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pubmed_659_11520 | A small minority of juveniles are responsible for the majority of detected juvenile crime in Ireland. This situation presents significant policy concerns. The current paper, based on findings from a comparative analysis builds on a multi-step research design process to provide evidence-based knowledge to inform the design of a new targeted intervention. An initial social network analysis of national crime and intelligence data produced localized basic criminal network maps illustrating co-offending and intelligence relationships between adults and juveniles in specific Police sub-districts (Part 1). These network maps then provided an enquiry frame for interviews with members of the police forces in three case study locations (Part 2). A comparative analysis of the three studies (Part 3) identified diversity in network structure and inherent resilience. The analysis also identifies core similarities in juveniles' vulnerabilities and risks to recruitment. These factors are important considerations for an intervention seeking to disrupt networks and create safe "exit" environments for juveniles. | 10.1177/0306624X221095043 |
pubmed_526_12973 | Military fathers of young children often endure repeated separations from their children, and these may disrupt the early parent-child relationship. Postdeployment reunification also poses challenges; disruptions that have occurred must often be repaired in the context of heightened emotions on the part of each family member at a time when fathers are themselves readjusting to the routines and responsibilities of family life. The current study employed qualitative research with the central aim of informing a richer understanding of these experiences. Interviews were conducted with 14 military fathers of young children who had experienced separation from their families during deployment. Narratives were coded using principles of grounded theory, and common parenting themes were extracted. Fathers shared their hopes that their young children would develop qualities of strength, confidence, and self-sufficiency. They also discussed difficulty in supporting the development of these qualities in their young children due to problems dealing with the negative emotions and difficult behaviors that their children exhibited. Reliance on their parenting partner was commonly cited as an effective strategy as fathers transitioned back to family life. Implications for intervention programs include the provision of parenting and self-care skills and inclusion of the father's parenting partner in the intervention. | 10.1002/imhj.21465 |
pubmed_761_5780 | The prevalence of vitamin D deficiency in intensive care units ranges typically between 40 and 70%. There are many reasons for being or becoming deficient in the ICU. Hepatic, parathyroid and renal dysfunction additionally increases the risk for developing vitamin D deficiency. Moreover, therapeutic interventions like fluid resuscitation, dialysis, surgery, extracorporeal membrane oxygenation, cardiopulmonary bypass and plasma exchange may significantly reduce vitamin D levels. Many observational studies have consistently shown an association between low vitamin D levels and poor clinical outcomes in critically ill adults and children, including excess mortality and morbidity such as acute kidney injury, acute respiratory failure, duration of mechanical ventilation and sepsis. It is biologically plausible that vitamin D deficiency is an important and modifiable contributor to poor prognosis during and after critical illness. Although vitamin D supplementation is inexpensive, simple and has an excellent safety profile, testing for and treating vitamin D deficiency is currently not routinely performed. Overall, less than 800 patients have been included in RCTs worldwide, but the available data suggest that high-dose vitamin D supplementation could be beneficial. Two large RCTs in Europe and the United States, together aiming to recruit >5000 patients, have started in 2017, and will greatly improve our knowledge in this field. This review aims to summarize current knowledge in this interdisciplinary topic and give an outlook on its highly dynamic future. | pubmed_761_5780 |
pubmed_573_5400 | UNLABELLED
Physical therapist practice is grounded in patient management principles encompassing all body systems and focuses on prevention, education, and functional outcomes. As such, management of the integumentary system crosses all practice settings, emphasizing the importance that basic integumentary content be adequately addressed during entry-level education.
PURPOSE
The purpose of this qualitative study was to compare the self-reported integumentary knowledge and skill of recent graduates to profession-determined expectations for education.
SUBJECTS
Participants were 7 licensed physical therapists experienced in wound management.
METHODS
Semi-structured interview data were recorded, transcribed, and coded. A matrix compiling professional expectations for integumentary education was utilized to identify topics as absent, covered only briefly, or covered only during clinical rotations.
RESULTS
Compression, vascular screening, infection, factors impacting healing, modalities, dressings, wound measurements, topicals, and sutures/staples were among the most commonly reported areas of deficiency.
DISCUSSION
While integumentary care makes up a small percentage of physical therapy practice, it is a significant part of a comprehensively educated therapist. This study found participants did not perceive themselves to have received the minimum entry-level integumentary knowledge and skill deemed necessary by the profession. Study results are supported by current literature and demonstrate the need for integumentary curriculum review in entry-level programs. | pubmed_573_5400 |
pubmed_600_19000 | We consider clustering of particles in the lattice gas model above the critical point. We find the probability for large density fluctuations over scales much larger than the correlation length. This fundamental problem is of interest in various biological contexts such as quorum sensing and clustering of motile, adhesive, cancer cells. In the latter case, it may give a clue to the problem of growth of recurrent tumors. We develop a formalism for the analysis of this rare event employing a phenomenological master equation and measuring the transition rates in numerical simulations. The spontaneous clustering is treated in the framework of the eikonal approximation to the master equation. | 10.1103/PhysRevE.90.062702 |
pubmed_653_3129 | AIM
EPCs were cultured in high-glucose-medium to induce oxidative stress. Concentration of malonaldehyde (MDA) and nitrogen monoxidum (NO) in culture medium were measured. The function of EPCs and protein expression of GPx-1 and eNOS were determined. Antioxidant alpha lipoic acid (ALA) was used as an intervention factor to explore the mechanism by which glucose induces the damage of EPCs.
METHODS
EPCs were isolated and cultured from 15 Wistar rats (180-200 g). After planted for 4 days and 24 hours of attachment, cells were treated in 3 conditions: normal control group (NC) were cultured with 5 mmol/L glucose; high-glucose group (HS) were cultured with 30 mmol/L glucose; ALA group were cultured with 30 mmol/L glucose+ ALA(40 μg/L). Protein and gene expression of GPx-1 and eNOS were determined by Western blot and reverse transcription(RT-PCR); NO, MDA levels in culture medium were measured after 48 hours of treatment.
RESULTS
(1) Effect of different treatment on the secretion of MDA in EPCs: MDA levels in medium treat with high glucose (HS group) after 48h was significantly higher than that in NC group (P<0.05) and decreased after ALA intervention. (2) Effect of different treatment on the protein expression of GPx-1 in EPCs: Protein expression of GPx-1 was significantly lower in EPCs treated with high glucose than that in NC group after 48 hours of treatment while significantly normalized after ALA intervention (P<0.05). (3) Effect of different treatment on eNOS expression and NO secretion: eNOS expression was significantly lower in EPCs treated with high glucose than that in NC group after 48 hours of treatment (P<0.05). NO levels in medium was lower in HS group than in NC group (P<0.05). eNOS expression and NO level were increased after ALA intervention compared with HS group(P<0.05).
CONCLUSION
High-glucose culture induces oxidative stress in EPCs, EPCs cultured in high-glucose medium displays an impaired function shown as an lower anti-oxidative capacity, decreased eNOS expression and NO secretion, Impaired anti-oxidative capacity and NO secretion by high-glucose treatment can be improved by ALA intervention. | pubmed_653_3129 |
pubmed_902_23327 | BACKGROUND
Proteins have long been considered a principal target for oxidants as a result of their abundance in biological systems. However, there is increasing evidence about the significant antioxidant activity in proteins such as albumin. It is leading to new concepts that even consider albumin not only as an antioxidant but as the major antioxidant in plasma known to be exposed to continuous oxidative stress. Evidence presented here establishes a previously unrecognized relationship between proteins' antioxidant capacity and structural stress.
METHODOLOGY/PRINCIPAL FINDINGS
A chemiluminiscence based antioxidant assay was achieved to quantify the antioxidant capacity of albumin and other proteins. The capabilities of proteins as antioxidants were presented, but in addition a new and powerful component of the protein antioxidant capacity was discovered. The intrinsic component, designated as Response Surplus (RS), represents a silent reserve of antioxidant power that awakens when proteins face a structural perturbation (stressor) such as temperature, short wave UV light, the same reactive oxygen species, and more extreme changes like glucose or aldehyde-mediated structural modifications. The work also highlights the importance of structural changes in protein antioxidant properties and the participation of sulfhydryl groups (SHs) in the RS antioxidant component. Based on recent evidence about the SH group chemistry, a possible model for explaining RS is proposed.
CONCLUSIONS/SIGNIFICANCE
The data presented show the significant antioxidant behavior of proteins and demonstrate the existence of a previously unrecognized antioxidant response to the stress. Several implications, including changes in elementary concepts about antioxidants and protein function, should emerge from here. | 10.1371/journal.pone.0008971 |
pubmed_762_3952 | Tibial pilon fractures are difficult to manage because of their severity. These injuries are frequently open and contaminated, with marked comminution of the articular surface and metaphysis. The results of open reduction and internal fixation are dependent on the severity of the initial injury and the quality and stability of the reduction. The literature reports numerous complication rates associated with open reduction and internal fixation of pilon fractures. The Ilizarov technique of external fixation has fewer complications, and allows restoration of joint surfaces, reconstruction of length, and alignment of the extremity while maintaining a sufficient range of joint motion. Two cases of pilon fractures in which the Ilizarov method was utilized are reported, along with a review of the literature. | pubmed_762_3952 |
pubmed_644_23446 | Giant tonsillolith is a rare clinical entity. Commonly, it occurs between 20-77 years of age. We had a twelve years old female patient, who had odynophagia due to a giant tonsillolith. The stone was removed and tonsillectomy was performed. We reviewed the literature on this rare clinical entity and found that this is the fourth case of giant tonsillolith in a child and largest ever tonsillolith to be reported in English literature. | 10.1186/1757-1626-1-50 |
pubmed_501_1909 | We have studied the pharmacokinetics of orally administered chlorambucil and melphalan in patients with hematologic malignancies and solid tumors. With a standard oral dose of 0.6 mg/kg, chlorambucil showed much more rapid systemic appearance than did melphalan and had a mean peak plasma concentration and area under the plasma disappearance curve which was 3-4 times greater than that observed in patients receiving melphalan. Melphalan had extremely variable systemic availability which was not observed with chlorambucil, and was not related to problems in tablet formulation. Chlorambucil undergoes extensive active metabolism to phenylacetic acid mustard, whereas melphalan undergoes rapid chemical degradation and has little, if any, active metabolism. On a pharmacokinetic basis, chlorambucil's greater in vitro stability, its more rapid and predictable systemic availability after oral dosing, and its extremely low urinary excretion make it a more predictable alkylating agent for clinical use than melphalan, especially for patients with reduced renal function. | 10.1007/978-3-642-81488-4_16 |
pubmed_126_7051 | PURPOSE/OBJECTIVES
To describe the development and evaluation of a documentation tool for chemotherapy and infusion therapy for an outpatient oncology setting.
DATA SOURCES
Journal articles, documentation tools, and cancer chemotherapy guidelines.
DATA SYNTHESIS
Greater demands and expansion of treatments and procedures in the outpatient setting have necessitated documentation methods that conserve time, accommodate documentation of a variety of therapies, and communicate ongoing monitoring and evaluation of care. Flow sheet documentation is an acceptable documentation method that has been used extensively to meet these objectives.
CONCLUSIONS
Use of this flow sheet has improved the quality and accommodated the scope of infusion therapy in the authors' setting. Documentation time has decreased, and standardization of documentation has occurred.
IMPLICATIONS FOR NURSING PRACTICE
Nurses can use the flow sheet to document concisely chemotherapy and infusion therapy administration over a period of time. It also provides for continuity in patient assessment and education through easy accessibility of this information within the patient's chart. | pubmed_126_7051 |
pubmed_213_15588 | Feeding young rats an Mg-deficient diet for 4 weeks increased serum-Fe concentration from 38.2 to 43.7 mumol/L and non Hb-Fe content in liver from 6.33 to 9.31 mmol/kg dry weight. The increase in non Hb-Fe occurred in all liver cell fractions. In heart and kidney, Fe content was not significantly changed by Mg deficiency. Lipid peroxidation measured by formation of malondialdehyde was only increased in liver mitochondria from Mg-deficient rats. Therefore, an Mg-deficiency-induced increase in non Hb-Fe may be involved in the increased lipid peroxidation of liver mitochondria, but cannot represent a general mechanism in the toxicity of Mg deficiency. | pubmed_213_15588 |
pubmed_349_6580 | Antipsychotic medications are increasingly prescribed to pediatric and adolescent patients with psychotic diseases in spite of limited knowledge on the long-term effects of dissimilar antipsychotic drugs on developing brain. In this study, we quantified the levels of two major serotonin 5-HT1A , and 5-HT2A receptors in brain regions of developing rats after 3 weeks of treatment with typical (fluphenazine) and atypical (clozapine and olanzapine) antipsychotics, and compared to similarly treated adult rats treated with olanzapine, risperidone, and quetiapine examined in previous studies. Fluphenazine, clozapine, and olanzapine all increased 5-HT1A receptors in medial prefrontal cortex (MPC) and dorsolateral frontal cortex (DFC) of juvenile and adult rats. Clozapine and olanzapine also increased 5-HT1A labeling in hippocampal CA1 and CA3 regions of juvenile but not adult animals. Repeated treatments with clozapine and olanzapine, but not fluphenazine, decreased 5-HT2A receptors in MPC and DFC in developing and mature animals. In addition, both clozapine and olanzapine selectively reduced 5-HT2A labeling in hippocampal CA1 and CA3 regions of juvenile animals. These findings suggest that forebrain 5-HT receptor subtypes in juvenile animals are more sensitive than adults to the long-term effects of antipsychotic drugs, which may account for differences in clinical effects of antipsychotic drugs between young vs. adult psychiatric patients. | 10.1002/syn.21988 |
pubmed_54_20186 | There is a long-standing debate regarding the functional organization of motor cortex. Intracortical microstimulation (ICMS) studies have provided two contrasting views depending on the duration of stimulation. In the rat, short-duration ICMS reveals two spatially distributed forelimb movement representations, the rostral forelimb area (RFA) and caudal forelimb area (CFA), eliciting identical movements. In contrast, long-duration ICMS reveals spatially distributed, complex, multijoint movement areas, with grasping found exclusively in the rostral area and reach-shaping movements of the arm located in the caudal area. To provide corroboration for which interpretation is correct, we selectively inactivated the RFA/grasp area during the performance of skilled forelimb behaviors using a reversible cortical cooling deactivation technique. A significant impairment of grasping in the single-pellet retrieval task and manipulations of pasta was observed during cooling deactivation of the RFA/grasp area, but not the CFA/arm area. Our results indicate a movement-based, rather than a muscle-based, functional organization of motor cortex, and provide evidence for a conserved homology of independent grasp and reach circuitry shared between primates and rats. | 10.1523/JNEUROSCI.2500-14.2014 |
pubmed_432_13631 | Twenty-four patients with asthma of suspected allergic origin were subjected to a total of twenty-five bronchial provocations with the relevant allergen. Eighteen of them reacted with bronchial obstruction: eleven with an isolated early reaction, five with a dual reaction and two with only a late reaction. Extensive lung function tests were performed. The patterns of early and late reactions were qualitatively very similar regarding variables of pulmonary physiological function, but there were quantitative differences. Patients with dual reactions showed significantly greater changes in FEV1, RV and TGV during the early response than those with isolated early reactions. Maximum mid-expiratory flow rates with the patients breathing air and a mixture of He and O2 were measured before and 6 hr after the challenges. Four of five patients with both an immediate and a late response showed a decrease in the response to helium during the latter phase, suggesting increasing involvement of the small airways. An increase in the slope of the alveolar plateau (phase III) was observed in four of the five patients with dual responses and all five had increased CC%. It was concluded that the changes in pulmonary function occurring during the dual responses were widespread, involving the airways generally and resembling those in the clinically more severe asthma. Usually, individuals with dual reactions showed stronger reactions. In two cases, however, a late reaction was obtained without any preceding early reaction. | 10.1111/j.1365-2222.1986.tb00754.x |
pubmed_0_6773 | We describe ground states of correlated electron systems in which the electron fractionalizes into separate quasiparticles which carry its spin and its charge, and into real Majorana fermions which carry its Fermi statistics. Such parent states provide a unified theory of previously studied fractionalized states: their descendants include insulating and conducting states with neutral spin S=1/2 fermionic spinons, and states with spinless fermionic charge carriers. We illustrate these ideas on the honeycomb lattice, with field theories of such states and their phase transitions. | 10.1103/PhysRevLett.105.057201 |
pubmed_187_2895 | Collapsin-1, a member of the semaphorin family, activates receptors on specific growth cones, thereby inhibiting their motility. Neuropilin, a previously cloned transmembrane protein, has recently been identified as a candidate receptor for collapsin-1. We have completed the cloning of chick collapsin-3 and -5 and show that collapsin-1, -2, -3, and -5 bind to overlapping but distinct axon tracts. We infer that in situ, there are distinct receptors with different affinities for collapsin-1, -2, -3, and -5. In contrast, these four collapsins all bind recombinant neuropilin with similar affinities. Strong binding to neuropilin is mediated by the carboxy third of the collapsins, while the semaphorin domain confers their unique binding patterns in situ. We propose that neuropilin is a common component of a semaphorin receptor complex, and that additional differentially expressed receptor components interact with the semaphorin domains to confer binding specificity. | 10.1016/s0896-6273(00)80370-0 |
pubmed_697_12236 | Importance
Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has a favorable prognosis, and p16 immunohistochemistry is a surrogate marker of high-risk HPV infection and strong prognosticator. Given this favorable prognosis, treatment de-escalation for p16-positive OPSCC is now being considered with the goal of decreasing treatment-associated morbidity without compromising tumor control. The role of adjuvant chemotherapy in this setting is becoming increasingly unclear.
