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pubmed_884_8257 | The complete covalent structure of the bacteriophage lambda repressor has been determined by sequential Edman degradation, gas chromatographic-mass spectrometric peptide sequencing, and DNA sequencing of the repressor gene cI. The repressor is a single-chain, acidic protein containing 236 amino acids. The amino terminal 40 residues are highly polar and basic. Lysines and arginines in the sequence tend to be clustered. | 10.1021/bi00599a024 |
pubmed_852_18239 | We propose an approach to generate true random number sequences based on the discretized encoding of the time interval between photons. The method is simple and efficient, and can produce a highly random sequence several times longer than that of other methods based on threshold or parity selection, without the need for hashing. A proof-of-principle experiment has been performed, showing that the system could be easily integrated and applied to quantum cryptography and other fields. | 10.1364/JOSAA.30.000124 |
pubmed_196_1297 | The nitric oxide (NO) pathway plays a role in maintaining the function of the prostate. An impairment in the activity of the NO system may have an impact in the manifestation of lower urinary tract symptomatology and benign prostatic hyperplasia. Arginase enzymes (Arg) counteract the generation of NO by depleting the intracellular pool of L-arginine, known to be the substrate of the NO synthases. This study investigated the expression of arginase type I and II in the human prostate. Nondiseased prostate tissue was obtained during pelvic surgeries (prostatectomy, cystoprostatectomy). Tissue sections were exposed to antibodies directed against Arg I and II, cGMP, the phosphodiesterase 5 and nNOS. The expression of mRNA transcripts encoding for Arg I and Arg II was investigated using molecular biology. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of mRNA encoding for Arg I and II, immunofluorescence specific for Arg I was seen in the stromal smooth musculature, and labelling for PDE5 and cyclic GMP was also observed. Nerve fibres containing nNOS were identified running across the smooth musculature. Immunostainings for Arg II did not yield signals. These findings are in support of the notion that, in the prostate, Arg is involved in the modulation of the activity of the NO system. | 10.1111/and.13349 |
pubmed_414_1550 | Our knowledge about particle size in relation to activation of the innate immune system is limited. Therefore, the acute effect of particle exposure on the innate immune system was studied in a lung model using the intracellular bacterium Listeria monocytogenes. Female Balb/cA mice were instilled intratracheally with polystyrene particles (PSP) of different diameters (0.064, 0.202, 1.053 and 4.646 mum) simultaneously with or 1 day prior to inoculation of 10(5) bacteria. Mice were sacrificed 1 day after Listeria challenge, and the numbers of viable bacteria in the lungs and the spleen were determined as a measure of cellular activation. In separate experiments, bronchoalveolar lavage (BAL) fluid was collected. Only mice exposed to the smallest PSP (0.064 and 0.202 mum) had significantly reduced bacterial numbers in the lung after particles and Listeria were given simultaneously. When particles were given 1 day prior to Listeria challenge also the largest 4.646 mum PSP, but not the medium size 1.053 mum PSP, reduced bacterial numbers. The number of neutrophils in BAL fluid was increased for all PSP-exposed groups after 24 h, and tended to be highest in the group exposed to 4.646 mum PSP. TNF-alpha, IL-1beta and MIP-2 were significantly increased in BAL fluid after exposure to the largest compared with the smallest PSP. In conclusion, activation of the innate immune system by chemical-free particles was size-dependent. Ultrafine and coarse particles appeared to activate cells by different mechanisms, which implies qualitative differences between the health effects of ambient air particulate matter size fractions. | 10.1111/j.1365-3083.2009.02244.x |
pubmed_462_19356 | A serum-free, fetal bone organ culture model that permits the simultaneous determination of modeling and growth parameters was used to examine the effects of a near physiologic and a pharmacologic dose of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]. The fetuses of pregnant mice were removed on day 17 of gestation, and three medial metatarsal rudiments were cleaned and after preculturing were cultured as pair-matched groups for 4 days in MEM supplemented with 0.2% BSA. 1,25-(OH)2D3 was added to the cultures at concentrations of 10(-12) or 10(-6) M. Cultures treated with the carrier and devitalized bones served as controls. For resorption studies, pregnant mice were given 45Ca on day 17 of pregnancy and fetal metatarsals harvested 24 h later. Resorption was determined by the amount of 45Ca released into the media. DNA synthesis was estimated by determining the incorporation of [3H]thymidine, collagen synthesis by measuring the incorporation of [3H]proline, mineralization by the incorporation of 45Ca, and proteoglycan synthesis by the incorporation of 35S. The amount of radiolabel was detected in media, as well as in noncultured, dead, and cultured rudiments. The total length of the rudiments and length of the calcified diaphyses were measured daily. In addition, rudiments from all experimental groups were prepared for light and electron microscopy. The high dose (10(-6) M) of 1,25-(OH)2D3 suppressed total rudiment growth but not the growth of the calcified diaphysis, 1,25-(OH)2D3 also decreased DNA, collagen, and proteoglycan synthesis, reduced calcification, and increased bone resorption in a dose-related manner. There were morphologic and ultrastructural changes in the osseous tissues and cells, particularly with the high dose of vitamin D, that supported the biochemical findings of suppressed activity of the osteogenic and chondrogenic cells. However, the suppression of collagen production and bone cell proliferation observed with the pharmacologic dose of vitamin D may be partially attributable to the decrease in bone mass (from increased resorption), thus resulting in less osseous tissue surface for these events to occur as endochondral osteogenesis progressed. The lower dose of vitamin D, however, had effects on 35S and 45Ca incorporation that could not be attributed to a decreased osseous tissue mass. This study emphasizes the importance of measuring specialized activities of the various cell populations in bone rudiment culture models to more fully understand the changes in tissue metabolism that result in changes in rudiment growth and modeling. | 10.1002/jbmr.5650070106 |
pubmed_795_12035 | Thiocolchicoside, a muscle-relaxant agent, is administered by the oral, intra-muscular and topical route. After oral administration the extent of bioavailability compared with intra-muscular administration is low, due to a first pass effect. In this paper, the delivery of thiocolchicoside through oral mucosa is studied to improve the bioavailability. Thiocolchicoside in vitro permeation through porcine oral mucosa and in vivo buccal transport in humans were investigated. Two dosage forms, a bioadhesive disc and a fast dissolving disc for buccal and sublingual administration of thiocolchicoside, respectively, were designed. The in vitro permeation of thiocolchicoside through porcine buccal mucosa from these dosage forms was evaluated and compared with in vivo absorption. Results from in vitro studies demonstrated that thiocolchicoside is quite permeable across porcine buccal mucosa and that permeation enhancers, such as sodium taurocholate and sodium taurodeoxycholate, were not able to increase its flux. The in vivo thiocolchicoside absorption experiments, in which the drug loss from oral cavity was measured, indicated that both formulations could be useful for therapeutic application. The fast dissolving (sublingual) form resulted in a quick uptake of 0.5 mg of thiocolchicoside within 15 min whereas with the adhesive buccal form the same dose can be absorbed over an extended period of time. | 10.1016/s0378-5173(02)00545-8 |
pubmed_537_10521 | Polycystic kidney disease (PKD) is a common genetic disease characterized by the proliferation of epithelial cells, formation of cysts, and the progression of renal deficiency. We have investigated a possible role of glycosphingolipids in the proliferation of human kidney cells in this disease. The levels of glucosylceramide and lactosylceramide and the activity of glucosylceramide synthase (GlcT-1) and lactosylceramide synthase (GalT-2) were elevated 2-fold and 3-fold, respectively, in the PKD tissue compared to control. Lactosylceramide, but not glucosylceramide (10 microM) derived from PKD exerted a 4-fold stimulation in the proliferation of these cells. However, at a concentration of 40 microM, lactosylceramide and glucosylceramide both stimulated cell proliferation on the order of 10-fold and 2.5-fold, respectively, as compared to control. This phenomenon may be due to the enrichment of lactosylceramide containing shorter chain fatty acids (C16:0-C18:0). Lactosylceramide, but not glucosylceramide exerted a time-dependent stimulation in the phosphorylation of mitogen-activated protein kinase (p44 MAPK) in normal human kidney proximal tubular cells. Moreover, the kidneys and cultured cells from the PKD patients contained higher levels of the p44 MAPK as compared to normal human kidneys. In sum, our studies indicate that lactosylceramide present in the PKD kidney may stimulate cell proliferation via activation of the p44 MAPK, and contribute to the pathophysiology in this disease. | pubmed_537_10521 |
others_3_16582 | Generation of anti-idiotypic antibodies using antibody libraries and phage-display technology produces fully human antibodies with exquisite binding specificity that can be used in assays for both early- and late-stage development, avoiding continual assay validation. The in vitro production method confers consistency of reproduction and a guaranteed long-term supply, allowing faster optimization of PK and IR assays, and effective management of the resources and costs associated with the complex assay development process | 10.1089/gen.34.17.08 |
pubmed_791_11273 | The vaginal microbiota is thought to play a role in modulating risk of high-risk human papillomavirus (hrHPV) infection. We examined the relationship between the vaginal microbiota and persistent hrHPV infection in HIV-negative and HIV-positive women. We used 16S-rRNA sequencing to characterize the vaginal microbiota of two serial samples taken six months apart from 211 Nigerian women (67%, 142/211 HIV-positive and 33%, 69/211 HIV-negative) and evaluated the association between the vaginal microbiota and persistent hrHPV infection using generalized estimating equation logistic regression models and linear discriminant analysis effect size (LEfSe) algorithm to identify phylotypic biomarkers of persistent hrHPV infection. The high diversity microbiota, Community State Type IV-B, was the most prevalent in both HIV-negative (38% at baseline, 30% at the follow-up visit) and HIV-positive (27% at baseline, 35% at the follow-up visit) women. The relationship between the vaginal microbiota and persistent hrHPV was modified by HIV status. In HIV-negative women, women with Lactobacillus dominant microbiota had lower odds (OR: 0.35, 95% CI 0.14-0.89, p = 0.03) of persistent hrHPV compared to women with Lactobacillus deficient microbiota. While among HIV-positive women, the odds of being persistently infected with hrHPV was higher in women with Lactobacillus dominant microbiota (OR: 1.25, 95% CI 0.73-2.14 p = 0.41). This difference in effect estimates by HIV was statistically significant (p = 0.02). A high diversity vaginal microbial community with paucity of Lactobacillus species was associated with persistent hrHPV infection in HIV-negative women but not in HIV-positive women. | 10.1038/s41598-020-76003-7 |
pubmed_302_11757 | Hyperuricemia is associated with hypertension and vascular disease, but whether this represents a causal relationship or an epiphenomenon remains unknown. We recently reported a model of mild hyperuricemia in rats that results in increased blood pressure and mild renal fibrosis. In this study, we examined the effect of hyperuricemia on the renal vasculature. Rats fed 2% oxonic acid and a low-salt diet for 7 wk developed mild hyperuricemia (1.8 vs. 1.4 mg/dl, P < 0.05), hypertension [147 vs. 127 mmHg systolic blood pressure (SBP), P < 0.05], and afferent arteriolar thickening, with a 35% increase in medial area (P < 0.05). Allopurinol or benziodarone prevented the hyperuricemia, hypertension, and arteriolopathy. Hydrochlorothiazide treatment did not prevent the hyperuricemia or arteriolopathy despite controlling blood pressure. In contrast, the arteriolopathy and hypertension were prevented by both enalapril and losartan. Uric acid also directly stimulated vascular smooth muscle cell proliferation in vitro, and this was partially inhibited by losartan. Thus hyperuricemia induces a renal arteriolopathy in rats that is blood pressure independent and involves the renin-angiotensin system. | 10.1152/ajprenal.00283.2001 |
pubmed_989_22165 | This work presents a droplet applicator module to generate stable droplets with different muzzle energies for the reproducible endoscopic stimulation of the laryngeal adductor reflex (LAR). The LAR is a protective reflex of the human larynx; an abnormal LAR performance may cause aspiration pneumonia. A pathological LAR can be detected by evaluating its onset latency. The reflex can be triggered by shooting a droplet onto the laryngeal mucosa, which is referred to as Microdroplet Impulse Testing of the LAR (MIT-LAR). Stimulation intensity variation is desired as the reflex threshold may vary inter-individually. The kinetic energy of a droplet after detachment from the nozzle, i.e., its muzzle energy, is considered an appropriate metric for the LAR stimulation intensity. In this work, a suitable nozzle channel geometry is identified based on the experimental evaluation of droplet formation using three different nozzle channel geometries. Two nontoxic additives are evaluated regarding their effect on fluid properties and droplet formation. The range of achievable droplet muzzle energies is determined by high-speed cinematography in association with a physically motivated model of the macroscopic droplet motion. The experimental results show that sodium chloride is a suitable additive to enhance droplet stability in the studied parameter range with the proposed system. Droplet muzzle energy variation from 0.02 J to 1.37 J was achieved while preserving the formation of a single stimulation droplet. These results are an important prerequisite for a safe and reproducible LAR stimulation by MIT-LAR, which could also help to further elucidate the physiological mechanisms underlying this laryngeal reflex. | 10.1063/5.0004351 |
pubmed_363_16159 | Human macrophages (Mphi) respond to Mycobacterium tuberculosis (Mtb) infection by undergoing apoptosis, a cornerstone of effective antimycobacterial host defense. Virulent mycobacteria override this reaction by inducing necrosis leading to uncontrolled Mtb replication. Accordingly, Mphi death induced by inoculation with Mtb had the characteristics of apoptosis and necrosis and correlated with moderate increase of mitochondrial permeability transition (MPT), mitochondrial cytochrome c release, and caspase-9 and -3 activation. We hypothesized that changes in intramitochondrial Ca(2+) concentration ([Ca(2+)](m)) determine whether Mphi undergo either apoptosis or necrosis. Therefore, we induced mechanism(s) leading to predominant apoptosis or necrosis by modulating [Ca(2+)](m) and examined their physiological consequences. Adding calcium ionophore A23187 to Mphi inoculated with Mtb further increased calcium flux into the cells which is thought to lead to increased [Ca(2+)](m), blocked necrosis, stabilized MPT, decreased mitochondrial cytochrome c release, lowered caspase activation, and accompanied effective antimycobacterial activity. In contrast, Mphi infected with Mtb in presence of the mitochondrial calcium uniporter inhibitor ruthenium red showed increased mitochondrial swelling and cytochrome c release and decreased MPT and antimycobacterial activity. Thus, in Mtb-infected Mphi, high levels of mitochondrial membrane integrity, low levels of caspase activation, and diminished mitochondrial cytochrome c release are hallmarks of apoptosis and effective antimycobacterial activity. In contrast, breakdown of mitochondrial membrane integrity and increased caspase activation are characteristic of necrosis and uncontrolled Mtb replication. | 10.4049/jimmunol.169.9.5181 |
others_392_9067 | Neotelmatoscopus ctenophorus, a remarkable new non-Phlebotomine psychodid collected from the Kolli hills, Salem District, Tamil Nadu, India is described. A key is provided to the known species of Neotelmatoscopus. © 1994, Taylor & Francis Group, LLC. All rights reser | 10.1080/01650429409361548 |
pubmed_93_7050 | Impaired cutaneous blood flow and sweating dysfunction might be among the earliest manifestations of diabetic autonomic neuropathy. This study assessed the pathophysiological basis underlying skin vasomotion changes and their relation with progressive sudomotor dysfunction and other autonomic and somatic measures in subclinical diabetic feet. Laser Doppler skin perfusion was assessed on 68 diabetic and 25 control subjects. The low-frequency vasomotion was transformed into three frequency intervals 0.0095-0.021, 0.021-0.052 and 0.052-0.145 Hz, respectively, for the investigation of endothelial, neurogenic and myogenic effects on microcirculatory alterations. The diabetic patients were categorized into three groups by increasing severity of sudomotor dysfunction: SSR+ (sympathetic skin response present; 27 patients), SSR- (SSR absent; 23 patients) and at-risk (SSR absent and of preulcerative cracked skin; 18 patients). All diabetic patients underwent nerve conduction and cardiovascular autonomic studies. The total spectral and endothelial activity was significantly decreased only in the at-risk group. The SSR- group had lower neurogenic vasomotion than the SSR+ group (p<0.05). Although no statistical difference was noted between any group in absolute myogenic spectrum, the SSR- group had higher normalized myogenic activity than the SSR+ group (p<0.01). The larger drop in orthostatic pressure was paralleled by a reduction in the myogenic amplitude (r=-0.33, p<0.01). These results suggested that early impairment of low-frequency flow motion correlated closely with the presence of sudomotor dysfunction of subclinical feet mainly in neurogenic and endothelial components. Impaired systemic vascular tone as manifested by orthostatic hypotension was proportional to the degree of myogenic dysregulation in diabetic patients. | 10.1016/j.mvr.2011.06.002 |
pubmed_57_22108 | INTRODUCTION
Novel peroxisome proliferator-activated receptor (PPAR) modulators (selective PPAR modulators [SPPARMs]) and dual PPAR agonists may have an important role in the treatment of cardiometabolic disorders owing to lipid-modifying, insulin-sensitizing and anti-inflammatory effects.
