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[Spontaneous models of human diseases in dogs: ichthyoses as an example].
Ichthyoses encompass a heterogeneous group of genodermatoses characterized by abnormal desquamation over the entire body due to defects of the terminal differentiation of keratinocytes and desquamation, which occur in the upper layer of the epidermis. Even though in humans more than 40 genes have already been identified, the genetic causes of several forms remain unknown and are difficult to identify in Humans. Strikingly, several purebred dogs are also affected by specific forms of ichthyoses. In the Golden retriever dog breed, an autosomal recessive form of ichthyosis, resembling human autosomal recessive congenital ichthyoses, has recently been diagnosed with a high incidence. We first characterized the disease occurring in the golden retriever breed and collected cases and controls. A genome-wide association study on 40 unrelated Golden retriever dogs, using the canine 49.000 SNPs (single nucleotide polymorphisms) array (Affymetrix v2), followed by statistical analyses and candidate gene sequencing, allowed to identify the causal mutation in the lipase coding PNPLA1 gene (patatin-like phospholipase domain-containing protein). Screening for alterations in the human ortholog gene in 10 autosomal recessive congenital ichthyoses families, for which no genetic cause has been identified thus far, allowed to identify two recessive mutations in the PNPLA1 protein in two families. This collaborative work between "human" and "canine" geneticists, practicians, histopathologists, biochemists and electron microscopy experts not only allowed to identify, in humans, an eighth gene for autosomal recessive congenital ichthyoses, but also allowed to highlight the function of this as-yet-unknown skin specific lipase in the lipid metabolism of the skin barrier. For veterinary medicine and breeding practices, a genetic test has been developed. These findings illustrate the importance of the discovery of relevant human orthologous canine genetic diseases, whose causes can be tracked in dog breeds more easily than in humans. Indeed, due to the selection and breeding practices applied to purebred dogs, the dog constitutes a unique species for unravelling phenotype/genotype relationships and providing new insights into human genetic diseases. This work paves the way for the identification of rare gene variants in humans that may be responsible for other keratinisation and epidermal barrier defects. | {
"pile_set_name": "PubMed Abstracts"
} |
Environmental Stress: Salinity Ruins a Plant's Day in the Sun.
New research reveals how low levels of salinity in soil inhibit a plant's ability to respond to shade through a signaling mechanism involving the plant stress hormone abscisic acid. | {
"pile_set_name": "PubMed Abstracts"
} |
Melanosis of the bladder: a rare endoscopic and histopathological finding.
Melanosis of the bladder represents a rare condition characterized by anomalous deposits of melanin-containing pigment. To our knowledge, so far, just 5 cases have been reported in the literature. We describe a case of a simply melanosis of the bladder confirmed by histochemical stains and immunohistochemistry analysis. | {
"pile_set_name": "PubMed Abstracts"
} |
Multiple marker mapping of quantitative trait loci of Finnish dairy cattle by regression.
A total of 453 bulls belonging to 11 half-sib families of Finnish Ayrshires were genotyped for six microsatellite markers on chromosome 9. The data were used in an attempt to map quantitative trait loci applying regression as a multimarker approach. For association analysis with a granddaughter design, the EBV for 12 traits were used: milk yield, protein yield, fat percentage, protein percentage, daughter weight, bull growth, calf mortality, days open, fertility treatments, nonreturn rate, SCC, and clinical mastitis. The empirical values of significance thresholds were determined using a permutation test on the experimental data. Although no significant effects were found, the results indicate some support for the existence of a locus on chromosome 9 that affects milk and protein yields. | {
"pile_set_name": "PubMed Abstracts"
} |
Aspiration and sclerotherapy: a nonsurgical treatment option for hydroceles.
We demonstrated that hydrocele aspiration and sclerotherapy with doxycycline is an effective and safe nonsurgical treatment option for hydrocele correction. The medical records of patients who underwent hydrocele aspiration and sclerotherapy were analyzed in a retrospective cohort study for success rates as well as improvement in scrotal size and discomfort after a single hydrocele aspiration and sclerotherapy treatment. Patients who reported decreased scrotal size, improved physical symptoms and satisfaction with the procedure were considered as having success with hydrocele aspiration and sclerotherapy. A total of 29 patients (mean age 52.8 years) presenting with 32 nonseptated hydroceles underwent hydrocele aspiration and sclerotherapy with doxycycline between 2005 and 2012. Of the hydroceles 27 (84%) were successfully treated with a single aspiration and sclerotherapy procedure. Overall mean followup was 20.8 months. Three patients reported moderate pain which resolved in 2 to 3 days. Of those patients in whom hydrocele aspiration and sclerotherapy failed, 1 had hydrocele successfully resolved with a second aspiration and sclerotherapy treatment, 3 did not have success with a second procedure and underwent hydrocelectomy, and 1 wanted immediate surgical correction. Hydrocele aspiration and sclerotherapy was successful in correcting 84% of simple nonseptated hydroceles with a single treatment. This result is an increase from previously reported success rates involving a single hydrocele aspiration and sclerotherapy procedure with tetracycline (75%). The success rate of a single hydrocele aspiration and sclerotherapy procedure is similar to the reported success rates involving hydrocelectomy while avoiding the hospital expense and many other complications. We conclude that the hydrocele aspiration and sclerotherapy procedure is a reasonable, nonsurgical and underused treatment option for nonseptated simple hydroceles. | {
"pile_set_name": "PubMed Abstracts"
} |
hs-CRP is strongly associated with coronary heart disease (CHD): A data mining approach using decision tree algorithm.
Coronary heart disease (CHD) is an important public health problem globally. Algorithms incorporating the assessment of clinical biomarkers together with several established traditional risk factors can help clinicians to predict CHD and support clinical decision making with respect to interventions. Decision tree (DT) is a data mining model for extracting hidden knowledge from large databases. We aimed to establish a predictive model for coronary heart disease using a decision tree algorithm. Here we used a dataset of 2346 individuals including 1159 healthy participants and 1187 participant who had undergone coronary angiography (405 participants with negative angiography and 782 participants with positive angiography). We entered 10 variables of a total 12 variables into the DT algorithm (including age, sex, FBG, TG, hs-CRP, TC, HDL, LDL, SBP and DBP). Our model could identify the associated risk factors of CHD with sensitivity, specificity, accuracy of 96%, 87%, 94% and respectively. Serum hs-CRP levels was at top of the tree in our model, following by FBG, gender and age. Our model appears to be an accurate, specific and sensitive model for identifying the presence of CHD, but will require validation in prospective studies. | {
"pile_set_name": "PubMed Abstracts"
} |
Early Conversion to Belatacept in Kidney Transplant Recipients With Low Glomerular Filtration Rate.
Our aim was to determine the impact of converting from tacrolimus to belatacept in patients with stable low estimated glomerular filtration rate (eGFR) early after kidney transplant. This is a single-center retrospective case control study. During this study period, we had a clinical protocol to convert patients to belatacept if they had a stable but low GFR and they were at least 1-month posttransplant. Eligible patients had stable but low eGFR usually < 40 mL/min per 1.73 m. We used direct matching to select 1 control case for each patient converted to belatacept. The primary outcome was the change in eGFR from the point of belatacept conversion to 4 months postconversion (delta eGFR). There were 30 patients in the conversion group and 30 in a direct matched control group. The median preconversion eGFR for the entire cohort was 23.0 mL/min per 1.73 m with an interquartile range of 15.7 to 31.4. The delta eGFR was 11.0 (12.9) mL/min per 1.73 m in belatacept group and 4.8 (10.5) mL/min per 1.73 m in the control group (P = 0.045). Acute rejection postconversion occurred in 5 (16.7%) in the conversion group and none of the control group (P = 0.052). Although the delta improvement in eGFR was about 6 mL/min better in the Belatacept group, there was no difference in the slope of inverse creatinine during the 12-month period after conversion between the groups. We conclude that early belatacept conversion in kidney transplant recipients with stable low eGFR may only result in a modest increase in GFR. | {
"pile_set_name": "PubMed Abstracts"
} |
Integrated QSPR--pharmacodynamic model of genomic effects of several corticosteroids.
The results from a quantitative structure-property relationship (QSPR) model was integrated into a fifth-generation pharmacokinetic/pharmacodynamic (PK/PD) model of corticosteroid receptor/gene-mediated effects. The proposed model was developed using previously reported tyrosine aminotransferase (TAT) activity data following a 50 mg/kg intravenous dose of methylprednisolone in male adrenalectomized (ADX) rats. Induced TAT activity is a classical measure of corticosteroid genomic effects and the typical time course shows an initial lag-time, a slow rise to peak response, and a gradual return toward baseline values. The TAT activity profiles were subsequently predicted for two additional steroids (dexamethasone and hydrocortisone), which were confirmed experimentally. Two groups of male ADX Wistar rats (n = 18 each) were given either 0.1 mg/kg dexamethasone or 50 mg/kg hydrocortisone by penile vein injections. Plasma drug concentrations and liver TAT activity were measured at various time points. Baseline TAT activity was significantly lower in this study as compared to previous reports. Model simulations well captured the pharmacodynamic data once initial conditions were corrected for observed baseline values. Additional TAT profiles reported in the literature for prednisolone were also reasonably predicted using the final model. This study serves as a demonstration of how in vitro pharmacologic data and QSPR modeling results may be incorporated into existing mechanistic PK/PD models to anticipate the effects of other chemically related compounds. | {
"pile_set_name": "PubMed Abstracts"
} |
PET/CT for the staging and follow-up of patients with malignancies.
Positron emission tomography (PET) and computed tomography (CT) complement each other's strengths in integrated PET/CT. PET is a highly sensitive modality to depict the whole-body distribution of positron-emitting biomarkers indicating tumour metabolic activity. However, conventional PET imaging is lacking detailed anatomical information to precisely localise pathologic findings. CT imaging can readily provide the required morphological data. Thus, integrated PET/CT represents an efficient tool for whole-body staging and functional assessment within one examination. Due to developments in system technology PET/CT devices are continually gaining spatial resolution and imaging speed. Whole-body imaging from the head to the upper thighs is accomplished in less than 20 min. Spatial resolution approaches 2-4mm. Most PET/CT studies in oncology are performed with (18)F-labelled fluoro-deoxy-D-glucose (FDG). FDG is a glucose analogue that is taken up and trapped within viable cells. An increased glycolytic activity is a characteristic in many types of cancers resulting in avid accumulation of FDG. These tumours excel as "hot spots" in FDG-PET/CT imaging. FDG-PET/CT proved to be of high diagnostic value in staging and restaging of different malignant diseases, such as colorectal cancer, lung cancer, breast cancer, head and neck cancer, malignant lymphomas, and many more. The standard whole-body coverage simplifies staging and speeds up decision processes to determine appropriate therapeutic strategies. Further development and implementation of new PET-tracers in clinical routine will continually increase the number of PET/CT indications. This promotes PET/CT as the imaging modality of choice for working-up of the most common tumour entities as well as some of the rare malignancies. | {
"pile_set_name": "PubMed Abstracts"
} |
The Mediterranean: high discovery rates for a well-studied trematode fauna.
Our knowledge of trematode diversity in Mediterranean Sea fishes is based on many contributions since the early 1800s (e.g. by Rudolphi, Stossich, Looss, Bartoli, Bray and Gibson). We have updated data from the Natural History Museum Host-Parasite Database and listed 302 digenean trematode species allocated to 146 genera in 29 families from 192 fish species (27% of the known fish-fauna) belonging to 76 families. The most diverse (with 31-41 species) digenean families (Opecoelidae Ozaki, 1925, Didymozoidae Monticelli, 1888 and Hemiuridae Looss, 1899) represent more than a third of the total richness (36% of species) and have been most frequently recorded (43% of the records). The overall mean number of species per host is close to recent global estimates for digenean richness in teleosts (1.57 vs 2.04, respectively), indicating a high diversity in the Mediterranean. The most diverse host families are also the best studied. However, three speciose host families (Rajidae de Blainville, Gobiidae Cuvier and Myctophidae Gill) appear under-studied and no digenean reports exist for 94 of 169 fish families present in the Mediterranean. Thus, although Mediterranean fishes appear well studied, further efforts are needed. Nevertheless, the descriptions of a large number of new taxa since 2000 indicate that focused efforts have resulted in a high discovery rate (2.4 species per year). Many of these new (often cryptic) taxa are the result of combined morphological and molecular methods, which promise more reliable estimates of digenean diversity in this region. We provide host-parasite lists for 192 species of fish in the Mediterranean comprising 890 host-parasite associations. | {
"pile_set_name": "PubMed Abstracts"
} |
Physiology: Dynamic instabilities in the inflating lung.
In lung diseases such as asthma, expiratory flow becomes limited, airways can collapse and the vital exchange of gases is compromised. Here we model the inflation of collapsed regions of the lung during inspiration in terms of avalanches propagating through a bifurcating network of airways, and find that the accompanying cascade of dynamic pressure instabilities -- avalanche 'shocks' -- manifests as negative elastic resistance of the lung. Our analysis of this apparent thermodynamic paradox provides a better understanding of aeration in the deep regions of the lung, which may find application in medical conditions in which gas exchange is impaired. | {
"pile_set_name": "PubMed Abstracts"
} |
Long-term care hospitals in Turkey: a review.
A long-term care hospital (LTCH) is a specialized facility for patients with serious health problems who require continuous and intensive care but not comprehensive diagnostic methods. LTCHs provide prolonged complex care and wound care in the period following the acute stage of disease. When intensive care unit (ICU) stay is prolonged in the United States of America, the patients may be transferred to an LTCH. Medicare suggests hospitalization > 25 days in LTCHs. The LTC system in Europe differs from that in other non-European countries and differences are also seen among European countries. In practice, patients who need LTC in Turkey are hospitalized in ICUs. Long term care is a new concept for the Turkish health system and there are no studies on LTCHs in Turkey. A significant proportion of intensive care beds in Turkey are used for long-term hospitalized patients with complex problems. This is a clear waste of resources. The establishment of LTCHs in Turkey would prevent from this waste and provide the opportunity to increase experience of complex treatments. | {
"pile_set_name": "PubMed Abstracts"
} |
Steerable catheters in minimally invasive vascular surgery.
Remote-controlled catheter navigation systems have recently been introduced into minimally invasive vascular surgery and some of them have already been applied in clinical practice. Steerable catheters with improved manoeuvrability play an important role in these innovations for conventional catheterization. This review details the development of various steerable catheters, both in use clinically and under investigation. Comprehensive comparison and analysis in several key aspects are followed to reveal both the advantages and limitations of these catheters, as well as the requirements for relevant techniques. Steerable catheters are able to select direction in the distal end, and superior to conventional counterparts in many aspects. Differences between magnetic and active catheters mainly lie in function, safety, configuration of operating room and cost. They have similar requirements for miniaturization and slave insertion mechanisms. Steerable catheters are rapidly evolving and still require technological refinements to extend current capabilities. | {
"pile_set_name": "PubMed Abstracts"
} |
Baseline stress myocardial perfusion imaging results and outcomes in patients with stable ischemic heart disease randomized to optimal medical therapy with or without percutaneous coronary intervention.
