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pubmed_861_13233
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L-DOPA (3,4-dihydroxyphenyl-L-alanine) is a preferred drug for Parkinson's disease, and is currently in great demand every year worldwide. Biocatalytic conversion of L-tyrosine by tyrosinases is the most promising method for the low-cost production of L-DOPA in both research and industry. Yet, it has been hampered by low productivity, low conversion rate, and low stability of the biocatalyst, tyrosinase. An alternative tyrosinase TyrVs from Verrucomicrobium spinosum with more efficient expression in heterologous host and better stability than the commercially available Agaricus bisporus tyrosinase was identified in this study. Additionally, it was prepared as a novel nano-biocatalyst based on the distinct one-step in situ immobilization on the surface of polyhydroxyalkanoate (PHA) nano-granules. The resulting PHA-TyrVs nano-granules demonstrated improved L-DOPA-forming monophenolase activity of 9155.88 U/g (Tyr protein), which was 3.19-fold higher than that of free TyrVs. The nano-granules also exhibited remarkable thermo-stability, with an optimal temperature of 50 °C, and maintained more than 70% of the initial activity after incubation at 55 °C for 24 h. And an enhanced affinity of copper ion was observed in the PHA-TyrVs nano-granules, making them even better biocatalysts for L-DOPA production. Therefore, a considerable productivity of L-DOPA, amounting to 148.70 mg/L h, with a conversion rate of L-tyrosine of 90.62% can be achieved by the PHA-TyrVs nano-granules after 3 h of biocatalysis under optimized conditions, without significant loss of enzyme activity or L-DOPA yield after 8 cycles of repeated use. Our study provides an excellent and robust nano-biocatalyst for the cost-effective production of L-DOPA.
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10.1007/s00253-019-09851-7
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pubmed_456_19102
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The splice variant sVEGFR1-i13 is a truncated version of the cell membrane-spanning VEGFR1 receptor that is devoid of its transmembrane and tyrosine kinase domains. We recently showed the contribution of sVEGFR1-i13 to the progression and the response of squamous lung carcinoma to anti-angiogenic therapies. In this study, we identify VEGF165, a splice variant of VEGF-A, as a regulator of sVEGFR1-i13 expression in these tumors, and further show that VEGF165 cooperates with the transcription factor SOX2 and the splicing factor SRSF2 to control sVEGFR1-i13 expression. We also demonstrate that anti-angiogenic therapies up-regulate sVEGFR1-i13 protein level in squamous lung carcinoma cells by a mechanism involving the VEGF165/SOX2/SRSF2 network. Collectively, our results identify for the first time a signaling network that controls VEGFR1 pre-mRNA alternative splicing in cancer cells.
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10.1038/s41598-018-36728-y
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pubmed_531_10913
|
Twenty one Chlamydia trachomatis reference strains and 40 clinical isolates belonging to the lymphogranuloma venerum (LGV) and trachoma biovars were genotyped by differential restriction mapping of the major-outer-membrane-protein gene (MOMP) obtained by the polymerase-chain reaction (PCR). AluI digestion of the PCR product distinguishes eight MOMP-genotypes corresponding to 8 serovars. Six additional enzymes (NlaIII, CfoI, EcoRI, HinfI, DdeI and FokI) further permit the discrimination of 10 MOMP-genotypes corresponding to the 10 remaining serovars of the species. AluI alone allows direct typing of 78% of the clinical isolates. AluI digestion patterns of mouse C. trachomatis biovar, a C. pneumoniae and two C. psittaci strains, studied for comparison, were clearly distinguishable from one another and from the C. trachomatis LGV and trachoma strains. These results indicate that MOMP genotyping by PCR is a valuable molecular tool for studying C. trachomatis epidemiology.
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10.1016/0378-1097(91)90447-i
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pubmed_678_24880
|
BACKGROUND
Minors with a stated age <18 years unaccompanied by a responsible adult form an increasing part of refugees to Europe. They are older than other asylum-seeking children and many come from countries with a high tuberculosis (TB) incidence. During the 2015 refugee crisis, 35,369 of 162,877 refugees (22%) seeking asylum in Sweden were unaccompanied minors, which gave us the opportunity to study their burden of TB infection and disease.
METHODS
Of the unaccompanied minors seeking asylum in Sweden during 2015, 2936 (8.3%) were allocated to northern Stockholm. Of these, 2422 were from countries with an incidence of TB exceeding 100/105, and were screened for TB infection with a Mantoux tuberculin skin test or a QuantiFERON-TB Gold®. Those from countries with a lower TB incidence were screened only if they had other risk factors for TB exposure.
RESULTS
Of those screened, 349 had a positive test and were referred to the northern paediatric TB clinic at Astrid Lindgren Children's Hospital. Of these, 16 had TB disease and 278 latent tuberculosis infection (LTBI), while we considered 53 uninfected. In addition, eight sought medical attention with symptomatic TB outside the screening system. Cohort rates were 6.8% of LTBI and 0.5% of TB in minors from Afghanistan and 26-32% of LTBI and 3.4-3.5% of TB among those from Eritrea, Ethiopia or Somalia.
CONCLUSION
We conclude that TB infection and disease is common among asylum-seeking unaccompanied minors, especially among those from the Horn of Africa.
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10.1080/23744235.2017.1292540
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pubmed_1001_7640
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To improve the radical-scavenging activity of catechin, a planar catechin analogue was designed and synthesized by Fukuhara [J. Am. Chem. Soc. 124 (2002) 5952]. Although the planar catechin is less active than quercetin, it is much more active than catechin in its ability to scavenge galvinoxyl radical, suggesting that the rational design was successful. However, an interesting question remains: what is the basis for the enhanced radical-scavenging activity of the planar catechin? By DFT calculations, we determined that the galvinoxyl radical is scavenged through an electron-transfer mechanism rather than a hydrogen-atom-transfer mechanism. Moreover, the antioxidant anion, derived from proton dissociation, plays a key role in the radical-scavenging process. Hence, the different radical-scavenging activities of the three antioxidants may result from the different ionization potentials of their anions.
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10.1016/j.bioorg.2005.01.002
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pubmed_203_18730
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Adrenodoxin (Adx) is a [2Fe-2S] ferredoxin involved in electron transfer reactions in the steroid hormone biosynthesis of mammals. In this study, we deleted the sequence coding for the complete interaction domain in the Adx cDNA. The expressed recombinant protein consists of the amino acids 1-60, followed by the residues 89-128, and represents only the core domain of Adx (Adx-cd) but still incorporates the [2Fe-2S] cluster. Adx-cd accepts electrons from its natural redox partner, adrenodoxin reductase (AdR), and forms an individual complex with this NADPH-dependent flavoprotein. In contrast, formation of a complex with the natural electron acceptor, CYP11A1, as well as electron transfer to this steroid hydroxylase is prevented. By an electrostatic and van der Waals energy minimization procedure, complexes between AdR and Adx-cd have been proposed which have binding areas different from the native complex. Electron transport remains possible, despite longer electron transfer pathways.
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10.1016/j.bbrc.2005.08.077
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pubmed_970_1484
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Associative memory is one of the first cognitive functions negatively affected by healthy and pathological aging processes. Non-invasive brain stimulation (NIBS) techniques are easily administrable tools to support memory. However, the optimal stimulation parameters inducing a reliable positive effect on older adult's memory performance remain mostly unclear. In our randomized, double-blind, cross-over study, 28 healthy older adults (16 females; 71.18 + 6.42 years of age) received anodal transcranial direct (tDCS), alternating current in the theta range (tACS), and sham stimulation over the left ventrolateral prefrontal cortex (VLPFC) each once during encoding. We tested associative memory performance with cued recall and recognition tasks after a retention period and again on the following day. Overall, neither tDCS nor tACS showed effects on associative memory performance. Further analysis revealed a significant difference for performance on the cued recall task under tACS compared to sham when accounting for age. Our results suggest that tACS might be more effective to improve associative memory performance than tDCS in higher aged samples.
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10.3389/fnagi.2020.00066
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pubmed_4_4464
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For directing scientists, consumers, industry and stakeholders on mitigation strategies, there is a need to understand the acrylamide-forming potential of important Indian foods. Flour obtained from total 16 varieties of 9 Indian cereals, legumes and roots and tubers was heated at 160 °C for 20 min, acrylamide was extracted and quantified by UPLC-UV. Acrylamide level was above the European Commission indicative value in potato- and cereal-based food products, it ranged from 3436.13 to 5562.56 μg/kg in roots and tubers (potato and sweet potato). Among the cereals, maize (2195.31 μg/kg) and wheat (161.12 μg/kg) had the highest and lowest contents, respectively, whereas rice, sorghum and pearl millet showed intermediate values. Among the 2 legumes, soybean contained higher acrylamide (337.08-717.52 μg/kg) than chickpea (377.83-480.49 μg/kg). Analysis of variance revealed that roots and tubers acrylamide was highly significantly greater than the content in cereals (p < 0.0001) and in legumes (p < 0.0001) while there was no significant difference between cereals and legumes (p = 0.443). These results support the combination of pulses and minor cereals (chickpea, soybean, millets and sorghum) in cereal-based foods for improving the nutritional value and reducing acrylamide formation.
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10.1016/j.fct.2017.08.011
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pubmed_78_1802
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The aim of the study was to examine the relationship between therapeutic climate and the effectiveness of CBT treatment for sexual offenders in U.K. prisons. To this end a measure of group atmosphere was administered to members and leaders of 12 treatment groups running the same prison-based sexual offender treatment program. Treatment outcome was measured using a case-by-case methodology clinically significant change analysis--to identify the percentage of individuals within each group who had significantly changed on measures of pro-offending attitudes targeted in treatment. The results of the group process measure indicated leaders generally viewed groups more positively than members. Clear differences were also found between groups (ostensibly running the same treatment program) in terms of group climate. Analysis of members' process data indicated that there was a clear relationship between how cohesive the members reported the group to be and the extent to which freedom of action and expressions of feelings were encouraged in groups, as well as treatment outcome as measured by significant reductions in pro-offending attitudes. These results are discussed in terms of what they say about attitudes and goals of those involved in running treatment and how the effectiveness of treatment programs can be maximized.
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10.1177/107906320501700204
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pubmed_202_13143
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The anticonvulsant activity of ucb L059 ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) was evaluated in a range of animal models. ucb L059 was active after oral and intraperitoneal administration in both rats and mice, with a unique profile of action incorporating features in common with several different types of antiepileptic drugs. The compound was active, with ED50 values generally within the range of 5.0-30.0 mg/kg, in inhibiting audiogenic seizures, electrically induced convulsions and convulsions induced chemically by pentylenetetrazole (PTZ), bicuculline, picrotoxin and N-methyl-D-aspartate (NMDA). ucb L059 retarded the development of PTZ-induced kindling in mice and reduced PTZ-induced EEG spike wave discharge in rats. The R enantiomer, ucb L060, had low intrinsic anticonvulsant activity, showing the stereospecificity of action of the molecule although the actual mechanism of action remains unknown. Neurotoxicity, evaluated with an Irwin-type observation test, the rotarod test and open-field exploration, was minimal, with only mild sedation being observed, even at doses 50-100 times higher than the anticonvulsant doses; at pharmacologically active doses, the animals appeared calm but slightly more active. ucb L059 thus presents as an orally active, safe, broad-spectrum anticonvulsant agent, with potential antiepileptogenic and anti-absence actions.
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10.1016/0014-2999(92)90855-x
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pubmed_804_23264
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Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane-feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba2+ current through Cav1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite.
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10.1016/j.ejmech.2018.03.024
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pubmed_970_4690
|
Monte Carlo (MC) simulations, built around chain-connectivity-altering moves and a wall-displacement algorithm, allow us to simulate freely-jointed chains of tangent hard spheres of uniform size under extreme confinement. The latter is realized through the presence of two impenetrable, flat, and parallel plates. Extreme conditions correspond to the case where the distance between the plates approaches the monomer size. An analysis of the local structure, based on the characteristic crystallographic element (CCE) norm, detects crystal nucleation and growth at packing densities well below the ones observed in bulk analogs. In a second step, we map the confined polymer chains into self-avoiding random walks (SAWs) on restricted lattices. We study all realizations of the cubic crystal system: simple, body centered, and face centered cubic crystals. For a given chain size (SAW length), lattice type, origin of SAW, and level of confinement, we enumerate all possible SAWs (equivalently all chain conformations) and calculate the size distribution. Results for intermediate SAW lengths are used to predict the behavior of long, fully entangled chains through growth formulas. The SAW analysis will allow us to determine the corresponding configurational entropy, as it is the driving force for the observed phase transition and the determining factor for the thermodynamic stability of the corresponding crystal morphologies.
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10.3390/polym12040799
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pubmed_964_19356
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Salmeterol is a selective long-acting beta 2-agonist bronchodilator considered to have added anti-inflammatory effects, but this is controversial. We investigated the effects of a single dose of salmeterol, 100 micrograms, on the physiological and inflammatory responses to inhaled allergen and compared these with the effects of a single dose of beclomethasone, 500 micrograms, and of placebo. Eight atopic adults with mild stable asthma, treated only with inhaled short-acting beta 2-agonist when needed, attended the laboratory sequentially for screening tests, two single-blind control inhalation tests preceded 30 min by placebo or salmeterol and three allergen inhalation tests preceded by placebo, salmeterol or beclomethasone double-blind in random order. Airway responsiveness to methacholine (assessed as the provocative concentration of methacholine producing 20% fall in forced expiratory volume in one second (PC20)), induced sputum eosinophils, blood eosinophils and serum eosinophil cationic protein (ECP) were examined before and 7-48 h after treatment. The statistical power to detect twofold changes in blood and sputum parameters was > or = 90%. Salmeterol inhaled before allergen challenge completely prevented the early asthmatic response, late asthmatic response and fall in methacholine PC20 at 24 h, and produced additional bronchodilatation. These effects were similar to those obtained by the inhalation of a single dose of salmeterol before the control inhalation test, and significantly better than those observed after a single dose of beclomethasone inhaled before the allergen test. Beclomethasone had no effect on the early asthmatic response or on the fall in methacholine PC20 at 24 h but partially inhibited the late asthmatic response. Neither salmeterol nor beclomethasone had any significant effect on sputum or blood inflammatory changes 7-48 h after allergen inhalation. In conclusion, whilst salmeterol had no demonstrable anti-inflammatory action in sputum after allergen challenge in asthma, neither did a single dose of the positive anti-inflammatory control, beclomethasone. The latter result excludes a more positive judgement on the possible anti-inflammatory action of salmeterol. However, the results do indicate that potent functional effects of a single dose of salmeterol can mask the airway inflammatory cell influx caused by inhaled allergen.
