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pubmed_133_3999
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1. To aid in the prediction of drug interactions with alprazolam, the human CYP involved in the 1'- and 4-hydroxylation of alprazolam were characterized using human liver microsomes, expressed enzymes and selective chemical inhibitors. 2. The formation of 4-hydroxyalprazolam and 1'-hydroxyalprazolam at an alprazolam concentration of 62.5 microM were reduced by the prototypic CYP3A inhibitor, troleandomycin (50 microM), by 97 and 9900 respectively. Only microsomes from B-lymphoblastoid cells expressing CYP3A4 were capable of catalysing the 1'- and 4-hydroxylation of alprazolam. 3. The formation rates of 1'-hydroxyalprazolam and 4-hydroxyalprazolam at an alprazolam concentration of 1 mM were significantly correlated (n = 19, r = 0.95, p<0.01) indicating that the same enzyme(s) mediated these biotransformations. A significant (p<0.01) correlation was observed between alprazolam 4- and 1'-hydroxylase activity and CYP3A-mediated midazolam 4-hydroxylase, midazolam 1'-hydroxylase, dextromethorphan N-demethylase and erythromycin N-demethylase activities. 4. In conclusion, in adult human liver the CYP3A subfamily members are the principal enzymes involved in the 1'- and 4-hydroxylation of alprazolam. Thus, clinically significant drug drug interactions between alprazolam and other CYP3A substrates are to be expected.
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10.1080/004982599238173
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pubmed_547_3422
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BACKGROUND: Recent reports have shown that risperidone, which has established antipsychotic efficacy, is effective and safe in a once-daily dosing regimen. METHOD: The efficacy and safety of once-daily risperidone were assessed in a retrospective study of 27 patients with a variety of psychiatric disorders who were attending a community day treatment program. Their DSM-IV diagnoses included schizophrenia, schizoaffective disorder, bipolar disorder, major depression with psychosis, and posttraumatic stress disorder. They had received once-daily risperidone for a mean of more than 18 months. RESULTS: Disorders of most patients were controlled with once-daily dosages of 1 to 6 mg/day of risperidone. The nighttime once-daily risperidone dosage was well tolerated by patients. In addition, there was no increase in antipsychotic-related side effects, and compliance was enhanced. CONCLUSION: Risperidone was well tolerated, and no patient needed antiparkinsonian medications even at high dosages of risperidone once daily.
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10.4088/pcc.v02n0205
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pubmed_149_2354
|
BACKGROUND
Self-extubation is an adverse patient event that can lead to severe complications. Gaps in clinical practice from the lack of nursing awareness and decision making capacity have often resulted in cases of preventable self-extubation. Review of current evidence suggests that initiatives to support nursing clinical decision making can help prevent adverse patient events such as self-extubation.
AIMS
The aim of this study was to reduce the incidence of self-extubation by 50% in a cardiology intensive care unit over 1 year.
METHODS
A quality improvement project was undertaken with a PEST model of nursing care introduced from January 2017 to December 2017 in the cardiology intensive care unit to guide nursing staff to assess and render appropriate interventions along patient domains such as pain, endotracheal tube securement, sedation, and tie to prevent incidences of self-extubation.
RESULTS
Incidences of self-extubation have reduced to 5 cases in 2017, reflecting a 50% improvement from 10 cases in 2016.
CONCLUSIONS
Formalizing practice standards into an easy-to-remember mnemonics or framework can improve patient outcomes. Policy makers must be aware that initiatives to facilitate decision making can improve patient safety.
|
10.1097/DCC.0000000000000364
|
pubmed_603_1786
|
3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) are hallucinogenic amphetamines with addictive properties. The hippocampus is involved in learning and memory and seems particularly vulnerable to amphetamine's neurotoxicity. We evaluated the neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus obtained from Wistar rat embryos (E-17 to E-19). Mature neurons after 10 days in culture were exposed for 24 or 48 h either to MDMA (100-800 μM) or DOI (10-100 μM). Both the lactate dehydrogenase (LDH) release and the tetrazolium-based (MTT) assays revealed a concentration- and time-dependent neuronal death and mitochondrial dysfunction after exposure to both drugs. Both drugs promoted a significant increase in caspase-8 and caspase-3 activities. At concentrations that produced similar levels of neuronal death, DOI promoted a higher increase in the activity of both caspases than MDMA. In the mitochondrial fraction of neurons exposed 24h to DOI or MDMA, we found a significant increase in the 67 kDa band of apoptosis inducing factor (AIF) by Western blot. Moreover, 24h exposure to DOI promoted an increase in cytochrome c in the cytoplasmatic fraction of neurons. Pre-treatment with an antibody raised against the 5-HT(2A)-receptor (an irreversible antagonist) greatly attenuated neuronal death promoted by 48 h exposure to DOI or MDMA. In conclusion, hallucinogenic amphetamines promoted programmed neuronal death involving both the mitochondria machinery and the extrinsic cell death key regulators. Death was dependent, at least in part, on the stimulation of the 5-HT(2A)-receptors.
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pubmed_603_1786
|
pubmed_266_8098
|
Perception of biotic and abiotic stresses often leads to stomatal closure in plants1,2. Rapid influx of calcium ions (Ca2+) across the plasma membrane has an important role in this response, but the identity of the Ca2+ channels involved has remained elusive3,4. Here we report that the Arabidopsis thaliana Ca2+-permeable channel OSCA1.3 controls stomatal closure during immune signalling. OSCA1.3 is rapidly phosphorylated upon perception of pathogen-associated molecular patterns (PAMPs). Biochemical and quantitative phosphoproteomics analyses reveal that the immune receptor-associated cytosolic kinase BIK1 interacts with and phosphorylates the N-terminal cytosolic loop of OSCA1.3 within minutes of treatment with the peptidic PAMP flg22, which is derived from bacterial flagellin. Genetic and electrophysiological data reveal that OSCA1.3 is permeable to Ca2+, and that BIK1-mediated phosphorylation on its N terminus increases this channel activity. Notably, OSCA1.3 and its phosphorylation by BIK1 are critical for stomatal closure during immune signalling, and OSCA1.3 does not regulate stomatal closure upon perception of abscisic acid-a plant hormone associated with abiotic stresses. This study thus identifies a plant Ca2+ channel and its activation mechanisms underlying stomatal closure during immune signalling, and suggests specificity in Ca2+ influx mechanisms in response to different stresses.
|
10.1038/s41586-020-2702-1
|
pubmed_877_3595
|
INTRODUCTION
Acute liver failure (ALF) is an indication for emergency liver transplantation (LT). Although centers performing only deceased donor liver transplants (DDLT) have shown improved outcomes in this situation, they still have relatively long waiting lists. An alternative would be living donor liver transplantation (LDLT), which has shown equivalent outcomes in the elective situation but there is limited evidence of its results in ALF.
AIM
The purpose of this study was to assess the outcomes in patients with ALF undergoing emergency LDLT in our center in Delhi, India.
METHODS
We prospectively collected data on 479 patients who underwent LT in our hospital between January 2009 and December 2015 to evaluate the outcomes of those with ALF. The ALF patients were listed for transplantation after they met the Kings' College criteria and rapid evaluation was done following a protocol consisting of three phases. Patients with grade III/IV encephalopathy were put on mechanical ventilation. Data regarding their postoperative course, morbidity, and mortality were analyzed.
RESULTS
Thirty-six (7.5%) out of the 479 patients underwent emergency LT for ALF. Their mean age was 27.5 years (range 4-59 years) and the male to female ratio of 2:3. Preoperative intubation was required in 15 of 25 patients who had encephalopathy. Wilson's disease was the most common cause of ALF in children while in adults, it was acute viral hepatitis. The time interval between listing and transplantation was a mean of 36 ± 12.4 h. The mean graft to recipient weight ratio (GRWR) was 1.06 ± 0.3. The recipients were extubated postoperatively after a mean period of 2.6 days and their mean ICU stay was 6.3 days. Postoperative infection was the most common complication and required upgradation of antifungal and antibiotic treatments. Neurological complications occurred in five patients. Thirty-one of 36 (86.1%) patients survived and progressive cerebral edema and sepsis were the most common causes of mortality. Patients who died had higher model for end-stage liver disease scores, longer cold ischemia time (CIT), and higher grades of encephalopathy (though 80% patients with encephalopathy survived). There was no donor mortality. At long-term follow up of a median of 56 months, 29 (80.5%) of 36 patients were still alive.
CONCLUSIONS
In our experience, LDLT is an alternative procedure to DDLT in patients with ALF and is associated with good outcomes even in patients with high grades of encephalopathy.
|
10.1007/s12664-017-0812-y
|
pubmed_530_22295
|
How do infants predict the next future event, when such a prediction requires estimating the event's probability? The literature suggests that adult humans often fail this task because their probability estimates are affected by heuristics and biases or because they can reason about the frequency of classes of events but not about the probability of single events. Recent evidence suggests instead that already at 12 months infants have an intuitive notion of probability that applies to single, never experienced events and that they may use it to predict what will happen next. We present a theory according to which infants' intuitive grasp of the probability of future events derives from their representation of logically consistent future possibilities. We compare it and other theories against the currently available data. Although the evidence does not speak uniquely in favor of one theory, the results presented and the theories currently being developed to account for them suggest that infants have surprisingly sophisticated reasoning abilities. These conclusions are incompatible with most current theories of adult logical and probabilistic reasoning.
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10.1016/b978-0-12-397919-3.00001-0
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pubmed_283_7365
|
KL-6, an epitope of MUC1 mucin expressed on type II pneumocytes and bronchiolar epithelia in humans, is a sensitive serum marker for interstitial pneumonia. However, an in vivo model for KL-6 has not been established because no KL-6 epitope is expressed in animals other than humans and apes. To investigate whether KL-6 is detectable in human MUC1-expressing (hMUC1-exp) mice and whether KL-6 level reflects the degree of lung injury, we examined serum and bronchoalveolar lavage fluid (BALF) levels of KL-6 and surfactant protein-D (SP-D) in either lipopolysaccharide (LPS)- or bleomycin (BLM)-induced lung injury models. KL-6 was expressed on type II pneumocytes and bronchiolar epithelial cells in naïve hMUC1-exp mice. Serum KL-6 levels in these mice were comparable to those in humans, and KL-6 levels in BALF were significantly higher than those in sera. In the LPS model, KL-6 levels in sera and BALF were slightly increased, although SP-D levels were markedly increased. During the inflammatory phase in the BLM model, KL-6 levels in sera were greatly increased, but those in BALF were decreased. Serum KL-6 levels were positively correlated with BALF albumin levels, a representative marker for increased the alveolar-capillary permeability. SP-D levels in sera and BALF were significantly increased compared to the corresponding levels in the LPS model. The increase in serum KL-6 levels appeared to be associated with the disruption of alveolar-capillary barrier after BLM-induced lung injury. This hMUC1-exp mouse can be used for assessment of KL-6 in vivo during lung injury.
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pubmed_283_7365
|
pubmed_118_7900
|
First Nations and Métis, two of Canada's constitutionally recognized Indigenous groups, suffer from poorer overall health than non-Indigenous Canadians. Current smoking, a known predictor of chronic health conditions, is close to twice as prevalent among Indigenous youth as it is among non-Indigenous Canadian youth. However, little population-level research has examined the correlates of current smoking among this population. Guided by a health framework centered on Indigenous-specific determinants, we used data from the 2012 Aboriginal Peoples Survey to examine the correlates of current smoking among First Nations and Métis youth aged 15-17 years living outside of First Nations reserves. Using binary logistic regression, we investigated how culturally specific factors, namely knowledge of an Indigenous language, participation in traditional activities, and family members' attendance at residential schools, were correlated with current smoking. We also considered demographic, geographic, socioeconomic and health-related correlates. Overall, an estimated 20.6% of First Nations and Métis youth reported current smoking. We found no significant associations between culturally specific activities and current smoking in the multivariate analyses, although those who spoke an Indigenous language were more likely to smoke. Those who participated in sports more often were less likely to smoke, and respondents who reported heavy drinking and who were from families with lower income were more likely to smoke. Gender, body mass index, urban/rural geography and regional geography, and mother's highest level of education were not significantly correlated with smoking. The results of our study support prior research that has found a disturbingly high prevalence of current smoking among Indigenous youth, compared to their non-Indigenous counterparts. Our results highlight the importance of considering sports participation, co-occurring health-risk behaviours and socioeconomic factors when developing interventions aimed at reducing the prevalence of smoking among First Nations and Métis youth.
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10.1007/s10935-016-0456-1
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pubmed_575_12942
|
High ethanol levels can severely inhibit the growth of yeast cells and fermentation productivity. The ethanologenic yeast Saccharomyces cerevisiae activates several well-defined cellular mechanisms of ethanol stress response (ESR); however, the involved regulatory control remains to be characterized. Here, we report a new transcription factor of ethanol stress adaptation called Znf1. It plays a central role in ESR by activating genes for glycerol and fatty acid production (GUP1, GPP1, GPP2, GPD1, GAT1, and OLE1) to preserve plasma membrane integrity. Importantly, Znf1 also activates genes implicated in cell wall biosynthesis (FKS1, SED1, and SMI1) and in the unfolded protein response (HSP30, HSP104, KAR1, and LHS1) to protect cells from proteotoxic stress. The znf1Δ strain displays increased sensitivity to ethanol, the endoplasmic reticulum (ER) stressor β-mercaptoethanol, and the cell wall-perturbing agent calcofluor white. To compensate for a defective cell wall, the strain lacking ZNF1 or its target SMI1 displays increased glycerol levels of 19.6% and 27.7%, respectively. Znf1 collectively regulates an intricate network of target genes essential for growth, protein refolding, and production of key metabolites. Overexpression of ZNF1 not only confers tolerance to high ethanol levels but also increases ethanol production by 4.6% (8.43 g/liter) or 2.8% (75.78 g/liter) when 2% or 20% (wt/vol) glucose, respectively, is used as a substrate, compared to that of the wild-type strain. The mutually stress-responsive transcription factors Msn2/4, Hsf1, and Yap1 are associated with some promoters of Znf1's target genes to promote ethanol stress tolerance. In conclusion, this work implicates the novel regulator Znf1 in coordinating expression of ESR genes and illuminates the unifying transcriptional reprogramming during alcoholic fermentation. IMPORTANCE The yeast S. cerevisiae is a major microbe that is widely used in food and nonfood industries. However, accumulation of ethanol has a negative effect on its growth and limits ethanol production. The Znf1 transcription factor has been implicated as a key regulator of glycolysis and gluconeogenesis in the utilization of different carbon sources, including glucose, the most abundant sugar on earth, and nonfermentable substrates. Here, the role of Znf1 in ethanol stress response is defined. Znf1 actively reprograms expression of genes linked to the unfolded protein response (UPR), heat shock response, glycerol and carbohydrate metabolism, and biosynthesis of cell membrane and cell wall components. A complex interplay among transcription factors of ESR indicates transcriptional fine-tuning as the main mechanism of stress adaptation, and Znf1 plays a major regulatory role in the coordination. Understanding the adaptive ethanol stress mechanism is crucial to engineering robust yeast strains for enhanced stress tolerance or increased ethanol production.