The COURAGE trial reported similar clinical outcomes for patients with stable ischemic heart disease (SIHD) receiving optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). The current post hoc substudy analysis examined the relationship between baseline stress myocardial ischemia and clinical outcomes based on randomized treatment assignment. A total of 1,381 randomized patients (OMT n = 699, PCI + OMT n = 682) underwent baseline stress myocardial perfusion single-photon emission computed tomographic imaging. Site investigators interpreted the extent of ischemia by the number of ischemic segments using a 6-segment myocardial model. Patients were divided into those with no to mild (<3 ischemic segments) and moderate to severe ischemia (≥ 3 ischemic segments). Cox proportional hazards models were calculated to assess time to the primary end point of death or myocardial infarction. At baseline, moderate to severe ischemia occurred in more than one-quarter of patients (n = 468), and the incidence was comparable in both treatment groups (P = .36). The primary end point, death or myocardial infarction, was similar in the OMT and PCI + OMT treatment groups for no to mild (18% and 19%, P = .92) and moderate to severe ischemia (19% and 22%, P = .53, interaction P value = .65). There was no gradient increase in events for the overall cohort with the extent of ischemia. From the COURAGE trial post hoc substudy, the extent of site-defined ischemia did not predict adverse events and did not alter treatment effectiveness. Currently, evidence supports equipoise as to whether the extent and severity of ischemia impact on therapeutic effectiveness. | {
"pile_set_name": "PubMed Abstracts"
} |
Peripheral adrenoceptors in hypotension of hemodialyzed uremic patients.
Hypotension is a common problem in patients on hemodialysis. To further investigate this problem, the number of platelet alpha 2-adrenoceptors and the activity of lymphomonocyte beta 2-adrenoceptors were measured in 10 hemodialyzed patients with normal blood pressure and in 10 sex- and age-matched persistently hypotensive hemodialyzed patients. Density of alpha 2-adrenoceptors was assessed by the specific binding of 3H-yohimbine to intact platelets, while the function of beta 2-adrenoceptors was estimated by the production of cAMP after the exposure of lymphomonocytes to isoprenaline. The maximal number of alpha 2-adrenoceptors was increased in the hypotensive compared to the normotensive group (262.13 vs. 77.21 fmol/mg protein; p < 0.01). Plasma norepinephrine was higher in the hypotensive than in the normotensive uremic patients (640 +/- 195 vs. 344 +/- 156 pg/ml; p < 0.01). Plasma epinephrine did not differ in the two groups (90 +/- 30 vs. 94 +/- 24 pg/ml). The amount of cAMP, produced by stimulation of lymphomonocytes, was lower in the hypotensive than that in the normotensive uremic patients (7.7 +/- 2.4 vs. 15.6 +/- 5.4 pmol/10(6) cells; p < 0.002). The increased number of alpha 2-adrenoceptors together with a high level of norepinephrine and reduced activity of adenylate cyclase (coupled with beta 2-adrenoceptors) support the hypothesis that hypotension in the hemodialyzed uremic patients may be related to a defect in adrenoceptor coupling mechanisms. | {
"pile_set_name": "PubMed Abstracts"
} |
Mutagenicity test for unstable compounds, such as 5,6-dihydroxyindole, using an Escherichia coli HB101/pBR322 transfection system.
A mutagenicity test for unstable chemical compounds has been devised. The test makes use of (i) in vitro treatment of plasmid pBR322 with the putative mutagen (ii) subsequent transfection of Escherichia coli HB101; (iii) selection either on tetracycline- or ampicillin-containing Eugon agar (iv) cross-antibiotic replica plating and recovery of single antibiotic resistant colonies (v) restriction analysis of pBR322 isolated from single antibiotic resistant colonies. In this work the test has been used to assess the mutagenicity of 5,6-dihydroxyindole, a cytotoxic intermediate of melanin biosynthesis. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of general anesthetics and pressure on aerobic metabolism of monkey kidney cells.
The authors examined the inhibition of aerobic metabolism in monkey kidney cell cultures exposed to halothane, enflurane, and isoflurane. The ability of hyperbaric pressure to reverse the halothane-induced metabolic inhibition also was examined. Incubation of two monkey kidney cell lines for 24 h with clinically equipotent concentrations (2.6 MAC) of halothane, enflurane, or isoflurane vapors increased the concentration of lactate in the media by 126 to 244% relative to nonexposed control cultures. The increased rate of lactate accumulation was proportional to the concentration of halothane and was accompanied by a decrease in media pH. Removal of halothane restored the normal rate of lactate production. Hyperbaric pressures of 25, 50, and 100 atmospheres did not alter the halothane-stimulated rate of lactate production relative to non-anesthetic-treated controls, although pressure alone did depress the rate of lactate accumulation in all cultures. The stimulation of lactate production likely reflects the known ability of halothane to inhibit mitochondrial respiration. The failure of pressure to reverse the stimulation of lactate production by halothane suggests that inhibition of mitochondrial metabolism cannot be reversed by pressure. | {
"pile_set_name": "PubMed Abstracts"
} |
Perinatal expression of HSP70 and VEGF in neonatal rat lung vessels exposed to nicotine during gestation.
We assessed the influence of maternal nicotine exposure during gestation on perinatal expression of HSP70 and VEGF in rat lung parenchyma and lung vessels. Adult white Sprague-Dawley virgin rats were mated with adult male rats over 2 days, with two females for every male. After confirming pregnancy, 30 gravid rats (dams) were then randomly assigned to two equal groups (one experimental and one control; n=15 in each). Experimental dams were treated with subcutaneus (s.c.) (-)-nicotine tartrate, 3 mg/kg body weight/day, during pregnancy from gestational days 9 through 21. After sacrifice, lungs were removed en bloc and formalin-fixed, and paraffinembedded tissue sections were evaluated by immunohistochemistry using a three-step streptavidin-biotin-peroxidase method with monoclonal antibodies directed against HSP70 or VEGF. HSP70 and VEGF expression was increased in the vascular smooth muscle cells of the experimental group (t1) compared to the control group (t(2))t(1)=7.593, t(2)=4.666, p<0.05). The number of bronchioles that stained positively with HSP70 was higher in the nicotineexposed group than in the control group (t(1)=9.274, t(2)=6.956, p<0.05). In conclusion, gestational nicotine exposure increased the expression of VEGF and HSP70 in rat lung parenchyma, especially in the airway epithelium and vascular smooth muscle cells. In vascular smooth muscle cells, these molecules may contribute to nicotine-related hypoxic pulmonary hypertension. | {
"pile_set_name": "PubMed Abstracts"
} |
International medical graduates and general practice training: How do educational leaders facilitate the transition from new migrant to local family doctor?
Objectives: To document medical educators' experience and initiatives in training international medical graduates (IMGs) to become general practitioners (GP). Design: Qualitative social-constructivist emergent design with descriptive and interpretive analyses. Setting: GP vocational training in Australia, Canada, Ireland, New Zealand, the Netherlands, and UK. Participants: Twenty-eight leaders of GP training. Intervention: Data collected from public documents, published literature and 27 semi-structured interviews. Main outcome measures: Tensions in training and innovations in response to these tensions. Results: Medical educators identified tension in teaching IMGs as it could be different to teaching domestic graduates in any or all aspects of a training program. They felt an ethical responsibility to support IMGs to provide quality health care in their adopted country but faced multiple challenges to achieve this. They described initiatives to address these throughout GP training. Conclusions: IMG's differing educational needs will benefit from flexible individualized adaptation of training programs. | {
"pile_set_name": "PubMed Abstracts"
} |
Glycine site associated with the NMDA receptor modulates long-term potentiation.
Recent work has shown that kynurenic acid and several quinoxaline derivatives act as non-competitive NMDA receptor antagonists by binding to the glycine site associated with this receptor. In this study, we have tested the effect of the most potent and selective of these compounds, 7-chlorokynurenic acid (Cl-Kyn), on the induction of long-term potentiation, an event known to involve activation of NMDA receptors. It was found that 30 microM Cl-Kyn reversibly abolished the development of both short-term and long-term potentiation in the CA1 region of hippocampal slices. The effectiveness of Cl-Kyn matched its ability to inhibit 3H-glycine binding and the association of 3H-TCP with the NMDA receptor in binding experiments (Ki 0.7-1 microM). Weak interactions of Cl-Kyn with AMPA receptor sites were observed and may account for a partial, reversible reduction in the epsp. However, blockade of long-term potentiation by Cl-Kyn was completely reversed by simultaneous application of the glycine site agonist D-serine and thus must be attributed to its interaction with the glycine site. These results indicate that the glycine site coupled to the NMDA receptor potently modulates channel function during physiological events related to synaptic activation. | {
"pile_set_name": "PubMed Abstracts"
} |
Prognostic CT findings of diplopia after surgical repair of pure orbital blowout fracture.
Diplopia is a common sequela of blowout fracture even after proper surgical management. We investigated the prognostic factors of diplopia after surgery of pure blowout fracture. We retrospectively reviewed CT images of 181 patients with pure orbital blowout fracture who underwent at least six months of postoperative follow-up. We evaluated the following CT factors: (1) fracture site (orbital floor, medial wall of the orbit, or both), (2) fracture type (closed flap, open flap), (3) fracture size, (4) volume of herniated orbital soft tissue, (5) ratio of volume of herniated orbital soft tissue to fracture size, (6) number of points of contact between extraocular muscle (EOM) and bony edge, (7) presence of EOM thickening, (8) EOM swelling ratio, (9) presence of displacement of EOM, (10) presence of deformity of EOM, (11) presence of tenting of EOM, and (12) presence of entrapment of EOM. The associations between diplopia at six months after surgical repair and various risk factors were analyzed using logistic regression models for univariable and multivariable analyses. EOM tenting and deformity and ratio of volume of herniated orbital soft tissue to fracture size were found to be statistically significant risk factors of diplopia at six months after repair on univariable analysis (all P < 0.05). Patients who showed EOM tenting or deformity on CT images had 5.22 and 10.85 times greater probability of diplopia after surgery, respectively (P-value, <0.001 and 0.026; 95% confidence interval of odds ratio, 2.071-13.174 and 1.323-88.915, respectively). On the other hand, ratio of volume of herniated orbital soft tissue to fracture size was not significant on multivariable analysis (P = 0.472). The prognosis of patients was predicted by CT evaluation. Patients who have tenting or deformity of EOM on CT scan are more likely to have postoperative diplopia. | {
"pile_set_name": "PubMed Abstracts"
} |
Lactose malabsorption and irritable bowel syndrome. Effect of a long-term lactose-free diet.
Lactose malabsorption may induce abdominal symptoms indistinguishable from those of the irritable bowel syndrome (IBS), however the exact relationship between the two conditions and the optimal differential diagnostic workup are still to be defined. We prospectively studied the prevalence of lactose malabsorption (by means of a hydrogen breath test) and the clinical effect of a long-term lactose-free diet in 230 consecutive patients with a suggested diagnosis of irritable bowel syndrome, no organic disease of the GI tract, and no history of milk intolerance. Lactose malabsorption was diagnosed in 157 patients (68.2%). In 48 (43.6%) of the 110 patients who complied with the diet symptoms subsided, in 43 they were somewhat reduced and in 17 they remained unchanged. Symptoms never fully subsided in lactose malabsorbers non-compliant with the diet or in normal lactose absorbers who adhered to a lactose-free regimen. Partial improvement was observed in 20% of these subjects. No relation was demonstrated between pre-trial symptoms and the outcome of the diet. The occurrence of symptoms during the lactose breath test strongly suggested a favorable response to diet, but did not help in predicting whether symptoms would subside or be reduced. Conversely, their absence during the test was not associated with an acceptable negative predictive value. The high prevalence of lactose malabsorption in the patients under study suggests that in Italy IBS and lactose malabsorption are frequently associated. A test for diagnosing lactose malabsorption should always be included in the diagnostic workup for IBS and a long-term lactose-free regimen recommended if the test is positive. | {
"pile_set_name": "PubMed Abstracts"
} |
[Long-acting medications for the treatment of hyperkinetic disorders - a systematic review and European treatment guidelines. Part 2: a quantitative evaluation of long-acting medications].
A panel of experts from several European countries has accomplished a systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorders, on the basis of which practical recommendations for the application of these medications have been developed. The current article outlines results of this analysis, comparing the effect sizes and numbers-needed to-treat for extended-release stimulant preparations and atomoxetine (ATX). It is concluded (1) that long-acting preparations should be licensed and used. (2) However, they should not completely replace short-acting medications, in view of costs as well as the greater flexibility of dosing. Individual choices of therapy are necessary. (3) Both ATX and retarded-release stimulants should be available. | {
"pile_set_name": "PubMed Abstracts"
} |
Safety of enhanced renin-angiotensin-aldosterone system inhibition with aliskiren in nondiabetic patients with chronic kidney disease.
Various methods of combination renin-angiotensin-aldosterone system blockade help achieve more potent antiproteinuric effects, but may be associated with higher risk of side effects. Therapies involving direct renin inhibitor, aliskiren, may promote renal fibrosis by stimulating (pro)renin receptor due to increased renin levels. The aim of the study was to compare the effects of combination treatment with angiotensin receptor blockers, telmisartan (80 mg/d) and aliskiren (300 mg/d) with those of combination treatment with 80 mg/d telmisartan and mineralocorticoid receptor blocker (50 mg/d eplerenone) and telmisartan (160 mg/d) alone on the urinary excretion of transforming growth factor β1 (TGF‑β1), renal function, and serum potassium levels. A randomized open-label controlled cross-over study was performed in 18 white patients (7 women and 11 men; mean age, 42.4 ±1.9 years) with proteinuric nondiabetic chronic kidney disease and estimated glomerular filtration rate of 85.2 ±4.6 ml/min. The urinary excretion of TGF‑β1 was stable despite a significant increase in plasma renin levels after treatment with telmisartan and aliskiren. There were no differences in renal function and serum potassium levels between the compared treatments. Moreover, there were no episodes of hypotension or acute renal impairment. Combination therapy with telmisartan and aliskiren may be safe in young nondiabetic patients with normal renal function at low vascular risk. This treatment may be an alternative for a subset of patients in whom standard RAA system blockade is ineffective. | {
"pile_set_name": "PubMed Abstracts"
} |
Development of MATLAB software to control data acquisition from a multichannel systems multi-electrode array.
A Multichannel Systems (MCS) microelectrode array data acquisition (DAQ) unit is used to collect multichannel electrograms (EGM) from a Langendorff perfused rabbit heart system to study sudden cardiac death (SCD). MCS provides software through which data being processed by the DAQ unit can be displayed and saved, but this software's combined utility with MATLAB is not very effective. MCSs software stores recorded EGM data in a MathCad (MCD) format, which is then converted to a text file format. These text files are very large, and it is therefore very time consuming to import the EGM data into MATLAB for real-time analysis. Therefore, customized MATLAB software was developed to control the acquisition of data from the MCS DAQ unit, and provide specific laboratory accommodations for this study of SCD. The developed DAQ unit control software will be able to accurately: provide real time display of EGM signals; record and save EGM signals in MATLAB in a desired format; and produce real time analysis of the EGM signals; all through an intuitive GUI. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials.