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10.1183/09031936.96.09030449
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pubmed_339_18199
|
Non-specific interstitial pneumonia is characterized pathologically by uniform interstitial inflammation and fibrosis. This disease is most commonly demonstrated on high resolution CT as subpleural ground-glass opacity mixed with irregular linear opacities. The authors report a case of non-specific interstitial pneumonia with high resolution findings consistent with a "crazy paving pattern". This appearance, represented by smoothly thickened interlobular septa with a background of geographic areas of ground-glass opacity, is unusual for non-specific interstitial pneumonia and was indistinguishable from other interstitial or alveolar lung diseases.
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10.1259/bjr.74.878.740189
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pubmed_937_10294
|
Stathmin is a member of a novel class of microtubule-destabilizing proteins that regulate the dynamics of microtubule polymerization and depolymerization. Stathmin promotes microtubule depolymerization during interphase and late mitosis. This microtubule depolymerizing activity of stathmin is regulated by changes in its level of phosphorylation that occur during cell cycle progression. These modifications allow it to play a critical role in the regulation of the dynamic equilibrium of microtubules during different phases of the cell cycle. Stathmin is expressed at high levels in a wide variety of human cancers. Inhibition of stathmin expression in malignant cells interferes with their orderly progression through the cell cycle and abrogates their transformed phenotype. Thus, stathmin provides an attractive molecular target for disrupting the mitotic apparatus and arresting the growth of malignant cells. In this review, we describe the current understanding of the role of stathmin in the regulation of the mitotic spindle and discuss its potential as a therapeutic target of cancer therapy.
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pubmed_937_10294
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pubmed_435_439
|
PURPOSE
Patients with postoperative urinary retention (POUR) can develop bladder atrophy, urinary incontinence, and hypertension. The purpose of this quality improvement project was to implement standardized guidelines for bladder scanning for patients who have total knee or hip replacement to decrease POUR and incontinent episodes.
DESIGN
A retrospective descriptive study was implemented in a 425-bed Magnet community hospital.
METHODS
Patients were bladder scanned within the first hour of postanesthesia care unit admission. Straight catheterization was performed for those who had more than 400 mL of retained urine. The protocol included both total knee and total hip replacement surgeries with spinal anesthesia. Compliance with scanning, percentages with POUR, and incontinent episodes were reviewed.
FINDINGS
POUR was detected in 46% of total knee replacement patients and 36% of total hip replacement patients. Incontinence rates for knee replacement patients decreased by 14% and by 2% for patients with total hip replacements.
CONCLUSIONS
A bladder scanning protocol decreases postoperative incontinence. Bladder scanning also helps to decrease POUR by decreasing the potential risk of complications.
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10.1016/j.jopan.2019.03.012
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pubmed_651_7818
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Experiments on rabbits with experimental myocardial infarction were made to determine the content of adenyl nucleotides and Ca2+-dependent ATPase activity of myosin outside the zone of necrosis. It was found that on the 5th day the animals injected with 40 mg/kg riboxine intravenously on a daily basis manifested a 36% increase in the content of AMP and a 81% increase in the CA2+-dependent ATPase activity as compared with untreated controls. Injection of riboxine did not produce any appreciable changes in the content of ATP and ADP. Riboxine appears to stimulate the utilization of the energy of macroenergic binding of adenyl nucleotides with myocardial cells.
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pubmed_651_7818
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pubmed_288_7867
|
Recent genetic and molecular analyses have revealed how several strategies enable bacteria to persist and overcome insect immune defences. Genetic and genomic tools that can be used with Drosophila melanogaster have enabled the characterization of the pathways that are used by insects to detect bacterial invaders and combat infection. Conservation of bacterial virulence factors and insect immune repertoires indicates that there are common strategies of host invasion and pathogen eradication. Long-term interactions of bacteria with insects might ensure efficient dissemination of pathogens to other hosts, including humans.
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10.1038/nrmicro1870
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pubmed_125_11507
|
BACKGROUND
Undernourished people have an increased risk of premature mortality from both infectious and non-communicable diseases. Aside from screening purposes, assessment of nutritional status is a useful tool in management and evaluation of various chronic diseases. Body-Mass-Index (BMI) is today the most commonly used marker of nutritional status however, this method presents a challenge in many low resource settings and immobile patients. Mid-upper arm circumference (MUAC) is another anthropometric measure that requires minimal equipment and little training. So far, MUAC cutoffs for undernutrition are well established in children < 5 years but there is still no consensus for a specific cutoff in adults. The objective of this study was to compare MUAC with BMI and suggest a MUAC cut-off corresponding to a BMI of 18.5 kg/m2 to identify underweight in adults.
METHODS
A cross-sectional study was conducted at two urban public hospitals in Nepal. The following variables where collected: MUAC, weight, height, sex, age and self-reported medical history.
EXCLUSION CRITERIA
< 19 years of age, pregnancy and oedema. Sensitivity and specificity for a MUAC value corresponding to BMI < 18.5 was calculated. ROC analysis was performed for male and female as well as Pearson's correlation of MUAC and BMI.
RESULTS
A total of 302 people between 18 and 86 years of age, 197 women and 105 men, were included. Of these, 90 people suffered from rheumatic heart disease. MUAC was highly correlated with BMI in both women r = 0.889 and men r = 0.846. Best statistically derived MUAC cutoff corresponding to a BMI < 18.5 kg/m2 was 24.5 cm (Youdens Index = 0.75; sensitivity 92.86; specificity 82.48), with high predictive value (AUROCC> 0.9). The setting based optimal MUAC cutoff was also 24.5 cm. No considerable variation was found in sex- and disease specific subgroups.
CONCLUSION
MUAC is strongly correlated with BMI in adults in Nepal. For simplicity, a MUAC of 24.5 cm is the optimal statistically and setting based cutoff in both women and men to identify underweight (BMI < 18.5 kg/m2).
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10.1186/s12889-020-09294-0
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pubmed_617_5076
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The aim of this study was to investigate the feasibility of employing S-carboxymethyl-L-cysteine as a treatment of chronic obstructive pulmonary disease in dogs. To this end the pharmacokinetic parameters of orally administered S-carboxymethyl-L-cysteine were determined in the dog, cow and sheep. Six healthy beagle dogs, six endogenous Greek sheep and four Holstein Fresian calves were orally dosed with 10 mg/kg body weight of S-carboxymethyl-L-cysteine. No significant differences in T(max) and T(1/2) were reported between the species. However, significantly higher AUC((0-last)), 21.56+/-6.67 microg h ml(-1) and AUC((0-infinity)), 21.63+/-6.68 microg h ml(-1) were seen in the dogs compared to the sheep and calves. The calculated V(D) was significantly higher in the sheep (10.4+/-2.7 L kg(-1)) and the calves (3.8+/-0.7 L kg(-1)) compared to the dogs (1.0+/-0.6 L kg(-1)). The rank order of increasing C(L) was sheep (3.4+/-2.7 L h(-1)kg(-1))>calves (2.7+/-0.4 L h(-1) kg(-1))>dogs (0.5+/-0.2 L h(-1)kg(-1)). The result for the dogs was significantly lower that the calculated C(L) for the sheep and calves. All these results indicate that the oral administration of S-carboxymethyl-L-cysteine may be useful during the therapeutic management of chronic obstructive pulmonary disease in dogs.
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10.1016/j.ejps.2009.12.003
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pubmed_641_4539
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The optimal method of oxygen supplementation during upper gastrointestinal endoscopy has not been clearly defined. The aim of this study was to compare oxygen supplementation via nasal prongs with that via a catheter passed into the low oropharynx to eliminate the effect of mouth breathing. Patients were stratified according to the American Society of Anesthesiologists (ASA) classification of physical status into lower-risk (ASA 1 and 2) and higher-risk (ASA 3) groups. The lower-risk group received intranasal, intrapharyngeal, or no oxygen supplementation, and higher-risk patients received either intranasal or intrapharyngeal oxygen. Continuous arterial oxygen saturation (SpO2) was recorded, using a pulse oximeter, before and during endoscopy. Critical desaturations (SpO2 < or = 90%), minimum SpO2 during endoscopy, and maximum desaturation from the baseline oxygen on air, were evaluated. There was no significant difference in the number of patients desaturating, minimum SpO2, or in the maximum desaturation from the baseline between the groups receiving intranasal or intrapharyngeal oxygen supplementation. In lower-risk patients receiving no supplementary oxygen (n = 27), ten patients (37%) desaturated, compared with one of 52 patients (2%) receiving supplementary oxygen (p < 0.001). There was also a significant difference between these groups in the minimum SpO2 (91% vs 97%, p < 0.001) and the maximum desaturation from the baseline (-5.2% vs +0.7%, p < 0.001) during endoscopy. We conclude that the intranasal and intrapharyngeal methods of oxygen supplementation are of similar efficacy, and that supplementary oxygen significantly decreases the incidence of critical arterial oxygen desaturation that occurs even in healthy patients undergoing upper gastrointestinal endoscopy.
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10.1055/s-2007-1008967
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pubmed_507_4127
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Novel washout-resistant bone substitute materials consisting of gelatin-containing calcium silicate cements (CSCs) were developed. The washout resistance, setting time, diametral tensile strength (DTS), morphology, and phase composition of the hybrid cements were evaluated. The results indicated that the dominant phase of beta-Ca(2)SiO(4) for the SiO(2)-CaO powders increased with an increase in the CaO content of the sols. After mixing with water, the setting times of the CSCs ranged from 10 to 29 min, increasing with a decrease in the amount of CaO in the sols. Addition of gelatin into the CSC significantly prolonged (P < 0.05) the setting time by about 2 and 8 times, respectively, for 5% and 10% gelatin. However, the presence of gelatin appreciably improved the anti-washout and brittle properties of the cements without adversely affecting mechanical strength. It was concluded that 5% gelatin-containing CSC may be useful as bioactive bone repair materials.
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10.1007/s10856-009-3948-1
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pubmed_614_7504
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The aim of our study is to investigate the molecular mechanism of gomisin J from Schisandra chinensis on the oleic acid (OA)-induced lipid accumulation in HepG2 cells. Gomisin J attenuated lipid accumulation in OA-induced HepG2 cells. It also suppressed the expression of lipogenic enzymes and inflammatory mediators and increased the expression of lipolytic enzymes in OA-induced HepG2 cells. Furthermore, the use of specific inhibitors and fetuin-A siRNA and liver kinase B1 (LKB1) siRNA transfected cells demonstrated that gomisin J regulated lipogenesis and lipolysis via inhibition of fetuin-A and activation of an AMP-activated protein kinase (AMPK)-dependent pathway in HepG2 cells. Our results showed that gomisin J suppressed lipid accumulation by regulating the expression of lipogenic and lipolytic enzymes and inflammatory molecules through activation of AMPK, LKB1, and Ca(2+)/calmodulin-dependent protein kinase II and inhibition of fetuin-A in HepG2 cells. This suggested that gomisin J has potential benefits in treating nonalcoholic fatty liver disease.
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10.1021/acs.jafc.5b04089
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pubmed_942_12809
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PURPOSE
To evaluate the effectiveness of a screening instrument (the Swedish Communication Screening at 18 months of age; SCS18), derived from the Swedish MacArthur-Bates Communicative Development Inventory, in identification of 18-month-old children who will be severely language disabled by 3 years of age, the authors (a) analyzed which SCS18's component yielded the best prediction, (b) compared the productivity figures of the SCS18 with those of the traditional method of identification, and (c) tried different cutoff criteria of the SCS18.
METHOD
Half of the child health care (CHC) centers in a Swedish county were randomly selected to use the SCS18 (e.g., a checklist supporting parents in assessing their child's word production, word comprehension, and communicative gestures). Remaining CHC centers used an informal assessment. Expressive and receptive language was subsequently judged with an observation for 3-year-olds that is routine in the county. An unselected population of 2,080 children participated at 18 months of age and again at 3 years of age.
RESULT
Number of spoken words yielded the best prediction, and SCS18 was superior to the traditional method. A sensitivity of 50%, however, was not enough, and a stricter criterion resulted in too many false positives to be acceptable as routine.
CONCLUSION
Although the SCS18 has strength, the age of 18 months seems to be too early for identification of severe language disability.
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10.1044/1092-4388(2006/020)
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pubmed_581_16350
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BACKGROUND
Current literature reporting on the impact of BMI on outcomes of orthopaedic surgical procedures is varied and inconsistent. The purpose of our study was to evaluate if body mass index (BMI) affects outcomes of primary anterior cruciate ligament reconstruction (ACLR) in an Asian population.
METHODS
We retrospectively reviewed prospectively collected data of 141 consecutive patients who underwent primary ACLR by a single surgeon, the senior author of this study. Flexion range, International Knee Documentation Committee (IKDC) score, KT-1000 translation, Tegner activity level scale, Lysholm score and satisfaction were assessed preoperatively and at 2 years postoperatively. The patients were then stratified into two groups: normal-BMI and high-BMI in accordance with WHO classification. Outcomes were then compared between the two groups. All statistical analysis were performed on IBM SPSS Statistics 20.
RESULTS
There were 81 patients in the normal-BMI group (BMI, 18.5 to 24.9) and 60 patients in the high-BMI group (BMI ≥25). Preoperatively, the only differences were in the gender proportions as well as the pre-injury Tegner score. 2-years postoperatively, patients in the normal-BMI group had better flexion (139° vs. 130°; P=0.0001), Tegner scores (5.7 vs. 4.8; P=0.005) and satisfaction rate (99% vs. 90%; P=0.041). There were no differences in graft failure or complication rates.
CONCLUSIONS
Obese patients had poorer range of motion and Tegner scores as compared to their nonobese counterparts following primary ACLR.
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10.21037/atm.2017.06.04
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pubmed_633_7177
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We measured molecular forms of PYY in the distal half of rat small intestine using a new method for tissue extraction, three sequential reverse phase chromatography steps, and PYY radioimmunoassay and mass spectrometry to measure their levels. The extraction method called RAPID, developed to minimize artifactual degradation of PYY during tissue extraction and sample preparation, uses Reduced temperature, Acidified buffer, Peptidase inhibitors, Isotopically enriched mass spectrometry standards, and Dilution to inhibit and monitor endogenous peptide degradation during tissue processing. Synthetic peptides [PYY(1-36)-NH(2), PYY(3-36)-NH(2), PYY(1-36)-Gly-OH, and PYY(3-36)-Gly-OH] selectively enriched with (13)C(3)-alanine were added as internal standards to the extraction buffer. By collecting mass spectra rather than multiple-reaction-monitoring (MRM) profiles, we simultaneously screen for any PYY forms that were present in the immunoreactive fractions. PYY(1-36)-NH(2), PYY(3-36)-NH(2), PYY(1-36)-Gly-OH, and PYY(3-36)-Gly-OH were identified and quantified at 64.3±4.5, 6.1±0.9, 0.9±0.1, and <0.3pmol/g of tissue, respectively (n=3). Thus, we found that in rat distal small intestine proPYY is processed to PYY(1-36)-NH(2) with little conversion to PYY(3-36)-NH(2). These data suggest that production of PYY(3-36)-NH(2) (a form with greater potency than PYY(1-36)-NH(2) for inhibition of feeding and gastric emptying) occurs after the peptide leaves its cell of synthesis by enzymatic action in the circulation.
