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pubmed_498_4207
|
Kikuchi-Fujimoto disease (KFD) is a rare disease that is clinically manifested mainly by fever and lymphadenopathy. KFD was originally believed to occur primarily in East Asia women, this disease was subsequently described in all ethnic groups worldwide. The important differential diagnostic feature of KFD is the detection of CD123-expressing plasmocytoid dendritic cells (PDCs) in the tissue of the affected lymph node. The standard immunohistochemical staining method has sufficient sensitivity and specificity to detect CD123, but it gives no way of judging the possible phenotypic heterogeneity of cells with CD123 expression.
OBJECTIVE
To identify the phenotypic heterogeneity of CD123-expressing cells in the affected lymph nodes in patients with KFD by a sequential immunoperoxidase labeling and erasing (SIMPLE) method.
MATERIAL AND METHODS
Excision biopsies of lymph nodes were examined in 3 patients with KFD. After an immunohistochemical reaction using a single antibody, the tissue specimen was digitized with a Pannoramic 250 Flash III scanner (3DHISTECH, Hungary), then the cover glass was removed from the section, the specimen was hydrated and placed in a specialized buffer. Then the following primary antibody was applied to the washed tissue specimen and further immunohistochemical reaction and scanning were performed. As a result, each tissue specimen was sequentially stained in reactions with 4 antibodies. The microphotographs of specimens stained in a reaction with anti-CD123 antibody showed positive cells for their identification in the Pannoramic Viewer program (3DHISTECH, Hungary) on the remaining microphotographs displaying the expression of the other 3 markers. The selected fields of view were exported to a JPG format.
RESULTS
Assessing the co-expression of the antigens CD123, MNDA, CD68, and TCL1A detected 4 CD123+ cell subpopulations: No. 1. CD68+/ MNDA+/ TCL1A+; No. 2. CD68+/ MNDA+/ TCL1A-; No. 3. CD68+/ MNDA-/ TCL1A+; No. 4. CD68-/ MNDA-/ TCL1A+.
CONCLUSION
SIMPLE has shown the phenotypic heterogeneity of CD123-positive cells (some of them may be PDCs) and could identify 4 immunophenotypically distinct subpopulations in the affected lymph nodes in patients with KFD. Further investigations are needed to define the role of subpopulations in the pathogenesis of KFD and other diseases.
|
10.17116/patol20218304136
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pubmed_48_19499
|
Parenting styles are robust predictors of offspring outcomes, yet little is known about their neural underpinnings. In this study, 44 parent-adolescent dyads (Mage of adolescent = 12.9) completed a laboratory guessing task while EEG was continuously recorded. In the task, each pair member received feedback about their own monetary wins and losses and also observed the monetary wins and losses of the other member of the pair. We examined the association between self-reported parenting style and parents' electrophysiological responses to watching their adolescent winning and losing money, dubbed the observational Reward Positivity (RewP) and observational feedback negativity (FN), respectively. Self-reported authoritarian parenting predicted reductions in parents' observational RewP but not FN. This predictive relationship remained after adjusting for sex of both participants, parents' responsiveness to their own wins, and parental psychopathology. 'Exploratory analyses found that permissive parenting was associated with a blunting of the adolescents' response to their parents' losses'. These findings suggest that parents' rapid neural responses to their child's successes may relate to the harsh parenting behaviors associated with authoritarian parenting.
|
10.1093/scan/nsw130
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pubmed_580_16262
|
A theory is proposed to relate the elution times of the adsorption front shocks of breakthrough curves recorded during classical dynamic frontal analysis (FA) experiments with selected compounds and their adsorption isotherms in solid/supercritical fluid adsorption systems. The actual density and viscosity of binary mixtures of CO2 and methanol were obtained from the NIST REPPROP software. Diluted solutions of S-naproxen were considered (<2% in mass) but the possible effects of the analyte concentration on the viscosity and the density of the eluent percolating through the column were neglected. This allows the determination of the excess adsorption isotherm (or Gibbs excess isotherm) of the adsorbed analyte in the whole column at constant mass and volumetric flow rate of pure CO2 and of the modifier solution. A local Langmuir adsorption isotherm and a constant saturation capacity were assumed in the calculations. The variation of the adsorption-desorption constant with the eluent density was taken from the experimental variation of the retention factor of S-naproxen on a chiral column packed with Whelk-O1 particles. The results show that the isotherm parameters obtained from the best adjustment of the Langmuir model to the SFC excess adsorption data deviates by less than 7% from the assumed saturation capacity and from the average of the equilibrium constant along the chromatographic column. In practice, this conclusion holds true provided that the precision of the measurement of elution times of front shocks of breakthrough curves is better than 1% and that the maximum surface coverage qexp,max/qS is at least equal to 20%.
|
pubmed_580_16262
|
pubmed_915_9637
|
BACKGROUND
Pediatric cardiomyopathies are a clinically and genetically heterogeneous group of heart muscle disorders associated with high morbidity and mortality. Although knowledge of the genetic basis of pediatric cardiomyopathy has improved considerably, the underlying cause remains elusive in a substantial proportion of cases.
METHODS
Exome sequencing was used to screen for the causative genetic defect in a pair of siblings with rapidly progressive dilated cardiomyopathy and death in early infancy. Protein expression was assessed in patient samples, followed by an in vitro tail-anchored protein insertion assay and functional analyses in zebrafish.
RESULTS
We identified compound heterozygous variants in the highly conserved ASNA1 gene (arsA arsenite transporter, ATP-binding, homolog), which encodes an ATPase required for post-translational membrane insertion of tail-anchored proteins. The c.913C>T variant on the paternal allele is predicted to result in a premature stop codon p.(Gln305*), and likely explains the decreased protein expression observed in myocardial tissue and skin fibroblasts. The c.488T>C variant on the maternal allele results in a valine to alanine substitution at residue 163 (p.Val163Ala). Functional studies showed that this variant leads to protein misfolding as well as less effective tail-anchored protein insertion. Loss of asna1 in zebrafish resulted in reduced cardiac contractility and early lethality. In contrast to wild-type mRNA, injection of either mutant mRNA failed to rescue this phenotype.
CONCLUSIONS
Biallelic variants in ASNA1 cause severe pediatric cardiomyopathy and early death. Our findings point toward a critical role of the tail-anchored membrane protein insertion pathway in vertebrate cardiac function and disease.
|
10.1161/CIRCGEN.119.002507
|
pubmed_518_19610
|
The quantification of phase synchrony between neuronal signals is of crucial importance for the study of large-scale interactions in the brain. Two methods have been used to date in neuroscience, based on two distinct approaches which permit a direct estimation of the instantaneous phase of a signal [Phys. Rev. Lett. 81 (1998) 3291; Human Brain Mapping 8 (1999) 194]. The phase is either estimated by using the analytic concept of Hilbert transform or, alternatively, by convolution with a complex wavelet. In both methods the stability of the instantaneous phase over a window of time requires quantification by means of various statistical dependence parameters (standard deviation, Shannon entropy or mutual information). The purpose of this paper is to conduct a direct comparison between these two methods on three signal sets: (1) neural models; (2) intracranial signals from epileptic patients; and (3) scalp EEG recordings. Levels of synchrony that can be considered as reliable are estimated by using the technique of surrogate data. Our results demonstrate that the differences between the methods are minor, and we conclude that they are fundamentally equivalent for the study of neuroelectrical signals. This offers a common language and framework that can be used for future research in the area of synchronization.
|
10.1016/s0165-0270(01)00372-7
|
pubmed_1069_11536
|
In a prospective study in AIDS patients with chronic diarrhea, the overall prevalence of intestinal cryptosporidiosis was 15.6% (43/275). The prevalence was higher in homosexual patients (33.3%) than in intravenous drug abusers (10.6%) (p < 0.001). Extraintestinal infection was present in 30% (13/43) of the patients with known intestinal cryptosporidiosis. Eight of the 13 (61.5%) patients with extraintestinal cryptosporidiosis had Cryptosporidium in the bile and 7 of 13 (16.28%) had it in the sputum. Of the seven patients with Cryptosporidium in the sputum, four had respiratory symptoms and an abnormal chest radiograph, although another pulmonary pathogen was isolated simultaneously. Two other patients from whom Cryptosporidium was the sole respiratory pathogen isolated had no respiratory symptoms and normal chest radiographs. The seventh patient had pulmonary symptoms, interstitial infiltrate on chest radiograph and excessive activity on a pulmonary Gallium scan; Cryptosporidium was the only organism detected in induced sputum and bronchoalveolar lavage specimens. The mean CD4+ lymphocyte count in patients with extraintestinal cryptosporidiosis was 55 cells/mm3.
|
10.1007/BF01690873
|
pubmed_894_20628
|
Various maturation forms of the plant protein thaumatin were expressed in yeast, using a promoter fragment of the glyceraldehyde- 3P -dehydrogenase (GAPDH) gene. Plasmids encoding preprothaumatin were shown to direct the synthesis of a processed form of the plant protein. The important role of signal sequences in the expression of the plant protein in yeast was indicated by the observation that plasmids encoding processed thaumatin forms were only poorly expressed, if at all. Nucleotide sequence analysis of the 843 nucleotide GAPDH promoter fragment revealed a characteristic structure with two regions of dyad symmetry containing translational starts of GAPDH and a putative 38 amino acid peptide. A promoter fragment from which the upstream region was deleted proved to be less efficient in thaumatin expression.
|
10.1016/0092-8674(84)90394-5
|
pubmed_926_20071
|
Chronic exertional compartment syndrome (CECS) is a rare condition that usually affects distance runners and other running athletes. It is characterized by pain and pressure in one or multiple muscle compartments with repetitive physical activity. Reduction in pain typically occurs with cessation of activity. Evaluation of CECS consists of a thorough history of patient symptoms and ruling out of other causes of symptoms. Post-exercise pressure measurements can help confirm the diagnosis when symptoms are consistent and imaging evaluation negative for other causes. Non-operative treatment is a viable option for hindfoot runners and patients with anterior compartment syndrome of the leg. Limited-incision fasciotomy has been shown to be the most effective treatment and remains the gold standard for treatment. Minimal-incision open fasciotomy and endoscopic fasciotomy have surgical outcomes similar to wide-open fasciotomy. Military patients treated with fasciotomy have higher failure rates compared to civilians. Pediatric patients have similar outcomes compared to adults.
|
10.1080/00913847.2017.1384289
|
pubmed_405_22466
|
The connection between adolescent dating violence (ADV) and substance use is important to consider because of the serious consequences for teens who engage in these behaviors. Although prior research shows that these two health problems are related, the context in which they occur is missing, including when (i.e., the timeline) in the relationship these events occur. To fill this gap, eight sex-specific focus groups were conducted with 39 high school-aged teens, all of whom had experienced prior relationship violence. Adolescents discussed using alcohol and/or drugs at the start of the dating relationship and after the relationship ended as a way to cope with the break-up. Alcohol and drugs were also used throughout to cope with being in an abusive relationship. The intersection of ADV and substance use occurred during instances when both partners were using alcohol and/or drugs, as well as when only one partner was using. These findings provide support for prevention and intervention programs that consider the intersection of ADV and substance use.
|
10.1177/0886260514556768
|
pubmed_962_17230
|
BACKGROUND
Peroxisome proliferator-activated receptor gamma inhibits the growth and induces apoptosis of gastric cancer cells. A common polymorphism at codon 12 of this gene (Pro12Ala) has been shown to confer protection against diabetes and colorectal cancer.
AIM
To study the association between peroxisome proliferator-activated receptor gamma gene polymorphism, Helicobacter pylori infection and gastric cancer in Chinese.
METHODS
One hundred and four consecutive patients with non-cardia gastric adenocarcinoma and 104 matched controls were examined. Peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism.
RESULTS
The frequency of peroxisome proliferator-activated receptor gamma G (Ala12) allele was significantly higher among cancer patients (19.2%) than in control (8.7%; OR 2.5, 95% CI 1.1-5.8). While H. pylori infection was more prevalent in gastric cancer patients (OR 3.0; 95% CI 1.6-5.7), the combination of peroxisome proliferator-activated receptor gamma G allele and H. pylori infection further increased the risk of gastric cancer (OR 12.8, 95% CI 3.2-50.5). The presence of the Ala12 did not increase the risk of gastric cancer in H. pylori-negative subjects.
CONCLUSION
Our study suggests the potential association between peroxisome proliferator-activated receptor gamma polymorphism and H. pylori infection in the development of non-cardia gastric cancer.
|
10.1111/j.1365-2036.2006.02739.x
|
pubmed_994_17277
|
A 'molecular shuttle' is an interlocked molecular assembly in which a macrocyclic ring is able to move back and forth between two recognition sites. This large-amplitude translational motion was first characterized in solution in 1991. Since that report, many mechanically interlocked molecules (MIMs) have been designed, synthesized and shown to mimic the complex functions of macroscopic switches and machines. Here, we show that this fundamental concept-the translational motion of a molecular shuttle-can be organized, initiated and made to operate inside a crystalline, solid-state material. A metal-organic framework (MOF) designated UWDM-4 was prepared that contains a rigid linker that is a molecular shuttle. It was demonstrated by variable-temperature (1)H-(13)C cross-polarization/magic-angle spinning (CP/MAS) and (13)C 2D exchange correlation spectroscopy (EXSY) solid-state NMR at 21.1 T on a (13)C-enriched sample that the macrocyclic ring undergoes rapid shuttling along the rigid axle built between struts of the framework.
|
10.1038/nchem.2258
|
pubmed_682_6606
|
Shortly after completing residency or fellowship, army dermatologists routinely deploy to combat zones as field surgeons. The US Army generally does not deploy dermatologists for their expertise in diagnosing and managing cutaneous diseases; rather, as field surgeons they provide routine, emergency, and trauma care for active-duty soldiers and coalition forces. In this article, we review the various functions of the deployed dermatologist and highlight the importance of maintaining basic emergency medical skills that could be generalized to the civilian population in case of local or national emergencies.
|
pubmed_682_6606
|
pubmed_447_12761
|
This study aimed to demonstrate the role of acetylcholine receptors in the rostral ventrolateral medulla (RVL) in the central regulation of the cardiovascular system in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The effects of cholinergic drugs, microinjected into the rostral ventrolateral medullary vasopressor area, on blood pressure and heart rate in anesthetized and artificially ventilated rats were investigated. Unilateral microinjection of carbachol (1 nmol/site), physostigmine (300 pmol/site) or 3,4-diaminopyridine (500 pmol/site) into the RVL elicited a pressor and tachycardiac response, of which only the pressor response was significantly greater in SHR than in WKY. Bilateral microinjection of atropine (1 nmol/site) caused a depressor and bradycardiac response. The depressor response produced by atropine injected in the RVL was also significantly greater in SHR than in WKY. These results suggest that there are tonic cholinergic mechanisms in the RVL of the rats, which exert an excitatory cardiovascular action, and that the enhanced responsiveness to acetylcholine receptor stimulation in the RVL may contribute to the sustained elevation of blood pressure in the SHR.
|
10.1016/0014-2999(91)90809-5
|
pubmed_249_16750
|
OBJECTIVE
To relate psychological profiles, cerebral asymmetry and the hypothalamus-pituitary-adrenal axis (HPA) reactivity to clinical characteristics of common obesity.
