in the dentate hilus, the stratum oriens and the stratum radiatum of Ammon's horn, the subiculum and the cortex. Starting 3 h after kainic acid administration preprosomatostatin mRNA was expressed in a subpopulation of granule and pyramidal cells which did not normally express it. Preprosomatostatin mRNA-positive cells were markedly increased in the subiculum. Immunohistochemical examination confirmed that preprosomatostatin mRNA in granule and pyramidal cells was translated into peptide. In contrast, c-fos mRNA was induced in most hippocampal and cortical neurons starting 1.5 h after the kainic acid injection. When diazepam was injected to suppress the generalized seizures, preprosomatostatin mRNA was still expressed in pyramidal and subicular cells but not in granule cells.
{ "pile_set_name": "PubMed Abstracts" }
Review of treatment of acute scaphoid fractures: R1. Scaphoid fractures are common. Clinical suspicion and early diagnosis and treatment are vital in order to avoid complications such as avascular necrosis. The management of these fractures depends on fracture characteristics, specifically the degree of displacement. With consideration of patient factors, such as occupation, the treatment can be non-operative or operative. There has been much debate in the recent literature regarding the best management of these fractures. The purpose of this review was to identify the current evidence for non-operative and operative treatment. Undisplaced and minimally displaced fractures can be managed non-operatively with a scaphoid cast. Surgical treatment is used for fractures with displacement of >1 mm.
{ "pile_set_name": "PubMed Abstracts" }
Mechanism of cartilage destruction in osteoarthritis. Osteoarthritis (OA) is one of the most common diseases among the elderly. For many years, OA was considered a normal result of the aging process with few treatment options. Remarkable progress in understanding OA cartilage has been achieved in recent years. The application of technical advances to clinical studies of chondrocytes and cartilage tissue metabolism will provide important new insights concerning the pathophysiology of OA and identify new therapeutic strategies to regulate and inhibit the degenerative process of OA. However, many problems remain unresolved. In this review we try to focus on recent advances in the field of cartilage metabolism and molecular markers to facilitate the determination of a patients prognosis and the need for cartilage protective treatment.
{ "pile_set_name": "PubMed Abstracts" }
Diagnostic imaging of aortic atherosclerosis and its complications. Thoracic aortic atherosclerosis has been shown to be an important cause of severe morbidity and mortality. At the present time, the case of performance, detailed information obtainable, and availability make TEE the procedure of choice for the imaging of thoracic aortic atherosclerosis; however, further technical advances in MR and CT, particularly in MR plaque characterization and the use of plaque specific contrast agents, may allow for a less invasive and more complete evaluation of thoracic aortic atherosclerosis in the near future. Gadolinium-enhanced 3DMRA is the procedure of choice for the noninvasive detection of plaque in the proximal aortic arch vessels. Furthermore, both CT and MRI are better suited to evaluate penetrating atherosclerotic ulcers and their complications such as intramural hematoma, pseudoaneurysm formation, and aortic rupture.
{ "pile_set_name": "PubMed Abstracts" }
Characterization of a species of non-specific cross-reacting antigen (NCA) expressed by human monocytic cell lines: structure and expression during cell differentiation. It has been documented that human monocytes/macrophages are reactive with antibodies directed to carcinoembryonic antigen (CEA) and non-specific cross-reacting antigens (NCAs), a group of glycoproteins antigenically cross-reactive with CEA, yet the molecules responsible for this antigenic activity have not been fully clarified. In the present study, among 7 myelomonocytic cell lines tested, 2 monoblastoid lines, U-937 and THP-1, were found to express NCA-50/90, a glycosylphosphatidylinositol-anchored cell-adhesion molecule chiefly expressed on granulocytes. The 2 cell lines showed a reaction pattern with 5 distinct anti-CEA and anti-NCA monoclonal antibodies, similar to that of CHO transfectants expressing recombinant NCA-50/90. Immunoprecipitation and SDS-PAGE analyses identified glycoproteins of about 95 and 55 kDa in U-937 and THP-1 cells, respectively. Deglycosylation of the 2 antigens with N-glycanase gave the same apparent molecular mass of about 45,000, which was also the same as that of the deglycosylated form of the recombinant NCA-50/90. Upon Northern-blot analysis, only one band of approximately 2.5 kb was detected in both cell lines with a cDNA probe for NCA-50/90, which has a broad specificity to the CEA gene family members. cDNA cloning demonstrated that the 2.5-kb clones encode the peptide of NCA-50/90. The expression of NCA-50/90 by U-937 and THP-1 was down-regulated at both the protein and mRNA levels during cell differentiation from monoblastoid to monocyte/macrophage-like cells induced by stimulation with phorbol 12-myristate 13-acetate. Our observations suggest that NCA-50/90 is a differentiation antigen of cells of the monocyte/macrophage lineage as well as of the granulocyte lineage.