We aimed to investigate the efficacy of canagliflozin (based on its effect on liver function and blood glucose levels) and its safety in high alanine aminotransferase (ALT) patients (ALT >30 U/L). This post hoc analysis of canagliflozin in type 2 diabetes mellitus (T2DM) patients was divided into Study 1 (pooled analysis of 12- and 24-week placebo-controlled, monotherapy studies) and Study 2 (52-week monotherapy/combination therapy study). The canagliflozin 100 mg group data were compared with placebo or baseline ALT subgroup (baseline ALT >30 or ≤30 U/L) data. The primary endpoint was change in ALT level from baseline. Secondary endpoints were changes in efficacy-related parameters. Adverse events (AEs) were evaluated. The mean ALT change at 12 weeks was -10.3 ± 11.7 and -3.2 ± 17.6 U/L in the canagliflozin vs. placebo group in the high ALT subgroup (P = 0.0206); no significant difference was shown in the low ALT subgroup (Study 1). In both ALT subgroups, glycosylated hemoglobin (HbA1c) and body weight were significantly reduced in the canagliflozin vs. placebo group (all P < 0.0001). The mean change in ALT at 52 weeks was -16.0 ± 18.8 U/L in the high ALT subgroup (P < 0.0001, Study 2). The incidence of AEs or serious AEs in the high ALT subgroup in the canagliflozin group was similar to that in the placebo group (Study 1) or low ALT subgroup (Studies 1 and 2). In T2DM patients with impaired liver function, canagliflozin may improve liver function, reduce HbA1c and body weight, and be well tolerated. | {
"pile_set_name": "PubMed Abstracts"
} |
Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia.
Modafinil, a novel cognitive enhancer, selectively improves neuropsychological task performance in healthy volunteers and adult patients with attention deficit hyperactivity disorder (ADHD). It has been argued that persistent cognitive deficits in patients with schizophrenia are responsible for the failure of many patients to rehabilitate socially even when psychotic symptoms are in remission. The present study examined the potential of modafinil as a cognitive enhancer in schizophrenia. Twenty chronic patients with a diagnosis of schizophrenia were entered into a double-blind, randomized, placebo-controlled crossover study using a 200 mg dose of modafinil. Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD. Improvement was seen on short-term verbal memory span, with trends towards improved visual memory and spatial planning. This was accompanied by slowed response latency on the spatial planning task. No effect on stop-signal performance was seen. Importantly, significant improvement in attentional set shifting was seen, despite no effect of modafinil on this task being seen in healthy volunteers or ADHD patients. Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis, structure and dispersion interactions in bis(1,8-naphthalendiyl)distibine.
Naph2Sb21 was synthesized by a reaction of 1,8-dilithionaphthalene NaphLi2 with SbCl3 and its solid state structure is reported on. 1 shows intermolecular interactions in the solid state, which were studied by quantum chemical calculations with dispersion corrected density functional theory, supermolecular ab initio approaches and symmetry adapted perturbation theory. The same methods were employed to compare the solid state interactions in the crystal of 1 to those in real (for E = P) and hypothetical (for E = As and Bi) crystal structures of Naph2E2. Dispersion interactions were found to provide the most important stabilising contribution in all cases, seconded by electrostatic attraction between pnictogen atoms and π-systems of neighbouring naphthyl groups. | {
"pile_set_name": "PubMed Abstracts"
} |
Dictyopyrones, novel alpha-pyronoids isolated from Dictyostelium spp., promote stalk cell differentiation in Dictyostelium discoideum.
Dictyopyrones A and B (DpnA and B), whose function(s) is not known, were isolated from fruiting bodies of Dictyostelium discoideum. In the present study, to assess their function(s), we examined the effects of Dpns on in vitro cell differentiation in D. discoideum monolayer cultures with cAMP. Dpns at 1-20 microM promoted stalk cell formation to some extent in the wild-type strain V12M2. Although Dpns by themselves could hardly induce stalk cell formation in a differentiation-inducing factor (DIF)-deficient strain HM44, both of them dose-dependently promoted DIF-1-dependent stalk cell formation in the strain. In the sporogenous strain HM18, Dpns at 1-20 microM suppressed spore formation and promoted stalk cell formation in a dose-dependent manner. Analogs of Dpns were less effective in affecting cell differentiation in both HM44 and HM18 cells, indicating that the activity of Dpns should be chemical structure specific. It was also shown that DpnA at 2-20 microM dose-dependently suppressed spore formation induced with 8-bromo cAMP and promoted stalk cell formation in V12M2 cells. Interestingly, it was shown by the use of RT-PCR that DpnA at 10 microM slightly promoted both prespore- and prestalk-specific gene expressions in an early phase of V12M2 and HM18 in vitro differentiation. The present results suggest that Dpns may have functions (1) to promote both prespore and prestalk cell differentiation in an early stage of development and (2) to suppress spore formation and promote stalk cell formation in a later stage of development in D. discoideum. | {
"pile_set_name": "PubMed Abstracts"
} |
Human dihydrofolate reductase: reduction of alternative substrates, pH effects, and inhibition by deazafolates.
The kinetics of the NADPH-dependent reduction of 7,8-dihydrofolate, folate, and 7,8-dihydrobiopterin by human dihydrofolate reductase have been examined over the pH range from 4.0 to 9.5. The V and V/K profiles obtained with the three substrates indicate that a single ionizing residue at the active site of the enzyme must be protonated for catalysis. Both the maximum velocity of the reactions and the rate of interaction of the substrates with the enzyme-NADPH complex decrease in the order dihydrofolate greater than dihydrobiopterin much greater than folate. From the pK values of the V/K profiles, it can be concluded that, while dihydrofolate behaves as a sticky substrate and dihydrobiopterin exhibits slight stickiness, folate is not a sticky substrate. Further support for this conclusion comes from the results of deuterium isotope effects. The pK values obtained from both the V and V/Kfolate profiles are similar to the intrinsic pK value of 5.6 for both the free enzyme and the enzyme-NADPH complex. The folate analogue, 5-deazafolate, is not a substrate, but it undergoes strong interaction with the enzyme. This interaction, which is enhanced by the presence of NADPH, is due to protonation of the bound ligand that does not involve the single ionizing group at the active center of the enzyme. Difference spectra yield evidence for the protonation of bound 5-deazafolate and show that, on binding to the enzyme-NADPH complex, the pK of the N-8 atom is raised to about 10 from a value of about 4 in solution. The results are in accord with those of a recent paper on the three-dimensional structure of the enzyme-5-deazafolate complex [Davies, J.F., Delcamp, T.J., Prendergast, N.J., Ashfors, V.A., Freisheim, J.H., & Kraut, J. (1990) Biochemistry 29, 9467-9479] which indicate that there is hydrogen bond formation between N-8 of the ligand and the carbonyl group of Ile-7. However, the present findings do not support the idea that bound 5-deazafolate resembles the transition-state complex for folate reduction. Quinazolines also interact strongly with the enzyme but in a pH-independent manner. The dissociation constants for the binary complexes are an order of magnitude lower than that for the binding to the enzyme of unprotonated 5-deazafolate. This difference reflects the hydrophobic nature of the amino acid residues at the active site that are near the N-5 and N-8 nitrogens of bound pterins. | {
"pile_set_name": "PubMed Abstracts"
} |
Accuracy of tobramycin delivery by four i.v. infusion methods.
The accuracy of tobramycin delivery by four methods of intermittent intravenous infusion was studied in 11 healthy male volunteers. Subjects received intravenous tobramycin (as the sulfate salt) 1.5 mg/kg by each of four infusion methods in a nonblinded, randomized, four-way crossover design. The methods used for intravenous infusion were (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric infusion pump (MP), (3) metered chamber via volumetric infusion pump (MC), and (4) syringe pump (SP). Doses were diluted to a volume of 50 mL, except for the two minibag methods, for which the dilution was necessarily greater because of manufacturer overfill. Intravenous flow rates for both primary fluid and drug administration were set at 100 mL/hr, and the duration of drug infusion was documented by observation for each administered dose. The fluid volume of 12 minibags was measured to assess manufacturer overfill. Fluid remaining in the secondary i.v. tubing for the minibag methods was collected after the infusion. Seventeen blood samples were obtained before and at various time intervals after each dose and analyzed in duplicate for tobramycin content by fluorescence polarization immunoassay. A mean of 10% of each dose remained in the secondary i.v. tubing at the completion of the infusion for the minibag methods, whereas less than 1% of each dose remained in the secondary tubing for the SP method.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
A systematic review of studies on heart transplantation for patients with end-stage Chagas' heart disease.
Uncertainties regarding indications for the procedure, proper immunosuppressive regimen, and the fear of Trypanosoma cruzi infection reactivation are major concerns regarding heart transplantation (HTx) for patients with end-stage Chagas' heart disease. To review indications for HTx, current immunosuppressive therapy, posttransplant morbidities, and outcome in Chagas' heart transplant recipients. Review of articles linking HTx and Chagas' disease at PubMed and Scielo database from 1966 onward. HTx can reasonably be indicated in patients with an annual probability of death of 70%. HTx has been associated with a similar incidence of rejection episodes in Chagas' and non-Chagas' heart transplant recipients. A lower incidence of infection episodes has been observed in Chagas' in comparison to non-Chagas' heart transplant recipients. T. cruzi infection reactivation is easily treated with either benznidazole or allopurinol and portends a very low mortality rate. Other posttransplant morbidities have a similar incidence in Chagas' and in non-Chagas' patients. Survival probability for Chagas' HTx recipients at 1 month, 1 year, 4 years, and 10 years follow-up is 83%, 71%, 57%, and 46%, respectively. Such an outcome is better than that seen in non-Chagas' heart transplant recipients. HTx is safe and efficacious for patients with end-stage Chagas' heart disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Ruptured dissecting vertebral artery aneurysm detected by repeated angiography: case report.
A case of a ruptured dissecting aneurysm of the vertebral artery, which was detected by repeated angiography (third time), is reported. A 59-year-old woman, whose preoperative angiogram showed no abnormality, underwent a bifrontal craniotomy and the total removal of the right frontal glioma. However, a subarachnoid hemorrhage was detected by computed tomography the day after the surgery. Conventional angiography performed on the same day revealed no definite abnormality. Nevertheless, 9 days after surgery, a second subarachnoid hemorrhage occurred. The dissecting aneurysm of the vertebral artery was revealed by angiography. It is important to suspect this type of aneurysm as a differential diagnosis when the cause of the subarachnoid hemorrhage is not clarified in the first angiogram. | {
"pile_set_name": "PubMed Abstracts"
} |
The expression of CDK1 is associated with proliferation and can be a prognostic factor in epithelial ovarian cancer.
Overexpression of cyclin-dependent kinase 1 (CDK1) has been noted to correlation with several human cancers. However, the effects of CDK1 on ovarian cancer development remain unclear. The aim of this study was to examine the effect of CDK1 and related mechanism in the proliferation and resistance to chemotherapeutic drugs of epithelial ovarian cancer (EOC). Immunohistochemical analysis was performed in 119 human ovarian cancer samples, and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for CDK1 in EOC samples and cell lines to evaluate their protein levels and molecular interaction. Kaplan-Meier survival analysis showed that strong expression of CDK1 exhibited a significant correlation with poor prognosis in human EOC (P = 0.02). Meanwhile, we found that knockdown CDK1 by shCDK1 promoted the apoptosis rate and increased the sensitivity to chemotherapy drugs. Thus, CDK1 might serve as a prognostic marker, and it might be of great value for experimental therapies in EOC. | {
"pile_set_name": "PubMed Abstracts"
} |
Evolution of intrinsic vacancies and prolonged lifetimes of vacancy clusters in black phosphorene.
Due to the relatively low formation energies and highly mobile characteristics of atomic vacancies in phosphorene, understanding their evolution becomes crucial for its structural integrity, chemical activities and applications. Herein, by combining first-principles calculations and kinetic Monte Carlo simulation, we investigate the time evolution and formation of atomic vacancy clusters from isolated monovacancies (MVs), aiming to uncover the mechanisms of diffusion, annihilation, and reaction of these atomic vacancies. We find that while isolated MVs possess a highly mobile characteristic, they react and form MV pairs which possess much lower mobility and high stability under ambient conditions. We also show that the disappearance of MVs at the edge is quite slow due to the relatively high energy barrier, and as a result, around 80% of MVs remain even after two years under ambient conditions. Our findings on one hand provide useful information for the structural repairing of phosphorene through chemical functionalization of these vacancy clusters, and on the other hand, suggest that these rather stable vacancy clusters may be used as activated catalysts. | {
"pile_set_name": "PubMed Abstracts"
} |
A general method for preparation of peptides biotinylated at the carboxy terminus.
A method for the preparation of a biotinylated resin that can be elongated by standard methods of solid-phase peptide synthesis to give peptides biotinylated at the carboxy terminus is described. This methodology is particularly important for the preparation of biotinylated peptides in which a free amino terminus is required. Coupling of N epsilon-9-fluorenylmethoxycarbonyl-(Fmoc)-N alpha-tert-butyloxycarbonyl(Boc)-L- lysine to p-methylbenzhydrylamine resin, followed by removal of the Fmoc protecting group and reaction with (+)-biotin-4-nitrophenyl ester yielded N alpha-Boc-biocytin-p-methyl-benzhydrylamine resin. The utility of this resin was tested by the synthesis of a biotinylated peptide, Gly-Asn-Ala-Ala-Ala-Ala-Arg-Arg-biocytin-NH2, for use as an in vitro substrate for myristoyl-CoA:protein N-myristoyltransferase (NMT), the enzyme that catalyzes protein N-myristoylation. Analysis of the peptide derivative by HPLC and mass spectrometry revealed a single major product of the expected mass, indicating that the biotin group survived cleavage and deprotection with HF. The biotinylated peptide served as a substrate for NMT, and the resulting myristoylated peptide could be quantitatively recovered by adsorption to immobilized avidin. | {
"pile_set_name": "PubMed Abstracts"
} |
Goblet cell carcinoid of the appendix: laparoscopic appendectomy or right hemicolectomy?
Goblet cell carcinoids are uncommon tumours with histological features of both adenocarcinoma and carcinoid tumour. They occur predominantly in the appendix and although the malignant potential remains unclear, adenocarcinoids appear to be more aggressive than conventional carcinoids. In this case report, we present a goblet cell carcinoid with laparoscopic operative treatment in two stages. A 43-year-old female patient with constant dullness in the right lower quadrant was diagnosed with acute appendicitis and underwent laparoscopic appendectomy. Macroscopically, a diffusely inflamed appendix was found with no sign of perforation. Histopathological examination revealed a goblet cell carcinoid with characteristics of aggressive behaviour, indicating the need for laparoscopic right hemicolectomy in which, however, neither residual tumour nor metastatic lymph nodes could be found. The postoperative course was uneventful. As they may present the same clinical presentation, pathological diagnosis is required to distinguish goblet cell carcinoid from acute appendicitis. Two-stage surgery for goblet cell carcinoid is advocated in the literature, but the debate still continues as to whether the goblet cell carcinoid should be treated by appendectomy alone, as for most carcinoids, or by right hemicolectomy, as for the appendiceal adenocarcinoma. | {
"pile_set_name": "PubMed Abstracts"
} |
[Change of the expression of adrenomedullin in lung and effect on contraction of isolated tracheal strip of asthmatic guinea pigs].