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10.1128/AEM.00588-21
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pubmed_964_19346
|
Expression of bcl-2 is most commonly associated with the t(14;18) translocation present in most folicular lymphomas (1). More recently, bcl-2 oncoprotein has been identified in normal tissues and in nonhematologic malignancies. In this study, we investigate the use of bcl-2 as a marker to distinguish metastatic breast carcinoma from primary lung and gastric cancers, and we evaluate the role of bcl-2 as an independent prognostic factor in breast carcinoma and its relationship to other breast cancer markers. bcl-2 immunostains were done on 371 adenocarcinomas of the breast, lung, and stomach. Additionally, 231 samples of metastases from patients with breast or gastric cancer were evaluated for bcl-2 expression. All breast cancer tissue samples had immunohistochemical data on expression of estrogen and progesterone receptors, p53, neu/cerb2, and MIB-1. A large proportion (79.3%) of invasive breast carcinomas expressed bcl-2, whereas only 5.6% and 8.3% of pulmonary and gastric carcinomas did. Moreover, staining was moderate to intense in 70.2% of the breast cancers, compared with only one specimen of lung carcinoma (1.9%) and gastric carcinoma (0.9%) that showed moderate staining. There was agreement of bcl-2 expression between primary and metastatic sites in all specimens except one. Expression of bcl-2 in breast adenocarcinomas was significantly associated with hormone receptor positivity and low histologic grade. Nonetheless, 20.6% of bcl-2-positive specimens were estrogen receptor negative and 24.2% of bcl-2-positive specimens were progesterone receptor negative. Neither the presence nor the absence of bcl-2 expression significantly predicted disease-free survival or overall survival in patients with breast cancer. We conclude that adenocarcinomas with intense bcl-2 staining are more likely to be of breast than of pulmonary or gastric origin. We recommend the addition of bcl-2 to a panel of antibodies (estrogen receptor, GCDFP-15, and S100) that might contribute to the identification of a larger proportion of metastatic breast carcinomas, because almost one-half of the estrogen-receptor negative cancers were bcl-2 positive.
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pubmed_964_19346
|
pubmed_26_23431
|
HIV-1 Nef plays important roles in HIV-1 replication and pathogenesis. It is translated from completely spliced HIV-1 RNA, and its expression is inherently regulated at the levels of viral DNA transcription and RNA splicing. Here we show that Sam68 cytoplasmic mutants potently suppress Nef expression. The suppression requires Sam68 domain aa 269-321 and is correlated with its ability to induce stress granules. In addition, the suppression is specific to Nef, and direct binding to nef mRNA 3'UTR confers the suppression specificity. Furthermore, nef mRNA is targeted to and enriched in these induced stress granules. Importantly, Nef suppression occurs in the context of HIV-1 infection of CD4+ T lymphocytes with little MHC I and CD4 downregulation. Taken together, these results demonstrate that stress granule induction and nef mRNA sequestration account for this translational suppression of Nef expression and offer a strategy for development of anti-HIV therapeutics to buttress our fight against HIV/AIDS.
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10.1016/j.molcel.2008.11.024
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pubmed_608_1980
|
Introduction: This paper reviews studies that have assessed the treatment of psychiatric disturbances in dystonia, tic disorders, Tourette syndrome, Huntington's disease, and essential tremor. Areas covered: We searched for papers in English in Pubmed using the following keywords: blepharospasm, cervical dystonia, arm dystonia, laryngeal dystonia, spasmodic dysphonia, tic disorders, Tourette syndrome, Huntington's chorea, essential tremor, depression, anxiety, obsessive compulsive disorders, attention deficit hyperactivity disorders, psychosis, apathy. Expert commentary: Although psychiatric disturbances are frequent in hyperkinetic movement disorders, few controlled studies have assessed the treatment of psychiatric disturbances in such disorders. In dystonia, none of the controlled studies conducted to date have demonstrated the efficacy of drug treatment for depression or anxiety. In TS, controlled studies have demonstrated the usefulness of drug treatment on obsessive compulsive disorders and attention deficit hyperactivity disorders. Behavioral interventions may also play a role. No controlled studies have been conducted on HD nor have any studies addressed the treatment of psychiatric disturbances in ET. We conclude that there is the need of controlled studies to better evaluate pharmacological and non-pharmacological treatment of psychiatric disturbances in hyperkinetic movement disorders.
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10.1080/14737175.2019.1555475
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pubmed_939_16910
|
BACKGROUND
The expanded scope of pharmacist practice allows for increased comprehensive care and improved patient outcomes at the cost of increased workload and time demands on pharmacists. There are limited descriptive metrics for the time that pharmacists spend on various activities during the workday. An evaluation of the time spent on different activities would allow for potential optimization of workflow, with a focus primarily on devoting more time to direct patient care activities.
OBJECTIVE
To quantify the amount of time that hospital and clinic-based pharmacists spend on clinical activities, including direct and indirect patient care, and nonclinical activities.
METHODS
An observational fixed-interval, work-sampling study was conducted at 2 hospitals, Vancouver General Hospital and Richmond Hospital, both in British Columbia. Trained observers followed individual pharmacists for a set period. The pharmacists' activities were recorded in 1-min increments and classified into various categories.
RESULTS
In total, 2044 min of activity, involving 11 individual pharmacists, were observed. Clinical activities accounted for 82% of total time, 12% (251 min) on direct patient care activities and 70% (1434 min) on indirect patient care activities. The most common direct clinical activity was conducting patient medication history interviews (73 min; 4% of total time), and the most common indirect clinical activity was assessment and evaluation (585 min; 29%). The most common nonclinical activities were walking (91 min; 4% of total time), looking for something (57 min; 3%), and teaching pharmacy students on practicum (60 min; 3%).
CONCLUSIONS
Although the pharmacists spent most of their time on clinical activities, face-to-face time with patients (direct clinical activities) seemed low, which highlights an area for potential improvement. The pharmacists spent much more time documenting information in pharmacy-specific monitoring forms (i.e., assessment and evaluation) than they spent writing notes or recommendations in the chart, for sharing with other health care professionals.
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pubmed_939_16910
|
pubmed_106_10764
|
An electrochemical method for the determination of trace levels of mercury based on a multi-walled carbon nanotubes (MWNT) film coated glassy carbon electrode (GCE) is described. In 0.1 mol L(-1) HCl solution containing 0.02 mol L(-1) KI, Hg(2+) was firstly preconcentrated at the MWNT film and then reduced at -0.60 V. During the anodic potential sweep, reduced mercury was oxidized, and then a sensitive and well-defined stripping peak at about -0.20 V appeared. Under identical conditions, a MWNT film coated GCE greatly enhances the stripping peak current of mercury in contrast to a bare GCE. Low concentrations of I(-) remarkably improve the determining sensitivity, since this increases the accumulation efficiency of Hg(2+) at the MWNT film coated GCE. The stripping peak current is proportional to the concentration of Hg(2+) over the range 8 x 10(-10)-5 x 10(-7) mol L(-1). The lowest detectable concentration of Hg(2+) is 2 x 10(-10) mol L(-1) at 5 min accumulation. The relative standard deviation (RSD) at 1 x 10(-8) mol L(-1) Hg(2+) was about 6% ( n=10). By using this proposed method, Hg(2+) in some water samples was determined, and the results were compared with those obtained by atomic absorption spectrometry (AAS). The two results are similar, suggesting that the MWNT-film coated GCE has great potential in practical analysis.
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10.1007/s00216-003-2136-2
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pubmed_518_16133
|
Laboratory and in situ experiments were done to investigate the influences of cultivation on temperate semi-arid grassland (for 17 years spring wheat planted once every two years without fertilisation) on soil N2O emission and quantitative variations of related soil microbes. In the laboratory (25 degrees C and soil moisture 18%), cultivation increased soil transformations of fertilizer nitrogen (100 micrograms N/g as NaNO3, urea, or as urea with dicyandiamide 1 microgram N/g). The N2O emissions from the cultivated and uncultivated soils with or without nitrogen additions were relatively low, and mainly originated from the nitrification. The soil N2O emission due to cultivation decreased somewhat upon no fertilization or NaNO3 addition, but significantly upon urea addition. The role of dicyandiamide as nitrification inhibitor was only considerable in the cultivated soil, and had small influence on decreasing N2O emission in the two soils. The influence of cultivation on soil N2O emission was also reflected by the number variations of microbes related with soil nitrogen transformation in the two soils. Compared to the uncultivated grassland, in situ ammonifiers and denitrifiers in the cultivated grassland quantitatively averagely increased, and aerobic no-symbiotic azotobacters were quantitatively similar, leading to the continued decrease of organic matter content and the decrease of N2O emission from the cultivated grassland soil.
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pubmed_518_16133
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pubmed_617_21378
|
OBJECTIVE
To determine whether maternal polycystic ovary syndrome (PCOS) is associated with adverse pregnancy outcomes in a population of Italian parturients.
STUDY DESIGN
Retrospective study carried out in an academic hospital in Bologna, Italy, including 516 consecutive Italian women who delivered between January and April 2006. PCOS women, women with hyperandrogenic features not configuring PCOS (Intermediate group) and non-hyperandrogenic controls were identified by a telephone survey of 229 women. Statistical analysis was performed using ANOVA or chi-square.
RESULTS
PCOS women, accounted for 6.6% of our cohort. Gestational diabetes mellitus (GDM) was significantly more frequent in the PCOS group than in the other groups (20% vs. 3.6% and 4%; P<0.01). The association of GDM and pregnancy-induced hypertension occurred in one subject in the PCOS group but in none of the other groups (P<0.001). Preterm birth was more frequent in the PCOS group than in control group (20% vs. 6.9%; P<0.05), whereas mean length of gestation was not different. The higher occurrence of adverse outcomes may be, at least partly, related to a higher weight gain during pregnancy in PCOS group with respect to the other groups (P<0.05).
CONCLUSIONS
Women affected by PCOS carry an increased risk of adverse pregnancy outcomes.
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10.1016/j.ejogrb.2009.11.010
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pubmed_600_10576
|
BACKGROUND
Triatoma infestans is the main vector of Chagas disease in the southern cone countries. Present control strategies based on indoor and outdoor residual insecticide spraying are not sufficient to control disease transmission, particularly in Bolivia. Techniques based on the management of the human environment may be good alternatives or supplements.
METHODS
Social and entomological surveys were carried out in four villages of Bolivia situated in the dry inter-Andean Valleys and the Chaco region. Risk factors for house infestation by T. infestans were identified, and an eco-health intervention based on education and community participation was carried out to reduce the risks of house infestation. It consisted of implementing simple and low cost vector control techniques such as coating of mud walls, cleaning activities and removal of poultry that enter rooms to lay eggs.
RESULTS
The eco-health intervention significantly reduced the number of infested bedrooms, the mean abundance of T. infestans in bedrooms and beds, especially in the Chaco region. Mud wall coating was well accepted and could be proposed as a supplementary tool to the National Program of Chagas Disease Control to enhance the effects of insecticide sprayings.
CONCLUSIONS
Even if cleaning activities were still neglected, community participation proved to be effective in reducing house infestation.
|
10.1093/trstmh/tru205
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pubmed_647_2641
|
Available data, though sparse, consistently show that women who engage in recreational physical activity during pregnancy have approximately 50% reduction in the risk for gestational diabetes mellitus compared with inactive women. Physically active women have approximately 40% reduction in preeclampsia risk. Available data support the American College of Obstetrician and Gynecologists' recommendations that promote exercise during pregnancy.
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10.1097/00003677-200507000-00007
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pubmed_763_8570
|
RATIONALE AND OBJECTIVES
There has been a trend toward lowering tube potential in computed tomography angiography (CTA) examinations to reduce radiation dose or contrast medium dose. The aim of this study was to evaluate the influence of tube potential on peripheral artery in-stent lumen visibility in CTA examinations.
MATERIALS AND METHODS
Nine different peripheral artery stents were placed in a vessel phantom (inner diameter: 5 mm, surrounded by water) and scanned consecutively using a 128-row CT scanner with 70, 80, 100, 120, and 140 kV and two different concentrations of contrast medium to simulate contrast-enhanced blood. Medium-smooth and ultra-sharp reconstruction kernels with filtered back projection (B30f, B46f) and iterative reconstruction technique (I30f, I46f) were used. Visible in-stent lumen diameter and artifact width were evaluated using a semiautomatic software tool. All stents were scanned with digital angiography, which was regarded as the reference standard.
RESULTS
Averaged over all stents, visible in-stent lumen diameter ranged from 1.30 ± 0.21 mm (CM2/70 kV/I30f) to 3.13 ± 0.32 mm (CM1/120 kV/I46f). In-stent lumen diameters were significantly higher for 120 and 140 kV compared to 70 kV (2.39 ± 0.73 and 2.39 ± 0.66 mm vs 1.99 ± 0.69 mm; P = 0.01 and P = 0.005). Ultra-sharp reconstruction kernels lead to significantly better in-stent lumen visibility than smooth reconstruction kernels (B46f: 2.74 ± 0.34 mm vs B30f: 1.57 ± 0.36 mm; P < 0.001, respectively). Furthermore, in-stent lumen visibility was improved for iterative reconstructions compared to filtered back projection (I46f: 2.93 ± 0.30 mm vs B46f: 2.74 ± 0.34 mm; P < 0.001). Contrast medium concentration did not influence in-stent lumen visibility.
CONCLUSIONS
Despite all known benefits of low kV CTA protocols, the use of a very low tube potential may hamper in-stent lumen visibility. A sharp kernel may be of value when evaluating the inner lumen of vascular stents.
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pubmed_763_8570
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pubmed_344_21815
|
Catheter-induced left main coronary artery (LMCA) vasospasm is a rare complication of coronary angiography that confounds the decision for coronary artery bypass graft (CABG) surgery. We report two cases of catheter-induced LMCA vasospasm. The first case was a 68-year-old woman who presented 6 years after CABG for presumed severe LMCA atherosclerotic disease. Coronary angiography demonstrated totally occluded CABGs and normal native coronary arteries, including a normal LMCA. The second case was a 56-year-old man with severe LMCA stenosis, who was scheduled for unprotected LM percutaneous coronary intervention (PCI). Repeat angiography 2 days later showed no stenosis. These cases emphasize the need for meticulous technique and a high index of suspicion of LMCA vasospasm. Intravascular ultrasound (IVUS) at the time of angiography may help to identify minimal atherosclerotic disease suggesting vasospasm. Alternatively, noninvasive testing, such as computed tomography (CT) angiography, may diagnose LM spasm in these patients prior to CABG surgery.
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10.1002/ccd.22462
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pubmed_1075_15895
|
The surface coverage of certain dry fermented sausages such as Italian salami by some species of Penicillium provides their characteristic flavor and other beneficial properties. One of them is the protective effect by means of a uniform film of white mold against undesirable microorganisms. The aim of this work was to identify and to isolate the fungal species present in mature Italian type of salami and to evaluate if it is possible to obtain some of them as starters. In addition, the effects of temperature (14 °C and 25 °C), water activity (a w) (0.90, 0.95 and 0.995) and 2.5 % sodium chloride (NaCl) on fungal growth were determined. Similarly, the proteolytic and lipolytic activity and the ability to produce toxic secondary metabolites were evaluated in order to characterize some possible starter strain. All species found belong to the genus Penicillium, including a performing starter as Penicillium nalgiovense and some potentially toxicogenic species. All the strains showed a higher growth rate at 25 °C. The production of extracellular proteases and lipases was significantly higher at 25 °C than at 14 °C with and without sodium chloride. Only Penicillium expansum produced patulin. On the other hand, Penicillium griseofulvum was the only species that produced ciclopiazonic acid but none of the strains produced penicillin. The species present on salami, Penicillium nalgiovense, Penicillium minioluteum, Penicillium brevicompactum and Penicillium puberulum were unable to produce any of the evaluated toxins. These findings suggest that some fungal isolates from the surface of salami such as P. nalgiovense are potentially useful as starters in sausage manufacture.