Objective
To compare survival between surgically managed patients with p16-positive OPSCC who received adjuvant chemoradiotherapy and patients who received adjuvant radiotherapy alone.
Design, Setting, and Participants
This was a cohort study of patients with OPSCC diagnosed from June 1996 to June 2010, with follow-up through December 2014, at a single tertiary referral center. One hundred ninety-five surgically managed, p16-positive patients without a history of head and neck cancer or distant metastasis at time of diagnosis were included.
Exposures
Patients were dichotomized into adjuvant radiotherapy and adjuvant chemoradiotherapy groups.
Main Outcomes and Measures
Overall survival was the primary outcome, and disease-free survival was the secondary outcome. Propensity-weighted multivariate Cox proportional hazards analysis was conducted to quantify the effect of adjuvant chemotherapy on survival.
Results
The study included 195 patients with p16-positive, surgically managed OPSCC. Median duration of follow-up was 87 months (interquartile range, 68-116 months). Ninety patients received adjunct chemoradiotherapy (mean age, 54.3 years), 88 patients received adjuvant radiotherapy (mean age, 56.4 years), and 17 patients received surgery alone. The 5-year overall survival rate for patients who received adjuvant chemoradiotherapy was 82% (95% CI, 73%-90%) and 84% (95% CI, 76%-91%) for patients who received adjuvant radiotherapy alone. The 5-year disease-free survival rate for patients who received adjuvant chemoradiotherapy was 79% (95% CI, 71%-88%) and 79% (95% CI, 70%-88%) for patients who received radiotherapy alone. After weighting cases by the inverse probability of receiving adjuvant chemotherapy and controlling for age, comorbidity, smoking, pathological T stage, and pathological N stage, the receipt of adjuvant chemotherapy was not significantly associated with disease-free survival (adjusted hazard ratio, 0.91; 95% CI, 0.59-1.42) but was associated with a statistically insignificant yet clinically meaningful increase in all-cause mortality (adjusted hazard ratio, 1.46; 95% CI, 0.91-2.33).
Conclusions and Relevance
Among patients with p16-positive OPSCC managed surgically with adjuvant radiotherapy, the addition of adjuvant chemotherapy provided no additional disease-free survival benefit and was associated with worse overall survival. These results should help inform future clinical trials aiming to deescalate treatment for p16-positive patients. | 10.1001/jamaoto.2016.3353 |
pubmed_51_554 | In situ surface enhanced infrared absorption spectroscopy (SEIRAS) with an attenuated total reflection (ATR) configuration has been used to monitor the adsorption kinetics of bovine hemoglobin (BHb) on a Au nanoparticle (NP) film. The IR absorbance for BHb molecules on a gold nanoparticle film deposited on a Si hemispherical optical window is about 58 times higher than that on a bare Si optical window and the detection sensitivity has been improved by 3 orders of magnitude. From the IR signal as a function of adsorption time, the adsorption kinetics and thermodynamics can be explored in situ. It is found that both the electrostatic interaction and the coordination bonds between BHb residues and Au NP film surface affect the adsorption kinetics. The maximum adsorption can be obtained in solution pH 7.0 (close to the isoelectric point of the protein) due to the electrostatic interaction among proteins. In addition, the isotherm of BHb adsorption follows well the Freundlich adsorption model. | 10.1021/la300819u |
pubmed_394_19546 | OBJECTIVE
This study had for aim to evaluate practices and knowledge of infectious hazards, to determine the prevalence of viral infections related to occupational blood exposure among health care workers, and to propose a preventive policy.
DESIGN
This descriptive multicentric and transversal epidemiological survey was carried out from 2003 to 2004 in 10 Moroccan cities. Two thousand eight hundred and forty four persons were contacted and 2086 accepted to answer the questionnaire (73.3 %).
RESULTS
The mean age was 40.8+/-7.8 years and seniority 15.6+/-7.4 years. Blood was the most incriminated product (96.1%), followed by dirty linen and hospital waste. Instruments most often mentioned as dangerous were hollow needles (80.3%). The most feared infections were viral hepatitis (77.5%) and HIV (89.3%). Only 40.6% of the personnel were adequately vaccinated against hepatitis B. Post-vaccine serology was performed on only 1.8% of the vaccinated staff. During the last 12 months, 58.9% of the personnel underwent at least one occupational blood exposure 5.8% of which was reported. Universal precautions appeared poorly used as only 65.6% wore gloves for invasive acts and 61.5% correctly disinfected their hands. Re-sheathing used needles was frequent (51.2%).
CONCLUSIONS
Infectious hazards in healthcare facilities are not sufficiently taken into account: the recent creation of occupational health services in hospital facilities should contribute to improve working conditions, make hepatitis B vaccination available and mandatory, and lead to more information and education on hazards related to occupational blood exposure for healthcare personnel. | 10.1016/j.medmal.2008.09.009 |
pubmed_781_6229 | Statins, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, are potential drugs for chronic heart failure treatment in clinical studies. However, there may be differences in the effects on heart failure between lipophilic and hydrophilic statins. In this study, we investigated whether hydrophilic rosuvastatin (RSV) and lipophilic pitavastatin (PTV) exert different effects on the left ventricular diastolic function. Subjects were hypercholesterolemia patients with left ventricular diastolic dysfunction. This was an open-label, randomized, parallel, comparative, prospective study. The subjects received treatment with RSV or PTV for 24 weeks, and their low density lipoprotein (LDL)-cholesterol levels were controlled by these statins according to the guideline. The primary endpoint was defined as the change in left ventricle (LV) diastolic function (E/E') estimated by echocardiography, and the secondary endpoint was the plasma B-type natriuretic peptide (BNP) level. No serious adverse effects were observed during the entire study period in any patient, nor were there any significant differences in changes in the body mass index, blood pressure, or heart rate. Statin treatment did not significantly alter the primary endpoint, E/E'. The change ratio of BNP was not significantly different between PTV and RSV groups. However, BNP was significantly increased in the RSV (p=0.030) but not the PTV (p>0.999) group. This study revealed that although neither RSV nor PTV improved LV diastolic dysfunction, BNP, a biomarker of LV wall stress, was increased in the RSV but not the PTV group. Observation for a longer period is necessary to clarify the different effects of these statins on LV diastolic dysfunction. (UMIN-ID: UMIN000003571). | 10.1248/bpb.b15-00126 |
pubmed_746_7408 | In this study, the affinity of two different cell types toward a specific cell binding sequence (Gly-Phe-Hyp-Gly-Glu-Arg or GFOGER) derived from type I collagen using peptide template (PT)-assembled collagen peptides of different triple helicity as a model for natural collagen is examined. A series of biophysical studies, including melting curve analysis and circular dichroism spectroscopy, demonstrated the presence of stable triple-helical conformation in the PT-assembled (GPO)3-GFOGER-(GPO)3, (GPO)-GFOGER-(GPO), and (Pro-Hyp-Gly)5 solution. Conversely, non-templated peptides, except (GPO)3-GFOGER-(GPO)3, showed no evidence of assembly into triple-helical structure. Biological assays, including cell adhesion, competitive inhibition, and immunofluorescence staining, revealed a correlation of triple-helical conformation with the cellular recognition of GFOGER in an integrin-specific manner. The triple helix was shown to be important, but not crucial for cell adhesion to native collagen. Hep3B and L929 cells displayed significant differences in the recognition of GFOGER, mainly because of the differences in their expression of specific integrin receptors for collagen. For example, PT-assembled (GPO)3-GFOGER-(GPO)3 was shown to perform comparably to collagen for L929, but not Hep3B, cell adhesion. The result showed that a specific cell binding motif may not fully mimic the extracellular matrix (ECM) microenvironment, suggesting the need to use a combination of two or more cell binding sequences for targeting a wide range of integrin receptors expressed by a specific cell type to better mimic the ECM. | 10.1021/bm700587j |
pubmed_632_17602 | Cancer continues to be one of the major causes of death worldwide. Despite many advances in the understanding of this complex disease, new approaches are needed to improve the efficacy of current therapeutic treatments against aggressive tumors. Natural products are one of the most consistently successful sources of drug leads. In recent decades, research activity into the clinical potential of this class of compounds in cancer has increased. Furthermore, a highly promising field is the use of metals and their complexes in the design and development of metal-based drugs for the treatment of cancer. Metal complexes offer unique opportunities due to their ability to alter pharmacology, improving the efficacy and/or reducing the negative side effects of drug molecules. In addition, transition metals as copper, iron, and manganese, among others, can interact with active sites of enzymes, playing important roles in multiple biological processes. Thus, these complexes not only possess higher activities but also reach their targets more efficiently. This review article highlights recent advances on the emerging and expanding field of metal-based drugs. The emphasis is on new therapeutic strategies consisting of metal complexes with natural product like-compounds as a starting point for the rational design of new antitumor agents. | 10.2174/1871520618666180420165821 |
pubmed_240_24461 | BACKGROUND
Obesity is a risk factor for colorectal cancer, and colonoscopy can be technically challenging in obese patients. It has been proposed (with little supporting data) that prone positioning of obese patients might facilitate a difficult colonoscopy.
AIM
The aim of this study was to determine if starting colonoscopy in the prone position for obese patients decreases cecal intubation times.
METHODS
This was a prospective, randomized study conducted at the North Texas VA Medical Center. Patients with a body mass index of ≥30 kg/m(2) undergoing elective colonoscopy were randomized 1:1 to either initial prone positioning or standard, left-lateral positioning. The outcome measurements were cecal intubation time, frequency of repositioning, sedative medications used, reports of pain, complications, and procedure tolerability.
RESULTS
Fifty patients were randomized to have colonoscopy starting in the standard, left-lateral decubitus position, and 51 to the prone position. The average cecal intubation time for the standard group was 550 vs. 424 s in the prone group (p = 0.03). Patient repositioning was used in 28 % of patients in the standard group versus 8 % in the prone group (p = 0.009). There was no difference in subjective reports of pain between groups (p = 0.95) or in average pain scores (p = 0.79). Follow-up interviews were conducted in 93 % of patients, all of whom said that they would be willing to have repeat colonoscopy in the same position.
CONCLUSIONS
Performance of colonoscopy in the prone position for obese patients results in significantly shorter cecal intubation times and decreased need for patient repositioning. Prone positioning is well accepted and does not significantly increase procedure-related discomfort. | 10.1007/s10620-012-2468-x |
pubmed_869_995 | Pulmonary hypertension (PH) is a fatal disease characterized by endothelial dysfunction, hypercontraction and proliferation of vascular smooth muscle cells, and migration of inflammatory cells for which no satisfactory treatment has yet been developed. It has been recently demonstrated that Rho-kinase, an effector of the small GTPase Rho, is involved in the pathogenesis of arteriosclerosis and that long-term inhibition of Rho-kinase markedly ameliorates monocrotaline-induced PH in rats. However, it remains to be examined whether direct inhibition of Rho-kinase also ameliorates PH with a different etiology and whether endothelial nitric oxide synthase (eNOS) is involved in the beneficial effects of Rho-kinase inhibition. This study was designed to address those 2 important issues in a hypoxia-induced PH model using wild-type (WT) and eNOS-deficient (eNOS) mice. Long-term blockade of Rho-kinase with fasudil (100 mg/kg/d) for 3 weeks markedly improved PH and right ventricular hypertrophy in WT mice with a lesser but significant inhibition noted in eNOS mice. Fasudil upregulated eNOS with increased Akt phosphorylation in WT but not in eNOS mice. These results suggest that long-term inhibition of Rho-kinase also ameliorates hypoxia-induced PH in mice, for which eNOS activation may partially be involved. | 10.1097/01.fjc.0000248244.64430.4a |
pubmed_483_19972 | The present work aim to develop pH responsive nanosystem comprising lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes for the effective treatment of lung cancer. FTIR results showed that, compatibility nature of selected excipients for the synthesis of LF-CaP-Cs. The XRD results showed developed LF-CaP-Cs were non crystalline in nature. The selected developed LF-CaP-Cs were in cubic phase with average particle size of 259.4 ± 19 nm with a charge of -2.28 ± 0.7 mV. The encapsulation efficiency for LF within LF-CaP-Cs was about 78.76 ± 0.5%. RP-HPLC analysis showed that LF release rate gets significantly enhanced with higher peak area at pH 4.0 compared to pH 5.0/pH 7.4. The in-vitro release of LF-CaP-Cs showed that LF release gets significantly increased at pH 4.0 (84.04 ± 0.4%) compared to pH 7.4 (48.32 ± 1.6%) at 12 h. Further, CAM assay showed the superior anti-angiogenesis potential of developed LF-CaP-Cs compared to LF-Cs/blank Cs. The cytotoxicity effect of LF-CaP-Cs (28 ± 1.8 μg/mL) was significantly higher than that of free LF (40 ± 0.9 μg/mL). The results of cellular uptake study proved the localization of LF at cellular level and AO/EB staining results revealed that the A549 cell undergoes apoptosis in A549 cells. | 10.1016/j.chemphyslip.2019.03.016 |
pubmed_842_23557 | BACKGROUND AND OBJECTIVES
The incidence of inflammatory heart diseases is not yet as high as those of other cardiovascular diseases; however, inflammatory heart diseases do have relatively high mortality rate. Therefore, update information on the economic burden of inflammatory heart diseases are necessary in order to appropriate policy making on these diseases.