AREAS COVERED
This review summarizes the efficacy of new PPAR agonists and SPPARMs that are under development for the treatment of atherogenic dyslipidemia and non-alcoholic fatty liver disease (NAFLD).
EXPERT OPINION
ABT-335 is a new formulation of fenofibrate that has been approved for concomitant use with statins. K-877, a SPPARM-α with encouraging preliminary results in modulating atherogenic dyslipidemia, and INT131, a SPPARM-γ with predominantly insulin-sensitizing actions, may also have favorable lipid-modifying effects. Although the development of dual PPAR-α/γ agonists (glitazars) and the SPPARM-δ GW501516 has been abandoned because of safety issues, another SPPARM-δ (MBX-8025) and a dual PPAR-α/δ agonist (GFT-505) have shown promising efficacy in decreasing plasma triglyceride and increasing high-density lipoprotein cholesterol concentrations, as well as improving insulin sensitivity and liver function. The beneficial effects of GFT-505 are complemented by preclinical findings that indicate reduction of hepatic fat accumulation, inflammation and fibrosis, making it a promising candidate for the treatment of NAFLD/nonalcoholic steatohepatitis (NASH). Long-term trials are required to test the efficacy and safety of these new PPAR agonists in reducing cardiovascular outcomes and treating NAFLD/NASH. | 10.1517/14656566.2014.876992 |
pubmed_122_5124 | BACKGROUND
Congenital scoliosis (CS) may lead to more serious pulmonary complications compared with idiopathic scoliosis after spinal fusion surgery. However, little has been reported about postoperative pulmonary complication events in patients with CS after spinal fusion surgery.
OBJECTIVE
To investigate the incidence of and predictive factors of postoperative pulmonary complications following posterior spinal instrumentation and fusion surgery for the treatment of CS.
METHODS
We retrospectively reviewed the records of 174 patients with CS (128 females and 46 males, mean age 16.4 years) treated with posterior spinal instrumentation and fusion surgery between January 2012 and April 2017. We extracted demographic, medical history, and clinical data, and investigated the major predictive factors for postoperative pulmonary complications by logistic regression and receiver-operating characteristic curves analyses.
RESULTS
A total of 26 (14.9%) patients developed postoperative pulmonary complications, consisting of pleural effusion (10.9%), pneumonia (6.9%), pneumothorax (1.1%), atelectasis (2.3%), hypoxemia (6.3%), and respiratory failure (1.1%). Logistic regression analysis revealed that the predictive factors for postoperative pulmonary complications were age > 18.1 years (P = 0.039), a Cobb angle of > 77° (P = 0.011), operation time of > 430 min (P = 0.032), and blood transfusion volume > 1500 ml (P = 0.015).
CONCLUSIONS
Postoperative pulmonary complications are among the main complications following posterior spinal instrumentation and fusion surgery in patients with CS. Such patients aged >18.1 years, with Cobb angles > 77°, operation times > 430 min, and/or blood transfusion volume of > 1500 ml may be more likely to develop postoperative pulmonary complications. | 10.1371/journal.pone.0207657 |
pubmed_41_24981 | Fructose and dicarbonyl compounds resulting from fructose in heated foods have been linked to pathophysiological pathways of several metabolic disorders. Up to now, very little has been known about the Maillard reaction of fructose in food. Heyns rearrangement compounds (HRCs), the first stable intermediates of the Maillard reaction between amino components and fructose, have not yet been quantitated as protein-bound products in food. Therefore, the HRCs glucosyllysine and mannosyllysine were synthesized and characterized by NMR. Protein-bound HRCs in cookies containing various sugars and in commercial bakery products were quantitated after enzymatic hydrolysis by RP-HPLC-ESI-MS/MS in the multiple reaction monitoring mode through application of the standard addition method. Protein-bound HRCs were quantitated for the first time in model cookies and in commercial bakery products containing honey, banana, and invert sugar syrup. Concentrations of HRCs from 19 to 287 mg/kg were found, which were similar to or exceeded the content of other frequently analyzed Maillard reaction products, such as N-ε-carboxymethyllysine (10-76 mg/kg), N-ε-carboxyethyllysine (2.5-53 mg/kg), and methylglyoxal-derived hydroimidazolone 1 (10-218 mg/kg) in the analyzed cookies. These results show that substantial amounts of HRCs form during food processing. Analysis of protein-bound HRCs in cookies is therefore useful to evaluate the Maillard reaction of fructose. | 10.1021/acs.jafc.7b04172 |
pubmed_1037_17673 | INTRODUCTION
In septic shock, mitochondrial dysfunction, and hypoperfusion are the main triggers of multi-organ failure. Little is known about the crosstalk between mitochondrial dysfunction and hemodynamic alterations, especially in the post-resuscitation phase. Here, we assess whether hypoperfusion and lactate levels are associated with oxygen consumption linked to mitochondrial bioenergetic activity in lymphocytes of patients admitted with septic shock.
PATIENTS AND METHODS
Prospective cohort study in patients with septic shock defined as the requirement of vasopressors to maintain a mean arterial pressure 65 mm Hg after initial fluid administration. Basal mitochondrial and Complex I respiration was measured to evaluate mitochondrial activity. Both variables and capillary refill time were compared with arterial lactate post-fluid resuscitation. We also compared mitochondrial activity measurements between patients with and without hypoperfusion status.
RESULTS
A total of 90 patients were included in analysis. The median arterial lactate at the time of septic shock diagnosis was 2.0 mmol/Dl (IQR 1.3-3.0). Baseline respiration at the time of septic shock diagnosis was correlated with lactate (Spearman -0.388, 95% CI -0.4893 to -0.1021; P = 0.003), as well as Complex I respiration (Spearman -0.403, 95% CI -0.567 to -0.208; P < 0.001). Patients with hypoperfusion status had no difference in basal respiration when compared with patients who did not have hypoperfusion status (P = 0.22) nor in Complex I respiration (P = 0.09).
CONCLUSION
Changes in lymphocytic mitochondrial metabolism are associated with post-resuscitation arterial lactate in septic shock; however, they are not associated with the presence of a hypoperfusional status. In this scenario, it is therefore suggested that systemic perfusion and mitochondrial metabolism have different courses. | 10.1097/SHK.0000000000001868 |
pubmed_383_13425 | The initial focus of the COVID-19 pandemic was on the surge capacity of hospitals. Moving forward, however, the attention needs to shift toward keeping people healthy at home. In this paper, we discuss critical insights from the home and community care sector, which shed light on pre-pandemic fault lines that have widened. The paper, however, takes a positive look at how a better future can be built, particularly for those most vulnerable in society. We offer three key insights and analyses as well as examples of how one national homecare organization in Canada, SE Health, is facing the pandemic. We discuss the following key insights: (1) pre-pandemic systemic biases and barriers were exasperated during the pandemic, which impacted the most vulnerable; (2) nurse leaders were faced with unprecedented fear and anxiety from both patients and their staff colleagues; and (3) the pandemic provided an opportunity for significant learning, innovation and capacity development. The pandemic is far from over - we are in a marathon, not a sprint. The paper concludes with how nurse leaders can lead the way in navigating through the pandemic and build a better "new normal." | 10.12927/cjnl.2021.26420 |
pubmed_705_3433 | Acute GVHD (aGVHD) is one of the major problems after allogeneic BMT. The diagnosis of aGVHD is difficult to establish, relying mainly on clinical evaluations and symptoms of aGVHD, often resembling those of organ toxicity, infection or drug rash. In 21 patients after BMT several serum cytokine levels (soluble interleukin-2 receptor (sIL-2R), sTNF-R, SCF, IL-6, IL-8, G-SCF and ICAM-1) were determined in order to evaluate their value as an indicator for aGVHD. The maximum levels of sIL-2R (and none of the other evaluated cytokines) correlated significantly (r = 0.8, P = 0.008) with the severity of aGVHD. We also found a significant correlation between the day of engraftment (neutrophil count >0.5 x 10(9)/l) and the severity of aGVHD (r = 0.5, P = 0.03): engraftment was earlier in patients without aGVHD (median of day 11) than in those with aGVHD (median of day 18). No correlation between sIL-2R and fever or organ toxicity could be found. Our data suggest that the sIL-2R level might be an indicator for aGVHD, reflecting the severity of the disease. In patients with late engraftment the risk of aGVHD seems to be increased, therefore these patients especially should be monitored closely, possibly using sIL-2R levels. | 10.1038/sj.bmt.1701041 |
pubmed_564_15687 | The evaluation, diagnosis, and treatment of childhood epilepsy or isolated seizures deserve special consideration. Whenever possible, a working diagnosis of an epilepsy syndrome should be implemented early in the course of evaluation to help plan the necessary investigations and acute and chronic treatment. The plan will evolve over a number of years as the patient's syndrome is better defined. The overall neurologic status of the child and response to therapy are important prognostic factors. Treatment proceeds after balancing antiepileptic drug efficacy versus adverse drug effects. The length of treatment, discussion of prognosis, and likelihood for genetic transmission are all related to the proper diagnosis of epilepsy syndromes. | pubmed_564_15687 |
pubmed_289_25151 | The Protein Model Portal (PMP) has been developed to foster effective use of 3D molecular models in biomedical research by providing convenient and comprehensive access to structural information for proteins. Both experimental structures and theoretical models for a given protein can be searched simultaneously and analyzed for structural variability. By providing a comprehensive view on structural information, PMP offers the opportunity to apply consistent assessment and validation criteria to the complete set of structural models available for proteins. PMP is an open project so that new methods developed by the community can contribute to PMP, for example, new modeling servers for creating homology models and model quality estimation servers for model validation. The accuracy of participating modeling servers is continuously evaluated by the Continuous Automated Model EvaluatiOn (CAMEO) project. The PMP offers a unique interface to visualize structural coverage of a protein combining both theoretical models and experimental structures, allowing straightforward assessment of the model quality and hence their utility. The portal is updated regularly and actively developed to include latest methods in the field of computational structural biology. Database URL: http://www.proteinmodelportal.org. | 10.1093/database/bat031 |
pubmed_431_5952 | Breast cancer risk is higher among obese women and women with diabetes. Adiponectin is a protein exclusively secreted by adipose tissue, circulating levels of which have been associated with breast cancer risk. Whether genetic variants within the adiponectin pathway are associated with breast cancer risk is unknown. To explore the association of genetic variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with breast cancer risk, we conducted a case control study of female patients with breast cancer and healthy female controls from New York City recruited between 1999 and 2004. We genotyped 733 hospital-based breast cancer cases and 839 controls for 10 haplotype-tagging single nucleotide polymorphisms (SNP) of ADIPOQ and ADIPOR1. Two ADIPOQ SNPs (rs2241766 and rs1501299), which have been associated with circulating levels of adiponectin, were associated with breast cancer risk [rs1501299*GG: odd ratios (OR), 1.80; 95% confidence interval (95% CI), 1.14-2.85; rs2241766*TG: OR, 0.61; 95% CI, 0.46-0.80]. One ADIPOR1 SNP (rs7539542), which modulates expression of adiponectin receptor 1 mRNA, was also associated with breast cancer risk (OR, 0.51; 95% CI, 0.28-0.92). Based on the known function of rs2241766 and rs1501299, we categorized individuals by adiponectin signaling status and found that, when compared with high signalers, intermediate signalers had a 4.16-fold increase in breast cancer risk (95% CI, 0.49-35.19), and low signalers had a 6.56-fold increase in breast cancer risk (95% CI, 0.78-54.89; P(trend) = 0.001). This is the first report of an association between functionally relevant variants of the adiponectin pathway and breast cancer risk. The results warrant further studies of the adiponectin pathway in breast cancer. | 10.1158/0008-5472.CAN-08-0533 |
pubmed_726_22291 | Malaria has been endemic in Guangzhou for more than 50 years. The goal of this study was to use a negative binomial regression to identify the relationship between meteorological variables and malaria reported. Our results revealed that each 1°C rise of temperature corresponds to an increase of 0.90% in the monthly number of malaria cases. Likewise, a one percent rise in relative humidity led to an increase of 3.99% and a one hour rise in sunshine led to an increase of 0.68% in the monthly number of cases. Our findings may be useful for developing a simple, precise malaria early warning system. | 10.1186/1756-3305-6-155 |
pubmed_339_687 | BACKGROUND
TS/A cells (a Balb/c-derived tumor cell line), when injected into syngenic mice, give rise to rapidly growing tumors. In this study, a vaccination protocol was established which was able to elicit an immune response effective in controlling tumor growth.
MATERIALS AND METHODS
T19.2.1, a TS/A clone enginereed to stably express the mycobacterial cell wall-associated 19-kDa lipoprotein, was used as cell vaccine to immunize Mycobacterium Bovis-BCG pre-immunized Balb/c mice.