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pubmed_1075_15895
|
pubmed_416_20260
|
Topical application of human recombinant basic fibroblast growth factor (bFGF) promotes wound healing. bFGF, however, has been reported to have little in vitro effects on keratinocyte compared with other cell types such as endothelial cells or fibroblasts. The aim of this study was to investigate the mechanism(s) of bFGF-stimulated keratinocyte migration. Normal human keratinocytes, seeded on coverslips that were noncoated or coated with type I collagen or fibronectin, were stimulated with bFGF to evaluate their ability to spread. Keratinocyte migration was measured using a Boyden chamber assay. The lysates of keratinocytes, which were plated on noncoated, type I collagen-coated or fibronectin-coated plastic dishes and stimulated with bFGF, were subjected to pulldown assays to detect guanine triphosphate-loaded Rac. Morphologically, keratinocytes formed lamellipodia only when they were stimulated with bFGF on the collagen-coated coverslips. Keratinocyte migration was significantly enhanced by bFGF. Guanine triphosphate-loaded Rac was detected only in the lysate of bFGF-stimulated keratinocytes on collagen-coated dishes. This in vitro study shows that bFGF exerts a stimulatory effect on keratinocyte migration in the presence of type I collagen as a scaffold, and, at least, Rac activation is involved.
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10.1111/j.1743-6109.2006.00143.x
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pubmed_721_8289
|
Proximal femoral bone stock deficiencies exist during many femoral revision arthroplasties, thus providing inadequate support and fixation for conventional-length cemented femoral components. The authors analyzed the long-term clinical and roentgenographic results of 165 hips requiring femoral revision arthroplasty with a long-stem femoral prosthesis. Intraoperative complications occurred in 23% of hips, with femoral perforations in 16% and femoral fractures in 5%. Of 110 hips with at least 5 years of follow-up study (average, 6.7 years), functional ratings were graded excellent in 34%, good in 36%, fair in 17%, and poor in 13%. Failures occurred in 17 hips (12%) and were attributed to aseptic loosening (11 hips), femoral component fracture (2), femoral shaft fracture (1), and sepsis (3). Symptomatic trochanteric separations occurred in 16% of hips. Rerevision or resection arthroplasty was required in 7 hips (5%) and recommended for another 10 hips (7%). Cemented long-stem femoral components (versus cemented conventional-length stems) decrease the extent and progression of femoral lucencies, thereby lowering the incidence of mechanical failures and improving long-term functional results in cemented femoral revision arthroplasty.
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10.1016/s0883-5403(87)80045-1
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pubmed_1013_23130
|
Our purpose was to identify the reasons why members of the population, aged 18-60 years, are vaccinated against COVID-19 at the mass vaccination point in Bages, Spain. This is 1 of 42 provisional spaces outside of health centres which have been set up in Catalonia in the context of the COVID-19 pandemic, and where people from all over Catalonia could go to be vaccinated by appointment.
METHODOLOGY
We performed a cross-sectional study of users attending mass vaccination points in Bages during the months of July, August, and September 2021.
RESULTS
A total of 1361 questionnaires were statistically analysed. The most common reasons for vaccination were fear of infecting family (49.52%) and fear of self-infection (39.45%), followed by socialising (31.00%) and travel (30.56%). However, by applying a logistic regression model to each reason for vaccination, it was possible to estimate the associations regarding age, sex, marital status, educational level, production sector, mass vaccination point, previous COVID-19 infection, and COVID-19 infection of a family member.
RELEVANCE
The data generated will inform decisions and formulations of appropriate campaigns that will promote vaccination in specific population groups.
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10.3390/vaccines10040597
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pubmed_328_12273
|
BACKGROUND
Chronic obstructive pulmonary disease (COPD) has been associated with atrial fibrillation (AF). More insight into the epidemiology and underlying mechanisms is required to optimize management.
METHODS
The Rotterdam Study is a large, population-based cohort study with long-term follow-up. Time dependent Cox proportional hazard models were constructed to study the effect of COPD on incident AF, adjusted for age, sex and pack years of cigarette smoking, and additionally stratified according to exacerbation frequency, left atrial size and baseline systemic inflammatory levels.
RESULTS
1369 of 10,943 subjects had COPD, of whom 804 developed AF. The AF incidence rate was 14 per 1000 person years in COPD and 8 per 1000 person years in subjects without COPD. The adjusted hazard ratio (HR) for COPD subjects to develop AF as compared to subjects without COPD was 1.28 (95%CI [1.04, 1.57]). COPD subjects with frequent exacerbations had a twofold increased AF risk (HR 1.99 [1.42, 2.79]) and COPD subjects with a left atrial size ≥40 mm also had an elevated AF risk (HR 1.77 [1.07, 2.94]). COPD subjects with baseline systemic inflammatory levels above the median had significantly increased AF risks (hsCRP≥1.83 mg/L: HR 1.51 [1.13, 2.03] and IL6 ≥ 1.91 ng/L: HR 2.49 [1.18, 5.28]), whereas COPD subjects below the median had in both analyses no significantly increased AF risk.
CONCLUSIONS
COPD subjects had a 28% increased AF risk, which further increased with frequent exacerbations and an enlarged left atrium. The risk was driven by COPD subjects having elevated systemic inflammatory levels.
|
10.1016/j.ijcard.2018.09.056
|
pubmed_871_8511
|
There is increasing evidence that kappa-opioid receptor agonists modulate cocaine-maintained behavior, and limited findings implicate the involvement of kappa-opioid receptors in ethanol-maintained behaviors. The purpose of the present study was to investigate the effects of bremazocine, a kappa-opioid agonist, on the self-administration of smoked cocaine base and oral ethanol in rhesus monkeys (Macaca mulatta). To determine the selectivity of bremazocine, the effects of bremazocine pretreatment on the oral self-administration of phencyclidine (PCP), saccharin, and food were also examined. Adult male rhesus monkeys were trained to self-administer oral ethanol, PCP, saccharin (n = 8), food (n = 6), or smoked cocaine base (n = 6) and water during daily sessions. Bremazocine (0.00032-, 0.001-, and 0.0025-mg/kg i.m.) injections were given 15 min before session. The 4 days of stable behavior before pretreatment served as baseline. Demand curves (consumption x fixed ratio; FR) were obtained for smoked cocaine base, ethanol, and PCP by varying the cost (FR) of drug deliveries and measuring consumption (deliveries). Bremazocine (0.001 mg/kg) was administered at each FR value in nonsystematic order. Results indicate that bremazocine dose dependently reduced cocaine, ethanol, PCP, and saccharin intake. Food intake was affected less by bremazocine than the other substances in five of the six monkeys. Generally, bremazocine treatment reduced the demand for cocaine, ethanol, and PCP as well as other measures of response strength. These results extend the findings that kappa-agonists reduce the self-administration of drug and nondrug reinforcers to smoked cocaine base and oral ethanol, PCP, and saccharin in rhesus monkeys.
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10.1124/jpet.301.3.993
|
pubmed_1127_2976
|
BACKGROUND
Given the emphasis on early vascular access via the umbilical vein in neonatal resuscitation it is essential that participants in neonatal resuscitation simulation training be given the opportunity to practice both the placement and use of an emergency umbilical venous catheter. By integrating available parts from the Laerdal catalog, combined with a few other inexpensive components, into a Laerdal SimBaby we were able to create a single, integrated neonatal simulator that could be used to practice both the placement and use of an emergent umbilical vein catheter.
METHODS
To integrate an umbilical cannulation task trainer into the Laerdal SimBaby we used a specially modified replaceable umbilical cord and reservoir from the Laerdal Neonatal Resuscitation Baby. To this reservoir we attached a flanged outlet drain and drainage tube which allows for the infusion of medications and fluids. The modified SimBaby with integrated umbilical cannulation task trainer was validated for both face and content by simulation participants and a panel of neonatal resuscitation experts.
RESULTS
The umbilical cannulation task trainer integrated well into the SimBaby and in no way altered the function of the mannequin. The modified Laerdal SimBaby was thought to work well by both participants and experts. Simulation participants liked having the chance to practice emergency umbilical vein cannulation and thought that the simulated umbilical cord was an important component in their learning experience. The expert panel thought that the modified SimBaby could be used for emergency umbilical vein cannulation skills training and that the addition gave the modified SimBaby major advantage over other simulators they had used to teach newborn resuscitation.
DISCUSSION
We have developed a modification to the Laerdal SimBaby involving the integration of a usable umbilical cannulation task trainer. The modification was easily accomplished using available parts from the Laerdal catalog and a few other inexpensive components. Given the emphasis on early vascular access via the umbilical vein and the complexities involved with the administration of medications and fluids via this route we believe that a usable umbilical cannulation task trainer is essential to neonatal resuscitation simulation training. When modified as described the Laerdal SimBaby can act as a high-fidelity newborn simulator that allows participants to practice both the placement and use of an emergency umbilical vessel catheter. Given our positive experience we think others could apply the above modification to their own SimBaby.
|
10.1097/SIH.0b013e31817bcaeb
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pubmed_820_5706
|
A new chromatographic method based on affinity supermacroporous monolithic cryogels is developed for binding and analyzing inclusion bodies during fermentation. The work demonstrated that it is possible to bind specific IgG and IgY antibodies to the 15 and 17 amino acids at the terminus ends of a 33 kDa target protein aggregated as inclusion bodies. The antibody treated inclusion bodies from lysed fermentation broth can be specifically retained in protein A and pseudo-biospecific ligand sulfamethazine modified supermacroporous cryogels. The degree of binding of IgG and IgY treated inclusion bodies to the Protein A and sulfamethazine gels are investigated, as well as the influence of pH on the sulfamethazine ligand. Optimum binding of 78 and 72% was observed on both protein A and sulfamethazine modified cryogel columns, respectively, using IgG labeling of the inclusion bodies. The antibody treated inclusion bodies pass through unretained in the sulfamethazine supermacroporous gel at pH that does not favour the binding between the ligand on the gel and the antibodies on the surface of inclusion bodies. Also the unlabeled inclusion bodies went through the gel unretained, showing no non-specific binding or trapping within the gel. These findings may very well be the foundation for the building of a powerful analytical tool during fermentation of inclusion bodies as well as a convenient way to purify them from fermentation broth. These results also support our earlier findings [Kumar, A., Plieva, F.M., Galaev, I.Yu., Mattiasson, B., 2003. Affinity fractionation of lymphocytes using a monolithic cyogel. J. Immunol. Methods 283, 185-194] with mammalian cells that were surface labeled with specific antibodies and recognized on protein A supermacroporous gels. A general binding and separation system can be established on antibody binding cryogel affinity matrices.
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10.1016/j.jbiotec.2005.09.007
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pubmed_4_15779
|
Campylobacter concisus was previously shown to be associated with inflammatory bowel disease including Crohn's disease (CD) and ulcerative colitis (UC). C. concisus has two genomospecies (GS). This study systematically examined the colonization of GS1 and GS2 C. concisus in the human gastrointestinal tract. GS1 and GS2 specific polymorphisms in 23S rRNA gene were identified by comparison of the 23S rRNA genes of 49 C. concisus strains. Two newly designed PCR methods, based on the polymorphisms of 23S rRNA gene, were developed and validated. These PCR methods were used to detect and quantify GS1 and GS2 C. concisus in 56 oral and enteric samples collected from the gastrointestinal tract of patients with IBD and healthy controls. Meta-analysis of the composition of the isolated GS1 and GS2 C. concisus strains in previous studies was also conducted. The quantitative PCR methods revealed that there was more GS2 than GS1 C. concisus in samples collected from the upper and lower gastrointestinal tract of both patients with IBD and healthy controls, showing that GS2 C. concisus is better adapted to the human gastrointestinal tract. Analysis of GS1 and GS2 composition of isolated C. concisus strains in previous studies showed similar findings except that in healthy individuals a significantly lower GS2 than GS1 C. concisus strains were isolated from fecal samples, suggesting a potential difference in the C. concisus strains or the enteric environment between patients with gastrointestinal diseases and healthy controls. This study provides novel information regarding the adaptation of different genomospecies of C. concisus in the human gastrointestinal tract.
|
10.3389/fphys.2017.00543
|
pubmed_612_672
|
OBJECTIVES
Differentiation between post-operative inflammation and bacterial infection remains an important issue in infants following congenital heart surgery. We primarily assessed kinetics and predictive value of C-reactive protein for bacterial infection in the early (days 0-4) and late (days 5-28) period after cardiopulmonary bypass surgery. Secondary objectives were frequency, type, and timing of post-operative infection related to the risk adjustment for congenital heart surgery score.
METHODS
This 3-year single-centre retrospective cohort study in a paediatric cardiac ICU analysed 191 infants accounting for 235 episodes of CPBP surgery. Primary outcome was kinetics of CRP in the first 28 days after CPBP surgery in infected and non-infected patients.
RESULTS
We observed 22 infectious episodes in the early and 34 in the late post-operative period. CRP kinetics in the early post-operative period did not accurately differentiate between infected and non-infected patients. In the late post-operative period, infected infants displayed significantly higher CRP values with a median of 7.91 (1.64-22.02) and 6.92 mg/dl (1.92-19.65) on days 2 and 3 compared to 4.02 (1.99-15.9) and 3.72 mg/dl (1.08-9.72) in the non-infection group. Combining CRP on days 2 and 3 after suspicion of infection revealed a cut-off of 9.47 mg/L with an acceptable predictive accuracy of 76%.
CONCLUSIONS
In neonates and infants, CRP kinetics is not useful to predict infection in the first 72 hours after CPBP surgery due to the inflammatory response. However, in the late post-operative period, CRP is a valuable adjunctive diagnostic test in conjunction with clinical presentation and microbiological diagnostics.
|
10.1017/S1047951121003231
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pubmed_269_20879
|
Protein phosphorylation is a central mechanism of cellular signal transduction in living organisms. Phosphoproteomic studies systematically catalogue and characterize alterations in phosphorylation states across multiple cellular conditions and are often incorporated into global proteomics experiments. Previously, we found that spin column-based Fe3+-NTA enrichment integrated well with our workflow but remained a bottleneck for methods that require higher throughput or a scale that is beyond the capacity of these columns. Here, we compare our well-established spin column-based enrichment strategy with one encompassing magnetic beads. Our data show little difference when using either method in terms of the number of identified phosphopeptides as well as their physicochemical properties. In all, we illustrate how the potentially scalable and automation-friendly magnetic Fe3+-NTA beads can seamlessly substitute spin column-based Fe3+-NTA agarose beads for global phosphoproteome profiling. SIGNIFICANCE: Protein phosphorylation plays a key role in regulating a multitude of biological processes and can lead to insights into disease pathogenesis. Methodologies which can efficiently enrich phosphopeptides in a scalable and high-throughput manner are essential for profiling dynamic phosphoproteomes. Here we compare two phosphopeptide enrichment workflows, a well-established spin column-based strategy with agarose Fe3+-NTA beads and a strategy using magnetic Fe3+-NTA beads. Our data suggest that the scalable and automation-friendly magnetic bead-based workflow is an equivalent, but more flexible, enrichment strategy for phosphoproteome profiling experiments.