MATERIALS AND METHODS
This study used a number of resources to obtain data, national health insurance statistics, the Korean Health Panel, and the causes of death report by the Korean National Statistical Office. The total costs of inflammatory heart diseases were estimated as the sum of direct medical care costs, direct non-medical care and indirect costs.
RESULTS
The total direct cost of inflammatory heart disease was higher in Korean men than that of Korean women and cost due to inpatient was higher than that of outpatients cost. The costs to cover premature death were highest among all of the components used to determine the total costs for inflammatory heart disease, representing 66.3% of these costs in Korea.
CONCLUSION
Inflammatory heart disease has a relatively high mortality rate, and the costs that are associated with premature deaths consume the greatest proportion of the costs associated with this disease. In spite of some limitations of study, this could be a reliable evidence of economic burden of inflammatory heart disease. | 10.4070/kcj.2011.41.12.712 |
pubmed_362_25802 | The potential climate change impacts of the development in Chinese household waste management, with less landfilling, more incineration with energy recovery, and source-separated food waste treated in biorefineries, were assessed through a life cycle assessment. When the waste management system interacts with a fossil-based energy system, landfilling produces a load of 144 kg CO2-eq/ton wet waste, while incineration shows a saving of 36 kg CO2-eq/ton wet waste. The introduction of food waste source separation lowers climate change impacts by an additional 33 kg CO2-eq/ton at a 60% sorting efficiency. As the Chinese energy system lowers its climate change impact over the next 30 years, energy recovery from waste treatment will change its relative contribution to climate change. In nonfossil energy systems, landfilling is estimated to have a climate change load of 180-240 kg CO2-eq/ton wet waste, while incineration, including combinations with the source-separation of food waste, will have a load of 310-540 kg CO2-eq/ton wet waste. These large intervals are due to waste composition uncertainty. However, considering a 20 year CH4 characterization factor representing a shorter time perspective, the impacts from landfilling are more dramatic due to the large methane release. This significant climate change impact calls for an increased focus on the developments in Chinese household waste management. The key issues identified may also apply to other countries. | 10.1021/acs.est.1c07921 |
pubmed_788_7454 | OBJECTIVE
Hox genes are involved in hematopoietic lineage commitment and differentiation. In this study, we investigated the roles of Hoxb3 in hematopoiesis by examining the phenotypes of a Hoxb3 knockout mutant mouse line.
RESULTS
Despite previous reports describing the apparently normal phenotype of these mutant mice, we found that by 6 months of age, Hoxb3(-/-) mice began to exhibit significantly impaired B lymphopoiesis in the bone marrow (BM). The cellularity was reduced by 30% in mutant BM compared to age- and sex-matched heterozygous and wild-type controls. The population size of B220(+)CD43(+) progenitor B cells showed a twofold reduction while that of B220(+)CD43(-)IgM(-) precursor B cells was decreased fivefold. Sorting-purified Hoxb3(-/-) progenitor B cells displayed significantly reduced proliferative response to IL-7 in culture, consistent with our findings of reduced IL-7 receptor expression in Hoxb3(-/-) progenitor B cells. However, the peripheral B cell pool in the spleen of Hoxb3(-/-) mice was maintained with a similar size as in wild-type littermates.
CONCLUSION
Analysis of T-cell development in the thymus and B1 cell compartment in the peritoneal cavity showed no significant changes. Thus, our findings suggest that the Hoxb3 gene plays an essential role in regulating B lymphopoiesis in the BM of adult mice. | 10.1016/j.exphem.2006.10.014 |
pubmed_878_6798 | Polyploidy or whole-genome duplication is recurrent in plant evolution, yet only a small fraction of whole-genome duplications has led to successful speciation. A major challenge in the establishment of nascent polyploids is sustained karyotype instability, which compromises fitness. The three putative diploid progenitors of bread wheat, with AA, SS (S ∼ B), and DD genomes occurred sympatrically, and their cross-fertilization in different combinations may have resulted in fertile allotetraploids with various genomic constitutions. However, only SSAA or closely related genome combinations have led to the speciation of tetraploid wheats like Triticum turgidum and Triticum timopheevii. We analyzed early generations of four newly synthesized allotetraploid wheats with genome compositions S(sh)S(sh)A(m)A(m), S(l)S(l)AA, S(b)S(b)DD, and AADD by combined fluorescence and genomic in situ hybridization-based karyotyping. Results of karyotype analyses showed that although S(sh)S(sh)A(m)A(m) and S(l)S(l)AA are characterized by immediate and persistent karyotype stability, massive aneuploidy and extensive chromosome restructuring are associated with S(b)S(b)DD and AADD in which parental subgenomes showed markedly different propensities for chromosome gain/loss and rearrangements. Although compensating aneuploidy and reciprocal translocation between homeologs prevailed, reproductive fitness was substantially compromised due to chromosome instability. Strikingly, localized genomic changes in repetitive DNA and copy-number variations in gene homologs occurred in both chromosome stable lines, S(sh)S(sh)A(m)A(m) and S(l)S(l)AA. Our data demonstrated that immediate and persistent karyotype stability is intrinsic to newly formed allotetraploid wheat with genome combinations analogous to natural tetraploid wheats. This property, coupled with rapid gene copy-number variations, may have laid the foundation of tetraploid wheat establishment. | 10.1073/pnas.1319598110 |
pubmed_93_3628 | Community support services (CSSs) have been developed in Canada and other Western nations to enable persons coping with health or social issues to continue to live in the community. This study addresses the extent to which awareness of CSSs is structured by the social determinants of health. In a telephone interview conducted in February-March 2006, 1152 community-dwelling older adults (response rate 12.4%) from Hamilton, Ontario, Canada were made to read a series of four vignettes and were asked whether they were able to identify a CSS they may turn to in that situation. Across the four vignettes, 40% of participants did name a CSS as a possible source of assistance. Logistic regression was used to determine factors related to awareness of CSSs. Respondents most likely to have awareness of CSS include the middle-aged and higher-income groups. Being knowledgeable about where to look for information about CSSs, having social support and being a member of a club or voluntary organisations are also significant predictors of awareness of CSSs. Study results suggest that efforts be made to improve the level of awareness and access to CSSs among older adults by targeting their social networks as well as their health and social care providers. | 10.1111/j.1365-2524.2011.01013.x |
pubmed_49_19541 | The new imaging procedures should improve the preoperative assessment of patients with renal pelvis carcinoma. At the Department of Urology, University of Freiburg from 1976-1986 48 patients with renal pelvis carcinoma were treated. 92% of tumors (69% looked like renal pelvis carcinoma preoperatively, 23% like kidney tumors without histological determination) were detected preoperatively. Advanced tumor stages (T4N+M1) (21%) were diagnosed correctly in 7/10 cases preoperatively and have a poor prognosis. | pubmed_49_19541 |
pubmed_341_69 | BACKGROUND AND OBJECTIVES
Neonatal jaundice is one of the most prevalent clinical conditions requiring evaluation and management within the first few days of life. Phototherapy is the single most common intervention used for the treatment of neonatal jaundice. The aim of our study was to evaluate the efficacy and tolerability of phototherapy with reflectors compared to conventional phototherapy in controlling neonatal hyperbilirubinaemia.
PATIENTS AND METHODS
In this randomized controlled study, we studied neonates for one year (from June 2010 to June 2011) who were full term and healthy with uncomplicated jaundice and who were admitted to the neonatal intensive care unit (NICU) of El-Nasr General Hospital, Port-Said, Egypt. The subjects were randomized in two groups: group A (n = 30) received phototherapy with reflectors and group B (n = 30) received conventional phototherapy. Serum bilirubin levels were measured on admission and every 12 h thereafter. With declining readings, bilirubin was measured once daily until hospital discharge.
RESULTS
There was no significant difference in total serum bilirubin on admission between the two groups. On discharge, bilirubin levels significantly decreased in group A compared to group B. There was a reduction in the duration of the hospital stay in group A compared to group B. The only observed complication in the groups was hyperthermia, which was not significantly different between the two groups.
CONCLUSION
The present study examined the efficacy and tolerability of phototherapy with reflectors in comparison to conventional phototherapy and found that phototherapy with reflectors was significantly better at controlling bilirubin levels in neonates with indirect hyperbilirubinaemia and at shortening hospitalization time. | 10.1016/j.ijpam.2015.09.003 |
pubmed_509_22691 | AIMS: To determine whether mothers of children with congenital toxoplasmosis have chorioretinal lesions consistent with toxoplasmosis. METHODS: Prospective cohort study. Ophthalmologists in our study have examined 173 children with congenital toxoplasmosis in a hospital outpatient setting. These children were referred to us by their primary care physicians. One hundred and thirty mothers of these children had retina examinations of both eyes at least once. Main outcome measure was lesion(s) consistent with ocular toxoplasmosis. RESULTS: Of 130 mothers examined between 1991-2005, 10 (7.7%, 95% Confidence Interval 3.8%, 13.7%) had chorioretinal lesions which likely represent resolved toxoplasmic chorioretinitis. Most of these were small peripheral chorioretinal lesions. None reactivated between 1991-2005. CONCLUSIONS: Chorioretinal lesions consistent with quiescent ocular toxoplasmosis occur in mothers of children with congenital toxoplasmosis in the United States. | pubmed_509_22691 |
pubmed_570_10413 | OBJECTIVE
To review our method of perform needle biopsies of renal masses.
METHODS
We analysed 150 consecutive imaging-guided percutaneous biopsies. The pathological diagnosis was verified on clinical outcome in 129 cases (40 surgical resection, 53 thermal ablation, two medical treatment and 34 watchful waiting). Twenty-six patients underwent fine-needle aspiration biopsy (FNAB), 45 core-needle biopsy (CB) and 58 FNAB + CB. After review by two expert pathologists, cumulative accuracy of all FNAB (84) and all CB (103) was calculated. The rate of complications and mass management other than surgery was estimated.
RESULTS
The final diagnosis was malignancy in 97 cases (benign mass in 32). FNAB correctly diagnosed 64/84 masses (76.2%), CB 96/103 (93.2%). Of 58 masses submitted for both FNAB and CB, CB provided a 22.5% accuracy improvement. Major and minor complications occurred in 0% and 5.3%. Renal biopsy altered clinical management in 89/129 cases (68.9%), in terms of choosing therapeutic options other than surgery.
CONCLUSION
CB is more accurate than FNAB and should be preferred in renal mass biopsy. FNAB may precede CB when an expert pathologist can immediately evaluate the samples. Renal biopsy influences renal mass management. | 10.1007/s00330-010-1938-9 |
pubmed_484_9354 | The Amide I contours of six globular proteins of varied secondary structure content along with a peptide model for collagen and pulmonary surfactant protein C have been simulated very closely by using a modified GF matrix method. The starting point for the method uses the three-dimensional structure as obtained from the Protein Data Bank. Elements of the interactions between peptide groups (e.g., transition dipole coupling) are very sensitive to tertiary structure, thus the current formalism demonstrates that the Amide I contour may be useful for a more detailed probe of 3-D conformation that goes beyond the traditional use of this band to probe the percentages of particular elements of secondary structure. For example, postulated changes to a known structure can be tested by comparing the new simulated band to the experimental band. A number of refinements to the transition dipole interaction calculation have been made. Most of the important interactions between the C=O oscillators that define the Amide I mode appear to have been identified, including through space transition dipole coupling, through valence bond and through hydrogen bond coupling. The eigenvector matrix produced by the method permits the contribution of each peptide group to the spectrum to be precisely determined. Analysis of the results shows that the often-used structure-frequency correlations are at best approximate and at worst misleading. The subbands from helices, sheets, turns, and loops are much broader and more overlapped than has been commonly assumed. Furthermore, the traditional alpha-helical marker band may be substantially distorted in short segments. Difference spectra based on isotope editing, a technique thought capable of revealing the spectral contributions of individual peptide groups, are shown to be prone to misinterpretation. | 10.1021/ja0400685 |
pubmed_773_10781 | A double-antibody radioimmunoassay method, using synthetic human connecting peptide as an immunizing antigen and standard, was evaluated for clinical assay of blood and urine samples. Normal fasting blood connecting peptide immunoreacivity (CPR) was 2.45 +/- 0.96 ng/ml, increasing promptly after a 50 g oral glucose load, but somewhat slower than insulin. Molar concentration of CPR exceeded that of insulin. CPR responses to glucose were subnormal in diabetics, very low in juvenile-type cases, and often poor in patients on insulin treatment. Fasting CPR levels were elevated in patients on corticosteroid treatment and with uraemia. A patient with insulin "auto-antibody" had high serum CPR. A considerable amount of CPR appeared in urine. Normal daily excretion of CPR was 1.52 +/- 0.55 mug/kg or 55.1 +/- 18.2 ng/mg creatinine. Urine CPR was very low in juvenile-type diabetics, and elevated in patients on corticosteroid treatment. The results confirm that blood and urine CPR are useful measures of the endocrine pancreatic function. | 10.1007/BF01219516 |
pubmed_489_259 | In this paper, we present a receding horizon solution to the optimal sensor scheduling problem. The optimal sensor scheduling problem can be posed as a partially observed Markov decision problem whose solution is given by an information space (I-space) dynamic programming (DP) problem. We present a simulation-based stochastic optimization technique that, combined with a receding horizon approach, obviates the need to solve the computationally intractable I-space DP problem. The technique is tested on a sensor scheduling problem, in which a sensor must choose among the measurements of N dynamical systems in a manner that maximizes information regarding the aggregate system over an infinite horizon. While simple, such problems nonetheless lead to very high dimensional DP problems to which the receding horizon approach is well suited. | 10.1109/TSMCB.2012.2236313 |
pubmed_745_2727 | Twelve boys with haemophilia and factor VIII inhibitors have received initial treatment for each episode of bleeding with prothrombin-complex concentrate. The follow-up period for these boys has ranged from two months to 14 years, and a total of 732 bleeding episodes were reviewed. Each boy underwent a full clinical and radiological assessment of knee-joint function, and this was compared with knee-joint function in 29 patients with severe haemophilia but without factor VIII antibodies. A change of treatment from prothrombin-complex concentrate to some other form of therapy was considered to be required in only 4% of the bleeding episodes. Of 10 severe bleeding episodes, five episodes clearly were controlled with prothrombin-complex concentrate, but five episodes necessitated alternative treatment. Four of the 12 families considered prothrombin-complex concentrate as relatively ineffective. All boys who were older than 10 years of age showed grade-1 or grade-2 impairment of knee-joint mobility, as well as radiological evidence of moderate-to-severe knee-joint changes. In the group of haemophiliac patients who were older than 10 years of age and did not have factor VIII antibodies, only 10 of the 58 knee-joints that were examined showed grade-1 or grade-2 functional impairment. Although prothrombin-complex concentrates were effective in the control of the majority of minor bleeding episodes, they were effective in only 50% of severe episodes of bleeding and did not prevent the early development of haemophilic arthropathy. | 10.5694/j.1326-5377.1987.tb133415.x |
pubmed_532_10596 | What is the topic of this review? This article reviews data from studies on human participants and animal models showing how electrical stimulation in deep brain structures (deep brain stimulation) can influence autonomic function. What advances does it highlight? Focusing on the control of the cardiovascular system and bladder function, it highlights the potential for development of deep brain stimulation as a new treatment option for patients with autonomic dysfunction. Deep brain stimulation (DBS) in humans has come of age as a tool to treat movement disorders including Parkinson's disease tremor and dystonia as well as a panoply of other disease states including headache, epilepsy, obesity, eating disorders, depression, obsessive compulsive disorder, Tourette's syndrome, addiction and chronic pain. Increasingly, practitioners of DBS are reporting autonomic side effects, which intriguingly, sometimes result in improved autonomic function. Focussing on the effects of stimulation at periaqueductal and periventricular sites on cardiovascular function and control of micturition, this review shows that data obtained from studies in animals is now being confirmed in humans. Lowering of blood pressure and improved baroreflex function can be evoked in humans by DBS at these midbrain sites as well as increased bladder capacity. The findings highlight the tantalizing possibility that DBS could be developed for treatment of dysfunctional autonomic states in humans. | 10.1113/expphysiol.2013.072694 |
pubmed_750_25753 | Morphological tampering of cellular architecture is a frequent phenomenon, leading to a spectrum of histological melange at light microscopic level. One such group of tumors which exhibit diagnostic and therapeutic dilemmas are the Clear cell tumors. Clear Cell Odontogenic Carcinoma (CCOC) is an infrequent tumor, which is aggressive by nature among the odontogenic tumors. A case of CCOC of mandible in a denture wearer is presented with the emphasis on diagnostic work up and clarified and unclarified facts of the tumor. | 10.4103/jomfp.JOMFP_117_18 |
pubmed_60_8426 | Trauma patients with thoracic aortic injury (TAI) suffer blunt cardiac injury (BCI) at variable frequencies. This investigation aimed to determine the frequency of BCI in trauma patients with TAI and compare with those without TAI. All trauma patients with TAI who had admission electrocardiography (ECG) and serum creatine kinase-MB (CK-MB) from January 1999 to May 2009 were included as a study group at a level I trauma center. BCI was diagnosed if there was a positive ECG with either an elevated CK-MB or abnormal echocardiography. There were 26 patients (19 men, mean age 45.1 years, mean ISS 34.4) in the study group; 20 had evidence of BCI. Of 52 patients in the control group (38 men, mean age 46.9 years, mean ISS 38.7), eighteen had evidence of BCI. There was a significantly higher rate of BCI in trauma patients with TAI versus those without TAI (77% versus 35%, P < 0.001). | 10.1155/2011/848013 |
pubmed_24_11130 | BACKGROUND
Oxidative stress may play a critical role in the pathogenesis and development of obesity-associated co-morbidities. Reactive oxygen and nitrogen species are produced as a consequence of normal aerobic metabolism and removed and/or inactivated in vivo by both endogenous (uric acid, bilirubin, thiols) and diet-derived (exogenous) antioxidants. The purpose of this study is to measure the total plasma antioxidant capacity (TAC), as well as the corrected TAC (cTAC, an index of exogenous provided antioxidants) in morbidly obese patients before and after surgical weight reduction.