RESULTS
Mice receiving the two-step vaccination protocol were able to develop a strong anti-TS/A DTH reaction. Moreover, following a challenge with wild-type TS/A cells, some vaccinated animals rejected the tumor and the remaining animals showed a significantly increased survival in respect to controls.
CONCLUSION
The expression on TS/A cells of the mycobacterial 19-kDa antigen, recognised in the context of a pre-existing memory immune response, promotes the immunological recognition of the otherwise non-immunogenic wild-type TS/A cells. | pubmed_339_687 |
pubmed_482_2796 | This study evaluates the potential for fluorescence lifetime imaging (FLIm) to enhance intraoperative decisionmaking during robotic-assisted surgery of oropharyngeal cancer. Using a custom built FLIm instrument integrated with the da Vinci robotic surgical platform, we first demonstrate that cancer in epithelial tissue diagnosed by histopathology can be differentiated from surrounding healthy epithelial tissue imaged in vivo prior to cancer resection and ex vivo on the excised specimen. Second, we study the fluorescence properties of tissue imaged in vivo at surgical resection margins (tumor bed). Fluorescence lifetimes and spectral intensity ratios were calculated for three spectral channels, producing a set of six FLIm parameters. Current results from 10 patients undergoing TORS procedures demonstrate that healthy epithelium can be resolved from cancer (P < .001) for at least one FLIm parameter. We also showed that a multiparameter linear discriminant analysis approach provides superior discrimination to individual FLIm parameters for tissue imaged both in vivo and ex vivo. Overall, this study highlights the potential for FLIm to be developed into a diagnostic tool for clinical cancer applications of the oropharynx. This technique could help to circumvent the issues posed by the lack of tactile feedback associated with robotic surgical platforms to better enable cancer delineation. | 10.1002/tbio.201900017 |
pubmed_1108_4681 | The most common metastatic sites of cholangiocarcinoma are the retroperitoneal lymph nodes, peritoneum, liver and lungs, and cutaneous metastases of cholangiocarcinoma are rare. Although cutaneous metastases of internal malignancies most commonly present clinically as nontender nodules appearing in a particular area of body, other presentations can occur. Cutaneous metastases of cholangiocarcinoma can appear as a solitary tumour at the therapeutic drainage site. We report a 60-year-old man with unusual cutaneous metastases from hilar cholangiocarcinoma, which presented as multiple indurated plaques and papules on the anterior chest. | 10.1111/j.1365-2230.2008.03022.x |
pubmed_197_19294 | UNLABELLED
BACKGROUND, OBJECTIVES AND METHODS: An accurate, sensitive and precise assay for reliable determination of the ristocetin cofactor activity of von Willebrand factor (VWF:RCo) in plasma and von Willebrand Factor (VWF)-containing concentrates has been evaluated. The assay is based on a commercially available automated protocol with modifications including a combination of adding additional ristocetin and the use of two calibration curves for the high and low measuring ranges.
RESULTS
Addition of extra ristocetin resulted in improved measurement of VWF recoveries from various VWF-containing concentrates that were underestimated using the standard automated protocol. The modifications resulted in improved assay performance over an extended measuring range (2.00-0.03 IUmL(-1) ). Accuracy was tested using VWF deficiency plasma spiked with the 1st international standard (IS) for VWF concentrate. Seven dilutions, ranging from 1.80 to 0.05IUmL(-1) , were analyzed and resulted in measured concentrations between 80% and 100% of the assigned potency of the standard. Linearity was determined from the regression plot of the same concentrate dilutions and resulted in a correlation coefficient of 0.998. The repeatability, expressed as coefficient of variation, was 2% in the normal range (0.90IUmL(-1) ) and 8% at the level of 0.05IUmL(-1) . The corresponding reproducibility results were 2% and 15% at the normal and low measuring ranges, respectively.
CONCLUSIONS
Analysis of patients with von Willebrand disease (VWD) indicates that the modified automated BCS(®) protocol has a superior discrimination power compared with the standard protocol. This is especially true in samples with low VWF, as in patients with type 3 VWD. | 10.1111/j.1538-7836.2010.04029.x |
pubmed_800_10656 | Brodmann showed areas 26, 29, 30, 23, and 31 on the human posterior cingulate gyrus without marking sulcal areas. Histologic studies of retrosplenial areas 29 and 30 identify them on the ventral bank of the cingulate gyrus (CGv), whereas standardized atlases show area 30 on the surface of the caudomedial region. This study evaluates all areas on the CGv and caudomedial region with rigorous cytologic criteria in coronal and oblique sections Nissl stained or immunoreacted for neuron-specific nuclear binding protein and nonphosphorylated neurofilament proteins (NFP-ir). Ectosplenial area 26 has a granular layer with few large pyramidal neurons below. Lateral area 29 (29l) has a dense granular layer II-IV and undifferentiated layers V and VI. Medial area 29 (29m) has a layer III of medium and NFP-ir pyramids and a layer IV with some large, NFP-ir pyramidal neurons that distinguish it from areas 29l, 30, and 27. Although area 29m is primarily on the CGv, a terminal branch can extend onto the caudomedial lobule. Area 30 is dysgranular with a variable thickness layer IV that is interrupted by large NFP-ir neurons in layers IIIc and Va. Although area 30 does not appear on the surface of the caudomedial lobule, a terminal branch can form less that 1% of this gyrus. Area 23a is isocortex with a clear layer IV and large, NFP-ir neurons in layers IIIc and Va. Area 23b is similar to area 23a but with a thicker layer IV, more large neurons in layer Va, and a higher density of NFP-ir neurons in layer III. The caudomedial gyral surface is composed of areas 23a and 23b and a caudal extension of area 31. Although posterior area 27 and the parasubiculum are similar to rostral levels, posterior area 36' differs from rostral area 36. Subregional flat maps show that retrosplenial cortex is on the CGv, most of the surface of caudomedial cortex is areas 23a, 23b, and 31, and the retrosplenial/parahippocampal border is at the ventral edge of the splenium. Thus, Brodmann's map understates the rostral extent of retrosplenial cortex, overstates its caudoventral extent, and abridges the caudomedial extent of area 23. | 10.1002/cne.1320 |
pubmed_585_8588 | OBJECTIVE
Little is known about the composition of middle cerebral artery (MCA) plaques and how they relate to clinical status. Using high-resolution magnetic resonance imaging (HR-MRI), we aimed to examine the occurrence of high signal on T1-weighted fat-suppressed images (HST1) of MCA plaques, which are highly suggestive of fresh or recent intraplaque hemorrhage.
METHODS
We retrospectively analyzed the HR-MRI and clinical data of 107 adult patients with high-grade (>70%) MCA stenosis. On HR-MRI, HST1 within an MCA plaque was defined as an area with an intensity >150% of the signal of adjacent muscles. The relationship between HST1 and clinical presentations was analyzed.
RESULTS
A total of 109 stenotic MCAs (46 symptomatic and 63 asymptomatic) on 981 image slices were analyzed. HST1 was revealed on HR-MRI in 11 vessels (10.1%, 9 symptomatic and 2 asymptomatic). The occurrence rate of HST1 between symptomatic and asymptomatic MCAs was significantly different (19.6% vs 3.2%, p = 0.01).
INTERPRETATION
HST1 within MCA plaque on HR-MRI is associated with ipsilateral stroke. Our results provide new insight into the vascular biology of MCA atherosclerosis. | 10.1002/ana.22626 |
pubmed_1022_13894 | BACKGROUND
Migraine headache and the presence of a patent foramen ovale have been associated with each other, although the precise pathophysiological mechanism(s) are uncertain. The purpose of this systematic review was to identify the extent of patent foramen ovale prevalence in migraineurs and to determine whether closure of a patent foramen ovale would improve migraine headache.
METHODS
An electronic literature search was performed to select studies between January 1980 and February 2013 that were relevant to the prevalence of patent foramen ovale and migraine, and the effects of intervention(s) on migraine attacks. Of the initial 368 articles presented by the initial search, 20 satisfied the inclusion criteria assessing patent foramen ovale prevalence in migraineurs and 21 presented data on patent foramen ovale closure.
RESULTS
In case series and cohort studies, patent foramen ovale prevalence in migraineurs ranged from 14.6% to 66.5%. Case-control studies reported a prevalence ranging from 16.0% to 25.7% in controls, compared with 26.8% to 96.0% for migraine with aura. The extent of improvement or resolution of migraine headache attack symptoms was variable. In case series, intervention ameliorated migraine headache attack in 13.6% to 92.3% of cases. One single randomized trial did not show any benefit from patent foramen ovale closure. The data overall do not exclude the possibility of a placebo effect for resolving migraine following patent foramen ovale closure.
CONCLUSION
This systematic review demonstrates firstly that migraine headache attack is associated with a higher prevalence of patent foramen ovale than among the general population. Observational data suggest that some improvement of migraine would be observed if the patent foramen ovale were to be closed. A proper assessment of any interventions for patent foramen ovale closure would require further large randomized trials to be conducted given uncertainties from existing trial data. | pubmed_1022_13894 |
pubmed_586_9290 | High-pressure liquid chromatography was used to study (a) the relative efficiencies of methanol, chloroform, light petroleum (B.P. 40-60 degrees) and methanol-chloroform (9:1) for extracting neutral and acidic cannabinoids from cannabis resin; (b) the decomposition patterns of the resulting solutions under various storage conditions, and (c) the cannabinoid profile of a cross section through a block of cannabis resin. The results show that (a) methanol is the most effective extracting solvent of those tested; (b) acidic cannabinoids in solution decompose in darkness by varying amounts depending on the temperature, solvent, storage time and particular cannabinoid; (c) neutral cannabinoids in solution are relatively stable in darkness; (d) daylight causes appreciable decomposition of both acidic and neutral cannabinoids in solution, (e) the cannabinoid profile of a resin is complex with lower levels of acidic material in the outer layers. | 10.1111/j.2042-7158.1977.tb11313.x |
pubmed_1048_8292 | Biomass burning (BB) is a significant source of atmospheric particles in many parts of the world. Whereas many studies have demonstrated the importance of BB emissions in central and northern Europe, especially in rural areas, its impact in urban air quality of southern European countries has been sparsely investigated. In this study, highly time resolved multi-wavelength absorption coefficients together with levoglucosan (BB tracer) mass concentrations were combined to apportion carbonaceous aerosol sources. The Aethalometer model takes advantage of the different spectral behavior of BB and fossil fuel (FF) combustion aerosols. The model was found to be more sensitive to the assumed value of the aerosol Ångström exponent (AAE) for FF (AAEff) than to the AAE for BB (AAEbb). As result of various sensitivity tests the model was optimized with AAEff=1.1 and AAEbb=2. The Aethalometer model and levoglucosan tracer estimates were in good agreement. The Aethalometer model was further applied to data from three sites in Granada urban area to evaluate the spatial variation of CMff and CMbb (carbonaceous matter from FF or BB origin, respectively) concentrations within the city. The results showed that CMbb was lower in the city centre while it has an unexpected profound impact on the CM levels measured in the suburbs (about 40%). Analysis of BB tracers with respect to wind speed suggested that BB was dominated by sources outside the city, to the west in a rural area. Distinguishing whether it corresponds to agricultural waste burning or with biomass burning for domestic heating was not possible. This study also shows that although traffic restrictions measures contribute to reduce carbonaceous concentrations, the extent of the reduction is very local. Other sources such as BB, which can contribute to CM as much as traffic emissions, should be targeted to reduce air pollution. | 10.1016/j.scitotenv.2016.11.007 |
pubmed_230_16908 | Phenotypic plasticity is adaptive in variable environments but, given its costs, may be disfavored if only one environment is commonly encountered. Yet species in relatively constant environments often adjust phenotypes successfully in rare or novel environments. Developmental biases may reduce the costs of plasticity in common environments, favoring the maintenance of plasticity. We explored this proposition by studying the flexibility of visually guided host-selection behavior in cabbage white butterflies (Pieris rapae), wherein common and rare environments consisted of green and red host types, respectively. We demonstrated in greenhouse assays that adult females display an innate bias toward green color during host search but alter that bias through learning in red-host assemblages such that, after several hours of experience, red hosts are located as efficiently as green hosts. Full-sib analyses suggested there was genetic variation in host and color choice that was more pronounced in the red-host environment. We found no evidence of genetic correlations in behavior across host environments or of fitness costs of plasticity in color choice. Our results support the idea that learning may persist in less variable environments through the evolution of innate biases that reduce operating costs in common environments. | 10.1086/597609 |
pubmed_749_216 | Fatty acid synthase (FASN) is an enzyme responsible for the de novo synthesis of long-chain fatty acids. During oncogenesis, FASN plays a role in growth and survival rather than acting within the energy storage pathways. Here, the function of FASN during early embryonic development was studied using its specific inhibitor, C75. We found that the presence of the inhibitor reduced blastocyst hatching. FASN inhibition decreased Cpt1 expression, leading to a reduction in mitochondria numbers and ATP content. This inhibition of FASN resulted in the down-regulation of the AKT pathway, thereby triggering apoptosis through the activation of the p53 pathway. Activation of the apoptotic pathway also leads to increased accumulation of reactive oxygen species and autophagy. In addition, the FASN inhibitor impaired cell proliferation, a parameter of blastocyst quality for outgrowth. The level of OCT4, an important factor in embryonic development, decreased after treatment with the FASN inhibitor. These results show that FASN exerts an effect on early embryonic development by regulating both fatty acid oxidation and the AKT pathway in pigs. | 10.1371/journal.pone.0170624 |
pubmed_368_3623 | INTRODUCTION
The drastic epidemiological transition has created a huge void in evidence with regard to the health statistics of elderly population. Data are sparse on the oral mucosal conditions prevalent among the elderly Indian population. This study aimed to review the oral biopsies reported in the institute over the last 21 years and to examine the trends in geriatric oral pathologies.
METHODOLOGY
A total of 964 histologically confirmed geriatric (age ranging 50-97 years) oral lesions among 4000 cases reported were retrieved from the files of Department of Oral Pathology and Microbiology of KLE VK institute, Belgaum, Karnataka commencing since 1992 till 2012. These cases were retrospectively evaluated for various parameters such as age, gender, duration, location and type of lesions.
RESULTS
The geriatric oral lesions were seen to occur predominantly in men (65%), especially the sixth decade of life (47%). The most common location was the buccal mucosa (29%). The malignant neoplastic lesions accounted for the majority of the geriatric lesions (36%) followed by non-neoplastic lesions (27%), potentially malignant disorders (26%) and benign neoplasms, which formed a minor proportion of (11%). The oral squamous cell carcinoma was the single most common geriatric lesion accounted. Gender and age-wise correlation analyses among the various lesion categories showed statistical significance.
