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Systems toxicology approaches for understanding the joint effects of environmental chemical mixtures.
Environmental mixtures of chemicals constitute a prevalent issue in ecotoxicology and the development of new methods to reduce the uncertainties associated with their ecological risk assessment is a critical research need. Historically, a number of models have been explored to predict the potential combined effects of chemicals on species. These models, especially concentration addition and the independent action, have been applied to a number of mixtures. While often providing a good prediction of joint effect, there are cases where these models can have limitations: notably in cases where there are interactions for which they fail to adequately predict joint effects. To support the better mechanistic understanding of interactions in mixture toxicology a framework to support experimental studies to investigate the basis of observed interactions is proposed. The conceptual framework is derived from the extension of a three stage scheme which has previously been applied to understand chemical bioavailability. The framework considers that interactions in mixtures result from processes related to 1) the speciation, binding and transport of chemicals in the exposure medium (external exposure); 2) the adsorption, distribution, metabolism and excretion of chemicals within the organisms (toxicokinetics); 3) associations governing the binding and toxicity of the chemical(s) at the target site (toxicodynamics). The current state of the art in (eco)toxicology in relation to investigation of the mechanisms of interactions between chemicals is discussed with particular emphasis towards the multi-disciplinary tools and techniques within environmental chemistry; toxicology; biochemistry and systems biology that can be used to address such effects. | {
"pile_set_name": "PubMed Abstracts"
} |
Sensory impairment in late-life schizophrenia.
We reviewed 27 published studies examining a possible association between sensory (visual or hearing) impairment and late-life psychosis with paranoid features. A majority of these investigations supported the postulated association between hearing impairment and late-onset schizophrenia or paranoid disorder. Many of the published studies, however, had important methodological limitations. In a case-control study, we assessed visual and hearing impairments in 87 middle-aged and elderly subjects (16 with late-onset schizophrenia, 25 with early-onset schizophrenia, 20 with mood disorder, and 26 normal comparison subjects). Visual and hearing impairments were assessed in a blind manner by means of standardized quantitative assessments. Compared with normal subjects, both of the schizophrenia groups and the mood disorder group had greater impairment in most variables of corrected visual acuity and in self-reported hearing deficit, but not in uncorrected (constitutional) visual acuity or on pure-tone audiometry. Our results suggest that the observed relationship between sensory impairment and late-life psychosis may be due, at least in part, to a suboptimal correction of sensory deficits in older psychiatric patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Overview of 5-year followup outcomes in the drug abuse treatment outcome studies (DATOS).
Followup results from the Drug Abuse Treatment Outcome Studies (DATOS) 1-year and 5-year followups were used to describe the long-term outcomes of drug treatment and to further clarify the relationship between treatment duration and post-treatment outcomes in four treatment modalities: outpatient methadone, long-term residential (LTR), outpatient drug free (ODF), and short-term inpatient. Methods replicating those used in earlier analyses of the DATOS 1-year followup of 2,966 patients admitted to treatment in 1991-1993 and those of the Treatment Outcome Prospective Study patients admitted in 1979-1981 were employed. DATOS is a non-experimental longitudinal study conducted within the natural settings of 96 treatment programs in the U.S.A. The study followed patients during and after treatment at specified periods of time. Prevalence of drug use and behaviors were evaluated for the year prior to treatment; and the post-treatment time frames defined by the 1- and 5-year followups. In addition, the multivariate analytic technique of generalized estimating equations was used to examine the relationship of treatment duration and outcomes across both followups while also controlling for patient characteristics and pretreatment levels of behaviors. The 5-year stratified followup sample included 1,393 of the same individuals in the 1-year followup sample. Analyses were restricted to patients participating in both followups. Reductions in prevalence of cocaine use in the year after treatment (compared to the preadmission year) by patients were associated with longer treatment durations (particularly 6 months or more in LTR and ODF). In addition, reductions in illegal activity and increases in full-time employment were related to treatment stays of 6 months or longer for patients in LTR. The DATOS results from the 1-year and 5-year post-treatment followup combined suggest the stability of outcomes of substance abuse treatment. While results are generally consistent with the full 1-year followup, reduced sample size and bias of the sample toward patients with longer treatment retention may have attenuated the findings. | {
"pile_set_name": "PubMed Abstracts"
} |
The development of reactive saccade latencies.
Saccadic reaction time (SRT) of 4-, 6- and 8-month-old infants' was measured during tracking of abruptly changing trajectories, using a longitudinal design. SRTs decreased from 595 ms (SE=30) at 4 months of age to 442 ms (SE=13) at 8 months of age. In addition, SRTs were lower during high velocities (comparing 4.5 and 9 degrees/s) and vertical (compared to horizontal) saccades. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of interleukin-8 on estradiol and progesterone production by bovine granulosa cells from large follicles and progesterone production by luteinizing granulosa cells in culture.
Interleukin 8 (IL-8) is a chemoattractant involved in the recruitment and activation of neutrophils and is associated with the ovulate process. We examined the possible role of IL-8 in steroid production by bovine granulosa cells before and after ovulation. The concentration of IL-8 in the follicular fluid of estrogen-active dominant (EAD) and pre-ovulatory follicles (POF) was higher than that of small follicles (SF). CXCR1 mRNA expression was higher in the granulosa cells of EAD and POF than that of SF. In contrast, CXCR2 mRNA expression was lower in granulosa cells of EAD and POF than in SF. IL-8 inhibited estradiol (E2) production in follicle-stimulating hormone (FSH)-treated granulosa cells at 48 h of culture. IL-8 also suppressed CYP19A1 mRNA expression in FSH-treated granulosa cells. IL-8 stimulated progesterone (P4) production in luteinizing hormone (LH)-treated granulosa cells at 48 h of culture. Although IL-8 did not alter the expression of genes associated with P4 production, it induced StAR protein expression in LH-treated granulosa cells. The expression of CXCR1 mRNA in corpus luteum (CL) did not change during the luteal phase. In contrast, the expression of CXCR2 mRNA in middle CL was significantly higher than in early and regression CL during the luteal phase. In luteinizing granulosa cells, an in vitro model of granulosa cell luteinization, CXCR2 mRNA expression was downregulated, whereas CXCR1 mRNA expression was unchanged. IL-8 also stimulated P4 production in luteinizing granulosa cells. These data provide evidence that IL-8 functions not only as a chemokine, but also act as a regulator of steroid synthesis in granulosa cells to promote luteinization after ovulation. | {
"pile_set_name": "PubMed Abstracts"
} |
Xanthine oxidoreductase activity assay in tissues using stable isotope-labeled substrate and liquid chromatography high-resolution mass spectrometry.
Studies of pathological mechanisms and XOR inhibitor characterization, such as allopurinol, febuxostat, and topiroxostat, require accurate and sensitive measurements of XOR activity. However, the established assays have some disadvantages such as susceptibility to endogenous substances such as uric acid (UA), xanthine, or hypoxanthine. Here, we aimed to develop a novel XOR activity assay utilizing a combination of high-performance liquid chromatography (LC) and high-resolution mass spectrometry (HRMS) for tissues such as the liver, kidney, and plasma. Stable isotope-labeled [(15)N2]-xanthine was utilized as substrate and the production of [(15)N2]-uric acid was determined. [(15)N2]-UA production by XOR was dependent on the amounts of [(15)N2]-xanthine and enzyme and the time of reaction. Because high concentrations of endogenous xanthine and hypoxanthine affect XOR activities, we employed a multi-component analysis using LC/HRMS to improve the accuracy of XOR activity assay. Quantification of [(15)N2]-UA was validated and showed good linearity, accuracy, and precision. We measured the XOR activities of retired ICR mice using [(15)N2]-xanthine and LC/MS. The XOR activities in plasma, kidney, and liver samples were 38.1±0.7, 158±5, 928±25pmol/min/mg of protein, respectively (mean±SD, n=5). Furthermore, we measured the XOR activities in the same samples using the LC/ultraviolet and LC/fluorescence (FL) methods. The level of [(15)N2]-xanthine oxidation by XOR was equal to that of xanthine oxidation and approximately 7.9-8.9 times higher than that of pterin oxidation. We found a good correlation between XOR activities examined using LC/MS assay with [(15)N2]-xanthine and those examined using LC/FL assay with pterin. This result suggested that although both the LC/MS assay with [(15)N2]-xanthine and the LC/FL assay with pterin were useful, the former provided information regarding XOR activities that more directly reflected the physiological condition than the latter. | {
"pile_set_name": "PubMed Abstracts"
} |
Brain and sense organ anatomy and histology of two species of phyletically basal non-Antarctic thornfishes of the Antarctic suborder Notothenioidei (Perciformes: Bovichtidae).
The predominantly non-Antarctic family Bovichtidae is phyletically basal within the perciform suborder Notothenioidei, the dominant component of the Antarctic fish fauna. In this article we focus on the South Atlantic bovichtids Bovichtus diacanthus, the klipfish from tide pools at Tristan da Cunha, and Cottoperca gobio, the frogmouth from the Patagonian shelf and Falkland Islands. We document the anatomy and histology of the brains, olfactory apparatus, retina, and cephalic lateral line system. We also use the microvascular casting agent Microfil to examine ocular vascular structures. We provide detailed drawings of the brains and cranial nerves of both species. Typical of perciforms, the brains of both species have a well-developed tectum and telencephalon and robust thalamic nuclei. The telencephalon of C. gobio is prominently lobed, with the dorsomedial nucleus more conspicuous than in any other notothenioid. The corpus cerebelli is relatively small and upright and, unlike other notothenioids, has prominent transverse sulci on the dorsal and caudal surfaces. Areas for lateral line mechanoreception (eminentia granularis and crista cerebellaris) are also conspicuous but olfactory, gustatory, and somatosensory areas are less prominent. The anterior lateral line nerve complex is larger than the posterior lateral line nerve in B. diacanthus, and in their cephalic lateral line systems both species possess branched membranous tubules (which do not contain neuromasts) with small pores. These are especially complex in B. diacanthus where they become increasingly branched and more highly pored in progressively larger specimens. Superficial neuromasts are sparse. Both species have duplex (cone and rod) retinae that are 1.25-fold thicker and have nearly 5-fold more photoreceptors and than those of most Antarctic notothenioids. Convergence ratios are also high for bovichtids. Bovichtus diacanthus has a yellow intraocular filter in the dorsal aspect of the cornea. Both species are unique among notothenioids in possessing all three vascular structures present in the generalized teleostean eye: the choroid rete mirabile, the lentiform body (also a rete), and the falciform process. When comparing the phyletically derived Antarctic clade exemplified by the families Artedidraconidae, Bathydraconidae, and Channichthyidae to the phyletically basal bovichtids, we observe phyletic regression and reduction in some regions of the brain and in some sensory modalities that are well displayed in bovichtids. In the phyletically derived families the brain is less cellular and nuclei are smaller and less prominent. In some species reduction in the size of the telencephalon, tectum, and corpus cerebelli imparts a "stalked" appearance to the brain with the neural axis visible between the reduced lobes. There is also a phyletic reduction in the number of ocular vascular structures from three in bovichtids to one or none in artedidraconids, bathydraconids, and channichthyids. There are no morphological features of bovichtid brains and sense organs that presage the divergence of the phyletically derived members of the clade in the Antarctic marine environment with its cold and deep continental shelves. We conclude that this environment does not require sensory or neural morphology or capabilities beyond those provided by the basic perciform body plan. | {
"pile_set_name": "PubMed Abstracts"
} |
Interferon gamma enhances lymphokine-activated killer cell adhesion but not lysis of head and neck squamous cell carcinoma.
To determine if treatment with recombinant human interferon gamma (rHuIFN-gamma) increases the adhesion to, and lysis of, head and neck squamous cell carcinoma (SCC) cells by lymphokine-activated killer (LAK) and peripheral blood mononuclear (PBM) effector cells in vitro and to evaluate the role of cell surface adhesion molecules in these processes. Two human SCC cell lines, JHU-020-SCC and JHU-022-SCC, were used. Lymphokine-activated killer cells were generated by interleukin-2 stimulation of PBM cells obtained from the hemapheresis blood donor packs of healthy individuals. Adhesion assays were performed to assess the level of binding of both effector populations to SCC cells, which were treated with either fresh media or rHuIFN-gamma (100 U/mL). Binding was measured by flow cytometric detection of effector cells labeled with fluorescein-conjugated anti-CD45 monoclonal antibody. Monoclonal antibodies to the cell adhesion molecules HLA-DR, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1 were used in blocking experiments to determine their contribution to the process of effector-SCC cell adhesion. Cytotoxicity experiments were performed using a colorimetric assay to determine the cytotoxic response generated by LAK and PBM cells against SCC cells, with and without prior rHuIFN-gamma treatment of the tumor cells. Effector cell binding level and percent cytotoxicity of SCC cells. Recombinant human interferon gamma treatment of JHU-020-SCC cells resulted in increased adhesion to both LAK cells and PBM cells (P < .001). The presence of anti-lymphocyte function-associated antigen 1 antibody resulted in elimination of the enhanced adhesion seen with rHuIFN-gamma pretreatment of SCC cells (P =.03), but antibody to intercellular adhesion molecule 1 and HLA-DR did not reduce the level of effector binding. The greatest cytotoxic response against both JHU-020-SCC and JHU-022-SCC was seen with LAK cells (P < or = .001). Pretreatment of tumor targets by rHuIFN-gamma (100 U/mL) resulted in no enhancement of cytotoxic response by either LAK or PBM cells; at the effector-target ratio of 30:1, there was a significant decrease in LAK cell-mediated cytotoxic response against rHuIFN-gamma-treated SCC cells (P < or = .02). Recombinant human interferon gamma treatment of head and neck SCC cells does increase binding of both LAK cells and PBM cells to tumor cells, in part via the lymphocyte function-associated antigen 1 ligand mechanism. The cytotoxic effect mediated by LAK cells against head and neck SCC cells is reduced after rHuIFN-gamma treatment, suggesting that the activity of this cytokine may be more important in regulating antigen-specific cytotoxic response mediated by cytotoxic T-lymphocytes. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of hypoxia on the ventral root motor-evoked potential in the in vitro spinal cord preparation.
This study investigated the effects of hypoxia and glucose on motor functions of spinal cord, monitoring ventral root motor-evoked potential in the in vitro cervical cord preparations. To study ischemia-induced changes in ventral root motor-evoked potential of spinal cord. Previous studies demonstrated ischemic changes caused by local circulatory impairment might be a major pathophysiologic basis of neuron damage in cord compression. Ventral root motor-evoked potential elicited by stimulation of ventrolateral funiculus was recorded from the ventral root in the isolated spinal cord preparations obtained from a newborn rat. The preparations were exposed to artificial cerebrospinal fluid equilibrated with severe or mild hypoxia for 90 minutes. Inhibitory and excitatory neurotransmitter antagonists were added to artificial cerebrospinal fluid to investigate synaptic transmission. The artificial cerebrospinal fluids containing various concentrations of glucose were used to study the glucose's effects. Ventral root motor-evoked potential consisted of the early and late components, which were excitatory transsynaptic potentials. The amplitudes were increased in the early phase of severe hypoxia and declined in the prolonged exposure. In mild hypoxia, there was a sustained increase of the amplitudes. The application of inhibitory neurotransmitter antagonists abolished the augmentation of the amplitudes in the early phase of severe hypoxia. Hypoxia without glucose accelerated hypoxic change. Inhibitory synaptic transmission was depressed preferentially in the early phase of severe hypoxia or in mild hypoxia. Excitatory and inhibitory transmissions were suppressed in prolonged severe hypoxia. Glucose deficiency aggravated hypoxic inhibition of synaptic transmissions. | {
"pile_set_name": "PubMed Abstracts"
} |
On the diffusion constant of water in wheat.