METHODS
Sixty consecutive adult female overweight and obese patients attending the outpatient endocrine department were included in this study. Clinical evaluation specifically selected a priori the following indexes: obesity age of onset, parenthood obesity, carbohydrate craving, binge eating with purging, obesity degree (defined by the body mass index (BMI)--weight (kg)/height (m(2))), body fat distribution (defined by the abdominal--thigh ratio (A/T)) and initial weight loss after medical treatment. Psychological evaluation was performed with the Minnesota Multiphasic Personality Inventory (MMPI). In the last 30 patients, the Edinburgh Inventory of Manual Preference (EIMP) and the corticotrophin-releasing hormone (CRH) test were also performed.
RESULTS
Clinical characteristics defined a priori were independent variables as evaluated by contingency table analysis. Factorial analysis of variance (ANOVA) revealed a significantly different MMPI profile, according to parental obesity, with post-hoc significantly higher scores on the hypochondriasis (Hs), paranoia (Pa), psychasthenia (Pt) and schizophrenia (Sc) scales in patients with obese parents. Obese patients presented significantly higher dichotomized manual preference indexes in relation to overweight patients. Parental obesity, binge eating behaviour with purging, body fat distribution and the dichotomized manual preference index were independent significant factors for the ACTH response in the CRH test, together explaining 41% of the response variability. Age of onset of obesity and the dichotomized manual preference index were independent and significant factors for the cortisol response, together explaining 37% of its variability. A non-normal distribution was found for the ACTH response: high- and low-responders presented significantly different MMPI profiles, with high-responders presenting higher scores on all clinical scales except masculinity/femininity (Mf).
CONCLUSION
Overweight/obese subjects with parental obesity present a distinctive personality profile and a higher ACTH response in the CRH test. Cerebral asymmetry may be a relevant factor for obesity development and is associated with the HPA reactivity. HPA reactivity is a sensitive index integrating clinical, psychological and neural asymmetric factors. International Journal of Obesity (2001) 25, 24-32
|
10.1038/sj.ijo.0801500
|
pubmed_38_13802
|
BACKGROUND
The prevalence of gestational diabetes (GDM) is constantly increasing all around the world. Aim of this study is to report prevalence and regional differences of GDM, oral glucose tolerance tests (OGTT) and register-based GDM risk factors [age and body mass index (BMI)] among Finnish women.
METHODS
Data from the Finnish Medical Birth Register including all deliveries in Finland during 2004-06 (N = 174 634) were used. The criteria for GDM were abnormal results in OGTT, GDM diagnosis based on ICD-10 classification or use of insulin treatment during pregnancy. Pregnant women with type I diabetes were excluded, but women with pregestational diabetes (type II) were included since they also can receive GDM diagnosis.
RESULTS
The prevalence of GDM was 10-11% and OGTTs 22-28% between the period 2004 until 2006. Regional differences were 2-fold both in prevalence of GDM (8-15%) and OGTTs (19-34%). Proportions of obese women varied between 28% and 35% and women aged >40 years between 3% and 4%. The regional differences in GDM prevalence were not attenuated when risk factors were taken into account. Overweight and age ≥years explained only a fourth of the variation in GDM prevalence.
CONCLUSION
Proportion of women undergoing OGTT increased but the prevalence of GDM did not during the study period. Two-fold regional differences in OGTT prevalence explained higher proportion of variation in prevalence of GDM than risk factors available from birth registry, age and BMI.
|
10.1093/eurpub/ckq193
|
pubmed_752_5581
|
To achieve the goal of eliminating measles and rubella two key strategies have been defined: sustain very low level of population susceptibility and strengthen surveillance system by rigorous case investigation and rapid control measures implementation. Surveillance of measles, rubella and CRS are included into the Spanish Surveillance System (RENAVE); surveillance is mandatory, passive, nationwide and case-based with laboratory information integrated. Information flows from sub national to national level (National Centre for Epidemiology) and then, to the WHO-Europe through ECDC. In the final phase of elimination, good surveillance and documented evidences are keys. Information on epidemiology of measles, rubella and CRS cases and outbreaks, pattern of importation, genotypes circulating and performance of measles and rubella surveillance are required at national and international level. Also all investigated and discarded measles or rubella cases should be reported. Currently the system faces some challenges gathering needed information for documenting the elimination. As long as the disease incidence declines, increases difficulties in identifying clinical measles and rubella because of non-specific prodromal signs and atypical cases. Differential diagnosis for fever and rash including measles and rubella should be performed in all clinical settings. Three clinical specimens must be collected to confirm or discard cases and to allow the virus characterization in order to know the pattern of importation of measles and rubella.
|
pubmed_752_5581
|
pubmed_968_10895
|
BACKGROUND AND PURPOSE
Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke.
METHODS
We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes (DNMT3A, TET2, and ASXL1) with any stroke, ischemic stroke, and hemorrhagic stroke.
RESULTS
CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03-1.27]; P=0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke.
CONCLUSIONS
CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.
|
10.1161/STROKEAHA.121.037388
|
pubmed_785_16093
|
OBJECTIVE
To investigate the pathogenic infection and its drug resistance in expressed prostatic secretion (EPS) and its correlation with serum PSA, and provide some evidence for the systematic and normalized diagnosis and treatment of prostatitis.
METHODS
Three EPS swabs were collected from each of the 320 prostatis patients following measurement of the serum PSA level, 1 for bacterial culture and identification, 1 for detection of Mycoplasma and drug sensitivity, and the other for examination of Chlamydia trachomatis antigen by colloidal gold immunoblot.
RESULTS
Totally 244 strains were isolated from the 320 EPS samples, including 188 bacterial strains (dominated by Staphylococcus and sensitive to vancomycin or linezolid) and 44 Mycoplasma and Chlamydia strains (mainly Ureaplasma urealyticum and susceptible to josamycin or doxycycline). The serum PSA level was significantly higher in the pathogen-positive than in the pathogen-negative group ([6.98 +/- 0.56] microg/L vs [2.32 +/- 0.12] microg/L, P < 0.05).
CONCLUSION
Prostatitis may lead to the elevation of the serum PSA level and the pathogens involved vary in their resistance to different antibacterial spectrums. Therefore, appropriate and individualized antibiotic therapy should be selected according to etiological diagnosis and the results of drug sensitivity test.
|
pubmed_785_16093
|
pubmed_635_15065
|
Valuable insights into the role of experience in shaping perception can be obtained by studying the effects of blindness or other forms of sensory deprivation on the intact senses. Blind individuals are particularly dependent on their hearing and there is extensive evidence that they can develop superior auditory skills, either as a result of plasticity within the auditory system or through the recruitment of functionally relevant occipital cortical areas that lack their normal visual inputs. Because spatial processing normally relies on close interactions between vision and hearing, much of the research in this area has focused on the effects of blindness on auditory localization. Although enhanced auditory skills have been reported in many studies, some aspects of spatial hearing are impaired in the absence of vision. In this case, the effects of crossmodal plasticity may reflect a balance between adaptive changes that compensate for blindness and the role vision normally plays, particularly during development, in calibrating the brain's representation of auditory space.
|
10.1007/s00441-015-2175-y
|
pubmed_20_425
|
The recent emergence of targeted nucleases has opened up new opportunities for performing genetic modifications with human pluripotent stem cells (hPSCs). These modifications can range from the creation of a routine knock-out to the more challenging single point-mutation. For both the new and established user, deciding on the best approach for the specific modification of interest can be an arduous task, as new and improved technologies are rapidly and continuously being developed. The choices between the reagents and methodologies depends entirely on the end-goal of the experiments and the locus to be modified. Investigators need to decide on the best nuclease to use for each experiment from among Zinc-Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 that would result in the highest likelihood of success with the fewest pitfalls. Furthermore, there have been significant improvements over the first-generation nucleases, such as the development of the dimeric CRISPR RNA-guided Fok1 nucleases (RFNs, marketed as NextGEN™ CRISPR) that reduces the "off-target" mutation rate, providing further options for investigators. Should researchers need to perform a point mutation, then considerations must be made between using single-stranded oligo-deoxynucleotides (ssODN) as the donor for homology-directed repair or utilizing a selection cassette within a donor vector in combination with an excision-only piggyBac™ transposase to leave a seamless edit. In this review, we will provide a general overview of the current technologies, along with methodologies for generating point mutations, while considering both their pros and cons.
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pubmed_20_425
|
pubmed_258_8039
|
The retropepsin (PR) of the Bovine leukemia virus (BLV) plays, as in other retroviruses, a crucial role in the transition from the non-infective viral particle to the infective virion by processing the polyprotein Gag. PR is expressed as an immature precursor associated with Gag, after an occasional -1 ribosomal frameshifting event. Self-hydrolysis of PR at specific N- and C-terminal sites releases the monomer that dimerizes giving rise to the active protease. We designed a strategy to express BLV PR in E. coli as a fusion protein with maltose binding protein, with a six-histidine tag at its N-terminal end, and bearing a tobacco etch virus protease hydrolysis site. This allowed us to obtain soluble and mature recombinant PR in relatively good yields, with exactly the same amino acid composition as the native protein. As PR presents relative promiscuity for the hydrolysis sites we designed four fluorogenic peptide substrates based on Förster resonance energy transfer (FRET) in order to characterize the activity of the recombinant enzyme. These substrates opened the way to perform kinetic studies, allowing us to characterize the dimer-monomer equilibrium. Furthermore, we obtained kinetic evidence for the existence of a conformational change that enables the interaction with the substrate. These results constitute a starting point for the elucidation of the kinetic properties of BLV-PR, and may be relevant not only to improve the chemical warfare against this virus but also to better understand other viral PRs.
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10.1371/journal.pone.0271671
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pubmed_880_15878
|
Galectin-3 is a β-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAcβ1-4(Fucα1-3)GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine β1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in non-lymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S.mansoni.
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10.1371/journal.pone.0019216
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pubmed_155_2999
|
Questions about costs and benefits of radiologic diagnostic methods have lead to the formation of a standing American College of Radiology Committee on Efficacy. In the past several years this committee has defined a hierarchy of efficacies associated with radiographic procedures and developed methods for assigning a numerical value to diagnostic efficacy. A national study of common x-ray examinations in the emergency setting has been conducted. These studies suggest that diagnostic thinking of clinicians was influenced by the results of the x-ray procedures they requested in more than 92% of cases. Medicolegal consideration were a prime concern of the clinician only 6% of the time overall when selecting the most frequent radiologic procedures conducted in hospitals. Considerable uncertainty about clinical diagnoses was typically present at the time radiologic examinations were requested; three-fourths of the time the most important diagnosis under consideration was judged to be less likely after x-ray examination than before. About one-eighth of the time the radiographic information focused attention on a new "most important" diagnosis. The committee plans further studies to include other imaging modalities and practive settings.
|
10.2214/ajr.131.1.173
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pubmed_822_4661
|
The zona pellucida (ZP) surrounds the mammalian oocyte and mediates species-selective sperm-oocyte interactions. Bovine ZP consists of glycoproteins ZP2, ZP3, and ZP4. Neither ZP3 nor ZP4 alone shows inhibitory activity for the binding of sperm to the ZP; however, this activity is seen with the ZP3/ZP4 heterocomplex. Here, we constructed a series of bovine ZP3 mutants to identify the ZP4-binding site on ZP3. Each ZP3 mutant was co-expressed with ZP4 using a baculovirus-Sf9 cell expression system and examined for interaction with ZP4 as well as inhibitory activity for sperm-ZP binding. N-terminal fragment Arg-32 to Arg-160 of ZP3 interacted with ZP4 and inhibited sperm-ZP binding, whereas fragment Arg-32 to Thr-155 showed much weaker interaction with ZP4. Mutation of N-glycosylated Asn-146 to Asp in the N-terminal fragment Arg-32 to Glu-178 of ZP3 did not interrupt the interaction of this fragment with ZP4, but it did reduce the inhibitory activity of the complex for sperm-ZP binding. In contrast, mutation of N-glycosylated Asn-124 to Asp did not significantly reduce the activity. Taken together, these results suggest that one of the ZP4 binding sites exists in the flexible hinge region of ZP3 and that the N-glycosylation in this region is involved in the sperm binding.
|
10.3390/biom5043339
|
pubmed_893_15308
|
BACKGROUND
Clinical decision making in abdominal aortic aneurysms (AAA) relies completely on diameter. At this point, improved decision tools remain an unmet medical need. Our goal was to identify changes at the molecular level specifically leading up to AAA rupture.
METHODS AND RESULTS
Aortic wall tissue specimens were collected during open elective (eAAA; n=31) or emergency repair of ruptured AAA (rAAA; n=17), and gene expression was investigated using microarrays. Identified candidate genes were validated with quantitative real-time polymerase chain reaction in an independent sample set (eAAA: n=46; rAAA: n=18). Two gene sets were identified, 1 set containing 5 genes linked to terminal progression, that is, positively associated with progression of larger AAA, and with rupture (HILPDA, ANGPTL4, LOX, SRPX2, FCGBP), and a second set containing 5 genes exclusively upregulated in rAAA (ADAMTS9, STC1, GFPT2, GAL3ST4, CCL4L1). Genes in both sets essentially associated with processes related to impaired tissue remodeling, such as angiogenesis and adipogenesis. In gene expression experiments we were able to show that upregulated gene expression for identified candidate genes is unique for AAA. Functionally, the selected upregulated factors converge at processes coordinated by the canonical HIF-1α signaling pathway and are highly expressed in fibroblasts but not inflammatory cells of the aneurysmatic wall. Histological quantification of angiogenesis and exploration of the HIF-1α network in rAAA versus eAAA shows enhanced microvessel density but also clear activation of the HIF-1α network in rAAA.
CONCLUSIONS
Our study shows a specific molecular fingerprint for terminal AAA disease. These changes appear to converge at activation of HIF-1α signaling in mesenchymal cells. Aspects of this cascade might represent targets for rupture risk assessment.