CONCLUSION
The study provides valuable information about major oral pathologies in our scenario that contribute to significant morbidity and mortality among the geriatric population. It also sheds light about the diseases that need to be targeted in future Indian public health policies and initiatives for geriatric care. | 10.1111/ger.12143 |
pubmed_4_19255 | The first tandem cross-coupling/oxa-Michael addition/dehydrogenation process via rhodium chemistry is described, which provides a straightforward and atom-economical protocol for the synthesis of a wide range of valuable γ-alkylidenebutenolides. This method is of particular interest because of employing widely available and low cost vinyl carboxylic acids and electron-deficient alkenes as building blocks. Moreover, the methodology can be applied to a gram scale synthesis with 1 mol% catalyst loading. | 10.1039/c7cc04973k |
pubmed_135_8577 | Primordium formation is extremely important for yield of <i>Pleurotus tuoliensis</i>. However, the molecular mechanism underlying primordium formation is largely unknown. This study investigated the transcriptional properties during primordium formation of <i>P. tuoliensis</i> by comparing transcriptome. Clean reads were assembled into 57,075 transcripts and 6874 unigenes. A total of 1397 differentially expressed genes were identified (26 DEGs altered in all stages). GO and KEGG enrichment analysis showed that these DEGs were involved in "oxidoreductase activity", "glycolysis/gluconeogenesis", "MAPK signaling pathways", and "ribosomes". Our results support further understanding of the transcriptional changes and molecular processes underlying primordium formation and differentiation of <i>P. tuoliensis</i>. | 10.3390/genes13101747 |
pubmed_15_2317 | Transcript profiling is an invaluable strategy to study differential gene expression. Here we describe a detailed protocol for applying a subtractive hybridization technique, representational difference analysis (RDA), as a molecular strategy for the identification of differentially expressed genes in studies of host-fungus interaction. Bioinformatics tools that can be used in the analysis of expressed sequence tags (ESTs) are also detailed. | 10.1007/978-1-61779-539-8_26 |
pubmed_1075_11942 | The ring-opening polymerization of two caprolactone monomers catalyzed by zinc undecylenate (ZU) is reported. Polymerizations were performed in bulk with benzyl alcohol (BnOH) as an initiator at 90 and 110 °C, respectively. A slower polymerization rate was observed for γ-octyloxy-ε-caprolactone as compared to ε-caprolactone. Diblock copolymers were synthesized by the sequential monomer addition at 90 and 110 °C. The kinetic studies performed for the ring-opening polymerization of ε-caprolactone and γ-octyloxy-ε-caprolactone and the successful synthesis of diblock copolymers by the sequential monomer addition confirmed the controlled/living nature of zinc undecylenate catalyzed reactions. | 10.1002/marc.201200147 |
others_133_6742 | Abstract: Genetic heterogeneity of the population used in the experimental studies with living organisms as model objects is one of the reasons for the poor replicability of the results. Nonhuman primates represent the phylogenetically closest model to humans and it is possible to use it in the studies of genetic basis of diseases with a hereditary predisposition. However, primates represent a population that is significantly limited in number when kept in captivity. We have studied the genetic homogeneity of the population of male rhesus macaques by polymorphisms of genes oprm1, npy, maoa, crh, and 5-htt. Cluster analysis (method of K-means) was used for the assessment considering data of genotyping, origination of the animals, blood count, and veterinary examination. Two significant clusters of animals were identified which differ in the values of blood count parameters within the reference range. The identified clusters are not associated with the origin, age, housing conditions, and the level of morbidity of animals. Clustering made it possible to identify a subpopulation of animals with frequency of carriers of maoa gene VNTR polymorphism with seven repeats 25% higher compared to the entire population. Thus, cluster analysis of nongenetic data may be of use to assess the homogeneity of the distribution of genetic variants in a population and to select a genetically more homogeneous subpopulation in order to reduce the problem of small samples in biomedical research. © 2022, Pleiades Publishing, I | 10.1134/S1022795422030097 |
pubmed_587_7185 | Extreme sampling of sibling pairs has been shown to be efficient in terms of statistical power and sample sizes (in number of sibling pairs needed to genotype) to detect a quantitative trait locus (QTL) when the residual distribution is normal. In the present study, the efficiency of extreme sampling strategies to detect each locus under an oligogenic model is analytically explored with a test statistic based on identical-by-descent (IBD) statuses of independent sibling pairs. In the oligogenic model, the joint effect of oligogenes is the sum of the effects of each locus. Under this model, detecting each single locus will depend, in part, on the allele frequencies and magnitudes of effect of the other loci. Effects of two QTLs with different magnitudes of displacement and acting nonepistatically are considered. Three types of extreme sampling-that is, extreme concordant high (ECH), extreme concordant low (ECL), and extreme discordant (ED)-are primarily considered herein. Among these, ED sampling under the oligogenic model is shown to be most efficient in most situations considered here in terms of allele frequency and mode of inheritance. Differences in results between ECH and ECL sampling are purely arbitrary, brought up mostly by the directions of displacement effects. However, power to detect a locus with the lesser (in magnitude) displacement effect does not necessarily increase with extremity of sampling. Combinations of extreme discordant and extreme concordant sibling pairs are briefly discussed. | 10.1023/a:1014403827957 |
pubmed_251_12736 | Various chemometric experimental designs have been employed for the optimisation of capillary electrophoresis (CE) methods. Similar designs have been utilised in the assessment of the robustness of CE methods. The designs employed include central composites, fractional factorials, Plackett-Burman, simplex and overlapping-resolution mapping. Optimisation studies have largely concentrated on the use of these designs on selection of the optimal electrolyte composition. The robustness testing studies performed have involved the use of screening designs to identify the critical parameters affecting responses such as migration times and resolution. Further designs such as central composites have then been employed to set method limits following robustness studies. It is concluded that the use of experimental designs and statistical data evaluation in conjunction with personal computer-controlled CE autosamplers and instruments are of great benefit in the optimisation and robustness evaluation of CE methods. | 10.1002/elps.11501601346 |
pubmed_69_4907 | Many theories of motor control suggest that we select our movements to reduce energy use. However, it is unclear whether this process underlies short-term motor adaptation to novel environments. Here we asked whether adaptation to walking on a split-belt treadmill leads to a more economical walking pattern. We hypothesized that adaptation would be accompanied by a reduction in metabolic power and muscle activity and that these reductions would be temporally correlated. Eleven individuals performed a split-belt adaptation task where the belt speeds were set at 0.5 and 1.5 m s(-1). Adaptation was characterized by step length symmetry, which is the normalized difference in step length between the legs. Metabolic power was calculated based on expired gas analysis, and surface EMG was used to record the activity of four bilateral leg muscles (tibialis anterior, lateral gastrocnemius, vastus lateralis and biceps femoris). All participants initially walked with unequal step lengths when the belts moved at different speeds, but gradually adapted to take steps of equal length. Additionally, net metabolic power was reduced from early adaptation to late adaptation (early, 3.78 ± 1.05 W kg(-1); and late, 3.05 ± 0.79 W kg(-1); P < 0.001). This reduction in power was also accompanied by a bilateral reduction in EMG throughout the gait cycle. Furthermore, the reductions in metabolic power occurred over the same time scale as the improvements in step length symmetry, and the magnitude of these improvements predicted the size of the reduction in metabolic power. Our results suggest that increasing economy may be a key criterion driving locomotor adaptation. | 10.1113/jphysiol.2012.245506 |
pubmed_660_14564 | OBJECTIVES
The aim of the study was to assess the frequency of pyramidal lobe (PL) detected in iodine-131 (I-131) scans of thyroid bed in patients after thyroidectomy for differentiated thyroid cancer (DTC) and to investigate influence of PL on endogenous thyrotropin (TSH) stimulation as well as on the effects of the radio-iodine ablation in one-year follow-up.
PATIENTS AND METHODS
This study was designed as a retrospective analysis of 302 radio-iodine neck scans of patients thyroidectomized due to DTC. The study population was selected from patients with PL detected in thyroid bed scintigraphy. Patients without PL were included to the control group. The study and the control groups did not differ in age, sex of patients, histological type and stage of the DTC.
RESULTS
Pyramidal lobes were found in 30.5% of all patients. Patients in the study group underwent repeat surgery more often than controls without PL. Preablative TSH level in patients with PL was statistically lower than in the control group, in contrast to free thyroid hormones, which were higher in patients with PL. Preablative and postablative TSH-stimulated thyroglobulin (Tg) and antibodies against thyroglobulin (TgAbs) were measured in both groups, and comparison did not reveal differences. Moreover, for the per-patient analysis, sites of uptake in whole body scintigraphy performed 1 year after radio-iodine remnant ablation (RRA) did not differ between the study and the control groups.
CONCLUSION
Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with DTC. | pubmed_660_14564 |
pubmed_851_9681 | An endophytic fungus, Mycosphaerella nawae ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages. Furthermore, the cytotoxicity of (-)mycousnine enamine was lower than that of cyclosporin A, and its therapeutic index (TC50/EC50) was 4,463.5, which is five-fold higher than that of cyclosporin A. We conclude that (-)mycousnine enamine (2), the semi-synthestic product prepared from the native product (-)mycousnine (1) of the endophyte M. nawae is a novel effective immunosuppressant showing low toxicity and high selectivity. | 10.3389/fmicb.2017.01251 |
pubmed_431_8530 | BACKGROUND
Diplopia related to neurosurgical procedures is often consecutive to oculomotor nerve lesions. We hereby report an oculomotor dysfunction secondary to an orbital roof effraction and its treatment.
HISTORY AND SIGNS
Following surgery for a left anterior communicating artery aneurysm, a 45-year-old woman reported vertical diplopia associated with a left orbital hematoma. The diagnosis of third cranial nerve palsy was excluded by orbital imaging which revealed an orbital roof defect with incarceration of the levator palpebrae and superior rectus.
THERAPY AND OUTCOME
As neurosurgeons advised against muscle adhesiolysis, diplopia was corrected by a two-step procedure on the oculomotor muscles. We first corrected horizontal and torsional deviations by operating on the healthy eye, before correcting the vertical deviation on the fellow eye. This two-step extraocular muscle surgery allowed restoration of binocular single vision in a useful field of gaze.
CONCLUSIONS
Diplopia can occur as a rare orbital complication during neurosurgical procedures. Surgery of extraocular muscles can provide good functional results. | 10.1055/s-2008-1027312 |
pubmed_585_14258 | OBJECTIVE
Fufang Kushen injection was selected as the model drug, to optimize its alcohol-purification process and understand the characteristics of particle sedimentation process, and to investigate the feasibility of using process analytical technology (PAT) on traditional Chinese medicine (TCM) manufacturing.
METHOD
Total alkaloids (calculated by matrine, oxymatrine, sophoridine and oxysophoridine) and macrozamin were selected as quality evaluation markers to optimize the process of Fufang Kushen injection purification with alcohol. Process parameters of particulate formed in the alcohol-purification, such as the number, density and sedimentation velocity, were also determined to define the sedimentation time and well understand the process.
RESULT
The purification process was optimized as that alcohol is added to the concentrated extract solution (drug material) to certain concentration for 2 times and deposited the alcohol-solution containing drug-material to sediment for some time, i.e. 60% alcohol deposited for 36 hours, filter and then 80% -90% alcohol deposited for 6 hours in turn. The content of total alkaloids was decreased a little during the depositing process. The average settling time of particles with the diameters of 10, 25 microm were 157.7, 25.2 h in the first alcohol-purified process, and 84.2, 13.5 h in the second alcohol-purified process, respectively.