Diffusion-weighted magnetic resonance imaging (MRI) was used to obtain diffusion constants for water in the embryo and endosperm of wheat. Our experiments showed a significant difference between the diffusion constant for the two components. It was also shown that water diffusion in both the endosperm and embryo deviates from the typically observed Gaussian behavior in bulk fluids, showing a time-dependent diffusion constant. Diffusion constants for the embryo and endosperm were shown to differ by an order of magnitude. Using a model for restricted diffusion, information on the endosperm pore size and the embryo cell dimensions could be obtained. | {
"pile_set_name": "PubMed Abstracts"
} |
Photodynamic therapy in periodontal therapy: microbiological observations from a private practice.
In recent years, the combination of laser light and photosensitizer known as photodynamic therapy (PDT) has been used in periodontal therapy. However, there are not enough clinical studies to fully evaluate the effects of PDT on the periodontal tissues. This microbiological study examined the effects of PDT on the periodontal bacteria in combination with scaling and root planing (SRP) in the same group of patients by randomly selecting PDT or SRP for use in different quadrants of the mouth. For the present study, PDT was compared with a diode laser (980 nm) and an Nd:YA G laser (1,064 nm). Microbiological samples were examined and evaluated over a period of three months. Significant bacterial reduction has been observed in all cases. The diode laser with SRP presented long-term positive results, while PDT showed a significant bacteria reduction during the entire observation period. | {
"pile_set_name": "PubMed Abstracts"
} |
Preparation of calcium phosphate nanocapsule including deoxyribonucleic acid-polyethyleneimine-hyaluronic acid ternary complex for durable gene delivery.
Our plasmid delivery systems comprising deoxyribonucleic acid (DNA), polyethyleneimine (PEI), and hyaluronic acid (HA) have already achieved the high-extragene expression in tumor tissues. Repeated transfection with certain cytokine genes effectively induced tumor regression and complete disappearance of the tumor in some cases. Frequent injection is sometimes difficult depending on the tumor site. However, single injection often leads to an unsatisfactory efficacy owing to the short duration of the gene expression. In this study, we prepared calcium phosphate (CaP) nanocapsule including plasmid DNA complexes as a durable gene transfection system, which would be slowly degraded, and release DNA complex in the body. CaP nanocupsule including DNA complexes with a diameter of approximately 200 nm was prepared by immersing HA-coated DNA-PEI complex in simulated body fluid. It showed gene expression in cultured cells with duration longer than 2 weeks. By this slow-releasing system, significant tumor-growth suppression and, finally, complete tumor disappearance were observed after single injection into the tumor. Capsulated DNA complex with Ca thus seems promising as a sustained gene expression device. | {
"pile_set_name": "PubMed Abstracts"
} |
Paddle cilia (discocilia) in chemosensitive structures of the gastropod mollusk Pleurobranchaea californica.
Scanning electron microscopy of various regions of the body of the marine gastropod Pleurobranchaea californica (McFarland) has revealed a characteristic cell type that bears cilia with dilated discoid-shaped tips. The tips of the cilia consist of an expansion of the ciliary membrane around a looped distal extension of the axoneme. These kinocilia have been observed in numerous other marine invertebrates and are generally referred to as paddle cilia (Tamarin et al. 1974) or discocilia (Heimler 1978). Although many functions have been proposed for paddle cilia, little empirical evidence supports any of the proposals. In Pleurobranchaea we have found that the distribution of this ciliated cell type corresponds exactly to areas of the body known from behavioral studies (Lee et al. 1974; Davis and Matera 1981) to mediate chemoreception. Transmission electron microscopy of the epithelium lining the rhinophores and tentacles of Pleurobranchaea revealed details of the ultrastructure of these ciliated cells and showed that they are primary receptors. These ciliated receptors lie in a yellow-brown pseudostratified columnar epithelium that superficially resembles the olfactory mucosa of vertebrates. | {
"pile_set_name": "PubMed Abstracts"
} |
Molecular surveillance of Theileria ovis, Theileria lestoquardi and Theileria annulata infection in sheep and ixodid ticks in Iran.
A molecular study was undertaken to detect Theileria ovis, Theileria lestoquardi and Theileria annulata in sheep and tick vectors. Investigation was conducted from 2010 to 2011 in the south of Khorasan Razavi Province, Iran. A total of 150 blood samples were collected from 30 different sheep flocks. In addition, ixodid ticks were sampled from the same flocks. The stained blood smears were microscopically examined for the presence of piroplasms and a semi-nested polymerase chain reaction-restriction (PCR) was used for subsequent molecular speciation. Salivary glands were isolated from the ticks and subsequently analysed by semi-nested PCR. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to differentiate between T. lestoquardi and T. annulata from PCR-positive samples. Theileria species infection was microscopically detected in 18.6% of blood smears. The presence of T. ovis and T. lestoquardi or T. annulata was detected by semi-nested PCR in 58.6% and 6.6% of blood samples respectively. In total, 169 ixodid ticks were collected from different areas of the province. The most prevalent ticks were Rhipicephalus turanicus (n = 155; 91.7% of the total), followed by Hyalomma anatolicum anatolicum (n = 8; 4.7%) and Hyalomma marginatum turanicum (n = 6; 3.5%). From an organ pooling of 33 ticks, three pools of salivary glands from R. turanicus were positive for Theileria species by semi-nested PCR. Of the three R. turanicus samples testing positive for Theileria species, two (6.1%) were positive for T. ovis and one (3.0%) for T. lestoquardi or T.annulata. Amongst the 11 PCR-positive samples for T. lestoquardi or T. annulata, 10 were positive for T. lestoquardi and one sample was positive for both T. lestoquardi and T. annulata using PCR-RFLP. The results also demonstrated that PCR-RFLP could be used for the detection of T. ovis. Based on the results, it can be concluded that T. ovis has a higher prevalence than T. lestoquardi, and that R. turanicus could be a possible vector for T. ovis and T. lestoquardi. Finally, the PCR-RFLP based on Msp1 restriction enzyme is a simple method for differentiation of Theileria species in sheep and ixodid ticks. | {
"pile_set_name": "PubMed Abstracts"
} |
Hyperthermic intraperitoneal chemotherapy during primary tumour resection limits extent of bowel resection compared to two-stage treatment.
To compare the clinical outcome of a one-stage, primary tumour resection and hyperthermic intraperitoneal chemotherapy (HIPEC) procedure, versus a two-stage procedure of tumour resection and secondary HIPEC in colorectal cancer (CRC) patients with synchronous peritoneal carcinomatosis. A prospective database of all patients treated with HIPEC in the St. Antonius Hospital in the Netherlands between 2005 and 2012 was analysed. A total of 72 patients with synchronous peritoneal carcinomatosis (PC) from CRC were included. In 20 patients (27.8%) the primary tumour was resected simultaneously with HIPEC (early referral). In the other 52 patients (72.2%) the primary tumour was resected prior to the HIPEC procedure (late referral). During CRS + HIPEC following late referral, 22 (59.5%) of the 37 anastomoses of the earlier operation were resected, revealing malignancy in 12 (54.5%) on histopathological examination. In twenty (27.8%) patients a permanent colostomy was constructed after HIPEC. Ten of these patients had complete bowel continuity after earlier primary resection. The relaparotomy rate was higher in patients after a resection of a previous anastomosis (36.4%) compared to 12% in the rest of the patients (P = 0.02). Resection of the primary tumour simultaneously with HIPEC in patients with synchronous PC from CRC may prevent extended bowel resections and permanent colostomy. Our data support early referral of patients with PC from colorectal cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells.
Obesity is a major global health problem and is associated with low-grade inflammation and, in a number of cases, poor iron status. We speculated that the adipokine leptin might play a role in regulating iron metabolism in the overweight population because it shares a number of common biological features with IL-6, a major factor in the development of the anemia of chronic disease via its stimulatory actions on the production and release of the iron regulatory hormone hepcidin. To test this hypothesis, we exposed HuH7 human hepatoma cells to leptin and measured hepcidin mRNA expression by quantitative PCR. HuH7 cells were also transfected with a hepcidin promoter-luciferase reporter gene construct to investigate transcriptional regulation of hepcidin. In leptin-treated cells, hepcidin mRNA expression was enhanced significantly. Preincubation with a Janus kinase (JAK) 2 inhibitor significantly diminished this response. Hepcidin promoter activity was also increased in the presence of leptin. This effect was decreased either by mutation of the signal transducer and activator of transcription (STAT) 3 binding motif in the hepcidin promoter or by coexpressing a dominant-negative STAT3 mutant. These data suggest that leptin upregulates hepatic hepcidin expression through the JAK2/STAT3 signaling pathway. As a consequence, the increased production of leptin in overweight individuals might be a major contributor to the aberrant iron status observed in these population groups. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients.
To determine the effectiveness of antiretroviral therapy in controlling cerebrospinal fluid (CSF) HIV-1 replication and to assess factors related to virological response in advanced patients. A cross-sectional and longitudinal study. Consecutive paired CSF and plasma samples from HIV-1-infected patients were collected before starting or changing highly active antiretroviral therapy (HAART). In the cross-sectional analysis 75 patients were included, 55 (73%) with neurological disease, 28 (37%) naive for antiretroviral agents. A significant correlation between plasma and CSF levels at baseline was observed only in antiretroviral-experienced patients. The absence of neurological disease, lower plasma HIV-1 load and a previous exposure to indinavir were all associated with a baseline CSF HIV-1-RNA level less than 80 copies/ml at multivariate analysis. In 29 patients included in the longitudinal study a significant reduction in CSF HIV-1 RNA was observed. Plasma HIV-1-RNA change, CSF HIV-1-RNA level at baseline, overall months of antiretroviral treatment and the magnitude of difference between plasma and CSF HIV-1-RNA levels were all correlated to CSF HIV-1-RNA change during treatment. A significant difference in the magnitude of CSF HIV-1-RNA reduction was observed according to naive status and to the use of three or more drugs penetrating the blood-brain barrier. HAART effectively reduces HIV-1 replication in CSF. A variable response to antiretroviral therapy was observed in CSF, reflecting a different compartmentalization of infection during treatment. Naive status and the use of CNS-penetrating drugs substantially enhance antiviral response. A negative interaction between virological response and the duration of antiretroviral treatment suggests long-term selection of drug-resistant CSF HIV-1 strains. | {
"pile_set_name": "PubMed Abstracts"
} |
Epidemiological study of epilepsy by monitoring prescriptions of antiepileptic drugs.
The aim of this study is to evaluate a simple and effective method of acquiring epidemiological information about epilepsy. Data on antiepileptic drug prescriptions was collected, the utilization pattern being based on defined daily doses (DDDs). Antiepileptic drugs are epidemiological tracers of epilepsy due to their chronic and highly specific usage. Consequently, a prevalence rate for the whole population may be obtained by using DDDs. Data on antiepileptic drug prescriptions for a period of 6 months in 1992 and 6 months in 1993 indicate a utilization of approximately 7 DDDs of antiepileptic drugs per 1,000 inhabitants. The prevalence of epilepsy was estimated by correcting the exposure calculated in DDDs by a factor of 0.68. In our sample, the prevalence of the disease was 5.2 per 1,000 inhabitants in 1992 and 4.9 per 1,000 in 1993. Physician prescriptions were concentrated on four compounds, namely phenobarbital, carbamazepine, valproic acid and phenytoin, which together represented 90% of total antiepileptic drug prescriptions. | {
"pile_set_name": "PubMed Abstracts"
} |
Initial experience with magnetic resonance imaging of atrial scar and co-registration with electroanatomic voltage mapping during atrial fibrillation: success and limitations.
Ablation for atrial fibrillation (AF) frequently requires multiple procedures to achieve durable restoration of sinus rhythm. Early studies have suggested that delayed enhancement magnetic resonance imaging (DE-MRI) of the left atrium (LA) can assist in performing repeat ablation procedures. The purpose of this study was to investigate the utility of DE-MRI in delineating regions of LA low voltage and PV reconnection sites in patients undergoing repeat PV isolation for recurrent AF. We enrolled 10 patients undergoing repeat ablation for AF recurrence to undergo preprocedural DE-MRI of the LA in conjunction with high-density voltage mapping (>100 sites) of the LA during the ablation procedure. LA wall regions with hyperenhancement were segmented from DE-MRI images and retrospectively co-registered with the electroanatomic LA map. The association between scar on DE-MRI images and low-voltage regions of the LA was assessed, as was the association between scar gaps and electrogram-determined PV reconnection sites. Ten patients underwent successful DE-MRI imaging and repeat AF ablation without complication. In all 10 patients, the majority of PVs were found to have regained electrical continuity with the LA (30/37 PVs electrically active); all patients underwent successful reisolation of all PVs using standard ablation techniques. There was a significant association between scar identified by DE-MRI and low-voltage regions of the LA (-0.7±0.1 mV in scar regions; generalized estimating equations model clustered by patient, P<.001). However, there was no association between scar gaps and PV reconnection sites. We demonstrate the co-registration of DE-MRI scar imaging and electroanatomic LA mapping, with agreement between regions of scar on DE-MRI and low voltage by mapping. However, at our center, this technique did not provide accurate information on the location of PV reconnection sites in patients undergoing repeat ablation for AF. | {
"pile_set_name": "PubMed Abstracts"
} |
[Strategies for regulating multiple genes in microbial cell factories].
Microbial metabolic engineering and synthetic biology are important disciplines of microbial technology nowadays. Microbial cells are fast growing, easy to be cultivated in large scale, clear in genetic background and convenient in genetic modification. They play an important role in many domains. Microbial cell factory means an artificial microbial metabolic system that can be used in chemical production. The construction of a microbial cell factory needs transferring of multiple genes or a whole metabolic pathway, which may cause some problems such as metabolism imbalance and accumulation of mesostates. This review focuses on the regulation strategies of different levels involving simultaneous engagement of multiple genes. Future perspectives on the development of this domain were also discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Gastric adaptive relaxation and symptoms after vagotomy.
Gastric adaptive relaxation is reported to be impaired after vagotomy. This abnormality has been implicated in the pathogenesis of postvagotomy symptoms, but no association has previously been demonstrated between the two. Gastric adaptive relaxation was measured in 15 healthy volunteers and 33 patients more than 1 year after highly selective vagotomy or truncal vagotomy and drainage. Seventeen patients were asymptomatic. The remainder were symptomatic including seven patients with persistent diarrhoea. Fasted subjects were intubated with a Ryle's tube containing a pressure microtransducer within a flaccid (800 ml) plastic bag. Gastric corpus-fundus pressure was recorded during distension of the bag with air (15 ml/s) over 30 s. Pressure indices were derived from the areas under the pressure curves. Median (range) pressure indices were: healthy volunteers 12.7 (7.5-17.1) cmH2O, highly selective vagotomy 14.0 (9.8-15.9) cmH2O (n.s.), truncal vagotomy and drainage 14.5 (8.6-26.8) cmH2O (P = 0.04). All patients with diarrhoea had abnormally high pressure indices (P less than 0.001). Pressure indices in all other patient groups were within the normal range. We conclude that gastric adaptive relaxation remains abnormal in patients with postvagotomy diarrhoea but not in those who are asymptomatic or who have other symptoms. | {
"pile_set_name": "PubMed Abstracts"
} |
P2T: Part-to-Target Tracking via Deep Regression Learning.
Most existing part based tracking methods are part-to-part trackers, which usually have two separated steps including part matching and target localization. Different from existing methods, in this paper, we propose a novel part-totarget (P2T) tracker in a unified fashion by inferring target location from parts directly. To achieve this goal, we propose a novel deep regression model for part to target regression in an end-to-end framework via Convolutional Neural Networks. The proposed model is able to not only exploit part context information to preserve object spatial layout structure, but also learn part reliability to emphasize part importance for robust part to target regression. We evaluate the proposed tracker on 4 challenging benchmark sequences, and extensive experimental results demonstrate that our method performs favorably against state-of-the-art trackers because of the powerful capacity of the proposed deep regression model. | {
"pile_set_name": "PubMed Abstracts"
} |
Professional autonomy and work setting as contributing factors to depression and absenteeism in Canadian nurses.