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10.1016/j.regpep.2010.06.006
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pubmed_386_8831
|
BACKGROUND
Local excision for early rectal cancer has gained widespread interest. Currently available imaging modalities have low sensitivity to detect locoregional disease, which may result in understaging and a high risk of recurrence after local excision.
OBJECTIVE
The purpose of this work was to study the morbidity, mortality, and long-term oncologic outcomes in a select cohort of patients undergoing salvage surgery for local recurrence after local excision of early rectal cancer.
DESIGN
A retrospective review of patient charts was used to determine patterns of disease recurrence and outcomes as a single-institution case series.
SETTINGS
The study was conducted at a tertiary care cancer center.
PATIENTS
The study cohort included patients with early rectal cancer treated by local excision who then developed local recurrence for which a multimodal salvage surgery with curative intent was performed between 1997 and 2013 at our center.
MAIN OUTCOME MEASURES
Log rank tests were used to measure overall and disease-free survival.
RESULTS
Twenty-seven patients were identified, with a mean age of 66 ± 12 years. The median time to recurrence was 54 weeks (range, 7-326 weeks). Recurrent disease was luminal in 23 patients, regional (involving both mesorectal and pelvic lymph nodes) in 6 patients, and both luminal and nodal in 2 patients. For salvage surgery, neoadjuvant chemoradiation was used in 12 patients (44%), and radiation alone was used in 1 patient. Sphincter-preserving surgery was performed in 9 patients (33%). R0 resection was achieved in 25 patients (93%). Four patients received intraoperative radiation therapy. Five-year overall survival was 50% (95% CI, 30%-74%), and re-recurrence-free survival was 47% (95% CI, 25%-68%).
LIMITATIONS
This study was limited by its retrospective nature, small patient cohort, referral bias, and selection bias.
CONCLUSIONS
Even in highly selected patients who undergo surgery for local recurrence after transanal excision of early stage rectal cancer, oncologic outcomes are poor.
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10.1097/DCR.0000000000000283
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pubmed_713_1504
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Many cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences. We applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n = 2956) and multi-ethnic populations (COVID-19 GWAS n = 10,908) to better understand extant causal associations between Type II Diabetes (GWAS n = 659,316), BMI (n = 681,275), diastolic and systolic blood pressure, and pulse pressure (n = 757,601 for each) and COVID-19 hospitalization risk across populations. Although no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI 1.67, 0.96-2.92) and pulse pressure (OR, 95% CI 1.27, 0.97-1.66) in the multi-ethnic sample. Type II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.
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10.1038/s41598-021-86757-3
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pubmed_612_6577
|
Persistent hepatitis B virus (HBV) infection remains a serious medical problem worldwide, with an estimated global burden of 257 million carriers. Prophylactic and therapeutic interventions, in the form of a vaccine, immunomodulators, and nucleotide and nucleoside analogs, are available. Vaccination, however, offers no therapeutic benefit to chronic sufferers and has had a limited impact on infection rates. Although immunomodulators and nucleotide and nucleoside analogs have been licensed for treatment of chronic HBV, cure rates remain low. Transcription activator-like effector nucleases (TALENs) designed to bind and cleave viral DNA offer a novel therapeutic approach. Importantly, TALENs can target covalently closed circular DNA (cccDNA) directly with the potential of permanently disabling this important viral replicative intermediate. Potential off-target cleavage by engineered nucleases leading to toxicity presents a limitation of this technology. To address this, in the context of HBV gene therapy, existing TALENs targeting the viral core and surface open reading frames were modified with second- and third-generation FokI nuclease domains. As obligate heterodimers these TALENs prevent target cleavage as a result of FokI homodimerization. Second-generation obligate heterodimeric TALENs were as effective at silencing viral gene expression as first-generation counterparts and demonstrated an improved specificity in a mouse model of HBV replication.
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10.3390/v13071344
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pubmed_246_3861
|
Doxorubicin induced acute as well as chronic myocardial morphologic alterations. Twenty patients with normal cardiovascular function were randomized to 2 groups based on age and dose of doxorubicin. Group I received placebo 1 hour before doxorubicin administration; group II received acetylcysteine (N-acetyl-L-cysteine) (Nac) 1 hour before doxorubicin. Endomyocardial biopsies were performed at base line at 4 and 24 hours after doxorubicin administration. Biopsy tissue was viewed by electron microscopy, and stereoscopic techniques were used to determine tubular and mitochondrial area. The change of the tubular area was similar in the 2 groups, was maximum at 4 hours, and was proportionately spread throughout the cell. The mitochondrial swelling was also similar in the 2 groups and proportionate throughout the cell but was maximum at 24 hours. This study demonstrated that the acute doxorubicin-induced damage was diffuse and not prevented by Nac.
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pubmed_246_3861
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pubmed_912_17020
|
Extraskeletal osteosarcoma (EOS) is rare and commonly arises in the retroperitoneum, limbs, head and neck. There is no significant difference between EOS and other malignant tumors in soft tissue. Localized pain and swelling are the common presenting symptoms. Clinical diagnosis of EOS is difficult, imaging techniques may be helpful and careful, and the histopathological analysis is necessary. The common histological variants of EOS include: osteoblastoma, chondroblastoma, and fibroblastoma, and other unusual subtypes were reported occasionally. It should be distinguished with myositis ossificans, malignant mesenchymoma, giant cell tumor and parosteal osteosarcoma. We present an EOS arising in the penis. The primary site and histological category of the tumor were extremely rare. We hope the case will be helpful to the recognition of clinical signs, iconography and histopathology of EOS.
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10.1007/s11670-012-0164-1
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pubmed_210_9833
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SLE is a complex autoimmune disease with genetic, epigenetic, immune-regulatory, environmental and hormonal factors. Kidney inflammation and injury, termed lupus nephritis (LN), occurs in over half of patients with SLE and is a leading cause of disability and death. There is a high degree of short-term and long-term side effects associated with current LN therapies and they are not effective for many patients. Thus, novel therapies with reduced toxicity and improved efficacy are drastically needed. Many of the known LN susceptibility genes have functions that mediate inflammation via cytokine/chemokine production and activation of myeloid and B cells. Understanding the cellular and molecular mechanisms mediated by these variant gene products provides valuable insight for the development of improved and personalised diagnostics and therapeutics. This review describes variants in the TNIP1 (tumour necrosis factor α-induced protein 3-interacting protein 1) gene associated with risks for SLE and LN and potential roles for loss of function of its protein product ABIN1 in the activation of myeloid and B-cell-mediated injury in LN.
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10.1136/lupus-2020-000437
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pubmed_901_4642
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A single dose experiment was used to evaluate the analgesic effect of diflunisal, a new salicylic acid derivative. Three dose levels of diflunisal (125 mg, 250 mg, and 500 mg) were compared to one dose level of acetylsalicylic acid (ASA) (600 mg) and placebo. The maximal analgesis induced by 500 mg diflunisal was comparable to that of 600 mg ASA. The onset of action was slightly more rapid with ASA but the duration of the analgesic effect was far longer for diflunisal, extending beyond 8 hours after administration. Diflunisal is a promising drug for the treatment of post-operative pain because of its long-lasting effect.
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10.1177/030006057800600302
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pubmed_192_25913
|
Pulmonary arterial hypertension (PAH) is a rare vascular lung disease with a complex etiopathogeny characterized by an increased pulmonary arterial pressure of 25 mmHg or above assessed by right heart catheterization. The diagnosis is difficult due to the atypical presentation with shortness of breath requiring a sequential approach bringing at the end the clinician to perform a right heart catheterization. Nowadays, several therapies have proven to be efficient for treating PAH. Recently, international recommendations have moved to an initial combination therapy reducing the overall morbi-mortality of the patients. Therefore, early therapy appears to be a priority in PAH underlying the need for increasing the global knowledge around PAH.
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pubmed_192_25913
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pubmed_1082_21900
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The question of whether the impairment of the endosteal blood supply, which is induced by nailing with reaming of the medullary cavity, increases the risk of a postoperative infection cannot be conclusively answered by studying existing literature. The aim of this study was to investigate the effect of medullary reaming on the occurrence of local infection based on an infection model in the rabbit tibia (n = 44). An infection rate of 50% was found after unreamed nailing, as opposed to an infection rate of 64% after medullary reaming. The number of bacteria observed after reaming was significantly higher than after nail insertion without previous reaming. The differing susceptibilities to infection as observed in this model are statistically significant (p < or = 0.05).
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10.1097/00005373-199512000-00020
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pubmed_101_19078
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Bark beetles attack their hosts at uniform intervals to avoid intraspecific competition in the phloem. Bark texture and phloem thickness also affect bark beetle attacks, and the bark characteristics are not spatially homogeneous; therefore, the distribution patterns of entry holes can demonstrate an aggregated distribution. Polygraphus proximus Blandford (Coleoptera: Scolytinae) is a non-aggressive phloephagous bark beetle that feeds on Far Eastern firs. They have caused mass mortality in Russia and Japan. However, the distribution pattern of entry holes of P. proximus and spatial relationships with bark characteristics have not been studied. Thus, we investigated the distribution pattern of entry holes of P. proximus. The distribution of entry holes was significantly uniform in most cases. As the attack density increased, an aggregated distribution pattern within a short distance (< 4.0 cm) was observed. The rough bark had a significantly higher number of entry holes than the remaining bark. The distribution pattern of entry holes demonstrated a significantly aggregated spatial association with rough bark. Finally, rough bark around knots had significantly thicker phloem than the remaining barks. These suggest that P. proximus may preferentially attack rough bark to reproduce in the thicker phloem under a rough bark surface.
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10.1371/journal.pone.0246812
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pubmed_21_14350
|
Telomeres are the tips of chromosomes and consist of proteins and hexanucleotide tandem repeats of DNA. The DNA repeats are shortened at each mitotic division of normal cells, and the telomere length chronicles how many divisions the cell has undergone. Thus, telomere length is a marker of fundamental biological pathways. It has been possible to measure telomere length for more than 20 years, and it has been established that telomere length is associated with age, sex and lifestyle factors. Here, the current knowledge of telomere length as a biomarker of disease susceptibility and mortality will be reviewed. In addition, technical difficulties and the reasons why measurement of telomeres has still not been introduced into routine clinical practice will be discussed. Findings from recent studies conducted in many thousands of individuals indicate that telomere length is not-or at best only marginally-independently associated with risk of common disorders such as cardiovascular, pulmonary and neoplastic diseases. However, in sufficiently powered studies, short telomeres are repeatedly and independently found to be associated with increased risk of early death in the general population or in subsets of individuals. This indicates that measurement of telomeres could be a valuable prognostic biomarker in many clinical settings. However, whether short telomeres are a causal factor for or simply a marker of increased risk of early death must be determined. Finally, how Mendelian randomization studies could clarify this issue, and which clinical studies might be carried out to refine this very promising biomarker for routine clinical use will be considered.
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10.1111/joim.12083
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pubmed_955_21281
|
Recent advances in understanding of skeletal muscle differentiation implicate fibroblast growth factors (FGFs) as regulators of myogenesis; however, the identity and actions of factors that repress myogenesis in vivo remain to be established. This review will focus on the fibroblast growth factor family and the evidence for its role in regulating myogenesis in culture and in vivo.
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10.1016/0955-2235(94)90002-7
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pubmed_518_19901
|
BACKGROUND
There remains controversy concerning the association between myocardial dysfunction diagnosed soon after acute myocardial infarction (AMI), and subsequent quality of life.
AIMS
We searched for a correlation between criteria of myocardial dysfunction assessed within the first month after AMI, and quality of life perceived 1 year later.
METHODS
Six hundred and seventy-one patients were followed up and quality of life was assessed using the Nottingham Health Profile. Spearman correlation was used for univariate analyses. A logistic regression identified independent predictors of impaired quality of life.
RESULTS
Patients perceiving inferior quality of life were 61% for energy, 61% for sleep, 49% for physical mobility, 49% for pain, 63% for emotional reactions, and 28% for social isolation. Impaired quality of life was not associated with the initial Killip class. A low ejection fraction was associated with impaired physical mobility (OR=1.21, 95% CI=1.05-1.39). Presence of abnormally contracting myocardial segments was associated with impaired mobility (1.40, 1.09-1.80) and with increased pain (1.30, 1.02-1.66). The presence of diseased coronary vessels was associated with pain (1.25, 1.06-1.46).
CONCLUSION
Myocardial dysfunction was generally associated with impaired quality of life. This has to be considered when assessing improvement of quality of life after medical or surgical treatment of AMI.
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10.1016/s1388-9842(01)00171-4
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pubmed_100_12481
|
We showed previously that oxytocinergic (OTergic) projections from the hypothalamic paraventricular nucleus (PVN) to the dorsal brain stem mediate training-induced heart rate (HR) adjustments and that beneficial effects of training are blocked by sinoaortic denervation (SAD; Exp Physiol 94: 630-640; 1103-1113, 2009). We sought now to determine the combined effect of training and SAD on PVN OTergic neurons in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats underwent SAD or sham surgery and were trained (55% of maximal capacity) or kept sedentary for 3 mo. After hemodynamic measurements were taken at rest, rats were deeply anesthetized. Fresh brains were frozen and sliced to isolate the PVN; samples were processed for OT expression (real-time PCR) and fixed brains were processed for OT immunofluorescence. In sham rats, training improved treadmill performance and increased the gain of baroreflex control of HR. Training reduced resting HR (-8%) in both groups, with a fall in blood pressure (-10%) only in SHR rats. These changes were accompanied by marked increases in PVN OT mRNA expression (3.9- and 2.2-fold in WKY and SHR rats, respectively) and peptide density in PVN OTergic neurons (2.6-fold in both groups), with significant correlations between OT content and training-induced resting bradycardia. SAD abolished PVN OT mRNA expression and markedly reduced PVN OT density in WKY and SHR. Training had no effect on HR, PVN OT mRNA, or OT content following SAD. The chronic absence of inputs from baroreceptors and chemoreceptors uncovers the pivotal role of afferent signaling in driving both the plasticity and activity of PVN OTergic neurons, as well as the beneficial effects of training on cardiovascular control.
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10.1152/ajpregu.00104.2011
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pubmed_545_11382
|
BACKGROUND
Hypothermic storage at 5°C has been investigated as an alternative to promote the prudent use of antibiotics for boar artificial insemination doses. However, this temperature is challenging for some ejaculates or boars.