To study the formation and localization of ADM mRNA in lung tissues and investigate the effects of ADM on isolated tracheal strip contraction induced by histamine in asthmatic guinea pig. The guinea pigs (n = 22) were randomly divided into two groups of 11 each: asthmatic group and control group. The formation and localization of ADM mRMA were observed by in site hybridization. The effect of exogenous ADM on contractions of isolated tracheal strip of the asthmatic guinea pigs to histamine was examined. There were strong positive expression for ADM mRNA in airway epithelial cells (AEC), smooth muscle cells (ASMC) in asthmatic group. The control group showed significantly decreased number of ADM mRNA positive cells in lung tissues. From 10(-11) mol/L to 10(-7) mol/L, ADM may cause concentration depend pentiation of the isolated tracheal strip contraction induced by histamine of asthmatic group which was higher significantly compared the control group (P < 0.05). 10(-8) mol/L ADM reached the maximal relaxation, with the increasing of ADM, neither asthmatic nor control group can increase the relaxation. There is ADM mRNA overproduction in AEC and ASMC and exogenous ADM may inhibit isolated tracheal strip contraction induced by histamine of asthmatic guinea pig, which may contribute to airway inflammation and hyperresponsiveness in asthma. | {
"pile_set_name": "PubMed Abstracts"
} |
Prediabetic neuropathy: does it exist?
It is now increasingly being appreciated that a substantial proportion of subjects with prediabetes may exhibit peripheral neuropathy and/or neuropathic pain. The reverse is also true, inasmuch as examining patients with idiopathic peripheral neuropathy will frequently reveal prediabetes. In the general population, the prevalence of neuropathy in prediabetes is intermediate between overt diabetes and subjects with normoglycemia. This prediabetic neuropathy is, generally, milder in comparison to diabetic neuropathy and mainly affects small fibers mediating sensory function. Hyperglycemia, microangiopathy, dyslipidemia and the metabolic syndrome have been implicated as pathogenic mechanisms. In practice, therapy of prediabetic neuropathy should be addressed towards normoglycemia and correction of cardiovascular risk factors. However, additional work is needed to establish the long-term results of this approach. | {
"pile_set_name": "PubMed Abstracts"
} |
Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance.
An invasive micropapillary component has been described in tumors of several organs and is nearly always associated with aggressive biologic behavior. We present 14 cases of salivary duct carcinoma (SDC) with an invasive micropapillary component (invasive micropapillary SDC) and compare the clinicopathologic findings of these cases with those of cases of conventional SDC. The mean age of the 14 patients (10 men, 4 women) was 65.8 years (range, 26-80 years). The mean size of the tumors was 2.4 cm (range, 1.3-5 cm). The parotid gland was involved in 12 patients and the submandibular gland in 2. Histologically, all tumors had an invasive micropapillary architecture admixed with features typical for SDC. Invasive micropapillary carcinoma was characterized by morula-like small cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells exhibited moderate- to high-grade nuclear features, conspicuous nucleoli, and eosinophilic cytoplasm. This component was distributed diffusely in 9 tumors and focally in 5. Angiolymphatic and perineural invasion was seen in all tumors. A residual pleomorphic adenoma was detected in four tumors. Of the 12 tumors examined, all were diffusely positive for cytokeratin 7 and epithelial membrane antigen (with a distinctive "inside-out" pattern) but negative for cytokeratin 20. Tumors were frequently immunoreactive for BRST-2 (gross cystic disease fluid protein-15) and androgen receptor protein. Aberrant expression of HER-2/neu or p53 was detected in seven tumors each. The mean Ki-67 labeling index was 33.1% (range, 6.3%-61.6%). All 14 patients with invasive micropapillary SDC had cervical or periglandular lymph node metastasis, and this value was significantly higher than for conventional SDCs. Local recurrence developed in 4 patients and distant metastatic disease in 9. Clinical follow-up (mean, 25.5 months) was available for 13 patients: 9 died of disease within 24 months after the diagnosis (mean, 17.6 months), 1 was alive with metastatic disease at 19 months, and 3 were free of disease. Overall survival of these patients with invasive micropapillary SDC was significantly shorter than that of patients with conventional SDC (n = 49) in our series (P = 0.031). Our results suggest that invasive micropapillary SDC is a distinct, aggressive variant of SDC, with a propensity for extensive lymph node metastasis and rapid disease progression. | {
"pile_set_name": "PubMed Abstracts"
} |
Water permeability of Necturus gallbladder epithelial cell membranes measured by nuclear magnetic resonance.
In order to assess the contribution of transcellular water flow to isosmotic fluid transport across Necturus gallbladder epithelium, we have measured the water permeability of the epithelial cell membranes using a nuclear magnetic resonance method. Spin-lattice (T1) relaxation of water protons in samples of gallbladder tissue where the extracellular fluid contained 10 to 20 mM Mn2+ showed two exponential components. The fraction of the total water population responsible for the slower of the two was 24 +/- 2%. Both the size of the slow component, and the fact that it disappeared when the epithelial layer was removed from the tissue, suggest that it was due to water efflux from the epithelial cells. The rate constant of efflux was estimated to be 15.6 +/- 1.0 sec-1 which would be consistent with a diffusive membrane water permeability Pd of 1.6 X 10(-3) cm sec-1 and an osmotic permeability Pos of between 0.3 X 10(-4) and 1.4 X 10(-4) cm sec-1 osmolar-1. Using these data and a modified version of the standing-gradient model, we have reassessed the adequacy of a fluid transport theory based purely on transcellular osmotic water flow. We find that the model accounts satisfactorily for near-isosmotic fluid transport by the unilateral gallbladder preparation, but a substantial serosal diffusion barrier has to be included in order to account for the transport of fluid against opposing osmotic gradients. | {
"pile_set_name": "PubMed Abstracts"
} |
Three-dimensional structure of O-acetylserine sulfhydrylase from Salmonella typhimurium.
The last step in cysteine biosynthesis in enteric bacteria is catalyzed by the pyridoxal 5'-phosphate-dependent enzyme O-acetylserine sulfhydrylase. Here we report the crystal structure at 2.2 A resolution of the A-isozyme of O-acetylserine sulfhydrylase isolated from Salmonella typhimurium. O-acetylserine sulfhydrylase shares the same fold with tryptophan synthase-beta from Salmonella typhimurium but the sequence identity level is below 20%. There are some major structural differences: the loops providing the interface to the alpha-subunit in tryptophan synthase-beta and two surface helices of tryptophan synthase-beta are missing in O-acetylserine sulfhydrylase. The hydrophobic channel for indole transport from the alpha to the beta active site of tryptophan synthase-beta is, not unexpectedly, also absent in O-acetylserine sulfhydrylase. The dimer interface, on the other hand, is more or less conserved in the two enzymes. The active site cleft of O-acetylserine sulfhydrylase is wider and therefore more exposed to the solvent. A possible binding site for the substrate O-acetylserine is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Understanding and Interpreting Educational Research Martella Ronald C et al Understanding and Interpreting Educational Research 704pp $80/£46.99 The Guildford Press 978 1 4625 0962 1462509622 [Formula: see text].
This American text is a comprehensive and substantial tool for research design. | {
"pile_set_name": "PubMed Abstracts"
} |
Perspectives on the current developments with neuromodulation for the treatment of epilepsy.
Introduction: As deep brain stimulation revolutionized the treatment of movement disorders in the late 80s, neuromodulation in the treatment of epilepsy will undoubtedly undergo transformative changes in the years to come with the exponential growth of technological development moving into mainstream practice; the appearance of companies such as Facebook, Google, Neuralink within the realm of brain-computer interfaces points to this trend.Areas covered: This perspective piece will talk about the history of brain stimulation in epilepsy, current-approved treatments, technical developments and the future of neurostimulation.Expert opinion: Further understanding of the brain alongside machine learning and innovative technology will be the future of neuromodulation for the treatment of epilepsy. All of these innovations and advances should pave the way toward overcoming the vexing underutilization of surgery in the therapeutic armamentarium against medically refractory seizures, given the implicit advantage of a neuromodulatory rather than neurodestructive approach. | {
"pile_set_name": "PubMed Abstracts"
} |
[Evaluation of the amplitude of changes in the distance between membranes in contact exposed to an external voltage].
A quantitative evaluation of the amplitude of changes in the distance between two membranes due to changes in transmembrane voltage has been theoretically performed. The results are in good agreement with the data of bilayer lipid membrane experiments. | {
"pile_set_name": "PubMed Abstracts"
} |
The early detection and diagnosis of bladder cancer: a critical review of the options.
Bladder cancer has a high worldwide incidence matched by a tendency to recur, necessitating close and regular follow-up. Current methods of investigation of bladder cancer involve cystoscopy, ultrasound scanning and contrast urography, with additional information provided by cytology. These methods, although having a high detection rate, are expensive, time-consuming, invasive and uncomfortable. There is, therefore, a need for an inexpensive, noninvasive, quick and simple investigation with a high sensitivity and specificity for the detection of bladder cancer. There are an increasing number of molecular assays available for the detection of bladder cancer. From bladder tumour antigens to nuclear matrix proteins to adhesion molecules, cytoskeletal proteins and growth factors, urology has looked at them all to support the early detection and diagnosis of bladder cancer. This review critically discusses both the commercial as well as the research-based diagnostic assays available (their mode of action, overall accuracy - both by stage and grade, and their uses and limitations from both a clinical as well as a practical point of view). Aiming to give an insight into the options currently available for noninvasive bladder cancer diagnosis, it also provides prospective comment on what new methods/technologies may be useful in the medium term. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of facility characteristics on the social adjustment of mentally ill residents of board-and-care homes.
Data from a survey of 851 mentally ill residents of 210 board-and-care homes in seven states were used to assess the extent to which facility characteristics such as size, rate of resident turnover, operation for profit, cost of care, staffing ratios, and location of the home encourage resident activity or permit resident apathy. Residents of smaller nonprofit homes engaged in more kinds of activities within the facility, made more excursions into the community, and were more likely to engage in productive activities than residents of larger for-profit homes. The effects of size and for-profit operation were accentuated for individuals with greater impairment in social functioning. | {
"pile_set_name": "PubMed Abstracts"
} |
Induction of squamous cell carcinoma with 3,4-benzo[a]pyrene in the human bronchus transplanted into nude mice.
By the intraluminal injection of 3,4-benzo[a]pyrene into human bronchial grafts in nude mice, squamous cell carcinoma was induced in one bronchial graft out of 17 benzo[a]pyrene-treated grafts. As benzo[a]pyrene is one of the most common carcinogens in the human environment, this experimental system should serve as an excellent model system for studying the process of carcinogenesis in the human respiratory tract. | {
"pile_set_name": "PubMed Abstracts"
} |
Inpatient management of diabetes mellitus.
Inpatient hyperglycemia is associated with increased morbidity and mortality. The length of hospital stay and cost of care is higher for patients with diabetes than for others. Current evidence suggests that tight control of hyperglycemia in critically ill hospitalized patients with diabetes or acute hyperglycemia has been shown to reduce the risk of morbidity and mortality. In view of risk of severe hypoglycemia with near normal blood glucose target, latest consensus is to adopt a less stringent target of 140-180 mg/dl. The development of insulin analogs with more physiologic time-action profiles, improved insulin delivery systems, and standardized protocols for subcutaneous insulin administration and intravenous insulin infusion have improved the safety and convenience of insulin therapy for treating inpatients. | {
"pile_set_name": "PubMed Abstracts"
} |
Instability and dynamics of thin viscoelastic liquid films.
The instability, rupture, and subsequent growth of holes in a thin Jeffreys-type viscoelastic film under the influence of long-range van der Waals force are investigated using both linear stability analysis and nonlinear numerical solutions. The linear stability analysis of full governing equations valid for arbitrary wave numbers shows that although fluid rheology does not influence the dominant length scale of the instability, it significantly affects the growth rate. It is shown that neglect of inertia and solvent dynamics results in a nonphysical singularity in the growth rate beyond a critical value of relaxation time. We further carry out numerical simulations of a set of long-wave, nonlinear differential equations (also derived in Rauscher et al., Eur. Phys. J. E 17, 373 (2005)) governing the evolution of the free surface. The nonlinear simulations, in their domain of validity, confirm the results of the linear analysis. Interestingly, results from nonlinear simulations further show that both for Newtonian and viscoelastic liquids, the shape and the dewetting dynamics of a hole are identical when examined in terms of a rescaled time which depends on rheological parameters. Thus, viscoelasticity of Jeffreys type merely accelerates the growth rate, without however affecting the important morphological characteristics. | {
"pile_set_name": "PubMed Abstracts"
} |
ppGpp-mediated stationary phase induction of the genes encoded by horizontally acquired pathogenicity islands and cob/pdu locus in Salmonella enterica serovar Typhimurium.
Salmonella enterica is highly diverse in terms of genome structure, which is at least partly due to the horizontal transfer of genetic elements from various sources. In this study, we examined the expression profiles of such genes in Salmonella Pathogenicity Islands (SPIs) and the cob/pdu locus, horizontally acquired large DNA segments, during growth under standard growth conditions. Transcripts from exponentially growing and early stationary phase Salmonellae were compared using various methods including cDNA microarray analysis. Nearly all genes encoded by SPIs and the cob/pdu locus were induced at the onset of the stationary phase in a stringent molecule ppGpp-dependent but stationary phase sigma, sigma38-independent manner. Although, it has been suggested that ppGpp acts in concert with DksA, we found the stationary phase induction of those SPI genes was not DksA dependent. It is suggested that ppGpp stimulates the expression of these stress-inducible genes encoded by horizontally acquired DNA, by itself or in concert with DksA. | {
"pile_set_name": "PubMed Abstracts"
} |
Death and help expected from nurses when dying.
This project was undertaken to ascertain the perceptions of a group of Taiwan's fourth-year bachelor of science in nursing (BSN) students regarding death and help expected from nurses during the dying process. Within the Chinese culture, death is one of the most important life issues. However, in many Chinese societies it is difficult for people to reveal their deepest feelings to their significant others or loved ones. It was in this context that this project was developed because little is known about how Taiwan's nursing students perceive death and the dying process. Using an open-ended, self-report questionnaire, 110 senior BSN students recorded their thoughts on: (1) their fears before physical death; (2) afterlife destinations; and (3) the help they would expect from nurses when dying. The data were analyzed using a three-layer qualitative thematic analysis. The students' reported needs during the dying process were directed towards three main goals: (1) help in reaching the 'triple targets of individual life'; (2) help in facilitating in-depth support so that both the dying person and significant others can experience a blessed farewell; and (3) help in reaching a destination in the afterlife. The results support the belief of dying as a transition occurring when life weans itself from the mortal world and prepares for an afterlife. | {
"pile_set_name": "PubMed Abstracts"
} |
High-rate continuous production of lactic acid by Lactobacillus rhamnosus in a two-stage membrane cell-recycle bioreactor.