The prevalence of major depression in Canadian nurses is double the national average for working women. The present study sought to delineate the role of professional autonomy, health care setting, and work environment characteristics as risk factors for depression and absenteeism in female nurses. A cross-sectional, secondary analysis was conducted on a large representative sample of female nurses working in hospitals and other settings across Canada (N = 17,437). Univariate and multivariate analyses were used to test the hypothesis that work environment factors are significant determinants of major depression and absenteeism in female nurses after accounting for other risk factors. Experiencing a major depressive episode in the past 12 months was significantly associated with lower autonomy (odds ratio [OR] = 0.93), higher job strain (OR = 2.2), being a licensed practical nurse (OR = 0.82), and working in a nonhospital setting (OR = 1.5). Higher absenteeism was associated with the same variables as well as having less control over one's work schedule. Efforts to increase autonomy of nurses and reduce job strain may help to address the high prevalence of major depression in this professional group. | {
"pile_set_name": "PubMed Abstracts"
} |
The relationship between maximum heart rate in a cardiorespiratory fitness test and in a maximum heart rate test.
It is suggested that individuals will not reach their heart rate maximum (HRmax) at an incremental cardiorespiratory fitness (CRF) test and commonly five beats per minute (bpm) are added to the highest heart rate (HR) reached. To our knowledge, there is not sufficient data justifying such estimation. Our aim was to assess whether individuals reached HRmax in an incremental CRF test to exhaustion. Fifty-one males and 57 females (aged 22-70 years) completed both an incremental CRF test (gradual increase in speed and/or inclination until volitional exhaustion) and a test designed to reach HRmax (with repeated work bouts at high intensity before maximal exertion) ≥48h apart. We investigated the relationship between the highest HR in the two tests using hierarchical linear regression analysis, with HRmax from the HRmax test as a dependent variable, and the highest HR reached at the CRF test (HRcrf), whether maximum oxygen uptake was reached on the CRF test, CRF, sex and age as independent variables. HRmax was 2.2 (95% confidence interval, 1.5-2.9) bpm higher in the test designed to reach HRmax than in the CRF test (p<0.001). Only HRcrf significantly predicted HRmax, with no contribution of the other variables in the model. HRmax was predicted from the highest HR reached in an incremental CRF test by multiplying HRcrf with 0.967, and adding 8.197 (HRmax=8.197+[0.967×HRcrf]) beats/min. Non-athletes reached close to HRmax in a standard CRF test. | {
"pile_set_name": "PubMed Abstracts"
} |
Identification and characterization of the type 2C protein phosphatase Ptc4p in the human fungal pathogen Candida albicans.
Type 2C protein phosphatases (PP2C) are monomeric enzymes and their activities require the presence of magnesium or manganese ions. There are seven PP2C genes, named from PTC1 to PTC7, in Saccharomyces cerevisiae. In the current study we identified the CaPTC4 gene in Candida albicans and demonstrated that the CaPtc4p protein is a typical PP2C enzyme, which is highly conserved in fungal species. Deletion of CaPTC4 renders Candida cells sensitive to sodium and potassium ions as well as to antifungal azole drugs. In addition, we have shown that CaPtc4p is localized in the mitochondrion, suggesting that CaPtc4p is likely to be involved in the regulation of a mitochondrial function related to ion homeostasis. | {
"pile_set_name": "PubMed Abstracts"
} |
[The potential nuclease activity of the T antigen of SV-40 virus].
SV40 T-antigens were isolated from an extract of golden hamster tumours by precipitation with ammonium sulphate with subsequent fractionation on DEAE cellulose. The degree of purification of the preparation proved to be about 100-fold; it, however, contained an admixture of several cell proteins. Treatment of the DNA of the calf thymus with the T-antigen preparation in the presence of magnesium ions decreased the viscosity of the DNA solution during the first hour of incubation. T-antigen inactivated by heating, and also a fraction of normal hamster tissues analogous to it produced no such effect. In case of centrifugation in the saccharose gradient the constant of DNA sedimentation fell after the treatment with T-antigen from 285 to 165, this corresponding to about4--5-fold reduction of molecular weight of the DNA. The data obtained indicated that the partially purified T-antigen preparation possessed endonuclease activity. | {
"pile_set_name": "PubMed Abstracts"
} |
Cognitive functioning in idiopathic generalised epilepsies: a systematic review and meta-analysis.
Cognitive function in idiopathic generalised epilepsies (IGE) is of increasing research attention. Current research seeks to understand phenotypic traits associated with this most common group of inherited epilepsies and evaluate educational and occupational trajectories. A specific deficit in executive function in a subgroup of IGE, juvenile myoclonic epilepsy (JME) has been a particular focus of recent research. This systematic review provides a quantitative synthesis of cognitive function outcomes in 26 peer-reviewed, case-control studies published since 1989. Univariate random-effects meta-analyses were conducted on seven cognitive factor-domains and separately on executive function. Patients with IGE demonstrated significantly lower scores on tests across all cognitive factor-domains except visual-spatial abilities. Effect sizes ranged from 0.42 to 0.88 pooled standard deviation units. The average reduction of scores on tests of executive function in IGE compared to controls was 0.72 standard deviation units. Contrary to current thinking, there was no specific deficit in executive function in JME samples, nor in other IGE syndromes. Of more concern, people with IGE are at risk of pervasive cognitive impairment. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors (TAFs) required for activated transcription interact with TATA box-binding protein conserved core domain.
TFIID is a multisubunit protein containing the TATA box-binding polypeptide (TBP) and associated factors (TFIID-TAFs) required for activated transcription by RNA polymerase II. TBPs from different eukaryotes contain a highly conserved carboxy-terminal domain and very divergent amino-terminal domains. Earlier studies proposed that the amino-terminal domains of metazoan TBPs are required for activated transcription. However, we report that a human TFIID complex containing an amino-terminal truncated TBP contains all the major TFIID-TAFs and supports in vitro transcriptional stimulation by different classes of activation domains and from a TATA-less promoter. Protein blotting experiments revealed direct interactions between the conserved domain of TBP and the two largest TAFs. The results suggest a model for the interaction of TFIID-TAFs with TBP. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of efficacy of nisoldipine, metoprolol, and isosorbide dinitrate in patients with stable exertional angina: a randomized, cross-over, placebo-controlled study.
We evaluated the acute antianginal effect of oral nisoldipine (10 mg), metoprolol (40 mg), and long-acting isosorbide dinitrate (20 mg) in 15 patients with stable exertional angina. The patients performed symptom-limited treadmill exercise at 2 h after the administration of placebo (Placebo stages 1 and 2) and each of the active drugs. After Placebo stage 1, the patients were randomized for cross-over evaluation of the acute effect of a single oral dose of placebo (Placebo stage 2), nisoldipine, metoprolol, or long-acting isosorbide dinitrate. All 15 patients developed angina during all of exercise tests and their exercise tests were terminated at the onset of angina. The time until development of 0.1 mV ST segment depression was increased by all three drugs compared to placebo, and it was significantly longer with metoprolol than with isosorbide dinitrate. Similarly, the time to ceasing exercise because of angina was also prolonged by all three drugs. The exercise time was longer with nisoldipine and metoprolol compared to isosorbide dinitrate, but there was no significant difference between nisoldipine and metoprolol. In conclusion, metoprolol and nisoldipine more effectively prolonged exercise compared to long-acting isosorbide dinitrate in patients with stable exertional angina. | {
"pile_set_name": "PubMed Abstracts"
} |
The Efficacy of Early Extracorporeal Shockwave Lithotripsy for the Treatment of Ureteral Stones.
To determine the efficacy of early extracorporeal shockwave lithotripsy (e-ESWL) in colic patients with ureteral stones and the patient criteria for the most effective e-ESWL. 335 patients who received ESWL due to ureteral stone, were divide in two groups: e-ESWL and d-ESWL by the critical cut-off point. we performed the sensitivity and specificity cut-off analyses to identified the critical cut off point. To assess the difference in the factors affecting ESWL success, univariate and multivariate logistic analyses were implemented with using variables: ESWL success; age; gender; BMI; comor-bidity; serum creatinine; stone size; stone location; stone laterality; Hounsfield unit (HU); presence of hydrone-phrosis; and presence of tissue rim. The subgroup analysis for the screened variables was conducted. Optimal e-ESWL was defined to occur within a 24-hour critical cut-off time. Multivariate regression anal-ysis concluded with screened variables: age, stone size, stone location, and HU, that ESWL success was 1.85-fold higher in the e-ESWL patient group. The subgroup analyses the following conditions: ? 65 years old by 1.784- fold; ?10 mm stone size by 1.866-fold; mid to distal stone location by 2.234-fold; and ? 815 HU by 2.130-fold. When all the conditions were met, the e-ESWL success was 3.22-fold higher. In case of colic due to ureteral stones, the patient is recommended to receive a lithotripsy within the first 24 hours. E-ESWL is recommended especially in patients who are ? 65 years, or with a ureteral stone HU ? 815, sized ? 10 mm, or in a mid to distal location. | {
"pile_set_name": "PubMed Abstracts"
} |
[Subclavian transposition and carotid-subclavian bypass in the treatment of subclavian steal syndrome].
The authors operated on 89 patients for subclavian-steal syndrome, between 1975 and 1984. A carotid-subclavian bypass was applied to 53 patients and transposition of the subclavian artery to another 36. All transpositions were open after an average follow-up period of 2.7 years, where an occlusion was recorded after 4.6 years from eight patients (19.5 per cent) to whom a bypass had been applied. Postoperative complications were equal in both groups. A complex of Horner symptoms was recorded from either group. Phrenoparalysis was recorded from six patients with carotid-subclavian bypass and from four patients with subclavian transposition. | {
"pile_set_name": "PubMed Abstracts"
} |
Apolipoprotein E polymorphism in a healthy Swedish population: variation of allele frequency with age and relation to serum lipid concentrations.
We analyzed blood samples from 407 healthy Swedish individuals, 244 men and 163 women, ages 17 to 86 years, for apolipoprotein (apo) E isoforms and serum triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol. Parallel genotyping by means of polymerase chain reaction (PCR)-amplified DNA was performed in 200 subjects. Identical results were obtained by genotyping and phenotyping in 95% of all subjects analyzed. The apo E allelic frequencies were 7.8% for epsilon 2, 71.9% for epsilon 3, and 20.3% for epsilon 4. Compared with other Caucasian populations, the present population had a high relative allelic frequency of epsilon 4. The epsilon 4 frequency decreased with increasing age and was significantly lower in individuals > 60 years of age (14.7%). When controlling for age and sex, there were strong correlations between total serum and LDL cholesterol and the various epsilon alleles. The epsilon 4 and epsilon 3 alleles correlated positively with serum cholesterol and the epsilon 4 allele correlated positively with LDL cholesterol. In contrast, HDL cholesterol and serum triglycerides did not show any correlation to the allele types. Thus, the results demonstrate a considerable age variation of the epsilon allele frequency among healthy Swedes and an influence of apo E alleles on serum and LDL cholesterol concentrations. | {
"pile_set_name": "PubMed Abstracts"
} |
Anorectal sarcomas.
The authors report on their observations of nine patients with anorectal sarcoma. They agree with others that best results can be expected from radical surgery. Even in operable patients anorectal sarcomas have a worse prognosis than other malignant lesions in the same region. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of laparoscopic curricula in American urology residency training.
The goal of this study is to evaluate the role of laparoscopic curricula and simulation technology in urology residency training from the perspectives of residents over a 2-year period. An anonymous survey was given to urology residents attending the American Urological Association Basic Sciences Course in 2008 and 2009. We evaluated laparoscopic simulator use within a curriculum and use of simulators outside of a curriculum. Face and content validity of simulators were analyzed on a 5-point Likert scale questionnaire. Responses were compared using the unpaired Student t test and chi-square with P<0.05 considered significant. There were 114 surveys (81.4% response rate) and 76 surveys (43% response rate) evaluated from 2008 and 2009, respectively. Access to a surgical simulator increased from 74.6% to 78%. The percentage of programs with a laparoscopic curriculum expanded from 16.9% to 44%. In 2009, simulators were used more frequently by residents in programs with curricula compared with residents without curricula (P=0.03). In 2008, 48% of residents and in 2009 72% of residents reported using simulators as "never" or "once or twice a year." Of residents, 93% stated that urology programs should use laparoscopic curricula and 82% think simulators should be involved in the curricula. One third of residents agreed that simulators are helpful for skill acquisition, and 80% described their current laparoscopic curriculum as inadequate. The number of urology programs that have invested in simulators continues to expand. Despite access to laparoscopic simulators, residents rarely use them. Residents in programs with laparoscopic curricula report using surgical simulators more often than residents without curricula. Laparoscopic curricula are important, and the incorporation of simulators enhances surgical education. | {
"pile_set_name": "PubMed Abstracts"
} |
Rhodium-catalyzed enantioselective hydrogenation of beta-phthalimide acrylates to synthesis of beta2-amino acids.
[Structure: see text] The enantioselective hydrogenation of beta-phthalimide acrylates provides the corresponding chiral beta2-amino acids in excellent enantiomeric excess catalyzed by Rh-monophosphorus. | {
"pile_set_name": "PubMed Abstracts"
} |
Plasma extravasation induced by neurokinins in conscious rats: receptor characterization with agonists and antagonists.
The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [beta Ala8]NKA(4-10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [beta Ala8]NKA(4-10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Acquired immunodeficiency syndrome/human immunodeficiency virus risk behavior among gay men in small cities. Findings of a 16-city national sample.
Most research on acquired immunodeficiency syndrome has been conducted in several of the country's largest cities, and little is known about the current level of human immunodeficiency virus risk taking among gay men in other geographical areas. The purpose of this study was to determine the frequency of risk behavior practices among gay men in smaller communities. A large sample of men who patronized gay bars in 16 small and moderate-size cities drawn from six states in four different regions of the country was surveyed to determine the frequency of high-risk behavior and factors influencing risk taking. Eighty-five percent of men in all cities' bars completed all survey measures. The community samples were 1991 men; mean age, 31.3 years; mean education, 10.6 years; 90% were white and 10% were of other ethnicities. All participants provided detailed information on their sexual behavior practices over the preceding 2 months and completed measures assessing their perceived peer norms concerning safer sex practices and risk avoidance, intentions to avoid risk, personal risk estimation, acquired immunodeficiency syndrome risk knowledge, perceived threat of acquired immunodeficiency syndrome/human immunodeficiency virus, and serostatus testing history. High-risk patterns were still common among gay men in these smaller cities; nearly one third of all men had engaged in unprotected anal intercourse an average of eight times in the past 2 months, usually outside monogamous relationships. High-risk behavior was most strongly associated with beliefs that safer sex practices would not be well accepted by peers, weak intentions to use condoms, underestimation of personal vulnerability to the acquired immunodeficiency syndrome, younger age, and higher levels of overall sexual activity. Nine percent of men tested said they were seropositive. Growing human immunodeficiency virus prevalence and continued high rates of risk behavior indicate that a new "front line" for human immunodeficiency virus prevention among homosexually active men has shifted to the country's smaller cities. Community prevention efforts in these areas are urgently needed to avert sharp increases in future human immunodeficiency virus infections in this population. | {
"pile_set_name": "PubMed Abstracts"
} |
Objective evaluation of fatigue by event-related potentials.
The purpose of this study was to assess the relationship between mental fatigue and event-related potentials (ERPs). Six healthy men (mean age: 22 years old) performed a simple calculation for 6 h. Auditory ERPs were recorded before and after the calculating task. The scores of subjective fatigue symptoms were significantly increased, and P300 latency of auditory ERPs was significantly prolonged by the calculating task (P<0.05). We suggest that the recording of ERPs may be useful for the objective evaluation of mental fatigue. | {
"pile_set_name": "PubMed Abstracts"
} |
[Early-onset colorectal carcinoma study].