{ "pile_set_name": "PubMed Abstracts" }
MLPA-based approach for initial and simultaneous detection of GBA deletions and recombinant alleles in patients affected by Gaucher Disease. The chromosomal region, in which the GBA gene is located, is structurally subject to misalignments, reciprocal and nonreciprocal homologous recombination events, leading to structural defects such as deletions, duplications and gene-pseudogene complex rearrangements causing Gaucher Disease (GD). Interestingly deletions and duplications, belonging to the heterogeneous group of structural defects collectively termed Copy Number Variations (CNVs), together with gene-pseudogene complex rearrangements represent the main cause of pitfalls in GD mutational analysis. In the present study, we set up and validate a Multiplex Ligation-dependent Probe Amplification (MLPA)-based approach to simultaneously investigate the potential occurrence of CNVs and complex rearrangements in 8 unrelated GD patients who had still not-well-characterized or uncharacterized alleles. The findings allowed us to complete the mutational analysis in 4 patients, identifying a rare deletion (g.-3100_+834del3934) and 2 novel recombinant alleles (g.4356_7031conJ03060.1:g.2544_4568; g.1942_7319conJ03060.1:g.1092_4856). These results demonstrate the diagnostic usefulness of MLPA in the detection of GBA deletions and recombinations. In addition, MLPA findings have also served as a basis for developing molecular approaches to precisely pinpoint the breakpoints and characterize the underlying mechanism of copy number variations.
{ "pile_set_name": "PubMed Abstracts" }
Ontogeny of reproductive abnormalities induced by deregulation of anti-müllerian hormone expression in transgenic mice. Anti-müllerian hormone, normally responsible for the regression of müllerian ducts in male fetuses, induces stunting, germ cell loss, and seminiferous tubule formation in ovaries of bovine freemartin fetuses and of transgenic mice, which express the human anti müllerian hormone gene under the control of the metallothionein promoter. Because the latter have been studied only after birth, we undertook a detailed chronological study of their reproductive organs. Müllerian ducts of transgenic female fetuses regressed at the same time as those of normal or transgenic males. Maximal reduction of germ cell number occurred between 16 days postcoitus and birth, when most transgenic oocytes were still in the leptotene stage of the meiotic prophase, whereas normal oocytes had already reached the pachytene phase. Interference with progression of the meiotic prophase and germ cell loss in the fetal ovary are probably responsible for subsequent ovarian regression and retardation of follicle growth. Seminiferous tubule formation was not detectable prior to birth and occurred only rarely in postnatal ovaries. Aromatase activity of fetal transgenic ovaries was decreased, as well as serum concentration of testosterone in adult transgenic males, suggesting that high levels of anti-müllerian hormone may impair Leydig cell steroidogenesis.
{ "pile_set_name": "PubMed Abstracts" }
COX-2 mediates hepatitis B virus X protein abrogation of p53-induced apoptosis. The oncogenic hepatitis B virus X protein (HBx) and cyclooxygenase (COX)-2 are highly co-expressed in chronic hepatitis, cirrhosis and well-differentiated hepatocellular carcinoma (HCC). Although HBx is shown to activate COX-2, the functional consequences of this interaction in hepatocarcinogenesis remain unknown. Using an engineered hepatoma cell system in which the expression of wild-type p53 can be chemically modulated, we show here that COX-2 mediates HBx actions in opposing p53. Enforced expression of HBx sequestrates p53 in the cytoplasm and significantly abolishes p53-induced apoptosis. The anti-apoptotic Mcl-1 protein is suppressed by p53 but reactivated by HBx. The abrogation of apoptosis is completely reversed by specific COX-2 inhibition, suggesting that HBx blocks p53-induced apoptosis via activation of COX-2/PGE(2) pathway. We further show that COX-2 inhibition blocks HBx reactivation of Mcl-1, linking this protein to the anti-apoptotic function of COX-2. These results demonstrate that COX-2 is an important survival factor mediating the oncogenic actions of HBx. Over-expression of HBx and COX-2 may provide a selective clonal advantage for preneoplastic or neoplastic hepatocytes and contribute to the initiation and progression of HCC.