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10.1016/j.jprot.2022.104561
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pubmed_534_16144
|
Constructed wetlands are generally used for the removal of waste from contaminated water. In the swine production system, wastes are traditionally flushed into an anaerobic lagoon which is then sprayed on agricultural fields. However, continuous spraying of lagoon wastewater on fields can lead to high N and P accumulations in soil or lead to runoff which may contaminate surface or ground water with pathogens and nutrients. In this study, continuous marsh constructed wetland was used for the removal of contaminants from swine waste. Using pyrosequencing, we assessed bacterial composition within the wetland using principal coordinate analysis (PCoA) which showed that bacterial composition from manure influent and lagoon water were significantly different (P=0.001) from the storage pond to the final effluent. Canonical correspondence analysis (CCA) showed that different bacterial populations were significantly impacted by ammonium--NH4 (P=0.035), phosphate--PO4(3-) (P=0.010), chemical oxygen demand--COD (P=0.0165), total solids--TS (P=0.030), and dissolved solids--DS (P=0.030) removal, with 54% of the removal rate explained by NH4+PO4(3-) according to a partial CCA. Our results showed that different bacterial groups were responsible for the composition of different wetland nutrients and decomposition process. This may be the major reason why most wetlands are very efficient in waste decomposition.
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pubmed_534_16144
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pubmed_345_10206
|
The authors showed that at the present time military much more servicemen, suffering from obstructive pulmonary disease, may receive medical examination in outpatient conditions. Series of researches allow us to perform a medical examination on an outpatient basis. The calculation of the cost-effectiveness of health services to such patients during a military medical examination in the hospital and clinics was made. Savings during the examination in the clinic for 1 patient was 2829 rubbles.
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pubmed_345_10206
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pubmed_299_5814
|
Ceramides are a central unit of all sphingolipids which have been identified as sites of biological recognition on cellular membranes mediating cell growth and differentiation. Several glycosphingolipids have been isolated, displaying immunomodulatory and anti-tumor activities. These molecules have generated considerable interest as potential vaccine adjuvants in humans. Accurate analyses of these and related sphingosine analogues are important for the characterization of structure, biological function, and metabolism. We report the complementary use of direct laser desorption ionization (DLDI), sheath flow electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and high-field nuclear magnetic resonance (NMR) analysis for the rapid, accurate identification of hexacosanoylceramide and starting materials. DLDI does not require stringent sample preparation and yields representative ions. Sheath-flow ESI yields ions of the product and byproducts and was significantly better than monospray ESI due to improved compound solubility. Negative ion sheath flow ESI provided data of starting materials and products all in one acquisition as hexacosanoic acid does not ionize efficiently when ceramides are present. NMR provided characterization of these lipid molecules complementing the results obtained from MS analyses. NMR data was able to differentiate straight chain versus branched chain alkyl groups not easily obtained from mass spectrometry.
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pubmed_299_5814
|
pubmed_842_9757
|
We performed molecular dynamics simulations to investigate hydrophobic interactions between two parallel hydrophobic plates immersed in water. The two plates are separated by a distance D ranging from contact to a few nanometers. To mimic the attractive hydrophobic force measurement in a surface force experiment, a driving spring is used to measure the hydrophobic force between two hydrophobic plates. The force-distance curves, in particular the force variations from spontaneous drying to hydrophobic collapse are obtained. These details are usually not accessible in the surface force measurement due to the unstable jump into contact. The length-scale effect on the hydrophobic drying during normal approach and the hydrophobic hysteresis during retraction has been studied. We find that the critical distance at which a spontaneous drying occurs is determined by the shorter characteristic dimension of the plate, whereas the hydrophobic hysteresis is determined by the longer characteristic dimension of the plate. The variations of the potential of mean force versus separation during approach and retraction are also calculated. The results show that water confined between two parallel hydrophobic plates is in a thermodynamic metastable state. This comparably high energy state leads to the spontaneous drying at some critical distance.
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10.1021/la203646f
|
pubmed_533_7160
|
Tumors are often comprised of microenvironments (TMEs) with a high proportion of cells and molecules that regulate immunity. Peritoneal cavity (PerC) cell culture reproduces key features of TMEs as lymphocyte proliferation is suppressed by PerC macrophages (Mϕs). We monitored the expression of T cell stimulatory (Class II MHC, B7) and inhibitory (PD-L1) molecules by PerC APCs before and after culture and report here that IFNγ-driven PD-L1 expression increased markedly on PerC Mϕs after TCR ligation, even more so than seen with direct APC activation by LPS. Considering the high APC composition of and pronounced PD-L1 expression by PerC cells, it was surprising that blocking PD-1/PD-L1 interaction by mAb neutralization or genetic ablation did not relieve suppression. This result parallels TME challenges observed in the clinic and validates the need for further study of this culture model to inform strategies to promote anti-tumor immunity.
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10.1016/j.cellimm.2017.12.013
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pubmed_1140_10933
|
This study assessed microstructural development in four regions of the human cerebral cortex during preterm maturation using diffusion tensor imaging (DTI), compared to the macrostructural development of cortical gyration evaluated using three-dimensional volumetric T1-weighted MR imaging. Thirty-seven premature infants of estimated gestational age (EGA) ranging from 25 to 38 weeks were prospectively enrolled and imaged in an MR-compatible neonatal incubator with a high-sensitivity neonatal head coil. Cortical gyration was measured quantitatively as the ratio of gyral height to width on the volumetric MR images in four regions bilaterally (superior frontal, superior occipital, precentral, and postcentral gyri). Mean diffusivity (D(av)), fractional anisotropy (FA-the fraction of D(av) that is anisotropic), and the three DTI eigenvalues (components of diffusivity radial and tangential to the pial surface of cortex) were measured in the same cortical regions. Cortical gyration scores, FA, and radial diffusivity were all significantly correlated with EGA (P < 0.0001). However, in multivariate analysis, no significant relationship (P > 0.05) was found between DTI parameters and cortical gyration beyond their common association with estimated gestational age. Pre- and postcentral gyri had significantly lower anisotropy than the superior occipital and superior frontal gyri (P < 0.05), indicating that DTI is sensitive to regional heterogeneity in cortical development. Maturational changes in the DTI eigenvalues of cortical gray matter were found to differ from those that have previously been described in developing white matter, with a significant age-related decline in the radial diffusivity (P < 0.0001) but not in the tangential diffusivities (P > 0.05).
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10.1016/j.neuroimage.2005.04.027
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pubmed_33_5917
|
Folic acid is an essential nutrient that is required for one-carbon biosynthetic processes and for methylation of biomolecules. Deficiency of this micronutrient leads to disturbances in normal physiology of cell. Chronic alcoholism is well known to be associated with folate deficiency, which is due in part to folate malabsorption. The present study deals with the regulatory mechanisms of folate uptake in liver during chronic alcoholism. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20 % solution) orally for 3 months, and the molecular mechanisms of folate uptake were studied in liver. The characterization of the folate transport system in liver basolateral membrane (BLM) suggested it to be a carrier mediated and acidic pH dependent, with the major involvement of proton coupled folate transporter and folate binding protein in the uptake. The folate transporters were found to be associated with lipid raft microdomain of liver BLM. Moreover, ethanol ingestion decreased the folate transport by altering the Vmax of folate transport process and downregulated the expression of folate transporters in lipid rafts. The decreased transporter levels were associated with reduced protein and mRNA levels of these transporters in liver. The deranged folate uptake together with reduced folate transporter levels in lipid rafts resulted in reduced folate levels in liver and thereby to its reduced levels in serum of ethanol-fed rats. The chronic ethanol ingestion led to decreased folate uptake in liver, which was associated with the decreased number of transporter molecules in the lipid rafts that can be ascribed to the reduced synthesis of these transporters.
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10.1007/s12263-012-0318-2
|
pubmed_1005_16556
|
OBJECTIVE
To model the risk of radiation-induced malignancy from computed tomography urography (CTU) in evaluation of gross hematuria and contrast this with the benefits of urinary tract cancer detection when compared to renal ultrasound.
METHODS
A PUBMED-based literature search was performed to identify model inputs. Estimates of radiation-induced malignancy rates were obtained from the Biological Effects of Ionizing Radiation VII report with dose extrapolation using the linear no-threshold model.
RESULTS
Male gender and age over 50 years were associated with a relative risk of upper tract malignancy of 2.04 and 2.95, respectively. The risk of upper tract malignancy missed by renal ultrasound ranged from 0.055% in females under 50 to 0.51% in males over 50. Risk of CTU-induced malignancy with associated loss of life expectancy ranged from 0.25% and 0.027 years in females under 50 to 0.08% and 0.0054 years in males over 50. For CTU to be superior to renal ultrasound, an undiagnosed upper tract malignancy would have to carry a loss of life expectancy of 49.2 years in females under 50, 13.4 years in males under 50, 2.6 years in females over 50, and 1.1 years in males over 50.
CONCLUSION
In low-risk patients, CTU for evaluation of gross hematuria may carry a significant risk of radiation-induced secondary malignancy relative to the diagnostic benefit offered over renal ultrasound.
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10.1016/j.urology.2019.04.055
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pubmed_369_10587
|
Derangement of the nuclear factor κB (NF-κB) pathway initiates and/or sustains many types of human cancer. B-cell malignancies are particularly affected by oncogenic mutations, translocations, and copy number alterations affecting key components the NF-κB pathway, most likely owing to the pervasive role of this pathway in normal B cells. These genetic aberrations cause tumors to be 'addicted' to NF-κB, which can be exploited therapeutically. Since each subtype of lymphoid cancer utilizes different mechanisms to activate NF-κB, several different therapeutic strategies are needed to address this pathogenetic heterogeneity. Fortunately, a number of drugs that block signaling cascades leading to NF-κB are in early phase clinical trials, several of which are already showing activity in lymphoid malignancies.
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10.1111/j.1600-065X.2012.01105.x
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pubmed_148_7425
|
The use of homografts appears to be a promising method of repairing the sequelae of chronic otitis. The authors describe their method of removing the temporal, dissecting the tympano-ossicular system and labelling and preserving the grafts. A homograft bank can be set up and this is a very necessary preliminary in the regular application of this type of surgery.
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pubmed_148_7425
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pubmed_1070_14050
|
Programmed -1 ribosomal frameshift (-1 PRF) allows for alternative reading frames within one mRNA. First found in several viruses, it is now believed to exist in all kingdoms of life. Strong stimulators for -1 PRF are a heptameric slippery site and an RNA pseudoknot. Here, we present a new algorithm KnotInFrame, for the automatic detection of -1 PRF signals from genomic sequences. It finds the frameshifting stimulators by means of a specialized RNA-pseudoknot folding program, fast enough for genome-wide analyses. Evaluations on known -1 PRF signals demonstrate a high sensitivity.
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10.1093/nar/gkn578
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pubmed_1131_2435
|
UNLABELLED
: Our primary objective is to review the safety and tolerability profile of olaparib, a novel anticancer therapy, and to discuss key considerations for symptom management in patients with advanced ovarian cancer. Olaparib is the first of a new class of anticancer therapies, poly (ADP-ribose) polymerase (PARP) inhibitors that target tumors that have deficits in homologous recombination repair (such as BRCA mutations) by a process known as synthetic lethality. Through this process, neither the deficiency in homologous recombination repair nor PARP inhibition alone is cytotoxic, but the combination of these two conditions leads to cell death. In December 2014, olaparib received accelerated approval by the U.S. Food and Drug Administration (FDA) as monotherapy for patients with known or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who had been treated with at least three lines of chemotherapy. Most adverse events (AEs) reported during olaparib clinical trials conducted in patients with recurrent ovarian cancer and measurable disease were of grade 2 or less severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. Fatigue and gastrointestinal AEs are among the most common in ovarian cancer clinical trials and can be particularly bothersome to patients. We focus on interventions to address these AEs in patients who are candidates for treatment with olaparib and allow them to remain on therapy for as long as clinically indicated.
IMPLICATIONS FOR PRACTICE
Olaparib therapy represents a new approach to treating recurrent ovarian cancer. Some associated adverse events can have a substantial effect on quality of life. It is therefore important for patients, caregivers, and health care providers to have realistic expectations and a thorough understanding of the safety and tolerability profile of olaparib to prevent or alleviate key symptoms so that therapy can continue uninterrupted if possible. This report summarizes a practical approach to supportive care for patients receiving olaparib therapy.
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10.1634/theoncologist.2015-0268
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pubmed_999_9091
|
To identify gender- and age-related associations between adult dental checkups and unmet dental care needs, we analyzed data of 14,000 participants, from the Seventh Korea National Health and Nutrition Examination Survey (2016-2018). Data were collected via self-report questionnaires and interviews. The complex sample chi-square test and multiple logistic regression analysis indicated that 31.7% of participants had unmet dental care needs. Within the previous 12 months, 56.5% did not undertake dental checkups, and 29.3% did not use a dental service. Odds ratios (ORs) of the unmet dental needs were 8.87 (confidence interval (CI) = 7.80-10.09, p < 0.001) for those who did not use dental services and 1.28 (CI = 1.13-1.44, p < 0.001) for those who did not have dental checkups. Significant age-dependent associations between those not receiving dental checkups and the rate of unmet dental care included men and women aged 50-59 years and women ≥70 years. However, unmet dental care needs for men aged ≥70 years not undergoing dental checkups were not statistically significant (p = 0.311). Overall, it was found that the use of dental service and dental checkups were the influencing factors for unmet dental care needs.
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10.3390/ijerph18073750
|
pubmed_980_26650
|
BACKGROUND
The 'obesity paradox' suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events (TRAEs). This study assesses whether BMI is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy.
PATIENTS AND METHODS
This multicentric retrospective study, conducted from 1 March 2013 to 29 April 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. BMI was categorized using the World Health Organization criteria. Co-primary outcomes included the association between BMI and progression-free survival and overall survival, stratified by treatment type, sex, and age. Secondary endpoints were the association of BMI with overall response and TRAEs. Multivariate analyses were carried out.
RESULTS
A total of 1214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed [n = 738 (61%)]. Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between BMI and progression-free survival (P = 0.88)/overall survival (P = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to BMI category, did not differ significantly regardless of age. TRAEs were not associated with BMI.
CONCLUSION
The observed lack of an association between BMI and survival demonstrates that BMI is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution.
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10.1016/j.annonc.2020.12.012
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pubmed_447_4200
|
Anterior uveitis is frequently caused by systemic disease, and it is appropriate not only to diagnose the iritis but also to determine, if possible, the underlying condition. Although diagnosis of an anterior uveitis is usually straightforward, medical management occasionally is not. Satisfactory treatment may be achieved in many cases with cycloplegics and topical corticosteroid therapy, but the management protocol must be tailored to suit the patient. Frequent assessment of the patient is required during the 2- to 3-week period usually required for resolution of an anterior uveitis.
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pubmed_447_4200
|
pubmed_742_2644
|
Highly regioselective acylation of helicid with fatty acid vinyl esters catalyzed by the lipase from Thermomyces lanuginosus has been successfully performed for the first time. For the enzymatic caproylation of helicid, under the optimal conditions, initial reaction rate was 33.2 mM/h, and substrate conversion and regioselectivity were greater than 99%. In addition, the acyl recognition of the enzyme in the regioselective acylation of helicid was investigated. The results showed that although 6'-O-acyl derivatives of helicid were exclusively obtained with all the tested acyl donors, the enzymatic reaction rate varied widely with different acyl donors, presumably owing to their different interactions with the active site of the lipase. It is also interesting that the different configuration of only one hydroxyl group at C-3 in helicid couldn't affect the lipase-catalyzed esterification and helicid has the same regioselectivity as that of D-glucose and arbutin.
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10.1371/journal.pone.0080715
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pubmed_467_22384
|
AIMS/HYPOTHESIS
Impaired wound healing significantly impacts morbidity and mortality in diabetic patients, necessitating the development of novel treatments to improve the wound healing process. We here investigated the topical use of acellular embryonic stem cell extracts (EXTs) in wound healing in diabetic db/db mice.
METHODS
Wounds were induced in diabetic db/db mice, which were subsequently treated with EXTs, with 3T3 fibroblast cell line protein extracts (3T3XTs) or with saline as a control. Pathology and mechanistic assays were then performed.