Early-onset colorectal carcinoma (before the age of 45 years) are a distinct clinical group characterized by frequent distal location, poor cellular differentiation and aggressive evolution. A systematic study of early-onset cancers without familial predisposition in the context of the CIT program of "la Ligue Nationale Contre le Cancer" has been set up to characterize molecular mechanisms of carcinogenesis of these tumors. Preliminary results of transcriptome analysis show different gene-expression profiles among age. The next step will consist in validating a molecular signature specific for early-onset carcinoma. Genomic profile does not differ from that observed in late-onset colon cancers. | {
"pile_set_name": "PubMed Abstracts"
} |
Partial characterization of the lettuce infectious yellows virus genomic RNAs, identification of the coat protein gene and comparison of its amino acid sequence with those of other filamentous RNA plant viruses.
Purified virions of lettuce infectious yellows virus (LIYV), a tentative member of the closterovirus group, contained two RNAs of approximately 8500 and 7300 nucleotides (RNAs 1 and 2 respectively) and a single coat protein species with M(r) of approximately 28,000. LIYV-infected plants contained multiple dsRNAs. The two largest were the correct size for the replicative forms of LIYV virion RNAs 1 and 2. To assess the relationships between LIYV RNAs 1 and 2, cDNAs corresponding to the virion RNAs were cloned. Northern blot hybridization analysis showed no detectable sequence homology between these RNAs. A partial amino acid sequence obtained from purified LIYV coat protein was found to align in the most upstream of four complete open reading frames (ORFs) identified in a LIYV RNA 2 cDNA clone. The identity of this ORF was confirmed as the LIYV coat protein gene by immunological analysis of the gene product expressed in vitro and in Escherichia coli. Computer analysis of the LIYV coat protein amino acid sequence indicated that it belongs to a large family of proteins forming filamentous capsids of RNA plant viruses. The LIYV coat protein appears to be most closely related to the coat proteins of two closteroviruses, beet yellows virus and citrus tristeza virus. | {
"pile_set_name": "PubMed Abstracts"
} |
[Pharmacokinetics of alpha1-antitrypsin replacement therapy in severe congenital emphysema].
Alpha1-antitrypsin (AAT) deficiency is a codominant autosomal genetic disorder that predisposes a patient to chronic obstructive pulmonary disease and emphysema. Specific treatment is systemic, consisting of intravenous infusion of AAT. The protocol currently recommended by the Spanish Registry is infusion of 180 mg/kg every 21 days. The objective of this study was to assess the pharmacokinetic behavior of AAT and estimate the level of protection, defined as the percentage of time that the AAT plasma concentration was above the assumed protective threshold of 50 mg/dL with the usual protocol and with other alternative ones. Plasma concentrations at 4 times were analyzed for 9 patients to profile the pharmacokinetics of AAT. The data were fitted to a single compartment open model with the WinNonlin software package. The duration of protection was estimated by simulating the evolution of AAT plasma activity over time according to the model constructed based on data recorded in the study. Five men and 4 women (mean weight, 69 kg; range, 59-84 kg) were given a mean AAT dose of 12.06 g (range, 11-15 g). The mean (SD) volume infused was 516.67 (88.17) mL. The half-life of AAT was 8.7 days and the volume of distribution was 127.6 mL/kg. The currently recommended treatment protocol (180 mg/kg every 21 days) gave a level of protection of 67% (considering 60 mg/dL to be protective threshold) or 76% (for a threshold of 50 mg/dL). Protection values for the alternative protocol of 120 mg/kg every 14 days were 82% and 100%, respectively. For the alternative protocol of 60 mg/kg every 7 days, protection was 100% for both thresholds. Profiling the pharmacokinetic behavior of AAT has enabled the coverage time to be assessed for several treatment protocols. The regimen of 120 mg/kg every 14 days had the most appropriate profile. | {
"pile_set_name": "PubMed Abstracts"
} |
Optimum edge detection filter.
Edge detection and enhancement are required in a number of important image processing applications. In this paper we consider the problem of optimizing spatial frequency domain filters for detecting a class of edges in images. The filter is optimum in that it produces maximum energy in the vicinity of the location of the edge for a given spatial resolution I and the bandwidth ?. We show that the filter transfer function can be specified in terms of the prolate spheroidal wavefunctions for a given space-bandwidth product I?. Further we show that for values of I? less than 2, the optimal filter represents the Laplacian operator in image space followed by a low pass filter with a cutoff frequency ?. | {
"pile_set_name": "PubMed Abstracts"
} |
Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro.
Icariin, a principal flavonoid glycoside in Herba Epimedii, is hypothesized to possess beneficial effects on bone mass. Icariin is metabolized to icariside II and then to icaritin in vivo. In the present study, we investigated the in vitro effects of icariin, icariside II and icaritin on both osteoblasts and osteoclasts. After treatment with these compounds at concentrations 10(-5)-10(-8) mol/l, osteoblasts were examined for proliferation, alkaline phosphatase activity, osteocalcin secretion and matrix mineralization, as well as expression levels of bone-related proteins. The formation of osteoclasts was assessed by counting the number of multinucleated TRAP-positive cells. The activity of isolated rat osteoclasts was evaluated by measuring pit area, actin rings and superoxide generation. Icariside II and icaritin increased the mRNA expression of ALP, OC, COL-1 and OPG, but suppressed that of RANKL. In addition, these compounds reduced the number of multinucleated TRAP-positive cells and the osteoclastic resorption area. Also decreases were observed in superoxide generation and actin ring formation that are required for osteoclast survival and bone resorption activity. These findings suggest that icaritin, which was more potent than icariin and icariside II, enhanced the differentiation and proliferation of osteoblasts, and facilitated matrix calcification; meanwhile it inhibited osteoclastic differentiation in both osteoblast-preosteoclast coculture and osteoclast progenitor cell culture, and reduced the motility and bone resorption activity of isolated osteoclasts. | {
"pile_set_name": "PubMed Abstracts"
} |
Accounting for measurement error in human life history trade-offs using structural equation modeling.
Revealing causal effects from correlative data is very challenging and a contemporary problem in human life history research owing to the lack of experimental approach. Problems with causal inference arising from measurement error in independent variables, whether related either to inaccurate measurement technique or validity of measurements, seem not well-known in this field. The aim of this study is to show how structural equation modeling (SEM) with latent variables can be applied to account for measurement error in independent variables when the researcher has recorded several indicators of a hypothesized latent construct. As a simple example of this approach, measurement error in lifetime allocation of resources to reproduction in Finnish preindustrial women is modelled in the context of the survival cost of reproduction. In humans, lifetime energetic resources allocated in reproduction are almost impossible to quantify with precision and, thus, typically used measures of lifetime reproductive effort (e.g., lifetime reproductive success and parity) are likely to be plagued by measurement error. These results are contrasted with those obtained from a traditional regression approach where the single best proxy of lifetime reproductive effort available in the data is used for inference. As expected, the inability to account for measurement error in women's lifetime reproductive effort resulted in the underestimation of its underlying effect size on post-reproductive survival. This article emphasizes the advantages that the SEM framework can provide in handling measurement error via multiple-indicator latent variables in human life history studies. | {
"pile_set_name": "PubMed Abstracts"
} |
[Efficacy of ciprofloxacine antibiotic prophylaxis of infectious complications after TUR of the prostate].
We compared efficacy of preoperative prophylactic antibiotic treatment (PPAT) with cyprofloxacine used orally (0.5 g), intravenously (0.4 g) and routine antibiotics in TUR of the prostate. A multicenter open randomized study covered 120 patients. PPAT efficacy was estimated by the rate of urinary infection (UI), frequency and duration of antibiotic treatment in the postoperative period, hospitalization duration. All the patients were divided into three groups: 39 patients of group 1 received oral cyprofloxacine 90-120 min before TUR of the prostate, 38 patients of group 2 received intravenous cyprofloxacine 30-60 min before TUR, 43 patients of group 3 (control) received routine antibiotic prophylaxis. The following results were obtained: 24-48 hours after the operation no cases of UI in group 1, 11.5 and 11.6% in groups 2 and 3, respectively, (p = 0.048); 7 days after TUR--UI in all the groups (2.6, 20, 23.3%, respectively); 14 days after TUR--UI in 5.1, 28.6, 27.9% patients, respectively. Mean duration of hospital stay was 11.7 +/- 7.6 days in group 1, 12.1 +/- 8.1 days in group 2, 12.5 +/- 7.8 days in group C (p > 0.05). Postoperative antibiotics were given to 16.7, 34.1 and 68.9% patients, respectively. Thus, cyprofloxacine in group 1 lowered UI risk and postoperative antibiotics significantly, in group 2 it had no influence on UI rate but reduced postoperative antibiotics significantly. | {
"pile_set_name": "PubMed Abstracts"
} |
Early onset cannabis use and progression to other drug use in a sample of Dutch twins.
One possible explanation of the commonly reported associations between early onset cannabis use and elevated risks of other illicit drug use is that early onset cannabis use increases access and availability to other drugs. It was this argument that in part motivated policy changes in the Netherlands that led to the de facto legalization of cannabis there. This study examines, using a co-twin control design, whether previously observed associations between early onset cannabis use and elevated lifetime rates of other illicit drug use would also be observed in a sample of 219 same sex Dutch twin pairs discordant for cannabis use before age 18. After adjustment for covariates, rates of lifetime party drug use (OR=7.4, 95% CI=2.3-23.4), hard drug use (OR=16.5, 95% CI=2.4-111.3), but not regular cannabis use (OR=1.3, 95% CI=0.3-5.1) were significantly elevated in individuals who reported early onset cannabis use, relative to their co-twin who had not used cannabis by age 18. The elevated odds of subsequent illicit drug use in early cannabis users relative to their non early using co-twins suggests that this association could not be explained by common familial risk factors, either genetic or environmental, for which our co-twin methodology provided rigorous control. | {
"pile_set_name": "PubMed Abstracts"
} |
Acute pancreatitis due to hereditary angioedema.
Hereditary angioedema (HAE) is an infrequent disorder characterized by abnormalities in the levels and/or function of complement C1 esterase inhibitor. Clinical manifestations of HAE are due to recurrent episodic swelling of the subcutaneous or submucosal tissue. When swelling involves the gastrointestinal mucosa, patients may present with nausea, vomiting, diarrhea, and severe abdominal pain. However, HAE is almost never suspected as a potential cause of acute pancreatitis. To describe a patient with HAE-associated pancreatitis requiring intensive medical care that responded favorably to conservative and supportive measures. Various tests were performed, including abdominal imaging, measurement of pancreatic enzymes levels, liver function tests, measurement of complement levels, and endoscopic retrograde cholangiopancreatography. The results of these tests confirmed the diagnosis of HAE-associated acute pancreatitis. No other obvious origin, such as gallstones or alcohol use, was identified. This case illustrates the need for a high clinical suspicion of acute pancreatitis when caring for patients with HAE who present with abdominal symptoms. There continues to be an urgent need for better and additional therapeutic options for HAE patients, including those to prevent and abort ongoing attacks. | {
"pile_set_name": "PubMed Abstracts"
} |
Skeletal muscle-specific myosin binding protein-H is expressed in Purkinje fibers of the cardiac conduction system.
Heart contraction is coordinated by conduction of electrical excitation through specialized tissues of the cardiac conduction system. By retroviral single-cell tagging and lineage analyses in the embryonic chicken heart, we have recently demonstrated that a subset of cardiac muscle cells terminally differentiates as cells of the peripheral conduction system (Purkinje fibers) and that this occurs invariably in perivascular regions of developing coronary arteries. Cis regulatory elements that function in transcriptional regulation of cells in the conducting system have been distinguished from those in contractile cardiac muscle cells; eg, 5' regulatory sequences of the desmin gene act as enhancer elements in skeletal muscle and in the conduction system but not in cardiac muscle. We hypothesize that Purkinje fiber differentiation involves a switch of the gene expression program from that characteristic of cardiac muscle to one typical of skeletal muscle. To test this hypothesis, we examined the expression of myosin binding protein-H (MyBP-H) in Purkinje fibers of chicken hearts. This unique myosin binding protein is present in skeletal but not cardiac myocytes. A site-directed polyclonal antibody (AB105) was generated against MyBP-H. Immunohistological analysis of the myocardium mapped the AB105 antigen predominantly to A bands of myofibrils within Purkinje fibers. Western blot analysis of whole extracts from the ventricular wall of adult chicken hearts revealed that the AB105 epitope was restricted to a single protein of approximately 86 kD, the same size as MyBP-H in skeletal muscle. Biochemical properties of the Purkinje fiber 86-kD protein and RNase protection analyses of its mRNA indicate that Purkinje fiber 86-kD protein is indistinguishable from skeletal muscle MyBP-H. The results provide evidence that skeletal muscle MyBP-H is expressed in a subset of cardiac muscle cells that differentiate into Purkinje fibers of the heart. | {
"pile_set_name": "PubMed Abstracts"
} |
A comparative study of vitreous-body and zonular glycoconjugates that bind to the lectin from Ulex europaeus.
Eyes from adult rodents, rabbits and humans were fixed in formalin, embedded in paraffin and incubated with a horseradish peroxidase-conjugated lectin from Ulex europaeus to localize vitreous-body and zonular glycoconjugates. Rodent eyes had reaction product for peroxidase activity in fibrous structures in the posterior chamber, vitreous base and vitreous cortex. The zonules and the internal limiting membrane region of the retina also were stained. Rabbit eyes had more stained fibrous material in the vitreous base than rodent eyes and the attachment region of the zonules on the lens capsule, the anterior hyaloid membrane and tracts in the vitreous cortex were more heavily stained in rabbits. There was heavy staining of the thick vitreous base in the human eyes as well as staining of zonules, anterior hyaloid membrane and vitreous cortex. The localization of this lectin may be specific for fucose in glycoproteins or other glycoconjugates, although this was not demonstrated here. However, the location of lectin binding sites correlates well with known sites of uptake of tritiated fucose and tritiated glucosamine in rabbit eyes. Eyes from the larger species studied had more lectin-binding glycoconjugates in fibrous structures in the vitreous body than those from smaller species. The amount of glycoconjugate identified in some of the lectin-binding sites may be related to some extent to the degree of stress incident upon those sites. | {
"pile_set_name": "PubMed Abstracts"
} |
Bedside ultrasound in early diagnosis of neurogenic heterotopic ossification in patients with acquired brain injury.
To illustrate ultrasound (US) and power Doppler US (PDUS) aspects of neurogenic heterotopic ossification (NHO) in consecutive patients with severe acquired brain injury, to evaluate the role of bedside US and PDUS in early diagnosis of NHO, to study incidence and outcome of NHO in this neurorehabilitative setting. Ninety-two consecutive patients with severe acquired brain injury underwent clinical and laboratory screening to pose suspect of NHO. In 6/92 patients bedside US examination confirmed the clinical suspect of NHO. US diagnosis of NHO was then confirmed by other imaging methods. All affected patients started therapy with indometacin, disodium etidronate, 6-methylprednisolone and they were followed-up for 1 year to evaluate the outcome. The incidence of NHO in this setting was 6.5% (only one patient with multifocal involvement). In hip NHO US demonstrated the classical pattern of zone phenomenon, and PDUS demonstrated vascular signals within mineralized NHO and in the outer hypoechoic area. No vascular signal was observed in the central hypoechoic core. In knee and elbow NHO only a heterogeneously hypoechoic mass or hyperechoic mineralized mass were respectively evident, with vascular signals within the lesions at PDUS. Spectral wave analysis (SWA) demonstrated low resistance vessels in NHO. After 1 year of therapy only one patient showed a severe ankylosis of the hips. Bedside US is a safe, cheap and useful tool in diagnosis of NHO and it allows to start therapy in early stages of NHO formation. PDUS adds data about neoangiogenetic activity of early NHO. | {
"pile_set_name": "PubMed Abstracts"
} |
Membranous glomerulopathy with Bowman's capsular and tubular basement membrane deposits.