{ "pile_set_name": "PubMed Abstracts" }
Frequency of Discordant Lesions and False-negative Cancers at Stereotactic Vacuum-assisted Biopsy. This study aimed to determine frequency of discordant lesions and discordant false-negative cancers at stereotactic vacuum-assisted biopsy (SVAB). Institutional database was searched for discordant SVAB results between January 1, 2005 and December 31, 2012, in this retrospective institutional review board-approved Health Insurance Portability and Accountability Act-compliant study. Patient age, indication for initial mammogram, breast density, lesion size, Breast Imaging Reporting and Data System categorization, operator experience, biopsy needle gauge, biopsy histology, and final surgical histology of discordant lesions were collected and entered into a Microsoft Excel spreadsheet. Discordant rate and false-negative rates were calculated. Fisher exact test was used to assess prevalence of discordance using 11-Gauge needles versus 9-Gauge needles. Patient age, lesion Breast Imaging Reporting and Data System, operator days of experience, mammographic density, and lesion size were evaluated for association with false-negative discordant lesions using an exact Mann-Whitney U test. A total of 1861 SVABs were performed, 224 (12%) with an 11-Gauge VAB device and 1637 (88%) with a 9G Suros or Eviva device. Majority (1409 of 1861; 76%) of SVABs targeted calcifications. Twenty-three of 1861 (1.2%) discordant lesions were identified in 23 women. Seven of 23 (30%) discordant lesions were found to be cancers after final surgical pathology. Needle gauge was not associated with discordance. Operator experience was not associated with false-negative discordance. A relatively low discordance rate (1.2%) was observed. However, a high percentage (30%; range in literature 11.7%-53.8%) of our discordant lesions were false negatives. This study emphasizes the need for careful radiological-pathologic review after SVAB and for repeat biopsy or surgical excision in the setting of discordance.
{ "pile_set_name": "PubMed Abstracts" }
Formylation of Eukaryotic Cytoplasmic Proteins: Linking Stress to Degradation. Unlike prokaryotes, N-terminal formylation has been confined to a handful of mitochondrial proteins in eukaryotes. A recent study unveils a new role for eukaryotic cytoplasmic N-terminal formylation linking diverse cellular stresses to N-terminal-dependent protein degradation. These findings suggest broad cellular implications in higher eukaryotes for N-terminal methionine formylation.
{ "pile_set_name": "PubMed Abstracts" }
Time-domain analysis of neural tracking of hierarchical linguistic structures. When listening to continuous speech, cortical activity measured by MEG concurrently follows the rhythms of multiple linguistic structures, e.g., syllables, phrases, and sentences. This phenomenon was previously characterized in the frequency domain. Here, we investigate the waveform of neural activity tracking linguistic structures in the time domain and quantify the coherence of neural response phases over subjects listening to the same stimulus. These analyses are achieved by decomposing the multi-channel MEG recordings into components that maximize the correlation between neural response waveforms across listeners. Each MEG component can be viewed as the recording from a virtual sensor that is spatially tuned to a cortical network showing coherent neural activity over subjects. This analysis reveals information not available from previous frequency-domain analysis of MEG global field power: First, concurrent neural tracking of hierarchical linguistic structures emerges at the beginning of the stimulus, rather than slowly building up after repetitions of the same sentential structure. Second, neural tracking of the sentential structure is reflected by slow neural fluctuations, rather than, e.g., a series of short-lasting transient responses at sentential boundaries. Lastly and most importantly, it shows that the MEG responses tracking the syllabic rhythm are spatially separable from the MEG responses tracking the sentential and phrasal rhythms.
{ "pile_set_name": "PubMed Abstracts" }
Preservation for future use of the autologous saphenous vein during femoro-popliteal bypass surgery is inexpedient. To investigate the usefulness of greater saphenous vein preservation for future vascular reconstructions during femoro-popliteal bypass surgery. Post-hoc analysis of data acquired in a randomized multi-centre clinical trial comparing two different vascular prostheses (ClinicalTrials.gov ID: NCT 00523263). The true frequency of ipsilateral saphenous vein use in subsequent femoro-popliteal and coronary bypass surgery was investigated through case-record analysis with a median follow-up of 60 months in 100 consecutive patients, that received a prosthetic femoro-popliteal bypass between 1996 and 2001. An ipsilateral secondary femoro-popliteal bypass was performed in 11 patients (11%) at a mean interval of 34 months (range 1-96). The ipsilateral saphenous vein was applied for these procedures in 8 cases (8%). The cumulative probability of receiving a subsequent bypass was 8% at 3 years and 10% at 5 years follow-up respectively. One patient (1%) underwent CABG at 8 years follow-up with the use of ipsilateral lower leg saphenous vein segments only. Preservation of the greater saphenous vein in supragenicular femoro-popliteal bypass surgery is not a valid argument for application of prosthetic material.