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10.1161/JAHA.117.006798
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pubmed_932_12054
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With a density functional theory method, we studied computationally the size dependence of adsorption properties of metal nanoparticles for CO as a probe on Pd(n) clusters with n = 13-116 atoms. For large particles, the values slowly decrease with cluster size from the asymptotic value for an (ideal) infinite surface. For clusters of 13-25 atoms, starting well above the asymptotic value, the adsorption energies drop quite steeply with increasing cluster size. These opposite trends meet in an intermediate size range, for clusters of 30-50 atoms, yielding the lowest adsorption energies. These computational results help to resolve a controversy on the size-dependent behavior of adsorption energies of metal nanoparticles.
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10.1021/nl300515z
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pubmed_214_19307
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We present rheological evidence demonstrating the glass-like nature of bicontinuous interfacially jammed emulsion gels (bijels). Under small amplitude oscillatory shear, bijels exhibited rheological signatures akin to α and β relaxation that are also invariable to interfacial tension changes, behaviors which are reminiscent of caged particle dynamics found in colloidal glasses, and well described by a previously reported adaptation of mode-coupling theory for colloidal glass rheology. Guided by their rheological signatures and supported by particle detachment and attraction energy approximations, we rationalize that bijels can be represented as 2-dimensional (2D) colloidal glasses that percolate in 3-dimensional (3D) space, and attractive interactions are not required for their stability. To provide further support for this conjecture, we qualitatively compare the rheology of bijels and a capillary suspension that is stabilized by strong, rigid capillary bridges between the particles, beyond their limit of linear viscoelasticity. Our results demonstrate that the strong adsorption of particles to the continuous interface and the lack of strong attractive interparticle forces enable recovery by interfacial tension into new jammed configurations after shear deformation. These behaviors are qualitatively different from those in the capillary suspension, where the breaking of attractive interparticle bonds results in dramatic changes to the microstructure and rheology over a narrow range of shear amplitudes. Our findings unveil bijels as 2D colloidal glasses weaving in 3D space and establish that interparticle attractions are not required for stability in bijels, and interfacial jamming alone is sufficient to impart viscoelasticity and gel-like rheology to these materials.
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10.1039/d2sm00407k
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pubmed_916_15069
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The aim of this study was to determine the microbiological quality of raw cow milk from direct sale points. Raw cow milk samples were collected from 5 randomly selected direct sale points for microbiological evaluation. The samples were analyzed to determine total aerobic bacterial count, somatic cell count (SCC), counts of Enterobacteriaceae, Enterococcus, Escherichia coli, and Staphylococcus, and presence of Salmonella, Listeria monocytogenes, and inhibitory substances. The mean counts of total aerobic bacterial in samples from all direct sale points were between 9.2×10(4) and 3.6×10(7) cfu/mL. Milk samples collected from 5 direct sale points revealed counts Enterobacteriaceae ranging from 6.4×10(1) to 1.7×10(6) cfu/mL. Escherichia coli were detected in 12 milk samples with counts ranging from 5.0×10(0) to 1.1×10(2) cfu/mL. Staphylococcus spp. bacteria were found in all milk samples, at counts ranging from 1.6×10(3) to 5.1×10(4) cfu/mL. Listeria monocytogenes bacteria were detected in 1 sample, and SCC in all samples ranged from 78,000 to 1,730,000/mL. The examined samples did not contain Salmonella rods or inhibitory substances. In the samples examined in this study, international hygiene standards were exceeded for total aerobic bacterial count (n=48) as well as for SCC (n=19). Two milk samples contained pathogenic bacteria (Listeria monocytogenes and Staphylococcus aureus) that pose a potential hazard for consumer health.
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pubmed_916_15069
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pubmed_201_6161
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In view of the compelling anti-diabetic effects of gastric bypass surgery (GBS) in the treatment of morbid obesity, it is important to clarify its enhancing effect on pancreatic islets, which is closely linked with diabetes remission in obese patients, as well as the underlying mechanisms. The present study evaluated the effects of GBS on glycemic control and other pancreatic changes in db/db mice. The db/db mice were divided into Control, Sham and GBS group. A significant improvement in fasting plasma glucose levels and glucose intolerance were observed post-surgery. At 4 weeks after surgery, further noteworthy changes were observed in the GBS group, including improved islet structure (revealed by immunohistochemical analysis), enhanced insulin secretion, pancreatic hyperplasia and a marked increase in the ratio of β-cells to non-β endocrine cells. Furthermore, notable changes in the levels of Notch-1, pancreatic and duodenal homeobox 1 (PDX-1) and neurogenin 3 (Ngn3) were observed in the GBS group, indicating a potential role of Notch signaling in pancreatic islet regeneration after surgery. In addition, results obtained in PDX-1 knockout (KO), Notch-1 KO and Ngn3 KO mouse models with GBS suggested that elevated PDX-1 resulted in the inhibition of Notch-1, further facilitated Ngn3 and thus promoted pancreatic β-cell regeneration after GBS. The present findings demonstrated that GBS in db/db mice resulted in pancreatic islet regeneration through the PDX-1/Notch-1/Ngn3 signaling pathway, which also reflected the important role of the gastrointestinal system in metabolism control.
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10.3892/etm.2017.4896
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pubmed_191_5237
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Thyrotropin-secreting pituitary adenomas (TSH-omas) are rare tumors (0.5% of all pituitary adenomas) showing an invasive behavior and usually sporadic, although a few cases are associated with multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant inherited syndrome. This disorder is linked to loss of heterozygosity (LOH) on 11q13 and inactivating mutations of MEN1 gene, which is located in the same chromosomal region. As other types of anterior pituitary adenomas, TSH-omas are the result of a monoclonal outgrowth where the intrinsic genetic defects involving oncogenes or tumor suppressor genes occur in a progenitor cell. However, so far no activating mutations of particular oncogenes or inactivating mutations of tumor suppressor genes have been identified. Starting from the observation that 3-30% of sporadic pituitary adenomas show LOH on 11q13, and that allelic losses on the long arms of chromosome 11, beside 10 and 13, are significantly associated with the transition from the non-invasive to the invasive phenotype, we decided to investigate LOH on 11q13 and mutations of menin in a large series of TSH-omas. Thirteen tumors were evaluated. DNA was extracted from tumors by standard methods and genomic DNA from peripheral blood leukocytes was used as control. LOH was screened by using 3 polymorphic markers on 11q13: D11S956, PYGM, INT-2. In 3 out of 15 cases we could demonstrate LOH on 11q13, but none of the tumors showed menin mutation after sequence analysis. These data strongly suggest that menin does not play a causative role in the development of TSH-omas, and are in agreement with other studies demonstrating a limited role of menin in pituitary sporadic tumorigenesis.
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10.1007/BF03343929
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pubmed_1061_9318
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There is an increasing demand for public health workers due to the unmet needs of the poor and underserved populations. However, through field placement experiences, students can actively engage in their own learning while also addressing critical needs of rural and medically underserved populations. In this mixed-methods evaluation, we explored experiences of emerging public health practitioners who participated in the Region IV Public Health Training Center's Pathways to Practice Scholars program between 2014 and 2018. Based on student confidence level ratings and descriptions of field placement experiences, scholars participated in meaningful and enriching field placement experiences in rural areas or on behalf of medically underserved populations. Across all eight Council on Linkages Core Competency Domains, students recorded increased pre- to post-confidence scores, and for many, the field placement experience appeared to affirm their interest in addressing the needs of these communities in the future.
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10.1177/1524839919879924
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pubmed_1140_1019
|
BACKGROUND
In previous literature, the stability and temporal evolution of psychobehavioral responses to an outbreak remained undefined, because of the exclusively cross-sectional nature of such study designs.
METHODS
Using random-digit dialing, we sampled 4481 Hong Kong residents in 6 population-based surveys that were conducted at different times during and after the 2003 outbreak of severe acute respiratory syndrome (SARS).
RESULTS
Respondents' State-Trait Anxiety Inventory score (range, 10-40) showed a decreasing temporal trend, from a high mean value of 24.8 during the peak of the Amoy Gardens outbreak to a postepidemic mean baseline value of 14.5. Those who perceived a higher likelihood of contracting or dying of SARS had significantly higher anxiety scores. Female respondents, individuals aged 30-49 years, and individuals with only a primary education or less were predisposed to greater anxiety. There was a positive dose-response gradient between anxiety level and uptake of personal protective measures. Males respondents, individuals at the extremes of age, and individuals with lower educational levels were less likely to engage in self-protective behavior. The presence of symptoms was the only consistent predictor for greater use of health services. There was remarkable stability in the magnitude and the direction of associations between predictors and outcomes over time.
CONCLUSIONS
Our findings can assist in modifying public service announcements in the future, which should be tailored to psychobehavioral surveillance intelligence to achieve the desired behavioral outcomes. Future research should explore the use of more-sophisticated techniques, including structural equation modeling and game-theoretical frameworks, to analyze population psychology and behavior, and it should integrate such findings with transmission dynamics modeling.
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10.1086/429923
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pubmed_181_4404
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Previously we have shown that loss of non-canonical NF-κB signaling impairs self-renewal of hematopoietic stem/progenitor cells (HSPCs). This prompted us to investigate whether persistent activation of the non-canonical NF-κB signaling will have supportive effects on HSPC self-renewal. NF-κB-inducing kinase (NIK) is an important kinase that mainly activates the non-canonical pathway through directly phosphorylating IKKα. In contrast to our expectations, constitutive activation of NIK in the hematopoietic system leads to bone marrow (BM) failure and postnatal lethality due to intrinsic impairment of HSPC self-renewal and extrinsic disruption of BM microenvironment through enhancing osteoclastogenesis. The impaired HSPC function is associated with reduced cell proliferation and increased apoptosis and inflammatory cytokine responses. RNAseq analysis of control and NIK-activated HSPCs reveals that these effects are through non-canonical NF-κB signaling without significant changes in the canonical pathway. Gene set expression analysis of RNAseq data reveals globally decreased stem cell signature, increased maturation signature, and increased inflammatory responses. Many genes (Mpl, Tifab, Emcn, Flt3, Bcl2, and others) that regulate HSPC self-renewal, lineage commitment, and apoptosis are significantly downregulated-and those genes that regulate inflammatory responses and cell cycle inhibition (Cdkn2a and Cdkn2b) are significantly upregulated-by activation of NIK. Importantly, our data demonstrate that activation of NIK-non-canonical signaling has distinct phenotypes-smaller spleen size, decreased white blood cell counts, and reduced HSPC proliferation-compared to activation of canonical signaling. Collectively, these data indicate that the balanced non-canonical NF-κB signaling is essential for maintaining normal hematopoiesis and NIK-non-canonical signaling contributes to the development of BM failure. Stem Cells 2017;35:777-786.
|
10.1002/stem.2523
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pubmed_149_9423
|
Photorhabdus akhurstii can produce a variety of proteins that aid this bacterium and its mutualistic nematode vector, Heterorhabditis indica to kill the insect host. Herein, we characterized (by heterologously expressing in E. coli) an open reading frame (1713 bp) of the toxin complex protein, TcaB from P. akhurstii strains IARI-SGHR2 and IARI-SGMS1 and assessed its toxic effect on G. mellonella larvae. The intra-hemocoel injection of purified TcaB (molecular weight-63 kDa) caused fourth instar larval bodies to blacken and die with LD50 values of 67.25 (IARI-SGHR2) and 52.08 (IARI-SGMS1) ng per larva at 12 h. Additionally, oral administration of the toxin caused larval mortality with LD50 values of 709.55 (IARI-SGHR2) and 598.44 (IARI-SGMS1) ng per g diet per larva at 7 days post feeding. Injection of purified TcaB caused loss of viability of fourth instar G. mellonella hemocytes at 6 h post incubation; cells displayed morphological changes typical of apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and disintegration. Injection of TcaB also elevated the phenoloxidase activity in insect hemolymph which triggers an extensive immune response that potentially leads to larval death. Similar to other bacterial toxins TcaB possesses potent biological activity which may enable it to be used as an efficient agent for pest management.
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10.1016/j.pestbp.2019.03.019
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pubmed_6_26888
|
BACKGROUND
Self-regulated learning (SRL) is an important contributing element to the academic success of students. Literature suggests that the understanding of SRL among medical students is obscure as there is still some uncertainty about whether high performing medical students use SRL. This study explored the characteristics of high performing medical students from the SRL perspective to gain a better understanding of the application of SRL for effective learning.
METHODS
Twenty-one students who scored at the 90th percentile in written knowledge-based assessment consented to participate in this study. Each student wrote a guided reflective journal and subsequently attended a semi-structured interview. Students were prompted to explain the rationales for their answers. The data were then analysed using thematic analysis to identify patterns among these students from the SRL perspective. Two coders analysed the data independently and discussed the codes to reach a consensus.
RESULTS
High performing students set goals, made plans, and motivated themselves to achieve the goals. They put consistent efforts into their studies and applied effective learning strategies. They also employed coping mechanisms to deal with challenges. High performing students regularly evaluated their performance and adopted new strategies.
CONCLUSIONS
This study reported that high performing students applied SRL and described the rationales of practice. Medical schools could design SRL-driven interventions to enhance the learning experiences of medical students. Recommendations are made for students on how to apply SRL.
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10.1186/s12909-021-02712-w
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pubmed_970_15875
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Gut microbiota play an important role in maintaining intestinal health and are involved in the metabolism of carbohydrates, lipids, and amino acids. Recent studies have shown that the central nervous system (CNS) and enteric nervous system (ENS) can interact with gut microbiota to regulate nutrient metabolism. The vagal nerve system communicates between the CNS and ENS to control gastrointestinal tract functions and feeding behavior. Vagal afferent neurons also express receptors for gut peptides that are secreted from enteroendocrine cells (EECs), such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and 5-hydroxytryptamine (5-HT; serotonin). Gut microbiota can regulate levels of these gut peptides to influence the vagal afferent pathway and thus regulate intestinal metabolism via the microbiota-gut-brain axis. In addition, bile acids, short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and Immunoglobulin A (IgA) can also exert metabolic control through the microbiota-gut-liver axis. This review is mainly focused on the role of gut microbiota in neuroendocrine regulation of nutrient metabolism via the microbiota-gut-brain-liver axis.
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10.3390/microorganisms8040527
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pubmed_617_9846
|
Vertical pipes comprised of loose silica and lined by chert nodules have been observed in the abandoned Mafeking Quarry in central Manitoba, Canada. Discovery of microfossils within these features of the same age as the carbonate host rock indicates that they are a dissolution/replacement structure rather than infill of karst features by younger sediments. These features occur on the low thermal maturity edge of the intercratonic Williston Basin, are not associated with any known tectonic or hydrothermal activity, and show no sign of localized discharge of high-temperature fluids. Modern low-temperature brine springs with silica-filled discharge channels occur nearby, which suggests the silica chimneys are relic spring channels. Geochemical models have shown that dissolution/replacement reactions would be expected due to mixing of brine spring water with shallow groundwater in the region. Results indicate that silica pipe features in the rock record cannot be assumed to be indicative of hydrothermal activity. At the same time, results increase the astrobiological significance of low-temperature siliceous deposits.