It is important to produce L(+)-lactic acid at the lowest cost possible for lactic acid to become a candidate monomer material for promising biodegradable polylactic acid. In an effort to develop a high-rate bioreactor that provides high productivity along with a high concentration of lactic acid, the performance of membrane cell-recycle bioreactor (MCRB) was investigated via experimental studies and simulation optimization. Due to greatly increased cell density, high lactic acid productivity, 21.6 g L(-1) h(-1), was obtained in the reactor. The lactic acid concentration, however, could not be increased higher than 83 g/L. When an additional continuous stirred tank reactor (CSTR) was attached next to the MCRB a higher lactic acid concentration of 87 g/L was produced at significant productivity expense. When the two MCRBs were connected in series, 92 g/L lactic acid could be produced with a productivity of 57 g L(-1) h(-1), the highest productivity among the reports of L(+)-lactic acid that obtained lactic acid concentration higher than 85 g/L using glucose substrate. Additionally, the investigation of lactic acid fermentation kinetics resulted in a successful model that represents the characteristics of lactic acid fermentation by Lactobacillus rhamnosus. The model was found to be applicable to most of the existing data with MCRBs and was in good agreement with Levenspiel's product-inhibition model, and the Luedeking-Piret equation for product-formation kinetics appeared to be effective in representing the fermentation kinetics. There was a distinctive difference in the production potential of cells (cell-density-related parameter in Luedeking-Piret equation) as lactic acid concentration increases over 55 g/L, and this finding led to a more precise estimation of bioreactor performance. | {
"pile_set_name": "PubMed Abstracts"
} |
Developing a CHARGE syndrome checklist: Health supervision across the lifespan (from head to toe).
Health supervision and management considerations for individuals with CHARGE syndrome are often complex, and a comprehensive approach is essential. The Atlantic Canadian CHARGE syndrome team developed a checklist organized by body system and age to aid healthcare providers in their approach to the ongoing care of these individuals. The checklist was evaluated qualitatively using a modified Delphi method with widespread consultation from expert healthcare practitioners, parents, and individuals with CHARGE syndrome. These are the first comprehensive guidelines across the lifespan of CHARGE syndrome that suggest a consistent approach to medical surveillance, investigations, and management for the physician and the multi-disciplinary team caring for these individuals. We anticipate that these guidelines will provide improvements in care by preventing missed diagnoses, allowing for anticipatory counseling, and facilitating early referral for interventions and treatments. © 2017 Wiley Periodicals, Inc. | {
"pile_set_name": "PubMed Abstracts"
} |
Oseltamivir: a review of its use in influenza.
Oseltamivir is a prodrug of oseltamivir carboxylate (Ro 64-0802, GS4071), a potent and selective inhibitor of the neuraminidase glycoprotein essential for replication of influenza A and B viruses. Studies in volunteers with experimental human influenza A or B showed that administration of oral oseltamivir 20 to 200 mg twice daily for 5 days reduced both the quantity and duration of viral shedding compared with placebo. Subsequent assessment of the drug at a dosage of 75 mg twice daily for 5 days in otherwise healthy adults with naturally acquired febrile influenza showed that oseltamivir reduced the duration of the disease by up to 1.5 days and the severity of illness by up to 38% compared with placebo when initiated within 36 hours of symptom onset (earlier initiation of therapy was associated with faster resolution). The incidence of secondary complications and the use of antibacterials were also reduced significantly in oseltamivir recipients. A liquid formulation of oseltamivir (2 mg/kg twice daily for 5 days) has been shown to be effective in the treatment of children with influenza, and data presented in abstracts suggest that the drug may also be of use in high-risk populations such as the elderly or those with chronic cardiac or respiratory disease. In addition to treatment efficacy, the drug has demonstrated efficacy when used for seasonal or household prophylaxis. Oral oseltamivir (75 mg once or twice daily for 6 weeks) during a period of local influenza activity significantly prevented the development of naturally acquired influenza by >70% compared with placebo in unvaccinated otherwise healthy adults. The drug also demonstrated efficacy when used adjunctively in previously vaccinated high-risk elderly patients (92% protective efficacy). Short term administration of oseltamivir (75 mg once daily for 7 days) may significantly reduce the risk of illness in household contacts of infected persons when administered within 48 hours of symptom onset in the infected person. Oseltamivir 75 mg twice daily for 5 days was well tolerated in clinical trials in healthy adults and high-risk patients, with nausea and vomiting being the most commonly reported events. Gastrointestinal events were mild and transient and both nausea and vomiting were less likely when oseltamivir was taken with food. Oseltamivir is a well tolerated orally active neuraminidase inhibitor which significantly reduces the duration of symptomatic illness and hastens the return to normal levels of activity when initiated promptly in patients with naturally acquired influenza. It therefore represents a useful therapeutic alternative to zanamivir (especially in patients who prefer oral administration or who have an underlying respiratory disorder) and the M2 inhibitors amantadine and rimantadine (because of its broader spectrum of anti-influenza activity and lower likelihood of resistance) in patients with influenza. In addition, although annual vaccination remains the best means of influenza prevention, there may be a place for oseltamivir in providing household prophylaxis or adjunctive prophylaxis in high-risk vaccinated patients during an outbreak of the disease or for use in patients in whom vaccination is unsuitable or ineffective. | {
"pile_set_name": "PubMed Abstracts"
} |
Functional study of Csrbohs in defence response against Xanthomonas citri ssp. citri.
NADPH oxidases, encoded by rbohs (respiratory burst oxidase homologues), transfer electrons from NADPH to molecular oxygen (O2) to generate superoxide anion (O2•-), which is the first step in the formation of hydrogen peroxide (H2O2) in the plant-pathogen interaction system. In the present work, six citrus rbohs (Csrbohs) genes were identified in citrus, and their possible involvement in resistance to Xanthomonas citri ssp. citri (Xcc) was examined. Inoculation with Xcc promoted the H2O2 production and induced expression of the Csrbohs, especially CsrbohD. Results showed that CsrbohD was markedly induced in the resistant genotype kumquat 'Luofu' [Fortunella margarita (Lour.) Swingle] compared with grapefruit 'Duncan' [Citrus paradisi (Linn.) Macf.]. Virus-induced gene silencing (VIGS) of CsrbohD resulted in reduced resistance to Xcc in grapefruit, but not in kumquat. Compared with non-silenced plants, canker-like symptoms were observed earlier, and they were more extensive in the CsrbohD-silenced grapefruit. Silencing of CsrbohD also suppressed the Xcc induced reactive oxygen species (ROS) burst, and resulted in accumulation of more Xcc bacterial colonies. Taken together, these data indicate that CsrbohD promotes resistance to Xcc, especially in grapefruit. | {
"pile_set_name": "PubMed Abstracts"
} |
Vascular emergencies in liver trauma.
The use of CT in the diagnosis and management of liver trauma is responsible for the shift from routine surgical versus non-surgical treatment in the management of traumatic liver injuries, even when they are of high grade. The main cause of complication and of death in liver trauma is related to vascular injury. The goal of this review focussed on the vascular complications of liver trauma is to describe the elementary lesions shown by CT in liver trauma including laceration, parenchymal hematoma and contusions, partial devascularisation, subcapsular hematomas, hemoperitoneum, active bleeding, pseudoaneurysm of the hepatic artery, bile leak, and periportal oedema, to illustrate the possible pitfalls in CT diagnosis of liver trauma and to underline the key-points which may absolutely be present in a CT report of liver trauma. Then we will remind the grading system based on the CT features and we will analyze the interest and limitations of such grading systems. Last we will discuss the diagnostic strategy at the early phase in patients with suspected liver trauma according to their clinical conditions and underline the conditions of arterial embolization, and then we will discuss the diagnosis strategy at the delayed phase according to the suspected complications. | {
"pile_set_name": "PubMed Abstracts"
} |
A Call for Evidence-based Decision Making When Selecting Outcome Measurement Instruments for Summary of Findings Tables in Systematic Reviews: Results from an OMERACT Working Group.
Systematic reviews often struggle with how to combine information when more than 1 instrument is used across studies being synthesized. Different techniques have been suggested based on frequency of use in the literature, or on consensus. We explore an approach blending 2 initiatives: OMERACT (Outcome Measurement in Rheumatology) and COSMIN (Consensus On Selection of Measurement Instruments), and investigate the effects of an evidence-based measurement approach on selection of outcomes. Readings were circulated to attendees registered for a preconference workshop on pain measurement. Three instruments were considered and exercises conducted to engage people in the content and measurement performance of these tools. Consensus was sought that an evidence-based approach could be created for selection of instruments for summary of findings (SoF) tables. The blending of COSMIN and OMERACT approaches led to an evidence-based approach that depended both on a clear definition of target concept and a review of measurement performance of the instrument. Participants emphasized that conceptual clarity and practical considerations should come before measurement property results. Evidence-based approaches can be adopted for selection of instruments for SoF tables. A research agenda was formulated. | {
"pile_set_name": "PubMed Abstracts"
} |
Direct thrombolytic therapy for thrombosis of a centrifugal flow left ventricular assist device.
In patients receiving left ventricular assistance for end-stage heart failure, pump-related thrombosis is a potentially fatal complication that may manifest as hemolysis and abnormally high pump power consumption. The optimal approach to treat this complication is unclear, especially in patients who are not heart transplant candidates or who have a high surgical risk. We report the successful use of direct thrombolytic therapy for recurrent hemolysis and thrombosis-related pump failure in a patient with the HeartWare ventricular assist device (HVAD), a third-generation, centrifugal flow pump. We know of only one previous case in which direct thrombolytic therapy has been used to treat the failure of a third-generation device. On the basis of our experience in the present case, we believe that direct thrombolytic therapy is a feasible option in these patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Fine structure of a developing insect olfactory organ: morphogenesis of the silkmoth antenna.
The olfactory organ of the silkmoth Antheraea polyphemus is the feathered antenna which carries about 70,000 olfactory sensilla in the male. It develops within 3 weeks from a leaf-shaped epidermal sac by means of segmental primary and secondary indentations which proceed from the periphery towards the centerline. During the first day post-apolysis, the antennal epidermis differentiates into segmentally arranged, alternating sensillogenic and non-sensillogenic regions. Within the first 2 days post-apolysis, the anlagen of olfactory sensilla arise from electron-dense mother cells in the sensillogenic epidermis. The axons of the developing sensilla begin to form the primary innervation pattern during the second day. The sensilla develop approximately within the first 10 days to their final shape, while the indentations are completed during the same period of time. The indentations are most probably driven by long basal extensions of epidermal cells, the epidermal feet. Primary indentations follow the course of segmentally arranged tracheal bundles and form the segments of the antenna. The secondary indentations follow the course of the primary segmental nerves which are reconstructed by this process. During the remaining time of development, the cuticle of the antenna and the sensory hairs is secreted by the epidermal and the hair-forming cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Calcium handling by renal tubules during oxygen deprivation injury to the kidney prior to reoxygenation.
Efforts to more precisely define the mechanism(s) of ischemic injury to renal epithelial tissue, both during O2 deprivation and reflow, have led to the expanding use of freshly isolated renal tubules. This tissue is prepared in a manner that eliminates the impact of changes in vascular resistance and influences of hormones, as well as temporal changes in pH and in regional pO2, and has permitted investigators to focus on the definitive cellular responses to O2 deprivation itself. When such studies are evaluated it becomes clear that in vitro anoxia, for up to 60 minutes, is not associated with any increase in total tissue Ca2+ as measured by atomic absorption techniques, whereas severe hypoxia is attended by a time-dependent increase in total tissue Ca2+. In both severe hypoxia and anoxia, however, the Ca2+ uptake rate is increased, but during hypoxia the less severe acidosis, as well as the continued, albeit modest, mitochondrial energization, appears to facilitate mitochondrial (and thus total tissue) Ca2+ accumulation. In vivo and in vitro, the administration of calcium channel blockers (CCB) attenuates renal oxygen-deprivation-induced injury and one, often overlooked, effect of verapamil, a prototypical CCB, is to reduce K+ loss from treated tissue via inhibition of Ca2(+)-mediated K+ efflux pathways. This may be the cause of the higher levels of K+ reported for several tissues, including kidney tubules, during CCB treatment. In addition, reduced rates of Ca2+ uptake effected by CCB may modify cytosolic free Ca2+ levels such that activation of phospholipases is impaired.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Appropriate NR1-NR1 disulfide-linked homodimer formation is requisite for efficient expression of functional, cell surface N-methyl-D-aspartate NR1/NR2 receptors.
A c-Myc epitope-tagged N-methyl-D-aspartate receptor NR1-2a subunit was generated, NR1-2a(c-Myc), where the tag was inserted after amino acid 81. NR1-2a(c-Myc) /NR2A receptors when expressed in mammalian cells are not trafficked to the cell surface nor do they yield cell cytotoxicity post-transfection. NR1-2a(c-Myc) was, however, shown to assemble with NR2A subunits by immunoprecipitation and [(3)H]MK801 radioligand binding assays. Immunoblots of cells co-transfected with wild-type NR1-2a/NR2A subunits yielded two NR1-2a immunoreactive species with molecular masses of 115 and 226 kDa. Two-dimensional electrophoresis under non-reducing and reducing conditions revealed that the 226-kDa band contained disulfide-linked NR1-2a subunits. Only the 115-kDa NR1-2a species was detected for NR1-2a(c-Myc)/NR2A. The c-Myc epitope is inserted adjacent to cysteine 79 of the NR1-2a subunit; therefore, it is possible that the tag may prevent the formation of NR1 disulfide bridges. A series of cysteine --> alanine NR1-2a mutants was generated, and the NR1-2a mutants were co-expressed with NR2A or NR2B subunits in mammalian cells and characterized with respect to cell surface expression, cell cytotoxicity post-transfection, co-association by immunoprecipitation, and immunoblotting following SDS-PAGE under both reducing and non-reducing conditions. When co-expressed with NR2A in mammalian cells, NR1-2a(C79A)/NR2A displayed similar properties to NR1-2a(c-Myc)/NR2A in that the 226-kDa NR1 immunoreactive species was not detectable, and trafficking to the cell surface was impaired compared with wild-type NR1/NR2 receptors. These results provide the first biochemical evidence for the formation of NR1-NR1 intersubunit disulfide-linked homodimers involving cysteine 79. They suggest that disulfide bridging and structural integrity within the NR1 N-terminal domain is requisite for cell surface N-methyl-D-aspartate receptor expression. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of amide constituents from pepper on adipogenesis in 3T3-L1 cells.
Several amide constituents (piperlonguminine and retrofractamides A, B, and C) from the fruit of Piper chaba promoted adipogenesis of 3T3-L1 cells. Among them, retrofractamide A was the most active and significantly increased the amount of adiponectin released into the medium and the uptake of 2-deoxyglucose into the cells. Retrofractamide A also increased mRNA levels of adiponectin, peroxisome proliferator-activated receptor gamma2 (PPARgamma2), glucose transporter 4 (GLUT4), and insulin receptor substrate 1 (IRS-1), but did not act as a PPARgamma agonist different from troglitazone. | {
"pile_set_name": "PubMed Abstracts"
} |
Treatment of dermal depth burn wounds with an antimicrobial agent-releasing silicone gel sheet.