RESULTS
The in vivo topical administration of EXTs facilitates wound closure, contraction and re-epithelialization. Moreover, EXTs reduced the number of wound-infiltrating CD45+ inflammatory cells and increased the rate of repair and of angiogenesis as compared to controls. Interestingly, the EXT effect was partly enhanced by the use of a collagen-based biocompatible scaffold. In vivo, topical administration of EXTs increased the percentage of regulatory T cells in the wounded tissue, while in vitro EXT treatment reduced T cell-mediated IFN-γ production. Proteomic screening revealed 82 proteins differentially segregating in EXTs as compared to 3T3 extracts, with APEX1 identified as a key player for the observed immunomodulatory effect of EXTs.
CONCLUSIONS
EXTs are endowed with immunoregulatory and anti-inflammatory properties; their use improves wound healing in diabetic preclinical models.
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10.1007/s00592-020-01500-0
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pubmed_73_3758
|
This manuscript presents data from 90-day toxicology studies designed to characterize the subchronic effects of a smokeless tobacco blend and an aqueous extract of that blend when administered to rodents in NTP-2000 feed. Positive control (nicotine tartrate) and treatment groups were matched for a range of nicotine levels. The doses evaluated were 0.3, 3, and 6 mg nicotine/kg body weight/day in Wistar Hannover rats and 6, 60, and 120 mg nicotine/kg/day in CD-1 mice. Variables evaluated included plasma nicotine and cotinine, body weights, feed consumption, clinical observations, clinical and anatomic pathology (including organ weights), and histopathology. Plasma nicotine and cotinine levels were dose-responsive. Key effects such as body weight reductions and organ weight changes occurred in rats and mice predominantly at the highest doses of test articles and positive control in the absence of treatment-related gross or histopathological changes. Organ weight changes were attributed mainly to the lower body weights of treated vs. control groups. The blend- and extract-induced effects generally paralleled each other and the nicotine-induced effects. Based on these studies, the doses evaluated spanned the no observable adverse effect level, the lowest observable adverse effect level and the maximum tolerated dose.
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10.1016/j.etp.2010.05.013
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pubmed_90_597
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The fluorescence characteristics of intracellular fluorescein, formed by the hydrolysis of fluorescein diacetate in peripheral human lymphocytes, were studied by fluorometry on cell suspensions and compared to those of albumin bound and free fluorescein in solution. The absorption and fluorescence spectra of both intracellular fluorescein and fluorescein in aqueous solutions of albumin and glycerol were red shifted by 2-10 nm as compared to the spectra of fluorescein in phosphate buffered saline. The fluorescence polarization (P) of both intracellular fluorescein and a mixture of albumin-bound and free fluorescein showed a decrease towards low emission wavelengths and an increase toward high excitation wavelengths. The results were found to be consistent with a simple model assuming that part of the intracellular fluorescein is dissolved in the aqueous phase of the cytoplasm, giving P less than 0.1, while the rest is bound to macromolecules, giving P = 0.33. The fraction of bound intracellular fluorescein was estimated to be about 70%. Fluorescein was found to bind with high affinity and more rigidly (P = 0.43) to albumin than to intracellular macromolecules in general.
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10.1002/cyto.990010406
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pubmed_6_3728
|
Spore-based Bacillus spp. products are considered to have a higher probiotic potential compared to products containing only lactic acid bacteria because their viability in the gastrointestinal (GI) tract is higher, even when GI environmental conditions are unfavorable. The aim of this study was to assess the effect of a Bacillus subtilis, Bacillus licheniformis and Pediococcus acidilactici spore-based potential probiotic on the natural levels of postprandial endotoxemia. A total of 11 dogs completed the study: group 1-healthy dogs: n = 5; group 2-dogs with apparent dysbiosis: n = 6. For 30 days, the dogs were fed the probiotic product; clinical examinations and blood sampling were done before and after completion of the probiotic treatment. Endotoxin levels were assessed pre-meal, 6 h and 12 h post-meal, before initiation and after completion of the treatment. The results showed a decrease in endotoxin levels after treatment, especially 12 h post-meal (group 1: 20.60%; group 2: 44.93%). This study reports new information with regard to natural endotoxemia levels in dogs and suggests that a multi-strain formula (spore-based) consisting of B. subtilis, B. licheniformis and P. acidilactici is able to diminish endotoxin values.
|
10.3390/ani11051367
|
pubmed_969_6791
|
1. A 5-year retrospective study of 1743 episodes of self-poisoning in 1608 adult patients, was undertaken to determine the frequency of self-poisoning with psychopharmacological agents, the frequency of each toxic agent usage and the epidemiological characteristics of the poisoned population. 2. The annual incidence of self-poisoning in Zagreb was 38.7 per 100,000 adult inhabitants. The anxiolytic-antipsychotic-antidepressant usage ratio was 8.8:1.5:1.0 in total self-poisoning, whereas it was 4.9:1.5:1.0 in patients with a previous history of self-poisoning. The use of anxiolytics decreased and the use of antidepressants increased during the 5 years. 3. The female-male ratio was 3.8:1 and 77% of self-poisoned persons were aged 15-44 years. The incidence of self-poisoning was 74% higher in the urban than in the rural population. The proportion of self-poisoned persons was 204% higher among the unemployed than in the population as a whole. There were 76% more repetitors among highly educated and 43% fewer repetitors among students than in the general population. The use of antipsychotics was 120% higher in males than in females. The use of antidepressants was 107% higher in the highly educated. 4. The increased use of antidepressants in self-poisoning is an alarming signal and caution in their prescription seems to be indicated.
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10.1177/096032719101000502
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pubmed_1105_11899
|
BACKGROUND
Inactivating mutations of DAX-1 give rise to the X-linked form of adrenal hypoplasia congenita (AHC). Affected fetuses are at risk of early postnatal Addisonian crisis, but the variable phenotypic expression of DAX-1 insufficiency renders this diagnosis challenging.
METHODS
We describe the familial transmission of AHC over several generations. The proband was diagnosed with adrenal insufficiency at age 3.5 years: molecular analysis revealed a novel, 373-bp deletion including the second exon of DAX-1. Given the familial history of several unexplained deaths in male infants related to the proband via his maternal great-grandmother, we hypothesized that all these boys had been affected with AHC. Another female member of the family being pregnant with a male fetus at the time, we performed DAX-1 analysis on the mother and the newborn. The mother was heterozygous for the deletion, and the newborn hemizygous: he presented an adrenal crisis at 10 days of life, and is now doing well on hormone replacement therapy.
CONCLUSION
The unfortunate deaths of male infants at each generation of this family underlie the importance of early and precise diagnosis of this rare condition, stressing the value of genetic diagnosis in six potential female carriers of this family entering their reproductive years.
|
10.1159/000091831
|
pubmed_1079_3403
|
Involuntary emotional expression disorder (IEED) is a syndrome characterized by involuntary episodes of emotional expression, particularly crying or laughing, that occur in patients with a neurological illness, including neuro-degenerative diseases. The authors assessed the frequency and clinical correlates of IEED among 131 patients with Parkinson's disease. IEED was present in 16.8% of patients overall and in 15.3% of depressed patients. The only clinical correlate of IEED diagnosis was greater severity of Parkinson's disease. The lack of an association between IEED and depression suggests that, in spite of some symptom overlap, the two disorders are distinct neuropsychiatric syndromes in Parkinson's disease.
|
10.1176/appi.neuropsych.21.4.406
|
pubmed_419_2575
|
In order to fabricate functional organoids and microtissues, a high cell density is generally required. As such, the placement of cell suspensions in molds or microwells to allow for cell concentration by sedimentation is the current standard for the production of organoids and microtissues. Even though molds offer some level of control over the shape of the resulting microtissue, this control is limited as microtissues tend to compact towards a sphere after sedimentation of the cells. 3D bioprinting on the other hand offers complete control over the shape of the resulting structure. Even though the printing of dense cell suspensions in the ink has been reported, extruding dense cellular suspensions is challenging and generally results in high shear stresses on the cells and a poor shape fidelity of the print. As such, additional materials such as hydrogels are added in the bioink to limit shear stresses, and to improve shape fidelity and resolution. The maximum cell concentration that can be incorporated in a hydrogel-based ink before the ink's rheological properties are compromised, is significantly lower than the concentration in a tissue equivalent. Additionally, the hydrogel components often interfere with cellular self-assembly processes. To circumvent these limitations, we report a simple and inexpensive xanthan bath based embedded printing method to 3D print dense functional linear tissues using dilute particle suspensions consisting of cells, spheroids, hydrogel beads, or combinations thereof. Using this method, we demonstrated the self-organization of functional cardiac tissue fibers with a layer of epicardial cells surrounding a body of cardiomyocytes.
|
10.1088/1758-5090/aca124
|
pubmed_1094_2966
|
BACKGROUND
Despite being used by more than 18 million people our understanding of the extent of the effects of antiretrovirals on the human body and other organisms remains incomplete. In addition, the direct effect of antiretrovirals on the gut microbiota of HIV-infected individuals has been largely overlooked in microbiome studies concerned with HIV-infected individuals.
METHODS
Here we tested 25 antiretrovirals on Bacillus subtilis and Escherichia coli using a broth microdilution assay to assess whether these drugs have an antibacterial effect.
RESULTS
We found that several widely used antiretroviral drugs have in vitro antibacterial activity against both gram-positive and gram-negative commensal bacteria. Efavirenz inhibited the growth of B. subtilis with a minimum inhibitory concentration (MIC) of 16 µg/ml (in all three replicates), while 2',3'-dideoxyinosine and zidovudine inhibited the growth of E. coli with an MIC of 16-32 µg/ml and 0.016-0.125 µg/ml (respectively).
CONCLUSIONS
Given the large and increasing number of individuals on antiretrovirals, and the lifelong nature of HIV treatment, this proof-of-concept report could have several potential implications, including an impact of antiretrovirals on bacterial coinfections, as well as potentials for drug discovery and repositioning.
|
10.3851/IMP3173
|
pubmed_848_17121
|
The cross-linking of the F-actin-caldesmon complex with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide in the presence of N-hydroxysuccinimide generated four major adducts which were identified on polyacrylamide gels. By cross-linking 3H-actin to 14C-caldesmon, these were found to represent 1:1 cross-linked complexes of actin and caldesmon displaying different electrophoretic mobilities. Tropomyosin did not noticeably affect the cross-linking process. The same four fluorescent species resulting from the cross-linking of caldesmon to F-actin labeled with N-[7-(dimethylamino)-4-methyl-3-coumarinyl]maleimide were subjected separately to partial cleavages with hydroxylamine or cyanogen bromide. These treatments yielded fluorescent 41- and 37-kDa fragments, respectively, from each cross-linked entity indicating unambiguously that caldesmon was cross-linked only to the NH2-terminal actin stretch of residues 1-12. This region is also known to serve for the carbodiimide-mediated cross-linking of the myosin subfragment-1 heavy chain (Sutoh, K. (1982) Biochemistry 21, 3654-3661). A covalent caldesmon-F-actin conjugate containing a protein molar ratio close to 1:19 was isolated following dissociation of uncross-linked caldesmon. It showed a low level of activation of the ATPase activity of skeletal myosin subfragment-1, and the binding of Ca2(+)-calmodulin to the derivative did not cause the reversal of the ATPase inhibition. In contrast, the reversible binding of caldesmon to F-actin cross-linked to myosin subfragment-1 did not inhibit the accelerated ATPase of the complex. The overall data point to the dual involvement of the actin's NH2 terminus in the inhibitory binding of caldesmon and in actomyosin interactions in the presence of ATP.
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pubmed_848_17121
|
pubmed_306_22658
|
BACKGROUND
Assessing the cost-effectiveness of treatments in rheumatoid arthritis (RA) is of growing importance due to the chronic nature of the disease, rising treatment costs, and budget-constrained health care systems. This analysis assesses the cost-effectiveness of modified-release (MR) prednisone compared with immediate-release (IR) prednisone for the treatment of morning stiffness due to RA.
METHODS
A health state transition model was used to categorize RA patients into four health states, defined by duration of morning stiffness. The model applied a 1-year time horizon and adopted a UK National Health Service (NHS) perspective. Health benefits were measured in quality-adjusted life years (QALYs) and the final output was the incremental cost-effectiveness ratio (ICER). Efficacy data were derived from the CAPRA-1 (Circadian Administration of Prednisone in Rheumatoid Arthritis) study, drug costs from the British National Formulary (BNF), and utility data from a direct elicitation time-trade-off (TTO) study in the general population. Sensitivity analyses were conducted.
RESULTS
Mean treatment costs per patient were higher for MR-prednisone (£649.70) than for IR-prednisone (£46.54) for the duration of the model. However, the model generated an incremental QALY of 0.044 in favor of MR-prednisone which resulted in an ICER of £13,577. Deterministic sensitivity analyses did not lead to significant changes in the ICER. Probabilistic sensitivity analysis reported that MR-prednisone had an 84% probability of being cost-effective at a willingness-to-pay threshold of £30,000 per QALY. The model only considers drug costs and there was a lack of comparative long-term data for IR-prednisone. Furthermore, utility benefits were not captured in the clinical setting.
CONCLUSION
This analysis demonstrates that, based on the CAPRA-1 trial and directly elicited public preference values, MR-prednisone is a cost-effective treatment option when compared with IR-prednisone for RA patients with morning stiffness over one year, according to commonly applied UK thresholds (£20,000-£30,000 per QALY). Further research into the costs of morning stiffness in RA is required.
|
10.2147/CEOR.S47867
|
pubmed_926_22839
|
PURPOSE
Totally implantable venous access devices (TIVADs) are commonly used in pediatrics for the administration of chemotherapy, antibiotics, or parenteral nutrition. TIVADs can be implanted using various techniques, including surgical cutdown (SC) and percutaneous puncture (PP). Recently, percutaneous TIVAD became popular in adults, but studies comparing between PP and SC group in pediatric patients are rare.
MATERIALS AND METHODS
Data were collected and analyzed retrospectively from 23 patients who underwent TIVAD at a single institution between January 2013 and December 2015. We examined the clinical characteristics, insertion techniques, and clinical outcome. We divided the patients into 2 groups and compared PP with ultrasonography and SC using the insertion technique. We compared success rate, procedural time, and the patency rate between the 2 groups.
RESULTS
Eleven TIVADS were inserted using PP, and 12 TIVADs were inserted using SC. No statistically significant difference in characteristics was found between the 2 groups. The procedural time in the PP group was shorter than that in the SC group, but the difference was not statistically significant (P=0.685). During follow-up, 1 patient in the SC group had an occlusion, and 1 patient in the PP group had an infection.
CONCLUSION
PP of the internal jugular vein with ultrasonography appears to be the method of choice for TIVAD insertion owing to its similar success rate in terms of implantation and complication rate to that in SC, with shorter procedural times in pediatric patients.
|
10.5758/vsi.2017.33.3.108
|
pubmed_489_22635
|
OBJECTIVE
To validate the Hong Kong Chinese translation of the Overactive Bladder Symptom Score questionnaire (OABSS-HKC).
DESIGN
Cross-sectional study.
SETTING
Five urology clinics of different regional hospitals in Hong Kong.
PARTICIPANTS
The Overactive Bladder Symptom Score questionnaire was translated and culturally adapted for Hong Kong Chinese, according to the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures. Chinese-speaking patients with overactive bladder symptoms were recruited from five urology clinics. The patients completed the OABSS-HKC, a 3-day micturition diary, International Prostate Symptom Scores, and the Patient Perception of Bladder Condition questionnaires (visit 1), and again after a 2-week interval (visit 2). Test-retest reliability was evaluated by the intraclass correlation coefficient and weighted Kappa coefficient. The relationship between OABSS-HKC total scores and items in the comparison measures was evaluated using Spearman's correlation coefficients.