OBJECTIVE
The present study aimed to identify putative biomarkers for semen resistance to hypothermic storage at 5°C by comparing the seminal plasma proteomes of boars with high and low seminal resistance to preservation at 5°C.
MATERIALS AND METHODS
From an initial group of 34 boars, 15 were selected based on the following criteria: ejaculate with ≤20% abnormal spermatozoa and at least 70% progressive motility at 120 hours of storage at 17°C. Then, based on the response to semen hypothermic storage at 5°C, boars were classified into two categories: high resistance-progressive motility of >75% in the three collections (n = 3); and low resistance-progressive motility of <75% in the three collections (n = 3). Seminal plasma proteins were analyzed in pools, and differential proteomics was performed using Multidimensional Protein Identification Technology.
RESULTS
Progressive motility was lower at 120 hours of storage in low resistance, compared to high resistance boars (P < .05). Acrosome and plasma membrane integrity were not affected by the boar category, storage time, or their interaction (P ≥ .104). Sixty-five proteins were considered for differential proteomics. Among the differentially expressed and exclusive proteins, the identification of proteins such cathepsin B, legumain, and cystatin B suggests significant changes in key enzymes (eg, metalloproteinases) involved in spermatogenesis, sperm integrity, and fertilizing potential.
DISCUSSION AND CONCLUSION
Differences in the seminal plasma suggest that proteins involved in the proteolytic activation of metalloproteinases and proteins related to immune response modulation could disrupt key cellular pathways during spermatogenesis and epididymal maturation, resulting in altered resistance to chilling injury. Further in vivo studies focusing on the immunological crosstalk between epithelial cells and gametes might explain how the immune regulators influence sperm resistance to hipothermic storage.
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10.1111/andr.12869
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pubmed_410_5834
|
In the routine dissections study for medical postgraduates, a rare anatomical variation between the right leg and the ankle was observed on the Asian male cadaver. The peronaeus tertius muscle in this cadaver's right leg divided into two tendons: the first tendon was attached to the base of the fifth metatarsal bone, and the second tendon was inserted into the base of the fourth metatarsal bone. The purpose of this paper is to provide detailed anatomical case reports, and to discuss the possible causes and mechanisms of the variation by reviewing relevant literature, so as to provide some reference for future anatomical and clinical related disease research.
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10.1007/s00276-022-02899-7
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pubmed_538_5364
|
There is no vaccine to prevent dengue fever, a mosquito-borne viral disease, caused by four serotypes of dengue viruses. In this study, which has been prompted by the emergence of dengue virus envelope domain III as a promising sub-unit vaccine candidate, we have examined the possibility of developing a chimeric bivalent antigen with the potential to elicit neutralizing antibodies against two serotypes simultaneously. We created a chimeric dengue antigen by splicing envelope domain IIIs of serotypes 2 and 4. It was expressed in Escherichia coli and purified to near homogeneity. This protein retains the antigenic identities of both its precursors. It elicited antibodies that could efficiently block host cell binding of both serotypes 2 and 4 of dengue virus and neutralize their infectivity (neutralizing antibody titers approximately 1:40 and ~1:80 for dengue virus serotypes 2 and 4, respectively). This work could be a forerunner to the development of a single envelope domain III-based tetravalent antigen.
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pubmed_538_5364
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pubmed_110_3249
|
When mouse erythroleukemia (MEL) cells were incubated in the presence of chloramphenicol (a specific inhibitor for mitochondrial protein synthesis) during the early stage of in vitro erythroid differentiation, the number of induced erythroid cells was greatly reduced. By use of cell fusion between two genetically marked MEL cells, this finding was further investigated. We found that the drug, along with other agents which inhibit mitochondrial protein synthesis, blocked the induction and turnover of the DMSO-inducible intracellular-erythroid-inducing activity (differentiation-inducing factor II) in a manner similar to that of cycloheximide, an inhibitor for nuclear protein synthesis. The inhibitory effect was confirmed by directly assaying differentiation-inducing factor II in the cell extracts. These results strongly suggest that mitochondrial protein synthesis is closely associated with in vitro erythroid differentiation of MEL cells.
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10.1128/mcb.8.8.3311-3315.1988
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pubmed_851_13314
|
We demonstrate that UV-light activation of polycrystalline ZnO films on flexible polyimide (Kapton) substrates can be used to detect and differentiate between environmental changes in oxygen and water vapor. The in-plane resistive and impedance properties of ZnO films, fabricated from bacteria-derived ZnS nanoparticles, exhibit unique resistive and capacitive responses to changes in O2 and H2O. We propose that the distinctive responses to O2 and H2O adsorption on ZnO could be utilized to statistically discriminate between the two analytes. Molecular dynamic simulations (MD) of O2 and H2O adsorption energy on ZnO surfaces were performed using the large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) with a reactive force-field (ReaxFF). These simulations suggest that the adsorption mechanisms differ for O2 and H2O adsorption on ZnO, and are governed by the surface termination and the extent of surface hydroxylation. Electrical response measurements, using DC resistance, AC impedance spectroscopy, and Kelvin Probe Force Microscopy (KPFM), demonstrate differences in response to O2 and H2O, confirming that different adsorption mechanisms are involved. Statistical and machine learning approaches were applied to demonstrate that by integrating the electrical and kinetic responses the flexible ZnO sensor can be used for detection and discrimination between O2 and H2O at low temperature.
|
10.1038/s41598-017-05265-5
|
pubmed_487_14262
|
OBJECTIVES
To identify and report cross-national patterns in contraceptive use among sexually active adolescents.
DESIGN
A cross-national cross-sectional survey.
SETTING
Data were collected in 2002 by self-report questionnaire from students in school classrooms.
PARTICIPANTS
A cluster sample of 33,943 students aged 15 years from 24 countries.
MAIN OUTCOME MEASURES
International standardized questions on ever having had sexual intercourse and contraceptive use at last sexual intercourse.
RESULTS
The percentages of students reporting having had sexual intercourse ranged from 14.1% in Croatia to 37.6% in England; 82.3% of those who were sexually active reported that they used condoms and/or birth control pills at last intercourse. Condom use only was most frequent and ranged from 52.7% in Sweden to 89.2% in Greece. Dual use of condoms and contraceptive pills was also relatively frequent, ranging from 2.6% in Croatia to 28.8% in Canada. The use of contraceptive pills was most frequent in northern and western Europe. No contraceptive use at last intercourse was reported by 13.2% of students.
CONCLUSIONS
A substantial minority of 15-year-olds have engaged in sexual intercourse. Condom use is the most frequent method of contraception reported by the sexually active respondents, followed by the dual use of condoms and contraceptive pills and contraceptive pills only. The proportions of poorly protected and unprotected youth remain high, and attention to international policy and practice determinants of young sexual behavior and contraceptive use is required.
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10.1001/archpediatrics.2007.8
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pubmed_1129_9005
|
OBJECTIVES
To study the recent trends in maternal and perinatal outcomes of triplet pregnancy from a perinatal centre in South India.
METHODS
All triplet pregnancies booked at Fernandez hospital, Hyderabad (a tertiary care perinatal centre in South India), or those referred between 2000 and 2014 were included in the study. The maternal, fetal and neonatal outcome and any interventions like cerclage, steroid administration were studied.
RESULTS
There were 82 triplet deliveries over the study period of 15 years (82 per 69,584 live births). Most of them (78%) conceived with assistance and 83% of the triplets were trichorionic triamniotic. Anaemia and pregnancy induced hypertension were the commonest medical disorders (40.2 and 22%, respectively). Mean gestational age at delivery was 32 ± 2.8 weeks and 91% were delivered by caesarean section. Preterm labour and preterm pre-labour rupture of membranes were present in 29 and 15%, respectively. Antenatal steroids were administered in 87.8 and 53.7% had a cerclage. There were 20.7% growth restricted fetuses and 5.6% still births among the triplets. The mean birthweight among the live born neonates was 1.5 kg, and birthweight discordancy of >25% was seen in 14%. Among the live born neonates, 80% required admission to the neonatal intensive care unit, 11% had culture positive sepsis, 3% had bronchopulmonary dysplasia, and 4% died during the hospital stay. None of them had periventricular leukomalacia or retinopathy requiring LASER. Mothers in the spontaneous conception group were younger and had more monochorionic triamniotic pregnancies than in the assisted conception groups (11.8 vs. 2.9%, p = 0.001). The incidence of PPROM was significantly more in the spontaneous conception group than in the ovulation induction, intrauterine insemination groups (29.4 vs. 2.9%, p = 0.03), we do not have an explanation for this. There was no difference in the other maternal, fetal or neonatal parameters based on the mode of conception.
CONCLUSION
Though triplet pregnancies are encountered infrequently, obstetricians should be familiar with their management. Appropriate antenatal, perinatal care with neonatal support can result in optimal outcome.
|
10.1007/s13224-017-1002-7
|
pubmed_409_20224
|
OBJECTIVE
to determine the effect of alternative regimens of nasal steroid administration on symptoms and quality of life.
DESIGN
randomized, double-blind, parallel-group comparison.
SUBJECTS
sixty ragweed-sensitive adults recruited from participants of previous studies and through media advertising.
INTERVENTIONS
200 micrograms of aqueous beclomethasone diproprionate nasal spray, twice daily, from 1 week before until 1 week after the ragweed-pollen season (regular) or 100 micrograms of the spray, taken as required, up to 400 micrograms daily; troublesome nasal symptoms were treated, in both groups, by increasing the daily dose to 800 micrograms until symptoms were controlled. If this treatment was insufficient, 120 mg of terfenadine, daily, was added.
RESULTS
One subject in the "as required"-treated group withdrew with uncontrolled nasal symptoms. In the remaining subjects, sneezing, stuffy nose, and rhinorrhea, measured by a daily diary, were significantly better controlled in the regular-treated group (p less than 0.025). Impairment of quality of life, including sleep disturbance, nonhay fever symptoms, practical problems, and uncomfortable emotions were greater in the as required-treated group (p less than 0.001). Subjects in the regular-treated group required less additional terfenadine (0.27 tablets per subject versus 1.40; p = 0.022). Eye symptoms and eye-drop use were similar in the two treated groups.
CONCLUSION
In patients with seasonal allergic rhinitis, regular use of inhaled steroids results in fewer symptoms and better quality of life than when the spray is taken only as required.
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10.1016/s0091-6749(05)80101-0
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pubmed_466_5316
|
In adult inbred rats of the AVN strain, branches of the crural interosseous nerve were dissected out from donors and transplanted into the brain of recipients, together with a cluster of Pacinian corpuscles, (either into a suction cavity or the cerebral cortex) into a slit 1-2 mm deep. The grafts were fixed and processed for electron microscopy 10 days to 6 months after the operation, and their ultrastructure was examined. Sporadic axons of small diameter grew into the nerve branches of some of the grafts from 11 days onward, and became myelinated during the 2nd month after the operation, but none of the transplanted Pacinian corpuscles became reinnervated. The corpuscles, however, survived denervation and grafting. Most of them retained a well-preserved inner core and an intact capsule, consisting of a normal complement of 29.2 +/- 1.0 (mean +/- SE) capsular layers (n = 8), as did the corpuscles previously examined after denervation in situ. Some of the corpuscles underwent degenerative changes, presumably due to a delayed or restricted revascularization. In this group of corpuscles, the inner core underwent disintegration and was gradually replaced by collagen fibrils, whereas the capsule remained preserved but the number of its layers eventually reduced by 40%. It is assumed that the lack of reinnervation of the grafted Pacinian corpuscles was due to the paucity of regenerating axons, and their failure to form correct projections along those Schwann cell columns connected with the corpuscles.
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10.1007/BF00688310
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pubmed_1135_2083
|
The p53 tumour suppressor gene plays an important role in angiogenesis and apoptosis. The association between Arg72Pro polymorphism and recurrent pregnancy loss (RPL) has been studied but with inconsistent results. A meta-analysis was conducted to examine whether p53 Arg72Pro polymorphism is a risk factor for RPL. Electronic searches of PubMed, Embase and Web of Knowledge were conducted to identify relevant studies. The final meta-analysis included six published articles with 730 RPL cases and 613 controls. The pooled results suggested that the variant genotype was associated with the RPL risk in additive model (Pro versus Arg; odds ratio [OR] = 1.28; 95% confidence interval [CI]: 1.06 to 1.54) and recessive model (Pro/Pro versus Arg/Pro + Arg/Arg; OR = 1.82; 95% CI: 1.21 to 2.73). In the stratified analysis by ethnicity, for white people the results were consistent. The Egger's regression asymmetry test suggested a lack of publication bias. Results of this meta-analysis suggest that p53 codon 72 polymorphism is associated with RPL, especially in white people. Identification of p53 codon 72 mutation would have some implication for primary prevention of RPL and screening of high-risk individuals. Large well-designed studies are needed to fully describe the association between this polymorphism and RPL.
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pubmed_1135_2083
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pubmed_660_5555
|
The ability of the radiomimetic anti-tumor enediyne C-1027 to induce DNA inter-strand crosslinks (ICLs), in addition to the expected DNA strand breaks, is unique among traditional DNA targeted cancer therapies. Importantly, radiation therapy and most radiomimetic drugs have diminished effect in hypoxic environments due to decreased induction of DNA strand breaks, which is an oxygen requiring process. However, C-1027's induction of ICLs is enhanced under hypoxia and it is actually more potent against hypoxic cells, overcoming this common tumor resistance mechanism. In this study, an analog of C-1027, 20'-deschloro-C-1027 was examined for its ability to induce DNA ICLs under hypoxic conditions. Deschloro-induced ICLs were detected under hypoxic cell-free conditions, with a concomitant reduction in the induction of DNA strand breaks. In cells deschloro behaved similarly, inducing cellular ICLs under hypoxic conditions with a reduction in DNA breaks. The cytotoxicity of deschloro treatment was similar in normoxic and hypoxic cells, suggesting that the ICL induction allows deschloro to retain its cytotoxic activity under hypoxia. It appears that rational engineering of the C-1027 family of radiomimetics holds promise toward overcoming the radioresistance associated with the hypoxic environment associated with solid tumors.
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pubmed_660_5555
|
pubmed_597_4869
|
We describe our experience in five cases of endovascular treatment for complex intracranial aneurysms. The senior author (ZW) has clinical experience with more than 6000 cases of brain aneurysms treated with endovascular techniques. Multiple endovascular therapies, such as treatment with Onyx, parent vessel occlusion, stent-assisted coiling, covered stent, can be used in an attempt to provide a solution to various clinical dilemmas associated with the management of these difficult lesions. Here, we focus on the latest five patients and lessons learnt in endovascular techniques for complex intracranial aneurysms.On the basis of the knowledge obtained over the years, multimodality endovascular techniques should be re-evaluated to improve patient outcomes.