METHODS
16 morbidly obese (5 male and 11 female) candidates for surgical intervention, median age 34 (range 22-56) years, median weight 128 (range 96-186) kg, median excess weight 62 (range 28-115) kg and median BMI 44.4 (range 33.7-60.1) kg/m2 were evaluated before and 6 months after implantation of an intragastric balloon. 15 healthy blood donors (4 male and 11 female) on a normal diet, median age 35 (range 21-52) years, median weight 64.3 (range 46-78) kg and median BMI 24.2 (range 23.7-25.2) kg/m2 were also evaluated. Blood samples for routine clinical chemistry, TAC and cTAC determination were drawn, and weight and BMI calculation were performed once in the control group, and in the morbidly obese patients (MO) before and 6 months after the balloon implantation.
RESULTS
6 months after balloon placement, weight and BMI of the MO patients were statistically significantly reduced from the preoperative values (P<0.001). Plasma TAC and cTAC values in the MO group were significantly lower preoperatively, compared to the control group (P<0.05 and P<0.001 respectively). cTAC values in the MO patients increased significantly following weight loss (P<0.001) and were restored to normal. However, the postoperative TAC values in the MO group did not change significantly and remained lower than in the normal controls. A significant decrease (P<0.001) in uric acid values was also noticed in the MO group after weight loss.
CONCLUSION
Plasma TAC and cTAC values are impaired in morbidly obese patients. Weight loss from an intragastric balloon is associated with significant increase in plasma cTAC values. Plasma TAC values, after the weight loss remain unchanged, possibly due to a decrease in uric acid, an important endogenous antioxidant. | 10.1381/096089206776116444 |
pubmed_352_6191 | The membrane polypeptide composition and the blood group Gerbich phenotype of red cells from 4.1 (-) hereditary elliptocytic patients and from Gerbich-negative donors, who display two unrelated genetic abnormalities, were compared. In homozygous 4.1 (-) hereditary elliptocytosis where the primary defect was presumably the absence of the membrane skeletal protein 4.1, there was approximatively a 70% reduction in the minor sialoglycoproteins beta and gamma. This was associated with a severe reduction of blood group Gerbich reactivity as determined with both murine monoclonal and human anti-Gerbich antibodies. In the heterozygous state in the presence of one haploid set of protein 4.1 gene there was only a modest decrease in glycoproteins beta and gamma and the Gerbich serological reactivity was within normal limits. In homozygous Gerbich-negative red cells which lack glycoproteins beta and gamma but do not display elliptocytic red cells, the levels of protein 4.1 was repeatedly found within or just below the lowest values of normal controls. In the heterozygous Gerbich-negative conditions, glycoproteins beta and gamma were present in reduced amounts but the blood group Gerbich reactivity fell within normal limits since the anti-Gerbich reagents used were unable to detect a dosage effect. The amount of protein 4.1 was normal. These results add further support to the view that protein 4.1 and the sialoglycoproteins beta and gamma are physically linked in vivo which in some way serve to maintain red cell shape and integrity. Of interest was the finding that absence of protein 4.1 had a greater influence on the level of membrane glycoproteins beta and gamma than did the absence of beta and gamma glycoproteins on band 4.1. | 10.1111/j.1365-2141.1987.tb06133.x |
pubmed_1061_10104 | Uptake of pre-exposure prophylaxis (PrEP) has dramatically increased but remains well below the estimated number of individuals who could benefit from PrEP in the United States, and uptake remains limited among young men who have sex with men (YMSM) and MSM of color. Reasons for not adopting PrEP as a prevention strategy among those at elevated risk for HIV is an important area of inquiry that could advise efforts to better position PrEP as an active part of prevention programs. As part of a mixed methods study investigating experiences with repeat HIV testing, we identified main themes emerging from in-depth interview data pertaining to reasons why YMSM report not using PrEP, among YMSM with frequent access to HIV testing services. Themes from 14 in-depth interviews with predominantly Latino MSM for not using PrEP included perceived burden of daily dosing, feeling that risk was not high enough to warrant PrEP, and beliefs that PrEP would have severe adverse events affecting the kidneys and bones. Less prominent but noteworthy themes included stigma as a PrEP user, social or provider influence on decisions not to use PrEP, and preference for current prevention strategy. No differences in PrEP discourse were noted across those at different levels of HIV risk. Results suggest that efforts are needed to engage communities and individuals around PrEP-related education, facilitate risk evaluation, and reduce PrEP stigma. New formulations and nondaily regimens may also be of particular interest to YMSM who may perceive daily PrEP regimens as highly burdensome. | 10.1089/apc.2019.0150 |
pubmed_10_11093 | A team of nursing students has won a prestigious RCNi award for organising a conference aimed at reducing health inequalities affecting people with learning disabilities. The Learning Disability Awareness Network (LDAN) team was crowned winner of the RCNi Andrew Parker Student Nurse award 2016 at a ceremony held at London's Westminster Park Plaza on May 6. | 10.7748/ns.30.42.23.s25 |
pubmed_353_20067 | Participants (N = 126) read one of four scenarios depicting an incident of child physical abuse inflicted by the father. Scenarios varied history of wife abuse (present vs. absent) and severity of child abuse (battering vs. death). Overall, the father was held highly responsible. Greater maternal culpability was assigned when a history of wife abuse was present. The degree to which the mother should have been able to predict the incident of child abuse and maternal responsibility were mitigated when the abuse resulted in the death of her child. Perceptions of maternal psychological stability were jeopardized as a function of the presence of wife abuse. Implications are discussed. | 10.1177/1077801208321331 |
pubmed_26_19548 | Clinical and morphological comparison of wound healing after transplantation of living cultured allofibroblast on days 1-2 after the injury, collagen-1-based dressing with PDGF-BB, and traditional dressing with levomecol ointment showed that bioactive dressing accelerated wound epithelialization (5-7 days vs. 20-22 days with gauze dressing); the incidence of suppurative complications decreased, no crust formed, and epithelialization was not associated with the formation of a hypertrophic cicatrix. Biological dressing based on living cultured allofibroblasts and collagen-1 with PDGF-BB exhibited equal stimulatory effects on burn wound healing. | 10.1007/s10517-008-0225-0 |
pubmed_269_12244 | Virtual planning has become part and parcel of digital dentistry to ensure more precise planning, better treatment outcomes, and more effective communication between dental practitioners, dental technicians, and patients. In dentistry, CAD software programs are one way to achieve virtual treatment planning. Among the most crucial and critical steps in treatment planning and execution are virtual articulation and occlusal analysis of the maxillary and mandibular arches. These steps have a great influence on the success of the final outcome. The present article proposes a detailed method for constructing a novel virtual articulator that can also be used for educational purposes to enable occlusal analysis and adjustment for a virtual tooth mock-up by simulating a virtual dynamic occlusion through the use of open-source Autodesk Meshmixer software. | pubmed_269_12244 |
pubmed_88_3900 | Regional anesthesia has become a routine part of the practice of anesthesiology in infants and children. Local anesthetic toxicity is extremely rare in infants and children; however, seizures, dysrhythmias, cardiovascular collapse, and transient neuropathic symptoms have been reported. Infants and children may be at increased risk from local anesthetics compared with adults. Larger volumes of local anesthetics are used for epidural anesthesia in infants and children than in adults. Metabolism and elimination of local anesthetics can be delayed in neonates, who also have decreased plasma concentrations of alpha(1)-acid glycoprotein, leading to increased concentrations of unbound bupivacaine. Most regional anesthetic procedures in infants and children are performed with the patient heavily sedated or anesthetized; because of this, and because a test dose is not a particularly sensitive marker of intravenous injection in the anesthetized patient, detection of intravascular local anesthetic injection is extremely difficult. The same local anesthetics used in adult anesthetic practice are also used in infants and children. Because of its extremely short duration of action, chloroprocaine has been used primarily for continuous epidural techniques in infants and children. The use of tetracaine has generally been limited to spinal and topical anesthesia. Lidocaine (lignocaine) has been used extensively in infants and children for topical, regional, plexus, epidural and spinal anesthesia. The association between prilocaine and methemoglobinemia has generally restricted prilocaine use in infants and children to the eutectic mixture of local anesthetics (EMLA). Because of its greater degree of motor block compared with other long-acting local anesthetics, etidocaine has generally been limited to plexus blocks in infants and children. Mepivacaine has been used for both plexus and epidural anesthesia in infants and children. Because postoperative analgesia is often the primary justification for regional anesthesia in infants and children, bupivacaine, a long-acting local anesthetic, is the most commonly reported local anesthetic for pediatric regional anesthesia. Given the lower toxic threshold of bupivacaine compared with other local anesthetics, the risk-benefit ratio of bupivacaine may be greater than that of other local anesthetics. Two new enantiomerically pure local anesthetics, ropivacaine and levobupivacaine, offer clinical profiles comparable to that of bupivacaine but without its lower toxic threshold. The extreme rarity of major toxicity from local anesthetics suggests that widespread replacement of bupivacaine with ropivacaine or levobupivacaine is probably not necessary. However, there are clinical situations, including prolonged local anesthetic infusions, use in neonates, impaired hepatic metabolic function, and anesthetic techniques requiring a large mass of local anesthetic, where replacement of bupivacaine with ropivacaine, levobupivacaine or (for continuous techniques) chloroprocaine appears prudent. | 10.2165/00128072-200204100-00003 |
pubmed_554_24247 | In recent times, photo-induced therapeutics have attracted enormous interest from researchers due to such attractive properties as preferential localization, excellent tissue penetration, high therapeutic efficacy, and minimal invasiveness, among others. Numerous photosensitizers have been considered in combination with light to realize significant progress in therapeutics. Along this line, indocyanine green (ICG), a Food and Drug Administration (FDA)-approved near-infrared (NIR, >750 nm) fluorescent dye, has been utilized in various biomedical applications such as drug delivery, imaging, and diagnosis, due to its attractive physicochemical properties, high sensitivity, and better imaging view field. However, ICG still suffers from certain limitations for its utilization as a molecular imaging probe in vivo, such as concentration-dependent aggregation, poor in vitro aqueous stability and photodegradation due to various physicochemical attributes. To overcome these limitations, much research has been dedicated to engineering numerous multifunctional polymeric composites for potential biomedical applications. In this review, we aim to discuss ICG-encapsulated polymeric nanoconstructs, which are of particular interest in various biomedical applications. First, we emphasize some attractive properties of ICG (including physicochemical characteristics, optical properties, metabolic features, and other aspects) and some of its current limitations. Next, we aim to provide a comprehensive overview highlighting recent reports on various polymeric nanoparticles that carry ICG for light-induced therapeutics with a set of examples. Finally, we summarize with perspectives highlighting the significant outcome, and current challenges of these nanocomposites. | 10.3390/nano8060360 |
pubmed_837_22967 | LiCl stimulated the formation of inositol monophosphate in PC12 cells that had been exposed to nerve growth factor (NGF) for 4-5 days. Half-maximal accumulation was observed at approximately 8 mM LiCl. Stimulation of formation of inositol bisphosphate plus inositol trisphosphate was half-maximal at approximately 1 mM LiCl. With membranes isolated from PC12 cells differentiated with NGF, the hydrolysis of added phosphatidylinositol 4,5-bisphosphate (PIP2) was stimulated by LiCl in a biphasic manner, with the first stimulation half-maximal at approximately 0.7 mM and the second half-maximal at approximately 15 mM LiCl. The apparent Km for PIP2 was lowered in the presence of 1.1 mM LiCl from approximately 200 to approximately 70 microM. Membranes from cells grown in the absence of NGF did not respond to LiCl. Although observations with intact cells are difficult to interpret without ambiguity, the results obtained with isolated membranes support our interpretation of the stimulatory action of lithium in the intact PC12 cells. | 10.1111/j.1471-4159.1988.tb03082.x |
pubmed_713_12818 | Objectives: Disruption of anisotropic phenotypes of the meniscus would contribute to OA progression. Exploring phenotype changes of the anisotropic meniscus in joint degeneration would help understand the biologic interaction between the meniscus and OA, and further facilitate the therapeutic strategies of meniscus injury-related joint degeneration. Meanwhile, engineering biomimetic meniscal tissue mimicking the anisotropy of the healthy meniscus remains a challenge. Methods & Results: Meniscal disruption of phenotype anisotropy (PBV growth, cellular phenotype and ECM depositions) was confirmed in OA patient samples. To recapitulate healthy meniscus phenotypes, 3D-bioprinted anisotropic TCM meniscus constructs with PBV growth and regional differential cell and ECM depositions were generated. Transplanted 3D-bioprinted meniscus into rabbit knees recapitulated phenotypes of native healthy meniscus and conferred long-term protection against secondary joint degeneration. Conclusion: 3D-bioprinted TCM meniscus not only restored the anisotropy of native healthy meniscus with PBV infiltration and better shape retention, but better maintained joint function and prevented secondary joint degeneration, which provided a new strategy for the clinical treatment of meniscus injury-related joint degenerative diseases. | 10.7150/thno.54864 |