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10.1089/ast.2009.0350
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pubmed_830_8510
|
BACKGROUND
Determining the optimal technique for autologous fat grafting requires elucidation of the engraftment process at the cellular level. The nude mouse xenograft model for autologous human fat grafting is an excellent tool to evaluate the incorporation of grafted fat into the recipient.
OBJECTIVES
The authors present a murine xenograft model that uses fluorescent in situ hybridization (FISH) to differentiate between murine (host) cells and human (grafted) cells.
METHODS
Fat grafts were harvested from human abdominoplasty specimens, fixed, embedded in paraffin blocks, and cut into 5 µm sections. The sections were stained and used for in situ hybridization with fluorescently labeled murine and human nucleic acid reagents. A fluorescence microscope was used for photographic analysis of the grafts, allowing identification of murine and human cell populations based on the wavelength at which they stained. DAPI (4,'6-diamidino-2-phenylindole) counterstaining was also applied to confirm that the images obtained represented cell nuclei.
RESULTS
At 20× magnification, strong species-specific staining of cells was seen within the tissue sections, which allowed the authors to easily discriminate between graft-derived and host-derived cells. Using this approach, human fat xenografts were revealed to comprise a complex matrix of closely interacting graft- and host-derived structures.
CONCLUSIONS
FISH has the potential to be a powerful technique for distinguishing between murine and human cells in the nude mouse xenograft model of human fat grafting. By applying this technique, it may be possible to evaluate the engraftment process at a cellular level, which may ultimately allow clinicians to obtain more predictable results with grafted fat.
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10.1177/1090820X12452422
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pubmed_297_26375
|
The invasiveness of glioma cells is the predominant clinical problem associated with this tumor type, and is correlated with pathological malignant grade. ZEB1 is highly expressed in glioma cells and associated with the aggressiveness of various types of cancer. In the present study, the expression of ZEB1 and ZEB2 was examined with the aim of determining the role of ZEBs in glioma. ZEB1 and ZEB2 were highly expressed in all glioma cells used in this study. Double knockdown of ZEB1 and ZEB2 suppressed tumor invasiveness more effectively than knockdown of either alone, in both in vitro and in vivo experiments. ZEB1 and ZEB2 were marginally expressed in grade II, but expressed at higher levels in grade IV. Importantly, ZEB-positive cells were more abundant in recurrent glioma with malignant transformation than in initial grade II tissue from the same case. These results indicate that the levels of ZEB1 and ZEB2 are positively correlated with histopathological grade and invasiveness of glioma, suggesting that δEF1 family proteins (ZEB1 and ZEB2) could be useful as prognostic markers and therapeutic targets in patients with glioma.
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10.3892/ol.2018.8852
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pubmed_1000_835
|
A pilot biomarker study was conducted to investigate the feasibility of using the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene in peripheral blood lymphocytes as a biomarker for detecting genetic effects of arsenic exposure. Blood and urine samples were obtained from workers highly exposed to arsenic in a copper roasting plant in Antofagasta, Chile. Individuals were classified according to their job titles into three potential exposure groups: high, medium, and low. To confirm exposure, arsenic concentration was determined in urine samples. The HPRT mutant frequencies were measured in lymphocytes from 15 individuals ranging in age from 24 to 66 years. The mean mutant frequencies for the three exposure groups were: low (9 x 10(-6)), medium (11 x 10(-6)), and high (24 x 10(-6)). An increased mutant frequency was observed in the highly exposed group, but the response was so slight that it is not likely that this assay will be capable of providing dose-response information across a range of lower, more typical environmental arsenic levels.
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10.1016/s0027-5107(99)00167-0
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pubmed_189_17215
|
OBJECTIVE
The main aim of this study was to assess through systematic review the efficacy of exercise and manual therapy (MT) interventions in individuals with primary headache.
METHODS
In this umbrella review, 2 authors reviewed systematic reviews by searching the Cochrane Database of Systematic Reviews, MEDLINE, PEDro, Web of Science, and Google Scholar. Systematic reviews that evaluated the effectiveness of MT. Exercise-based interventions, or both in patients with primary headaches were included. Methodological quality was analyzed using the ROBIS scale, and the strength of evidence was established according to the Grading Criteria of the Physical Activity Guidelines Advisory Committee.
RESULTS
Thirty-one systematic reviews containing 79 trials and involving 9103 patients were included. The 7 exercise-related systematic reviews reported beneficial effects on primary headache based on unclear to moderate evidence. Of the 23 MT-related systematic reviews, 11 reported enhanced effectiveness compared with usual care; however, overall heterogeneity and risk of bias were high. Systematic reviews that evaluated the effectiveness of MT, exercise-based interventions, or both in patients with primary headaches were included.
CONCLUSION
Results show that exercise could be an effective therapy for the treatment of primary headache, with moderate to limited quality of evidence regarding the positive effects in terms of pain intensity and frequency and duration of headache. Moderate quality of evidence was found regarding the ability of MT to reduce pain intensity in patients with tension-type headaches, but quality of evidence was limited in terms of frequency of headache and disability and pain reduction in patients with migraine.
IMPACT
Exercise could be an effective treatment in patients with primary headache. Manual therapy showed limited evidence to reduce pain intensity in patients with tension-type headache. It is not possible to establish a preferential exercise protocol or MT program, so psychosocial and behavioral variables need to be considered in future studies.
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10.1093/ptj/pzab308
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pubmed_1077_2370
|
Metastases are known to be responsible for approximately 90% of breast cancer-related deaths. Cyclooxygenase-2 (COX-2) is involved not only in inflammatory processes, but also in the metastasis of cancer cells; it is expressed in 40% of human invasive breast cancers. To comprehensively analyze the effects of cannabidiolic acid (CBDA), a selective COX-2 inhibitor found in the fiber-type cannabis plant (Takeda et al., 2008), on COX-2 expression and the genes involved in metastasis, we performed a DNA microarray analysis of human breast cancer MDA-MB-231 cells, which are invasive breast cancer cells that express high levels of COX-2, treated with CBDA for 48 hr at 25 µM. The results obtained revealed that COX-2 and Id-1, a positive regulator of breast cancer metastasis, were down-regulated (0.19-fold and 0.52-fold, respectively), while SHARP1 (or BHLHE41), a suppressor of breast cancer metastasis, was up-regulated (1.72-fold) and CHIP (or STUB1) was unaffected (1.03-fold). These changes were confirmed by real-time RT-PCR analyses. Taken together, the results obtained here demonstrated that i) CBDA had dual inhibitory effects on COX-2 through down-regulation and enzyme inhibition, and ii) CBDA may possess the ability to suppress genes that are positively involved in the metastasis of cancer cells in vitro.
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10.2131/jts.39.711
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pubmed_86_12646
|
Sixteen patients with esophageal malignancies received photodynamic therapy after 3 mg of hematoporphyrin derivative (Photofrin I) or 2 mg of Photofrin II per kilogram of body weight was injected intravenously two to six days prior to treatment. A tunable dye argon laser system delivered 630 nm light through quartz fibers passed through the biopsy channel of a gastroscope. All patients obtained improvement in swallowing, usually from total obstruction or clear liquids only to a regular diet within three weeks and with new techniques, at least liquids within three days of treatment. Karnofsky Performance Status (KPS) and esophageal grades were measured before treatment, 1 month following treatment, and periodically until death. Ten patients died an average of 3.7 months after initial treatment (range, 0.6 to 19 months). Six patients are alive at 11, 10, 5, 2.5, 2 months, and 1 month after treatment. The median survival of 12 patients treated more than 6 months ago was 6.5 months and of 9 patients with an initial KPS higher than 30, 8.1 months.
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10.1016/s0003-4975(10)60002-1
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pubmed_352_7325
|
A technique is described which utilises the full analysis and display capabilities of a commercial MRI system to produce digital maps of multi-parameter functions produced by MR contrast theory. The technique is utilised to determine the effects of nominating specific overall scan times on the optimum solutions as produced by the theory and it is shown that different solutions are obtained when the theory is applied using typical clinical constraints. The digital mapping approach is potentially of great value in prospectively determining pulse timing parameters to produce optimum contrast images, in producing contrast maps to aid retrospective image interpretation, and as a training aid for clinicians inexperienced in the interpretation MR images.
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10.1016/0730-4862(86)90030-2
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pubmed_1094_19090
|
Quantum systems can be characterized by their correlations. Higher-order (larger than second order) correlations, and the ways in which they can be decomposed into correlations of lower order, provide important information about the system, its structure, its interactions and its complexity. The measurement of such correlation functions is therefore an essential tool for reading, verifying and characterizing quantum simulations. Although higher-order correlation functions are frequently used in theoretical calculations, so far mainly correlations up to second order have been studied experimentally. Here we study a pair of tunnel-coupled one-dimensional atomic superfluids and characterize the corresponding quantum many-body problem by measuring correlation functions. We extract phase correlation functions up to tenth order from interference patterns and analyse whether, and under what conditions, these functions factorize into correlations of lower order. This analysis characterizes the essential features of our system, the relevant quasiparticles, their interactions and topologically distinct vacua. From our data we conclude that in thermal equilibrium our system can be seen as a quantum simulator of the sine-Gordon model, relevant for diverse disciplines ranging from particle physics to condensed matter. The measurement and evaluation of higher-order correlation functions can easily be generalized to other systems and to study correlations of any other observable such as density, spin and magnetization. It therefore represents a general method for analysing quantum many-body systems from experimental data.
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10.1038/nature22310
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pubmed_573_19242
|
While overall spending for dental services appears to be favorable during the period after the last recession, a review of a series of government and private agency reports indicates an increasing proportion of the population is unable to secure needed services due to cost factors. In addition, projections for annual increases in future spending for dental services are lower than for other professional health services.
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pubmed_573_19242
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pubmed_864_23879
|
Molecularly targeted drugs for cancer therapy represent a therapeutic advance, but the proportion of patients who receive clinical benefit is still very limited. We present here the rationale and initial results of our program to define molecules involved in lung carcinogenesis with the goal of identifying new therapeutic targets and/or predictive biomarkers for drug response. We have used gene expression analysis of 120 lung cancers followed by RNA interference, tumor-tissue microarray analysis, and functional analyses to systematically distinguish potential target molecules specifically expressed in cancer cells. Through this approach, we have identified oncoproteins that provide the starting point for the development of therapeutic antibodies, dominant negative peptides, small-molecule inhibitors, and therapeutic cancer vaccines. We believe that the approach we describe should result in new molecularly targeted therapies with minimal risk of adverse events.
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10.1038/clpt.2013.90
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pubmed_308_21216
|
The present study was designed to evaluate the antioxidant activity of 5 organic solvent extracts (petroleum ether, n-hexane, chloroform, ethyl acetate and methanol) of wheat grains, 3, 5 and 7 days old wheat seedlings. To determine the antioxidant activity of five extracts of four different samples, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity, total phenolic content and ferrous reducing power ability were carried out. 1,1-Diphenyl-2-picrylhydrazyl radical scavenging effect of chloroform and ethyl acetate extracts of 3 days old wheat seedlings was higher than wheat grains. Chloroform, ethyl acetate and methanol extracts of 3 days old wheat seedlings exhibited higher 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging effcet than extracts of other samples. The phenolic content was high in chloroform, ethyl acetate and methanol extract of 5 days old wheat seedlings. When compared with wheat grain, reducing power ability was high in chloroform, ethyl acetate and methanol extract of wheat seedlings, especially in 3 and 5 days old wheat seedlings. From the above results, it was concluded that chloroform, ethyl acetate and methanol extract of 3, 5 and 7 days old wheat seedlings showed better antioxidant activity than the wheat grain extracts. Hence, the results of the present study suggest the intake of wheat seedlings as a food supplement to combat the diseases caused by free radicals.
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10.4103/0250-474x.169025
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pubmed_0_16135
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This paper considers how we can conceptualize a "global response" to chronic, non-communicable diseases (NCDs)--including cardiovascular disease, cancer, diabetes, and tobacco-related diseases. These diseases are the leading cause of death and disability in developed countries, and also in developing countries outside sub-Saharan Africa. The paper reviews emerging and proposed initiatives for global NCD governance, explains why NCDs merit a global response, and the ways in which global initiatives ultimately benefit national health outcomes. As the global response to NCDs matures, and the number of initiatives and partnerships increases, it will become increasingly important to map their respective contributions, and to evaluate progress overall. It is not yet clear what institutional mechanism, if any, will rise above the sea of surrounding initiatives to play this global role. This paper therefore aims to provide a conceptual map for making sense of what individual initiatives contribute to global governance. This map also draws attention to the distinctively "global" public health functions that a global response to NCDs should seek to discharge.
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10.1111/j.1748-720X.2010.00508.x
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pubmed_1076_22125
|
Reported here are the microbiological and epidemiological details of a presumed outbreak of aerobic gram-negative bacilli infections affecting 19 hematological patients, which was traced to contaminated disinfectant. Over a 5-month period, the following organisms were isolated from the blood cultures of 19 neutropenic patients: Pseudomonas fluorescens (n = 13), Achromobacter xylosoxidans (n = 12), Comamonas testosteroni (n = 2) or Stenotrophomonas maltophilia (n = 1). The affected patients were all treated with an expensive regimen of broad-spectrum antibiotic therapy. The same bacteria were recovered from environmental samples as well as from the water pipes of an apparatus for dispensing disinfectant (didecyldimethylammonium chloride). Genotyping results indicated that many of the clinical strains were identical to strains isolated from the apparatus. It was eventually discovered that the night staff was in the habit of disinfecting the blood-culture bottles before use, thereby contaminating the bottles with bacteria contained in the disinfectant. Contamination of the apparatus resulted from faulty maintenance.