CONCLUSION
The optimized alcohol-purification process remains the marker compositions better and compared with the initial process, it's time saving and much economy. The manufacturing quality of TCM-injection can be controlled by process. PAT pattern must be designed under the well understanding of process of TCM production. | pubmed_585_14258 |
pubmed_1110_19285 | Patients with Chagas' disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas' disease on oesophageal function. Twenty male Swiss mice, 60 days of age, were used. The animals were infected with Y strain of Trypanosoma cruzi, injected intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the infected animals, from the 55th to 63rd day after inoculation on consecutive days, and from the 65th to 75th day on alternate days. We investigated food passage of time, wall structure and nitrergic neuronal population of the distal oesophagus. Our data revealed that the use of low doses of aspirin in chronic Chagas' disease caused an increase in the number of nitrergic neurons and partially prevented hypertrophy of the oesophagus. In addition, the aspirin administration impeded Chagas' diseases associated changes in intestinal transit time. Thus treatment with aspirin in the chronic phase of Chagas' disease changes the natural history of the disease and raises the possibility of using it as a new therapeutic approach to the treatment of this aspect of Chagas' disease pathology. | 10.1111/iep.12259 |
pubmed_405_23578 | We report a unique case of synchronous double hypopharyngeal tumors in a 39-year-old man. The patient presented with a 1-year history of a muffled voice and mild odynophagia. Laryngoscopy detected two grossly different tumors in the hypopharynx: a malignant fibrous histiocytoma (MFH) in the postcricoid area and a squamous cell carcinoma (SCC) in the posterior pharyngeal wall. Chemoradiotherapy was administered, and the patient was free of disease at 23 months of follow-up. Synchronous double cancers of the hypopharynx that feature different oncotypes are very rare, especially those that include an MFH. In fact, to the best of our knowledge, no case of synchronous MFH and SCC of the hypopharynx has been previously reported in the literature. Because the number of reported cases of MFH in the hypopharynx is so small, no consensus exists with respect to the preferred option among the various treatment choices. | pubmed_405_23578 |
pubmed_405_2309 | In the official joint policy document of the American Thoracic Society and European Respiratory Society (Hsia et al., Am J Respir Crit Care Med 181:394-418), the need for proper stereologic assessment of lungs was emphasized. In this document it was emphasized that for the quantitative analysis of lung histologic sections, one of the most robust and reliable methods is point and intercept counting (Knudsen et al., J Appl Physiol 108:412-421). One of the practical aspects of this method is how many points or intercepts are needed. The answer to this question has been considered from a theoretical perspective, and it depends on the relative magnitudes of the methodological and biologic variabilities. Although it is generally accepted that in a normal lung, one needs only 100-200 points to sufficiently lower the methodological variability, given the increased variability often seen in experimental emphysematous lung injury, the requisite number of points of intercepts has not been evaluated. In this study, we examined this question by focusing on some of the relevant sampling levels in mice with extensive elastase-induced emphysema. Using fixed samples of tissue blocks, we varied the number of sampling points or intercepts from about 25 to 1,000 in control and emphysematous lungs. Our results show that, at the sampling levels investigated, even with the increased heterogeneity in the lung tissue damage caused by elastase, the number of sampling points needed to detect changes is similar to what is needed for control mice. | 10.1002/ar.23085 |
pubmed_1057_5167 | The average yield of Australia's major grain crop, wheat, rose at its fastest rate ever during the last decade. The environmental biology behind this advance was predominantly ecological and nutritional - endemic root diseases were controlled through better management of inoculum levels, and the consequently healthier crops were more responsive to fertiliser, especially nitrogen. Applying nitrogen fertilisers became less risky; farmers used much more and thereby achieved much higher yields. Despite Australia's reputation for being drought prone, its crop yields have not hitherto been typically limited by water - poor health and poor nutrition have been more influential. Improvements in the management of health and nutrition have resulted in many crops now being limited by water, so the effectiveness with which that water is used in producing grain has become more important - capturing more of it, using it effectively in producing photosynthate, and ensuring that a large fraction of that photosynthate is converted into grain. Further improvement will come from the steady 1% per year achieved by breeders, overlain by agronomic advances based on deeper ecophysiological understanding of the interaction between roots and soil biota, how roots access resources in the subsoil, and the basis of spatial variation in yield across a paddock. | 10.1071/FP02020 |
pubmed_856_8166 | A hybrid AQI time series prediction model is proposed based on EWT-SE-VMD secondary decomposition, ICA (imperialist competitive algorithm) feature selection, and ESN (echo state network) neural network. Firstly, EWT (empirical wavelet transform) and VMD (variational mode decomposition) are used to decompose the original AQI time series into several stable and reliable subseries. Then, the ICA is used to select features of the above subseries for the ESN prediction model. Finally, the optimized feature variables are put into the ESN deep network to establish a prediction model of each AQI subseries and obtain the future AQI index. According to the experimental results of the daily AQI series in Beijing, Tianjin, and Shijiazhuang, we find that (a) among all decomposition methods, the proposed secondary decomposition method (EWT-SE-VMD) performs best in processing data; (b) it is proved that the proposed hybrid model has broad application prospect and research value in the AQI prediction field. | 10.1007/s11356-021-14186-w |
pubmed_313_17599 | Nanotechnology and carbon coating have been applied to silicon anodes to achieve excellent lithium-ion batteries, but the exclusive influence of carbon coating on solid-electrolyte interphase (SEI) formation is difficult to exhibit distinctly because of the impurity and morphological irregularity of most nanostructured anodes. Here, we design a silicon nanocone-carbon (SNC-C) composite structure as a model anode to demonstrate the significant influences of carbon coating on SEI formation and electrochemical performance, unaffectedly as a result of pure electrode component and distinctly due to regular nanocone morphology. As demonstrated by morphological and elemental analysis, compared to the SNC electrode, the SNC-C electrode maintains a thinner SEI layer (∼10 nm) and more stable structure during cycling as well as longer cycle life (>725 cycles), higher Coulombic efficiency (>99%), and lower electrode polarization. This well-defined structure clearly shows the interface stability attributed to carbon coating and is promising in fundamental research of the silicon anode. | 10.1021/acsami.6b13028 |
pubmed_607_13339 | In 11 men undergoing infrainguinal bypass surgery, simultaneous blood samples were analyzed by use of sensitive markers of thrombin activity (fibrinopeptide A, FPA) and platelet behavior (beta-thromboglobulin, beta-TG), as well as conventional clotting times. FPA levels were consistently higher in the venous outflow from the ischemic limb compared with the arterial inflow (p less than .01), while no venoarterial difference was noted for beta-TG. This suggests that there is increased thrombin generation, but not platelet activation localized to the ischemic limb. After a mean dose of 6800 units of heparin given during surgery, FPA levels fell significantly (p less than .03), and the activated clotting time (ACT) was prolonged to 230 to 260 sec, but beta-TG levels did not change. Anticoagulation during lower extremity vascular surgery may be usefully monitored by the activated clotting time because an ACT longer than 250 sec is correlated with lower FPA levels (less than 10 ng/ml), reflecting significant inhibition of coagulation. | pubmed_607_13339 |
pubmed_1102_5536 | As test-developers we have often been troubled by published reviews of patient-reported outcome measures (PROMs). Too often minor issues are judged important while other reviews exclude the best measures available. Perhaps this led several groups to make recommendations for evaluating the quality of PROMs. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist is the latest set of recommendations. While reviewing the COSMIN literature and reviews conducted using their recommendations several concerns became apparent. The checklist is not evidence-based, relying on the opinion of researchers experienced in health-related quality of life. PROMs measuring other types of outcomes are inadequately covered by the checklist. COSMIN choose to focus on Classical Test Theory and the checklists are not appropriate for use with PROMs developed using modern measurement. Such an approach only obstructs progress in the field of outcome measurement. The retrospective nature of the evaluations also penalizes new PROMs. While the checklists imply that composite, ordinal level measurement is acceptable, crucial aspects of instrument development and quality are excluded. Reviews based on the COSMIN checklist produce contradictory conclusions and fail to provide evidence to support the recommendations. These problems suggest that the checklists themselves lack reliability and validity. It is also clear that several reviewers lack the expertise to apply the checklists. Researchers require a good grounding in instrument development and psychometrics to produce quality reviews. The science of modern PROM development is still in an early phase. Few available PROMs have sufficient quality, limiting the need for complex reviews. Standards need to be agreed for high quality outcome measurement. The issue is who should set these standards? Most published reviews merely scratch the surface and lack essential detail. All reviews of PROMs should be treated with caution, irrespective of whether the COSMIN checklist was employed. | 10.1080/13696998.2021.1907092 |
pubmed_896_21628 | OBJECTIVES
Long-term opioid use can be associated with misuse and addiction. In the backdrop of increasing burden of cancer patients in India, it is important to assess the rate of opioid use disorders among those with chronic cancer pain. The objectives were to measure the rate of opioid use disorder in chronic cancer pain patients being managed with morphine and to assess its association with demographic and clinical characteristics.
MATERIALS AND METHODS
A cross-sectional study was conducted on chronic cancer pain patients who were prescribed morphine for ≥12 months, dosage of ≥60 mg/day. They were assessed using MINI version 7.0.0, WHO-ASSIST Hindi questionnaire, Addiction Behavior Checklist, and DSM-5 for opioid use disorder.
RESULTS
Forty patients who were treated with morphine for a total of 1479 months participated. The average morphine consumption was 159.50 ± 327.90 mg/day. Six (15%) showed possible inappropriate opioid analgesic use and none of the patients had opioid use disorder.
CONCLUSION
This study reports the absence of opioid use disorder due to vigilant use of morphine in chronic cancer patients. | 10.25259/IJPC_358_20 |
pubmed_1051_10721 | OBJECTIVE
To evaluate the psychometric properties of the traditional Chinese version of the Childbirth Experience Questionnaire (CEQ 2.0) and assess the childbirth experiences of Chinese women.
METHODS
A cross-sectional survey was conducted in Hong Kong from July 2020 to February 2021. In total, 975 mothers, who could read traditional Chinese and gave birth in 2020 or 2021, were included in the analysis. Data were fitted into the model proposed by the original developers using the confirmatory factor analysis. The data were then randomly split into training and validation sets for exploratory and confirmatory factor analyses. Childbirth experiences were assessed. Factor structure, internal construct validity, internal consistency, and known-group validity were assessed.
RESULTS
The originally proposed CEQ2.0 model showed a poor fit. An exploratory factor analysis identified a revised four-factor model (CEQ2.0-R) on a randomly split sample, which showed a satisfactory fit (CFI=0.912; TLI=0.884; SRMR=.053; RMSEA=0.072) on the other split sample. The revised scale comprised 13 items and four domains: (1)"Own capacity" (6 items), (2) "General support" (3 items), (3) "Perceived safety" (2 items), and (4) "Professional support" (2 items). CEQ2.0-R showed high internal construct validity and reliability. It can differentiate between participants with different characteristics, including parity, oxytocin augmentation, and companionship during labour. The childbirth experiences of the participants were merely positive, and participants reported that more support from midwives is needed.
CONCLUSIONS
CEQ2.0-R can adequately describe the childbirth experiences of women in Hong Kong. The questionnaire is easy to be administer and can be used to assess several domains of the childbirth experiences. It may be useful to evaluate the aspects of support needed during childbirth. | 10.1186/s12884-022-04456-x |
pubmed_714_20212 | The pigeon's main source of regulated heat production, shivering, is especially likely to be used for thermoregulation during the dark phase of the day when there is little heat from locomotor activity. However, food stored in the pigeon's crop is digested during the night, and digestion-related thermogenesis (DRT) will provide heat that should decrease the need for shivering to maintain body temperature (Tb). We investigated the conditions under which DRT alters the occurrence of nocturnal shivering thermogenesis in pigeons. In fasting experiments, in which DRT was minimal, variations in pectoral shivering were closely related to the kinetics of nocturnal Tb when the ambient temperature (Ta) was moderate (21 degrees C). In that case, shivering was low while Tb fell at the beginning of the night, moderate during the nocturnal plateau in Tb, and strong during the prelight increase in Tb. Similar kinetics of nocturnal Tb occurred when Ta = 28 degrees C, but shivering was negligible throughout the dark phase. In restricted feeding experiments, nocturnal DRT was varied by providing different amounts of food late in the light phase. When Ta = 21 degrees C, 11 degrees C, and 1 degrees C, nocturnal Tb and O2 consumption were directly related to the amount of food ingested. However, nocturnal shivering tended to decrease as the food load increased and was significantly reduced at the higher loads. Because nocturnal shivering did not become more efficient in producing heat as the size of the food load increased, we conclude that nocturnal DRT decreased the need for shivering thermogenesis. | 10.1152/ajpregu.1999.277.6.R1579 |
pubmed_1009_7617 | The admission of a child with an almost lethal level of isopropyl (alcohol 380 mg/dl) after sponge bathing for fever, and questionable ingestion, prompted the present experiment in animals. Twelve rabbits (2-2.6 kg) were divided into 4 groups of 3 each. Groups 1 and 2 were given isopropyl alcohol, 2 and 4 ml/kg respectively, by gavage. Groups 3 and 4 were placed in an inhalation chamber with group 3 having a towel soaked with isopropyl alcohol applied to the chest. Group 4 had a similar towel placed on the chest but with a plastic layer to preclude skin contact. Average blood levels (mg/dl) of isopropanol/acetone were then measured over 4 hr. Oral absorption produced the highest levels of isopropyl alcohol and acetone, followed by inhalation and dermal. Inhalation alone was of little significance. Acetone levels continued to rise even as isopropyl levels fell following oral exposure. With the inhalation plus skin absorption group, both isopropyl and acetone levels continued to rise throughout the 4 hr time period. These results indicate that skin absorption is a significant factor in isopropyl alcohol toxicity, and the delayed rise in acetone levels may be responsible for prolonged activity. | pubmed_1009_7617 |
pubmed_1032_6539 | Within a single integrated globalized economy featuring robust fluxes of interregional trades, the world economy is like a giant bathtub containing the world inventory of energy use. Based on different norms or ethic percepts, the energy use of the world economy is reallocated to nations and regions via global supply chain using normative accounting schemes. By combining typical statistics for world economy 2012, a new perspective is presented in this study to look into the energy use of regional economies from the side of genuine final consumers. Parallel to the final-demand-based accounting method, a total-consumption-based multi-region input-output accounting method is developed following the norm of consumption being the ultimate end and purpose of all producing activities. From a total-consumption-based perspective, the energy use of the United States economy is shown in magnitude 1.8 times that of mainland China, compared to a ratio of 88% from a territorial-based perspective. The consumer-product-related trade imbalances of major economies in terms of both currency and energy use are analyzed, with major interregional net trade flows illustrated. While the United States and mainland China are respectively revealed as the leading net exporter and net importer of currency, the energy trade deficit of the latter is in magnitude around four times the energy trade surplus of the former. The trade structures by geography and sector are respectively presented for the United States and mainland China as two distinct economies. It is found that around half of the United States' exports of energy use originate from transport and service industries, while nearly 90% of mainland China's exports of energy use come from heavy industry. The findings are supportive for nations to identify their roles in the global supply chain from the perspective of genuine final consumers and adjust the trade patterns for sustained energy use. | 10.1016/j.scitotenv.2019.01.108 |
pubmed_362_8970 | Dicationic ionic liquids (DILs) are a subclass of the ionic liquid (IL) family and are characterized by two cationic head groups linked by means of a spacer. While DILs are increasingly attracting interest due to their peculiar physico-chemical properties, there is still a lack of understanding of their intermolecular interactions. Herein, we report our investigations on the intermolecular vibrational modes of two bromide DILs and of a bistriflimide DIL. The minimal possible neutral cluster of ions was studied as a simplified model of these systems and was optimized at the DFT level. Normal modes of two sandwich-like conformers were then calculated using the harmonic approximation with analytical computation of the second derivatives of molecular energy with respect to the atomic coordinates. The calculated spectra were compared to far-infrared experimental spectra and two groups of peaks over three, for the two bromide DILs, and three over five, for the Tf2N- DIL, were described by the proposed neutral cluster model. Therefore, this model represents a reliable and computationally affordable model for the exploration of the intermolecular interactions of this kind of system. | 10.1039/c9ra05735h |
pubmed_431_23194 | Dianionic [MO(MAG(3))](2-)(MAG(3) = penta-anionic form of mercaptoacetyltriglycine, M = (186)Re, (99m)Tc) complexes have important applications in nuclear medicine. In vivo the complexes have a deprotonated carboxyl group that is important to their biodistribution. The solid-state structures of (99)Tc and Re complexes with mercaptoacetyltriglycine reported previously are monoanions with protonated carboxyl groups. In the present work, we report the preparation and X-ray crystal structure of Na(2)[ReO(MAG(3))].5H(2)O (1), which contains the physiologically relevant dianion. The dianion is a distorted square pyramid with the nitrogen and sulphur donor atoms forming the base and the oxo ligand at the apex. The terminal carboxyl group is deprotonated, uncoordinated and has a syn orientation with respect to the oxo ligand. The syn conformation of the dianion in 1 differs in conformation from the anti-monoanion in [Bu(4)N][ReO(MAG(3)H)] but is similar to the syn-monoanion in [Ph(4)P][(99)TcO(MAG(3) H)]. | 10.1155/MBD.1995.105 |
pubmed_495_7012 | An interphase cytogenetics analysis was performed to investigate whether replication and transcription could influence in situ resolution of immunoglobulin (Ig) heavy chain constant region genes. A plasmid probe recognizing five C gamma segments separated by known linear DNA distances was hybridized in situ and visualized by digital fluorescence microscopy. In interphase nuclei from phytohemagglutinin (PHA)-stimulated lymphocytes, the gamma genes were resolved as one to three signals per allele in the majority of nuclei, whereas in a minority, complex patterns of several signals per allele could be observed. The latter were restricted to nuclei in an early stage of the S phase, as assessed by hybridization experiments performed in cells grown in the presence of bromodeoxyuridine. To investigate whether the in situ resolution of the C gamma segments could vary as a function of the transcription activity of the locus, the C gamma probe was subsequently hybridized to nuclei from a mature B cell line (JVM-2), which produces gamma transcripts as shown by in situ RNA hybridization experiments. Primary human fibroblasts were further used as representative of a non-lymphoid cell type with transcriptionally inactive Ig genes. When Gl nuclei from the three cell types were compared in terms of the in situ resolution of the C gamma locus, JVM-2 cells were found to include the highest percentage of higher resolution patterns (three to five signals per allele in 28% of nuclei), fibroblasts the lowest (three signals per allele, 2%), while PHA-stimulated lymphocytes occupied an intermediate position between the other two cell types (three or four signals per allele, 15%). The data show that the in situ resolution of Ig C gamma genes varies throughout the cell cycle and is influenced by the transcriptional activity of the locus. The variability of the resolution patterns observed appears to reflect different levels of chromatin packaging, which in turn are likely to influence the probe accessibility to its target. These observations are relevant for the interpretation of data from interphase cytogenetics analysis of independent, but closely spaced, DNA segments. | 10.1007/BF00197411 |
pubmed_730_20851 | We have cloned and sequenced the p53-encoding cDNA of green swordtail (X. helleri) and southern platyfish (X. maculatus). These two fish species are often used to produce hybrids that develop melanomas after genetic crossing. Computer translation of derived cDNA sequences revealed that p53 polypeptides from these two species are virtually identical, exhibiting only two conservative amino acid substitutions. TP53 mRNA expression was detected in virtually all tissues tested. Comparison of these fish p53 polypeptide sequences with those of other vertebrates, including other fishes, amphibians, and mammals, revealed that conservation is especially high in several previously defined protein domains. In addition, sequencing of the 3' TP53 genomic region of X. maculatus reveals similarity to the human TP53 locus in overall organization. Knowledge of the Xiphophorus TP53 sequences will allow assessment of mutational alterations within tumors generated from numerous fish genetic crosses. | 10.1016/s0378-1119(98)00144-9 |
pubmed_26_25090 | BACKGROUND
Recent studies have identified reinforcing properties associated with tanning and suggest a possible physiologic mechanism and addiction driving tanning behavior.