Bowman's capsular and tubular basement membrane (TBM) deposits are an extremely unusual finding in non-lupus membranous glomerulopathy (MGN). We report three atypical cases of MGN with abundant Bowman's capsular and TBM deposits. In two cases, MGN was idiopathic; in the third case, MGN occurred in the renal allograft in the setting of HCV seropositivity. In addition to the usual glomerular capillary wall deposits, immunofluorescence and electron microscopy revealed extensive immune deposits within Bowman's capsule and TBMs, predominantly at the base of parietal and tubular epithelial cells. These cases suggest a potential pathomechanism of autoantibody to secreted epithelial antigens shared by visceral, parietal, and tubular epithelial cells. In all three cases, indirect immunofluorescence was unable to detect autoantibody to normal renal epithelial or matrix constituents. Furthermore, ELISA was unable to demonstrate circulating antibody to major extracellular matrix components. The implications of these findings for the pathogenesis of MGN are explored. | {
"pile_set_name": "PubMed Abstracts"
} |
Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers for B cell differentiation.
To delineate the phenotype and function of synovial T cells in rheumatoid arthritis (RA). T cells from normal subjects or from RA peripheral blood (PB), synovial fluid (SF), or synovial tissue (ST) were analyzed phenotypically and functionally. RA SF and ST T cells were found to be markedly enriched in CD45RAdim, CD45RO+, CD45RBdim mature memory cells, whereas in the PB, CD45RAbright naive T cells were more frequent than CD45RO+ memory T cells, and only a minority were CD45RBdim. SF and ST T cells proliferated less well and produced less interleukin-2 in response to mitogenic stimuli than did PB T cells. However, synovial T cells effectively promoted the production of Ig from normal B cells. Moreover, PB and synovial T cells differed in their capacity to down-regulate immunoglobulin production. Anti-CD3-stimulated PB T cells suppressed Ig production unless their proliferation was prevented with mitomycin C. In contrast, synovial T cells were potent helpers of B cell Ig production regardless of antecedent treatment with mitomycin C. To examine the relationship between the CD45RBdim phenotype and B cell help, CD45RBdim T cells were sorted from PB. As opposed to the findings with synovial T cells, suppression by control PB CD45RBdim T cells was observed, but only when large numbers were employed. B cell Ig production was enhanced after treatment of PB CD45RBdim T cells with mitomycin C. In contrast, healthy control sorted CD45RBbright or sorted CD4+, CD45RO+, CD45RBbright T cells did not support Ig secretion. After treatment with mitomycin C, both of these populations were more effective helpers of Ig production. RA synovium is enriched in differentiated CD45RBdim memory T cells with potent helper activity and diminished capacity to down-regulate B cells, strongly implying an active role for these cells in the production of Ig in the synovium, and thus in the propagation of disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Proliferation of anti-DNA-producing NZB B cells in a non-autoimmune environment.
This study demonstrates that purified NZB B cells, but not other NZB spleen cell populations, are capable of transferring anti-DNA antibody production into unirradiated H-2-compatible xid recipients. The number of autoantibody-producing B cells and the concentration of anti-DNA antibody found in the recipients correlated directly with the number of NZB B cells transferred. In addition, the number of anti-DNA-secreting lymphocytes found in the xid hosts increased exponentially with time post cell transfer. Several lines of evidence suggest that this phenomenon reflected the rapid proliferation of donor NZB B cells in the xid environment. Significantly, such proliferation was characteristic of donor cells that produced autoantibodies, but not of splenic B cells as a whole. These results suggest that stimulated NZB B cells can both induce and perpetuate autoantibody production in a normally non-autoimmune environment and in the absence of autoimmune helper cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Exclusive clinical experience with a lower profile device for resuscitative endovascular balloon occlusion of the aorta (REBOA).
A lower profile, FDA-approved device for aortic occlusion (AO) is available for REBOA. Patients who received AO with the new device from February 2016 to February 2017 at 2 urban tertiary care centers were enrolled. 60 consecutive patients underwent REBOA; 44 (73.3%) following blunt trauma. 52 (88.1%) were male; mean age of 40 ± 18 years. 49 REBOAs were deployed in Zone 1, 11 in Zone 3.67.7% of patients in arrest achieved return of spontaneous circulation (ROSC). Overall in-hospital survival was 43%; 19% for patients in arrest and 69% for patients with refractory hypotension. Access and vascular procedural complications included iliac intimal injury requiring stent-graft (1), patch angioplasty of the CFA (1), and balloon ruptures (3). 5 amputations were required; 2 immediate completion amputations due to initial injury, and 3 delayed amputations after efforts to salvage severely mangled extremities were unsuccessful. Smaller introducer sheaths for REBOA are safe and effective but do not eliminate the need for surgical common femoral artery access. Patients can benefit from REBOA with acceptable survival rates. | {
"pile_set_name": "PubMed Abstracts"
} |
Interindividual variation in posture allocation: possible role in human obesity.
Obesity occurs when energy intake exceeds energy expenditure. Humans expend energy through purposeful exercise and through changes in posture and movement that are associated with the routines of daily life [called nonexercise activity thermogenesis (NEAT)]. To examine NEAT's role in obesity, we recruited 10 lean and 10 mildly obese sedentary volunteers and measured their body postures and movements every half-second for 10 days. Obese individuals were seated, on average, 2 hours longer per day than lean individuals. Posture allocation did not change when the obese individuals lost weight or when lean individuals gained weight, suggesting that it is biologically determined. If obese individuals adopted the NEAT-enhanced behaviors of their lean counterparts, they might expend an additional 350 calories (kcal) per day. | {
"pile_set_name": "PubMed Abstracts"
} |
Passive immunity against Junín virus in mice.
Passive immunity, naturally acquired from immune mothers or artificially induced by the administration of homologous hyperimmune serum, conferred on suckling mice a high degree of resistance against infection with Junín virus. Maternal antibodies in the circulating blood of the young were not detectable in the first days after birth, but rised rapidly from the 8th to the 20th day of lactation. By cross-foster nursing experiments it was shown that the greater part of the transmission of passive immunity occurred after birth, although there was transmission of a significant, though small part, before birth. The virus passage from mothers to offspring was excluded, since Junín virus was not recovered from brains, livers, spleens and kidneys of uninfected young, born from infected mothers. | {
"pile_set_name": "PubMed Abstracts"
} |
Viability of the sporocysts of Sarcocystis cruzi after exposure to different temperatures and relative humidities.
The effect of temperature and relative humidity (RH) on the survival of sporocysts of S. cruzi were investigated in vitro. Under all experimental conditions (temperature of 4 degrees C, 37 degrees C, or room temperature; RH of 18%, 75%, or 100%) some sporozoites retained their viability to excyst for at least 90 days. The best conditions for survival were 4 degrees C at 100% RH (more than 240 days) and 37 degrees C at 18% RH (more than 180 days). Sporocysts maintained at room temperature at all humidities had the lowest level of survival. It is concluded that sporocysts of S. cruzi are able to survive in most environments for several months and that the fluctuation of the daily ambient temperature is likely to influence the viability of the sporocysts. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of dilevalol on renal function.
Renal function was measured in a total of 35 volunteers and patients who were given dilevalol, the R,R optical isomer of labetalol. Young normotensive volunteers (n = 6) and elderly normotensive volunteers (n = 12) received single 400- and 200-mg doses of dilevalol, respectively. Renal function was determined in these subjects on the same day before and after dosing. In addition, patients with mild to moderate essential hypertension (n = 11) and hypertensive patients with renal insufficiency (n = 6) were treated with placebo to establish baseline blood pressure and then were given dilevalol, 400 to 1,600 mg/day, for 2 to 6 weeks until blood pressure was controlled. Renal function was determined at the end of the baseline period and again at the end of dilevalol treatment. A subgroup of elderly hypertensives from the 2 protocols used to study hypertensive patients was treated as a separate study group. The only effect on parameters of renal function seen in any of the study groups was a statistically significant 15% decrease in glomerular filtration rate after single-dose treatment in the elderly normotensive group. Effective renal plasma flow, filtration fraction, renal blood flow and renal vascular resistance were unchanged before and after treatment in all groups. Mean arterial pressure was reduced significantly in all groups except in the elderly normotensive volunteers. Dilevalol appears to be a well-tolerated, effective therapeutic agent that is neutral regarding its effect on renal function and potentially useful in a variety of patient populations. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of bone-implant interface shear strength of hydroxyapatite-coated and alumina-coated metal implants.
We performed a transcortical push-out test to determine the effect of surface roughness of hydroxyapatite (HA)-coated implants on bone-implant shear strength in a canine model. Hydroxyapatite- and alumina-coated SUS316L with the same surface roughness (roughness average: Ra = 5 microns) and HA-coated Ti-6A1-4V (Ra = 8.4 microns), sintered HA (Ra = 0.9 micron), and dense alumina (Ra = 1.3 microns) were inserted into the dog's femur. The interface shear strength of the dense alumina was significantly lower than that of other implants at both 4 and 12 weeks after implantation. At 4 weeks after implantation, the interface shear strength of the alumina-coated SUS316L was significantly lower than that of other implants (P < .05) except the dense alumina, but at 12 weeks, there was no significant difference between the implant types except the dense alumina. This indicates that the surface roughness of the HA coating affects the enhancement of the bone-implant interface shear strength at the early period after implantation, and that a surface roughness of several micrometers does not influence the bond strength between bone and HA. A scanning electron microscopic study indicated that in almost all cases at 12 weeks, the failure site after push-out testing was the coating-substrate interface, not the coating-bone interface. Therefore, protection of the coating-substrate interface from direct shear loading is needed. | {
"pile_set_name": "PubMed Abstracts"
} |
Superfluous glutamine synthetase activity in Chinese Hamster Ovary cells selected under glutamine limitation is growth limiting in glutamine-replete conditions and can be inhibited by serine.
Passaging and expansion of animal cells in lean maintenance medium could result in periods of limitation of some nutrients. Over time, such stresses could possibly result in selection of cells with metabolic changes and contribute to heterogeneity. Here, we investigate whether selection of Chinese Hamster Ovary (CHO) cells under glutamine limitation results in changes in growth under glutamine-replete conditions. In glutamine-limiting medium, compared to control cells passaged in glutamine-rich medium, the selected cells showed higher glutamine synthetase (GS) activity and attained a higher peak viable cell density (PVCD). Surprisingly, in glutamine-replete conditions, selected cells still showed a higher GS activity but a lower PVCD. We show that in glutamine-replete medium, PVCD of selected cells was restored on (a) inhibition of GS activity with methionine sulfoximine, (b) supplementation of aspartate-without affecting GS activity, and (c) supplementation of serine, which is reported to inhibit GS in vitro. Consistent with the reported effect of serine, inhibition of GS activity was observed upon serine supplementation along with reduced growth of cells under glutamine-limiting conditions. The latter observation is important for the design of glutamine-free culture medium and feed used for GS-CHO and GS-NS0. In summary, we show that CHO cells selected under glutamine limitation have superfluous GS activity in glutamine-replete medium, which negatively affects their PVCD. This may be due to its effect on availability of aspartate which was the limiting nutrient for the growth of selected cells in glutamine-replete conditions. | {
"pile_set_name": "PubMed Abstracts"
} |
Hydrogen symbioses in evolution and disease.
Hydrogen is the source of energy that unites the metabolisms and fuels the innovative potentials of all living organisms. Autotrophs use hydrogen emitted into hydrothermal vents, where symbiotic communities that share hydrogen thrive. On the surface, life developed using photons to cleave water, releasing hydrogen carried into a reverse Krebs cycle to produce carbohydrates, from which hydrogen and its constituent electron and proton are extracted. Fluctuant electrogenic power is harnessed by extensive exchanges and symbiotic sharing schemes of hydrogen sources and carriers. These communicate with electrostatic nuclear centres, forming a positive feedback loop. If the proton-motive circuitry fails from loss of Redox potential, premature ageing and all-category disease can result. | {
"pile_set_name": "PubMed Abstracts"
} |
Impact of a 21-Gene Recurrence Score Test on the Choice of Adjuvant Chemotherapy for Hormone Receptor-positive Early-stage Breast Cancer: A Prospective Study.
Studies have recommended a 21-gene recurrence score (RS) to optimize adjuvant treatment for patients with early-stage breast cancer (EBC) with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) tumors. This study aimed to prospectively evaluate the impact of this RS in Chinese patients with breast cancer. We prospectively collected 227 patients with EBC with estrogen receptor-positive (ER+) and HER2- tumors. We used one-way analysis of variance to compare the distribution of different risk groups based on a 21-gene RS assay. A Kruskal-Wallis test and either a chi-square or Fisher's exact test were used as appropriate to compare continuous and categorical variables, respectively. Of the 227 eligible women enrolled, 61.2%, 30%, and 8.8% of patients were in the low (≤17), intermediate (18-30) and high (≥31) RS groups, respectively. Of the patients with a low RS, 74.8% were overestimated into the intermediate-risk group by St. Gallen risk. The overall impact of the 21-gene RS was reduced use of chemotherapy (78/227, 34.4%). In addition, Ki67 expression was positively associated with the 21-gene RS (R=0.68). Among patients with ER+/HER2- EBC, the 21-gene RS was an effective method for making a chemotherapy decision. Ki67 was associated with 21-gene RS. | {
"pile_set_name": "PubMed Abstracts"
} |
BNNT/Fe₃O₄ System as an Efficient Tool for Magnetohyperthermia Therapy.
Nanostructured materials have been widely studied aiming to biomedical applications, primarily for the purpose of carrying drugs or molecules of interest in a selected tissue or organ. In this context, boron nitride nanotubes (BNNTs), when functionalized with specific moieties, could be useful as nanovectors for delivery of proteins, drugs, and also RNAi molecules, due to their capacity to be uptaked by cells. The introduction of magnetic nanoparticles allows the use of such system as a hyperthermia agent. Thus, once it has been targeted to tumor areas, it could kill cancer cells by magnetohyperthermia therapy. In order to study this effect, magnetite nanoparticles were incorporated into hydroxilated BNNT. The system was characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and vibrating sample magnetometry (VSM). The results obtained show that magnetite nanoparticles are linked to the nanotubes. Magnetic measurements show that coercivity and magnetization were not disturbed after incorporation to the BNNT. Based on this, a new methodology for in vitro magnetohyperthermia experiments was developed, aiming to treat each cell group individually preserving its sterility. The biological assays of the system demonstrate its good cell viability and the great potential of this nanomaterial as a magnetohyperthermia agent for cancer treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
[Tissue engineering: new treatment of cartilage alterations in degenerative joint diseases in horses--preliminary results of a long term study].
Degenerative alterations in fetlock joints of the forelimb are common diagnoses for horses. The hyaline cartilage has a low capacity to regenerate and the treatment by veterinarians is often insufficient. As a final result, horses with articular cartilage defects are often not able to take part in competitions anymore. To establish an autologous cartilage repair method, we set artificial lesions (8 mm in diameter) into the fetlock joints of the forelimb of three horses. These defects were closed with autologous chondrocyte implants, which were fixed with titan-suture-anchors. After 3, 12 and 24 months, biopsies were taken by arthroscopy. One horse was euthanized after 9, another one after 24 months. The repair tissue was examined histologically and by biochemical analysis of hydroxyproline and glycosaminoglycan, which are typical cartilage related substances. After 9 months, the integration of the implant into native cartilage was demonstrated by electron microscopy. After 24 months, histological staining showed a similar morphology of the cartilage repair tissue compared with the surrounding native cartilage. Biochemical analysis of typical cartilage matrix molecules revealed formation of hyaline-like cartilage within tissue engineered autologous chondrocyte transplants. | {
"pile_set_name": "PubMed Abstracts"
} |
Fistular complication of gastric ectopia in the proximal oesophagus and pyriform sinus.