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10.1177/197140091002300417
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pubmed_89_15310
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Our purpose with this study was to analyze construct validity evidence for the Motor Coordination Test with Ball (MCTB). Our participant sample included 1620 students (741 girls; 879 boys) aged between 10-12 years. Evidence for construct-validity of the four tasks using exploratory factor analysis (EFA) and adequacy indices confirmed a good fit of a final two-dimensional model (BTS = .000; KMO = .83; loading .53 to .91; communalities ranging from .31 to .86; explained variance of 63.5%; goodness-of-fit index (GFI) = .99; adjusted GFI (AGFI) = .97; RMSR = .03), and confirmatory factor analysis (CFA) (X2/df = 4.9; GFI = .97; comparative fit index (CFI) = .92; TLI = .90; Root-Mean-Square Error of Aproximation (RMSEA) = .03). We concluded that, in a Brazilian sample, the MCTB has good construct validity for motor coordination tests with balls; this helps qualify this test for use in schools and in the sports context.
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10.1177/00315125221098318
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pubmed_149_25517
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Streptococcus pneumoniae has a complex cell wall that plays key roles in cell shape maintenance, growth and cell division, and interactions with components of the human host. The peptidoglycan has a heterogeneous composition with more than 50 subunits (muropeptides)-products of several peptidoglycan-modifying enzymes. The amidation of glutamate residues in the stem peptide is needed for efficient peptide cross-linking, and peptides with a dipeptide branch prevail in some beta-lactam-resistant strains. The glycan strands are modified by deacetylation of N-acetylglucosamine residues and O-acetylation of N-acetylmuramic acid residues, and both modifications contribute to pneumococcal resistance to lysozyme. The glycan strands carry covalently attached wall teichoic acid and capsular polysaccharide. Pneumococci are unique in that the wall teichoic acid and lipoteichoic acid contain the same unusually complex repeating units decorated with phosphoryl choline residues, which anchor the choline-binding proteins. The structures of lipoteichoic acid and the attachment site of wall teichoic acid to peptidoglycan have recently been revised. During growth, pneumococci assemble their cell walls at midcell in coordinated rounds of cell elongation and division, leading to the typical ovococcal cell shape. Cell wall growth depends on the cytoskeletal FtsA and FtsZ proteins and is regulated by several morphogenesis proteins that also show patterns of dynamic localization at midcell. Some of the key regulators are phosphorylated by StkP and dephosphorylated by PhpP to facilitate robust selection of the division site and plane and to maintain cell shape.
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10.1128/microbiolspec.GPP3-0018-2018
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pubmed_904_14183
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Delta-granule platelet storage pool deficiency (δ-PSPD) is a qualitative platelet function defect associated with variable bleeding phenotypes. Platelet electron microscopy (EM) is commonly utilized to evaluate for δ-PSPD, but intrapatient variability in platelet δ-granule numbers by EM is currently unknown. Fifteen young women aged 11 to 17 years presenting to a young women's hematology clinic for the evaluation of heavy menstrual bleeding underwent platelet EM testing at their initial hematology clinic visit and at 1 and 3 months later. Platelet aggregation of platelet-rich plasma by light transmission was also performed on all patients at their initial visit. Eight patients had average δ-granules per platelet consistently ≥2. Three patients were found to have average δ-granules per platelet <2 on initial testing, 2 of which reverted to ≥2 on subsequent testing. When initial average δ-granules per platelet was ≥2, initial repeat testing remained so in 83% (95% confidence interval [CI], 52%-98%) of cases and subsequent repeat testing remained so in 75% (95% CI, 43%-95%) of the cases. Platelet aggregation testing was abnormal in 53% of patients, and there was no apparent correlation between platelet EM findings and platelet aggregation testing. In this small group of young women presenting for the evaluation of bleeding symptoms, we found that almost half of the patients had substantial variability in platelet EM results. Given other identified limitations in platelet EM testing, and the intrapatient variability identified in this study, providers should use caution in utilizing EM in isolation to diagnose δ-PSPD.
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10.1177/1093526618803838
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pubmed_670_364
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In the silver fox, as in its wild ancestor, the red fox (Vulpes vulpes L.), the annual growing phase (anagen) of guard hair follicles occupies at least four months. Severe damage to the hair coat near the end of this growing period was reported in 1985 on many ranches in New Brunswick and Nova Scotia. A histological analysis of serial sections of skin biopsies showed a marked increase in nuclear aberrations in the hair matrix of anagen guard hair follicles. These nuclear aberrations indicated that cells were undergoing apoptosis, a controlled form of cell death. Tissues from affected and unaffected foxes for histological and toxicological analysis, as well as other data, were obtained during visits to 26 ranches in 1986 and 34 ranches in 1987. Histological sections of the 1987 skin samples showed the mean percentage of nuclear aberrations in 43 unaffected foxes to be 0.08 +/- 0.01 (SEM), while that for 49 affected foxes was 0.51 +/- 0.23. The four foxes with the most severe coat damage also had the highest incidences of guard hair matrix cells with nuclear aberrations, ranging from 20 to 100 times greater than the mean for unaffected foxes. The mitotic index of the hair matrix, which normally remains fairly constant during the hair growth phase, was similar for unaffected and affected foxes (1.83 +/- 0.06 and 1.97 +/- 0.07 respectively). Although our analyses of field data have not established a specific environmental factor associated with increased nuclear aberrations, the possible involvement of toxic agents in follicle damage may warrant further investigation.
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pubmed_670_364
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pubmed_623_23044
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BACKGROUND
Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania.
MATERIALS AND METHODS
Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values.
PRINCIPAL FINDINGS
Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001).
CONCLUSION/SIGNIFICANCE
The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with these characteristics.
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10.1371/journal.pntd.0005002
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pubmed_454_11575
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There are many medications presently available for management of Parkinson's disease. Levodopa is the most effective one. Pharmacotherapeutic efficacy of some forms of drug is not similar due to differences in composition (inactive ingredients, excipients, preservatives, colorants). Authors carried out an open labeled comparative study of pharmacotherapeutic efficacy of the original drug -- nakom and the generic one -- tidomed (both drugs include levodopa and carbidopa). The improvement as assessed by the UPDRS-3 was seen in patients receiving nakom de novo. The significant reduction of motor deficit and increase of daily activity and duration of action of a single dose were noted in patients with motor fluctuations treated with nakom.
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pubmed_454_11575
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pubmed_35_10385
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In central nervous system neurons L-type Ca2+ channels are involved in developmental processes, the integration and conduction of postsynaptic electric activity and synaptic plasticity. However, little is known about the channel isoforms underlying each of these functions or about the exact localization and targeting properties of the major L-type channel isoform alpha1C (CaV1.2) in neurons. We addressed these questions using high-resolution immunofluorescence analysis of the endogenous alpha1C and epitope-tagged recombinant channel isoforms expressed in mouse hippocampal neurons. Endogenous alpha1C and surface-expressed hemagglutinin (HA)-tagged alpha1C-HA were localized in small clusters distributed between the axon initial segment and the apical branches of the dendritic tree. The average cluster size was estimated to be eight channels per alpha1C-HA cluster. Analysis of the subcellular localization of alpha1C-HA clusters relative to known synaptic markers suggested the existence of two distinct populations of alpha1C clusters, extrasynaptic and synaptic, the latter associated with glutamatergic synapses in dendritic spines. Both glutamatergic and GABAergic neurons expressed alpha1C in the soma and dendrites. In contrast to the N-type channel GFP-alpha1B, GFP-alpha1C was excluded from distal axons and nerve terminals of mature neurons. In developing neurons, however, alpha1C and alpha1C-HA were robustly expressed in the growth cone, indicating that specific targeting properties of neuronal compartments change during differentiation. Synaptic and extrasynaptic localizations of alpha1C correspond to putative roles of L-type Ca2+ currents in synaptic modulation and in the propagation of dendritic Ca2+ spikes, respectively. The transiently expressed alpha1C in the growth cone may be involved in neurite extension and axonal pathfinding.
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10.1111/j.0953-816X.2004.03272.x
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pubmed_889_11518
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Background: Clostridium difficile infection (CDI) is prevalent in healthcare settings. The emergence of hypervirulent and antibiotic resistant strains has led to an increase in CDI incidence and frequent outbreaks. While the main virulence factors are the TcdA and TcdB toxins, antibiotic resistance is thought to play a key role in the infection by and dissemination of C. difficile. Methods: A CDI outbreak involving 12 patients was detected in a tertiary care hospital, in Lisbon, which extended from January to July, with a peak in February, in 2016. The C. difficile isolates, obtained from anaerobic culture of stool samples, were subjected to antimicrobial susceptibility testing with Etest®strips against 11 antibiotics, determination of toxin genes profile, PCR-ribotyping, multilocus variable-number tandem-repeat analysis (MLVA) and whole genome sequencing (WGS). Results: Of the 12 CDI cases detected, 11 isolates from 11 patients were characterized. All isolates were tcdA -/tcdB + and belonged to ribotype 017, and showed high level resistance to clindamycin, erythromycin, gentamicin, imipenem, moxifloxacin, rifampicin and tetracycline. The isolates belonged to four genetically related MLVA types, with six isolates forming a clonal cluster. Three outbreak isolates, each from a different MLVA type, were selected for WGS. Bioinformatics analysis showed the presence of several antibiotic resistance determinants, including the Thr82Ile substitution in gyrA, conferring moxifloxacin resistance, the substitutions His502Asn and Arg505Lys in rpoB for rifampicin resistance, the tetM gene, associated with tetracycline resistance, and two genes encoding putative aminoglycoside-modifying enzymes, aadE and aac(6')-aph(2″). Furthermore, a not previously described 61.3 kb putative mobile element was identified, presenting a mosaic structure and containing the genes ermG, mefA/msrD and vat, associated with macrolide, lincosamide and streptogramins resistance. A substitution found in a class B penicillin-binding protein, Cys721Ser, is thought to contribute to imipenem resistance. Conclusion: We describe an epidemic, tcdA -/tcdB +, multidrug resistant clone of C. difficile from ribotype 017 associated with a hospital outbreak, providing further evidence that the lack of TcdA does not impair the infectious potential of these strains. We identified several determinants of antimicrobial resistance, including new ones located in mobile elements, highlighting the importance of horizontal gene transfer in the pathogenicity and epidemiological success of C. difficile.
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10.3389/fmicb.2018.02994
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pubmed_499_8498
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Late-onset Alzheimer's disease (AD) is associated with sleep-related phenotypes (SRPs). The fact that whether they share a common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross-phenotype association study (CPASSOC), transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD (N = 455,258) and summary-level data for seven SRPs (sample size ranges from 359,916 to 1,331,010). AD shared a strong genetic basis with insomnia (r g = 0.20; p = 9.70 × 10-5), snoring (r g = 0.13; p = 2.45 × 10-3), and sleep duration (r g = -0.11; p = 1.18 × 10-3). The CPASSOC identifies 31 independent loci shared between AD and SRPs, including four novel shared loci. Functional analysis and the TWAS showed shared genes were enriched in liver, brain, breast, and heart tissues and highlighted the regulatory roles of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich lipoprotein particle clearance, chylomicron remnant clearance, and positive regulation of T-cell-mediated cytotoxicity pathways. Protein-protein interaction analysis identified three potential drug target genes (APOE, MARK4, and HLA-DRA) that interacted with known FDA-approved drug target genes. The CPASSOC and TWAS demonstrated three regions 11p11.2, 6p22.3, and 16p11.2 may account for the shared basis between AD and sleep duration or snoring. MR showed insomnia had a causal effect on AD (ORIVW = 1.02, P IVW = 6.7 × 10-6), and multivariate MR suggested a potential role of sleep duration and major depression in this association. Our findings provide strong evidence of shared genetics and causation between AD and sleep abnormalities and advance our understanding of the genetic overlap between them. Identifying shared drug targets and molecular pathways can be beneficial for treating AD and sleep disorders more efficiently.
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10.3389/fgene.2022.794202
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pubmed_129_13087
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The fate of DNA injected into in vitro fertilized eggs of Xenopus laevis during subsequent early embryogenesis was investigated by changing the time period and the area of injection. Form I/II plasmid DNA was found to be preferentially replicated in embryos which had been injected 60-65 min after fertilization into the animal half of the fertilized egg, irrespective of the presence of a eukaryotic origin of replication sequence element in the DNA probe used for injection. In the experiments where plasmid DNA and lambda-DNA were coinjected, only the latter was actively replicated, which suggests an inhibitory activity of this DNA on replication of coinjected plasmid DNA.
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10.1016/0922-3371(90)90075-8
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pubmed_1103_22677
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BACKGROUND AND PURPOSE
Despite ongoing clinical suspicion regarding the relationship between sacroiliac joint (SIJ) dysfunction and lower extremity symptoms, there is a paucity of scientific literature addressing this topic. The purpose of this study was to describe patterns of contrast extravasation during SIJ arthrography and postarthrography CT in patients with lower back pain and to determine whether there are pathways of communication between the SIJ and nearby neural structures.
METHODS
Fluoroscopically guided SIJ arthrography was performed on 76 SIJs. After the injection of contrast medium, anteroposterior, lateral, and oblique radiographs as well as 5-mm contiguous axial and direct coronal CT images were obtained. Contrast extravasation patterns were recorded for each joint. These observations included a search for contrast extravasation from the SIJ that contacted nearby lumbosacral nerve roots or structures of the plexus.
RESULTS
Sixty-one percent of all joints studied revealed one of five contrast extravasation patterns. Three of these observed patterns show a pathway of communication between the SIJ and nearby neural structures. These included posterior extravasation into the dorsal sacral foramina, superior recess extravasation at the sacral alar level to the fifth lumbar epiradicular sheath, and ventral extravasation to the lumbosacral plexus.
CONCLUSION
Three pathways between the SIJ and neural structures exist.
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pubmed_1103_22677
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pubmed_108_24050
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Hunter, JR, Gordon, BA, Bird, SR, and Benson, AC. Exercise supervision is important for cardiometabolic health improvements: a 16-week randomized controlled trial. J Strength Cond Res 34(3): 866-877, 2020-Exercise supervision enhances health and fitness improvements in clinical populations compared with unsupervised or home-based exercise, but effects of supervision type are unknown in healthy employees. Eighty-five Australian university employees (62 females; mean ± SD 43.2 ± 9.8 years) were randomized to personal (1:1; SUP, n = 28), nonpersonal (typical gym-based; NPS, n = 28) supervision or unsupervised control (CON, n = 29) exercise groups. Subjects received a 16-week individually tailored, moderate-to-high intensity aerobic and resistance exercise program completed at an onsite exercise facility (SUP and NPS) or without access to a specific exercise facility (CON). Repeated-measures ANOVA analyzed changes to cardiometabolic outcomes. Mean ± SD increases to V[Combining Dot Above]O2 peak were greater (p < 0.01) with SUP (+10.4 ± 11.1%) vs. CON (+3.8 ± 8.9%) but not different to NPS (+8.6 ± 8.2%). Compared to CON (+1.7 ± 7.7%), upper-body strength increases were greater with SUP (+12.8 ± 8.4%; p < 0.001) and NPS (+8.4 ± 7.3%; p < 0.05). Lower-body strength increases were greater with SUP (+26.3 ± 12.7%) vs. NPS (+15.0 ± 14.6%; p < 0.05) and CON (+4.1 ± 12.4%; p < 0.001), and NPS vs. CON (p < 0.01). Body fat reductions were greater with SUP (-2.2 ± 2.2%) vs. NPS (-0.6 ± 1.9%; p < 0.05) and CON (-0.7 ± 1.9%; p < 0.05). Access to an onsite exercise facility with personal or nonpersonal exercise supervision was important for improving several cardiometabolic outcomes, with greater improvements to lower-body strength and body composition from personal 1:1 exercise supervision.