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10.1007/s10096-007-0260-1
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pubmed_173_16591
|
The two-dimensional electron gas (2DEG) formed at the n-type (LaO)(+1)/(TiO2)(0) interface in the polar/nonpolar LaAlO3/SrTiO3 (LAO/STO) heterostructure (HS) has emerged as a prominent research area because of its great potential for nanoelectronic applications. Due to its practical implementation in devices, desired physical properties such as high charge carrier density and mobility are vital. In this respect, 4d and 5d transition metal doping near the interfacial region is expected to tailor electronic properties of the LAO/STO HS system effectively. Herein, we studied Nb and Ta-doping effects on the energetics, electronic structure, interfacial charge carrier density, magnetic moment, and the charge confinements of the 2DEG at the n-type (LaO)(+1)/(TiO2)(0) interface of LAO/STO HS using first-principles density functional theory calculations. We found that the substitutional doping of Nb(Ta) at Ti [Nb(Ta)@Ti] and Al [Nb(Ta)@Al] sites is energetically more favorable than that at La [Nb(Ta)@La] and Sr [Nb(Ta)@Sr] sites, and under appropriate thermodynamic conditions, the changes in the interfacial energy of HS systems upon Nb(Ta)@Ti and Nb(Ta)@Al doping are negative, implying that the formation of these structures is energetically favored. Our calculations also showed that Nb(Ta)@Ti and Nb(Ta)@Al doping significantly improve the interfacial charge carrier density with respect to that of the undoped system, which is because the Nb(Ta) dopant introduces excess free electrons into the system, and these free electrons reside mainly on the Nb(Ta) ions and interfacial Ti ions. Hence, along with the Ti 3d orbitals, the Nb 4d and Ta 5d orbitals also contribute to the interfacial metallic states; accordingly, the magnetic moments on the interfacial Ti ions increase significantly. As expected, the Nb@Al and Ta@Al doped LAO/STO HS systems show higher interfacial charge carrier density than the undoped and other doped systems. In contrast, Nb@Ti and Ta@Ti doped systems may show higher charge carrier mobility because of the lower electron effective mass.
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10.1039/c5cp05100b
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pubmed_365_1875
|
During last decade the analytical work of industrial toxicology and hygiene laboratory of the occupational medicine department of Desio Hospital (UOOML) developed towards more sophisticated and specialized techniques. This change required an updating and an increase of the analytical instruments and a continuous training of the laboratory staff, usually achieved by the incomes of the department. With this consideration in mind, we recognize the need for evaluating the laboratory activity by "indices" more susceptible of the qualitative aspect of the activity rather than the quantitative aspect.
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pubmed_365_1875
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pubmed_54_6233
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Intelligence and creativity are known to be correlated constructs suggesting that they share a common cognitive basis. The present study assessed three specific executive abilities - updating, shifting, and inhibition - and examined their common and differential relations to fluid intelligence and creativity (i.e., divergent thinking ability) within a latent variable model approach. Additionally, it was tested whether the correlation of fluid intelligence and creativity can be explained by a common executive involvement. As expected, fluid intelligence was strongly predicted by updating, but not by shifting or inhibition. Creativity was predicted by updating and inhibition, but not by shifting. Moreover, updating (and the personality factor openness) was found to explain a relevant part of the shared variance between intelligence and creativity. The findings provide direct support for the executive involvement in creative thought and shed further light on the functional relationship between intelligence and creativity.
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10.1016/j.intell.2014.05.007
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pubmed_874_11051
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Stomata are an attractive experimental system in plant biology, because the responses of guard cells to environmental signals can be directly linked to changes in the aperture of stomatal pores. In this review, the mechanics of stomatal movement are discussed in relation to ion transport in guard cells. Emphasis is placed on the ion pumps, transporters, and channels in the plasma membrane, as well as in the vacuolar membrane. The biophysical properties of transport proteins for H(+), K(+), Ca(2+), and anions are discussed and related to their function in guard cells during stomatal movements. Guard cell signaling pathways for ABA, CO2, ozone, microbe-associated molecular patterns (MAMPs) and blue light are presented. Special attention is given to the regulation of the slow anion channel (SLAC) and SLAC homolog (SLAH)-type anion channels by the ABA signalosome. Over the last decade, several knowledge gaps in the regulation of ion transport in guard cells have been closed. The current state of knowledge is an excellent starting point for tackling important open questions concerning stress tolerance in plants.
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10.1111/nph.12832
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pubmed_922_12464
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Combinations of metal(loid) contamination and antibiotics are considered to increase the abundance of resistance genes in the environment, whereas the combined effect of metal(loid)s and antibiotics on microbial communities and antibiotic resistance genes (ARGs) in the gut of soil fauna remains unknown. We investigated herein the alteration of ARGs and the gut microbial communities after the earthworm Metaphire sieboldi was exposed to arsenate and/or sulfamethoxazole using high-throughput quantitative PCR and Illumina sequencing analysis. Arsenic accumulation in the body tissues of arsenic-exposed earthworms exerted a significant inhibition on growth and survival. The synergistic interactions of arsenic and sulfamethoxazole increased significantly the incidence of ARGs and mobile genetic elements in the earthworm gut microbiota. In addition, co-exposure to arsenic and sulfamethoxazole altered the structure of the gut microbial communities, and the changes correlated with ARG profiles of the gut microbiota. Our results indicate that the gut of soil fauna is a neglected hotspot of antibiotic resistance.
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10.1021/acs.est.9b02277
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pubmed_776_7531
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In the neuro-ophthalmology clinic at St. Vincent's Hospital, Melbourne, 57 patients with blepharospasm and 50 patients with hemifacial spasm were treated with botulinum toxin. Schirmer tear tests were conducted on all the patients prior to each treatment and at 1 week following treatment where possible. The results were compared with a control group of 107 patients selected by age and sex. The blepharospasm patients were found to have a significantly lower tear secretion than that of the control group, using the Mann-Whitney test (median = 3.5 mm, compared with median-11.0 mm, p < .0001). This did not improve following treatment. The patients with hemifacial spasm did not have significantly different tear secretion from that of the control group (t = 1.0, p > .05). To investigate whether there was any relationship between the symptoms and the result of the Schirmer test, a survey was also conducted on the patients with blepharospasm and hemifacial spasm regarding symptoms, frequency, and type of drops/ointment used.
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pubmed_776_7531
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pubmed_678_3349
|
The microbial expression of intracellular, recombinant proteins in continuous bioprocesses suffers from low product concentrations. Hence, a process for the intracellular production of photoactivatable mCherry with Escherichia coli in a continuously operated cascade of two stirred-tank reactors was established to separate biomass formation (first reactor) and protein expression (second reactor) spatially. Cascades of miniaturized stirred-tank reactors were implemented, which enable the 24-fold parallel characterization of cascade processes and the direct scale-up of results to the liter scale. With PAmCherry concentrations of 1.15 g L-1 cascades of stirred-tank reactors improved the process performance significantly compared to production processes in chemostats. In addition, an optimized fed-batch process was outperformed regarding space-time yield (149 mg L-1 h-1). This study implicates continuous cascade processes to be a promising alternative to fed-batch processes for microbial protein production and demonstrates that miniaturized stirred-tank reactors can reduce the timeline and costs for cascade process characterization.
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10.1007/s10295-017-1927-y
|
pubmed_1037_3074
|
Human cytomegalovirus (HCMV) is an important opportunistic pathogen in allogeneic haematopoietic stem cell transplant (HSCT) recipients. High-throughput sequencing of target-enriched libraries was performed to characterise the diversity of HCMV strains present in this high-risk group. Forty-four HCMV-DNA-positive plasma specimens (median viral input load 321 IU per library) collected at defined time points from 23 HSCT recipients within 80 days of transplantation were sequenced. The genotype distribution for 12 hypervariable HCMV genes and the number of HCMV strains present (i.e. single- vs. multiple-strain infection) were determined for 29 samples from 16 recipients. Multiple-strain infection was observed in seven of these 16 recipients, and five of these seven recipients had the donor (D)/recipient (R) HCMV-serostatus combination D + R + . A very broad range of genotypes was detected, with an intrahost composition that was generally stable over time. Multiple-strain infection was not associated with particular virological or clinical features, such as altered levels or duration of antigenaemia, development of acute graft-versus-host disease or increased mortality. In conclusion, despite relatively low viral plasma loads, a high frequency of multiple-strain HCMV infection and a high strain complexity were demonstrated in systematically collected clinical samples from this cohort early after HSCT. However, robust evaluation of the pathogenic role of intrahost viral diversity and multiple-strain infection will require studies enrolling larger numbers of recipients.
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10.1007/s00430-021-00722-5
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pubmed_256_6311
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A case of non immune hidrops foetalis caused by severe hemolytic anemia secondary to a familiar thalassemia is presented. The diagnosis was made at 28 weeks of gestational age; treatment was intravascular transfusion, done in our service. The diagnosis, prenatal management and neonatal evolution are analyzed.
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pubmed_256_6311
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pubmed_471_19009
|
Alzheimer's disease is a chronic neurological ailment that seriously threatens human health and imposes a huge burden on families and the society at large. Emerging evidence suggests that neuroinflammation is an important pathological manifestation of neurodegenerative diseases, and currently considered a new research target. We previously found that artemisinin B from Artemisia annua Linn. has strong anti-inflammatory and immunological activities. In the present study, we assessed the anti-neuroinflammatory effects of artemisinin B in vitro and in vivo, exploring the underlying mechanisms. The results demonstrated that artemisinin B inhibited NO secretion from LPS-induced BV2 cells and significantly reduced the expression levels of the inflammatory cytokines IL-1β, IL-6 and TNF-α. This was accompanied by reduced gene expression levels of MyD88 and NF-κB as well as TLR4 and MyD88 protein levels. These inhibitory effects were further confirmed in AD model mice. This study also showed that artemisinin B improved spatial memory in dementia mice in the water maze and step-through tests, and altered the pathological features and the levels of inflammatory cytokines in the hippocampus and the cortex. These results suggested that artemisinin B might inhibit neuroinflammation and exert neuroprotective effects on cognitive functions by modulating the TLR4-MyD88-NF-κB signaling pathway. This study provides direct evidence for the potential application of artemisinin B in the treatment of neuroinflammatory diseases.
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10.1016/j.neuroscience.2018.10.041
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pubmed_674_20546
|
Adipocytes are the defining cell type of adipose tissue. Once considered a passive participant in energy storage, adipose tissue is now recognized as a dynamic organ that contributes to several important physiological processes, such as lipid metabolism, systemic energy homeostasis, and whole-body insulin sensitivity. Therefore, understanding the mechanisms involved in its development and function is of great importance. Adipocyte differentiation is a highly orchestrated process which can vary between different fat depots as well as between the sexes. While hormones, miRNAs, cytoskeletal proteins, and many other effectors can modulate adipocyte development, the best understood regulators of adipogenesis are the transcription factors that inhibit or promote this process. Ectopic expression and knockdown approaches in cultured cells have been widely used to understand the contribution of transcription factors to adipocyte development, providing a basis for more sophisticated in vivo strategies to examine adipogenesis. To date, over two dozen transcription factors have been shown to play important roles in adipocyte development. These transcription factors belong to several families with many different DNA-binding domains. While peroxisome proliferator-activated receptor gamma (PPARγ) is undoubtedly the most important transcriptional modulator of adipocyte development in all types of adipose tissue, members of the CCAAT/enhancer-binding protein, Krüppel-like transcription factor, signal transducer and activator of transcription, GATA, early B cell factor, and interferon-regulatory factor families also regulate adipogenesis. The importance of PPARγ activity is underscored by several covalent modifications that modulate its activity and its ability to modulate adipocyte development. This review will primarily focus on the transcriptional control of adipogenesis in white fat cells and on the mechanisms involved in this fine-tuned developmental process. © 2017 American Physiological Society. Compr Physiol 7:635-674, 2017.
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10.1002/cphy.c160022
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pubmed_397_24733
|
We describe a case of Hb S/beta-thalassemia (thal) involving a 468 bp deletion that removes the beta-globin gene promoter but leaves the coding regions intact. This is the second report of this deletion, and our family study establishes that this deletion causes beta0-thal with unusually high levels of Hb A2 and Hb F. As with other genotypes involving deletions of the 5' region of the beta-globin gene, our patient had a mild form of Hb S/beta-thal.
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10.1080/03630260500311651
|
pubmed_65_12898
|
BACKGROUND
Transmembrane 4 superfamily (TM4SF) molecules are exclusively found on hematopoietic cells. Several members of the TM4SF are reported to be associated with other cell surface molecules, including integrins, and might participate in signal transduction, but little is known about their role on eosinophils. In the present study, we determined the expression and function of TM4SF molecules on human eosinophils.
METHODS
Surface expression of TM4SF molecules on purified peripheral blood eosinophils was examined using indirect immunofluorescence and flow cytometry. Purified eosinophils were incubated with anti-TM4SF monoclonal antibodies (mAbs) for up to 24 h. Eosinophil activation was evaluated by measuring eosinophil homotypic aggregation as well as changes in surface expression of CD11b or CD62L by flow cytometry.
RESULTS
Freshly isolated eosinophils expressed CD9, CD37, CD53, CD63 and CD81. Incubation with anti-CD9 mAb but not with anti-CD37, CD53, CD63 or CD81 mAb induced significant eosinophil homotypic aggregation. Incubation with any of the anti-TM4SF mAb for 30 min failed to alter the expression of either CD11b or CD62L on eosinophils. In contrast, the expression of CD11b was significantly enhanced after 24 h of incubation with anti-CD53 mAb, while the expression of CD62L was significantly reduced with anti-CD81 mAb.
CONCLUSIONS
Cross-linking of some surface TM4SF molecules induced significant eosinophil homotypic aggregation, upregulation of CD11b expression, or CD62L shedding, consistent with activation of eosinophils. Our data suggest that several TM4SF molecules are functionally expressed on human eosinophils, and therefore might participate in allergic inflammation.
|
10.1159/000053592
|
pubmed_842_5798
|
AIMS/HYPOTHESIS
Endoplasmic reticulum (ER) stress has been implicated in the development of type 2 diabetes, via effects on obesity, insulin resistance and pancreatic beta cell health. C/EBP homologous protein (CHOP) is induced by ER stress and has a central role in apoptotic execution pathways triggered by ER stress. The aim of this study was to characterise the role of CHOP in obesity and insulin resistance.
METHODS
Metabolic studies were performed in Chop ( -/- ) and wild-type C57Bl/6 mice, and included euglycaemic-hyperinsulinaemic clamps and indirect calorimetry. The inflammatory state of liver and adipose tissue was determined by quantitative RT-PCR, immunohistology and macrophage cultures. Viability and absence of ER stress in islets of Langerhans was determined by electron microscopy, islet culture and quantitative RT-PCR.
RESULTS
Systemic deletion of Chop induced abdominal obesity and hepatic steatosis. Despite marked obesity, Chop ( -/- ) mice had preserved normal glucose tolerance and insulin sensitivity. This discrepancy was accompanied by lower levels of pro-inflammatory cytokines and less infiltration of immune cells into fat and liver.