Gastric ectopias in the upper oesophagus and hypopharynx are relatively rare and often misinterpreted. They may become symptomatic due to the onset of a fistula involving adjacent structures in the neck. This case report describes a 20-year-old patient with swallowing difficulties and laterocervical pain, with a diagnosis of fistula of the pyriform sinus due to secernent gastric mucosal ectopia. The significance of this case lies in the fact that accurate aetiopathogenic study and careful differential diagnostic procedures enabled the proper identification of this rare upper oesophageal pathology, which is often misdiagnosed due to the technical difficulties involved in conventional endoscopy of the digestive tract. | {
"pile_set_name": "PubMed Abstracts"
} |
Generalized linear mixture models for handling nonignorable dropouts in longitudinal studies.
This paper presents a method for analysing longitudinal data when there are dropouts. In particular, we develop a simple method based on generalized linear mixture models for handling nonignorable dropouts for a variety of discrete and continuous outcomes. Statistical inference for the model parameters is based on a generalized estimating equations (GEE) approach (Liang and Zeger, 1986). The proposed method yields estimates of the model parameters that are valid when nonresponse is nonignorable under a variety of assumptions concerning the dropout process. Furthermore, the proposed method can be implemented using widely available statistical software. Finally, an example using data from a clinical trial of contracepting women is used to illustrate the methodology. | {
"pile_set_name": "PubMed Abstracts"
} |
Description of electronic excited states using electron correlation operator.
The electron correlation energy in a chemical system is defined as a difference between the energy of an exact energy for a given Hamiltonian, and a mean-field, or single determinant, approximation to it. A promising way to model electron correlation is through the expectation value of a linear two-electron operator for the Kohn-Sham single determinant wavefunction. For practical reasons, it is desirable for such an operator to be universal, i.e., independent of the positions and types of nuclei in a molecule. The correlation operator models the effect of electron correlation on the interaction energy in a electron pair. We choose an operator expanded in a small number of Gaussians as a model for electron correlation, and test it by computing atomic and molecular adiabatic excited states. The computations are performed within the Δ Self-Consistent Field (ΔSCF) formalism, and are compared to the time-dependent density functional theory model with popular density functionals. The simplest form of the correlation operator contains only one parameter derived from the helium atom ground state correlation energy. The correlation operator approach significantly outperforms other methods in computation of atomic excitation energies. The accuracy of molecular excitation energies computed with the correlation operator is limited by the shortcomings of the ΔSCF methodology in describing excited states. | {
"pile_set_name": "PubMed Abstracts"
} |
Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council's General Practice Research Framework.
We aimed to evaluate low intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease (IHD). 5499 men aged between 45 years and 69 years at high risk of IHD were recruited from 108 practices in the UK that belong to the Medical Research Council's General Practice Research Framework. Initially, warfarin or placebo was randomly allocated to 1427 men; 1013 of these men later moved to a factorial stage of the trial, retaining their warfarin or placebo warfarin allocation and adding randomly allocated active or placebo aspirin. Another 4072 men entered directly into the factorial stage making a total of 5085 men. The four factorial treatment groups were: active warfarin and active aspirin (WA, n = 1277), active warfarin and placebo aspirin (W, n = 1268), and placebo warfarin and active aspirin (A, n = 1268), and placebo warfarin and placebo aspirin (P, n = 1272). The primary end-point was all IHD defined as the sum of coronary death and fatal and non-fatal myocardial infarction (MI). The mean International Normalised Ratio (INR) of those on active warfarin was 1.47. The mean warfarin dose was 4.1 mg a day (range 0.5 mg-12.5 mg). There were 410 IHD events (142 fatal, 268 non-fatal). The main effect of warfarin (i.e., WA and W vs A and P) was a reduction in all IHD of 21% (95% CI 4-35, p = 0.02) chiefly due to a 39% reduction (15-57, p = 0.003) in fatal events so that warfarin reduced the death rate from all causes by 17% (1-30, p = 0.04). The main effect of aspirin (i.e., WA and A vs W and P) was a reduction in all IHD of 20% (1-35, p = 0.04) almost entirely due to a 32% reduction (12-48, p = 0.004) in non-fatal events. Absolute reductions in all IHD due to warfarin or aspirin were 2.6 and 2.3 per 1000 person years, respectively. WA reduced all IHD by 34% (11-51, p = 0.006) compared with P. WA increased haemorrhagic and fatal strokes. Ruptured aortic or dissecting aneurysms occurred in 15 of those who were or had been on warfarin compared with three of those who had not (p = 0.01). These results add to evidence that aspirin reduces non-fatal IHD. Warfarin reduced all IHD chiefly because of an effect on fatal events. Combined treatment with warfarin and aspirin is more effective in the reduction of IHD than either agent on its own. | {
"pile_set_name": "PubMed Abstracts"
} |
Drivers of productivity and its temporal stability in a tropical tree diversity experiment.
There is increasing evidence that mixed-species forests can provide multiple ecosystem services at a higher level than their monospecific counterparts. However, most studies concerning tree diversity and ecosystem functioning relationships use data from forest inventories (under noncontrolled conditions) or from very young plantation experiments. Here, we investigated temporal dynamics of diversity-productivity relationships and diversity-stability relationships in the oldest tropical tree diversity experiment. Sardinilla was established in Panama in 2001, with 22 plots that form a gradient in native tree species richness of one-, two-, three- and five-species communities. Using annual data describing tree diameters and heights, we calculated basal area increment as the proxy of tree productivity. We combined tree neighbourhood- and community-level analyses and tested the effects of both species diversity and structural diversity on productivity and its temporal stability. General patterns were consistent across both scales indicating that tree-tree interactions in neighbourhoods drive observed diversity effects. From 2006 to 2016, mean overyielding (higher productivity in mixtures than in monocultures) was 25%-30% in two- and three-species mixtures and 50% in five-species stands. Tree neighbourhood diversity enhanced community productivity but the effect of species diversity was stronger and increased over time, whereas the effect of structural diversity declined. Temporal stability of community productivity increased with species diversity via two principle mechanisms: asynchronous responses of species to environmental variability and overyielding. Overyielding in mixtures was highest during a strong El Niño-related drought. Overall, positive diversity-productivity and diversity-stability relationships predominated, with the highest productivity and stability at the highest levels of diversity. These results provide new insights into mixing effects in diverse, tropical plantations and highlight the importance of analyses of temporal dynamics for our understanding of the complex relationships between diversity, productivity and stability. Under climate change, mixed-species forests may provide both high levels and high stability of production. | {
"pile_set_name": "PubMed Abstracts"
} |
Cefepine vs. ceftazidime treatment of pyelonephritis: a European, randomized, controlled study of 300 pediatric cases. European Society for Paediatric Infectious Diseases (ESPID) Pyelonephritis Study Group.
Cefepime has been used in clinical therapeutic trials for meningitis, serious infection and febrile neutropenia, comprising more than 800 pediatric patients. This agent has also been used in patients 12 years of age and older with uncomplicated and complicated urinary tract infections including pyelonephritis, but not in younger patients. In this study the safety and efficacy of cefepime were compared with those of ceftazidime for treatment of pyelonephritis in pediatric patients younger than 12 years of age. Two hundred ninety-nine pediatric patients (ages 1 month to 12 years) with pyelonephritis (300 episodes) were enrolled in a randomized, open label, multicenter trial. Individual results were evaluated by a blinded committee of experts. Cefepime was compared with ceftazidime, both administered parenterally at 50 mg/kg every 8 h. Patients were to receive the assigned study drug until at least 48 h after becoming afebrile. The i.v. treatment was then to be continued or replaced by oral trimethoprimsulfamethoxazole for a maximum of 12 to 14 days. The predominant causative pathogens were Escherichia coli, 88%; Proteus spp., 6%; Pseudomonas aeruginosa, 2%; and Klebsiella spp., 2%. Bacteriologic eradication was achieved in 96 and 94% of cefepime and ceftazidime patients, respectively, at the end of i.v. study drug treatment and was maintained in 94 and 91%, respectively, at the end of total study therapy. After study therapy bacteriologic eradication was maintained after 4 to 6 weeks in 86% of cefepime cases and in 83% of ceftazidime cases. A satisfactory clinical response occurred in 98 and 96% of cefepime and ceftazidime patients, respectively, at the end of i.v. treatment and in 93% at the end of total study therapy in both treatment arms. Drug-related clinical adverse events occurred in 14 cefepime patients (91%) and in 10 ceftazidime patients (7%). Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Thermal forming of glass microsheets for x-ray telescope mirror segments.
We describe a technology to mass-produce ultrathin mirror substrates for x-ray telescopes of near Wolter-I geometry. Thermal glass forming is a low-cost method to produce high-throughput, spaceborne x-ray mirrors for the 0.1-200-keV energy band. These substrates can provide the collecting area envisioned for future x-ray observatories. The glass microsheets are shaped into mirror segments at high temperature by use of a guiding mandrel, without polishing. We determine the physical properties and mechanisms that elucidate the formation process and that are crucial to improve surface quality. We develop a viscodynamic model for the glass strain as the forming proceeds to find the conditions for repeatability. Thermal forming preserves the x-ray reflectance and scattering properties of the raw glass. The imaging resolution is driven by a large wavelength figure. We discuss the sources of figure errors, and we calculate the relaxation time of surface ripples. | {
"pile_set_name": "PubMed Abstracts"
} |
Lactulose hydrogen and [14C]xylose breath tests in patients with ileoanal anastomosis.
To study the intestinal bacterial flora and mouth to pouch transit time after ileoanal anastomosis, lactulose hydrogen and [14C]xylose breath tests were performed on 19 patients with ileoanal anastomosis and J-pouch and 8 patients with conventional ileostomy. Evaluated by the [14C]xylose breath test, patients with ileoanal anastomosis and ileal pouch showed no difference in the bacterial flora of the proximal small bowel when compared with ileostomy patients. The lactulose hydrogen breath test showed a significant rise in breath hydrogen, indicating bacterial overgrowth, in 68% of patients with ileoanal anastomosis but in none with conventional ileostomy (p less than 0.01). It was concluded that this peak in breath hydrogen was produced by the bacteria in the pouch. Thus the lactulose hydrogen breath test can be used to measure mouth to pouch transit time in 2/3 of patients with ileoanal anastomosis. Mouth to pouch transit time was 63 +/- 9 min and it correlated inversely with stool frequency (p less than 0.05). | {
"pile_set_name": "PubMed Abstracts"
} |
Nuclear magnetic resonance study of the exchangeable histidine protons in bovine and wheat germ superoxide dismutases.
Nuclear magnetic resonance studies at 220 MHz of the exchangeable histidine NH protons in bovine erythrocyte superoxide dismutase (BESOD) [EC 1.15.1.1] and the two isoenzymes of wheat germ superoxide dismutase (WGSODI and WGSODII) have been carried out. NMR spectral similarities reveal substantial structural homology of WGSOD with BESOD. Comparison of the spectra of the apoproteins and copper-free, native, and reduced proteins suggests that zinc has a structural role in WGSOD similar to that previously reported for BESOD [Lippard, S. J., Burger, A. R., Ugurbil, K., Pantoliano, M. W., & Valentine, J. S. (1977) Biochemistry 16, 1136]. Four resonances are assigned to conserved histidine residues, three of which are coordinated to the zinc atom while the fourth is nonligating. | {
"pile_set_name": "PubMed Abstracts"
} |
Using endoscopy to teach cataract surgery.
Current methods of teaching cataract surgery include lectures, wet-lab sessions, and participation in real surgery. We describe a new method using a microendoscopic cyclophotocoagulation device during phacoemulsification cataract extraction and posterior chamber intraocular lens (IOL) implantation in 4 eyes of 4 patients. Endoscopic visualization during surgery aided in construction of the corneal incision, location of the capsulorhexis edge, and estimation of the lens groove depth. It also demonstrated clinical findings not observable with the surgical microscope such as misplaced IOL haptics and residual lens cortex. Use of the endoscope enhanced the educational value of the surgery and the final surgical outcome. | {
"pile_set_name": "PubMed Abstracts"
} |
Target-in-the-loop wavefront sensing and control with a Collett-Wolf beacon: speckle-average phase conjugation.
Adaptive optical systems for laser beam projection onto an extended target embedded in an optically inhomogeneous medium are considered. A new adaptive optics wavefront control technique--speckle-average (SA) phase conjugation--is introduced. In this technique mitigation of speckle effects related to laser beam scattering off the rough target surface is achieved by measuring the SA wavefront slopes of the target return wave using a conventional Shack-Hartmann wavefront sensor. For statistically representative speckle averaging we consider the generation of an incoherent light source, referred to here as a Collett-Wolf beacon, directly on the target surface using a rapid steering (scanning) auxiliary laser beam. Our numerical simulations and experiment show that control of the outgoing beam phase using SA phase conjugation can lead to efficient compensation of turbulence effects and results in an increase of the projected laser beam power density on a remote extended target. The impact of both target anisoplanatism and the Collett-Wolf beacon size on adaptive system performance is studied. | {
"pile_set_name": "PubMed Abstracts"
} |
Glucagon secretion is increased in patients with Type 2 diabetic nephropathy.
Currently little is known about the relationship between renal function, albuminuria and glucagon; we analyzed the secretion of glucagon (GLA) and C-peptide in Type 2 diabetic patients with different degrees of nephropathy. 357 patients with Type 2 diabetes including 119 cases without nephropathy and 238 cases with nephropathy were divided into four groups according to the stages of diabetic nephropathy. Patients with diabetic nephropathy were further classified according to the level of estimated glomerular filtration rate (eGFR). OGTT and insulin, C-peptide, glucagon releasing tests were performed in all patients. Characteristics of glucagon and C-peptide secretion in different groups were compared. Glucagon/glucose ratio (GLA/GLU) and glucagon/insulin ratio (GLA/INS) were used to represent the inhibition of glucose or insulin on glucagon secretion, respectively. With the progress of diabetic nephropathy, glucagon level increased significantly; the glucagon peak after glucose load delayed from 60 min to 120 min, whereas C-peptide level decreased significantly. Related factors analysis suggested that glucagon was independently correlated with eGFR. Further analysis showed that glucagon level was higher in group with eGFR<60 ml/min compared with that in group with eGFR≥60 ml/min. In addition, both GLA/INS and GLA/GLU were higher in group with eGFR<60 ml/min compared with those in group with eGFR≥60 ml/min. Patients with Type 2 diabetic nephropathy have worsened islet alpha and beta cell function. Therefore medications based on the regulation of glucagon secretion may improve glycemic control and also be beneficial for delaying the progress of diabetic nephropathy. | {
"pile_set_name": "PubMed Abstracts"
} |
Coordinated variation in leaf and root traits across multiple spatial scales in Chinese semi-arid and arid ecosystems.
• Variation in plant functional traits is the product of evolutionary and environmental drivers operating at different scales. Little is known about whether, or how, this variation is coordinated between aboveground and belowground organs across and within spatial scales. • We address these questions using a hierarchically designed dataset of pairwise leaf and root traits related to carbon and nutrient economy of 64 species belonging to 14 plant communities in northern Chinese semi-arid and arid regions. • While both root and leaf traits showed most of their variance among (individuals and) species within communities, leaf trait variance tended to be relatively higher at coarser spatial scales than root trait variance. While leaf nitrogen (N) per area to root N per length ratio increased and specific leaf area to specific root length and leaf [N] to root [N] ratios decreased from semi-arid to arid environments owing to climatic/edaphic shifts, the matching pairs showed a strong pattern of positive correlation that was upheld across spatial scales and geographic areas. • Thus, trade-offs in plant resource investment across organs within individual vascular plants are constrained within a rather narrow range of variation. A new challenge will be to test whether and how such trait coordination is also seen within and across other biomes of the world. | {
"pile_set_name": "PubMed Abstracts"
} |
Safety and efficacy of non-continuous echocardiography-guided pericardiocentesis: a single-center study of 478 patients.