RESULTS
The OABSS-HKC was successfully translated and culturally adapted. Fifty-one patients completed the validation study. A high level of reliability was observed between the OABSS-HKC total score answered at visit 1 and 2 for all subjects (intraclass correlation coefficient, 0.82) and among the four items answered (weighted Kappa coefficients, 0.57-0.75). The OABSS-HKC total score correlated significantly with numbers of micturitions, incontinence and urgency episodes recorded in the 3-day micturition diary, as well as the total International Prostate Symptom Scores and the Patient Perception of Bladder Condition score. However, the OABSS-HKC total score was not significantly associated with nocturia episodes, total voided volume, or number of pads used.
CONCLUSIONS
The OABSS-HKC total scores are reliable and moderately valid for the quantitative evaluation of overactive bladder symptoms in Hong Kong Chinese-speaking adults.
|
10.12809/hkmj133878
|
pubmed_973_1324
|
Platelet-rich plasma (PRP), containing various growth factors, may speed up wound and bone healing. Using osteoconductive alloplastic materials in reconstructive surgery, the amount of autogenous bone needed can be reduced. The purpose of this experiment was to study the effect of PRP on a mixture of autogenous bone and deproteinized bovine bone mineral (Bio-Oss) particles in goats. Four, round, critical size defects were made in the foreheads of 20 goats. In all goats the defects were filled with a mixture of autogenous particulate cancellous bone and (Bio-Oss) particles, in which 1 ml of PRP was added in two of the four defects. The goats were allocated to four subgroups each containing five goats, which were killed after 1, 2, 6 and 12 weeks. The results of the histological and histomorphometric examination showed that early and late bone healing were not enhanced when PRP was used.
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10.1016/j.ijom.2009.12.019
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pubmed_491_24777
|
The NOD-like receptors (NLRs, nucleotide-binding domain and leucine-rich repeat containing receptors) are a recently identified family of intracellular pathogen recognition receptors in vertebrates. Several subfamilies of NLRs have been characterized in mammals and implicated in immunity and apoptosis, but studies of NLRs in teleost species have been lacking. Here we analyzed three NLR-A subfamily members from miiuy croaker: NLRC3, NLRC5, and NLRX1. Structural analysis showed that miiuy croaker NLR-A subfamily members own the feature of 5'UTR intron which may influence their role in enhancing translation level. Comparative analysis revealed NLRX1 duplicated into NLRX1a and NLRX1b, then NLRX1a was lost in actinopterygii and NLRX1b formed NLRX1 that now we called. Simultaneously, molecular evolutionary analysis indicated that the ancestral lineages of NLRX1 in tetrapod and actinopterygii under positive selection pressure. The positively sites in actinopterygii are mainly located in NACHT domain which was the critical region for signal transduction, suggesting that the evolution of NLRX1 gene in the ancestor of actinopterygii is beneficial in immune response. Pathogens challenge demonstrated that the expressions of NLRC3 and NLRC5 in miiuy croaker were induced not only by Vibrio anguillarum but also by poly (I:C), whereas NLRX1 exhibited more sensitive response to bacteria than virus.
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pubmed_491_24777
|
pubmed_103_21541
|
Chronic contained rupture (CCR) of abdominal aortic aneurysm (AAA) with vertebral erosion is a rare condition. Although it has been reported previously, it is still liable to be misdiagnosed. We present a case of CCR of AAA with vertebral erosion. A brief analysis of similar cases reported in the last 5 years is presented. A 71-year-old male was admitted to our hospital because of severe prickling pain in his left thigh. Computerized tomography angiography revealed an AAA which had caused erosion of L3 vertebral body and the left psoas muscle. An aortotomy was performed, and the excised aortic aneurysm replaced with a Dacron graft. Postoperative computed tomography (CT) angiography indicated a normal aortic graft. The patient was discharged 13 days after the surgery. In conclusion, pain in lower back and leg could be associated with vertebral erosion caused by CCR of AAA. Ultrasonography, CT, or magnetic resonance imaging of abdomen should be routinely performed in cases of lumbago that have associated risk factors for AAA.
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10.1016/j.avsg.2016.09.025
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pubmed_723_1682
|
Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors' platinum resistance identifies novel approach to treating these tumors.
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10.1042/BCJ20190591
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pubmed_250_23461
|
Testosterone levels have been shown to decrease in the face of social defeat in several mammalian species. Among humans, the loss of social status has been studied primarily in the context of athletic competition, with winners having higher testosterone levels than losers. This study examined testosterone levels in relation to peer victimization (bullying) in a sample of 151 boys and girls aged 12-13. Statistically controlling for age and pubertal status, results indicated that on average verbally bullied girls produced less testosterone and verbally bullied boys produced more testosterone than their nonbullied counterparts. Similar trends were evident comparing social and physical bullying with testosterone. Sex differences are discussed in terms of empirically validated differences in coping styles, as girls tend to internalize, whereas boys tend to externalize, their abuse.
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10.1002/ab.20288
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pubmed_101_25180
|
During ripening, peach fruits (Prunus persica L. Batsch) rapidly progress to the senescent stage, resulting in a brief shelf life. Abscisic acid (ABA) plays an important role in regulating the ripening process, both in climacteric and non-climacteric fruits. A key enzyme for ABA biosynthesis in higher plants is 9-cis-epoxycarotenoid dioxygenase (NCED). In this study, two NCED isozymes, PpNCED1 and PpNCED5, were identified in peach fruits. While both NCED genes had similar transcriptional patterns (up-regulation) at the beginning of peach ripening, PpNCED5 showed a consistently lower expression level than PpNCED1. During the post-harvest stage, gene expression of PpNCED1 declined, while PpNCED5 expression increased relative to PpNCED1 expression. Considering the dynamic process of ABA accumulation during fruit ripening and senescence in peach, this study indicates that both NCED genes cooperatively control ABA biosynthesis in peach fruits. Moreover, spatio-temporal expression and transcriptional response to hormone and abiotic stress suggested that there is functional divergence between PpNCED1 and PpNCED5 genes in peach. A carotenoid-rich callus system was used to verify the function of PpNCED1 and PpNCED5. In the transgenic callus system, both PpNCED1 and PpNCED5 isozymes promoted ABA biosynthesis, which likely accelerated cell senescence through activating ROS signals. The results from this study provide evidence supporting an ABA biosynthetic regulation process via the two NCED genes in peach fruit, and suggest a mechanism of ABA-induced fruit ripening and senescence.
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10.1016/j.plantsci.2020.110739
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pubmed_570_11674
|
To provide a fundamental basis for understanding decision-making and decision confidence, we analyze a neuronal spiking attractor-based model of decision-making. The model predicts probabilistic decision-making with larger neuronal responses and larger functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) responses on correct than on error trials because the spiking noise-influenced decision attractor state of the network is consistent with the external evidence. Moreover, the model predicts that the neuronal activity and the BOLD response will become larger on correct trials as the discriminability ΔI increases and confidence increases and will become smaller as confidence decreases on error trials as ΔI increases. Confidence is thus an emergent property of the model. In an fMRI study of an olfactory decision-making task, we confirm these predictions for cortical areas including medial prefrontal cortex and the cingulate cortex implicated in choice decision-making, showing a linear increase in the BOLD signal with ΔI on correct trials, and a linear decrease on error trials. These effects were not found in a control area, the orbitofrontal cortex, where reward value useful for the choice is represented on a continuous scale but that is not implicated in the choice itself. This provides a unifying approach to decision-making and decision confidence and to how spiking-related noise affects choice, confidence, synaptic and neuronal activity, and fMRI signals.
|
10.1152/jn.00571.2010
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pubmed_10_13183
|
Herpes zoster is a rare cause of non-discogenic sciatica. A combination of case rarity and name similarity was nearly leading to an inopportune surgery in a 21 years old woman. The clinical presentation was completely similar to a cauda equina syndrome associated with urinary incontinence and bilateral leg involvement. Concurrently, lumbosacral imaging of another patient with exactly similar name in the picture archiving communications system (PACS) has shown a huge L5-1 disc herniation. Careful attention to all diverse causes of sciatica and identifying details of the images could prevent improper discectomy in our patient.
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pubmed_10_13183
|
pubmed_774_23337
|
Ligand-based NMR screening represents a powerful method in fragment-based drug discovery for the identification of chemical matter interacting with the receptor of interest. The large dynamic range of these methods allows the detection of weakly binding ligands. However, the methodology has not been extensively used for quantifying the strength of these interactions. This knowledge is important for ranking fragments according to their binding strength and for prioritizing structure-based and medicinal chemistry activities. Rapid NMR methods for measuring the dissociation constant in direct and competition modes are presented here. The theory underpinning these methods are presented, along with their application to the measurement of the binding affinities of several ligands of the heat shock protein 90.
|
10.1002/cmdc.201900152
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pubmed_407_11371
|
Peptide deformylase (PDF) catalyzes the removal of the formyl group from the N-terminal methionine residue in newly synthesized polypeptides, which is an essential process in bacteria. Four new inhibitors of PDF that belong to two different classes, hydroxamate/pseudopeptide compounds [PMT387 (7a) and PMT497] and reverse-hydroxamate/nonpeptide compounds [PMT1039 (15e) and PMT1067], have been developed. These compounds inhibited the growth of several pathogens involved in respiratory-tract infections, such as Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae, and leading nosocomial pathogens such as Staphylococcus aureus and Klebsiella pneumoniae with a minimum inhibitory concentration (MIC) in the range 0.1-0.8 mg ml(-1). Interestingly, the reverse-hydroxamate/nonpeptide compounds showed a 250-fold higher antimicrobial activity towards S. aureus, although the four compounds showed similar K(i) values against S. aureus PDF enzymes, with K(i) values in the 11-85 nM range. To provide a structural basis for the discovery of additional PDF inhibitors, the crystal structures of S. aureus PDF in complex with the four inhibitors were determined at resolutions of 1.90-2.30 Å. The inhibitor-bound structures displayed distinct deviations depending on the inhibitor class. The distance between the Zn(2+) ion and the carbonyl O atom of the hydroxamate inhibitors (or the hydroxyl O atom of the reverse-hydroxamate inhibitors) appears to be correlated to S. aureus inhibition activity. The structural information reported in this study should aid in the discovery of new PDF inhibitors that can be used as novel antibacterial drugs.
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10.1107/S0907444912011912
|
pubmed_591_21933
|
Cable bacteria have been reported in sediments from marine and freshwater locations, but the environmental factors that regulate their growth in natural settings are not well understood. Most prominently, the physiological limit of cable bacteria in terms of oxygen availability remains poorly constrained. In this study, we investigated the presence, activity and diversity of cable bacteria in relation to a natural gradient in bottom water oxygenation in a depth transect of the Eastern Gotland Basin (Baltic Sea). Cable bacteria were identified by FISH at the oxic and transiently oxic sites, but not at the permanently anoxic site. Three species of the candidate genus Electrothrix, i.e. marina, aarhusiensis and communis were found coexisting within one site. The highest filament density (33 m cm-2 ) was associated with a 6.3 mm wide zone depleted in both oxygen and free sulphide, and the presence of an electric field resulting from the electrogenic sulphur oxidizing metabolism of cable bacteria. However, the measured filament densities and metabolic activities remained low overall, suggesting a limited impact of cable bacteria at the basin level. The observed bottom water oxygen levels (< 5 μM) are the lowest so far reported for cable bacteria, thus expanding their known environmental distribution.
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10.1111/1462-2920.14349
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pubmed_548_25587
|
BACKGROUND
Clinical guidelines are an integral part of healthcare. Whilst much progress has been made in ensuring that guidelines are well developed and disseminated, the gap between routine clinical practice and current guidelines often remains wide. A key reason for this gap is that implementation of guidelines typically requires a change in the behaviour of healthcare professionals - but the behaviour change component is often overlooked. We adopted the Theoretical Domains Framework Implementation (TDFI) approach for supporting behaviour change required for the uptake of a national patient safety guideline to reduce the risk of feeding through misplaced nasogastric tubes.
METHODS
The TDFI approach was used in a pre-post study in three NHS hospitals with a fourth acting as a control (with usual care and no TDFI). The target behavior identified for change was to increase the use of pH testing as the first line method for checking the position of a nasogastric tube. Repeat audits were undertaken in each hospital following intervention implementation. We used Zou's modified Poisson regression approach with robust standard errors to estimate risk ratios for the use of pH testing. The projected return on investment (ROI) was also calculated.
RESULTS
Following intervention implementation, the use of pH first line increased significantly across intervention hospitals [risk ratio (95% CI) ranged from 3.1 (1.14 to8.43) p < .05, to 8.14 (3.06 to21.67) p < .001] compared to the control hospital, which remained unchanged [risk ratio (CI) = .77 (.47-1.26) p = .296]. The estimated savings and costs in the first year were £2.56 million and £1.41 respectively, giving an ROI of 82%, and this was projected to increase to 270% over five years.
CONCLUSION
The TDFI approach improved the uptake of a patient safety guideline across three hospitals. The TDFI approach is clinically and cost effective in comparison to the usual practice.
|
10.1186/s12913-014-0648-4
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pubmed_578_16796
|
The aim of this study was to evaluate the clinical utility of an image-guided Raman endoscopy technique for in vivo differential diagnosis of benign and malignant ulcerous lesions in the stomach. A rapid-acquisition image-guided Raman endoscopy system with 785 nm laser excitation has been developed to acquire in vivo gastric tissue Raman spectra within 0.5 s during clinical gastroscopic examinations. A total of 1102 in vivo Raman spectra were acquired from 71 gastric patients, in which 924 Raman spectra were from normal tissue, 111 Raman spectra were from benign ulcers whereas 67 Raman spectra were from ulcerated adenocarcinoma. There were distinctive spectral differences in Raman spectra among normal mucosa, benign ulcers and malignant ulcers, particularly in the spectral ranges of 800-900, 1000-1100, 1245-1335, 1440-1450 and 1500-1800 cm(-1), which primarily contain signals related to proteins, DNA, lipids and blood. The malignant ulcerous lesions showed Raman signals to be mainly associated with abnormal nuclear activity and decrease in lipids as compared to benign ulcers. Partial least squares-discriminant analysis (PLS-DA) was employed to generate multi-class diagnostic algorithms for classification of Raman spectra of different gastric tissue types. The PLS-DA algorithms together with leave-one tissue site-out, cross validation technique yielded diagnostic sensitivities of 90.8%, 84.7%, 82.1%, and specificities of 93.8%, 94.5%, 95.3%, respectively, for classification of normal mucosa, benign and malignant ulcerous lesions in the stomach. This work demonstrates that image-guided Raman endoscopy technique associated with PLS-DA diagnostic algorithms has for the first time promising clinical potential for rapid, in vivo diagnosis and detection of malignant ulcerous gastric lesions at the molecular level.