CONCLUSIONS/INTERPRETATION
These observations suggest that insulin resistance is not induced by fat accumulation per se, but rather by the inflammation induced by ectopic fat. CHOP may play a key role in the crosstalk between excessive fat deposition and induction of inflammation-mediated insulin resistance.
|
10.1007/s00125-011-2427-7
|
pubmed_875_23574
|
BACKGROUND
Since dendritic cells (DC) are involved in the development of autoimmune inflammation, researchers consider DC both as target cells for specific therapy of rheumatoid arthritis (RA) and as candidate cells for the development of cell-based methods to treat autoimmune diseases. The development of treatment strategies requires comprehensive research into the quantitative and qualitative characteristics of DC subtypes both ex vivo from RA patients and in vitro, to determine the possibility of inducing functionally mature DC in RA.
OBJECTIVE
To study the phenotypic and functional properties of myeloid (mDC) and plasmacytoid (pDC) DC isolated from the peripheral blood of patients with RA and induced in vitro.
MATERIALS AND METHODS
Blood samples were obtained from RA patients and healthy donors. Immature DC in the whole blood and in vitro induced DC were characterized by the positive expression of CD80, CD83, CCR7, IL-10, IL-4, IL-12 and IFN-α. R848 and lipopolysaccharide were used to determine DC maturation ability. From PBMCs of RA patients and health donors DCs with myeloid (imDC) and plasmacytoid (ipDC) phenotype were induced.
RESULTS
The relative count of mDC in the peripheral blood between studied groups did not differ. pDC count was significantly lower for RA patients. DC from RA patients were characterized by low expression levels of CD80 and CD83 on both populations cells and high expression of CCR7 only on pDC. An increase in pDC producing IL-12 and IFN-α and a decrease in mDC and pDC producing IL-4 and IL-10 were shown in RA. imDC and ipDC obtained from RA patients according to their phenotype and cytokine profile did not differ from those obtained from healthy donors.
CONCLUSIONS
There is an imbalance between subpopulations of DC in the peripheral blood of RA patients. DC of RA patients are less mature. The data suggest the involvement of DC in RA pathogenesis and confirm DC participation in balance shift towards Th1-type immune responses. At the same time, in vitro induced RA DC are phenotypically and functionally competent.
|
10.1016/j.humimm.2016.07.005
|
pubmed_182_5299
|
This paper presents the results of two studies on the invariance of the Profile of Mood States questionnaire across response time frames and circumstances of administration. We applied Spanish versions of the instrument to gather data from 1146 athletes. In the first study (N = 700), we tested the factor structure of the questionnaire in training sessions by using two different time frames: 'right now' (n = 350) and 'past week' (n = 350). In the second study (N = 446), we compared the factor structure of the questionnaire with data collected using the instruction 'right now' at two different circumstances: 'training' (n = 223) and 'competition' (n = 223). Data analysis was similar in both studies. We conducted multi-group confirmatory factor analyses and applied the scaled difference chi-square statistic to examine whether discrepancies in successive constrained models were significant. We observed configural equivalence between the two time frames. Furthermore, we observed metric equivalence but not scalar invariance between the different circumstances of measurement. The findings highlight the need for studies of equivalence before using a single self-report with more than one set of instructions, or under diverse circumstances. Invariance of mood scores should be examined and taken into account when interpreting individual and group mood state assessments.
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10.1371/journal.pone.0205892
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pubmed_873_5970
|
PURPOSE
Axitinib (Inlyta, New York, NY) is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of one previous systemic therapy. A case of bilateral retinal hemorrhages and cotton wool spots associated with axitinib is reported.
METHODS
A 62-year-old woman with a 4-year history of renal cell carcinoma with metastases was treated with axitinib at a maximum oral daily dose of 8 mg. Soon after beginning higher dose therapy, she developed blurred vision, floaters, and photopsias.
RESULTS
Funduscopic examination of both eyes revealed cotton wool spots and retinal hemorrhages that improved with cessation of therapy.
CONCLUSION
Axitinib may be associated with microangiopathic retinal toxicity.
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10.1097/ICB.0000000000000771
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pubmed_345_11664
|
BACKGROUND AND AIMS
Prediabetes increases cardiovascular risk and is associated with excess mortality. In preclinical models, metformin has been shown to exert anti-ageing effects. In this study, we sought to assess whether metformin modulates putative effector longevity programs in prediabetic subjects.
METHODS AND RESULTS
In a randomized, single-blind, placebo-controlled trial, 38 prediabetic subjects received metformin (1500 mg/day) or placebo for 2 months. At baseline and after treatment, we collected anthropometric and metabolic parameters. Gene and protein levels of SIRT1, mTOR, p53, p66Shc, SIRT1 activity, AMPK activation, telomere length, and SIRT1 promoter chromatin accessibility were determined in peripheral blood mononuclear cells (PBMCs). Plasma N-glycans, non-invasive surrogate markers of ageing, were also analysed. Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in subjects' PBMCs, and modified the plasma N-glycan profile. Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR activity). Plasma N-glycans were also favourably modified by metformin compared to placebo.
CONCLUSION
In individuals with prediabetes, metformin ameliorated effector pathways that have been shown to regulate longevity in animal models. ClinicalTrials. gov identifier: NCT01765946 - January 2013.
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pubmed_345_11664
|
pubmed_525_20099
|
The effect of sphingomyelin on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) in washed rabbit platelets was examined. Sphingomyelin had a powerful inhibitory effect on 12-HETE formation, while it produced only a small increase in thromboxane B2 and HHT formation. The sphingomyelin metabolite ceramide did not affect the formation of 12-HETE, thromboxane B2 and HHT. These results suggest that sphingomyelin is a selective inhibitor of platelet 12-lipoxygenase and may have functional effects in platelets.
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10.1016/s0014-2999(99)00473-2
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pubmed_640_442
|
Calcium appears to be an essential participant in axon excitation processes. Many other polyvalent metal ions have calcium-like actions on axons. We have used the voltage-clamped lobster giant axon to test the effect of several of these cations on the position of the peak initial (sodium) and steady-state (potassium) conductance vs. voltage curves on the voltage axis as well as on the rate parameters for excitation processes. Among the alkaline earth metals, Mg(+2) is a very poor substitute for Ca(+2), while Ba(+2) behaves like "high calcium" when substituted for Ca(+2) on a mole-for-mole basis. The transition metal ions, Ni(+2), Co(+2), and Cd(+2) also act like high calcium when substituted mole-for-mole. Among the trivalent ions, La(+3) is a very effective Ca(+2) replacement. Al(+3) and Fe(+3) are extremely active and seem to have some similar effects. Al(+3) is effective at concentrations as low as 10(-5)M. The data suggest that many of these ions may interact with the same cation-binding sites on the axon membrane, and that the relative effects on the membrane conductance and rate parameters depend on the relative binding constants of the ions. The total amount of Na(+) transferred during a large depolarizing transient is nearly independent of the kind or amount of polyvalent ion applied.
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10.1085/jgp.51.3.279
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pubmed_655_15472
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This study examined relationships between the economic, human, social, and cultural capital of families and adolescents' academic achievement. Data were collected from 387 14-yr.-old Hong Kong students (187 girls, 200 boys), who completed questionnaires to assess their perceptions of the various dimensions of family capital. Academic achievement was measured by performance in Chinese language, English language, and mathematics. The findings indicated that different combinations of the dimensions of family capital combined to contribute to moderate amounts of variance in adolescent girls' academic performance, whereas social capital was the only family measure to have a meaningful and significant modest association with adolescent boys' academic achievement.
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10.2466/pr0.1998.83.1.99
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pubmed_718_17503
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Psoriasis vulgaris has been recognized lately as an immunologically mediated inflammatory skin disease. To analyze the pathogenetic role of T lymphocytes in the generation of psoriatic skin lesions, 105 T cell clones (TCC) and 10 T cell lines (TCL) were differentially isolated from dermis and epidermis of psoriatic skin specimens. Supernatants prepared from these T cells were studied for their effects on keratinocyte proliferation in vitro. Conditioned media from 14 of 77 epidermal TCC, 7 of which were CD8+, and from 8 of 28 dermal TCC, 5 of which were CD8+, reproducibly enhanced keratinocyte proliferation, with more pronounced mitogenic activities found in dermal TCC. Another 9 epidermal and 3 dermal TCC did not affect keratinocyte growth and supernatants from the remaining clones, as well as from the 5 epidermal and 5 dermal TCL, inhibited keratinocyte replication to varying degrees. Both mitogenic and suppressive activities were largely abolished by addition of an antiserum to interferon-gamma (IFN-gamma), while addition of epidermal growth factor or irradiated psoriatic TCL had little effect on the activities of the supernatants. These studies reveal that a subpopulation of lesional psoriatic T lymphocytes is capable of enhancing keratinocyte proliferation in vitro via secreted products. Their mitogenic capacity most likely requires IFN-gamma, but the ultimate effect is apparently determined by the presence of additional cytokines. Activation of T cells secreting such combinations of factors in vivo may contribute to the keratinocyte alterations characteristic of psoriatic skin lesions.
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10.1002/eji.1830240315
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pubmed_648_13205
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Sepsis in intensive care units (ICUs) represent a threat with need for rapid and accurate diagnosis. We aimed to assess miR-122 as an early biomarker for diagnosis and outcome prediction in patients with hospital acquired sepsis in ICU. This case control study included 25 adults' patients with sepsis and 25 patients with local wound infections as a control group. C-reactive protein (CRP), total leucocytes count (TLC), liver function, and molecular determination of miR-122 levels were assessed. miR-122 had significant higher area under curve (AUC) when compared with CRP and TLC for differentiation of sepsis from wound infections. The cut off value for miR-122 was 0.16 folds expression with sensitivity, specificity and accuracy 100%. The TLC cut off value was 14.00 x103/cmm with 100% sensitivity, 84% specificity and 92% accuracy. While CRP cut off value was 41 mg/l with 76.0% sensitivity, 100% specificity, and 88.0% accuracy. Multivariate logistic analysis revealed non statistically significant difference between survivors and non survivors regarding sepsis biomarkers. Receiver operation curve (ROC) for different biomarkers, CRP, TLC and miR-122 to differentiate patients with poor outcome of sepsis compared to patients with recovery, revealed that AUC was 0.61, 0.6, and 0.45 respectively. miR-122 as a prognostic biomarker for sepsis had 66.6% sensitivity, 50% specificity, and 56.0% accuracy. The present study highlights important points in the use of biomarkers in diagnosis of sepsis in adults' patients above 50 years old. miR-122 is an accurate and specific biomarker for diagnosis of sepsis. miR-122 has limited predictive value for determination of the outcome of patients with sepsis even when used in combination with another biomarker such as CRP and TLC.
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pubmed_648_13205
|
pubmed_953_23113
|
Degradation processes in various biomasses are managed by complex metabolic dynamics created by diverse and extensive interactions and competition in microbial communities and their environments. It is important to develop visualization methods to provide a bird's-eye view when characterizing the entire sequential metabolic process in an environmental ecosystem. Here, we describe an approach for the visualization of the metabolic sequences in anaerobic fermentation ecosystems, characterizing the entire metabolic dynamics using a combination of microbial community profiles and metabolic profiles. By evaluating their time-dependent variation, we found that microbial community profiles and metabolite production processes were characteristically affected by the feeding of different glucose-based substrates (glucose, starch, cellulose), although the compositions of the major microbial community and the metabolites detected were likely to be similar in all experiments. This combinatorial approach to variation in microbial communities and metabolic profiles was used successfully to visualize metabolic sequences in anaerobic fermentation ecosystems, in addition to mining candidate microbiota for cellulose degradation. Thus, this approach provides a powerful tool for visualizing and evaluating metabolic sequences within the biomass degradation process in an environmental ecosystem. This is the first report to visualize the entire metabolic dynamic in an anaerobic fermentation ecosystem as metabolic sequences.
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10.1021/pr3008682
|
pubmed_798_3683
|
OBJECTIVE
To examine whether the 1-year prevalence of major depressive disorder (MDD), generalized anxiety disorder (GAD), and their comorbidity were associated with subsequent all-cause and cardiovascular disease (CVD) mortality during 15 years in Vietnam veterans.
METHODS
Participants (N = 4256) were from the Vietnam Experience Study. Service, sociodemographic, and health data were collected from service files, telephone interviews, and a medical examination. One-year prevalence of MDD and GAD was determined through a diagnostic interview schedule based on the Diagnostic and Statistical Manual of Mental Disorders (version IV) criteria. Mortality over the subsequent 15 years was gathered from US army records.
RESULTS
MDD and GAD were positively and significantly associated with all-cause and CVD mortality. The relationships between MDD and GAD and CVD mortality were no longer significant after adjustment for sociodemograhics, health status at entry, health behaviors, and other risk markers. Income was the covariate with the strongest impact on this association. In analyses comparing comorbidity and GAD and MDD alone, with neither diagnosis, comorbidity proved to be the strongest predictor of both all-cause and CVD mortality.
CONCLUSION
GAD and MDD predict all-cause mortality in a veteran population after adjusting for a range of covariates. However, those with both GAD and MDD were at greatest risk of subsequent death, and it would seem that these disorders may interact synergistically to affect mortality. Future research on mental disorders and health outcomes, as well as future clinical interventions, should pay more attention to comorbidity.
|
10.1097/PSY.0b013e31819e6706
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pubmed_893_10490
|
The impact of changing climate on terrestrial and underwater archaeological sites, historic buildings, and cultural landscapes can be examined through quantitatively-based analyses encompassing large data samples and broad geographic and temporal scales. The Digital Index of North American Archaeology (DINAA) is a multi-institutional collaboration that allows researchers online access to linked heritage data from multiple sources and data sets. The effects of sea-level rise and concomitant human population relocation is examined using a sample from nine states encompassing much of the Gulf and Atlantic coasts of the southeastern United States. A 1 m rise in sea-level will result in the loss of over >13,000 recorded historic and prehistoric archaeological sites, as well as over 1000 locations currently eligible for inclusion on the National Register of Historic Places (NRHP), encompassing archaeological sites, standing structures, and other cultural properties. These numbers increase substantially with each additional 1 m rise in sea level, with >32,000 archaeological sites and >2400 NRHP properties lost should a 5 m rise occur. Many more unrecorded archaeological and historic sites will also be lost as large areas of the landscape are flooded. The displacement of millions of people due to rising seas will cause additional impacts where these populations resettle. Sea level rise will thus result in the loss of much of the record of human habitation of the coastal margin in the Southeast within the next one to two centuries, and the numbers indicate the magnitude of the impact on the archaeological record globally. Construction of large linked data sets is essential to developing procedures for sampling, triage, and mitigation of these impacts.