There are limited contemporary data on the safety and efficacy of echocardiography-guided pericardiocentesis in Italy. The aim of the study was to evaluate safety and efficacy of pericardiocentesis, performed with non-continuous echocardiography monitoring. All the procedures performed at Department of Cardiovascular Disease, Ospedali Riuniti Ancona, from January 2001 to June 2013, were retrospectively analyzed to determine risks connected to the procedure and its success rate. Epidemiological data, procedure indications and etiology of the effusions were also recorded. In the study period, 478 pericardiocentesis were performed for cardiac tamponade (N.=161), to remove large amount of fluid (N.=215) or for diagnostic purposes (N.=102). Echocardiographic evaluation, performed just before the procedure, was used to define the site of entry, to measure the distance from the skin to the fluid, and to establish how to direct the needle. We observed an extremely low rate of complications (<1%), without any death. The procedure was fully successful in 98% of cases and achieved only partial fluid removal in the remained 10 patients. The etiology of the effusion was malignancy or post cardiothoracic surgery in almost 60% of cases. Over the years there was an increase of pericardiocentesis performed after a cardiothoracic surgery (P=0.002); There was a significant reduction of the average amount of drained fluid in the years 2010-2013 vs. the period 2001-2009. Echocardiography-guided pericardiocentesis is an effective and safe procedure, with a low rate of complications. | {
"pile_set_name": "PubMed Abstracts"
} |
Progress in simulation modelling for pharmacokinetics.
Simulation models for the prediction of pharmacokinetics in humans and other mammalian species, which are based on the physiology and mechanistic models of absorption, distribution, metabolism and elimination are reviewed. The structure of such models is explained with reference to papers describing the mathematical details and alternative representations of organ flow and distribution. Approaches to the modelling of more complex tissues such as tumours and the liver are also reviewed as well as some specific transport processes such as biliary secretion and methods of ADME property estimation by experimental and in silico models. Specific approaches to the modelling of gastro-intestinal transit are explained as is the extension of the approach to simulating drug-drug interactions following co-administration of more than one drug. | {
"pile_set_name": "PubMed Abstracts"
} |
[Experimental study on the pathophysiology of endotoxin shock as analysed by alterations in thromboxane B2 and 6-keto-PGF1 alpha levels].
To evaluate the pathophysiological role of thromboxane A2 (TXA2) in endotoxin shock, plasma concentrations of TXA2 and PGI2 following E. coli endotoxin (ET) administration were measured in dogs and rats by radioimmunoassay of their stable metabolites TXB2 and 6-keto-PGF1 alpha, respectively. Also, the effects of TXA2 synthetase inhibitor (OKY046) on eicosanoid levels, haemodynamics and survival were assessed. The following results were obtained: 1) Survival rates of the rats given 50 mg/kg of ET were 31% at 12 hrs and 17% at 24 hrs. Pretreatment with OKY046 markedly improved the survival rates. 2) Plasma concentrations of TXB2 were rapidly elevated in untreated control dogs and rats following ET administration, whereas plasma 6-keto-PGF1 alpha levels were gradually elevated. TXB2/6-keto-PGF1 alpha ratio showed an early elevation at 15 minutes after ET administration. The ratio became lower than base line, thereafter. 3) In contrast to the controls, animals pretreated with OKY046 did not exhibit significant elevations in plasma TXB2 levels. On the other hand, plasma levels of 6-keto-PGF1 alpha were not altered by OKY046 treatment. 4) In the control dogs given ET, the early elevations in pulmonary artery pressure (PAP) and reduction in lung compliance correlated with the early elevation in plasma TXB2/6-keto-PGF1 alpha ratio. 5) In OKY046-treated dogs, the early elevation in TXB2/6-keto-PGF1 alpha ratio was not seen and PAP increase and lung compliance reduction were prevented. The results suggest that TXA2 plays an important pathophysiological role in the development of endotoxin shock. | {
"pile_set_name": "PubMed Abstracts"
} |
Liquid-core capsules via interfacial polymerization: a free-radical analogy of the nylon rope trick.
Liquid-core capsules have wide-ranging applications in the high-efficiency encapsulation and controlled release of drugs, dyes, enzymes, and other substrates. Their great utility has driven the rapid development of various preparation techniques. However, there remains no convenient technique for the preparation of submicrometer liquid-core capsules with shell thicknesses less than 100 nm. Here, we demonstrate a new interfacial free-radical polymerization approach for the straightforward preparation of liquid-core polymer capsules. Conceptually, this interfacial free-radical polymerization is analogous to the classical "nylon rope trick" wherein hydrophobic and hydrophilic monomers alternately copolymerize to constrain the polymerization at interfaces, but its free-radical mechanism allows precise control of initiation, which makes it possible to finely disperse the immiscible phases prior to polymerization. | {
"pile_set_name": "PubMed Abstracts"
} |
[Low-level lead exposure and children's intelligence from recent epidemiological studies in the U.S.A. and other countries to progress in reducing lead exposure and screening in the U.S.A].
From the 1980s many well-designed epidemiological studies have confirmed that low-level, subclinical lead exposure in early life is associated with decrements in children's intelligence. Neurodevelopmental deficits from exposure to a low level of lead have been held to be not only an American problem, but also a worldwide issue in the past decade. Good epidemiological studies were reported from England, Scotland, Germany, Greece, Australia and New Zealand. Well-designed cross-sectional and prospective studies were carried out to quantify the magnitude of the relation between full scale IQ in children aged five years or more and the burden of lead (PbB or PbT) in early life of children. Of five cross-sectional studies of blood lead, two demonstrated a significant inverse association between lead and IQ even after adjustment for confounders. Two other studies, however, showed no firm evidence of inverse association after adjustment for confounders, and the remaining study demonstrated no significant inverse association of five cross-sectional studies of tooth lead, two indicated an inverse association between tooth lead and IQ, two others showed no significant inverse association after adjustment for confounders, and the remaining one manifested no association. Of four prospective studies, two revealed strong evidence of an inverse association between blood lead at the age of around two years and IQ. Another one, however, revealed an inverse association between mean postnatal blood level and IQ, while the remaining one demonstrated no significant inverse association between IQ and postnatal blood lead level after adjustment for confounders. In a comprehensive review of 26 epidemiological studies since 1979, including a meta-analysis, Pococok et al. indicated that doubling of the body lead burden (from 10 to 20 micrograms/dl) blood lead or (from 5 to 10 micrograms/g) tooth lead is typically associated with a mean deficit in full-scale IQ of around 1-2 IQ points. Lead in interior household dust, exterior surface soil, and old residential lead paint, which is deteriorated or removed, constitute the major sources of lead poisoning in children in the United States. Infants and children, who typically engage in hand to mouth activities, frequently come into contact with lead dust in soil and on the floor. Marked declines both in air lead and blood lead concentrations are evident parallel to the phase-down of lead in gasoline and soldered cans by U.S. food processors. The major source of lead in drinking water is from lead pipes used in household plumbing. The CDC revised its guidelines concerning childhood lead poisoning, stating that community prevention activities should be triggered when a large percentage of children in a community have blood lead levels of 10 micrograms/dl, the lowest level at which neurodevelopmental effects were believed to occur. For children with blood lead level concentrations between 10 and 14 micrograms/dl, more frequent rescreening may be needed. For concentrations between 15 and 19 micrograms/dl, in addition to more frequent screening, nutritional and educational advice should be given. In cases where these levels persist, there should be environmental investigation and intervention. All children with blood levels of 20 micrograms/dl or greater should receive environmental evaluation and medical examination. Such children may need pharmacological treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
Monitoring aggregate formation in organotypic slice cultures from transgenic mice.
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the HD gene. It encodes a protein known as huntingtin, which aggregates in the nuclei of affected neurons. These aggregates are an obvious therapeutic target, thus an organotypic slice culture assay has been designed to screen potential antiaggregation compounds using the R6/2 mouse model of HD. This assay allows the aggregates to be fully quantified using fluorescent confocal microscopy and gives additional information perturbing to drug solubility, delivery, toxicity, concentration, and efficacy of inhibitors. This information is essential to the planning and application of an in vivo drug trial in the R6/2 mice. | {
"pile_set_name": "PubMed Abstracts"
} |
Phencyclidine increased while isolation rearing did not affect progressive ratio responding in rats: Investigating potential models of amotivation in schizophrenia.
Schizophrenia is a debilitating neurodevelopmental disorder affecting 1% of the global population with heterogeneous symptoms including positive, negative, and cognitive. While treatment for positive symptoms exists, none have been developed to treat negative symptoms. Animal models of schizophrenia are required to test targeted treatments and since patients exhibit reduced effort (breakpoints) for reward in a progressive ratio (PR) task, we examined the PR breakpoints of rats treated with the NMDA receptor antagonist phencyclidine or those reared in isolation - two common manipulations used to induce schizophrenia-relevant behaviors in rodents. In two cohorts, the PR breakpoint for a palatable food reward was examined in Long Evans rats after: 1) a repeated phencyclidine regimen; 2) A subchronic phencyclidine regimen followed by drug washout; and 3) post-weaning social isolation. Rats treated with repeated phencyclidine and those following washout from phencyclidine exhibited higher PR breakpoints than vehicle-treated rats. The breakpoint of isolation reared rats did not differ from those socially reared, despite abnormalities of these rats in other schizophrenia-relevant behaviors. Despite their common use for modeling other schizophrenia-relevant behaviors neither phencyclidine treatment nor isolation rearing recreated the motivational deficits observed in patients with schizophrenia, as measured by PR breakpoint. Other manipulations, and negative symptom-relevant behaviors, require investigation prior to testing putative therapeutics. | {
"pile_set_name": "PubMed Abstracts"
} |
Kinetics of in vivo elimination of suicide gene-expressing T cells affects engraftment, graft-versus-host disease, and graft-versus-leukemia after allogeneic bone marrow transplantation.
Suicide gene therapy is one approach being evaluated for the control of graft-vs-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). We recently constructed a novel chimeric suicide gene in which the entire coding region of HSV thymidine kinase (HSV-tk) was fused in-frame to the extracellular and transmembrane domains of human CD34 (DeltaCD34-tk). DeltaCD34-tk is an attractive candidate as a suicide gene in man because of the ensured expression of HSV-tk in all selected cells and the ability to rapidly and efficiently purify gene-modified cells using clinically approved CD34 immunoselection techniques. In this study we assessed the efficacy of the DeltaCD34-tk suicide gene in the absence of extended ex vivo manipulation by generating transgenic animals that express DeltaCD34-tk in the peripheral and thymic T cell compartments using the CD2 locus control region. We found that DeltaCD34-tk-expressing T cells could be purified to near homogeneity by CD34 immunoselection and selectively eliminated ex vivo and in vivo when exposed to low concentrations of GCV. The optimal time to administer GCV after allogeneic BMT with DeltaCD34-tk-expressing transgenic T cells was dependent on the intensity of the conditioning regimen, the leukemic status of the recipient, and the dose and timing of T cell infusion. Importantly, we used a controlled graft-vs-host reaction to promote alloengraftment in sublethally irradiated mice and provide a graft-vs-leukemia effect in recipients administered a delayed infusion of DeltaCD34-tk-expressing T cells. This murine model demonstrates the potential usefulness of DeltaCD34-tk-expressing T cells to control GVHD, promote alloengraftment, and provide a graft-vs-leukemia effect in man. | {
"pile_set_name": "PubMed Abstracts"
} |
Fever without localizing signs in children: a review in the post-Hib and postpneumococcal era.
Fever without localizing signs in young infants and children has been a common problem for pediatric practitioners for decades. Prior to the introduction of vaccines against common childhood invasive pathogens, including Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae, extensive diagnostic workup of febrile infants and children was warranted to avoid missing serious bacterial infections. At that time, occult bacteremia occurred at a rate of 5.7%. Evaluation of febrile children was based on high and low risk criteria established by Dagan et al. and applied further in suggested clinical practice guidelines in 1993. After the introduction of effective Hib and PCV7 vaccines, the rate of serious bacterial infections has dramatically fallen, with occult bacteremia rates now 0-0.74%. Changes in the administration of intrapartum antibiotics to women at risk for transmitting Group B Streptococcus to neonates has significantly reduced the rates of early onset GBS disease in infants. Although the risk of serious infections is extremely low, management and evaluation of febrile children has remained essentially unchanged. This review summarizes the historical context of the management of the febrile child, discusses the developments that have been cause for re-evaluation and provides recommendations for management of the febrile child in this current era. | {
"pile_set_name": "PubMed Abstracts"
} |
Early-onset seizure variant of Rett syndrome: definition of the clinical diagnostic criteria.
Rett syndrome is a severe neurodevelopmental disorder affecting almost exclusively females. Among Rett clinical variants, the early-onset seizure variant describes girls with early onset epilepsy and it is caused by mutations in CDKL5. Four previously reported girls and five new cases with CDKL5 mutation, ranging from 14 months to 13 years, were evaluated by two clinical geneticists, classified using a severity score system based on the evaluation of 22 different clinical signs and compared with 128 classic Rett and 25 Zappella variant MECP2-mutated patients, evaluated by the same clinical geneticists. Clinical features were compared with previously described CDKL5 mutated patients. Both the statistical and the descriptive approach have been used to delineate clinical diagnostic criteria. All girls present epilepsy with onset varying from 10 days to 3 months. Patients may present different type of seizures both at onset and during the whole course of the disease; multiple seizure types may also occur in the same individual. After treatment with antiepileptic drugs patients may experience a short seizure-free period but epilepsy progressively relapses. Typical stereotypic hand movements severely affecting the ability to grasp are present. Psychomotor development is severely impaired. In the majority of cases head circumference is within the normal range both at birth and at the time of clinical examination. For the practical clinical approach we propose to use six necessary and eight supportive diagnostic criteria. Epilepsy with onset between the first week and 5 months of life, hand stereotypies, as well as severe hypotonia, are included among the necessary criteria. | {
"pile_set_name": "PubMed Abstracts"
} |
Aggregation and micellization of sodium dodecyl sulfate in the presence of Ce(III) at different temperatures: a conductometric study.
Aggregation properties of sodium dodecyl sulfate (SDS) in the presence of cerium(III) chloride, at various temperatures (298.15-323.15 K) have been measured by the electrical conductance technique. The experimental data on aqueous solutions as a function of SDS concentration show the presence of two inflexion points indicating the presence of two distinct interaction mechanisms: the first, occurring at SDS concentrations below the critical micelle concentration of the pure surfactant, which can be explained by the formation of aggregates between dodecyl sulfate (DS-) and Ce(III), while the second one, at SDS concentrations around the critical micelle concentration (cmc) of the pure surfactant which is due to the SDS micellization. The aggregation between DS- and Ce(III) was confirmed by static light scattering. The binding ratio of DS-/Ce(III) changes from 6 to 4, shows a slight dependence on the Ce(III) concentration and is independent of the temperature. The thermodynamic micellization parameters, Gibbs energy, enthalpy and entropy of micellization were calculated on the basis of the experimental data for the aggregation concentration, and the degree of counterion dissociation of the micelles. The SDS micellization is energetically favoured by increasing either the concentration of CeCl3 or the temperature. Such behaviour is clearly dominated by a decrease of the micellization (exothermic) enthalpy. The entropy of micellization approaches zero as the cerium(III) chloride concentration and temperature increase. | {
"pile_set_name": "PubMed Abstracts"
} |
[Study on the needling depth of point Yaotu with CT scanning].
To probe the safe depth and angle of needling the point Yaotu for treatment of prolapse of intervertebral disc. CT technique was used for scanning investigation of the depth and angle of needling the point Yaotu. When the acupuncture needle was inserted vertically to the external space of intervertebral foramen of human body with arrival of qi, the tip of needle could reach to 73 mm deep, which is the best needling depth and angle. The needle vertically inserting to the external space of intervertebral foramen at the point Yaotu is proper in treatment of prolapse of intervertebral disc. | {
"pile_set_name": "PubMed Abstracts"
} |
Suppression of response to foreign substances by intestinal macrophages.