pubmed_1089_23338 | Glycogen synthase kinase 3 (GSK3) acts as an important regulator during the proliferation and differentiation of neural progenitor cells (NPCs), but the roles of the isoforms of this molecule (GSK3α and GSK3β) have not been clearly defined. In this study, we investigated the functions of GSK3α and GSK3β in the context of neuronal differentiation of murine NPCs. Treatment of primary NPCs with a GSK3 inhibitor (SB216763) resulted in an increase in the percentage of TuJ1-positive immature neurons, suggesting an inhibitory role of GSK3 in embryonic neurogenesis. Downregulation of GSK3β expression increased the percentage of TuJ1-positive cells, while knock-down of GSK3α seemed to have no effect. When primary NPCs were engineered to stably express either isoform of GSK3 using retroviral vectors, GSK3β, but not GSK3α, inhibited neuronal differentiation and helped the cells to maintain the characteristics of NPCs. Mutant GSK3β (Y216F) failed to suppress neuronal differentiation, indicating that the kinase activity of GSK3β is important for this regulatory function. Similar results were obtained in vivo when a retroviral vector expressing GSK3β was delivered to E9.5 mouse brains using the ultrasound image-guided gene delivery technique. In addition, SB216763 was found to block the rapamycin-mediated inhibition of neuronal differentiation of NPCs. Taken together, our results demonstrate that GSK3β, but not GSK3α, negatively controls the neuronal differentiation of progenitor cells and that GSK3β may act downstream of the mammalian target of rapamycin complex1 signaling pathway. | 10.1089/scd.2013.0397 |
pubmed_1008_3836 | We report evidence that the enzyme transglutaminase (glutaminyl-peptide gamma-glutamyltransferase; R-glutaminyl-peptide:amine gamma-glutamyltransferase, EC2.3.2.13) participates in receptor-mediated endocytosis. Clustering and internalization of rhodamine-labeled alpha 2-macroglobulin (R alpha 2 M) in normal rat kidney (NRK) cells is inhibited by a wide spectrum of compounds that inhibit transglutaminases, including that from NRK cells. The pattern of clustering inhibition resembles the pattern of transglutaminase inhibition as follows: (i) The most potent transglutaminase inhibitors are dansylcadaverine and the transglutaminase-directed affinity label N-benzyloxy-carbonyl-5-diazo-4-oxonorvaline p-nitrophenyl ester; these were also the most potent inhibitors of clustering and internalization of R alpha 2M. (ii) The inhibition of clustering of R alpha 2M occurs in the same concentration range as that required for transglutaminase inhibition. (iii) Linear primary amines are more effective blockers than the iso-chain primary amines. (iv) The transglutaminase affinity label N-benzyloxycarbonyl-5-diazo-4-oxonorvaline p-nitrophenyl ester irreversibly inhibits a significant fraction of the NRK transglutaminase and the clustering and internalization of R alpha 2M. A closely related compound, N-trifluoroacetyl-6-diazo-5-oxonorleucine ethyl ester, does not significantly inhibit transglutaminase or clustering and internalization. (v) Clustering and internalization is inhibited 10-fold more effectively by the heptapeptide Ac-Gly2-LLeu-LLys-Gly3 than by the heptapeptides Ac-Gly2-LLeu-DLys-Gly3 or AcGly3-DLys-DLeu-Gly2. This is the pattern of stereospecificity for the inhibition of purified transglutaminases. | 10.1073/pnas.77.5.2706 |
pubmed_110_4195 | Three peaks of proteinases were observed with hemoglobin, bovine serum albumin and casein as substrates at the pH of 3.5, 6.5 and 8.5, in prenatal human cerebral cortex. Cathepsin D (EC 3.4.23.5) was the most prominent, with hemoglobin as the preferred substrate. The enzyme was partially purified by Concanavalin A - Sepharose affinity chromatography and the nature of the active site was assessed with proteinase inhibitors. Inhibitor studies showed that similar to pepstatin A, benzethonium chloride was also strongly inhibitory to the enzyme. The distribution of cathepsin D, a neuronal marker, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37), a oligodendroglial marker in foetal brain regions with increasing gestation revealed that neurogenesis and gliogenesis occur concomitantly from earlier periods of gestation. Glial marker acquisition was particularly high in medulla and in spinal cord between 20 and 25 weeks of gestation. | 10.1016/0736-5748(88)90035-4 |
pubmed_302_2473 | The sheep scab mite, Psoroptes ovis, causes severe dermatitis in infected sheep with severe welfare and production implications. The dermatitis has the characteristics of an immediate hypersensitivity type reaction which, by analogy to other mite species, including the house dust mites (Dermatophagoides spp.), is likely to be invoked by a variety of allergens including mite-derived proteinases. Here, the proteinases in P. ovis extracts were characterised using substrate gel analysis, inhibitor sensitivity and their ability to degrade a variety of potential natural protein substrates. These analyses showed that mites contain several proteinases which could be differentiated on the basis of molecular size and inhibitor sensitivity with cysteine, metalloproteinases and aspartyl proteinases predominating. These proteinases degraded collagen and fibronectin, possibly indicative of a role in lesion initiation, they degraded several blood proteins, a property which may aid mite feeding and they degraded immunoglobulin G, possibly aiding immuno-evasion. Because proteinases, particularly the cysteine class, are demonstrably allergenic in other mite infestations, these proteinases clearly merit further immunological and biochemical definition. | 10.1016/s0304-4017(02)00015-8 |
pubmed_900_13614 | We report the fabrication of a Langmuir-Blodgett (LB) film of magnetic nanoparticles (iron oxide) coated by poly(N-alkylmethacrylamide)s with various alkyl chain lengths. The iron oxide nanoparticle (nP) was first modified with a reactive polymer, poly(N-hydroxysuccinimide methacrylate) (pSucMA) by applying surface initiated atom transfer radical polymerization (ATRP) technique. Then the succinimide group was replaced by various amine derivatives. The monolayer behaviors of the resultant nanoparticles, as modified by various poly(N-alkylmethacrylamide)s, such as poly(octylmethacrylamide) (pOMA), poly(dodecylmethacrylamide) (pDDMA), polytetradecylmethacrylamide (pTDMA), and poly(hexadecylmethacrylamide) (pHDMA) were elucidated using surface pressure-area isotherm measurements. Results show that pTDMA-modified nanoparticles (nP-pTDMA) exhibit the highest collapse pressure with a steeply rising surface pressure. The monolayer of nP-pTDMA on the water surface was transferred onto a solid substrate using the LB technique. Atomic force microscopy (AFM) images of the transferred LB film show that nP-pTDMA particles form a uniform nanoparticle monolayer. The LB film of nP-pTDMA with multilayers was fabricated through sequential transfer of the particles monolayer onto the substrate surface. The resultant LB film of nanoparticles shows a superparamagnetic behavior at room temperature. | 10.1016/j.jcis.2007.04.026 |
pubmed_1061_23495 | Geniposide, the main medicinal ingredient of Gardenia jasminoides Ellis, is known to be a resistant agent to atherosclerosis. Some reports its mechanism against atherosclerosis remains completely unclear. Herein, we have investigated the protective effect of geniposide against atherosclerosis as well as clarified the mechanisms related with inhibiting the formation of foam cells and lowering reverse lipid transport via p38/MAPK signaling pathways. Macrophage Raw264.7 was induced by lysophosphatidic acid (LPA) to form foam cell as a cell model. ApoE-/- mice were fed with a high-fat diet for 16 weeks to cause atherosclerosis in carotid artery. After treatment with geniposide, CCK-8, oil red O stain, qRT-PCR and western blot were carried out to explore the effect of geniposide. Morphological changes, histological analyses were used to evaluate atherosclerosis in ApoE-/- mice. Geniposide significantly reduced serum total cholesterol (TC), triglyceride (TG) and LDL cholesterol levels in ApoE-/- mice compared with vehicle control. Meanwhile, geniposide dose dependently inhibited the development of atherosclerosis in ApoE-/- mice. Furthermore, geniposide observably inhibited the formation of foam cells induced by LPA, down-regulated the mRNA and protein levels of SR-A and up-regulated the mRNA and protein levels of ABCA1 or SR-B1 in vitro via inhibition of the p38MAPK and AKT signaling pathways. Our study shows that geniposide protected against atherosclerosis and inhibited the formation of foam cells by regulating the equilibrium on expression of diverse lipid transporters in cytomembrane which related with p38MAPK and AKT signaling pathways. Geniposide is a potential therapeutic drug for atherosclerosis. | 10.1016/j.ejphar.2019.172728 |
pubmed_343_8122 | OBJECTIVE
The aim of this study was to investigate whether concomitant treatment of dutasteride and sildenafil could prevent structural changes in the penis of a BPH rodent model.
METHODS
Thirty-two adult male rats were divided into the following groups: Ctrl, untreated control rats; BPH, untreated spontaneously hypertensive rats (SHRs); BPH + D, SHRs treated with dutasteride; and BPH + DS, SHRs treated with dutasteride and sildenafil. All treatments were performed during 40 days, following which the penises were collected for histomorphometrical analysis. The results were compared via one-way ANOVA with Bonferroni's post-test, considering p values <.05 as significant.
RESULTS
The smooth muscle density decreased by 28.6% and 21.4% in BPH + D and BPH + DS, respectively, when compared to the BPH group. The sinusoid space density reduced by 32.2% in BPH, when compared to the Ctrl group; this density was also reduced by 22.6% in BPH + D, when compared to the BPH group. The density of the elastic fibers increased 51.6% and 65.6% in BPH + D and BPH + DS, when compared to the BPH group.
CONCLUSION
Treatment with dutasteride promoted morphological changes in the corpus cavernous of this BPH model. Concomitant treatment with sildenafil did not prevent the morphological changes caused by dutasteride; on the contrary, it also promoted a further increase in elastic fibers. | 10.1080/13685538.2019.1653839 |
pubmed_893_5308 | Visual spatial attention has been shown to influence both contrast detection and suprathreshold contrast perception, as well as manual and saccadic reaction times (SRTs). Because SRTs are influenced also by stimulus contrast, we investigated if the enhancement of perceived contrast that accompanies attention could account for the shorter SRTs observed for attended targets locations. We conducted two dual-task experiments to assess psychophysical and oculomotor responses to non-foveal targets of various contrast for different spatial-attention-cueing conditions. Cues were either: valid, an arrow at fixation pointing in the direction of the upcoming target; invalid, an arrow pointing in a different direction from the target; or neutral, a small circle instead of an arrow. In both experiments, subjects were instructed to make a saccade to the location of a subsequent, briefly flashed target. In the first experiment, the psychophysical judgment was a two-alternative-forced-choice (2AFC) contrast-detection task, in which subjects reported whether the flashed target was at a near (3°) or far (6°) eccentricity. In the second experiment, the judgment was a contrast matching task, in which subjects reported whether the target's contrast was higher or lower than a remembered standard contrast. The results exhibit a robust, ∼40-50 ms reduction of SRTs with a valid compared to an invalid cue. Cueing effects on contrast detection and matching were small and inconsistent across subjects. Hence, the observed decrease in SRTs could not be accounted for fully by an enhancement in the target's effective contrast due to attention, as attended and unattended targets that were equally detectable or were perceived to have the same suprathreshold contrast showed substantial differences in SRT. | 10.1016/j.visres.2017.11.005 |
pubmed_908_21462 | Objective: Standardizing treatment of neonatal abstinence syndrome (NAS) is currently recommended; however, single institution prospective studies are lacking regarding the success of this approach. The study objective was to evaluate overall newborn response and length of stay (LOS) of neonates treated for NAS following the institution of a strict standardized treatment protocol. Methods: From 1 January 2014 to 30 June 2016, a prospective cohort study was performed collecting neonatal outcomes before and after the standardization of a strict NAS morphine weaning treatment protocol. The primary outcome measure was length of stay. The standardized protocol was fully instituted in June 2015. Results: A total of 395 neonates were treated for NAS during the study. The LOS for the 17 months prior to the initiation of this protocol was 23.31 (±6.2) days (233 neonates). The LOS in the 13 months after protocol initiation was 18.17 (±5.1) days (162 neonates). This was a difference of 5.14 days (95%CI 4.0-6.3 days) less in LOS (p < .0001). Conclusions: These data demonstrate that the initiation of a standardized NAS treatment protocol can significantly improve neonatal response and decrease LOS. It is recommended that institutions with nurseries that treat infants with NAS develop standardized treatment protocols to improve care for this complicated patient population. | 10.1080/14767058.2018.1465038 |
pubmed_482_6008 | OBJECTIVE
Many patients with bipolar disorder are treated exclusively in primary care settings, and the use of atypical antipsychotics as primary treatment for bipolar depression is increasing. Extrapyramidal symptoms (EPS) are common side effects of antipsychotic medications, and clinicians should actively monitor for these symptoms when prescribing antipsychotic medications. Accurate diagnosis of EPS is especially important as the symptoms can be highly distressing, and in some cases, life threatening. Our aim is to familiarize primary care providers and other clinicians prescribing antipsychotic medications with EPS and to aid in its rapid diagnosis and treatment.
METHOD
We describe a case of lurasidone induced dystonia with prominent laryngospasm and oculogyric crisis which was missed for many years in the primary care setting, largely due to misdiagnosis of symptoms as being related to anxiety and panic attacks.