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10.1371/journal.pone.0188142
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pubmed_1031_536
|
In higher animals, it is now generally accepted that neurosteroids are steroids that are synthesized in the brain itself, but it remains unclear where, in terms of the phylogeny of chordates, such neurosteroids are first synthesized? We have tried to detect progesterone immunohistochemically in the central nervous system of the amphioxus, Branchiostoma belcheri, an ancient species of chordate. We found immunoreactivity specific for progesterone in the giant neurons known as Rohde cells, at sites that included the perikaryon, in axons and in a thick coarse axon in addition to the gonads. Thus, the present progesterone-like substance appeared to be a phylogenetically ancient and ancestral neurosteroid. Rohde cells are known to be the source of Mauthner cells and to act as interneurons and, therefore, it seems possible that progesterone-like substance might be involved in primitive sigmoid movement, acting as a chemical signal. The presence of progesterone-like substance in amphioxus suggests that animals have evolved by effectively exploiting a rather limited number of active compounds. This report is the first, to our knowledge, to demonstrate that the Rohde cells in the spinal cord of amphioxus have progesterone-like substance, which might be involved in swimming.
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10.1016/s0016-6480(03)00099-6
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pubmed_28_24212
|
Marine pollution impacts coastal nations around the world, and more so: (a) in confined maritime areas with significant marine traffic, (b) where exploitation of natural and mineral resources is taking place, or (c) in regions witnessing pressure from tourism, local population growth, and industry. In this work, Digital Elevation Models, hydrographic, and climatic data are used together with computer simulations to understand the control of climate change on marine pollution. The results show that different climate change signals can potentially alter the flow and concentration of pollution in the European Seas, when compared to the present day. Ultimately, this work identifies the main sources of marine pollution as: (1) rivers and streams near cities and industrialised areas, (2) coastal areas experiencing sudden demographic pressures, (3) offshore shipping lanes in which oil and other marine debris are released, and (4) areas of rugged seafloor where industrial fishing takes place. This paper finishes by describing new educational material prepared to teach school children around the world. It explains why how a new training curriculum and e-game developed by Sea4All can be crucial in future Environmental Education and Education for a Sustainable Development.
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10.1038/s41598-021-82421-y
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pubmed_349_4259
|
BACKGROUND
Wrist arthroscopy is a dynamic diagnostic procedure and its indications are growing as a treatment modality in the adult population. The aim of the study was to retrospectively report our series of pediatric and adolescence with chronic wrist pain, with or without wrist instability who underwent wrist arthroscopy after failing at least 4 months of conservative management. Our secondary aim was to report the sensitivity and specificity of clinical examination and magnetic resonance imaging evaluation for various injury subgroups against the gold standard of the arthroscopic findings. Technical challenges, complications, and outcomes are also discussed.
METHODS
A retrospective review of the medical records of 32 pediatric and adolescent patients who underwent wrist arthroscopy was conducted. Preoperative clinical diagnosis, radiographic, and intraoperative findings including classifications of triangular fibrocartilage complex (TFCC) and interosseous ligaments were obtained. Patients were followed up to 1 year postoperatively and were discharged if symptom free.
RESULTS
Thirty-three wrist arthroscopies in 32 patients were performed from 1996 to 2004. There were 2 male and 30 female patients. At arthroscopy 16 wrists were found to have TFCC injuries, 11 wrists had scapholunate injuries, and 8 had lunotriquetral (LT) injuries. Clinical examination for diagnosis of TFCC injury was too sensitive and nonspecific; however, clinical diagnosis of scapholunate injury was sensitive and specific. LT injury was under diagnosed clinically. Magnetic resonance imaging was found to have a low sensitivity for diagnosis of LT injury but diagnosis of TFCC was sensitive and specific.
CONCLUSIONS
The sex ratio of 2 males:30 females was startling. Nevertheless, this therapeutic level 3 study supports a thorough search for pathology in any patient with persistent wrist symptoms because pathology was identified in 32 of the 33 wrists at arthroscopy.
LEVEL OF EVIDENCE
Level III-Therapeutic.
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10.1097/BPO.0000000000000887
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pubmed_1022_16195
|
UNLABELLED
Ataxia telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein activated in response to DNA damage. We recently reported that ATM plays a protective role in myocardial remodeling following β-adrenergic receptor stimulation. Here we investigated the role of ATM in cardiac remodeling using myocardial infarction (MI) as a model.
METHODS AND RESULTS
Left ventricular (LV) structure, function, apoptosis, fibrosis, and protein levels of apoptosis- and fibrosis-related proteins were examined in wild-type (WT) and ATM heterozygous knockout (hKO) mice 7 days post-MI. Infarct sizes were similar in both MI groups. However, infarct thickness was higher in hKO-MI group. Two dimensional M-mode echocardiography revealed decreased percent fractional shortening (%FS) and ejection fraction (EF) in both MI groups when compared to their respective sham groups. However, the decrease in %FS and EF was significantly greater in WT-MI vs hKO-MI. LV end systolic and diastolic diameters were greater in WT-MI vs hKO-MI. Fibrosis, apoptosis, and α-smooth muscle actin staining was significantly higher in hKO-MI vs WT-MI. MMP-2 protein levels and activity were increased to a similar extent in the infarct regions of both groups. MMP-9 protein levels were increased in the non-infarct region of WT-MI vs WT-sham. MMP-9 protein levels and activity were significantly lower in the infarct region of WT vs hKO. TIMP-2 protein levels similarly increased in both MI groups, whereas TIMP-4 protein levels were significantly lower in the infarct region of hKO group. Phosphorylation of p53 protein was higher, while protein levels of manganese superoxide dismutase were significantly lower in the infarct region of hKO vs WT. In vitro, inhibition of ATM using KU-55933 increased oxidative stress and apoptosis in cardiac myocytes.
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10.1371/journal.pone.0083513
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pubmed_990_16558
|
The most important level of the regulation of the beta-globin genes is by activation of all of the genes by the locus control region (LCR). Part of the developmental regulation of the locus is achieved by competition of the genes for the interaction with the LCR. Although this level of gene regulation is quantitatively of less importance than the direct repression mechanism for the early genes, it has important implications and has provided an excellent assay to probe the regulation of transcription at the single cell level. The results of these studies indicate that the LCR interacts with individual globin genes and that LCR/gene interactions are dynamic with complexes forming and dissociating continually. We conclude that transcription only appears to take place while the LCR and gene interact and that the level of transcription is determined by the frequency and duration of such interaction rather than by changes in the rate of transcription of the promoters. This mechanism has clear implications for the design of vectors for the purpose of gene therapy.
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pubmed_990_16558
|
pubmed_1023_3856
|
To determine the prevalence of high-risk thallium-201 (Tl-201) scintigraphic findings in patients with left main (LM) coronary artery disease (CAD), quantitative exercise Tl-201 scintigrams were analyzed in 295 consecutive patients with angiographic (greater than or equal to 50% stenosis) CAD, of which 43 (14%) had greater than or equal to 50% LM stenosis. A high-risk scintigram was defined as one that demonstrated (1) a LMCAD scintigraphic pattern (greater than or equal to 25% homogeneous decrease in Tl-201 activity in the middle and upper septal and posterolateral walls on the 45 degree left anterior oblique projection); (2) abnormal Tl-201 uptake or washout in multiple vascular scan segments indicative of multivessel disease; and (3) increased lung Tl-201 uptake on the initial anterior projection image. Of the 43 patients with LMCAD, 41 (95%) had an abnormal scintigram. Thirty-three (77%) had 1 or more high-risk scintigraphic findings, including 29 (67%) with a multivessel CAD scan pattern, of which 6 (14%) demonstrated a typical LMCAD pattern; and 18 (42%) with abnormal lung Tl-201 uptake. The prevalence of a high-risk scintigram in patients with LMCAD was significantly greater than that in 53 patients with 3-vessel disease (58%) (p = 0.05), 99 patients with 2-vessel disease (60%) (p = 0.04) and 100 patients with 1-vessel disease (41%) (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
|
10.1016/0002-9149(84)90013-4
|
pubmed_655_4645
|
Pallidotomy has become a widely used treatment for medically refractory Parkinson's disease. However, the optimal lesion size and location within the pallidum have not yet been determined, and the role of repeated pallidotomy remains undefined. The authors present two patients who had unsatisfactory results after their first unilateral pallidotomy but attained dramatic and long-lasting improvement with repeated surgery. The results obtained in these cases indicate that patients who have a good clinical outcome initially but relapse rapidly after surgery should be considered for repeated pallidotomy if the initial lesion was not placed in the optimal location.
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10.3171/jns.1998.89.4.0630
|
pubmed_982_1384
|
The study consisted of two sets of experiments, one in saliva and one in dental plaque. The xylitol concentration in saliva was determined enzymatically in 12 children (mean age 11.5 years) after a standardised use of various xylitol products: (A) chewing gums (1.3 g xylitol), (B) sucking tablets (0.8 g xylitol), (C) candy tablets (1.1 g xylitol), (D) toothpaste (0.1 g xylitol), (E) rinse (1.0 g xylitol), and (F) a non-xylitol paraffin. Unstimulated saliva was sampled 1, 3, 8, 16 and 30 min after use. The concentration in dental plaque was determined after mouthrinses with contrasting amounts of xylitol (LX = 2.0 g, HX = 6.0 g, and control) and supragingival plaque was collected and pooled after 5, 15 and 30 min. The mean xylitol concentration in saliva at baseline was approximately 0.1 mg/ml. All xylitol-containing products resulted in significantly increased levels (p < 0.05) immediately after intake and remained elevated for 8-16 min in the different groups. The highest mean value in saliva was obtained immediately after use of chewing gums (33.7 +/- 16.4 mg/ml) and the lowest was demonstrated after using toothpaste (8.2 +/- 4.9 mg/ml). No significant differences were demonstrated between chewing gums (A), sucking tablets (B), candy (C) and rinses (E). In dental plaque, the mean values were 8.6 +/- 5.4 and 5.1 +/- 4.0 mg/ml 5 min after HX and LX rinses. Concerning the higher concentration, the values remained significantly elevated (p < 0.05) during the entire 30-min follow-up. In conclusion, commonly advocated xylitol-containing products gave elevated concentrations of xylitol in unstimulated whole saliva and dental plaque for at least 8 min after intake.
|
10.1159/000094284
|
pubmed_890_1506
|
Spherical-crystal microscopes are used as high-resolution imaging devices for monochromatic x-ray radiography or for imaging the source itself. Crystals and Miller indices (hkl) have to be matched such that the resulting lattice spacing d is close to half the spectral wavelength used for imaging, to fulfill the Bragg equation with a Bragg angle near 90∘ which reduces astigmatism. Only a few suitable crystal and spectral-line combinations have been identified for applications in the literature, suggesting that x-ray imaging using spherical crystals is constrained to a few chance matches. In this article, after performing a systematic, automated search over more than 9 × 106 possible combinations for x-ray energies between 1 and 25 keV, for six crystals with arbitrary Miller-index combinations hkl between 0 and 20, we show that a matching, efficient crystal and spectral-line pair can be found for almost every Heα or Kα x-ray source for the elements Ne to Sn. Using the data presented here it should be possible to find a suitable imaging combination using an x-ray source that is specifically selected for a particular purpose, instead of relying on the limited number of existing crystal imaging systems that have been identified to date.
|
10.1063/1.4972248
|
pubmed_235_599
|
von Willebrand disease (VWD) is characterized by its heterogeneous clinical manifestation, which complicates its diagnosis and management. The clinical management of VWD has remained essentially unchanged over the last 30 years or so, using von Willebrand factor (VWF) concentrates, desmopressin, and anti-fibrinolytic agents as main tools to control bleeding. This is in contrast to hemophilia A, for which a continuous innovative path has led to novel treatment modalities. Despite current VWD management being considered effective, quality-of-life studies consistently reveal a higher than anticipated burden of VWD on patients, which is particularly true for women. Apparently, despite our perceived notion of current therapeutic efficiency, there is space for innovation with the goal of reaching superior efficacy. Developing innovative treatments for VWD is complex, especially given the heterogeneity of the disease and the multifunctional nature of VWF. In this perspective article, we describe several potential strategies that could provide the basis for future VWD treatments. These include genetic approaches, such as gene therapy using dual-vector adenoassociated virus and transcriptional silencing of mutant alleles. Furthermore, protein-based approaches to increase factor FVIII levels in VWD-type 3 or 2N patients are discussed. Finally, antibody-based options to interfere with VWF degradation (for congenital VWD-type 2A or acquired von Willebrand syndrome-type 2A) or increase endogenous VWF levels (for VWD-type 1) are presented. By highlighting these potential strategies, we hope to initiate an innovative path, which ultimately would allow us to better serve VWD patients and their specific needs.
|
10.1182/blood.2020008501
|
pubmed_958_309
|
OBJECTIVE
To investigate the relative importance of various risk and protective factors for mental health and social adjustment in young refugee children.
METHOD
Of 50 Iranian refugee preschool children who were first evaluated 12 months after arriving in Sweden, 39 were reevaluated in a follow-up study 2 1/2 years later. The effect of exposure to organized violence, age, gender, individual vulnerability, parental functioning, and peer relationships on the children's well-being and adjustment was investigated using multiple and logistic regression analyses.
RESULTS
Exposure to war and political violence and individual vulnerability before traumatic stress exposure were important risk factors for long-lasting post-traumatic stress symptomatology in children. Mothers' emotional well-being predicted emotional well-being in children, whereas children's social adjustment and self-worth were mainly predicted by the quality of their peer relationships.
CONCLUSIONS
The results underline the fact that refugee children's adaptation is the result of a complex process involving several interacting risk and protective factors. For many refugee children, current life circumstances in receiving host countries, such as peer relationships and exposure to bullying, are of equal or greater importance than previous exposure to organized violence.
|
pubmed_958_309
|
pubmed_51_6926
|
OBJECTIVES
In achondroplastic patients with slight complaints of medullary compression the cervical spinal cord regularly exhibits an intramedullary (CHII) lesion just below the craniocervical junction with no signs of focal compression on the cord. Currently, the prevalence of the lesion in the general achondroplastic population is studied and its origin is explored.
METHODS
Eighteen achondroplastic volunteers with merely no clinical signs of medullary compression were subjected to dynamic magnetic resonance imaging (MRI). The presence of a CHII lesion and craniocervical medullary compression in flexed and retroflexed craniocervical positions was explored. Several morphological characteristics of the craniocervical junction, possibly related to compression on the cord, were assessed.
RESULTS
A CHII lesion was observed in 39% of the subjects and in only one of these was compression at the craniocervical junction present. Consequently, no correlation between the CHII lesion and compression could be established. None of the morphological characteristics demonstrated a correlation with the CHII lesion, except thinning of the cord at the site of the CHII lesion.