Macrophages play an important role in the maintenance of homeostasis by changing their function according to the tissue and environment everywhere in the body. We have proposed that intestinal macrophages, which exist in the front line receiving environmental information, have an important function in forming a macrophage network for biophylaxis. In this review, we introduce intestinal macrophages as an example of the highly plastic and flexible cells adaptable to environmental information. Intestinal macrophages are hyporesponsiveness to foreign substances, especially lipopolysaccharide (LPS), and less expression of CD14 and TLR4/MD-2, receptors for LPS. However, those proteins expression was observed in the cytoplasm of intestinal macrophage. We also found that intestinal macrophages treated with IgA could restore in response to LPS. In conclusion, intestinal macrophages possess the plasticity to respond sensitively to change in their environment and are considered to be involved inflammatory bowel disease development. | {
"pile_set_name": "PubMed Abstracts"
} |
An essential role for Fgfs in endodermal pouch formation influences later craniofacial skeletal patterning.
Fibroblast growth factor (Fgf) proteins are important regulators of pharyngeal arch development. Analyses of Fgf8 function in chick and mouse and Fgf3 function in zebrafish have demonstrated a role for Fgfs in the differentiation and survival of postmigratory neural crest cells (NCC) that give rise to the pharyngeal skeleton. Here we describe, in zebrafish, an earlier, essential function for Fgf8 and Fgf3 in regulating the segmentation of the pharyngeal endoderm into pouches. Using time-lapse microscopy, we show that pharyngeal pouches form by the directed lateral migration of discrete clusters of endodermal cells. In animals doubly reduced for Fgf8 and Fgf3, the migration of pharyngeal endodermal cells is disorganized and pouches fail to form. Transplantation and pharmacological experiments show that Fgf8 and Fgf3 are required in the neural keel and cranial mesoderm during early somite stages to promote first pouch formation. In addition, we show that animals doubly reduced for Fgf8 and Fgf3 have severe reductions in hyoid cartilages and the more posterior branchial cartilages. By examining early pouch and later cartilage phenotypes in individual animals hypomorphic for Fgf function, we find that alterations in pouch structure correlate with later cartilage defects. We present a model in which Fgf signaling in the mesoderm and segmented hindbrain organizes the segmentation of the pharyngeal endoderm into pouches. Moreover, we argue that the Fgf-dependent morphogenesis of the pharyngeal endoderm into pouches is critical for the later patterning of pharyngeal cartilages. | {
"pile_set_name": "PubMed Abstracts"
} |
[Management of chemotherapy-induced emesis: what is the standard after 20 years of clinical research].
The knowledge of the importance, the physiopathological mechanisms, and the management of the chemotherapy-induced emesis has increased exponentially during the last 20 years. High-dosage metoclopramide (MCP) therapy has been introduced in the eighties and serotonine type-3 receptor antagonists (5-HT(3) antagonists) have been used since the late eighties and early nineties. Due to both classes of substances the results of the antiemetic therapies have improved drastically. After 20 years of intensive clinical research it seems to be appropriate to come to an intermediate conclusion. With the aid of an overview and a new analysis of the literature published on this topic so far, the current state of research is shown (including the fields in which further improvement will be necessary), and suggestions are made, wherever it seemed possible, to attain the "gold standard" in antiemetic therapy. In connection with all highly or very highly emetogenic chemotherapies, an antiemetic prophylaxis should be initiated on the day of therapy, especially when using platinum or most of the cyclophosphamide-based regimes for cancer treatment. The recommended prophylaxis consists of a combination of 5-HT(3) antagonists with a corticosteroid. To combat the so-called delayed emesis on the days following therapy, all patients should undergo an oral corticoid therapy, possibly in combination with MCP (especially platinum-therapy patients), less frequently with 5-HT(3) antagonists. With these means of prophylaxis emesis can be prevented/avoided completely in most patients, and nausea can at least be reduced. It is sufficient to administer a single dose of 5-HT(3) antagonists prior to chemotherapy. For ondansetron and granisetron, the best documented substances within this class of drugs, 8 mg (ondansteron) and 3 mg (granisetron) are considered standard dosages. Among the corticoids, most data have been accumulated for dexamethasone. A standard dose of 10 to 20 mg can be administered prior to chemotherapy. Right after and especially on the days following chemotherapy higher dosages seem to be indicated. Further therapy improvements, especially concerning emesis and nausea on the days following chemotherapy, are necessary and are currently object of clinical research. | {
"pile_set_name": "PubMed Abstracts"
} |
Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: identification of genetic indicators to predict patient outcome.
We conducted an analysis of chromosomal numerical aberrations and their clinical significance in hepatocellular carcinoma. We analyzed 87 hepatocellular carcinomas by array-based comparative genomic hybridization with an array containing 800 bacterial artificial chromosome clones. Frequent (>30%) chromosomal losses on 1p36.1, 4q21-25, 4q34-35.1, 8p23.3b-11.1, 13q14.1-14.3, 16p13.3, 16q22.1-24.3b, 17p13.3-13.1 and 17p13.3-11, and gains on 1q21-44f, 2q21.2, 2q34, 3q11.2, 5p14.2, 5q13.2-14, 7p22, 7p14.2, 7q21.1, 7q22.3, 7q34, 8q12-24.3 and 17q23, were observed. Recurrent (>5%) amplifications were detected on 1q25, 8q11 and 11q11, and we discovered a novel homozygous deletion at 14q32.11. The extent of chromosomal aberrations correlated significantly with various clinicopathological characteristics of the tumors, and increased in a stepwise manner with the progression of hepatocellular carcinoma. We also identified novel chromosomal alterations that were significantly associated with a range of malignant phenotypes. Multivariate analysis revealed that both chromosomal loss on 17p13.3 and gain on 8q11 are independent prognostic indicators. Our results contribute to a complete description of genomic structural aberrations in relation to hepatocarcinogenesis and provide a valuable basis from which we can begin to understand the characteristics of tumors, predict patient outcomes and discover novel therapeutic targets for hepatocellular carcinoma. | {
"pile_set_name": "PubMed Abstracts"
} |
A variable region gene subfamily encoding T cell receptor beta-chains is selectively conserved among mammals.
Studies of murine T cell receptor genes indicate that the VT beta repertoire, in contrast to the large VT alpha, VH, and VK repertoires, is limited to approximately 21 genes. Large differences between the various VT beta sequences allow classification into distinct subfamilies consisting of one or few members. The VT beta sequence of a gene, RTB92, expressed in a rabbit T cell line is most closely related to a VT beta gene expressed in the human cell line Molt-4. Genomic blots with RTB92 VT beta region used as probe indicated conservation of related VT beta gene subfamilies in man and pig, but no related sequences were seen in rat, mouse, or hamster. The relationship among these VT beta genes mirrors similarities and differences in MHC genes of the compared species and suggests coordinate evolution of these functionally related gene families. The constant region of RTB92 was shown to be rabbit CT beta 2 by reference to genomic clones. Comparisons with constant region sequences of human and murine CT beta 1 and CT beta 2 chains reveal no similarities in amino acid or nucleic acid sequence in the coding region characteristic of the respective isotypes. Intraspecies homologies between CT beta 1 and CT beta 2 sequences were much greater than those between CT beta 1 or CT beta 2 from other species. By contrast, comparisons of JT beta and 3' untranslated region sequences showed significant interspecies conservation of sequences in the beta 1 and in the beta 2 regions. | {
"pile_set_name": "PubMed Abstracts"
} |
Lithium adduct as precursor ion for sensitive and rapid quantification of 20 (S)-protopanaxadiol in rat plasma by liquid chromatography/quadrupole linear ion trap mass spectrometry and application to rat pharmacokinetic study.
A novel, rapid and sensitive liquid chromatography/quadrupole linear ion trap mass spectrometry [LC-ESI-(QqLIT)MS/MS] method was developed and validated for the quantification of protopanaxadiol (PPD) in rat plasma. Oleanolic acid (OA) was used as internal standard (IS). A simple protein precipitation based on acetonitrile (ACN) was employed. Chromatographic separation was performed on a Sepax GP-C18 column (50 × 2.1 mm, 5 μM) with a mobile phase consisting of ACN-water and 1.5 μM formic acid and 25 mM lithium acetate (90 : 10, v/v) at a flow rate of 0.4 ml/min for 3.0 min. Multiple-reaction-monitoring mode was performed using lithium adduct ion as precursor ion of m/z 467.5/449.4 and 455.6/407.4 for the drug and IS, respectively. Calibration curve was recovered over a concentration range of 0.5-100 ng/ml with a correlation coefficient >0.99. The limit of detection was 0.2 ng/ml in rat plasma for PPD. The results of the intraday and interday precision and accuracy studies were well within the acceptable limits. The validated method was successfully applied to investigate the pharmacokinetic study of PPD after intravenous and gavage administration to rat. | {
"pile_set_name": "PubMed Abstracts"
} |
Influence of iron on plasma interleukin-2 and gamma interferon level in iron deficiency anemia.
to find out the the influence of iron on the levels of plasma IL-2 and IFNgamma in iron deficiency anemia patient. the study subjects were patients with IDA (intended samples) selected from the accessible population that met the inclusion and exclusion criteria using consecutive sampling technique and by signing an informed consent. Blood samples were taken for measurement of IL-2 and IFNgamma concentrations as well as list of questionnaires for obtaining data on age, gender, body weight, infections suffered, use of immunosuppressive medicines, malnutrition, malignancy and genetic disorder, and IDA diagnosis. The levels of IL-2 and IFNgamma were measured before and after 8 weeks of iron tablet adminitration using immunoassay solid phase ELISA. Descriptive statistics was used to illustrate patient's characteristics and frequency distribution of various variables. The average difference of IL-2 and IFNgamma concentrations was also examined pre and post administration of iron tablets for 8 weeks using Wilkoxon sign rank test. in the study, 26 IDA patients were eligible, chosen from 64 IDA patients who were then given iron tablets for 8 weeks. By the end of the treatment, they were tested for complete blood analysis, serum ferritin, and cytokines of plasma. Sign rank test of Wilcoxon was used to find out direction and degree of difference between the two paired groups which showed a significant difference between pre and post iron tablet administration of hemoglobin (Z= -4.561; p<0.001), MCV (Z= -4.276; p<0.001), MCH (Z= -3.616; p<0.001) and feritin (Z= -3.556; p<0.001). After 8 weeks of iron tablets, the study also noted, increasing of plasma IL-2 and IFNgamma. Before treatment level of plasma IL-2 was 7.65 pg/l then became 29.3 pg/l after treatment (Z=- 3.508, p<0.001) and plasma IFNg before treatment was 10.15 pg/l became 46.7 pg/l after treatment (Z= -4.241, p<0.001). concentration of IL2 dan IFNgamma in plasma significantly increased after administration of iron tablets for 8 weeks as compared to that before iron treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
PUFA biosynthesis pathway in marine scallop Chlamys nobilis Reeve.
Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential in important physiological processes. However, the endogenous PUFA biosynthesis pathway is poorly understood in marine bivalves. Previously, a fatty acyl desaturase (Fad) with Δ5 activity was functionally characterized and an elongase termed Elovl2/5 was reported to efficiently elongate 18:2n-6 and 18:3n-3 to 20:2n-6 and 20:3n-3 respectively in Chlamys nobilis. In this study, another elongase and another Fad were identified. Functional characterization in recombinant yeast showed that the newly cloned elongase can elongate 20:4n-6 and 20:5n-3 to C22 and C24, while the newly cloned scallop Fad exhibited a Δ8-desaturation activity, and could desaturate exogenously added PUFA 20:3n-3 and 20:2n-6 to 20:4n-3 and 20:3n-6 respectively, providing the first compelling evidence that noble scallop could de novo biosynthesize 20:5n-3 and 20:4n-6 from PUFA precursors though the "Δ8 pathway". No Δ6 or Δ4 activity was detected for this Fad. Searching against our scallop transcriptome database failed to find any other Fad-like genes, indicating that noble scallop might have limited ability to biosynthesize 22:6n-3. Interestingly, like previously characterized Elovl2/5, the two newly cloned genes showed less efficient activity toward n-3 PUFA substrates than their homologous n-6 substrates, resulting in a relatively low efficiency to biosynthesize n-3 PUFA, implying an adaption to marine environment. | {
"pile_set_name": "PubMed Abstracts"
} |
Excited-state vibrations, lifetimes, and nonradiative dynamics of jet-cooled 1-ethylcytosine.
The S1 excited-state lifetime of jet-cooled 1-ethylcytosine (1ECyt) is ∼1 ns, one of the longest lifetimes for cytosine derivatives to date. Here, we analyze its S0 → S1 vibronic spectrum using two-color resonant two-photon ionization and UV/UV holeburning spectroscopy. Compared to cytosine and 1-methylcytosine, the S0 → S1 spectrum of 1ECyt shows a progression in the out-of-plane "butterfly" mode ν1 ', identified by spin-component scaled-second-order coupled-cluster method ab initio calculations. We also report time-resolved S1 state nonradiative dynamics at ∼20 ps resolution by the pump/delayed ionization technique. The S1 lifetime increases with the number of ν1 ' quanta from τ = 930 ps at v1 '=0 to 1030 ps at v1 '=2, decreasing to 14 ps at 710 cm-1 vibrational energy. We measured the rate constants for S1 ⇝ S0 internal conversion and S1 ⇝ T1 intersystem crossing (ISC): At the v' = 0 level, kIC is 8 × 108 s-1 or three times smaller than 1-methylcytosine. The ISC rate constant from v' = 0 to the T1(3ππ*) state is kISC = 2.4 × 108 s-1, 10 times smaller than the ISC rate constants of cytosine, but similar to that of 1-methylcytosine. Based on the calculated S1(1ππ*) state radiative lifetime τrad = 12 ns, the fluorescence quantum yield of 1ECyt is Φfl ∼ 7% and the intersystem crossing yield is ΦISC ∼ 20%. We measured the adiabatic ionization energy of 1-ethylcytosine via excitation of the S1 state as 8.353 ± 0.008 eV, which is 0.38 eV lower than that of amino-keto cytosine. Measurement of the ionization energy of the long-lived T1(ππ*) state formed via ISC reveals that it lies 3.2-3.4 eV above the S0 ground state. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolation of HIV-1 from seropositive people living in Cotonou, Benin.
Benin is located in West Africa and is situated between HIV-2 and HIV-1-endemic zones. The first cases of HIV-1 infection in Benin were reported in 1987. Since then, AIDS cases have been diagnosed there and the number of known HIV-seropositive people has rapidly increased. Blood samples were collected from 14 seropositive and 11 seronegative patients living in the main city, Cotonou, and their peripheral blood mononuclear cells were cultured. In seven of the seropositive cases, a retrovirus was detected by measurement of Mg2(+)-dependent reverse transcriptase activity and electron microscopy. HIV-1 antigen assay and genomic analysis indicated that the isolated viruses belong to the first serotype. In each positive case, an HIV-1 DNA probe hybridized to the RNA extracted from the virus and six isolates were found positive by the polymerase chain reaction using HIV-1-specific primers. | {
"pile_set_name": "PubMed Abstracts"
} |
New control strategies for neuroprosthetic systems.
The availability of techniques to artificially excite paralyzed muscles opens enormous potential for restoring both upper and lower extremity movements with neuroprostheses. Neuroprostheses must stimulate muscle, and control and regulate the artificial movements produced. Control methods to accomplish these tasks include feedforward (open-loop), feedback, and adaptive control. Feedforward control requires a great deal of information about the biomechanical behavior of the limb. For the upper extremity, an artificial motor program was developed to provide such movement program input to a neuroprosthesis. In lower extremity control, one group achieved their best results by attempting to meet naturally perceived gait objectives rather than to follow an exact joint angle trajectory. Adaptive feedforward control, as implemented in the cycle-to-cycle controller, gave good compensation for the gradual decrease in performance observed with open-loop control. A neural network controller was able to control its system to customize stimulation parameters in order to generate a desired output trajectory in a given individual and to maintain tracking performance in the presence of muscle fatigue. The authors believe that practical FNS control systems must exhibit many of these features of neurophysiological systems. | {
"pile_set_name": "PubMed Abstracts"
} |
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