RESULTS
In addition to summarizing this illustrative case, we present the most common forms of EPS and summarize the primary therapies for each type of EPS.
CONCLUSIONS
With increased management of bipolar disorder in the primary care setting and increased use of atypical antipsychotics as the primary therapy for bipolar disorder, it is essential that all practitioners are prepared to actively monitor for EPS, followed by its rapid diagnosis and treatment. | 10.1177/0091217420943786 |
pubmed_50_8298 | Pedicle screws are one the commonest used modality in spinal instrumentation. However, the method of pedicle screw fixation in cervical spine as compared to thoracic and lumbar spine is still technically demanding because it carries the risk of catastrophic damage to the surrounding neurovascular structures We have utilized virtual planning and 3D (3-dimension) printing to develop a patient specific jig to guide the accurate placement of pedicle screws. A patient with bifacetal dislocation C7 over D1 classified as flexion-distraction injury type 3 who was planned for decompression and fusion by posterior instrumentation at C6, C7, D1 and D2 was selected. A CT scan with 1 mm cuts was used to produce DICOM images of the same. Using these DICOM images virtual planning was done on MIMICS and 3 MATICS software to create patient specific jigs. These jigs were then 3D printed using a 3D printer and used for accurate placement of pedicle screws intra-operatively after adequate sterilization. Our procedure is low cost but high technology based. It is simple, accurate, and very cost effective. The technology transfer is very easy and can be adopted easily. | 10.1016/j.jcot.2018.07.010 |
pubmed_592_9907 | We report the case of a patient with short-bowel syndrome, who lost multiple central venous devices over the course of 2 years while treating his catheter-related septicemia. Genotyping proved that all infectious episodes were caused by a single genotype of a Staphylococcus epidermidis strain, persisting over time. | 10.1086/647201 |
pubmed_298_5665 | Artesunate (AS), a hemisuccinate derivative of artemisinin, is readily soluble in water and can easily be used in formulations for parenteral treatment of severe malaria. AS is rapidly hydrolyzed to the active metabolite dihydroartemisinin (DHA) and primarily eliminated by biliary excretion after glucuronidation. To investigate systematically the AS metabolism and pharmacokinetics, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of AS and its metabolites DHA and DHA glucuronide (DHAG) in human plasma samples was developed. Compared to previous methods, our method includes for the first time the quantification of the glucuronide metabolite using a newly synthesized stable isotope-labeled analogue as internal standard. Sample preparation was performed with only 50 μL plasma by high-throughput solid-phase extraction in the 96-well plate format. Separation of the analytes was achieved on a Poroshell 120 EC-C18 column (50*2.1 mm, 2.7 μm, Agilent Technologies, Waldbronn, Germany). The method was validated according to FDA guidelines. Calibration curves were linear over the entire range from 1 to 2,500 nM (0.4-961.1 ng/mL), 165 to 16,500 nM (46.9-4,691.8 ng/mL), and 4 to 10,000 nM (1.8-4,604.7 ng/mL) for AS, DHA, and DHAG, respectively. Intra- and interbatch accuracy, determined as a deviation between nominal and measured values, ranged from -5.7 to 3.5% and from 2.7 to 5.8%, respectively. The assay variability ranged from 1.5 to 10.9% for intra- and interbatch approaches. All analytes showed extraction recoveries above 85%. The method was successfully applied to plasma samples from patients under AS treatment. | 10.1007/s00216-014-7820-x |
pubmed_976_2807 | This study conducted a combined adsorption-sequential extraction analysis (CASA), by which five phases (i.e., exchangeable, carbonate, Mn-Oxide, organic, and Fe-Oxide phases) of adsorbed heavy metals were analyzed, to investigate temperature effects on single and competitive adsorptions of Zn(II) and Cu(II) onto natural clays. In the case of single adsorption of Zn, the exchangeable phase adsorption decreased from 65 to 40%, but the carbonate phase adsorption increased from 30 to 40%, with an increase in temperature from 15 to 55 degrees C. However, in its competitive adsorption with Cu, Zn was mostly present in the exchangeable phase (over 90%), and with an increase in temperature, the exchangeable phase adsorption decreased only 10%. In the case of Cu, over 50% among the total amount of adsorption was present in the carbonate phase in both cases of single and competitive adsorptions. The carbonate phase adsorption of Cu increased from 56 to 61% and from 60 to 66% in single and competitive adsorptions, respectively, with a temperature increase. These results show that in the case of Zn, the major mechanism of retention in natural clay soils might be exchangeable phase adsorption, especially in the case of competitive adsorption with Cu. However, in the case of Cu, the major mechanism might be carbonate phase adsorption, which is known to be a more immobile phase than exchangeable phase adsorption. It seems that the adsorption of Zn and Cu onto natural clays is an endothermic reaction, which represents that the adsorption equilibrium constants and capacities increase with a temperature increase, with the exception of exchangeable phase adsorption. | 10.1023/a:1022509401228 |
pubmed_1067_1433 | The nuclear envelope (NE) is a highly specialized membrane that delineates the eukaryotic cell nucleus. It is composed of the inner and outer nuclear membranes, nuclear pore complexes (NPCs) and, in metazoa, the lamina. The NE not only regulates the trafficking of macromolecules between nucleoplasm and cytosol but also provides anchoring sites for chromatin and the cytoskeleton. Through these interactions, the NE helps position the nucleus within the cell and chromosomes within the nucleus, thereby regulating the expression of certain genes. The NE is not static, rather it is continuously remodeled during cell division. The most dramatic example of NE reorganization occurs during mitosis in metazoa when the NE undergoes a complete cycle of disassembly and reformation. Despite the importance of the NE for eukaryotic cell life, relatively little is known about its biogenesis or many of its functions. We thus are far from understanding the molecular etiology of a diverse group of NE-associated diseases. | 10.1146/annurev.cellbio.21.090704.151152 |
pubmed_789_21631 | BACKGROUND
The chemotherapeutic drug oxaliplatin causes sinusoidal obstruction syndrome (SOS), which is analogous to that of monocrotaline-induced SOS. Sesame oil is a nutrient-rich antioxidant in alternative medicine. It contains phenol, sesamin, sesamol, and sesamolin, all of which contribute to its antioxidant property. The authors investigated the therapeutic effect of oral sesame oil against monocrotaline-induced SOS in rats.
METHODS
Male Sprague-Dawley rats were gavaged with monocrotaline (90 mg/kg) to induce SOS. Control rats were treated with saline only at 0 and 24 hours. Sesame oil (0.5, 1, 2, or 4 mL/kg, orally) was given 24 hours after monocrotaline in rats. Blood samples were collected at 24 and 48 hours after monocrotaline was given to assess the level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Histopathology was also assessed 48 hours after monocrotaline was given.
RESULTS
AST and ALT were significantly higher in monocrotaline-treated rats than in control rats. Oral sesame oil did not decrease AST and ALT in monocrotaline-treated rats. In addition, liver pathology revealed that oral sesame oil had no therapeutic effect against SOS.
CONCLUSION
Oral sesame oil is therapeutically ineffectual against monocrotaline-induced SOS. | 10.1177/0148607112445795 |
pubmed_135_6290 | In the cold deserts of the McMurdo Dry Valleys (MDV) the suitability of soil for microbial life is determined by both contemporary processes and legacy effects. Climatic changes and accompanying glacial activity have caused local extinctions and lasting geochemical changes to parts of these soil ecosystems over several million years, while areas of refugia may have escaped these disturbances and existed under relatively stable conditions. This study describes the impact of historical glacial and lacustrine disturbance events on microbial communities across the MDV to investigate how this divergent disturbance history influenced the structuring of microbial communities across this otherwise very stable ecosystem. Soil bacterial communities from 17 sites representing either putative refugia or sites disturbed during the Last Glacial Maximum (LGM) (22-17 kya) were characterized using 16 S metabarcoding. Regardless of geographic distance, several putative refugia sites at elevations above 600 m displayed highly similar microbial communities. At a regional scale, community composition was found to be influenced by elevation and geographic proximity more so than soil geochemical properties. These results suggest that despite the extreme conditions, diverse microbial communities exist in these putative refugia that have presumably remained undisturbed at least through the LGM. We suggest that similarities in microbial communities can be interpreted as evidence for historical climate legacies on an ecosystem-wide scale. | 10.3390/biology11101440 |
pubmed_939_6544 | Reactive oxygen species and reactive nitrogen species (RONS) are by-products of aerobic metabolism. RONS trigger a signaling cascade that can be transduced through oxidation-reduction (redox)-based post-translational modifications (redox PTMs) of protein thiols. This redox signaling is essential for normal cellular physiology and coordinately regulates the function of redox-sensitive proteins. It plays a particularly important role in the brain, which is a major producer of RONS. Aberrant redox PTMs of protein thiols can impair protein function and are associated with several diseases. This mini review article aims to evaluate the role of redox PTMs of protein thiols, in particular S-nitrosation, in brain aging, and in neurodegenerative diseases. It also discusses the potential of using redox-based therapeutic approaches for neurodegenerative conditions. | 10.3389/fnagi.2020.00254 |
pubmed_660_14861 | BACKGROUND & AIMS
Duchenne muscular dystrophy results from a mutation in the dystrophin gene, which leads to a dystrophin-deficiency. Dystrophic muscle is marked by progressive muscle injury and loss of muscle fibers. Activation of the PGC-1α pathway has been previously shown to decrease disease-related muscle damage. Oral administration of the flavonol, quercetin, appears to be an effective and safe method to activate the PGC-1α pathway. The aim of this investigation was to determine the extent to which long term dietary quercetin enrichment would decrease muscle injury in dystrophic skeletal muscle. We hypothesized that a quercetin enriched diet would rescue dystrophic muscle from further decline and increase utrophin abundance.
METHODS
Beginning at three-months of age and continuing to nine-months of age mdx mice (n = 10/group) were assigned to either to mdx-control receiving standard chow or to mdx-quercetin receiving a 0.2% quercetin-enriched diet. At nine-months of age mice were sacrificed and costal diaphragms collected. One hemidiaphragm was used for histological analysis and the second hemidiaphragm was used to determine gene expression via RT-qPCR.
RESULTS
The diaphragm from the mdx-quercetin group had 24% (p ≤ 0.05) more muscle fibers/area and 34% (p ≤ 0.05) fewer centrally nucleated fibers compared to the mdx-control group. Further, there were 44% (p ≤ 0.05) fewer infiltrating immune cells/area, a corresponding 31% (p ≤ 0.05) reduction in TNF gene expression, and a near 50% reduction in fibrosis. The quercetin-enriched diet increased expression of genes associated with oxidative metabolism but did not increase utrophin protein abundance.
CONCLUSIONS
Long-term quercetin supplementation decreased disease-related muscle injury in dystrophic skeletal muscle; however the role of PGC-1α pathway activation as a mediator of this response is unclear. | pubmed_660_14861 |
pubmed_415_18058 | BACKGROUND & AIMS
Patients with painful chronic pancreatitis (CP) might have abnormal brain function. We assessed cortical thickness in brain areas involved in visceral pain processing.
METHODS
We analyzed brain morphologies of 19 patients with painful CP and compared them with 15 healthy individuals (controls) by using a 3T magnetic resonance scanner. By using an automated method with surface-based cortical segmentation, we assessed cortical thickness of the primary (SI) and secondary (SII) somatosensory cortex; prefrontal cortex (PFC); frontal cortex (FC); anterior (ACC), mid (MCC), and posterior (PCC) cingulate cortex; and insula. The occipital middle sulcus was used as a control area. The pain score was determined on the basis of the average daily amount of pain during 1 week.
RESULTS
Compared with controls, patients with CP had reduced overall cortical thickness (P = .0012), without effects of modification for diabetes, alcoholic etiologies, or opioid treatment (all P values >.05). In patients with CP, the cortical thickness was decreased in SII (P = .002, compared with controls), PFC (P = .046), FC (P = .0003), MCC (P = .001), and insula (P = .002). There were no differences in cortical thickness between CP patients and controls in the control area (P = .20), SI (P = .06), ACC (P = .95), or PCC (P = .42). Cortical thickness in the affected areas correlated with pain score (r = 0.47, P = .003).
CONCLUSIONS
In patients with CP, brain areas involved in pain processing have reduced cortical thickness. As a result of long-term, ongoing pain input to the neuromatrix, cortical thickness might serve as a measure for overall pain system dysfunction, as observed in other diseases characterized by chronic pain. | 10.1016/j.cgh.2011.11.024 |
pubmed_900_7384 | Nine novel compounds designated negombins A-I (1-9) were isolated, together with latrunculin, from the Tanzanian sponge Negombata sp. The nine are sacculatane type diterpenes, previously only known from liverworts. The structures of the compounds were elucidated by interpretation of MS and 1D and 2D NMR spectra. A possible biogenesis initiated by the naturally rare chloronium ion is suggested, possibly hinting to a guest microorganism as the source of the compounds. Compound 4 is toxic to brine shrimp larvae. | 10.1021/ol070633j |
pubmed_720_25147 | IWA Anaerobic Digestion Model No. 1 (ADM1) is the most widely recognised and popular mathematical model for anaerobic digestion processes. However, the application of ADM1 to acidogenic fermentation is limited by its use of constant stoichiometry to describe the formation of products via carbohydrate fermentation. This study presents a modification of ADM1 using a variable acidogenic stoichiometric approach in which the hydrogen partial pressure (pH2) and pH are used to predict and regulate the acidogenic process. The fermentation of ethanol and its kinetics were introduced into the model structure. Experimental data from mixed acid-type fermentation in a 28.4 L anaerobic baffled reactor (ABR) fed with a sucrose solution with a chemical oxygen demand of 4000 mg L-1 were used to calibrate the model parameters. Two case studies involving continuous ethanol-type fermentation in an ABR and a continuous stirring tank reactor (CSTR) were used to validate the approach. The modified model achieved good predictions of the experimental data collected from butyric acid, propionic acid, mixed acid, and ethanol-type fermentation in the ABR and CSTR using the standard ADM1 parameter values without any parameter fitting beyond implementation of the variable acidogenic stoichiometry. The pH2 and pH thresholds in butyric acid, propionic acid, mixed acid, and ethanol-type fermentation could be predicted using this model, which was shown to be a valid mathematical tool for the regulation of fermentation type. | 10.1016/j.watres.2019.05.094 |
pubmed_132_11191 | BACKGROUND AND PURPOSE
DW-MRS is a promising tool for the noninvasive identification of the cellular response to cerebral ischemia. To date, the potential confounding effects of aging and the stage of ischemia are unknown. We, therefore, examined the cross-sectional effects of age and different stages of cerebral ischemia on the diffusion of brain metabolites.
MATERIALS AND METHODS
The ADCs of 3 major metabolites, including Cho, Cr, and NAA were measured by DW-MRS in healthy younger (n = 26, 24 ± 2.2 years of age) and older (n = 17, 63 ± 7.0 years of age) adults, as well as in patients with acute (n = 7, 57 ± 4.0 years of age) and subacute (n = 12, 62 ± 7.8 years of age) cerebral ischemia.