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10.1519/JSC.0000000000002980
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pubmed_878_2297
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Somatic embryogenesis was obtained from hypocotyls and cotyledons of one month old plantlets of Picea abies. Embryogenic yield was higher with expiants from somatic embryo-derived plantlets (80 %) than with plantlets issued from zygotic embryos (10 %). This report also describes production of embryogenic calli from needles of 14 month old somatic embryo-derived plants cultivated in greenhouse. The influence of the physiological status and genotype of the mother plant on somatic embryogenic potential is discussed.
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10.1007/BF00233093
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pubmed_642_15242
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Xueshuantong capsule (XST) is a patented traditional Chinese medicine used for the prevention and treatment of thrombosis. The molecular mechanism of anti-thrombotic effect of XST was investigated through the cross-talk among the platelets/leukocytes, endothelial cells (ECs), and flow shear stress. The Bioflux 1000 system was used to generate two levels of shear stress conditions: 0.1 and 0.9 Pa. Bioflux Metamorph microscopic imaging system was used to analyze the adhesion cell numbers. Protein expressions were detected by western blotting and flow cytometry. The flow-cytometry results showed that under 0.1 Pa flow, XST decreased ADP induced platelets CD62p surface expression in a concentration-dependent manner. Under 0.9 Pa flow, XST at a concentration of 0.15 g⋅L-1 reduced the platelets activation by 29.5%, and aspirin (ASA) showed no inhibitory effects. XST showed similar efficiency on monocytes adhesion both under 0.1 and 0.9 Pa flow conditions, and the inhibition rate was 30.2 and 28.3%, respectively. Under 0.9 Pa flow, the anti-adhesive effects of XST might be associated with the suppression of VE-cadherin and Cx43 in HUVECs. Blood flow not only acts as a drug transporter, but also exerts its effects to influence the pharmacodynamics of XST. Effects of XST on inhibiting platelets activation and suppressing platelets/leukocytes adhesion to injured ECs are not only concentration-dependent, but also shear stress-dependent. The mechanic forces combined with traditional Chinese medicine may be used as a precise treatment for cardiovascular diseases.
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10.3389/fphar.2019.00035
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pubmed_124_8097
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In aged animals the content of 5'-methylcytosine (m5C) in total thymus DNA (1,29 mol.%) and heart muscle (1,10 mol.%) is decreased by 30 and 40%, respectively as compared to that in the 8-months-old embryos. No differences in the GC-content and reassociation kinetics of these DNAs have been revealed. Consequently, the age differences in the m5C content are caused by the decrease in DNA methylation upon ageing. The degree of DNA methylation in various organs (thymus, heart) is different. Upon ageing the degree of genome methylation is decreased and the pattern of methylation is changed: the m5C content is decreased in the repeated sequences and remains practically unchanged in the unique ones. The level of methylation in thymus DNA of moderately (C0t = 4--400) and highly (C0t less than 4) repeated sequences is thereby decreased almost in the same degree. In heart DNA of aged cows the hypomethylation of highly repeated sequences is more pronounced as compared to the moderately repeated ones. The age- and tissue-specific decrease of DNA methylation is regarded as a possible mechanism responsible for the decrease of transcription and functional activity of the cells upon ageing.
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pubmed_124_8097
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pubmed_556_1144
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The long-run effect of the synergy between natural resource consumption and environmental sustainability varies across countries depending on the economic structure. However, the transboundary effect of natural resource capital underscores the importance of environmental convergence. Here, we map ecological performance, biocapacity, and carbon footprint of nations. We assess the socio-economic drivers of environmental performance and convergence using novel cross-country time series techniques. We find that the expansion of biocapacity of nations has an ameliorating effect on ecological performance. The hotspot countries of environmental performance include Australia, Brazil, China, Germany, India, Japan, Russia, and the US. We confirm the existence of environmental convergence across nations - implying that the disparity in carbon and ecological footprint between higher-income and lower-income countries will converge in the long-run. This accentuates the need for global partnership towards achieving environmental sustainability.
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10.1016/j.scitotenv.2020.141912
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pubmed_1115_8936
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Premature infants undergo intensive growth during the postnatal period. Adequate mineralization is dependent on sufficient intake of calcium (Ca) and phosphorus (P). However, Ca and P supplementation can be associated with some risks, for example development of nephrocalcinosis. We investigated pathophysiological risk factors in premature very low birth weight (VLBW) infants associated with the development of nephrocalcinosis. From June 1994 to September 1995 all preterm neonates with a birth weight below 1,500 g were screened prospectively. At regular intervals of 2 weeks, ultrasonography (US) of the kidneys was performed and parameters of mineral metabolism were assessed in blood and spot urine samples. For analysis, premature infants with nephrocalcinosis (group N) were compared with infants without nephrocalcinosis (group R) and with a retrospectively pair-matched subgroup of premature infants without nephrocalcinosis (control group C) taken from the same study. Nephrocalcinosis was detected in 20 of 114 preterm neonates (group N, 17.5%). Of these 20 infants with nephrocalcinosis, 16 presented with a tendency towards systemic acidosis (pH<7.25) on day 2-7, compared with only 4 of 20 premature infants of the control group. Premature infants of group N had a lower serum P at 2 weeks of life and 5 (versus 0 patients of the control group C) had transient hypophosphatemia (serum P<1.6 mmol/l). Moreover, the Ca/creatinine ratio in spot urine specimens tended to be higher (P<0.1) in patients developing nephrocalcinosis. There were no significant differences in the duration of ventilation, the length of stay in the intensive care unit, and duration and frequency of furosemide and steroid treatment between the groups N and C. VLBW premature infants developing nephrocalcinosis frequently presented with slightly impaired acid-base homoeostasis within the 1st week, followed by signs of impaired mineralization (and immature or impaired renal function) within 2 weeks. In VLBW premature infants, close observation of acid-base status and regular analysis of spot urine specimens (Ca, P, creatinine) during the first weeks of life may help to identify those premature infants at risk for nephrocalcinosis.
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10.1007/s00467-004-1428-x
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pubmed_1051_7498
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BACKGROUND
Acute heart failure patients are often encountered in emergency departments (ED) from 11% to 57% using emergency medical services (EMS). Our aim was to evaluate the association of EMS use with acute heart failure patients' ED management and short-term outcomes.
METHODS
This was a sub-analysis of a European EURODEM study. Data on patients presenting with dyspnoea were collected prospectively from European EDs. Patients with ED diagnosis of acute heart failure were categorized into two groups: those using EMS and those self-presenting (non- EMS). The independent association between EMS use and 30-day mortality was evaluated with logistic regression.
RESULTS
Of the 500 acute heart failure patients, with information about the arrival mode to the ED, 309 (61.8%) arrived by EMS. These patients were older (median age 80 vs. 75 years, p < 0.001), more often female (56.4% vs. 42.1%, p = 0.002) and had more dementia (18.7% vs. 7.2%, p < 0.001). On admission, EMS patients had more often confusion (14.2% vs. 2.1%, p < 0.001) and higher respiratory rate (24/min vs. 21/min, p = 0.014; respiratory rate > 30/min in 17.1% patients vs. 7.5%, p = 0.005). The only difference in ED management appeared in the use of ventilatory support: 78.3% of EMS patients vs. 67.5% of non- EMS patients received supplementary oxygen (p = 0.007), and non-invasive ventilation was administered to 12.5% of EMS patients vs. 4.2% non- EMS patients (p = 0.002). EMS patients were more often hospitalized (82.4% vs. 65.9%, p < 0.001), had higher in-hospital mortality (8.7% vs. 3.1%, p = 0.014) and 30-day mortality (14.3% vs. 4.9%, p < 0.001). The use of EMS was an independent predictor of 30-day mortality (OR = 2.54, 95% CI 1.11-5.81, p = 0.027).
CONCLUSION
Most acute heart failure patients arrive at ED by EMS. These patients suffer from more severe respiratory distress and receive more often ventilatory support. EMS use is an independent predictor of 30-day mortality.
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10.1186/s12873-022-00574-z
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pubmed_350_1124
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Vasopressin causes relaxations of isolated basilar and left circumflex coronary arteries of the dog. After removal of the endothelium the inhibitory effect of vasopressin is abolished in the basilar and reduced in the coronary arteries. By contrast, vasopressin causes contractions of femoral arteries, which are not affected by the removal of endothelium. Indomethacin, nordihydroguaiaretic acid, atropine, propranolol and cimetidine do not reduce the inhibitory effect of vasopressin in basilar arteries. However, the V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP blocks the vasopressin-induced relaxations, indicating that the effect of the hormone on the endothelium is mediated by activation of specific V1-vasopressinergic receptors.
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pubmed_350_1124
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pubmed_975_20712
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Paraffin sections were obtained of human fetal, adult, and pathological lung (pulmonary fibrosis after radiotherapy or chemotherapy). The localization of epithelial adhesion molecules E-cadherin and Ep-CAM (former epithelial surface 40 kDa glycoprotein) was investigated by immunoperoxidase and/or immunofluorescence techniques with monoclonal antibodies. During development, the epithelia of the primary pulmonary primordium, the secondary bronchi and the adult bronchial epithelium retained immunoreactivity for E-cadherin and Ep-CAM with lateral immunostaining of cell membranes. In normal adult lungs, Ep-CAM was detected in type I and II alveolar epithelial cells, whereas E-cadherin was confined to the basolateral domain of type II cells. In pulmonary fibrosis, Ep-CAM could be further detected on the cell surface of epithelial remnants. In contrast, E-cadherin expression was characterized by a change of the membrane localization to a spotty, cytoplasmic pattern in the alveolar epithelium, possibly indicating functional inactivation of the protein during fibrogenesis.
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10.1007/BF01457412
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pubmed_835_25475
|
OBJECTIVE
Implantation or replacement of a cardiovascular implantable electronic device (CIED) may be associated with complications, such as pocket hematomas and infections. This study aims to determine whether a lyophilized gentamycin-containing collagen implant (GCCI) reduces major CIED infections and pocket hematomas after implant.
SUBJECTS AND METHODS
A retrospective study was conducted among patients who underwent implantation or replacement of CIED at the Tor Vergata Polyclinic (Rome, Italy) between June 2007 and November 2019. The primary combined endpoint was infection and hematoma occurrence through 12 months of follow-up post-procedure. The rate of single infectious complications, pocket hematomas or both were also assessed.
RESULTS
We compared 475 patients treated with the GCCI (GCCI group) with 714 patients who did not receive it (control group). Complications occurred in 127 patients (11%); a statistically significant reduction of infections and pocket hematomas in the GCCI group was reported when compared with control patients (1% vs. 17%; p<0.0001). A total of 20 (2%) infectious events were reported, 102 (8%) patients developed a pocket hematoma, and 5 (0.4%) had both. The rate of single complications was significantly lower in GCCI group: infection 0.2% vs. 2.6% (p=0.002), pocket hematoma 0.6% vs. 13.8% (p<0.001). The association between antiplatelet/anticoagulation therapy and hematoma development was not statistically significant.
CONCLUSIONS
The GCCI is a medical device that can be used in addition to local hemostasis and prophylactic doses of systemic antibiotics with the aim of reducing infective complications and pocket hematoma after permanent CIED implantation or replacement.
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10.26355/eurrev_202207_29311
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pubmed_980_4681
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We investigated the daily variations in the concentration of atmospheric dioxins (PCDD/Fs and DL-PCBs) in paddy fields after the autumn harvest. The geometric mean of the concentrations of dioxins during the research period was 0.042 pg-TEQ/m3, and the concentrations ranged from 0.0058 to 0.53 pg-TEQ/m3. When the weather was calm with no rain or snow and the atmosphere was stable, relatively high concentrations of dioxins were observed. The characteristics of congeners and homologues produced through the combustion of PCDD/Fs were classified into four groups using principal component analysis and cluster analysis. In addition, agricultural chemicals (pentachlorophenol, PCP and chlornitrofen, CNP) were identified as the source of PCDD/Fs using a Bayesian semifactor model. When the dioxin concentrations were high, the combustion of TeCDFs and PeCDFs produced large emissions, representing the impact of open burning of rice straw. When the dioxin concentrations were low, the contribution of CNP was strong, indicating the effects of the release of previously used agricultural chemicals from the soil.
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10.1016/j.chemosphere.2020.129292
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pubmed_724_10794
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Cotesia vestalis (Haliday) (Hymenoptera: Braconidae) is an endoparasitoid of the larval stage of the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae) and injects a polydnavirus (CvBV) into its host during oviposition. In this paper we characterize CvBV202 and its product. CvBV202 is located on segment S2 of CvBV genome; it has a size of 984 bp and encodes a putative protein of 328 amino acids, including protein phosphatase domain and tyrosine-specific protein phosphatase domain. Gene transcripts were detected in extracts of the host as early as 2 h post-parasitization (p.p.) and continued to be detected for 6 days. Tissue-specific patterns of this gene expression showed that CvBV202 had a close relationship with the host's physiological alternations including immunosuppression, modulation of hormone titer, and nutrition metabolism. The protein was detected in the parasitized hosts at 12 h p.p. using western blot assay. The product of CvBV202 was found to be around 59 kDa, much larger than the predicted molecular weight of 37.8 kDa, suggesting that post-translational modification of CvBV202 occurs in host cells, corresponding with the existence of many post-translational modification sites. Immunofluorescence staining and confocal laser scanning microscopy revealed that CvBV202 and the fused protein eGFP-CvBV202 were observed both in the nuclear region and cytoplasm of the hemocytes of the naturally parasitized host larvae and rBac-eGFP-CvBV202-infected Tn-5B1-4 cells, respectively.