Silicone gel sheets containing 0.02 per cent Ofloxacin were used in the treatment of 24 patients with a total of 27 dermal depth burn wounds. The gel provided a continuing drug delivery system from the dressing to the wound. Clinically the silicone gel sheets did not adhere to the wound and could be removed easily without pain. No infection developed in any of the dermal depth burn wounds treated with the gel sheets. The silicone gel sheets were found to promote prompt epithelialization in 16 burn wounds of superficial dermal depth (mean 8.4 days) compared with ointment-impregnated gauze dressings (mean 14 days, P less than 0.01). There was less pain and discharge by macroscopic observation of the absorbent materials from both dressings. In nine wounds of mixed superficial and deep dermal burn, the silicone gel also provided prompt epithelialization (mean 12 days) compared to the control wounds (mean 22 days, P less than 0.01). | {
"pile_set_name": "PubMed Abstracts"
} |
Autism spectrum disorders associated with X chromosome markers in French-Canadian males.
It is now well established that genetic factors play an important role in the pathogenesis of autism disorder and converging lines of evidence suggest the implication of the X chromosome. Using a sample of subjects diagnosed with autism spectrum disorders, exclusively composed of males from French-Canadian (FC) origin, we tested markers covering the entire X chromosome using a family-based association study. Our initial analysis revealed the presence of association at two loci: DXS6789 (P=0.026) and DXS8043 (P=0.0101). In a second step, we added support to the association at DXS8043 using additional markers, additional subjects and a haplotype-based analysis (best obtained P-value=0.00001). These results provide support for the existence of a locus on the X chromosome that predisposes the FC to autism spectrum disorders. | {
"pile_set_name": "PubMed Abstracts"
} |
The conjugation protein TcpC from Clostridium perfringens is structurally related to the type IV secretion system protein VirB8 from Gram-negative bacteria.
Bacterial conjugation is important for the acquisition of virulence and antibiotic resistance genes. We investigated the mechanism of conjugation in Gram-positive pathogens using a model plasmid pCW3 from Clostridium perfringens. pCW3 encodes tetracycline resistance and contains the tcp locus, which is essential for conjugation. We showed that the unique TcpC protein (359 amino acids, 41 kDa) was required for efficient conjugative transfer, localized to the cell membrane independently of other conjugation proteins, and that membrane localization was important for its function, oligomerization and interaction with the conjugation proteins TcpA, TcpH and TcpG. The crystal structure of the C-terminal component of TcpC (TcpC(99-359)) was determined to 1.8-Å resolution. TcpC(99-359) contained two NTF2-like domains separated by a short linker. Unexpectedly, comparative structural analysis showed that each of these domains was structurally homologous to the periplasmic region of VirB8, a component of the type IV secretion system from Agrobacterium tumefaciens. Bacterial two-hybrid studies revealed that the C-terminal domain was critical for interactions with other conjugation proteins. The N-terminal region of TcpC was required for efficient conjugation, oligomerization and protein-protein interactions. We conclude that by forming oligomeric complexes, TcpC contributes to the stability and integrity of the conjugation apparatus, facilitating efficient pCW3 transfer. | {
"pile_set_name": "PubMed Abstracts"
} |
The Environmental Pollutants Perfluorooctane Sulfonate and Perfluorooctanoic Acid Upregulate Uncoupling Protein 1 (UCP1) in Brown-Fat Mitochondria Through a UCP1-Dependent Reduction in Food Intake.
The environmental pollutants perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) cause a dramatic reduction in the size of the major adipose tissue depots and a general body weight decrease when they are added to the food of mice. We demonstrate here that this is mainly due to a reduction in food intake; this reduction was not due to food aversion. Remarkably and unexpectedly, a large part of the effect of PFOA/PFOS on food intake was dependent on the presence of the uncoupling protein 1 (UCP1) in the mice. Correspondingly, PFOA/PFOS treatment induced recruitment of brown adipose tissue mitochondria: increased oxidative capacity and increased UCP1-mediated oxygen consumption (thermogenesis). In mice pair-fed to the food intake during PFOA/PFOS treatment in wildtype mice, brown-fat mitochondrial recruitment was also induced. We conclude that we have uncovered the existence of a regulatory component of food intake that is dependent upon brown adipose tissue thermogenic activity. The possible environmental consequences of this novel PFOA/PFOS effect (a possible decreased fitness) are noted, as well as the perspectives of this finding on the general understanding of control of food intake control and its possible extension to combatting obesity. | {
"pile_set_name": "PubMed Abstracts"
} |
High affinity DNAzyme-based ligands for transition metal cations - a prototype sensor for Hg2+.
Inspired by recent interest in DNAzymes as transition metal ion sensors, a survey of the effects of various transition metals on the intramolecular cleavage rate of an imidazole modified, M(2+)-independent, self-cleaving "9(25)-11" DNA is reported. In particular, 9(25)-11 activity was strongly inhibited by Hg(2+)(K(d)(APP)= 110 +/- 9 nM). It is postulated that the affinity and selectivity of 9(25)-11 for Hg(2+) stems from the fact that this synthetically modified DNAzyme contains imidazoles. This study demonstrates the utility of modified nucleotides in developing DNAzyme sensors for metals ions, especially those for which unmodified nucleic acids might not serve as inherently good ligands. | {
"pile_set_name": "PubMed Abstracts"
} |
Two-dimensional sample entropy analysis of rat sural nerve aging.
Entropy analysis of images are usually performed using Shannon entropy, which calculates the probability of occurrency of each gray level on the image. However, not only the pixel gray level but also the spatial distribution of pixels might be important for image analysis. On the other hand, sample entropy (SampEn) is an important tool for estimation of irregularity in time series, which calculates the probability of pattern occurrence within the series. Therefore, we propose here an extension of SampEn to a two-dimensional case, namely SampEn2D, as an entropy method for extracting features from images that accounts for the spatial distribution of pixels. SampEn2D was applied to histological segments of sural nerve obtained from young (30 days) and elderly (720 days) rats. Morphometric indexes, such as the total number of myelinated fibers and the average myelinated fibers area and perimeter were also calculated. Results show that SampEn2D can extract useful information from histological nerve images, classifying elderly rat image as more regular than young rat. As SampEn2D is related to irregularity/unpredictability, we can conclude that the proposed method is complementary to morphometric indexes. Further studies are being built to validate SampEn2D. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficacy of preoperative colonoscopic tattooing with indocyanine green on lymph node harvest and factors associated with inadequate lymph node harvest in colorectal cancer.
Objective: Adequate lymph node harvest (LNH) in colorectal cancer is closely related to survival. This study aimed to evaluate the effect of preoperative colonoscopic tattooing (PCT) with indocyanine green (ICG) on adequate LNH in colorectal cancer. Materials and methods: A total of 1079 patients who underwent surgical resection for colorectal cancer were divided into two groups: a tattooing group and a non-tattooing group. The patients were retrospectively analyzed for the number and adequacy of LNH according to tumor locations and stages. Univariate and multivariate analysis for factors associated with adequate LNH were done. Results: There was no significant difference between the two groups in the number and adequacy of LNH according to tumor locations. However, T1 colorectal cancer in the tattooing group had significantly higher adequate LNH (91.6% vs 82.1%, OR 2.370, p = .048) and T1 and N0 rectal cancer in the tattooing group also had higher adequate LNH although there was no statistical significance (100% vs 82.4%, OR 12.088, p = .095; 96.9% vs 84.8%, OR 5.570, p = .099) when compared to the non-tattooing group. Male sex and T1 stage were significantly associated with inadequate LNH in multivariate analysis (OR 0.556 (95% CI 0.340-0.909), p = .019; OR 0.555 (95% CI 0.339-0.910), p = .019, respectively). Conclusion: PCT with ICG did not improve adequate LNH in colorectal cancer but effectively improved adequate LNH in early colorectal cancer. Male sex and early cancer were risk factors for inadequate LNH in colorectal cancer, so PCT is needed for adequate LNH in these patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Discounting future health gains: an empirical enquiry into the influence of growing life expectancy.
We tested the influence of the growth in life expectancy over time on social time preferences for health. Growing life expectancy of future generations should raise social discount rates for health because of diminishing marginal utility of additional health gains and equity reasons reflecting the desire for a more equitable distribution of benefits over generations. This influence has, however, been largely ignored in empirical studies. We provide a first comprehensive analysis of how time preferences for health gains vary with projected growth rates, indicating the importance of subjective expectations about the growth in life expectancy in the elicitation of social time preference. Six hundred and fifty-six respondents, representative of the Dutch population, completed one of four questionnaires, differing in the projected growth in life expectancy. Results showed that individuals discount future health gains at different rates, depending on the latency period and on the projected or expected growth in life expectancy. As hypothesized, discount rates increased with higher growth rates. The association between observed discount rates and expectations regarding future life expectancy was confirmed, suggesting that discount rates for health may depend on future life expectancy. In light of our results, specifying life expectancy of future generations in time preference exercises appears appropriate. | {
"pile_set_name": "PubMed Abstracts"
} |
On-line characterization of the activity and reaction kinetics of immobilized enzyme by high-performance frontal analysis.
A microreactor by immobilized trypsin on the activated glycidyl methacrylate-modified cellulose membrane packed column was constructed. Immobilized trypsin mirrored the properties of the free enzyme and showed high stability. A novel method to characterize the activity and reaction kinetics of the immobilized enzyme has been developed based on the frontal analysis of enzymatic reaction products, which was performed by the on-line monitoring of the absorption at 410 nm of p-nitroaniline from the hydrolysis of N-alpha-benzoyl-DL-arginine-p-nitroanilide (BAPNA). The hydrolytic activity of the immobilized enzyme was 55.6% of free trypsin. The apparent Michaelis-Menten kinetics constant (Km) and Vmax values measured by the frontal analysis method were, respectively, 0.12 mM and 0.079 mM min(-1) mg enzyme(-1). The former is very close to that observed by the static and off-line detection methods, but the latter is about 15% higher than that of the static method. Inhibition of the immobilized trypsin by addition of benzamidine into substrate solution has been studied by the frontal analysis method. The apparent Michaelis-Menten constant of BAPNA (Km), the inhibition constant of benzamidine (Ki) and Vmax were determined. It was indicated that the interaction of BAPNA and benzamidine with trypsin is competitive, the Km value was affected but the Vmax was unaffected by the benzamidine concentration. | {
"pile_set_name": "PubMed Abstracts"
} |
[Isolation of a Tahyna-like virus (Bunyaviridae, Bunyavirus, California encephalitis complex) on northern Sakhalin Island].
The strain LEIV-11483 Sak of Tahyna virus or a virus closely related to it antigenically was isolated from Aedes spp. mosquitoes (predominantly A. communis) collected August 25, 1985, in the light coniferous subzone of the mid-taiga landscape zone in the north of Sakhalin Island (54 degrees N, 142 degrees E). Altogether, 17.8 thousand mosquitoes were examined which were collected in June-August, 1985, in the light and dark coniferous subzones of mid-taiga. In the human population, virus-neutralizing antibodies to Tahyna virus were found in 7-18%, to Batai virus in 3%, to Uukuniemi virus in none. | {
"pile_set_name": "PubMed Abstracts"
} |
A GT dinucleotide repeat polymorphism in intron 1 of the H-cadherin (CDH13) gene.
A polymorphic dinucleotide (GT) repeat sequence was isolated from a genomic clone containing the human H-cadherin (CDH13) gene at 16q24.1-q24.2. This polymorphic marker will be a useful tool in the genetic study of various cancers. | {
"pile_set_name": "PubMed Abstracts"
} |
Predictive performance of a new pharmacokinetic model for propofol in underweight patients during target-controlled infusion.
In a previous study, the modified Marsh and Schnider models respectively showed negatively- and positively-biased predictions in underweight patients. To overcome this drawback, we developed a new pharmacokinetic propofol model-the Choi model-for use in underweight patients. In the present study, we evaluated the predictive performance of the Choi model. Twenty underweight patients undergoing elective surgery received propofol via TCI using the Choi model. The target effect-site concentrations (Ces) of propofol were 2.5, 3, 3.5, 4, 4.5, and 2 μg/mL. Arterial blood samples were obtained at least 10 minutes after achieving pseudo-steady-state. Predicted propofol concentrations with the modified Marsh, Schnider, and Eleveld pharmacokinetic models were obtained by simulation (Asan pump, version 2.1.3; Bionet Co. Ltd., Seoul, Korea). The predictive performance of each model was assessed by calculation of four parameters: inaccuracy, divergence, bias, and wobble. A total of 119 plasma samples were used to determine the predictive performance of the Choi model. Our evaluation showed that the pooled median (95% CI) bias and inaccuracy were 4.0 (-4.2 to 12.2) and 23.9 (17.6-30.3), respectively. The pooled biases and inaccuracies of the modified Marsh, Schnider, and Eleveld models were clinically acceptable. However, the modified Marsh and Eleveld models consistently produced negatively biased predictions in underweight patients. In particular, the Schnider model showed greater inaccuracy at a target Ce ≥ 3 µg/mL. The new propofol pharmacokinetic model (the Choi model) developed for underweight patient showed adequate performance for clinical use. | {
"pile_set_name": "PubMed Abstracts"
} |
Consanguineous marriage in a newly developed country: the Qatari population.
This study examines the frequency of consanguineous marriage and coefficient of inbreeding in the State of Qatar. The study was conducted in semi-urban areas of Doha between January and May 2004. A sample of 1515 married Qatari females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (54.0%) with a coefficient of inbreeding of 0.02706. The commonest type of consanguineous marriage was between first cousins (34.8%). Double first cousin marriages were common (3.1%) compared with other populations. The consanguinity rate in the State of Qatar has increased from 41.8% to 54.5% in one generation. | {
"pile_set_name": "PubMed Abstracts"
} |
What causes increased passive stiffness of plantarflexor muscle-tendon unit in children with spastic cerebral palsy?
The term 'stiffness' is commonly used in the literature to refer to various components of 'hyperresistance' by which spastic muscles oppose to their passive lengthening, especially in children with cerebral palsy (CP). Originally, stiffness consists of mechanical resistance to passive movement in the absence of any muscle activation. Increased muscle stiffness in CP therefore refers to alterations to the mechanical properties of the tissue. It is closely linked to muscle shortening, yet the two phenomena are not equivalent. Both increased stiffness and shortening are present early in childhood in the plantarflexor muscles of children with spastic CP. This narrative review provides a comprehensive overview of the literature on passive stiffness of the plantarflexor muscles measured at the joint, muscles, fascicles, and fiber level in children with CP. Articles were searched through the Pub'Med database using the keywords "cerebral palsy" AND "stiffness". The ambiguous use of the term 'stiffness' has been supported by discrepancies in available results, influenced by heterogeneity in materials, methodologies and characteristics of the participants among studies. Increased stiffness at the joint and muscle belly level may be explained by altered structural properties at the microscopic level. This thorough investigation of the literature suggests that the pathophysiology and the time course of the development of stiffness and contracture remain to be elucidated. A consideration of both morphological and mechanical measurements in children with CP is important when describing the alterations in their plantarflexors. | {
"pile_set_name": "PubMed Abstracts"
} |
Pain relief following a single-dose intra-articular injection of methylprednisolone in the temporomandibular joint arthralgia-A multicentre randomised controlled trial.