RESULTS
Compared with younger adults, healthy older adults presented with significantly reduced ADC values of NAA (P = .000052), Cr (P = .000018), and Cho (P = .00075). Meanwhile, the ADC values of NAA (F(2,36) = 6.057, P = .006), Cr (F(2,36) = 5.634, P = .008), and Cho (F(2,36) = 8.167, P = .001) were significantly different among the acute cerebral ischemia group, subacute cerebral ischemia group, and healthy older controls. These metabolites decreased in the acute stage of cerebral ischemia but increased in the subacute stage, compared with age-matched controls.
CONCLUSIONS
The effect of age should be considered when analyzing diffusion of cerebral metabolites with DW-MRS. Our observations also suggest that metabolite diffusion data may be used to reveal changes in the intracellular environment, depending on the pathologic status of ischemia. | 10.3174/ajnr.A2793 |
pubmed_848_5090 | Issues in diagnosis and complex treatment of pediatric rhabdomyosarcoma were studied in 198 patients with morphologically verified disease. Tumors most often developed in the genitourinary organs (36.6%), head and neck (37%) and--less frequently--on the trunk and extremities (26.4%). The diagnostic workup included instrumental methods, ultrasonography and computed tomography. All modern modalities of cancer treatment, viz. surgery, drug and radiotherapy were used in those patients. As a rule, treatment was either combined or complex. Two-year-survival rate ranged from 83% for rhabdomyosarcoma of the orbit to 50% for those of the trunk and extremities and 47% for head and neck neoplasms. Two-year survival for patients with rhabdomyosarcoma of non-genitourinary sites was 54%. | pubmed_848_5090 |
pubmed_666_7209 | The pathological development of ovarian cancer (OC) is a complex progression that depends on multiple alterations of coding and non-coding genes. Therefore, it is important to capture the transcriptional-regulating events during the progression of OC development and to identify reliable markers for predicting clinical outcomes in patients. A dataset of 399 ovarian serous cystadenocarcinoma patients at different stages from The Cancer Genome Atlas (TCGA) was analyzed. Stage-specific transcription factor (TF)-long non-coding RNA (lncRNA) regulatory networks were constructed by integrating high-throughput RNA molecular profiles and TF binding information. Systematic analysis was performed to characterize the TF-lncRNA-regulating behaviors across different stages of OC. Cox regression analysis and Kaplan-Meier survival curves were used to evaluate the prognostic efficiency of TF-lncRNA regulations and cliques. The stage-specific TF-lncRNA regulatory networks at three OC stages (II, III, and IV) exhibited common structures and specific topologies of risk TFs and lncRNAs. A TF-lncRNA activity profile across different stages revealed that TFs were highly stage-selective in regulating lncRNAs. Functional analysis indicated that groups of TF-lncRNA interactions were involved in specific pathological processes in the development of OC. In a STAT3-FOS co-regulating clique, the TFs STAT3 and FOS were selectively regulating target lncRNAs across different OC stages. Further survival analysis indicated that this TF-lncRNA biclique may have the potential for predicting OC prognosis. This study revealed the topological and dynamic principles of TF-lncRNA regulatory networks and provided a resource for further analysis of stage-specific regulating mechanisms of OC. | 10.3389/fbioe.2020.00460 |
pubmed_678_13530 | BACKGROUND/AIM
Autism is a heterogeneous neurodevelopmental disorder. This study aimed to assess the clinical significance of amino acid profile assay in autism using cation-exchange chromatography with ninhydrin postcolumn derivatization.
MATERIALS AND METHODS
This study included 42 autistic children and 26 apparently healthy children. All participants were subjected to the assay of plasma amino acids (essential, nonessential, and nonstandard) using cation-exchange chromatography with postcolumn derivatization by ninhydrin.
RESULTS
The levels of most of the essential amino acids were significantly lower in autistic children than controls. As regards nonessential amino acids, significantly lower levels for plasma cysteine, tyrosine, and serine and significantly higher levels for plasma glutamic acid were recorded in autistic children than controls. Finally, the autistic group demonstrated significantly lower levels of α-aminoadipic acid, carnosine, and β-alanine and significantly higher levels of hydroxyproline, phosphoserine, β-amino-isobutyric acid, and ammonia as compared to controls.
CONCLUSION
The study revealed that autistic children exhibit distinct alterations in the plasma levels of some amino acids, which can in turn participate in the disease etiology and can be applied as a diagnostic tool for early detection of autism. | 10.3906/sag-1506-105 |
pubmed_1055_10639 | The effect of Al2O3/LiF dual coatings on the electrochemical performance of over-lithiated layered oxide (OLO) has been investigated. A uniform coating of Al2O3 and LiF is obtained on the surface of the layered pristine material. The OLO with a dual Al2O3/LiF coating with a ratio of 1 : 1.5 exhibits excellent electrochemical performance. An initial discharge capacity of 265.66 mA h g(-1) is obtained at a C-rate of 0.1C. This capacity is approximately 15 mA h g(-1) higher than that of pristine OLO. The capacity retention (92.8% at the 50th cycle) is also comparable to that of pristine OLO (91.4% at the 50th cycle). Coating the cathode with a dual layer comprising Al2O3 and LiF leads to improved charging and discharging kinetics, and prevents direct contact between the cathode and the electrolyte. | 10.1039/c6cp02007k |
pubmed_815_12397 | We have isolated a genomic locus from Chinese hamster ovary (CHO) cells that contains a full-length provirus. Nucleotide sequence analysis indicates that it is a defective member of the rodent type C retrovirus family with an env region that is similar to those of mouse amphotropic retrovirus and subgroup B feline leukemia virus. We were able to demonstrate that this provirus is a member of a closely related family of full-length proviruses in CHO cells and Chinese hamster liver. Hybridization probes generated from this genomic clone were used to characterize type C retrovirus RNA expression in CHO cells. Full-length genomic RNA and subgenomic envelope mRNA were detected in CHO cell lines but not in the human-derived 293 cell line. Interestingly, we discovered that the site of retrovirus integration lies within a G repeat sequence belonging to the short interspersed element family of retroposons. | 10.1128/JVI.68.12.7840-7849.1994 |
pubmed_407_11176 | Although seeds are a sink organ, chlorophyll synthesis and degradation occurs during embryogenesis and in a manner similar to that observed in photosynthetic leaves. Some mutants retain chlorophyll after seed maturation, and they are disturbed in seed storability. To elucidate the effects of chlorophyll retention on the seed storability of Arabidopsis (Arabidopsis thaliana), we examined the non-yellow coloring1 (nyc1)/nyc1-like (nol) mutants that do not degrade chlorophyll properly. Approximately 10 times more chlorophyll was retained in the dry seeds of the nyc1/nol mutant than in the wild-type seeds. The germination rates rapidly decreased during storage, with most of the mutant seeds failing to germinate after storage for 23 months, whereas 75% of the wild-type seeds germinated after 42 months. These results indicate that chlorophyll retention in the seeds affects seed longevity. Electron microscopic studies indicated that many small oil bodies appeared in the embryonic cotyledons of the nyc1/nol mutant; this finding indicates that the retention of chlorophyll affects the development of organelles in embryonic cells. A sequence analysis of the NYC1 promoter identified a potential abscisic acid (ABA)-responsive element. An electrophoretic mobility shift assay confirmed the binding of an ABA-responsive transcriptional factor to the NYC1 promoter DNA fragment, thus suggesting that NYC1 expression is regulated by ABA. Furthermore, NYC1 expression was repressed in the ABA-insensitive mutants during embryogenesis. These data indicate that chlorophyll degradation is induced by ABA during seed maturation to produce storable seeds. | 10.1104/pp.112.196881 |
pubmed_203_23052 | BACKGROUND & AIMS
Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of gastroesophageal acid reflux. TLESR is mediated via vagal pathways, which may be modulated by metabotropic glutamate receptors (mGluRs). Group I mGluRs (mGluR1 and 5) have excitatory effects on neurons, whereas group II (mGluR2 and 3) and group III (mGluR4, 6, 7, and 8) are inhibitory. This study determined the effect of mGluRs on triggering of TLESR and reflux in an established conscious ferret model.
METHODS
Esophageal manometric/pH studies were performed in ferrets with chronic esophagostomies. TLESR were induced by a gastric load of 25 mL glucose (pH 3.5) and 30 mL air.
RESULTS
In control treated animals, gastric load induced 3.52 +/- 0.46 TLESRs per 47-minute study, 89.7% of which were associated with reflux episodes (n = 16). The mGluR5 antagonist MPEP inhibited TLESR dose dependently, with maximal 71% +/- 7% inhibition at 35 micromol/kg (n = 9; P < .0001). MPEP also significantly reduced reflux episodes (P < .001) and increased basal lower esophageal sphincter pressure (P < .05). MPEP inhibited swallowing dose dependently, suggesting a common action on trigger mechanisms for swallowing and TLESR. The more selective analogue, MTEP, had more potent effects (90% +/- 6% inhibition TLESR at 40 micromol/kg; n = 8; P < .0001). In contrast, the group I agonist DHPG tended to increase TLESR. The group II agonist (2R, 4R)-APDC was ineffective, whereas the group III agonist L-(AP4 slightly reduced TLESR (33% at 11 micromol/kg; P < .05). The selective mGluR8 agonist (S)-3, 4-DCPG inhibited TLESR by 54% at 15 micromol/kg (P < .01).
CONCLUSIONS
mGluR5 antagonists potently inhibit TLESR and reflux in ferrets, implicating mGluR5 in the mechanism of TLESR. mGluR5 antagonists are therefore promising as therapy for patients with GERD. | 10.1053/j.gastro.2005.06.069 |
pubmed_520_8902 | Amoebic gill disease (AGD) and complex gill disease (CGD) are recurrent gill disorders in Atlantic salmon, resulting in significant aquaculture losses. The role of gill microbiomes in gill disease development is unclear. We undertook a longitudinal study to characterise the gill tissue and gill mucus microbiomes of farmed Atlantic salmon before, and during, a gill disease episode. Using a newly optimised DNA extraction protocol, we sequenced rRNA genes from microbiomes of gill samples taken from 105 individual salmon on a farm, over a summer season. The AGD aetiological agent, Neoparamoeba perurans, was PCR-quantified targeting 18S rRNA genes. Similar analyses were carried out on mucus samples. Mucus scrapings were suitable, non-lethal substitutes for characterisation of the gill prokaryotic community in this study. Gill tissue and gill mucus microbiomes changed during the campaign, correlating with N. perurans concentrations. Time explained 35% of the gill tissue and gill mucus microbiome variance, while N. perurans concentrations explained 5%. Genera including Dyadobacter, Shewanella and Pedobacter were maximally abundant in gill and mucus samples at the timepoint prior to the the detection of gill disorder signs, at T3. Shewanella was significantly more abundant before than during the gill disease episode, and we suggest this genus could be considered in future studies addressing relationships between gill disease and the gill microbiome. | 10.1038/s41598-022-17008-2 |
pubmed_713_25061 | Vesicular-arbuscular (VA) mycorrhizal fungi and ectomycorrhizal fungi were observed together in the same root system, and even within the same root apices, of seedlings of Eucalyptus dumosa A. Cunn. ex Schau. On a population basis, there was a succession of two overlapping mycorrhizal epidemics-VA mycorrhizas followed by ectomycorrhizas. This succession was interpreted as follows. Early build-up of VA mycorrhizas was related to initial higher inoculum potential of that fungus and to rapidity of colonization of individual roots. The ectomycorrhizal fungus was more successful later in achieving secondary infections by hyphal spread and in colonization of lateral root branches. The ectomycorrhizal fungus had no difficulty infecting pre-existing VA mycorrhizas, but the ectomycorrhizal sheath provided a barrier to subsequent VA mycorrhizal infections. While the proportion of VA mycorrhizas to ectomycorrhizas changed between two and five months, the overall proportion of mycorrhizal roots remained constant, suggesting that there could be competition between the different fungi for limiting substrate. | 10.1111/j.1469-8137.1987.tb00195.x |
pubmed_652_24358 | A series of novel marinopyrroles with sulfide and sulphone spacers were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Fluorescence-quenching (FQ) assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM), whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1) for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis) and inhibited cell proliferation. | 10.3390/md12084311 |
pubmed_444_23631 | To revert amyloid fibrils to their native state is a challenge in finding a solution to prevent neurodegenerative diseases. We have adopted a structure-property-energetics correlation-based approach with drugs (5-fluorouracil and hydroxyurea) having multiple hydrogen-bond donors and acceptors as inhibitors targeting different stages of bovine serum albumin fibrillation. We present here a quantitative comprehensive biophysical approach for identifying functionalities in molecules, which offers this feature in terms of polarity and hydrogen bonding. Our objective of identifying the functionality on a drug molecule that establishes effective intermolecular hydrogen bonding with β-strands of protein fibrils was achieved by combined calorimetric, spectroscopic, volumetric, and microscopic correlations. Relationships have been established among thermodynamic signatures, F19-NMR chemical shifts, hydrodynamic diameters, and thermal expansion coefficients to demonstrate that the open-chain molecule is a better inhibitor of fibrillation, but its efficiency decreases with the formation of amorphous aggregates, as compared to the molecule having a uracil ring. The results have provided quantitative insights into the role of polarity and hydrogen bonding in prevention of the fibrillation process. The approach adopted here highlights the physical chemistry underlying such biologically important processes and hence has significance in deriving guidelines for rational drug design. | 10.1021/acs.jpcb.0c06167 |
pubmed_39_14276 | BACKGROUND
Health care demand due to animal bites is frequent, especially in the emergency department (ED). In addition to the physical trauma caused by bites, one should be concerned with infectious diseases that can be transmitted. The range of the lesions depends on the animal species. Bites of Hydrochoerus hydrochaeris (capybaras) in humans are relatively uncommon. Capybaras are docile animals; however, their large rodent incisive teeth could cause serious injury. Localized care, antibiotic therapy when necessary, careful examination of the structures, tetanus and rabies immunization as indicated, and follow-up are recommended for wild animal bites. The authors hereby describe and discuss the medical management of a case of multiple lesions from capybara bites on the right thigh of a man.
CASE REPORT
A 54-year-old male patient was admitted to the ED with a compression bandage soaked with blood after being bitten by a capybara. At the clinical examination, the patient had two lacerating wounds and multiple abrasions on the anterior face of the right thigh. Rabies prophylaxis was administered and the wounds were irrigated and closed with sterile dressings. Oral amoxicillin/clavulanate potassium for 7 days was administered to the patient. The patient was followed up; 3 months after the attack he returned to his previous level of activity without any complication. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We recommend that practitioners and physicians should provide prompt attention due to potentially significant morbidities, particularly rabies. The adequate care of the wound will allow better aesthetic and functional results to victims of wild animal bites. | pubmed_39_14276 |
pubmed_989_12142 | The stomach is among the organs grossly affected organ by diabetic complications. The present study was aimed at investigating the protective role of zinc on stomach of streptozotocin (STZ)-induced diabetes mellitus. Female Swiss albino rats were divided in four experimental groups: Group I, control; group II, control + zinc sulfate; group III, STZ-induced diabetic animals; and group IV, STZ-diabetic + zinc sulfate. Diabetes was induced by intraperitoneal injection of STZ, at a dose of 65 mg/kg body weight. Zinc sulfate (100 mg/kg body weight) was given daily by gavage for 60 days to groups II and IV. At the end of the experiment, the rats were sacrificed, and the tissues were taken. In the diabetic group, hexose, hexosamine, fucose, and sialic acid levels, as well as tissue factor, adenosine deaminase, carbonic anhydrase, xanthine oxidase, lactate dehydrogenase, prolidase activities, advanced oxidized protein products, homocysteine, and TNF-α levels were increased in the stomach tissue homogenates. Whereas, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, paraoxonase, and aryl esterase activities were decreased in the diabetic group. The administration of zinc reversed all the deformities. These findings suggest that zinc has protective role in ameliorating several mechanisms of STZ-induced diabetic stomach injury. | 10.1007/s12011-020-02352-z |
pubmed_878_6981 | OBJECTIVE
To study the arsenic distribution, speciation, its effects on the balance of other elements and the DNA damage by subchronic arsenite exposure in mice.