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10.1039/c0an00336k
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pubmed_325_7895
|
Climate change is a driving force for livestock parasite risk. This is especially true for helminths including the nematodes Haemonchus contortus, Teladorsagia circumcincta, Nematodirus battus, and the trematode Fasciola hepatica, since survival and development of free-living stages is chiefly affected by temperature and moisture. The paucity of long term predictions of helminth risk under climate change has driven us to explore optimal modelling approaches and identify current bottlenecks to generating meaningful predictions. We classify approaches as correlative or mechanistic, exploring their strengths and limitations. Climate is one aspect of a complex system and, at the farm level, husbandry has a dominant influence on helminth transmission. Continuing environmental change will necessitate the adoption of mitigation and adaptation strategies in husbandry. Long term predictive models need to have the architecture to incorporate these changes. Ultimately, an optimal modelling approach is likely to combine mechanistic processes and physiological thresholds with correlative bioclimatic modelling, incorporating changes in livestock husbandry and disease control. Irrespective of approach, the principal limitation to parasite predictions is the availability of active surveillance data and empirical data on physiological responses to climate variables. By combining improved empirical data and refined models with a broad view of the livestock system, robust projections of helminth risk can be developed.
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10.3390/ani2010093
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pubmed_886_6157
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Strongyloidiasis can be perpetuated by autoinfection with the filariform larvae L3, causing asymptomatic chronic infections and creating a population of carriers, affecting not only developing countries. So far, very little is known about the proteins that interact with the human host, and few proteins from the infective Strongyloides stercoralis L3 have been characterized. Here, we report results obtained from a proteomic analysis of the proteins from S. stercoralis L3 larvae obtained from patients. Since the genome of S. stercoralis is not yet available, we used proteomic analysis to identify 26 different proteins, 13 of them released by short digestion with trypsin, which could represent surface-associated proteins. The present work extends our knowledge of host-parasite interactions by identifying proteins that could be of interest in the development of diagnostic tools, vaccines, or treatments for a neglected disease like strongyloidiasis.
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10.1017/S0031182010000314
|
pubmed_705_9824
|
UNLABELLED
We studied the methodical and clinical relevance of five determination assays for free PSA (f-PSA) in addition to the corresponding total PSA antigen (t-PSA).
METHODS
Both the total PSA- and free-PSA-values of frozen sera obtained pretherapeutically from 80 patients with carcinoma (PC) and 171 patients with benign hyperplasia of the prostate (BPH) were analysed by means of Enzymun-Test PSA/BM, PSA-RIACT/ CIS, CanAg PSA EIA/ Dia, Tandem-E PSA/Hyb, PSA IRMA/ IBL and Enzymun-Test PSA free/BM, F PSA-RIACT/CIS, CanAg Anti Free PSA/Dia, Tandem-R free PSA/Hyb, FREE PSA IRMA/IBL.
RESULTS
The coefficient of correlation between Hybritech PSA assay and the other assays was determined in patients with benign and malignant prostatic diseases. There was a strong overall correlation with all assays measuring total or free PSA, respectively. A satisfying correlation is also shown using a limited scale up to 50 ng/mL for total PSA and 5 ng/mL for free PSA. At 95% specificity sensitivities of total PSA between 40% and 50% of the ratio (Q) = free PSA/total PSA between 4% and 28% were calculated. In a second step only patients with total PSA values below the cutoff level of 16.5 [micrograms/l] (BM), 13.9 [micrograms/l] (CIS), 14.7 [micrograms/l] (Dia), 15.7 [micrograms/l] (Hyb) and 16.8 [micrograms/l] (IBL) were considered. Using the BM assays, of these patients 9 of 162 with BPH and 14 of 47 with PC [CIS: 14 of 162 with BPH and 4 of 48 with PC/Dia: 13 of 162 with BPH and 11 of 48 with PC/Hyb: 6 of 156 with BPH (missing values = 6) and 11 of 40 with PC/IBL: 11 of 160 with BPH (missing values = 1) and 13 of 33 with PC (missing values = 2)] were below the ratio Q = free PSA/total PSA. Considering both steps (total PSA and Q) using the BM assay 47 patlents with PC were detected correctly and 18 patients with BPH would have been biopsied unnecessarily (positive biopsy rate = pos. br.: 72%) [CIS: 38 patients with PC and 23 patients with BPH (pos. br.: 62%)/Dia: 43 patients with PC and 22 patients with BPH (pos. br.: 66%)/Hyb: 51 patients with PC and 15 patients with BPH (pos. br.: 77%)/IBL: 46 patients with PC and 20 patients with BPH (pos. br.: 70%)]
CONCLUSIONS
High total PSA levels of all assays are a very good indicator for the presence of prostate cancer. There is still concern to improve the differentiation between BPH and PC, when an intermediate or low value (< 95% specificity) is observed. The determination of Q is only useful in this range and it might be helpful for the clinicians decision to apply or avoid biopsy.
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pubmed_705_9824
|
pubmed_305_12995
|
Complexity and inconsistencies in resistance mapping publications of soybean sudden death syndrome (SDS) result in interpretation difficulty. This review integrates SDS mapping literature and proposes a new nomenclature system for reproducible SDS resistance loci. Soybean resistance to sudden death syndrome (SDS) is composed of foliar resistance to phytotoxins and root resistance to pathogen invasion. There are more than 80 quantitative trait loci (QTL) and dozens of single nucleotide polymorphisms (SNPs) associated with soybean resistance to SDS. The validity of these QTL and SNPs is questionable because of the complexity in phenotyping methodologies, the disease synergism between SDS and soybean cyst nematode (SCN), the variability from the interactions between soybean genotypes and environments, and the inconsistencies in the QTL nomenclature. This review organizes SDS mapping results and proposes the Rfv (resistance to Fusarium virguliforme) nomenclature based on supporting criteria described in the text. Among ten reproducible loci receiving our Rfv nomenclature, Rfv18-01 is mostly supported by field studies and it co-localizes to the SCN resistance locus rhg1. The possibility that Rfv18-01 is a pleiotropic resistance locus and the concern about Rfv18-01 being confounded with Rhg1 is discussed. On the other hand, Rfv06-01, Rfv06-02, Rfv09-01, Rfv13-01, and Rfv16-01 were identified both by screening soybean leaves against phytotoxic culture filtrates and by evaluating SDS severity in fields. Future phenotyping using leaf- and root-specific resistance screening methodologies may improve the precision of SDS resistance, and advanced genetic studies may further clarify the interactions among soybean genotypes, F. virguliforme, SCN, and environments. The review provides a summary of the SDS resistance literature and proposes a framework for communicating SDS resistance loci for future research considering molecular interactions and genetic breeding for soybean SDS resistance.
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10.1007/s00122-018-3063-0
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pubmed_597_15873
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An R-module A is called GF-regular if, for each a ∈ A and r ∈ R, there exist t ∈ R and a positive integer n such that r(n)tr(n)a = r(n)a. We proved that each unitary R-module A contains a unique maximal GF-regular submodule, which we denoted by M GF(A). Furthermore, the radical properties of A are investigated; we proved that if A is an R-module and K is a submodule of A, then MGF(K) = K∩M GF(A). Moreover, if A is projective, then MGF(A) is a G-pure submodule of A and MGF(A) = M(R) · A.
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10.1155/2013/750808
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pubmed_787_1240
|
The light-driven splitting of water into its constituting elements gives access to a valuable fuel from an abundant substrate, using sunlight as the only energy source. Synthetic diiron complexes as functional models of the [FeFe] hydrogenase H2ase enzyme active site have moved into the centre of focus as potentially viable catalysts for the reductive side of this process, i.e. the reduction of protons to molecular hydrogen. The active site of the enzyme, as well as its mimics in an artificial system, are required to accumulate two electrons from single electron transfer events and to combine them with two protons to form hydrogen. Whereas in biology this reaction is not coupled to photosynthesis and thus proceeds in the dark, additional aspects need to be considered when designing a functional artificial system for the light-driven reduction of protons. Suitable photosensitizers have to be chosen that not only provide sufficient driving force for the reduction of the synthetic diiron catalyst, but also allow for selective excitation to minimize photodegradation. Electron transfer efficiencies have to be optimized for all steps and the sequential nature of the catalyst reduction requires a sufficient stability of potentially labile intermediates of the catalytic cycle. In this perspective, systems for the light-driven conversion of protons to molecular hydrogen are discussed where the catalyst is based on model complexes of the [FeFe] H2ase active site. Covalently linked dyads, supramolecular assemblies and multi-component systems will be examined with an emphasis on mechanistic electron transfer schemes, the properties of the individual components, their scope and their potential limitations.
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10.1039/b911129h
|
pubmed_247_11443
|
CBA/N mice submitted to autologous bone marrow reconstitution after lethal irradiation and simultaneous Cyclosporin A (CsA) treatment develop a chronic graft-versus-host disease with autoimmune characteristics. When compared to normal controls, diseased mice show an overrepresentation of V beta 8-expressing T cells (65-80% of all CD3+ lymphocytes), together with a marked increase in the titres of serum Ig that specifically bind to F(ab')2 fragments of anti-V beta 8 F23.1 antibodies. Such 'V beta 8-like' Ig V regions are abundantly represented among the IgG2b and mAbs of an unselected collection of hybridomas derived from these mice. These mAbs are not multireactive Ig as they fail to bind to a panel of various antigens and antibodies, but often show simultaneous reactivity with anti-idiotypic mAbs to F23.1 and auto-binding. These molecules may provide the structural basis of V-region specific complementarities, driving the expansion of restricted T and B cell repertoires associated with pathological autoimmunity.
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10.1093/intimm/3.8.777
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pubmed_592_6375
|
A stability-indicating liquid chromatographic method for the simultaneous analysis of aspirin and warfarin in warfarin sodium/aspirin combination (DuP 647) tablets has been developed and validated. This paper presents linearity, accuracy, precision, robustness, recovery, limits of detection and quantitation, and cross-validation data. The method has been shown to be specific and stability-indicating, and to give results comparable to existing methods for the individual components. Solution stability has been optimized for routine analysis.
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10.1016/0731-7085(96)01813-4
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pubmed_316_6639
|
Glucose transport by FRTL-5 cells, a rat thyroid cell line, was found to be TSH dependent. The effect of TSH on the uptake of 2-deoxy-D-glucose, a nonmetabolizable glucose analogue, was prompt, being 200% over basal value after 10 min and maximal after 12 h (600-700% increase). The TSH effect was dose dependent, with half-maximum stimulation at 10 microU TSH/ml, and maximum stimulation at 1 mU TSH/ml. TSH enhanced also the uptake of 3-O-methyl-D-glucose by FRTL-5 cells. The TSH activation of glucose transport had the following characteristics: it was mimicked by (Bu)2-cAMP (1 mM) and by agents that increase cAMP levels in thyroid cells, such as forskolin (10 microM) and cholera toxin (50 micrograms/ml); it involved the facilitated glucose transport system in that it was inhibited in a dose-related manner by both cytochalasin B and phloretin; it showed a glucose stereochemical sensitivity, being affected by D-glucose and 3-O-methyl-glucose, and not by L-glucose; it was characterized by an increase in the maximum velocity (Vmax) of glucose uptake (from 15.3 to 66.0 fmol/min X micrograms DNA) without change in the Michaelis-Menten constant (Km) (5.3 mM); the effect on the Vmax was due to an increase in the number of surface glucose transporters as indicated by the enhancement of the D-glucose-sensitive fraction of [3H]cytochalasin B binding sites that in thyroid plasma membranes of cells exposed to TSH for 2 and 8 h, increased from 5.0 (basal value) to 10.4 and 23.1 pmol/mg protein, respectively. These data indicate that in FRTL-5 cells TSH stimulates the glucose transport system by an enhancement of the number of functional glucose transporters in the thyroid plasma membrane.
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10.1210/endo-120-6-2576
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pubmed_516_5491
|
Gastric cancer and colon cancer are major causes of mortality and morbidity worldwide. Many cancers manifest due to changes in gene expression, particularly those involved in cellular proliferation and apoptosis. Apoptosis is an important process that removes damaged or deleterious cells and contributes to normal cellular and tissue homeostasis. Apoptosis is a tightly regulated process mediated by caspases, and the involvement of the Bcl-2 superfamily of membrane bound proteins, among others. Thus, the therapeutic induction of apoptosis has been proposed as a novel method to eliminate cancer cells. The oxidative pentose pathway (OPP) and the glutathione (GSH) antioxidant defense system play an important role in the regulation of cell growth and apoptosis. The OPP regulates intracellular redox status and provides NADPH for the synthesis of GSH, an important antioxidant. GSH is required to inactivate intracellular reactive oxygen species (ROS) which induce apoptosis and cell injury. Depletion of GSH increases the sensitivity of cells to ROS. Many chemotherapeutic agents induce apoptosis through ROS-mediated cell damage. Therefore, we speculate that the therapeutic inhibition of the OPP and/or the GSH defense system may increase the sensitivity of gastric and colon cancer cells to anti-cancer therapy. Moreover, we hypothesize that the short-chain fatty acid, butyrate, will induce apoptosis in gastric cancer cells and, secondly, that differences in butyrate metabolism will exist between these cancer cell lines.
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10.4161/cbt.5.6.2868
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pubmed_795_16095
|
(S)-5, 6-Difluoro-4-cyclopropylethynyl-4-trifluoromethyl-3, 4-dihydro- 2-(1H)-quinazolinone (DPC 963), a specific non-nucleoside inhibitor of human immunodeficiency virus-1 reverse transcriptase, is primarily metabolized in humans to the glucuronide conjugate of 8-OH DPC 963 (M8). Electrospray ionization-liquid chromatography/mass spectrometry analyses of urine from subjects dosed with DPC 963 also revealed the presence of other minor metabolites including glucuronide conjugate of 6-OH DPC 963 (M7). An oxidative defluorination pathway involving a putative p-benzoquinone imine capable of being reduced to the hydroquinone (M7) is postulated. The formation of the benzoquinone imine [detected as a glutathione (GSH) adduct, M5] was primarily carried out by CYP3A4, whereas M8 was formed mainly by the polymorphic CYP2B6. The kinetic studies with human liver microsomes showed that the apparent K(m) and V(max) values for the formation of M5 were 65.8 microM and 25.6 pmol/min/mg of protein, respectively. The formation of M8 showed K(m) and V(max) values of 15.1 microM and 22.9 pmol/min/mg of protein, respectively. The microsomal studies also revealed the occurrence of a possible oxirene intermediate that was trapped as GSH adducts M3 and M4. It was demonstrated, for the first time, that CYP3A4 was capable of directly oxidizing the triple bond of the cyclopropyl ethynyl group to an unstable oxirene. The apparent K(m) and V(max) values for the formation of an oxirene (detected as the GSH adduct M3) were 1.9 mM and 10.2 pmol/min/mg of protein, respectively. These results suggest that CYP2B6 has a higher affinity than CYP3A4 toward DPC 963. This consequently leads to greater levels of CYP2B6-catalyzed product, M8, than CYP3A4-mediated bioactivation of DPC 963 to benzoquinone imine or oxirene intermediates.
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10.1124/dmd.31.1.122
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pubmed_707_15105
|
Objective: Radiotherapy or chemoradiotherapy has been preferred as the clinical therapeutic modalities to combat locally advanced esophageal squamous cell carcinoma (ESCC). The aim of this retrospective study is to ascertain combinatorial efficacy of anlotinib with concurrent radiotherapy (CCRT) rather than CCRT alone. Methods: Locally advanced ESCC patients registered between August 2018 to April 2019 in the third People's hospital of Zhengzhou, the First affiliated hospital of Zhengzhou University, Anyang Cancer Hospital, the Affiliated Hospital of Qingdao University were selected for this retrospective study; and these patients segregated into two groups subsequently who received combinatorial regimen with CCRT and anlotinib compared for treatment-related toxicity, response rates, safety, survival outcomes, than CCRT alone. Results: Progression free survival (PFS) was 0.577 (95% CI, 0.333-0.902, P = 0.014); the median overall survival time was 5 months (95% CI, 4.1-7.5) for the CCRT group, whereas 9 months (95% CI, 7.3-18.0) for the group received 'anlotinib with CCRT' (HR = 0.578, 95% CI, 0.337-0.924, P = 0.021). Overall objective response rates were considerable with a statistical difference between the two groups at 6 months (P1 = 0.027, P2 = 0.015) and 12 months (P1 = 0.012, P2 = 0.027). Overall adverse events are mitigated in combinatorial regimen than CCRT alone except the incidence of hypertension, which was higher in 'anlotinib with CCRT' group than CCRT group (P = 0.023). Total 13 patients exhibited hand-foot skin reactions in the group that received anlotinib in combination with CCRT. Anlotinib in combination with CCRT enhanced the overall survival (OS) rates, whereas incidence of treatment-related toxicity is minimized than CCRT alone. Conclusion: Combinatorial regimen of anlotinib with CCRT significantly enhanced clinical efficacy, safety and may benefit for treating the locally advanced ESCC patients.