OBJECTIVE
This article attempts to synthesize the existing literature on tanning and addiction to investigate possible associations.
METHODS
We investigated a variety of substance dependence models to define what constitutes dependence/addiction and to determine how current studies on tanning meet these criteria.
RESULTS
In some individuals, tanning has met Diagnostic and Statistical Manual criteria for a substance-related disorder or tanning-modified Cut Down, Annoyed, Guilt, Eye-opener criteria. Trial studies have demonstrated the induction of withdrawal symptoms in frequent tanners.
LIMITATIONS
Additional studies are needed to investigate the associated dependency and addiction more fully and to elucidate its similarities to other better-known addictive syndromes.
DISCUSSION
Tanning is a problem behavior, both as a health risk and as a possible dependency. Future studies, especially in the area of cognitive mapping and cue-related stimuli are needed. Imaging studies may be important in elucidating whether the same areas of the brain are involved in tanning addiction as in other addictive syndromes. | 10.1111/j.1600-0781.2009.00392.x |
pubmed_439_23746 | FeS nanoparticles were easily aggregated and oxidized in the natural environment. It was important to stabilize the iron sulfide nanoparticle composite with a stabilizer. Biochar could be used as an effective carrier to inhibit the agglomeration and oxidization of FeS nanoparticles. An efficient and novel bio-adsorbent (CFeS-WS) from walnut shell (WS) and cellulose composites-stabilized iron sulfide nanoparticle was synthesized by the modified method. The removal of U(vi) ions from an aqueous solution by CFeS-WS was carried out. The experimental results indicated that numerous functional groups were observed on the surface of CFeS-WS. In addition, the biochar was loaded successfully with cellulose and FeS nanoparticle composites. The cellulose and biochar effectively prevented the agglomeration of FeS nanoparticles. The adsorption process of U(vi) ions by CFeS-WS was more consistent with the pseudo second-order kinetic model and Langmuir isotherm model. The adsorption process of U(vi) ions was an endothermic and chemical reaction process. The proposed reaction mechanism of the U(vi) ion removal by CFeS-WS mainly consisted of the ion exchange reaction, reduction reaction, hydrogen bonding and functional group, and pore of the adsorbent filling. According to the results of the recycle experiment, it indicated that the chemical stability of CFeS-WS was good. | 10.1039/d1ra08087c |
pubmed_617_11238 | Prebiotics recently have been shown to increase immune responses and disease resistance in certain fish species; therefore, the current study was conducted to evaluate the commercially available dairy-yeast prebiotic, GroBiotic-A, for use with juvenile goldfish Carassius auratus. The study consisted of two 10-week feeding trials in which juvenile goldfish were fed practical diets that were either unsupplemented or supplemented with the dairy-yeast prebiotic at 2% by dry weight. Juvenile fish were sorted by size and stocked into 12 units within each of two culture systems: one indoor system supplied with recirculated well water and one system located outdoors with a continuous flow of pond water to provide a source of phytoplankton and zooplankton. Both diets were fed to fish in six units within each system at the same fixed percentage of body weight twice daily. Culture system (i.e., presence or absence of phytoplankton and zooplankton) was the primary factor influencing (P < 0.0001) percent weight gain, feed efficiency, and survival of goldfish during the feeding trials. No dietary effect was detected, although there was a significant (P < 0.05) interaction between culture system and diet, with supplementation of the dairy-yeast prebiotic tending to improve weight gain and feed efficiency of fish in the presence of phytoplankton/zooplankton. During a controlled disease challenge with an intraperitoneally administered dose of Aeromonas hydrophila that was equivalent to a predetermined LD50 (dose lethal to 50% of test fish), average survival values ranged between 67% and 83% for fish that previously had access to phytoplankton/zooplankton compared with 17-33% for fish that had no access to phytoplankton/zooplankton. The dairy-yeast prebiotic, however, did not enhance resistance of goldfish to the bacterial pathogen and did not greatly alter microbiota of the anterior or posterior gastrointestinal tract based on denaturing gradient gel electrophoresis analysis. In conclusion, the dairy-yeast prebiotic did not improve feed efficiency in goldfish or resistance to a bacterial pathogen as previously observed in golden shiners Notemigonus crysoleucas and hybrid bass (white bass Morone chrysops X striped bass M. saxatilis). | 10.1577/H08-063.1 |
pubmed_447_17149 | This report analyses the frequency, the pattern and the severity of mycotic infection in a necropsy series of 103 bone marrow transplantations. Fungal infection was documented in 33 (32%) of all death cases. The risk of mycotic infection was increased in patients with graft failure and after retransplantation. At post mortem examination, most cases showed invasive fungal infections. The most frequent organ manifestations were the lungs, the gastrointestinal tract, the kidneys, the heart and the brain. In 19 of 33 patients (57%), mycotic disease was the primary cause of death. Fungal infections still cause major problems in clinical diagnosis, because there remain cases that will be documented only if post mortem examination is performed. | pubmed_447_17149 |
pubmed_107_6393 | The aim of this study was to assess lumbar spine bone density in a group of chilean postmenopausal females and to estimate the frequency of vertebral osteopenia in the national urban female population. A clinical assessment and lumbar spine bone density measurement were performed to 171 healthy women over 40 years of age and not receiving medications that modify bone turnover. Calcium ingestion was recalled in 77 of these. Fifty women (29.2%) had osteopenia, defined as a bone density of less than 0.92 g/cm2. Extrapolating this figure to the national urban population, an osteopenia frequency of 21.7% was estimated. Body mass index was 25.5 +/- 3.8 and 57% of the sample was overweight. Calcium ingestion was 740.3 +/- 331.7. These two parameters did not correlative with bone density. Women with osteopenia were older and had a longer postmenopausal lapse than those with normal bone density. The completion of further clinical an epidemiological studies is recommended to know the real magnitude of osteoporosis in Chile. | pubmed_107_6393 |
pubmed_614_17767 | Amphibian predator-insect prey relationships are common in terrestrial habitats, but amphibian larvae are preyed upon by a variety of aquatic hemipterans in aquatic habitats. This paper suggests that the survival of the nymphs of the endangered aquatic hemipteran Kirkaldyia (=Lethocerus) deyrolli (Belostomatidae: Heteroptera) is directly and indirectly affected by the abundance of their amphibian larval prey (tadpoles). Young nymphs of K. deyrolli mainly feed on tadpoles, regardless of differences in prey availability. Nymphs provided with tadpoles grow faster than nymphs provided with invertebrate prey. Therefore, tadpole consumption seems to be required to allow the nymphs to complete their larval development. In addition, the survival of K. deyrolli nymphs was greater during the period of highest tadpole density (June) than during a period of low tadpole density (July). Higher tadpole density moderates predation pressure from the water scorpion Laccotrephes japonensis (Nepidae: Heteroptera) on K. deyrolli nymphs; i.e., it has a density-mediated indirect effect. These results suggest that an abundance of tadpoles in June provides food for K. deyrolli nymphs (a direct bottom-up effect) and moderates the predation pressure from L. japonensis (an indirect bottom-up effect). An abundance of amphibian prey is indispensable for the conservation of this endangered giant water bug species. | 10.3390/insects2040435 |
pubmed_120_18114 | AIM
To express dopamine D1 receptor in baculovirus-Sf9 cell system, and to investigate the effects of l-12-chloroscoulerine (l-CSL) on the recombinant D1 receptor (D1R).
METHODS
The recombinant baculovirus, Autographa californica nuclear polyhedrosis virus bearing D1R (AcNPV- D1R) was generated, and then was used to produce recombinant D1R in Sf9 insect cells. Expression of D1R in Sf9 cells was monitored by [3H]SCH23390 binding assay. The effects of l-CSL on recombinant D1R were investigated by [3H]SCH23390 binding assay and cAMP assay.
RESULTS
The recombinant baculovirus AcNPV bearing D1R cDNA was generated, and was successfully expressed in Sf9 insect cells. The expression level of (Bmax) was (0.94+/-0.06) nmol/g protein. The Kd value of [3H]SCH23390 was (1.9+/-0.3) nmol/L, which was consistent with the previous results from calf striatum tissues. l-CSL had a high affinity to recombinant D1R with Ki value of (6.3+/-1.4) nmol/L, and increased the intracellular cAMP level in a concentration-dependent manner with EC50 value of 0.72 micromol/L and 95 % confidence limit was 0.67-0.77 micromol/L. Thus l-CSL has the D1 receptor agonism.
CONCLUSION
An efficient baculovirus-Sf9 insect cell system for dopamine D1 receptor was constructed and l-CSL presented the D1 receptor agonism on cellular-molecular level directly. | pubmed_120_18114 |
pubmed_305_16682 | High-throughput sequencing of full-length transcripts using long reads has paved the way for the discovery of thousands of novel transcripts, even in well-annotated mammalian species. The advances in sequencing technology have created a need for studies and tools that can characterize these novel variants. Here, we present SQANTI, an automated pipeline for the classification of long-read transcripts that can assess the quality of data and the preprocessing pipeline using 47 unique descriptors. We apply SQANTI to a neuronal mouse transcriptome using Pacific Biosciences (PacBio) long reads and illustrate how the tool is effective in characterizing and describing the composition of the full-length transcriptome. We perform extensive evaluation of ToFU PacBio transcripts by PCR to reveal that an important number of the novel transcripts are technical artifacts of the sequencing approach and that SQANTI quality descriptors can be used to engineer a filtering strategy to remove them. Most novel transcripts in this curated transcriptome are novel combinations of existing splice sites, resulting more frequently in novel ORFs than novel UTRs, and are enriched in both general metabolic and neural-specific functions. We show that these new transcripts have a major impact in the correct quantification of transcript levels by state-of-the-art short-read-based quantification algorithms. By comparing our iso-transcriptome with public proteomics databases, we find that alternative isoforms are elusive to proteogenomics detection. SQANTI allows the user to maximize the analytical outcome of long-read technologies by providing the tools to deliver quality-evaluated and curated full-length transcriptomes. | 10.1101/gr.222976.117 |
pubmed_724_4766 | UNLABELLED
Evidence suggests that medication safety may be improved through more accurate assessment of renal function and appropriate dosing of renally cleared medications. The purpose of this article is to describe patient renal risk groups, associated medication errors, and ways that nurses can improve renal assessment.
METHODS
Medication safety data were collected through voluntary reporting, computerized triggers, pharmacist surveillance, and retrospective chart review. Data were analyzed across 3 renal risk groups.
RESULTS
Findings indicated that regarding the detected medication errors, elderly women were more likely to have hidden renal risk and that prescribing errors involving a wrong dose occurred more often in patients with high and hidden renal risk. Antibiotic and diabetic medications were the primary drug categories involved in these medication errors.
RECOMMENDATIONS
Results indicated that identification of patients with hidden renal risk can be improved by routinely assessing serum creatinine and estimated creatinine clearance levels during renal assessments. Clinical nurse specialists can use this evidence to promote safer nursing care of renal patients. | 10.1097/01.NUR.0000311795.69476.2f |
pubmed_704_14650 | Autoinflammatory syndromes are characterized by periodic febrile attacks in combination with increased inflammatory markers. The dysregulation of different cellular signaling pathways leads to an excessive immune response, which can in turn promote multisystemic inflammatory processes. Due to overlapping symptoms, variable expressivity and pleiotropy, a purely clinical diagnosis of autoinflammatory diseases is difficult in many cases. Because an early and definitive diagnosis can greatly improve the quality of life of many patients, molecular genetic methods have become an important part of the diagnostic process. With the development of next-generation sequencing (NGS), the genetic diagnosis of patients with autoinflammatory diseases has significantly improved. Considerable progress has not only been made in the genetic characterization of undiagnosed patients, but additionally in identifying numerous new disease-associated genes; however, the plethora of molecular genetic analytical methods makes it difficult to select the method with the highest diagnostic specificity and sensitivity. The NGS technologies have also led to a large increase in the number of identified variants, making the clinical evaluation of these variants more complex. Consensus-driven and standardized molecular diagnostic guidelines, both for the diagnostic process and for the interpretation of the obtained results, have therefore become essential. | 10.1007/s00393-020-00847-7 |
pubmed_323_377 | BACKGROUND
S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC).
METHODS
S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigated using MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model.
RESULTS
S100A14 was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner grade and vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant and independent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidence interval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro and in vivo.