{ "pile_set_name": "PubMed Abstracts" }
A copy number variation genotyping method for aneuploidy detection in spontaneous abortion specimens. Chromosomal abnormalities such as aneuploidy have been shown to be responsible for causing spontaneous abortion. Genetic evaluation of abortions is currently underperformed. Screening for aneuploidy in the products of conception can help determine the etiology. We designed a high-throughput ligation-dependent probe amplification (HLPA) assay to examine aneuploidy of 24 chromosomes in miscarriage tissues and aimed to validate the performance of this technique. We carried out aneuploidy screening in 98 fetal tissue samples collected from female subjects with singleton pregnancies who experienced spontaneous abortion. The mean maternal age was 31.6 years (range: 24-43), and the mean gestational age was 10.2 weeks (range: 4.6-14.1). HLPA was performed in parallel with array comparative genomic hybridization, which is the gold standard for aneuploidy detection in clinical practices. The results from the two platforms were compared. Forty-nine out of ninety-eight samples were found to be aneuploid. HLPA showed concordance with array comparative genomic hybridization in diagnosing aneuploidy. High-throughput ligation-dependent probe amplification is a rapid and accurate method for aneuploidy detection. It can be used as a cost-effective screening procedure in clinical spontaneous abortions. © 2016 John Wiley & Sons, Ltd.
{ "pile_set_name": "PubMed Abstracts" }
Segmentation and representation of consonant blends in kindergarten children's spellings. The purpose of this study was to describe the growth of children's segmentation and representation of consonant blends in the kindergarten year and to evaluate the extent to which linguistic features influence segmentation and representation of consonant blends. Specifically, the roles of word position (initial blends, final blends), class of blends, homorganicity, and nasality were considered. Forty kindergarten children completed a developmental spelling measure (26 words with initial or final blends) 3 times at 6-week intervals. Responses were analyzed for logical representation of speech sounds to describe developmental change and differential accuracy of segmentation and representation across blend types. Kindergarten children showed varied ability to segment and represent consonant blends and were differentially successful depending on the linguistic features of the blends. Children were more likely to represent initial blends than final blends, final nonnasal blends than final nasal blends, nonhomorganic blends than homorganic blends, and initial nasal blends than final nasal blends. During the period of emergence, the properties of phonemes that comprise consonant blends influence children's ability to segment and represent blends. This finding has implications for how phonemic awareness and spelling instruction and intervention might proceed.
{ "pile_set_name": "PubMed Abstracts" }
From staff nurse to head nurse: a trying transition. The new head nurse is often unprepared for the role transition required by this new position. In this retrospective analysis of their first six months as head nurses, the authors, with a sense of humor, define a transition process consisting of three maturational stages. If nursing administrators and new head nurses anticipate and recognize these stages and their effects on nursing staff and care delivery, some of the resulting problems may be alleviated.
{ "pile_set_name": "PubMed Abstracts" }
Sustained Epstein-Barr virus detection in paediatric liver transplantation. Insights into the occurrence of late PTLD. Epstein-Barr virus (EBV) infection is the main cause of post-transplant lymphoproliferative disease (PTLD). Little is known on chronic carrier state and its relation with late PTLD. We aimed to study EBV infection in the long-term after paediatric liver transplantation (OLT). We conducted a retrospective review of 34 children monitored for a median of 5.8 years (range 1.5-17.7). 21 were IgG seronegative (group A) and 13 seropositive (group B) before OLT. Primary infection was the appearance of VCA-IgM or VCA-IgG or Real-Time Polymerase Chain Reaction (RT-PCR) in patients previously IgG seronegative; positive VCA-IgM or EA-IgG or RT-PCR lasting longer than 6 months was defined sustained viral detection (SVD). 18/21 patients of group A had a primary infection at a median time of 3 months after transplant (0.5-60). 14/18 of group A and 0/13 of group B had a SVD (P < 0.0001). Viral loads greater than 500 copies/10(5) mononuclear cells occurred in 12/18 patients in group A and 0/13 patients in group B (P < 0.0001). The 3 patients who developed late PTLD (median time after OLT 47 months, range 15-121) were from group A, and presented with SVD before developing PTLD. In conclusion, EBV infection in seronegative patients at OLT is associated with greater viral loads and sustained viral detection. Late PTLD occurred only in naïve patients with markers of SVD. Three to 4 monthly long-term monitoring of EBV in pre-OLT naïve patients might help preventing the occurrence of late PTLD.