CONCLUSIONS
CHII lesions are a frequent finding in achondroplasia, and are generally unaccompanied by clinical symptoms or compression on the cord. Further research focusing on the origin of CHII lesions and their clinical implications is warranted.
KEY POINTS
• MRI now reveals exquisite detail of the cervical spinal cord. • Cervical cord lesions are observed in one third of the achondroplastic population. • These lesions yield high signal intensity on T2 weighted MRI. • They are generally unaccompanied by clinical symptoms or cord compression. • Their aetiology is unclear and seems to be unrelated to mechanical causes.
|
10.1007/s00330-012-2488-0
|
pubmed_239_15938
|
Symbiotic microbial communities augment host phenotype, including defense against pathogen carriage and infection. We sampled the microbial communities in 11 adult mosquito host species from six regions in southern Ontario, Canada over 3 years. Of the factors examined, we found that mosquito species was the largest driver of the microbiota, with remarkable phylosymbiosis between host and microbiota. Seasonal shifts of the microbiome were consistently repeated over the 3-year period, while region had little impact. Both host species and seasonal shifts in microbiota were associated with patterns of West Nile virus (WNV) in these mosquitoes. The highest prevalence of WNV, with a seasonal spike each year in August, was in the Culex pipiens/restuans complex, and high WNV prevalence followed a decrease in relative abundance of Wolbachia in this species. Indeed, mean temperature, but not precipitation, was significantly correlated with Wolbachia abundance. This suggests that at higher temperatures Wolbachia abundance is reduced leading to greater susceptibility to WNV in the subsequent generation of C. pipiens/restuans hosts. Different mosquito genera harbored significantly different bacterial communities, and presence or abundance of Wolbachia was primarily associated with these differences. We identified several operational taxonomic units (OTUs) of Wolbachia that drive overall microbial community differentiation among mosquito taxa, locations and timepoints. Distinct Wolbachia OTUs were consistently found to dominate microbiomes of Cx. pipiens/restuans, and of Coquilletidia perturbans. Seasonal fluctuations of several other microbial taxa included Bacillus cereus, Enterococcus, Methylobacterium, Asaia, Pantoea, Acinetobacter johnsonii, Pseudomonas, and Mycoplasma. This suggests that microbiota may explain some of the variation in vector competence previously attributed to local environmental processes, especially because Wolbachia is known to affect carriage of viral pathogens.
|
10.3389/fmicb.2017.00526
|
pubmed_920_18001
|
The interest in minimising fuel consumption and greenhouse gas emissions among road specialists is increasing. Thus, methods for reducing asphalt concrete mixing and compaction temperatures by a few tens of degrees Celsius without compromising the long-term performance has become a topic of significant interest. This study is focused on the analysis of warm mix asphalt (WMA) prepared with locally available materials in order to determine the suitable technology applicable to the specific traffic and climatic conditions of Romania. WMA was prepared using different warm mix additives (organic additives, chemical additive, and synthetic zeolite) at different mixing and compaction temperatures, and bitumen blends with these additives were analysed by carrying out the dynamic shear rheometer test and evaluating the penetration index. In conclusion it was noted that most additives did not lead to a significant change of bitumen's characteristics, but the organic additive had a big influence on the bitumen's properties. The characteristics of WMA are very similar to those of HMA. The mixing and compaction temperatures could be reduced by approximately 40 °C when WMA was blended with the additives without compromising the performance of the asphalt mixture, compared to hot mix asphalt.
|
10.3390/ma14133534
|
pubmed_444_2289
|
Human factors, as perceived by the maintenance workforce, were used as the measure for comparing work areas within a petroleum company. These factors were then compared to an objective measure of reliability (Mean Time Between Failures) in order to determine which factors would be most predictive of plant reliability and process safety. Maintenance personnel were surveyed using scales based on Problem-solving, Vigilance, Design and maintenance, Job-related feedback and Information about change. Analysis of Variance was used to assess the strength of these variables in relation to Reliability Level. Significant differences were observed between different reliability levels based on workforce perceptions of problem-solving requirements and the design and maintainability of plant. Conclusions were that perceptions of human factors in the workplace can be predictive of group-level performance, and that if issues relating to design and maintainability are not addressed at the design stage, greater problem-solving abilities will be required from maintenance personnel. Practitioner summary: Workforce perceptions of plant performance could provide a statistically valid measure of current and future reliability. A survey of perceptions of human factors was conducted with maintenance personnel in a petroleum company. Results indicated significant relationships between reliability and requirements for Problem-solving, as well as Design and Maintenance of equipment. Abbreviations: HFIT: human factors investigation tool, FPSO: floating production, storage and offtake, MTBF: mean time between failures, CPS: cognitive problem- solving, WDS: work design questionnaire, SPSS: statistical package for the social sciences, PAF: principal axis factoring, ANOVA: analysis of variance, ANCOVA: analysis of co-variance, M: mean, SD: standard deviation.
|
10.1080/00140139.2020.1823489
|
pubmed_1140_17234
|
Selective cargo capture into ER-derived vesicles is driven by the Sec24p subunit of the COPII coat, which contains at least three independent cargo-binding sites. One of these, the "A-site," interacts with a NPF motif found on the SNARE, Sed5p. We have characterized the Sec24p-Sed5p interaction through mutation of the putative ER export motifs of Sed5p and the cargo-binding A-site of Sec24p. Mutational analysis of Sed5p suggests that the NPF motif is the dominant ER export signal. Mutation of the NPF binding pocket on Sec24p led to a dramatic reduction in the capture of Sed5p into COPII vesicles, whereas packaging of other ER-Golgi SNAREs was normal. Of all the cargoes tested, only Sed5p was depleted in vesicles made with Sec24p A-site mutants. Surprisingly, vesicles generated with the mutant Sec24p were unable to fuse with the Golgi apparatus. This inability to fuse was not the result of the lack of Sed5p, because vesicles specifically depleted of Sed5p generated by antibody inhibition targeted and fused normally. We propose that the A-site of Sec24p is a multipurpose cargo-binding site that must recognize additional unidentified cargo proteins, at least one of which is essential at a late stage of vesicle fusion.
|
10.1091/mbc.e05-03-0262
|
pubmed_1027_20444
|
PURPOSE
To address the lack of fundamental thermophysical data for trehalose and its aqueous systems by measuring equilibrium and non-equilibrium properties of such systems.
METHODS/RESULTS
Differential scanning calorimetry (DSC) and dynamic mechanical analysis were used to measure glass transition temperatures of trehalose and its solutions. X-ray diffractometry was used to verify the structure of amorphous trehalose. Controlled-stress rheometry was used to measure viscosity of several aqueous trehalose systems at ambient and sub-ambient temperatures. Over this temperature range, the density of these solutions was also measured with a vibrating tube densimeter. The equilibrium phase diagram of aqueous trehalose was determined by measuring the solubility and freezing point depression.
CONCLUSIONS
Our solubility measurements, which have allowed long times for attainment of chemical equilibrium, are substantially different from those reported earlier that used different techniques. Our measurements of the glass transition temperature of trehalose are higher than reported values. A simple model for the glass transition is presented to describe our experimental observations.
|
10.1023/a:1012192725996
|
pubmed_236_13124
|
The structure of E. coli adenylate kinase with bound AMP and AMPPNP at 2.0 A resolution is presented. The protein crystallizes in space group C2 with two molecules in the asymmetric unit, and has been refined to an R factor of 20.1% and an Rfree of 31.6%. In the present structure, the protein is in the closed (globular) form with the large flexible lid domain covering the AMPPNP molecule. Within the protein, AMP and AMPPNP, and ATP analog, occupy the AMP and ATP sites respectively, which had been suggested by the most recent crystal structure of E. coli adenylate kinase with Ap5A bound (Müller and Schulz, 1992, ref. 1) and prior fluorescence studies (Liang et al., 1991, ref. 2). The binding of substrates and the positions of the active site residues are compared between the present structure and the E. coli adenylate kinase/Ap5A structure. We failed to detect a peak in the density map corresponding to the Mg2+ ion which is required for catalysis, and its absence has been attributed to the use of ammonium sulfate in the crystallization solution. Finally, a comparison is made between the present structure and the structure of the heavy chain of muscle myosin.
|
10.1002/prot.340190304
|
pubmed_160_3635
|
The title complex, [Cu(SO(4))(C(10)H(9)N(3))(CH(3)OH)], is a mononuclear species with the Cu(II) ion in a Jahn-Teller-distorted '4 + 1' square-pyramidal geometry. The basal plane is defined by the pyridyl N-atom donors of the bipyridyl-amine (bpa) ligand and two O-atom donors of the sulfate ligand. The coordination geometry is completed by the axial coordination of a methanol O-atom donor. The axial bond length displays the usual elongation: Cu-O(axial) = 2.168 (2), Cu-O(basal) = 2.016 (2) (average) and Cu-N(basal) = 1.951 (3) Å (average). In the crystal structure, the complex mol-ecules are linked through N-H⋯O and O-H⋯O hydrogen bonds into chains along [100].
|
10.1107/S1600536810038675
|
pubmed_741_14536
|
Physical inactivity has been cited as a possible cause of osteoporosis. Because involutional bone loss in the female can begin as early as age 40, the purpose of this investigation was to compare the skeletal status of two groups of premenopausal middle-aged (30-49 yr) women of diverse physical activity levels. Bone mineralization was determined by x-ray densitometry (middle phalanx of fifth finger and os calcis) and photon absorptiometry (distal and midshaft radius) in 42 marathon runners and 38 sedentary females. Mean values for bone mineral content (BMC) and bone density were greater in the marathon runners at the midshaft radius (P less than 0.05) and at the middle phalanx of the fifth digit (P less than 0.001). Mean density of the os calcis was higher in the physically inactive women (P less than 0.001). Following normalization of the data for differences in age and body size, regression analysis suggests that the runners maintain their bone mass longer at the distal radius, a site frequently fractured in women after midlife.
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pubmed_741_14536
|
pubmed_548_20789
|
Type 1 diabetes is associated with skeletal muscle atrophy. Skeletal muscle is an endocrine organ producing myokines such as interleukin-15 (IL-15) and interleukin-6 (IL-6) in response to contraction. These factors may mediate the effects of exercise on skeletal muscle metabolism and anabolic pathways. Lack of correlation between muscle IL-15 mRNA and protein levels after exercise training has been observed, while regulatory effects of IL-6 on IL-15 expression have also been suggested. This study determined post-exercise changes in muscle IL-15 and IL-6 mRNA expression and IL-15 protein levels in healthy and streptozotocin-induced diabetic rats in both the fast flexor hallucis longus (FHL) and slow soleus muscles. Resistance training preserved FHL muscle weight in diabetic rats and increased IL-15 protein levels in both the soleus and FHL muscles. However, the temporal pattern of this response was distinct in normal and diabetic rats. Moreover, discordance between post-exercise muscle IL-15 mRNA and protein expression was observed in our study, and diabetes suppressed post-exercise increases in FHL muscle IL-6 mRNA expression. Our study indicates that training, skeletal muscle phenotype, and metabolic status all influence the temporal pattern of post-exercise changes in IL-15 expression. Muscle IL-15 protein levels increase following training, suggesting this may be an adaptation contributing to increased capacity for secretion of this myokine that is not depressed by the diabetic state.
|
10.1007/s12020-014-0501-x
|
pubmed_827_13021
|
A general framework is developed for separating classical and quantum correlations in a multipartite system. Entanglement is defined as the difference in the correlation information encoded by the state of a system and a suitably defined separable state with the same marginals. A generalization of the Schmidt decomposition is developed to implement the separation of correlations for any pure, multipartite state. The measure based on this decomposition is a generalization of the entanglement of formation to multipartite systems, provides an upper bound for the relative entropy of entanglement, and is directly computable on pure states. The example of pure three-qubit states is analyzed in detail, and a classification based on minimal, four-term decompositions is developed.
|
10.1103/PhysRevLett.92.077904
|
pubmed_26_3801
|
Developed more than a decade ago, the Chronic Care Model (CCM) is a widely adopted approach to improving ambulatory care that has guided clinical quality initiatives in the United States and around the world. We examine the evidence of the CCM's effectiveness by reviewing articles published since 2000 that used one of five key CCM papers as a reference. Accumulated evidence appears to support the CCM as an integrated framework to guide practice redesign. Although work remains to be done in areas such as cost-effectiveness, these studies suggest that redesigning care using the CCM leads to improved patient care and better health outcomes.
|
10.1377/hlthaff.28.1.75
|
pubmed_990_955
|
Our previous studies showed that the phosphaturic effect of parathyroid hormone (PTH) is blunted during acute-phase endotoxemia in anesthetized rats. However, the possibility that the antiphosphaturia was secondary to hyponatriuresis due to endotoxin (Et)-induced acute renal failure could not be ruled out. The objective of this study was to evaluate phosphate (Pi) excretion during early- and late-phase endotoxemia in conscious rats fed by total parenteral nutrition. Male Wistar rats weighing 270 g were used. Urine samples were taken to determine the Pi excretion rate for 12 h just after Et (E. coli B055) challenge (early-phase endotoxemia), and for 12 h after a 36-h recovery period following Et challenge (late-phase endotoxemia). Rats given isovolumetric saline instead of Et served as controls. Et injection reduced endogenous creatinine clearance markedly (0.88 +/- 0.12 ml/min, P < 0.0001, n = 7) and caused hyponatriuresis (0.80 +/- 0.19 microliters/min, P < 0.001) compared with saline injection (1.78 +/- 0.10 ml/min and 3.12 +/- 0.39 microliters/min, respectively, n = 8) during the early phase. Greater phosphaturia and hypocalciuria were observed simultaneously during early- (Pi excretion = 4.18 +/- 1.38 micrograms/min, P < 0.05; calcium excretion = 0.70 +/- 0.14 micrograms/min, P < 0.05) and late-phase (4.76 +/- 1.72 micrograms/min, P < 0.05; 0.60 +/- 0.18 micrograms/min, P < 0.05, respectively) endotoxemia (n = 8) in comparison with the respective control values (1.61 +/- 0.39 and 1.40 +/- 0.21 micrograms/min, early; 0.34 +/- 0.14 and 1.97 +/- 0.55 micrograms/min, late, n = 6). Et adminidstration resulted in a significantly increased plasma PTH concentration during the late phase (34.7 +/- 7.0 pg/ml, P < 0.05) compared with saline administration (15.4 +/- 2.4 pg/ml). In conclusion, these data suggest that the hyperphosphaturia during endotoxemia lasting longer than 12 h is attributable to elevated PTH secretion.
|
10.1055/s-2007-978842
|
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