CONCLUSION
These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC. | 10.7314/apjcp.2013.14.6.3831 |
pubmed_14_17651 | Following up previous experience with External Quality Assessment (EQA) and Proficiency Testing Programs (PTP) on drugs of abuse (DoA) testing in Italy and in other European countries, the government of the Lombardy Region, first among Italian regions, established in 1995 a compulsory EQA scheme for laboratories authorized to perform these tests. The purpose of the present work is the description of the program and the overall evaluation of the results obtained in the first three annual cycles (1995-1998). During each annual cycle laboratories received 22 urine samples; some samples were collected from patients ("real samples") and some were "spiked" urine samples. Both types of samples could contain the following substances/classes of substances: opiates, cocaine, cannabinoids, methadone, buprenorphine, benzodiazepines, barbiturates. Type A laboratories used an immunological screening method; they expressed the results as concentrations. Type B laboratories, authorized to perform screening methods followed by confirmatory techniques, searched for and identified single substances and provided an interpretation on possibly taken drugs. During the study period the laboratories produced about 21,000 analytical results. Among them, false-negative results were 0.9% of true positives, and false-positive results were 0.7% of true negatives. Performance using the spiked samples was better than using real samples, and performance of type B laboratories better than that of type A. The results obtained during the program are consistent with those of other quality control programs. This program, in addition, has provided information on the status of DoA testing in the Lombardy region's laboratories, in particular on their analytical performance, on the quality of interpretation of results and on a degree of improvement achieved during the program. | 10.1515/CCLM.2002.027 |
pubmed_760_21828 | This study aims to assess the effectiveness and reliability of a new combined approach to treat the maxillary atrophy and chronic rhinosinusitis (CRS) and other rhino-sinusal pathologies. This 1-step procedure consisting functional endoscopic sinus surgery (FESS) and maxillary sinus-lift with simultaneous implant placement for patients with a severe reabsorbed maxillary bone and sinuses' disease. In case of disventilation and maxillary sinuses flogosis, the mucociliary clearance and physiological ventilation have to be aided, in order to make a safer and predictable sinus-lift surgery. This new surgical approach provides the restitution ad integrum of sinus health and at the same time, its grafting. If possible, implants were placed during the same surgical procedures. A 1 center retrospective study was performed in a private clinic of Rome, from January 2006 to November 2013. Seventy-eight adult patients with maxillary atrophy and sinus disventilation no responding to 3-week pharmacological therapy were admitted. All of them underwent to medical history, clinical examination, nasal endoscopies, and computed tomography (CT) scan of nose and paranasal sinuses. Patients were divided in 2 groups using Lund Mackay CT scoring. A 1-step surgery based on FESS and maxillary sinus-lift was performed. Simultaneous implant placement was performed when a crestal thickness of at least 4 mm was present on CT examination. Patient's symptoms scoring was evaluated through visual analogical scale both pre- and postoperatively. Computed tomography scores were usually not in accordance with presurgical clinical condition. Patients with clinical symptoms of disventilatory sinus and low evidence of CRS on CT showed relevant improvements in symptoms' scores after endoscopic surgery. All implants achieved good primary stability; Only 1 patient had lost implant due to peri-implantitis during 1-year follow-up period (1.3%). | 10.1097/SCS.0000000000003151 |
pubmed_361_16299 | Human T lymphotropic virus type I (HTLV-I) was isolated from peripheral blood- and cerebrospinal fluid-derived mononuclear cells of a 13-y-old boy and from the peripheral blood lymphocytes of both his parents. All three had IgG antibodies to HTLV-I and varying degrees of the clinical features of tropical spastic paraparesis (TSP). The son also had IgM antibodies specific for HTLV-I in his serum. Isolations were successfully made from peripheral blood lymphocytes and cerebrospinal fluid lymphocytes stimulated with interleukin-2 or cocultivated with umbilical cord blood mononuclear cells. Established cell lines contained HTLV-I antigen by immunfluorescence and cell-associated virus by electron microscopy; cells became transformed in vitro as determined by their continuous growth in the absence of exogenous interleukin-2. This boy is the youngest TSP patient known to be reported, and the isolation of HTLV-I from all three family members suggests the causative role of this virus in TSP. | 10.1093/infdis/160.3.371 |
pubmed_534_16435 | Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study enrolled a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) enrolled 498 patients. We have combined these two samples to study the effects of hostility on study discontinuation as well as to examine correlates and predictors of hostility. Individual data from 1154 patients with complete data were used for analyses. Survival analysis demonstrated that higher hostility was associated with earlier all-cause treatment discontinuation. Furthermore, regression analysis indicated that increased hostility was associated with more severe positive symptoms, lower adherence to pharmacological treatment, younger age, impaired insight, and more drug or alcohol consumption. The clinical implications of the results point to the importance of establishing therapeutic alliance while managing patient's symptoms of hostility with antipsychotics such as olanzapine combined with psychosocial interventions to improve insight and reduce substance use. | pubmed_534_16435 |
pubmed_663_23619 | Eighteen seventy-four was a high point in evolutionary embryology. Thanks to Charles Darwin, the theory of evolution by natural selection provided a revolutionary new way of viewing the relationships and origins of organisms on Earth. Thanks to Ernst Haeckel, embryos were the way to study evolution (Haeckel in Generelle morphologie der organismen, vols 1, 2. Verlag Georg Reimer, Berlin, 1866)-it really was embryos in evolution-and recapitulation was in the air. Thanks to Anton Dohrn, a new research facility was on the ground, designed, located and structured to facilitate the study of embryos in evolution. Anton Dohrn devised, designed, financed, supervised the construction and then administered the Naples Zoological Station specifically so that researchers from all nations would have a facility where Darwin's theory of evolution by natural selection could be tested. The zoologists who took advantage of the brand new facility within weeks of its opening late in 1873 established lines of research into evolutionary embryology, the field we now know as evolutionary developmental biology (evo-devo), the study of embryos in evolution. I examine the approach taken by Ambrosius Hubrecht, the first Dutch embryologist to undertake research at the station, and then evaluate the research of three British zoologists-E. Ray Lankester, Albert Dew-Smith, and Francis Maitland (Frank) Balfour. All four sought insights into origins, especially vertebrate origins that rested on comparative embryology, homology, germ layers, and a Darwinian approach to origins. | 10.1007/s12064-009-0057-0 |
pubmed_183_21822 | Membrane type 1 matrix metalloproteinase (MT1-MMP) is a protease produced by airway epithelial cells in various diseases. Since other MMPs are involved in bronchial epithelial repair, we investigated the role of MT1-MMP in naphthalene-induced small airway injury and repair in wild-type (WT) and MT1-MMP-knockout (KO) mice. The degree of injury was similar in both strains, but the MT1-MMP KO mice were unable to reconstitute a normal, fully differentiated airway epithelium 28 days after injury. MT1-MMP was required for the proliferative response in distal airway epithelial cells, resulting in decreased cell density and airway epithelial cell differentiation in MT1-MMP KO mice. Surprisingly, EGF-mediated signaling was unaltered in MT1-MMP KO mice and therefore unrelated to the proliferative response. However, keratinocyte growth factor receptor (KGFR) expression was significantly upregulated before the proliferative response and markedly less evident in the distal airway epithelium of MT1-MMP KO mice. These results indicate MT1-MMP is involved in KGFR expression and epithelial cell proliferation after acute airway injury. | 10.1152/ajplung.00028.2007 |
pubmed_125_16470 | Application of probiotics in the food industry has been hampered by their sensitivity to challenging conditions that reduce their vitality in food matrices. A lot of attempts have been made to promote the growth of these probiotics in the aspect of nutrition demands. Among the other adverse conditions, oxygen stress can restrict the growth of probiotics and has not yet been paid enough attention to. In this study, the effect of a petunidin-based anthocyanin (ACN) on the growth of probiotic Lactobacillus plantarum ST-III was investigated under oxygen stress. The growth of ST-III was analyzed through spot assay on agar plates as well as plating-based enumeration of the viable cells in the liquid culture. Results indicated that ACN could efficiently improve the growth of ST-III under oxygen stress, whereas no effect was observed in the absence of oxygen stress. Further investigations indicated that ACN reduced the oxido-reduction potential of the culture; meanwhile, it exerted a positive transcriptional regulation on the thioredoxin system of ST-III, leading to a decrease in reactive oxygen species accumulation within the cells. Moreover, ACN enabled the growth of ST-III in reconstituted skim milk and promoted the formation of milk clots. These results revealed the role of a petunidin-based ACN in oxygen stress relief and highlighted its potential in manufacture and preservation of L. plantarum-based dairy products. | 10.3389/fmicb.2020.01211 |
pubmed_162_18623 | Breast cancer has been emerging as a most common threat among women, thus many efforts were made to find drugs for fighting breast cancer. So far, PI3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase) inhibitors have been believed to be effective drugs until frequent resistance emerged. Recently, PI3K H1047R mutation has been reported to sensitize breast cancer cells to PI3K inhibition by aspirin. Considering aspirin activates AMPK (AMP-activated protein kinase) simultaneously, it is possible that AMPK activators and PI3K inhibitors can synergistically inhibit breast cancers. Here we clearly observed synergistic suppression of cell growth in all three breast cancer cell lines (MCF-7, MDA-MB-361 and HCC38) when co-treating cells with PI3K inhibitor GDC-0941 and AMPK activator AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide). What is more, it is rather remarkable that the synergistic effect was much more dramatic in PIK3CA (PI3K catalytic subunit alpha) mutated (E545K) cells (MCF-7 and MDA-MB-361) than in PIK3CA wild-type cells (HCC38), which implied there is a relationship between PI3K genetic status and the efficacy of combination therapy. By using PIK3CA wild-type isogenic MCF-7 cell line, which exhibited attenuated cell proliferation compared with the parental MCF-7 cell line, we found endogenous reverse mutation of PIK3CA E545K alleles to wild-type sequence in MCF-7 cells dramatically impaired the synergy of PI3Ki&Ka (combinatorial PI3K inhibition and AMPK activation). Furthermore, PI3Ki&Ka significantly attenuated tumorigenesis of parental MCF-7 cells but not PIK3CA wild-type isogenic MCF-7 cells in tumor xenograft models. Taken together, our results suggest a promising precision therapy of PI3Ki&Ka in PIK3CA mutant breast cancers. | 10.1007/s10637-018-0563-3 |
pubmed_134_16424 | A population census of white-headed langurs (Trachypithecus leucocephalus) was conducted using sleeping-site counts and the line-transect method from July to August 2002 at the Longrui Karst Hills, Guangxi, China. This area had been the largest habitat of the langurs across their range before the 1990s. While our survey revealed 146 old sleeping-sites, no white-headed langurs or fresh sleeping-sites were found in this area. Our study indicated that there had previously been a large population of langurs at Longrui Karst Hills, but now the langurs are possibly locally extinct in this area. If langurs still exist within the area, the population density must be very low. Interviews with local people confirmed that the number of white-headed langurs has been decreasing since the 1980s. Poaching was very common in the past and continues to be a problem at present, and it is likely that this has caused the decrease in the white-headed langur population at Longrui Karst Hills. | 10.1007/s10329-004-0122-8 |
others_331_18972 | The degree of maxillary molar tooth-row eruption and wear were used to assign samples of the social giant mole-rat, Fukomys mechowii, from Zambia, into nine relative age classes in order to assess ontogenetic (age) variation and craniometric sexual dimorphism, with reference to body mass. Univariate and multivariate statistical analyses showed craniometric differences between age classes 13 and age classes 59, with age class 4 being intermediate between these two age class groupings. This suggests that age class 4 lies at a point on a hypothetical growth curve where growth begins to stabilize. The intermediate placement of age class 4 in multivariate space broadly coincided with body mass categorizations into juveniles (age classes 13; <100 g), subadults (age class 4; c. 100150 g), and adults (age classes 59; >150 g). The analyses also revealed the absence of sexual dimorphism in the relatively younger age classes 14 but its presence in the relatively older age classes 59, and these results are supported by data on body mass. These results may have implications in our understanding of the population and social structures, and reproductive strategies in this little-studied giant mole-ra | 10.3377/004.045.0218 |
pubmed_705_19255 | For a period of time after unilateral brain injury, surviving neural tissue surrounding the lesion may be vulnerable to extremely high behavioral demand. Previously, we found that lesions of the forelimb representation area of the sensorimotor cortex (FL-SMC) in rats increase in size substantially when the intact forelimb is immobilized with a plaster of paris cast during the first 15 days after surgery, which forces overuse of the impaired forelimb. The present study was designed to determine whether the adult brain is more vulnerable to forced overuse of the impaired forelimb during the first 7 days post-lesion than during the second 7 days post-lesion. Using behavioral tests of forelimb use and stereological analysis of remaining tissue volume 40 days after FL-SMC lesions, we found that forced overuse of the impaired forelimb during the first 7 days after the initial damage caused expansion of neural injury and greatly interfered with restoration of function. In contrast, forced overuse of the impaired forelimb during the second 7 days had no significant effect on lesion size but nevertheless interfered with restoration of function. Thus, surviving neural tissue in the damaged hemisphere and recovery of function appear to be vulnerable to prolonged forced overuse of the impaired forelimb throughout the first 15 days, but tissue loss was detectable only when the animal was forced to use the impaired forelimb during the first 7 days after injury. | 10.1016/s0006-8993(97)01356-5 |
others_264_5604 | Physiological importance of some non-linear regression models parameters (Beta 1, Beta 2, Logistic, Richards, Gompertz, Symmetrical sigmoid pattern, cut linear exponential, and Weibull) were studied in describing the time trend of accumulated dry matter and LAI of winter cereals under two nitrogen levels. Thus, a factorial experiment based on Randomized Complete Block design with four replications was performed. Treatments were zero, and optimum nitrogen levels (150, 120, 150, 120, 210 and 240 kg/ha for bread wheat, durum wheat, hull less barley, two-rowed barley, six-rowed barley and triticale, respectively), and winter cereals including durum and bread wheat (cv. Koohdasht), barley (Hordeum vulgare L.), two-rowed barley (cv. Khorram), six-rowed (cv. Sahra), hull less barley (line 17), and triticale (Triticum wittmak L.). The experiment was performed during the 2013/2014 and 2014/2015 seasons at the research field of Gonbad Kavous University, Iran. Results revealed for LAI that in Koohdasht cultivar, according to MAE, the prediction of both Logistic (0.32) and Beta (0.38) models in the zero nitrogen was better than nitrogen consumption while in wheat drum, no difference was observed between the models in both conditions. All models could describe time trend of accumulated dry matter under both fertilizer levels, but Gompertz, symmetrical expo linear models shown slightly better than others. Enhancement estimation of parameters of these models (maximum accumulated dry matter, RGR in linear phase, RGR in Expo linear phase, lost time to beginning of Expo linear phase, slope of dry matter and time of CGR max) are very crucial in modelling studies, cultivars comparison, growth analyses and simulation of growth and production of winter cereals. © 2021, Indian Society for Plant Physiology | 10.1007/s40502-021-00597-x |
pubmed_149_13308 | BACKGROUND
Men who have sex with men in Brazil are deferred from donation for 1 year since their last sexual contact. Legal proceedings in front of the Brazilian Supreme Court could compel blood collection agencies to discontinue use of sexual orientation questions.
METHODS
Data from male participants in a completed HIV risk factor case-control study were used to evaluate whether it is possible to differentiate donors at lower and higher risk for HIV using two analytical approaches: latent class and random forest analyses.