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10.1007/s11262-008-0225-1
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pubmed_958_8153
|
Cells of most of the chronic lymphoid leukemias of the B cell lineage express the CD5 molecule, and this CD5 + B cell subset may be expanded in nonorgan-specific autoimmune diseases. Since autoimmune features are common in lymphoproliferative disorders and the latter be a complication in autoimmune settings, CD5 + B cell may stand at the crossroads of these two conditions. Our hypothesis is, therefore, that there are differences in CD5 + B cells arising during ontogeny ("classical") and those whereby CD5 is induced by various stimuli ("induced"). There is also evidence to support a role for CD5 on B cells, sustaining the proliferation of activated B cells, whereas resting B cells undergo apoptosis.
|
pubmed_958_8153
|
pubmed_616_21097
|
A pillared MOF, [Zn(OBA)(H2DPT)0.5].DMF (TMU-34), based on dihydro tetrazine functionalized pillar spacer (H2DPT=3,6-di(pyridin-4-yl)-1,4-dihydro-1,2,4,5-tetrazine) and V-shape dicarboxylate linker (H2OBA=4,4'-oxybis(benzoic acid)) was synthesized by reflux and ultrasonic methods. The effects of sonication time, initial concentration of reagents and sonication power on size and morphology have been optimized. This MOF has been characterized by scanning electron microscopy, FT-IR spectra, X-ray powder diffraction and N2 adsorption at 77K. Bulk and nano samples of TMU-34 have been applied in cation sensing for detection of Al(III) in presence of other cations (Na(I), Mg(II), Sr(II), Al(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Pb(II), Hg(II),Cr(III), Li(I), Fe(III), K(I)). The results show that nano powder of TMU-34 with uniform separated plate-like morphology (TMU-34-F) has higher detection limit and short response time compared to bulk material. So, in this work we show the application of luminescent metal-organic frameworks synthesized by sonochemistry approach in effective cation detection.
|
10.1016/j.ultsonch.2017.09.009
|
pubmed_835_20800
|
The index case of COVID-19 in Nigeria was in February 2020. The pandemic has resulted in severe social, economic, and public health challenge in Nigeria. Nigeria has experienced pandemic fatigue (PF) characterized by its low testing capacity, poor public adherence to COVID-19 preventive measures, and the urge to return to normal. This viewpoint examines Nigeria's obvious PF amongst Nigerians and believed that community engagement would be a master key to reducing Nigeria's PF and preventing another wave of the pandemic in Nigeria. Community engagement (CE) is a viable way for monitoring the spread of the SARS-CoV-2. CE is cost-effective, improves the chances of people voluntarily presenting themselves for COVID-19 testing at the grass-root level, and could halt the spread of COVID-19 in Nigeria especially with the detection of the delta and omicron variants in Nigeria.
|
10.1177/22799036221107061
|
pubmed_31_6442
|
BACKGROUND
Understanding sexual networks involving acute human immunodeficiency virus (HIV)-1 infections (AHI) may lead to prevention opportunities to mitigate high rates of onward transmission. We evaluated HIV-1 phylogenetic and behavioral characteristics among persons with AHI and their referred partners.
METHODS
Between 2012 and 2014, 46 persons with AHI in Malawi participated in a combined behavioral and biomedical intervention. Participants referred sexual partners by passive referral. Demographics and sexual behaviors were collected through interviews and HIV-1 genetic relationships were assessed with phylogenetics.
RESULTS
Among 45 AHI participants with HIV-1 sequences, none was phylogenetically-linked with another AHI index. There were 19 (42%) AHI participants who referred a single partner that returned for testing. Most partners (n = 17) were HIV-infected, with 15 (88%) presenting with an established infection. There were 14 index-partner pairs that had sequences available; 13 (93%) pairs were phylogenetically-linked dyads. The AHI index was female in 7/13 (54%) dyads. Age-disparate relationships among dyads were common (≥5-year age difference in 67% of dyads), including 3/6 dyads involving a male index and a younger woman. Index participants with a referred partner were more likely to report no casual partners and to be living with their current partner than participants not in dyads.
CONCLUSIONS
Passive-partner referral successfully identified partners with genetically-similar HIV infections-the likely source of infection-but only 40% of index cases referred partners who presented for HIV-1 testing. Future work evaluating assisted partner notification may help reach susceptible partners or more people with untreated HIV-1 infections connected to acute transmission.
CLINICAL TRIALS REGISTRATION
NCT01450189.
|
10.1093/cid/ciy1006
|
pubmed_199_15011
|
A novel carbenicillin-hydrolyzing beta-lactamase has been discovered in a blood isolate of Aeromonas hydrophila. The enzyme resembles plasmid-determined carbenicillinases in substrate profile but differs in isoelectric point (pI 5.9) and molecular weight (22,000) and has been termed AER-1. No evidence for a plasmid location could be obtained in A. hydrophila, but the AER-1 gene and resistance to chloramphenicol, streptomycin, and sulfonamide could be transferred by mobilization with IncP plasmids to Escherichia coli, where the gene cluster inserted at a unique chromosomal site. The linked resistances are similar to those found on multiresistance beta-lactamase transposons, but since insertion of the A. hydrophila gene cluster was site specific and recA+ dependent, the cluster is not a functional transposon.
|
10.1128/AAC.27.4.479
|
pubmed_692_14728
|
The Toll-Like Receptor 2 (TLR2) plays an active and important role in Staphylococcus aureus-induced chronic ocular inflammation. The aim of this study was to investigate the expression and function of TLR2 of corneal stromal cells in ex vivo rabbit model of S. aureus keratitis. Corneal buttons with sclera rims placed in an ex vivo air-interface organ culture were assigned to two groups: corneas with epithelial and stromal abrasions. Each group was then divided into two sub-groups exposed to UV-killed S. aureus ATCC 6538P and S. aureus ATCC 29213, respectively. TLR2 and IL-8 mRNA expressions were analyzed by quantitative real-time RT-PCR. TLR2 localization was visualized by immunofluorescence analysis. The results demonstrated that TLR2 and IL-8 mRNA were significantly expressed in the stromal cells of the groups exposed to S. aureus strains. Moreover, it has been demonstrated that, after corneal injury, keratocytes differentiated into myofibroblasts became able to express TLR2 only when exposed to S. aureus. Identification of mechanisms regulation of corneal TLRs may lead to development of therapeutic interventions aimed at controlling corneal inflammation. This ex vivo model can be used to clarify the molecular events of bacterial-corneal tissue interactions and their inflammatory consequences.
|
10.1111/apm.12333
|
pubmed_857_3073
|
1. The effects of intravenous injections of adenosine agonists and antagonists on pulmonary ventilation were investigated in conscious male Sprague-Dawley rats. 2. Adenosine agonists reduced pulmonary ventilation, whereas an adenosine antagonist increased pulmonary ventilation. 3. The adenosine-induced decrease in ventilation could be partially blocked by pretreatment with either an adenosine or opioid antagonist and completely blocked by a combined pretreatment with adenosine and opioid antagonists. 4. Thus, endogenous adenosine appears to have an inhibitory role in the control of pulmonary ventilation in conscious rats, and the mechanism of action appears to involve both adenosine and opioid receptors.
|
10.1016/0306-3623(93)90172-t
|
pubmed_189_12395
|
OBJECTIVE
Millions of Americans may face hard decisions when it comes to providing nutrition for their loved ones with advanced dementia. This study aimed to ascertain whether there is a difference in feeding tube placement between White and Black patients with advanced dementia and whether this potential difference varied by patient's other demographic and clinical characteristics.
METHOD
This is a retrospective, observational study conducted at Novant Health, a 15-hospital system in the southeastern United States. Data were obtained from Epic systems and included all hospital admissions with a diagnosis of advanced dementia, a total of 21,939, between July 1, 2015, and December 31, 2018. Descriptive statistics and logistics analyses were conducted to assess the relationship between receiving percutaneous endoscopic gastrostomy (PEG) and race, controlling for demographic and clinical characteristics.
RESULTS
Among patients admitted with advanced dementia, the multivariable logistic regression, controlled for age, gender, LOS, palliative care, and vascular etiology showed that Blacks had higher odds of having PEG tubes inserted than White patients (OR 1.97; CI 1.51-2.55; P < 0.001). Patients with longer stays had higher odds of PEG tube insertion. Females had lower odds of PEG tube insertion than males. There was no statistical significance in PEG insertion based on age, etiology, and palliative care consult.
SIGNIFICANCE OF RESULTS
The reasons for the observed higher odds of receiving PEG tubes among Black patients than White patients are likely multifactorial and embedded in a different approach to end-of-life care conversations by providers and caregivers of Black and White patients. Providers may need to be more aware of potential unconscious biases when talking to caregivers, especially in race-discordant relationships, have courageous conversations with caregivers, and be more aware of the importance of keeping in mind families' and caregivers' culture, including spirituality, when making end-of-life decisions.
|
10.1017/S1478951521002042
|
pubmed_839_10170
|
OBJECTIVES
: To investigate the predictive value of electrophysiological measurements including validation of muscle membrane excitability on the development of intensive care unit (ICU)-aquired paresis.
DESIGN
: Prospective observational study.
SETTING
: University ICU.
PATIENTS
: Surgical ICU patients selected upon a simplified acute physiology score > or =20 on three successive days within 1 wk after ICU admission.
INTERVENTIONS
: We performed serial electrophysiological measurements with onset of critical illness including conventional electrophysiological parameters and compound muscle action potentials after direct muscle stimulation (dmCMAP). Patients' awareness and muscle strength were measured sequentially by Ramsay sedation scale and an additional questionnaire and by Medical Research Council score, respectively.
MEASUREMENTS AND MAIN RESULTS
: Among 56 sedated patients 34 patients revealed reduced dmCMAP values <3 mV indicating a myopathic process within 7.5 (5 of 11) days after admission to the ICU. Abnormal dmCMAP anticipated ICU-acquired paresis upon emergence from sedation with a sensitivity and specificity of 83.3% and 88.8%, respectively (positive predictive value of 0.91). Multivariate logistic regression analyses revealed that validating dmCMAP during early course of critical illness had significant diagnostic utility to anticipate ICU-acquired paresis (p = .004; odds ratio = .47; 95% confidence interval = .28-.79).
CONCLUSIONS
: Abnormal dmCMAP occurred within the first week after admission to the ICU and pointed towards a myopathic process as the primary cause of ICU-acquired paresis. Validation of dmCMAP with onset of critical illness allows an early prediction of ICU-acquired paresis and adds important information to clinical estimation of the patients' motor function.
|
10.1097/CCM.0b013e3181a92f28
|
pubmed_954_11217
|
Southern China experienced few cases of H7N9 during the first wave of human infections in the spring of 2013. The second and now the third waves of H7N9 infections have been localized mostly in Southern China with the Guangdong province an epicenter for the generation of novel H7N9 reassortants. Clusters of human infections show human-to-human transmission to be a rare but well-documented event. A recent cluster of infections involving hospital health care workers stresses the importance of care givers utilizing personal protective equipment in treating H7N9 infected or suspected patients.
|
10.3855/jidc.6759
|
pubmed_681_19386
|
AIMS
The aim of this study was to investigate telomerase activity and to assess the correlation between telomerase activity, tumor proliferative activity and p53 overexpression in osteosarcoma tumor samples.
METHODS
Using a telomerase polymerase chain reaction-enzyme-linked immunoassay based on the telomeric repeat amplification protocol method, we examined telomerase activity in 26 primary osteosarcoma specimens. P53 overexpression was identified using immunohistochemical staining, and tumor proliferative activity was assessed by immunohistochemical staining of PCNA.
RESULTS
Telomerase activity was detected at a relatively low level in five of 26 osteosarcoma tissue specimens. P53 was detected in eight of 21 cases. There was no significant correlation between telomerase activity and p53 overexpression (p=0.325). There was a significant correlation between PCNA staining and telomerase activity (p=0.0075).
CONCLUSION
Difference between the telomerase activity and p53 overexpression in osteosarcoma suggests that p53 and telomerase may not cooperate in tumor proliferation. Correlation of telomerase activity to PCNA expression suggests that telomerase activity may also useful for evaluate proliferative activity in osteosarcoma.
|
10.1016/s0748-7983(03)00117-3
|
pubmed_481_4180
|
The relationship between acetylcholine (ACh) efflux in medial prefrontal cortex (mPFC) and performance in a visual discrimination task and a variable interval (VI) schedule of reinforcement was studied in rats. Animals were pretrained in one of the two tasks and then unilaterally implanted with microdialysis guide cannula into the mPFC. Animals were then dialyzed, during 12 min collection intervals, in the operant chambers prior to task onset and during and after task performance. Each animal was dialyzed for a total of four sessions: two standard task sessions, one session in which a houselight was flashed at 0.5 Hz during the third 12 min block, and an extinction session (always the last session) in which reinforcement was withheld during the final three blocks. Response accuracy in the discrimination task was very high (> 95% correct) and stable across the four blocks with a progressive increase in omissions. The flashing houselight did not affect performance whereas the loss of reinforcement led to an increase in omissions. VI performance was associated with a high number of lever presses and a high reward rate that declined over the four blocks. Again, the flashing houselight did not affect VI performance whereas lever pressing declined markedly during the extinction session. ACh efflux did not change, relative to baseline, during performance in either task, or with the presentation of the flashing houselight or the loss of reinforcement. These data contrast with the changes in cortical ACh efflux observed in situations characterized by the presentation of novel stimuli or changing demands on attentional processing and, therefore, assist in the specification of hypotheses on the cognitive functions of cortical ACh.
|
10.1016/s0926-6410(97)00014-1
|
pubmed_282_18946
|
A 68-year-old woman, with a 75-pack-year smoking history and a history of chronic excess alcohol intake, presented with a 5-week history of worsening perianal pain and ulceration. She recently had an inpatient admission with back pain and urinary tract infection during which she developed diarrhea and fecal incontinence. Initially, the perianal ulceration was diagnosed as severe irritant contact dermatitis and treated with barrier creams and topical clobetasone 17-butyrate 0.05% weight for weight, oxytetracycline 3.0% weight for weight and nystatin cream (Trimovate®). Despite this, the ulceration progressed, resulting in hospital readmission 1 month later. There was no history of consumption of nicorandil (an antianginal therapy), of recurrent oral ulcers, or of inflammatory bowel disease. On examination, there were multiple areas of deep, sloughy ulceration bilaterally around the perianal and buttock regions with erythematous and violaceous edges (Figure 1). Complete blood count, blood film, rheumatoid factor, autoimmune and vasculitic profile, hepatitis screen, immunoglobulins and plasma protein electrophoresis were all normal. Punch biopsy revealed scanty dermal perivascular inflammatory cell infiltrate and occasional neutrophils (Figure 2). No evidence of granulomata, dysplasia, malignancy, or Langerhans histiocytes was identified, and periodic acid-Schiff staining was negative.