Temporomandibular joint (TMJ) arthralgia is a painful condition assumed to be associated with local inflammation. The objective of the present study was to determine the efficacy for reducing pain of a single-dose intra-articular (IA) injection of methylprednisolone to the TMJ. The hypothesis was that methylprednisolone would effectively reduce TMJ pain. This randomised, double-blind, parallel-group, multicentre, controlled study included visits for enrolment, treatment and 4-week follow-up. The study included patients 18 years and older who had been diagnosed with unilateral TMJ arthralgia. All participants were randomly assigned to receive 1 mL IA injections of methylprednisolone or saline. The primary outcome was change in recorded pain intensity on a visual analogue scale (VAS) at maximum jaw opening, analysed in the per protocol population. In total, 54 patients were randomly assigned to single-dose IA injections with methylprednisolone (n = 27) or saline (n = 27). Between baseline and the 4-week follow-up, VAS-rated pain intensity at maximum jaw opening decreased from a mean of 61.0 (95% confidence interval [CI]: 50.1; 70.7) to 33.9 (95% CI: 21.6; 46.2) in the methylprednisolone group and from 59.6 (95% CI: 50.7; 65.9) to 33.9 (95% CI: 23.8; 43.9) in the saline group. The between-group difference was not significant (P = 0.812). Treatment-related adverse events were doubled in the methylprednisolone group. Methylprednisolone provided no additional benefit for reducing pain, but caused more harm compared with saline following a single-dose IA injection in patients with TMJ arthralgia. | {
"pile_set_name": "PubMed Abstracts"
} |
Preventive measures reducing superficial mycobiotic contamination of grain.
Search for the preventive measures reducing the accumulation of mycotoxin producers in food raw material was carried out. Active ventilation was used; the impact of the electro-chemically activated air (ozone) and electro-chemically activated water (anolyte) on the micromycetes prevailing in grain raw material for food (GRMF) was determined. The GRMF was dried by active ventilation using the ozone-air mixture. Ozone (concentration 1250 ppb) disinfects the surface of the raw material and creates conditions unfavourable for the increase of mycobiotic contamination in drying upper layers of the grain mound. Within 8 days the contamination of GRMF in a mound decreased by 50%, while in its lower layers - more than 3 times. Ventilation of the mound with the above-mentioned concentration of the ozone-air mixture has ceased the active functioning of Fusarium avenaceum, F. graminearum, F. poae, F. solani, F. tricinctum F. sporotrichioides micromycetes and has considerably retarded the development of Alternaria alternata and other fungi. Anolyte (0.05% of chlorine concentration) reduced the mycobiotic contamination of GRMF by almost 2.5 times. The optimal treatment duration is from 0.5 to 1 hour. The optimal technical parameters, allowing the use of these measures for the preparation of grain food safety technologies, were elaborated; they are designed for more efficient protection of human health against micromycetes and their toxic metabolites, which are abundantly produced and released into the environment. | {
"pile_set_name": "PubMed Abstracts"
} |
Gender and marital status clarify associations between food insecurity and body weight.
Prior research shows that food insecurity is associated with being overweight in women, with few and ambiguous results in men. Little is known about the characteristics and roles of individuals who are most likely to be both food insecure and overweight or obese. This study analyzed associations between food insecurity and body weight, and whether gender and marital status are involved in that relationship. Using multiple regression models, we examined food insecurity, marriage, and body weight among 4338 men and 4172 women aged > or = 20 y in the 1999-2002 NHANES. Married men were more likely to be overweight than men in all other marital-status categories except for those living with partners. Divorced men were more likely than never-married men to live in a household with very low food security. Compared with fully food-secure men, marginally food-secure men were heavier, whereas men with low food security were lighter. Compared with fully food-secure women, marginally food-secure women also showed a tendency to be overweight (P = 0.05), whereas women with low food security were more likely to be obese. When considering the interaction between food insecurity and marital status, food insecurity was related to a greater likelihood of obesity among married women, those living with partners, and widows, when compared with never-married women. Sensitivity analyses suggest this effect was concentrated among marginally food-secure women. These findings indicate that food insecurity relates differently to body weight for men and women, and that partnering plays a strong part in this relationship for women. | {
"pile_set_name": "PubMed Abstracts"
} |
In vivo longitudinal variations in protein synthesis in developing ovine intestines.
Changes in fractional rates of protein synthesis (Ks) were investigated at different small and large intestinal sites in 1-, 5-, and 8-wk-old milk-fed and 8-wk-old weaned lambs, a species with early intestinal maturation similar to most domestic animals and humans, with the use of a flooding dose of L-[3H]valine. Between 1 and 8 wk of age, Ks did not change significantly in the duodenum, the cecum, or the colon of milk-fed lambs, but was depressed by 30% in the jejunum and by 39% in the ileum. This was because of reduced ribosomal capacity, i.e., total RNA-to-protein ratio (Cs) in the jejunum, and also alterations in both Cs and protein synthetic efficiency, i.e., rate of synthesis relative to RNA (KRNA) in the ileum. Ks values throughout the small intestine were significantly higher (45-55%) in weaned lambs than in 8-wk-old milk-fed animals. This enhancement of protein synthesis was mainly related to an increase in KRNA (27-40%). Ks decreased by 43% from the duodenum to the ileum in both milk-fed and weaned 8-wk-old animals, but not in 1- and 5-wk-old milk-fed lambs, because of a marked reduction in KRNA. It was concluded that changes in nutrients at weaning, weaning itself, or both, enhanced protein synthesis without any specific effect on small intestinal site. By contrast, intrinsic developmental factors were responsible only for the regional differences in small intestinal Ks that occurred at 8 wk of age. Longitudinal variations in protein synthesis may contribute to the establishment of the well-recognized jejunoileal gradients of brush-border enzymes and villus height that characterize the mature mammalian small intestine. | {
"pile_set_name": "PubMed Abstracts"
} |
Partial purification and characterization of a nerve growth factor-sensitive kinase and its substrate from PC12 cells.
The cell-free, nerve growth factor-sensitive incorporation of radioactive phosphate into a 100,000-dalton protein (Nsp100), observed in a previous study (End,D., Tolson, N., Hashimoto, S., and Guroff, G. (1983) J. Biol. Chem. 258, 6549-6555), has been characterized and the system fractionated. It is shown here that the decrease in incorporation due to treatment of the cells with nerve growth factor is transient, even in the continued presence of nerve growth factor. The decrease in radioactive phosphate incorporation is due to an inhibition of phosphorylation, not to a stimulation of a dephosphorylation. Evidence is presented to suggest that no soluble cofactors are needed for the phosphorylation and no soluble second messengers are responsible for the inhibition. It is demonstrated that the phosphorylation requires divalent cations; both Mg2+ and Mn2+ are effective in this regard. ATP is the preferred phosphate donor, the phosphorylation is maximal at pH values between 5 and 6, and Na+, K+, and Zn2+ are rather specific inhibitors. The system has been partially purified and the resolved components have been used to show that the kinase and the substrate are separate molecules, that the kinase, not the substrate, is the heat-labile portion, and that the kinase has a molecular weight of 110,000-130,000. Finally, evidence is presented to indicate that the kinase, not the substrate, is the component responsible for the decrease in phosphorylation seen after treatment of the cells with nerve growth factor. | {
"pile_set_name": "PubMed Abstracts"
} |
Estimation of Mueller matrices using non-local means filtering.
This article addresses the estimation of polarization signatures in the Mueller imaging framework by non-local means filtering. This is an extension of previous work dealing with Stokes signatures. The extension is not straightforward because of the gap in complexity between the Mueller framework and the Stokes framework. The estimation procedure relies on the Cholesky decomposition of the coherency matrix, thereby ensuring the physical admissibility of the estimate. We propose an original parameterization of the boundary of the set of Mueller matrices, which makes our approach possible. The proposed method is fully unsupervised. It allows noise removal and the preservation of edges. Applications to synthetic as well as real data are presented. | {
"pile_set_name": "PubMed Abstracts"
} |
Carcinosarcoma in the pouch of douglas.
Only one case of carcinosarcoma in the pouch of douglas has been reported in the English literature. The author herein reports a case of carcinosarcoma of the pouch of douglas. A rapidly growing tumor (10 cm in diameter) was found in the pelvic cavity of a 51-year-old woman, and an operation was performed for the clinical diagnosis of left ovarian malignancy. However, it was found that the tumor was located in the pouch of douglas, free of ovarian involvement. Because the tumor was impossible to resect totally, an incisional biopsy was performed. Histologically, the tumor showed a mixture of squamous cell carcinoma, atypical epithelial cells occasionally forming tubules, myxomatous spindle cell sarcoma, and chondrosarcoma. The tumor showed abundant vessels, hemorrhage and necrosis. Immunohistochemically, the squamous cell carcinoma and atypical epithelium components were positive for cytokeratins, CEA, CA125, and p53 protein. The spindle cell sarcoma and chondrosarcoma components were positive for vimentin and p53 protein. The overall Ki-67 labeling was 30%. The author diagnosed the present case as carcinosarcoma of heterologous type. The present case shows that carcinosarcoma can occur in the pouch of douglas. It may arise from misplaced Mullerian duct remnants in the pouch of douglas. | {
"pile_set_name": "PubMed Abstracts"
} |
Tissue culture of normal rat glomeruli: characterization of collagenous and non-collagenous basement membrane antigens on the epithelial and mesangial cells.
Immunofluorescent studies were performed on epithelial and mesangial cells derived from normal rat glomeruli, using specific antisera directed against insoluble glomerular basement membranes (GMB), or directed against either type IV procollagen or non-collagenous antigens purified from basement membrane polypeptides synthesized by a murine tumour. In marked contrast to the mesangial cells, the epithelial cells contained large amounts of GBM antigens, of type IV procollagen, and of non-collagenous glycoproteins in the first two days after subculture plating. At the same time, the mesangial cells did not exhibit any basement membrane antigens. Five to 10 days later, however, all the antisera tested stained the surface membrane and/or the extracellular material of both epithelial and mesangial cells. The data suggest that both cell lines synthesize and secrete cross-reacting type IV procollagen and non-collagenous basement membrane antigenic material into the culture medium. | {
"pile_set_name": "PubMed Abstracts"
} |
[Supporting roles of health centers in community health practice by municipalities].
Staff of community health centers are expected to support those of municipalities so that they can identify health relevant issues in their communities, plan strategies to resolve the issues, implement them and evaluate the action. To illustrate the role of community health centers, the authors report the process of health promotion practice in Taisho-cho, Kochi prefecture, which was supported by Kubokawa health center. The health center took the initiative in identifying issues in community health through analyzing available information. In a practice setting, the health center facilitated involvement and participation by the residents and cooperated with other community resources. The process of support is discussed from the point of view of community organization practice. | {
"pile_set_name": "PubMed Abstracts"
} |
Considerations in the improvement of human epidermal keratinocyte culture in vitro.
Large-scale expansion of epidermal keratinocytes is essential in the application of these cells for severe burn treatment in patients. Therefore, this study was designed to evaluate various conditions in the expansion of human epidermal keratinocytes. The epidermis was separated from the dermis of skin samples using dispase. The epidermis was trypsinized for keratinocyte isolation. Keratinocytes were cultured in various conditions, with or without a human dermal fibroblast feeder layer, mitomycin C treatment, and different culture media. Our results suggest that keratinocytes cultured on a human dermal fibroblast feeder layer were grown for several passages. Extensive deformation and rapid deterioration were observed in the cultured cells without a feeder layer and in serum-free medium. Human dermal fibroblasts treated with mitomycin C can provide optimal conditions for proliferation of keratinocytes. | {
"pile_set_name": "PubMed Abstracts"
} |
Induction and add-on therapy with mitoxantrone and interferon beta in multiple sclerosis.
We retrospectively analyzed data from 70 multiple sclerosis (MS) patients treated with mitoxantrone (MX) before Interferon-beta (IFN-beta) because of clinically and MRI very active isolated syndrome (CIS) or relapsing-remitting MS (induction therapy) or due to breakthrough/persistently active disease in spite of IFN-beta (add-on/combination therapy), or for increased disability suggesting a secondary progression (rescue therapy). After almost 2-year follow-up, relapse rate and disability decreased very significantly in the two former groups while MX was essentially ineffective as rescue therapy. Induction therapy is a valid option for very aggressive/active CIS and MS at onset. | {
"pile_set_name": "PubMed Abstracts"
} |
Molecular cloning and expression of the ARFC3 gene, a component of the replication factor C from the salt-tolerant, dimorphic yeast Arxula adeninivorans LS3.
The yeast replication factor C (RF-C) is a multi-polypeptide complex with five sub-units involved in chromosomal DNA replication. This factor, encoded by five genes, is well characterized for the yeast Saccharomyces cerevisiae. However, RF-C components from other yeast species have not been analysed yet. Here we report the cloning and characterization of ARFC3 from the dimorphic and osmo-tolerant yeast Arxula adeninivorans. This gene encodes one subunit of the RF-C complex. It is localized on chromosome 1 of the four Arxula chromosomes and comprises a coding region of 1014 bp, which corresponds to 338 amino acids. Two introns are contained within this gene. The ARFC3 transcript level is influenced by both salt and temperature. The latter also influences the morphological state (budding cells, mycelium). High salt concentration and high temperature result in a rapid decrease of the ARFC3 mRNA. | {
"pile_set_name": "PubMed Abstracts"
} |
In situ expression of the cell adhesion molecules in inflammatory bowel disease. Evidence of immunologic activation of vascular endothelial cells.
The cell adhesion between vascular endothelial cells and leukocytes is an important process for the immuno-inflammatory changes. To clarify the basic features of inflammatory bowel disease (IBD), studies of in situ localization of the cell adhesion molecules are required. We analyzed the immunohistochemical localization of the adhesion molecules (ICAM-1, LFA-1, Mac-1, VCAM-1, VLA-4, P- and E-selectins) in IBD, stressing phenotypical changes of endothelial cells. In the normal mucosa, ICAM-1 was expressed in capillaries and venules, LFA-1 in some lymphocytes and VLA-4 in most lymphocytes. VCAM-1 was expressed sporadically in venules and constantly in follicular dendritic cells (FDC) in lymphoid follicles. Both E- and P-selectins were sporadically expressed in venules. In actively inflamed mucosa in IBD, a marked increase of all these antigens was observed; ICAM-1+ inflammatory infiltrates (lymphocytes, plasma cells, and macrophages) and ICAM-1+ venules increased paralleled to the degree of inflammation. LFA-1+ and VLA-4+ mononuclear cells and Mac-1+ granulocytes increased in number. However, expression of VCAM-1 in venules or capillaries was not increased. FDC constantly expressed VCAM-1. E- and P-selectins+ venules increased in actively inflamed tissue particularly at the base of ulcers. Immunoelectron microscopy confirmed expression of these antigens along the plasma membranes (functional localization) and in rough endoplasmic reticulum or in perinuclear spaces (localization during the intracellular synthesis). Our study suggested that increased expression of the adhesion molecules in IBD promotes the recruitment of granulocytes and lymphocytes through blood vessels and the cell interaction between lymphocytes-antigen presenting cells or among lymphocytes, thereby sustaining the immuno-inflammatory process in IBD. The present study emphasizes the importance of microenvironmental changes including the endothelial activation in the immuno-inflammatory changes. | {
"pile_set_name": "PubMed Abstracts"
} |
Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil in a variety of experimental tumors.
Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil against various tumors was examined. Therapeutic ratio (ILSmax/ILS30) in L-1210 system was 4.5 by oral administration, while those of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil were 1.9 and 1.0, respectively. Therapeutic ratio of the compound in C-1498 system was 11, while those of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil were 3.3 and 2.5, respectively. 1-Hexylcarbamoyl-5-fluurouracil was also active against solid and ascites tumors by oral administration. It was markedly active against Nakahara-Fukuoka sarcoma, adenocarcinoma=755, and ascites sarcoma-180, and moderately active against Ehrlich ascites carcinoma. This compound had a wider tumor spectrum than 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil by oral administration. | {
"pile_set_name": "PubMed Abstracts"
} |
[Paleoclimate of La Guajira, Colombia; by the growth rings of Capparis odoratissima (Capparidaceae)].
There is great concern about the effect of climate change in arid and subarid areas of the tropics. Climate change combined with other anthropogenic activities such as deforestation, fires and over-grazing can accelerate their degradation and, consequently, the increases in losses of biological and economic productivity. Climate models, both local and global, predict that rainfall in the arid Peninsula of La Guajira in the Colombian Caribbean would be reduced and temperature would be increased as a result of climate change. However, as there are only suitable climate records since 1972, it is not possible to verify if, indeed, this is happening. To try to verify the hypothesis of reducing rainfall and rising temperatures we developed a growth ring chronology of Capparis odoratissima in the Middle Peninsula of La Guajira with 17 trees and 45 series which attain 48 years back. We use standard dendrochronological methods that showed statistically significant linear relationship with local climatic variables such as air temperature, sea surface temperature (SST), annual precipitation and wind speed; we also reach to successful relationship of the chronology with global climatic variables as the indices SOI and MEI of the ENSO phenomenon. The transfer functions estimated with the time series (1955 and 2003) do not showed statistically significant trends, indicating that during this period of time the annual precipitation or temperatures have not changed. The annual nature of C. odoratissima growth rings, the possibility of cross-dated among the samples of this species, and the high correlation with local and global climatic variables indicate a high potential of this species for dendrochronological studies in this part of the American continent. | {
"pile_set_name": "PubMed Abstracts"
} |
Justification of 150 mg clopidogrel in patients with high on-clopidogrel platelet reactivity.
The GRAVITAS trial showed that 150 mg clopidogrel did not improve outcome in patients with high on-clopidogrel platelet reactivity (HPR) screened by the VerifyNow assay. We aimed to determine the impact of 150 mg clopidogrel in stable angina patients with HPR identified with conventional aggregometry (LTA). Clopidogrel-naive stable angina patients before ad hoc percutaneous coronary intervention were recruited into a randomized, double-blind, placebo-controlled trial (NCT00638326). Twelve to 24 h after the 600-mg loading dose of clopidogrel, ADP(5μM)-stimulated maximal (AGGmax), late platelet aggregation (AGGlate) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI) were evaluated. Patients with HPR (AGGmax ≥ 34%) were randomly allocated to 75 or 150 mg clopidogrel after 4 weeks. After control platelet function measurements at day 28, 75 mg clopidogrel was administered to all patients until 1 year. The study was prematurely terminated at the stage of 200 enroled patients. Administration of 150 mg clopidogrel significantly reduced platelet aggregation (AGGmax: 45·0 ± 6·8 vs. 33·8 ± 15·1, P < 0·01; AGGlate: 27·1 ± 14·7 vs. 13·8 ± 18·0, P < 0·01) and VASP-PRI (57·5 ± 15·2 vs. 37·2 ± 17·1; P < 0·01), while platelet reactivity remained unchanged in patients with HPR receiving 75 mg clopidogrel. The higher maintenance dose of clopidogrel was associated with a significant reduction in cardiovascular (CV) death and myocardial infarction (MI) (0% vs. 11·4%, P = 0·04) and in CV death, MI or target vessel revascularization (24·6% vs. 3·1%; P = 0·01) during 1 year. One-month administration of 150 mg maintenance dose of clopidogrel reduces platelet reactivity and might decrease the risk of thrombo-ischaemic complications in stable angina patients with HPR identified by LTA. | {
"pile_set_name": "PubMed Abstracts"
} |
PNPCB heterocycles via thermal and Lewis acid catalyzed trans-hydroborations.
The compounds iPr2P(BH3)N3, tBu2PC[triple bond, length as m-dash]CR (R = Ph , tBu , Cy ) and Ph2PC[triple bond, length as m-dash]CR (R = Ph , tBu , Cy ) were reacted to give the products tBu2P(C[triple bond, length as m-dash]CR)NP(BH3)iPr2 (R = Ph , tBu , Cy ) and Ph2P(C[triple bond, length as m-dash]CR)NP(BH3)iPr2 (R = Ph , tBu , Cy ). Subsequent thermally induced or Lewis acid catalyzed intramolecular hydroboration of and afforded the PNPCB heterocyclic compounds Ph2P(C[double bond, length as m-dash]CHPh)NP(BH2)iPr2 and tBu2P(C[double bond, length as m-dash]CHPh)NP(BH2)iPr2, respectively. Compounds and were crystallographically characterized and the mechanisms and implications for the synthesis of inorganic heterocycles are considered. | {
"pile_set_name": "PubMed Abstracts"
} |
Immunostimulatory acivity of Calophyllum brasiliense, Ipomoea pes-caprae and Matayba elaeagnoides demonstrated by human peripheral blood mononuclear cells proliferation.
This study evaluates the effect of methanol extracts of three Brazilian medicinal plants on in vitro proliferation of human mononuclear cells. Lymphoproliferation assay was carried out by incubating human peripheral blood mononuclear cells from healthy donors (1 x 10(6) cells/mL) with extracts of Calophyllum brasiliense (roots), Ipomoea pes-caprae (whole plant) and Matayba elaeagnoides (bark), both at 10, 50, 100 and 200 microg/mL, alone or with phytohemagglutinin (PHA, 5 microg/mL), in 96-well microplates at 37 degrees C with 5% CO2, for 72 h. The quantification of cell proliferation assay was performed by blue tetrazolium (MTT) reduction with reading at 540 nm. Cells incubated with only the culture medium were used as negative control for cell proliferation, while the positive control consisted of cells and PHA. The results suggest that the extracts of all three studied plants induce T lymphocyte proliferation. I. pes-caprae showed immunostimulatory activity three times higher than the C. brasiliense extract, while that of the M. elaeagnoides extract was 1.5 times higher. The results demonstrate immunostimulatory effects of these three plants, therefore the continuity of these studies is recommended, in order to determine the active principles. | {
"pile_set_name": "PubMed Abstracts"
} |
Metaplastic carcinoma show different expression pattern of YAP compared to triple-negative breast cancer.
The purpose of this study is to examine the expression of Yes-associated protein (YAP) in metaplastic carcinoma and compare to those of triple-negative breast carcinoma (TNBC) for investigation of its implication. Tissue microarrays containing 34 cases of metaplastic carcinoma and 175 cases of TNBC were constructed and immunohistochemical staining was used to evaluate expression of the following proteins: YAP and phosphorylated YAP (pYAP). According to immunohistochemical staining results of cytokeratin 5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, STAT-1, androgen receptor, and GGT-1, metaplastic carcinoma and TNBC were sub-classified into six subtypes: basal-like type, molecular apocrine type, claudin-low type, immune-related type, mixed type, and null type. Comparing the expression of YAP and pYAP in metaplastic carcinoma and TNBC, the expression of nuclear YAP (p = 0.025), cytoplasmic pYAP (p = 0.010), and nuclear pYAP (p = 0.014) in tumor cell was higher in metaplastic carcinoma than TNBC. In metaplastic carcinoma, the nuclear YAP expression in tumor cell was associated with loss of E-cadherin (p = 0.020) and claudin type (p = 0.020), and the stromal YAP expression was associated with claudin 7 positivity (p = 0.003). In conclusion, the YAP expression in metaplastic carcinoma is higher than that in TNBC, representing the association of stemness and epithelial-mesenchymal transition features in metaplastic carcinoma. | {
"pile_set_name": "PubMed Abstracts"
} |
Signs and symptoms of Group A versus Non-Group A strep throat: A meta-analysis.
Both non-Group A streptococcal (non-GAS) pharyngitis and Group A streptococcal (GAS) pharyngitis are commonly found in patients with sore throat. It is not known whether or not they present with similar signs and symptoms compared to patients with non-streptococcal pharyngitis. MEDLINE was searched for prospective studies that reported throat culture for both GAS and non-GAS as a reference standard, and reported at least one sign, symptom, or the Centor score. Summary estimates of sensitivity, specificity, likelihood ratios (LR+ and LR-), and diagnostic odds ratios (DOR) were calculated using a bivariate random effects model. Summary receiver operating characteristic (ROC) curves were created for key signs and symptoms. Eight studies met our inclusion criteria. Tonsillar exudate had the highest LR+ for both GAS and non-GAS pharyngitis (1.53 versus 1.71). The confidence intervals of sensitivity, LR+, LR-, and DOR for all signs, symptoms, and the Centor score between two groups overlapped, with the relative difference between sensitivities within 15% for arthralgia or myalgia, fever, injected throat, tonsillar enlargement, and tonsillar exudate. Larger differences in sensitivities were observed for sore throat, cervical adenopathy, and lack of a cough, although the difference for lack of a cough largely due to a single outlier. Signs and symptoms of patients with GAS and non-GAS pharyngitis are generally similar. No signs or symptoms clearly distinguish GAS from non-GAS infection. Further work is needed to determine whether Group C streptococcus is a pathogen that should be treated. | {
"pile_set_name": "PubMed Abstracts"
} |
Differential expression of B29 (CD79b) and mb-1 (CD79a) proteins in acute lymphoblastic leukaemia.
CD79 is a heterodimeric molecule comprising two polypeptide chains, B29 (CD79b) and mb-1 (CD79a). It is physically linked in the surface of B cells to membrane immunoglobulin, forming the B cell antigen receptor complex. Expression of the mb-1 (CD79a) chain has been studied in leukaemias and shown to be present in most B lineage acute lymphoblastic leukaemias (ALL). In contrast, little is known about the expression of B29 (CD79b) in this condition. Two monoclonal antibodies (MoAb) were used in this study by immunocytochemistry and flow cytometry: HM57, against an intracellular epitope of the mb-1(CD79a) chain, and SN8, reacting with an extracellular epitope of B29 (CD79b). Our aim was to investigate the expression of B29 (CD79b) in the various immunological subtypes of B lineage ALL and compare its cytoplasmic and membrane expression. Seventy-nine cases were studied, including 13 chronic myeloid leukaemia in B lymphoid blast crisis (CML-BC) and 66 ALL, subclassified as early B (two), common (28), pre-B (23), mature (five) and biphenotypic with B lymphoid commitment (eight). Most cases expressed mb-1 (CD79a) in the cytoplasm. B29 (CD79b) was expressed in the cytoplasm in 65% (15/23) of pre-B-ALL and in 14% (4/28) common-ALL but it was detected in the cell membrane in only three cases of mature B-ALL, being negative in all other B lineage subtypes ALL. Three of the biphenotypic leukaemias coexpressed cytoplasmic B29 (CD79b) and mu-chain. This was also seen in two cases of CML-BC, while four cases expressed only cytoplasmic B29 (CD79b) without mu-chain. Our results suggest that during B cell differentiation, B29 (CD79b) is expressed later than mb-1 (CD79a) in the cytoplasm and parallels the cytoplasmic expression of mu-chain. B29 (CD79b) is present in the membrane at a later stage compared to its cytoplasmic expression and found in mature B blasts (B-ALL) that express membrane Ig as it is in normal and leukaemic B lymphocytes. | {
"pile_set_name": "PubMed Abstracts"
} |
Removing the Twiddling stigma: spontaneous lead retraction without patient manipulation.
After pacemaker or implantable cardioverter-defibrillator (ICD) implantation, it takes weeks for the leads to scar in place. Occasionally, newly implanted leads dislodge by retracting towards the device pocket. This phenomenon is generally called 'Twiddler's Syndrome,' with the invoked mechanism being patient manipulation of the device pocket. We present a case of a 27-year-old man who had complete retraction of the atrial lead, but not the ventricular lead, after a submuscular dual-chamber ICD implantation. The specifics of this case demonstrate that leads can spontaneously retract during normal arm movement, without any conscious or unconscious device manipulation by the patient. Leads must be firmly secured in the device pocket via their suture sleeves in order to minimize the risk of retraction, regardless of mechanism. | {
"pile_set_name": "PubMed Abstracts"
} |
Latent infection by bovine herpesvirus type-5 in experimentally infected rabbits: virus reactivation, shedding and recrudescence of neurological disease.
Latent infection with bovine herpesvirus type-5 (BHV-5) was established in rabbits inoculated with two South American isolates (EVI-88 and 613) by intranasal or conjunctival routes. Nine rabbits (613, 8/27; EVI-88, 1/34) developed neurological disease and died during acute infection and other three (613, n=2; EVI-88, n=1) developed a delayed neurological disease, at days 34, 41 and 56 post-inoculation (p.i.). Between days 56 and 62 p.i., the remaining rabbits were submitted to five daily administrations of dexamethasone (Dx) to reactivate the infection. Twenty-five out of 44 rabbits (56.8%) shed virus in nasal or ocular secretions after Dx treatment. Virus shedding was first detected at day two post-Dx and lasted from one to 11 days. The highest frequencies of virus reactivation were observed in rabbits inoculated conjunctivally (10/15 versus 15/29); and among rabbits infected with isolate 613 (12/16 versus 13/28). Virus reactivation upon Dx treatment was accompanied by neurological disease in nine rabbits (20.4%), resulting in six deaths (13.6%). Virus in moderate titers and mild to moderate non-suppurative inflammatory changes in the brain characterized the neurological infection. Three other rabbits showed severe neurological signs followed by death after 31 to 54 days of Dx treatment. Virus, viral nucleic acids and inflammatory changes were detected in their brains. The late-onset neurological disease, after acute infection or Dx treatment, was probably a consequence of spontaneous virus reactivation. These results demonstrate that BHV-5 does establish a latent infection in rabbits and that clinical recrudescence may occur upon reactivation. | {
"pile_set_name": "PubMed Abstracts"
} |
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