RESULTS
Male blood donors were divided into three distinct risk profile classes. Class 1 includes donors who are heterosexual (96.4%), are HIV negative (88.7%), have a main partner (99.4%), and practice unprotected sex (77.8%). Class 2 includes donors who are men who have sex with men /bisexuals' (100.0%), are HIV positive (97.4%), and were not aware of their sexual partners' HIV status (80.3%). Class 3 includes donors who are heterosexual (84.1%), practice unprotected vaginal/anal heterosexual sex (66.8% vs. 40.9%), and were both HIV positive and HIV negative (49.5% vs. 50.5%). We also found that asking donors about their partner(s)' HIV serostatus could replace asking about donors' sexual orientation and types of partners with relatively minor shifts in sensitivity (0.76 vs. 0.58), specificity (0.89 vs. 0.94), and positive predictive value (0.85 vs. 0.88).
CONCLUSION
Sexual orientation questions on the donor questionnaire could be replaced without great loss in the sensitivity, specificity, and positive predictive value. Social and sexual behaviors of donors and their partners are proxies for HIV risk and can help to develop modified questions that will need controlled trials to be validated. | 10.1111/trf.15388 |
pubmed_1055_21187 | Salmonellosis is a significant public health concern around the world. The injudicious use of antimicrobial agents in poultry production for treatment, growth promotion and prophylaxis has resulted in the emergence of drug resistant strains of Salmonella. The current study was conducted to investigate the prevalence of virulence and antimicrobial resistance genes from Salmonella isolated from South African and Brazilian broiler chickens as well as human clinical isolates. Out of a total of 200 chicken samples that were collected from South Africa 102 (51%) tested positive for Salmonella using the InvA gene. Of the overall 146 Salmonella positive samples that were screened for the iroB gene most of them were confirmed to be Salmonella enterica with the following prevalence rates: 85% of human clinical samples, 68.6% of South African chicken isolates and 70.8% of Brazilian chicken samples. All Salmonella isolates obtained were subjected to antimicrobial susceptibility testing with 10 antibiotics. Salmonella isolates from South African chickens exhibited resistance to almost all antimicrobial agents used, such as tetracycline (93%), trimethoprim-sulfamthoxazole (84%), trimethoprim (78.4%), kanamycin (74%), gentamicin (48%), ampicillin (47%), amoxicillin (31%), chloramphenicol (31%), erythromycin (18%) and streptomycin (12%). All samples were further subjected to PCR in order to screen some common antimicrobial and virulence genes of interest namely spiC, pipD, misL, orfL, pse-1, tet A, tet B, ant (3")-la, sul 1 and sul. All Salmonella positive isolates exhibited resistance to at least one antimicrobial agent; however, antimicrobial resistance patterns demonstrated that multiple drug resistance was prevalent. The findings provide evidence that broiler chickens are colonised by pathogenic Salmonella harbouring antimicrobial resistance genes. Therefore, it is evident that there is a need for prudent use of antimicrobial agents in poultry production systems in order to mitigate the proliferation of multiple drug resistance across species. | 10.4102/ojvr.v83i1.1067 |
pubmed_921_20588 | In order to investigate the correlations between constitutive proteinase expression and the degree of tumorigenicity of cancer cells we have studied a model system of three keratinocyte cell lines. RT-PCR studies showed that the cell lines express the genes of matrix metalloproteinase-2, -3, -7, -9, -10 and -11, indicating that they are able to synthesize the corresponding enzymes. Actual MMP synthesis was proven by zymography and Western blotting. In conditioned media gelatinolytic activities or immunoreactive forms of MMP-2, -3, -7, -9, -10 and -11 were detected. The signal intensities showed that MMP secretion increases in the order HaCaT < A5 < or = II-4RT, whereas only MMP-11 is secreted by all cell lines in equal amounts. Intracellularly, enhanced levels of one or both of the tumorigenic variants were only found for MMP-3, -9 and -10, suggesting special functions of these intracellular MMP pools for the tumorigenic cell lines. For MMP-11 exclusive expression in stromal fibroblasts of tumor tissues is widely accepted; however, our results and three other recent reports demonstrate that this concept is not generally valid. In conclusion, the three keratinocyte cell lines investigated here represent an excellent model for studying constitutive expression and secretion of MMPs in correlation to the degree of in vivo tumorigenicity. | 10.1515/BC.2000.064 |
pubmed_265_14490 | This study investigates possible sources for the variance of more than two orders of magnitude in the published values for the shear moduli of purified actin filaments. Two types of forced oscillatory rheometers used in some of our previous work agree within a factor of three for identical samples. Polymers assembled in EGTA and Mg2+ from fresh, gel-filtered ATP-actin at 1 mg/ml typically have an elastic storage modulus (G') of approximately 1 Pa at a deformation frequency of 0.1-1 Hz. G' is slightly higher when actin is polymerized in KCl with Ca2+ and Mg2+. Gel filtration removes minor contaminants from actin but has little effect on G' for most preparations of actin from acetone powder. Storage of actin monomers without frequent changes of buffer containing fresh ATP and dithiothreitol can result in changes that increase the G' of filaments by more than a factor of 10. Frozen storage can preserve the properties of monomeric actin, but care is necessary to prevent protein denaturation or aggregation due to freezing or thawing. | 10.1016/S0006-3495(98)77979-2 |
pubmed_990_22101 | Heparan sulfate is rapidly degraded by an endoglycosidase (heparanase) secreted by activated platelets. Since the cleavage and release of heparan sulfate would profoundly alter the local physiology of the endothelium, platelet heparanase activity should be tightly regulated. Consistent with this hypothesis, platelet heparanase was found to degrade endothelial cell heparan sulfate at pH 6.0 but not at pH 7.4, even though 25% of maximum activity was detected at pH 7.4. Loss of heparanase activity occurred rapidly (t1/2 is approximately equal to 20 min) and reversibly at physiologic pH but did not occur at acidic pH (<7.0). Inactivation of heparanase at pH 7.4 did not affect heparin binding and was reversed by 0.5 M NaCl or by heparan sulfate but not by chondroitin sulfate, suggesting inactive heparanase could be tethered on cell surfaces and the function regulated by heparan sulfate. Heparanase was gradually inactivated by trypsin and urokinase (t1/2 = 5 h) but resisted cleavage by leukocyte cathepsin G, leukocyte elastase, plasmin, and thrombin. These findings are consistent with a model in which platelet heparanase is active at the low pH of inflammation but inactive under physiologic conditions preventing inadvertent cleavage of heparan sulfate and loss of physiologic functions of endothelial cells. | 10.1002/(SICI)1097-4652(199806)175:3<255::AID-JCP3>3.0.CO;2-N |
others_314_85305 | Mosquito-transmitted flaviviruses, such as Dengue virus (DENV) or Zika virus (ZIKV), are responsible for significant economic damage and human misery. In infected cells, flaviviruses first assemble into an immature form within the endoplasmatic reticulum (ER), and then undergo further processing by furin protease in the trans-Golgi. Despite substantial efforts, previous cryogenic electron microscopy (cryo-EM) studies of immature flaviviruses were restricted to low to medium resolutions, limiting our understanding of maturation. To better grasp the process of maturation, we have carried out cryo-EM reconstructions of immature Spondweni virus (SPOV), an emerging human flavivirus belonging to the same serogroup as ZIKV (~75% amino acid identity). By combining localized reconstruction and focused refinement, we were able to improve the resolution to 3.8 [A], yielding unprecedented insight into the immature form. The structure elucidates how, at neutral pH, polar interactions conceal the furin recognition site within trimeric envelope (E) protein spikes. Furthermore, we identify how a strictly conserved pH sensor anchors the precursor membrane (prM) protein to immature E. We reconstructed mature forms of SPONV and DENV to 2.6[A] and 3.1[A], respectively. Comparison with immature virus shows a conserved binding pocket for a lipid headgroup, which forms as a consequence of the rearrangement of amphipathic stem-helices of E. We propose a structural role for the pocket and suggest it stabilizes mature E. Taken together, our data suggest a compelling rationale for low-pH triggered conformational rearrangement in the Golgi, which occurs during flavivirus matura | 10.1101/2020.06.07.138669 |
pubmed_151_8929 | BACKGROUND
Glaucoma is an optic neuropathy associated with visual field loss. There are different types of glaucoma, among them exfoliative glaucoma. Glaucoma can present as unilateral or bilateral. The present study aimed to show the association between gene expression and exfoliation in unilateral glaucoma cases.
METHODS
Included patients were suffering from exfoliative glaucoma in one eye, meanwhile the other eye was healthy and used as a control. Lens capsule and conjunctival biopsies were taken from both eyes. Gene expression was analyzed.
RESULTS
Both groups were completely different at baseline regarding intraocular pressure, visual acuity before the operation, visual field damage, optic nerve damage, etc. As for gene expression, the only significant difference was found in CYP1B1 from lens capsules. None of the other genes studied showed differential expression in either lens capsules or conjunctival biopsies.
CONCLUSION
No difference in gene expression was found between eyes with and without exfoliative glaucoma. Exfoliative glaucoma seems to be a bilateral disease, though the phenotype is not always clinically present. | 10.2147/OPTH.S166958 |
pubmed_1005_6316 | BACKGROUND
Previous studies reported an inverted relationship between nut consumption and the incidence of metabolic syndrome (MetS). The present study investigated the incidental risk for MetS according to peanut, almond, and fine nut consumption in the Korean population.
METHODS
In a community-based Korean cohort, 5306 Korean adults were divided into four groups according to their peanut, almond, and fine nut intake (<1/month, 1/month-0.5/week, 0.5-1/week, and ≥1/week, in which one serving = 15 g) and were followed-up for 10 years. A Cox proportional hazard model was used to evaluate the hazard ratios (HRs) with confidence intervals (CI) for MetS in each study group. Age subgroup (≥50 or <50 years) analysis was also conducted.
RESULTS
The age and multivariable-adjusted HRs with 95% CIs for MetS showed a significant inverse dose-response relationship between peanut, almond, and fine nut intake and the incidence of MetS in men and women (multivariable-adjusted HRs [95% CI] in men; 0.91 [0.76-1.09] in 1/month-0.5/week, 1.03 [0.80-1.31] in 0.5-1/week, 0.72 [0.56-0.93] in ≥1/week and in women; 0.81 [0.65-1.003] in 1/month-0.5/week, 0.76 [0.54-1.07] in 0.5-1/week, 0.57 [0.41-0.79] ≥1/week)). Subgroup analysis showed a significant difference in middle-aged men (≥1/week) and old-aged women (≥0.5/week).
CONCLUSION
The results of the present study suggested that peanut, almond, and fine nut intake (≥15 g/week) may be inversely related to incidence risk of MetS in the Korean general population. Additionally, the association between nut consumption and MetS incidence risk may differ in sex and age subgroups. | 10.1007/s12020-019-01980-3 |
pubmed_1053_4957 | Bronchopulmonary sequestration with associated nonimmune hydrops has been previously reported with generally poor prognosis for the neonate. We report a case of bronchopulmonary sequestration and associated pleural effusion successfully managed with a transthoracic catheter placement. The embryology and clinical pathophysiology of bronchopulmonary sequestration are discussed. | 10.1159/000263532 |
pubmed_710_15273 | This study aimed to explore the relationship between physical exercise (PE) and mobile phone dependence (MPD) in Chinese university students and verify the potential role of self-control (SC) in mediating the decrease of MPD by PE. Through the quota sampling, 608 students that complied with the requirements were surveyed from 10 universities in China. PE, MPD, and SC were assessed using standard scales. For data analysis, t-tests, correlation analysis, hierarchical regression, and regression analysis were carried out in turn. The results showed significant gender differences in PE, MPD, and SC. For male students, the level of PE and score of SC were higher than those in females, yet the MPD score was lower. PE and SC were negatively related to MPD (r = -0.124, p < 0.01; r = -0.563, p < 0.001), so both could remarkably predict MPD (β = -1.00, p < 0.05; β = -0.552, p < 0.001). Gender was also a significant predictor for MPD (β = 0.089, p < 0.05). PE could, to some extent, decrease MPD, in which SC played a significant mediating role-its mediating effect accounted for nearly 71% of the total effect. The present study shows that PE is negatively correlated with MPD, and SC mediates the decrease of MPD by PE for university students in China. This indicates that the improvement of SC by PE could be a highly trustworthy and practicable way to effectively address the issue of MPD in university students or other young people across the world. | 10.3390/ijerph16214098 |
pubmed_144_4265 | A stochastic modelling approach was developed to describe the distribution of Listeria monocytogenes contamination in foods throughout their shelf life. This model was designed to include the main sources of variability leading to a scattering of natural contaminations observed in food portions: the variability of the initial contamination, the variability of the biological parameters such as cardinal values and growth parameters, the variability of individual cell behaviours, the variability of pH and water activity of food as well as portion size, and the variability of storage temperatures. Simulated distributions of contamination were compared to observed distributions obtained on 5 day-old and 11 day-old cheese curd surfaces artificially contaminated with between 10 and 80 stressed cells and stored at 14°C, to a distribution observed in cold smoked salmon artificially contaminated with approximately 13 stressed cells and stored at 8°C, and to contaminations observed in naturally contaminated batches of smoked salmon processed by 10 manufacturers and stored for 10 days a 4°C and then for 20 days at 8°C. The variability of simulated contaminations was close to that observed for artificially and naturally contaminated foods leading to simulated statistical distributions properly describing the observed distributions. This model seems relevant to take into consideration the natural variability of processes governing the microbial behaviour in foods and is an effective approach to assess, for instance, the probability to exceed a critical threshold during the storage of foods like the limit of 100 CFU/g in the case of L. monocytogenes. | 10.1016/j.ijfoodmicro.2010.09.024 |
pubmed_573_16953 | A novel approach for Cd vapor generation was developed on the basis of a plasma-assisted chemical process. The generated Cd vapor was subsequently measured by atomic fluorescence spectrometry. Dissolved Cd species were readily converted into volatile species by reaction with hydrogen in a coaxial thin-film dielectric barrier discharge (DBD) plasma reactor. Both atomic and molecular Cd species were produced when a solution containing Cd(2+) was exposed to hydrogen-containing DBD plasma. Fast and efficient vapor generation of Cd was achieved simply in plain (neutral) water medium. Optimal conditions for the DBD-plasma Cd vapor generator were identified. The performance of this thin-film DBD plasma-chemical vapor generation (CVG) was evaluated through comparison with that arising from the conventional HCl-KBH4 system. The vapor generation efficiency of the proposed method (He-DBD) was found to be superior to the conventional CVG approach. Under the optimized conditions, the detection limits of Cd were found to be from 0.03 ng mL(-1) (Ar-DBD) to 0.008 ng mL(-1) (He-DBD) with a heated quartz tube atomizer (QTA); good repeatability (relative standard deviation (RSD) = 1.4%, n = 5) was obtained for a 1 ng mL(-1) standard. The new thin-film DBD plasma-CVG provides several additional advantages including simple setup, easy coupling with flow injection, low power consumption (≤18 W), cost-effectiveness, and long operation lifetime. The accuracy of the proposed method was validated through analysis of cadmium in reference material of simulated natural water sample GBW(E)080402 and rice reference material GBW10045. The concentration of cadmium determined by the present method agreed well with the reference values. | 10.1021/ac400368h |
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