{ "pile_set_name": "PubMed Abstracts" }
Immunodominance deters the response to other tumor antigens thereby favoring escape: prevention by vaccination with tumor variants selected with cloned cytolytic T cells in vitro. Variant cancer cells which arise from the parent tumor during tumor progression can escape immunity but retain antigens. We have mixed highly immunogenic (A+B+) murine parental cancer cells with less immunogenic (A-B+) variant cancer cells to construct a model of a cancer containing escape variants. When such mixtures of cancer cells were injected into normal mice, the variant cells grew out because immune responsiveness to the B antigen on the variant was hindered by dominance of the A antigen on the surrounding parental tumor cells. However, A-B+ variant cells inoculated alone at a separate site induced B specific cytolytic T cells and were rejected. Moreover, mice immunized with A-B+ cells rejected a challenge which contained a mixture of variant and parental cancer cells, while immunization with A+B+ cells was ineffective. Thus, variant tumor cells selected from parental tumor cells by cytolytic T cells in vitro can be used to induce protective immunity against variants expected to escape tumor immunity in vivo. The immunodominance of the A antigen may be related to its ability to induce a much more rapid CTL response than the B antigen, since we show in another model that the pre-existence of a CTL response to one antigen prevented the subsequent induction of CTL to another antigen injected at the same site, even if both antigens were equally efficient at inducing CTL. These results indicate that immunodominance can affect strong as well as weak antigens. Vaccination with individual antigens at separate sites rather than with multiple antigens at one site may, therefore, be needed to prevent tumor escape and tumor recurrence or to counteract infectious diseases.
{ "pile_set_name": "PubMed Abstracts" }
The role of surgery in pediatric gliomas. Pediatric glial tumors differ from adult gliomas in several ways that are of major therapeutic importance. First, the value of extensive tumor resection, which is controversial for malignant intrinsic brain tumors in adults, has been confirmed for a variety of childhood brain tumors, such as supratentorial high-grade and low-grade gliomas and infratentorial low-grade gliomas, ependymomas, and some medulloblastomas. Second, chemotherapy has been found to be effective in improving overall outcome in several childhood brain tumors, such as medulloblastoma and supratentorial high-grade glioma, but has yet to be proven to have a major benefit for adult tumors. In addition, chemotherapy is increasingly used to delay or avoid radiotherapy in young children with high-grade and incompletely resected low-grade tumors to avoid the morbidity of irradiation on the developing nervous system. Third, the prognosis for histologically similar tumors is often more favorable in children than adults. The present chapter will highlight the unique features of childhood glial tumors, discuss general principles in the clinical presentation, diagnostic evaluation, and treatment of these tumors, and then focus on the surgical management and outcome of the more common types of tumors.
{ "pile_set_name": "PubMed Abstracts" }
Computer-controlled milk feeding of group-housed calves: the effect of milk allowance and weaning type. Calves fed by computer-controlled milk feeders are often weaned gradually by reducing the size of the milk portions. However, reducing the number of milk portions instead may lower calves' occupation of the milk feeder and stimulate their concentrate intake, especially when they are offered a high milk allowance. Before weaning, but not during weaning, the calves on low milk allowance occupied the milk feeder more, consumed more concentrates, and had a lower daily gain. There was no interaction between milk allowance and weaning type. Weaning by reducing the number of milk portions resulted in more unrewarded visits to the milk feeder, but less time ingesting a similar amount of milk. The effect of milk allowance on milk feeder occupancy before weaning was not found when this allowance was halved during weaning.
{ "pile_set_name": "PubMed Abstracts" }
[Clinical differences observed in patients with dengue caused by different serotypes in the epidemic of 2001/2002, occurred in Rio de Janeiro]. The authors evaluated clinical and epidemiological differences among the serotypes of dengue in Rio de Janeiro's 2001-2002 outbreak of the disease. Out of 362 cases that had viral isolation samples, notified by the Information System for Notification Diseases (SINAN), from January/2001 to June/2002, 62 were caused by serotype 1,62 by serotype 2 and 238 by serotype 3. In comparison with serotype 2, an individual infected by serotype 3 had a 6.07 times higher chance (OR = 6.07; CI: 1.10-43.97) of presenting shock and a 3.55 times higher chance (OR = 3.55; CI: 1.28-9.97) of developing exanthema. When compared to serotype 1, serotype 3 had a 3.06 times higher chance (OR = 3.06; CI: 0.99-9.66) of causing abdominal pain and a 3.61 times higher chance of exanthema (OR = 3.61; CI: 1.16-11.51). It was found that individuals infected by serotype 3 of the virus presented signs indicating a more severe disease.
{ "pile_set_name": "PubMed Abstracts" }