|
pubmed_282_18946
|
pubmed_939_18306
|
Management of aggressive malignant musculoskeletal tumors is clinically challenging and awaits the identification of regulator(s) that can be therapeutically used to improve patient outcome. Autocrine motility factor (AMF), a secreted cytokine, is known to alter the bone microenvironment by linking to its receptor AMFR (AMF Receptor), leading to tumor progression. It was noted that both the ligand and its receptor belong to the moonlighting family of proteins, as they contribute to intracellular metabolic function such as glycolysis and gluconeogenesis by expressing glucose-6-phosphate isomerase AMF/GPI and higher protein degradation by expressing AMFR/gp78 functioning as ubiquitin ligase activity. Thus, AMF/GPI and AMFR/gp78 contribute to higher metabolic turnover of protein and glucose. Recently, a large-scale cohort study including 23 different histological types of musculoskeletal tumors revealed that patients with osteosarcoma, multiple myeloma, rhabdomyosarcoma, and angiosarcoma tend to express higher levels of AMF, whereas multiple myeloma patients expressed high levels of AMFR. Consistently, the cellular data showed that a variety of musculoskeletal tumors express AMF and components of bone microenvironment express AMFR. Thus, a novel outlook suggests a cellular link and cross-talk between musculoskeletal tumors and the skeletal milieu are regulated by AMF-AMFR signaling. This review will highlight the pharmacological need for AMF and AMFR inhibitors as unmet medical needs for patients with malignant musculoskeletal tumors.
|
10.1016/j.jbo.2020.100318
|
pubmed_1093_20847
|
Thyroid hormone (TH) is a pleiotropic agent that has widespread biological functions, i.e., it controls cellular growth, tissue development and homeostasis and neoplastic transformation. Suitable TH levels are critical for the development of various types of tissues and are essential for the regulation of metabolic processes throughout life. The serum concentrations of TH affect its biological activity. Moreover, at tissue level, TH action is regulated by the expression and activity of deiodinases, i.e., the enzymes that mediate the metabolic pathways by activating and/or inactivating TH. The type I and II deiodinases (D1 and D2) initiate TH action by converting thyroxine (T4) into the active TH form (T3), whereas type III deiodinase (D3) mediates the local attenuation of TH by converting T4 and T3 into the inactive metabolites rT3 and T2, respectively. The deiodinase system is a potent mechanism of pre-receptoral control of TH action; it is often altered in such pathological conditions as cancer. D3 is widely expressed in embryonic tissues and in placenta, where it blocks excessive maternal-to-fetal transfer of TH. In contrast, during late neonatal and adult life, D3 is expressed mainly in the central nervous system and skin. Interestingly, D3 expression is re-activated in various types of human cancers. Here we review recent evidence that D3 expression plays a crucial role in human carcinogenesis, and speculate as to its complex role in the regulation of cell proliferation in several neoplastic contexts. It is conceivable that the local modulation of TH action via deiodinases is a powerful molecular tool to manipulate the intracellular TH status, thus influencing the growth and maintenance of selected hormone-dependent cancers.
|
pubmed_1093_20847
|
pubmed_101_22522
|
WHAT IS KNOWN AND OBJECTIVE
There is limited data on the specific risks of anaphylaxis induced by beta-lactam drugs. The aim of this study was to compare the risks of reporting beta-lactam-induced anaphylaxis using the national pharmacovigilance database of Vietnam (NPDV).
METHODS
The multivariate generalised linear regression model was applied for signal generation and comparison of beta-lactams.
RESULTS
Between 2010 and 2016, there were 2,921 reports of anaphylaxis (19.93%) from 14,655 spontaneous reports of beta-lactam use in the NDPV. Anaphylaxis signal generation was also found for the subgroup J01D (cephalosporins and carbapenems) (ROR = 1.27 [1.16-1.39]) and beta-lactamase-sensitive penicillins (ROR = 1.74 [1.27-2.35]). In the third generation cephalosporin subgroup, different risks were identified for the following combinations of beta-lactams: 1) cefotaxime with cefoperazone+sulbactam; 2) cefixime/cefpodoxime/cefdinir with cefoperazone+sulbactam or ceftizoxime/cefoperazone/ceftazidime/ceftriaxone/cefotaxime. For the second generation cephalosporin subgroup, different risks were found for cefotiam compared to cefmetazole, cefaclor, cefamandole and cefuroxime.
WHAT IS NEW AND CONCLUSION
These findings identified and highlighted the different anaphylactic risks caused by various beta-lactams in the main subgroups.
|
10.1111/jcpt.13376
|
pubmed_1038_5423
|
Group B streptococcus (GBS), a common neonatal gram-positive pathogen, causes similar pathophysiology in human newborns and neonatal animal models of sepsis. Animal models of GBS sepsis demonstrate a two-phase response: 1) an acute phase (less than 1 h) of increased pulmonary artery pressure (Ppa) and reduced arterial oxygen pressure (PaO2) that is associated with increased serum thromboxane B2 (TxB2) and 2) a late phase (2-4 h) of persistently increased Ppa and reduced PaO2, reduced systemic arterial pressure, and progressive fall in cardiac output that is associated with increased serum TxB2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and tumor necrosis factor-alpha (TNF alpha). We hypothesized that pretreatment of piglets with both pentoxifylline (PTF), an inhibitor of TNF alpha production and activity, and indomethacin (INDO) would 1) inhibit GBS-induced TxB2, 6-keto-PGF1 alpha, and TNF alpha and 2) prevent both the acute- and late-phase physiologic responses of GBS sepsis. Combined PTF and INDO pretreatment of anesthetized, mechanically ventilated piglets infused with GBS (1.25 x 10(9) colony forming units/kg/h) for 4 h prevented GBS-induced increases in Ppa at 1 h (GBS + PTF + INDO: 1.8 +/- 0.07 kPa versus GBS alone: 4.7 +/- 0.1 kPa) and markedly attenuated increases in Ppa at 4 h (GBS + PTF + INDO: 2.1 +/- 0.1 kPa versus GBS alone: 4.4 +/- 0.1 kPa).(ABSTRACT TRUNCATED AT 250 WORDS)
|
10.1203/00006450-199203000-00006
|
pubmed_875_24400
|
OBJECTIVE
To determine the usefullness of the PROFUND index to assess the risk of global death after 4 years in polypathological patients.
PATIENTS AND METHODS
Multicenter prospective cohort (Internal Medicine and Geriatrics) study. Polypathological patients admitted between March 1st and June 30th 2011 were included. For each patient, data concerning age, sex, living at home or in a nursing residence, polypathology categories, Charlson, Barthel and Lawton-Brody indexes, Pfeiffer questionnaire, socio-familial Gijon scale, delirium, number of drugs, hemoglobin and creatinine values were gathered, and the PROFUND index was calculated. The follow-up lasted 4 years.
RESULTS
We included 441 patients, 324 from Internal Medicine and 117 from Geriatrics, with a mean age of 80.9 (8.7) years. Of them, 245 (55.6%) were women. Heart (62.7%), neurological (41.4%) and respiratory (37.3%) diseases were the most frequent. Geriatrics inpatients were older and more dependants and presented greater cognitive deterioration. After 4 years, 335 (76%) patients died. Mortality was associated with age, dyspnoea, Barthel index<60, delirium, advanced neoplasia and≥4 admissions in the last year. The area under the curve of the PROFUND index was 0.748, 95% CI 0.689-0.806, P<.001 in Internal Medicine and 0.517, 95% CI 0.369-0.666, P=.818 in Geriatrics patients, respectively.
CONCLUSIONS
The PROFUND index is a reliable tool for predicting long-term global mortality in polypathological patients from Internal Medicine but not from Geriatrics departments.
|
pubmed_875_24400
|
pubmed_242_20605
|
BACKGROUND
To determine patients' preferences for, and understanding of, FRAX® fracture risk conveyed through illustrations.
METHODS
Drawing on examples from published studies, four illustrations of fracture risk were designed and tested for patient preference, ease of understanding, and perceived risk. We enrolled a convenience sample of adults aged 50 and older at two medical clinics located in the Midwestern and Southern United States. In-person structured interviews were conducted to elicit patient ranking of preference, ease of understanding, and perceived risk for each illustration.
RESULTS
Most subjects (n = 142) were female (64%), Caucasian (76%) and college educated (78%). Of the four risk depictions, a plurality of participants (37%) listed a bar graph as most preferred. Subjects felt this illustration used the stoplight color system to display risk levels well and was the most "clear," "clean," and "easy to read". The majority of subjects (52%) rated the pictogram as the most difficult to understand as this format does not allow people to quickly ascertain their individual risk category.
CONCLUSIONS
Communicating risk to patients with illustrations can be done effectively with clearly designed illustrations responsive to patient preference.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01507662.
|
10.1186/s12911-014-0101-y
|
pubmed_436_7872
|
We describe here the pregnancy follow-up and outcome in a patient with Takayasu's arteritis, with a detailed account of the complications during gestation and delivery and the impact of the disease on the newborn's health.
|
10.1590/s0066-782x2008000500013
|
pubmed_110_6334
|
In patients with rheumatoid arthritis according to the criteria of the American Rheumatism Association (ARA) (4) the head of the femur was resected during reconstructive hip joint operation. The area of increased radiological translucence near to the joint space was histologically investigated. The rarefication of the trabecula was found distal of the articular cartilage. In this radiologically translucent area numerous osteoclasts and inflammatory cells could be found.
|
pubmed_110_6334
|
pubmed_581_17698
|
Endoglucanase production by Aspergillus oryzae ATCC 10124 cultivated in rice husks or peanut shells was optimized by experimental design as a function of humidity, time, and temperature. The optimum temperature for the endoglucanase activity was estimated by a univariate analysis (one factor at the time) as 50°C (rice husks) and 60°C (peanut shells), however, by a multivariate analysis (synergism of factors), it was determined a different temperature (56°C) for endoglucanase from peanut shells. For the optimum pH, values determined by univariate and multivariate analysis were 5 and 5.2 (rice husk) and 5 and 7.6 (peanut shells). In addition, the best half-lives were observed at 50°C as 22.8 hr (rice husks) and 7.3 hr (peanut shells), also, 80% of residual activities was obtained between 30 and 50°C for both substrates, and the pH stability was improved at 5-7 (rice hulls) and 6-9 (peanut shells). Both endoglucanases obtained presented different characteristics as a result of the versatility of fungi in different substrates.
|
10.1080/10826068.2017.1365247
|
pubmed_756_13962
|
Amongst the human papillomaviruses (HPVs), the genus Alphapapillomavirus contains HPV types that are uniquely pathogenic. They can be classified into species and types based on genetic distances between viral genomes. Current circulating infectious HPVs constitute a set of viral genomes that have evolved with the rapid expansion of the human population. Viral variants were initially identified through restriction enzyme polymorphisms and more recently through sequence determination of viral fragments. Using partial sequence information, the history of variants, and the association of HPV variants with disease will be discussed with the main focus on the recent utilization of full genome sequence information for variant analyses. The use of multiple sequence alignments of complete viral genomes and phylogenetic analyses have begun to define variant lineages and sublineages using empirically defined differences of 1.0-10.0% and 0.5-1.0%, respectively. These studies provide the basis to define the genetics of HPV pathogenesis.
|
pubmed_756_13962
|
pubmed_810_15883
|
The current clinical application of combination chemotherapy is guided by a historically successful set of practices that were developed by basic and clinical researchers 50-60 years ago. Thus, in order to understand how emerging approaches to drug development might aid the creation of new therapeutic combinations, it is critical to understand the defining principles underlying classic combination therapy and the original experimental rationales behind them. One such principle is that the use of combination therapies with independent mechanisms of action can minimize the evolution of drug resistance. Another is that in order to kill sufficient cancer cells to cure a patient, multiple drugs must be delivered at their maximum tolerated dose - a condition that allows for enhanced cancer cell killing with manageable toxicity. In light of these models, we aim to explore recent genomic evidence underlying the mechanisms of resistance to the combination regimens constructed on these principles. Interestingly, we find that emerging genomic evidence contradicts some of the rationales of early practitioners in developing commonly used drug regimens. However, we also find that the addition of recent targeted therapies has yet to change the current principles underlying the construction of anti-cancer combinatorial regimens, nor have they made substantial inroads into the treatment of most cancers. We suggest that emerging systems/network biology approaches have an immense opportunity to impact the rational development of successful drug regimens. Specifically, by examining drug combinations in multivariate ways, next generation combination therapies can be constructed with a clear understanding of how mechanisms of resistance to multi-drug regimens differ from single agent resistance.
|
pubmed_810_15883
|
pubmed_1089_24970
|
IMPORTANCE
January 2014 marks the 50th anniversary of the first surgeon general's report on smoking and health. This seminal document inspired efforts by governments, nongovernmental organizations, and the private sector to reduce the toll of cigarette smoking through reduced initiation and increased cessation.
OBJECTIVE
To model reductions in smoking-related mortality associated with implementation of tobacco control since 1964.
DESIGN, SETTING, AND PARTICIPANTS
Smoking histories for individual birth cohorts that actually occurred and under likely scenarios had tobacco control never emerged were estimated. National mortality rates and mortality rate ratio estimates from analytical studies of the effect of smoking on mortality yielded death rates by smoking status. Actual smoking-related mortality from 1964 through 2012 was compared with estimated mortality under no tobacco control that included a likely scenario (primary counterfactual) and upper and lower bounds that would capture plausible alternatives.
EXPOSURES
National Health Interview Surveys yielded cigarette smoking histories for the US adult population in 1964-2012.
MAIN OUTCOMES AND MEASURES
Number of premature deaths avoided and years of life saved were primary outcomes. Change in life expectancy at age 40 years associated with change in cigarette smoking exposure constituted another measure of overall health outcomes.
RESULTS
In 1964-2012, an estimated 17.7 million deaths were related to smoking, an estimated 8.0 million (credible range [CR], 7.4-8.3 million, for the lower and upper tobacco control counterfactuals, respectively) fewer premature smoking-related deaths than what would have occurred under the alternatives and thus associated with tobacco control (5.3 million [CR, 4.8-5.5 million] men and 2.7 million [CR, 2.5-2.7 million] women). This resulted in an estimated 157 million years (CR, 139-165 million) of life saved, a mean of 19.6 years for each beneficiary (111 million [CR, 97-117 million] for men, 46 million [CR, 42-48 million] for women). During this time, estimated life expectancy at age 40 years increased 7.8 years for men and 5.4 years for women, of which tobacco control is associated with 2.3 years (CR, 1.8-2.5) (30% [CR, 23%-32%]) of the increase for men and 1.6 years (CR, 1.4-1.7) (29% [CR, 25%-32%]) for women.
CONCLUSIONS AND RELEVANCE
Tobacco control was estimated to be associated with avoidance of 8 million premature deaths and an estimated extended mean life span of 19 to 20 years. Although tobacco control represents an important public health achievement, efforts must continue to reduce the effect of smoking on the nation's death toll.
|
10.1001/jama.2013.285112
|
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