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10.1177/15330338221080939
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pubmed_235_23831
|
Unravelling how the complexity of living systems can (have) emerge(d) from simple chemical reactions is one of the grand challenges in contemporary science. Evolving systems of self-replicating molecules may hold the key to this question. Here we show that, when a system of replicators is subjected to a regime where replication competes with replicator destruction, simple and fast replicators can give way to more complex and slower ones. The structurally more complex replicator was found to be functionally more proficient in the catalysis of a model reaction. These results show that chemical fueling can maintain systems of replicators out of equilibrium, populating more complex replicators that are otherwise not readily accessible. Such complexification represents an important requirement for achieving open-ended evolution as it should allow improved and ultimately also new functions to emerge.
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10.1002/anie.202016196
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pubmed_307_23925
|
We have found that insulin-like growth factor I (IGF-I) stimulates regeneration of the rat sciatic nerve. This paper reviews and adds some new data to our investigations on the effects of local administration of IGF-I to the sciatic nerve after infliction of a crush or freeze injury.
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10.3233/RNN-1990-13406
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pubmed_496_18828
|
The cycle of loading and unloading of a spherically-tipped probe against an adhesive, viscoelastic plane specimen is studied by numerical integration of the relations between crack speed and apparent surface energy previously found for a linear 3-element viscoelastic solid with a Maugis-Dugdale law of force across the crack. It is found that even when the rate of loading is so slow that the loading and unloading curves almost coincide, suggesting purely elastic behaviour, the pull-off force can be appreciably greater than the elastic (JKR) value. When the normal force is modulated with a small amplitude sinusoidal variation during unloading--in order to find the contact stiffness--the contact radius barely changes, and the stiffness is close to that for a rigid flat punch instead of having the expected JKR value.
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10.1016/j.jcis.2005.08.069
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pubmed_380_5962
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Bradykinin (BK) mimics ischemic preconditioning by generating reactive oxygen species (ROS). To identify intermediate steps that lead to ROS generation, rabbit cardiomyocytes were incubated in reduced MitoTracker Red stain, which becomes fluorescent after exposure to ROS. Fluorescence intensity in treated cells was expressed as a percentage of that in paired, untreated cells. BK (500 nM) caused a 51 +/- 16% increase in ROS generation (P < 0.001). Coincubation with either the BK B2-receptor blocker HOE-140 (5 microM) or the free radical scavenger N-(2-mercaptopropionyl)glycine (1 mM) prevented this increase, which confirms that the response was receptor mediated and ROS were actually being measured. Closing mitochondrial ATP-sensitive K+ (mitoKATP) channels with 5-hydroxydecanoate (5-HD, 1 mM) prevented increased ROS generation. BK-induced ROS generation was blocked by Nomega-nitro-m-arginine methyl ester (m-NAME, 200 microM), which implicates nitric oxide as an intermediate. Blockade of guanylyl cyclase with 1-H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10 microM) aborted BK-induced ROS generation but not that from diazoxide, a direct opener of mitoKATP channels. The protein kinase G (PKG) blocker 8-bromoguanosine-3',5'-cyclic monophosphorothioate (25 microM) eliminated the effects of BK. Conversely, direct activation of PKG with 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (100 microM) increased ROS generation (39 +/- 15%; P < 0.004) similar to BK. This increase was blocked by 5-HD. Finally, the nitric oxide donor S-nitroso-N-acetylpenicillamine (1 microM) increased ROS by 34 +/- 6%. This increase was also blocked by 5-HD. In intact rabbit hearts, BK (400 nM) decreased infarction from 30.5 +/- 3.0 of the risk zone in control hearts to 11.9 +/- 1.4% (P < 0.01). This protection was aborted by either 200 microM m-NAME or 2 microM ODQ (35.4 +/- 5.7 and 30.4 +/- 3.0% infarction, respectively; P = not significant vs. control). Hence, BK preconditions through receptor-mediated production of nitric oxide, which activates guanylyl cyclase. The resulting cGMP activates PKG, which opens mitoKATP. Subsequent release of ROS triggers cardioprotection.
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10.1152/ajpheart.00360.2003
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pubmed_343_11145
|
Maleamate amidohydrolase (NicF) is a key enzyme in vitamin B3 metabolism that catalyzes the hydrolysis of maleamate to produce maleic acid and ammonia. Unlike most members from the amidohydrolase superfamily it does not require a metal ion. Here, we use multiscale computational enzymology to investigate the catalytic mechanism, substrate binding, oxyanion hole, and roles of key active site residues of NicF from Bordetella bronchiseptica. In particular, molecular dynamics (MD) simulations, quantum mechanics/molecular mechanics (QM/MM) and QTAIM methods have been applied. The mechanism of the NicF-catalyzed reaction proceeds by a nucleophilic addition-elimination sequence involving the formation of a thioester enzyme intermediate (IC2 in stage 1) followed by hydrolysis of the thioester bond to form the products (stage 2). Consequently, the formation of IC2 in stage 1 is the rate-limiting step with a barrier of 88.8 kJ·mol-1 relative to the reactant complex, RC. Comparisons with related metal-dependent enzymes, particularly the zinc-dependent nicotinamidase from Streptococcus pneumonia (SpNic), have also been made to further illustrate unique features of the present mechanism. Along with -NH- donor groups of the oxyanion hole (i.e., HN-Thr146, HN-Cys150), the active site β-hydroxyl of threonine (HO-βThr146) is concluded to play a role in stabilizing the carbonyl oxygen of maleamate during the mechanism.
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10.1021/acs.jpca.9b05914
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pubmed_306_18121
|
BACKGROUND
Circumcision can be performed for a variety of techniques, including conventional dissection surgery or a Plastibell device, and has religious, ritual, or medical roots. In countries like Iran, circumcision is done purely on religious grounds. In this study, we outline 390 cases in our practice and describe the epidemiology, indications, surgical technique used, and the early complications.
MATERIALS AND METHODS
In this retrospective study, the charts for 390 circumcision cases were analyzed for the period March 2005 to August 2010. We reviewed all cases, noting age, indication, type of anesthesia used, technique, cosmetic appearance, and any potential early complications. All cases were followed up 1-4 weeks postoperatively and their notes were evaluated.
RESULTS
The age of children who underwent circumcision ranged from 3 weeks to 14 years, with a mean age of 4.25 years. The most common age for circumcision was 4-5 years (14.6%), and the least common age was 11-12 years (1.5%). In 372 cases (95%), the parents had opted for the procedure for religious reasons, and in 18 cases (5%), there was a medical indication, including phimosis (11 cases, 3%), urinary tract infection (5 cases, 1.2%), and balanoposthitis (2 cases, 0.8%). No major early complications were found in our series. Cosmetic appearance was satisfactory in all cases by 4 weeks after the operation.
CONCLUSION
Circumcision was performed for religious reasons in our cases, although medical indications sometimes modified the timing of the procedure. Conventional dissection surgery for circumcision was safe, effective, and without any major complications.
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10.2147/OAJU.S17913
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pubmed_411_18894
|
Bioelectric sensors lie, by definition, on the interface between biological elements and electronic circuits, irrespective of scale, manufacturing method, and working principle [...].
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10.3390/bios10080096
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pubmed_30_8561
|
The importance of a knowledge of statistical methods in relation to most aspects of dentistry is discussed. Definitions of terms used in descriptive statistical techniques are provided, together with a review of the techniques themselves.
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10.1038/sj.bdj.4806708
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pubmed_982_98
|
A procedure to map N-glycosylation sites is presented here. It can be applied to purified proteins as well as to highly complex mixtures. The method exploits deglycosylation by PNGase F in a diagonal, reverse-phase chromatographic setup. When applied to 10 microL of mouse serum, affinity-depleted for its three most abundant components, 117 known or predicted sites were mapped in addition to 10 novel sites. Several sites were detected on soluble membrane or receptor components. Our method furthermore senses the nature of glycan structures and can detect differential glycosylation on a given site. These properties--high sensitivity and dependence on glycan imprinting--can be exploited for glycan-biomarker analysis.
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10.1021/pr060186m
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pubmed_658_4987
|
PURPOSE
We determine if paternity is reduced among men with monorchidism (absent or removed testis) compared to men with unilateral cryptorchidism corrected during childhood by orchiopexy and controls. The group of men with an absent testis was determined among males presenting during childhood with only 1 descended testis.
MATERIALS AND METHODS
Data were obtained by medical record review and a detailed questionnaire. Only men who had been successful at or attempted paternity for whom we had complete data were included in the study from the entire cohort of 584 men with former cryptorchidism, 23 with absent testis, 26 treated with orchiectomy and 706 controls.
RESULTS
Percentages of men reporting success after attempting paternity did not differ among men with an absent testis (15 of 15, 100%), treated with orchiectomy (17 of 20, 85.0%), with corrected unilateral cryptorchidism (313 of 349, 89.7%) and controls (412 of 442, 93.2%). There was no difference for a subgroup of men with cryptorchidism judged to have an atrophic testis at orchiopexy (17 of 20, 85%) or those who underwent orchiectomy at initial attempted orchiopexy (8 of 10, 80%) and men who had subsequently undergone orchiopexy (9 of 10, 90.0%). Paternity was also not reduced in the group of men with only 1 testis (32 of 35, 91.4%) (monorchism plus orchiectomy) compared to either the corrected unilateral cryptorchid group or the control group. Of 637 testes 183 were recorded as impalpable on examination before surgery and 23 testes were absent, including 7 recorded as palpable. In fact, 12.1% (23 of 190) of testes that should have been recorded as impalpable were absent.
CONCLUSIONS
This study failed to indicate that paternity is diminished among men with a single testis compared with the general population, regardless of the origin of the loss. About 12% of unilateral impalpable testes judged to be impalpable on examination before surgery were found to be absent after surgical exploration.
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10.1097/01.ju.0000028222.74363.ad
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pubmed_828_16950
|
Biomass of cyanobacterial bloom from Lake Dianchi was used as a biosorbent for copper removal from aqueous solution. The maximum capacity was found at conditions of pH 4, initial concentration of copper was 10 mg/l and initial dose of biomass was 1.0 g/l. HNO(3) demonstrated the highest desorption efficiency compared with HCl, EDTA, and citric acid. Physical adsorption was assumed not to be the dominant mechanism of biosorption as revealed by scanning electron microscopy and surface area measurement of the biomass. Infrared ray spectra analysis of the biomass suggested that ion-exchange is the principal mechanism for biosorption. Considering the advantages-low cost, easy to collect, and huge in quantity-the Microcystis bloom biomass could be used as a sorbent for copper and other heavy metals removal.
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10.1007/s00284-010-9617-2
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pubmed_118_18047
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Background Neuropathic pain is one of the common complains of patients visiting neurology and orthopedic departments in hospitals. Management of neuropathic pain is difficult and is often symptomatic rather than being curative. Adherence to medication is necessary for pain management to be effective. However, there are various factors related to patient, physician, drug regimen and other socio-economic affecting adherence. Objective To study commonly prescribed drugs in neuropathic pain management and the medication adherence pattern including its associated factors. Method Patients already diagnosed as neuropathic pain were interviewed using structured questionnaire and data entered in Microsoft Office Excel 2007. Informed consent was taken from the patients. Result Among the 84 patients in the study, 69% were females. Majority 53.6% of patients had low back pain as cause of neuropathic pain. Anticonvulsants were mostly prescribed (75%) followed by non-steroidal anti-inflammatory drugs (52.4%) and Methylcobalamin (47.6%). More than 50% (n=49) patients were not adherent to the prescribed medication and majority (61.2%) of them were housewives. Significant association was observed between patient's adherence to gender, occupation, polypharmacy, drug regimen, cost and availability of medicine. Conclusion Anticonvulsants were commonly prescribed drugs in patients with neuropathic pain. Neuropathic pain was seen more in females with low back pain. Majority of patients were non-adherent and forgetfulness was the major reason for missing dose in them.
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pubmed_118_18047
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pubmed_644_5703
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As part of our attempt to develop a hybrid artificial liver support system using cultured hepatocytes, we investigated the long-term metabolic function of hepatocytes incubated in a packed-bed type reactor using reticulated polyvinyl formal (PVF) resin as a supporting material. Long-term (up to 1 week) perfusion culture experiments using the packed-bed reactor (20 mm i.d.) loaded with 500 PVF resin cubes (mean pore size 250 mum, 2 x 2 x 2 mm), together with conventional monolayer culture experiments as controls, were performed in serum-free or serum-containing medium. Ammonium metabolism and urea synthesis activities were evaluated quantitatively based on reaction kinetic analyses. Initial rates of ammonium metabolism and urea-N synthesis, as well as GPT enzyme activities, were adopted as indexes of the metabolic performance of the reactor and activities of the cultured hepatocytes.When serum-free medium was used in the perfusion cultures, ammonium metabolic and urea-N synthetic rates showed significant decay with elapse of the culture period, being less than 10% of those measured on day 1. This loss of activity was more prominent in the perfusion culture than in the monolayer cultures using this medium. In contrast, when serum-containing medium was used, approximately 50% of these activities obtained on day 1 were maintained even at the end of the cultures both in the perfusion and monolayer culture experiments.We concluded that the packed-bed reactor using PVF resin enabled high-density culture of hepatocytes, and showed a satisfactory ability to maintain the metabolic function of immobilized hepatocytes for relatively long periods of up to 1 week. This type of reactor is thus considered to represent a breakthrough in overcoming the difficulties involved in the development of a hybridtype artificial liver support system. (c) 1994 John Wiley & Sons, Inc.
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10.1002/bit.260430713
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pubmed_791_6748
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Sickle cell anemia (SCA) is the most common inherited hemolytic anemia worldwide. Here, we performed an exploratory study to investigate the systemic oxidative stress in children and adolescents with SCA. Additionally, we evaluated the potential impact of hydroxyurea therapy on the status of oxidative stress in a case-control study from Brazil. To do so, a panel containing 9 oxidative stress markers was measured in plasma samples from a cohort of 47 SCA cases and 40 healthy children and adolescents. Among the SCA patients, 42.5% were undertaking hydroxyurea. Multidimensional analysis was employed to describe disease phenotypes. Our results demonstrated that SCA is associated with increased levels of oxidative stress markers, suggesting the existence of an unbalanced inflammatory response in peripheral blood. Subsequent analyses revealed that hydroxyurea therapy was associated with diminished oxidative imbalance in SCA patients. Our findings reinforce the idea that SCA is associated with a substantial dysregulation of oxidative responses which may be dampened by treatment with hydroxyurea. If validated by larger prospective studies, our observations argue that reduction of oxidative stress may be a main mechanism through which hydroxyurea therapy attenuates the tissue damage and can contribute to improved clinical outcomes in SCA.
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10.1038/s41598-020-76075-5
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