METHODS
The 8-week-old C57BL/6N mice were matched by weight and divided into control group and supplementation group, which were given 0 or 10 microg/ml of sodium arsenite in the drinking water, and continuous exposed for 6 months.
RESULTS
Arsenic was found in various tissues and organs. The highest ones were in the kidney, lung and liver, reached (563.9 +/- 222.5), (458.6 +/- 191.0) and (279.8 +/- 81.2) ng/g, respectively while the lowest in the blood and brain, reached (82.2 +/- 26.7) ng/ml and (101.8 +/- 30.1) ng/g, respectively. Arsenic exists mainly in the form of dimethylarsinous acid (DMA). Compared to the control group, there was a significant difference (P < 0.05) between arsenic and chromium, copper, zinc, selenium, lead in some organs of arsenic exposed group, but not cadmium. Furthermore, the 8-hydroxydeoxyguanosine (8-OHdG) level of the exposed group was (149.1 +/- 1.0) ng/ml, which was significantly higher than the control group of (76.4 +/- 27.9) ng/ml.
CONCLUSION
Arsenic accumulated in various tissues and organs mainly in the form of DMA, which affected the balance of chromium, copper, zinc, selenium and lead in the body, and led to DNA damage after subchronic exposure. | pubmed_878_6981 |
pubmed_222_17096 | To clarify the changes occurring in diabetic animals in the responsiveness of the myocardium to alpha 1- and beta-adrenoceptor agonists, we examined both alpha- and beta-adrenoceptor-mediated electrophysiological and mechanical responses in the depolarized right ventricular papillary muscle of streptozotocin (STZ) induced diabetic rats and age-matched controls. Both methoxamine (10(-7)-10(-4) M) and isoproterenol (10(-9)-10(-6) M) enhanced the slow response action potential in a concentration-department manner. The amplitude and the APD50 (time required for 50% repolarization) of the methoxamine-induced slow response action potential were both markedly increased in STZ-induced diabetic rats in comparison with control rats, whereas those of the isoproterenol-induced slow response were significantly decreased. The methoxamine-induced contraction in depolarized muscle was slightly but not significantly increased in STZ-induced diabetic rats, whereas the isoproterenol-induced contractile response was significantly attenuated. The maximum number of binding sites (Bmax) for [3H]dihydroalprenolol and for [3H]prazosin were both significantly decreased in diabetic rats, compared with age-matched control rats, without any change in the affinity constants. The slow response action potential induced by methoxamine but not isoproterenol was attenuated by IAP (islet-activating factor) treatment (50 micrograms/kg, i.v. for 3 days). These results suggest that an alpha-adrenoceptor-mediated electrophysiological response is unmasked when the beta-adrenoceptor-mediated response is desensitized in the papillary muscle of STZ-induced diabetic rats. | pubmed_222_17096 |
pubmed_1081_3457 | INTRODUCTION
Spontaneous cervical artery dissection (sCAD) is a major cause of ischemic stroke in young and middle-aged adults, but the occurrence of multiple sCADs could suggest the presence of an underlying arteriopathy. Bilateral hypoglossal nerve palsy caused by extracranial internal carotid artery dissections have been rarely described. We present the case of a 3-vessel sCAD in a patient with repaired tetralogy of Fallot (ToF).
CASE REPORT
A 50-year-old man was admitted to our stroke unit for a sudden onset of left cervical pain, mild left ptosis, dysarthria, and dysphagia. His medical history was remarkable for surgically repaired ToF. Neurological examination showed left Claude-Bernard-Horner syndrome and bilateral hypoglossal palsy. Diffusion-weighted magnetic resonance imaging excluded parenchymal lesions while magnetic resonance angiography showed a pattern of bilateral extracranial internal carotid and right vertebral dissection.
CONCLUSIONS
This is the first case of multiple-vessel sCAD, and more associated with an unusual clinical presentation, in a patient with surgically repaired ToF, supporting the hypothesis that defective large artery elastogenesis plays a role in this congenital disorder, and suggesting the importance of continuous long-term vascular follow-up. | 10.1097/NRL.0000000000000190 |
pubmed_201_2741 | BACKGROUND
Mesenchymal/stromal stem cells (MSCs) are favorably regarded in anti-cancer cytotherapies for their spontaneous chemotaxis toward inflammatory and tumor environments associated with an intrinsic cytotoxicity against tumor cells. Placenta-derived or TRAIL-engineered adipose MSCs have been shown to exert anti-tumor activity in both in-vitro and in-vivo models of multiple myeloma (MM) while TRAIL-transduced umbilical cord (UC)-MSCs appear efficient inducers of apoptosis in a few solid tumors. However, apoptosis is not selective for cancer cells since specific TRAIL receptors are also expressed by a number of normal cells. To overcome this drawback, we propose to transduce UC-MSCs with a bicistronic vector including the TRAIL sequence under the control of IL-6 promoter (pIL6) whose transcriptional activation is promoted by the MM milieu.
METHODS
UC-MSCs were transduced with a bicistronic retroviral vector (pMIGR1) encoding for green fluorescent protein (GFP) and modified to include the pIL6 sequence upstream of the full-length human TRAIL cDNA. TRAIL expression after stimulation with U-266 cell conditioned medium, or IL-1α/IL-1β, was evaluated by flow cytometry, confocal microscopy, real-time PCR, western blot analysis, and ELISA. Apoptosis in MM cells was assayed by Annexin V staining and by caspase-8 activation. The cytotoxic effect of pIL6-TRAIL + -GFP + -UC-MSCs on MM growth was evaluated in SCID mice by bioluminescence and ex vivo by caspase-3 activation and X-ray imaging. Statistical analyses were performed by Student's t test, ANOVA, and logrank test for survival curves.
RESULTS
pIL6-TRAIL + -GFP + -UC-MSCs significantly expressed TRAIL after stimulation by either conditioned medium or by IL-1α/IL-1β, and induced apoptosis in U-266 cells. Moreover, when systemically injected in SCID mice intratibially xenografted with U-266, those cells underwent within MM tibia lesions and significantly reduced the tumor burden by specific induction of apoptosis in MM cells as revealed by caspase-3 activation.
CONCLUSIONS
Our tumor microenvironment-sensitive model of anti-MM cytotherapy is regulated by the axis pIL6/IL-1α/IL-1β and appears suitable for further preclinical investigation not only in myeloma bone disease in which UC-MSCs would even participate to bone healing as described, but also in other osteotropic tumors whose milieu is enriched of cytokines triggering the pIL6. | 10.1186/s13287-017-0655-6 |
pubmed_239_10177 | To date, the precise prevalence of co-morbidity of anxiety and depression in the perinatal period is not well known. We aimed to estimate the prevalence of co-morbid anxiety and depression in the antenatal and postnatal periods. Systematic searches of multiple electronic databases were conducted for studies published between January 1950 and January 2016. We included 66 (24 published and 42 unpublished) studies incorporating 162 120 women from 30 countries. Prevalence of self-reported antenatal anxiety symptoms and mild to severe depressive symptoms was 9.5% [95% confidence interval (CI) 7.8-11.2, 17 studies, n = 25 592] and of co-morbid anxiety symptoms and moderate/severe depressive symptoms was 6.3% (95% CI 4.8-7.7, 17 studies, n = 27 270). Prevalence of a clinical diagnosis of any antenatal anxiety disorder and depression was 9.3% (95% CI 4.0-14.7, 10 studies, n = 3918) and of co-morbid generalized anxiety disorder and depression was 1.7% (95% CI 0.2-3.1, three studies, n = 3085). Postnatally between 1 and 24 weeks postpartum, the prevalence of co-morbid anxiety symptoms and mild to severe depressive symptoms was 8.2% (95% CI 6.5-9.9, 15 studies, n = 14 731), while co-morbid anxiety symptoms and moderate/severe depressive symptoms was 5.7% (95% CI 4.3-7.1, 13 studies, n = 20 849). The prevalence of a clinical diagnosis of co-morbid anxiety and depression was 4.2% (95% CI 1.9-6.6, eight studies, n = 3251). Prevalence rates did not differ with regard to year of publication, country income, selection bias and attrition bias. The results suggest that co-morbid perinatal anxiety and depression are prevalent and warrant clinical attention given the potential negative child developmental consequences if left untreated. Further research is warranted to develop evidence-based interventions for prevention, identification and treatment of this co-morbidity. | 10.1017/S0033291717000617 |
pubmed_134_16506 | INTRODUCTION
The aim of the present study was to investigate different methods for determining osteoarthritis-related (OA) cartilaginous changes.
MATERIALS AND METHODS
Human tibial heads were investigated radiologically, macroscopically and microscopically. The height of the hyaline cartilage was measured with the aid of a computerised digital image analysis system.
RESULTS
The comparison of the different evaluation systems revealed, in part, appreciable variations in severity and produced correlations of r=-0.312-0.673. In none of the methods was a linear correlation between the histomorphometrically measured decrease in cartilage height and the increasing grade of OA evident.
DISCUSSION
The microscopic scores are superior, since they provide the most precise description of cartilaginous structure. The variation in cartilage height with increasing OA is not a linear process; measurement of the cartilage height alone is not a valid parameter for determining the grade of OA. | 10.1007/s00296-004-0582-6 |
pubmed_983_18654 | We have developed efficient methods for the preparation of N(6),5'-bis-ureidoadenosine derivatives and their 5'-carbamoyl-N(6)-ureido congeners. Treatment of 5'-azido-5'-deoxy-N(6)-(N-alkyl or -arylurea)adenosine derivatives (6a-d) with H(2)/Pd-C or Ph(3)P/H(2)O, followed by N-methyl-p-nitrophenylcarbamate gave N(6),5'-bis-ureido products 7a-d in 49-78% yield. Analogous derivatives in the 5'-carbamoyl-N(6)-ureido series were prepared by treatment of 2',3'-bis-O-TBS-adenosine (11) with N-methyl-p-nitrophenylcarbamate followed by acylation with appropriate isocyanates which gave 13a-d in 45-69% yield. A more versatile route for obtaining potentially vast libraries of compounds from both series was achieved by treatment of 5'-N-methylureido- or 5'-N-methylcarbamoyladenosine derivatives with ethylchlorformate to give N(6)-ethoxycarbonyl derivatives (9 and 14) in 55-63% yields, respectively. Simple heating of 9 or 14 in the presence of primary alkyl- or arylamines gave the corresponding N(6),5'-bis-ureido- or 5'-carbamoyl-N(6)-ureidoadenosine derivatives in good yields (33-72% and 39-83%; 10a-e and 15a-e, respectively). Significant antiproliferative activities (IC(50)≈4-10 μg/mL) were observed for a majority of the N(6),5'-bis-ureido derivatives, whereas the 5'-carbamoyl-N(6)-ureido derivatives were generally less active (IC(50) >100 μg/mL). A 2',3'-O-desilylated derivative (5'-amino-5'-deoxy-5'-N-methylureido-N(6)-(N-phenylcarbamoyl)adenosine, 16) was shown to inhibit binding of 16 of 441 protein kinases to immobilized ATP-binding site ligands by 30-40% in a competitive binding assay at 10 μM. Compound 16 was also shown to bind to bone morphogenetic protein receptor 1b (BMPR1b) with a Kd=11.5 ± 0.7 μM. | 10.1016/j.bmc.2011.11.043 |
pubmed_1110_21594 | The Mycobacterium tuberculosis genome encodes twenty cytochrome P450 enzymes, most or all of which appear to have specific physiological functions rather than being devoted to the removal of xenobiotics. However, in many cases their specific functions remain obscure. Considerable spectroscopic, biophysical, crystallographic, and catalytic information is available on nine of these cytochrome P450 enzymes, although gaps exist in our knowledge of even these enzymes. The available evidence indicates that at least three of the better-characterized enzymes are promising targets for antituberculosis drug discovery. This review summarizes the information on the nine relatively well-characterized cytochrome P450 enzymes, with a particular emphasis on CYP121, CYP125, and CYP142 from Mycobacterium tuberculosis and Mycobacterium smegmatis. | 10.1016/j.jinorgbio.2018.01.010 |
pubmed_677_1984 | BACKGROUND
Propofol is short-acting intravenous general anesthetics that reduces cardiovascular hemodynamics. The effects of propofol on intrinsic myocardial contractility, however, remain debatable. The aim of the current study was to test the hypothesis that inhibitory effects of propofol on left ventricular (LV) contractility and mechanical work capability of in situ ejecting rat hearts are attenuated after a brief regional ischemia and reperfusion.
METHODS
The authors obtained steady-state LV pressure-volume loops and intermittently obtained LV end-systolic pressure-volume relation and evaluated effects of propofol on LV function by end-systolic pressure (ESPmLVV), systolic pressure-volume area (PVAmLVV) at midrange LV volume (mLVV).
RESULTS
Propofol (5.2 +/- 0.3 approximately 11.1 +/- 3.7 microg.ml) significantly decreased ESP0.08 to 78 +/- 12% approximately 64 +/- 13% of prepropofol and PVA0.08 to 76 +/- 13%approximately 63 +/- 16% of prepropofol in normal hearts, whereas propofol at a lower concentration (4.1 +/- 1.0 microg/ml) did not. Although brief ischemic-reperfusion per se did not affect LV function, propofol after that, even at a lower concentration (4.1 +/- 1.0 microg/ml), significantly decreased ESP0.08 to 70 +/- 27% of prepropofol and PVA0.08 to 68 +/- 33% of prepropofol. Pretreatment with a protein kinase C (PKC) inhibitor, bisindolylmaleimide reduced the propofol (4.1 +/- 1.0 microg/ml)-induced greater decreases in ESP0.08 and PVA0.08 after brief ischemic-reperfusion to 94 +/- 33% and 92 +/- 39% of prepropofol. In the propofol-infused hearts after brief ischemic-reperfusion, protein kinase C-epsilon translocation to the nucleus-myofibril fraction was found.
CONCLUSION
In contrast to the study hypothesis, brief ischemic-reperfusion enhanced the inhibitory effects of propofol on LV systolic function; this enhancement is attributable to activation of protein kinase C. | 10.1097/00000542-200410000-00012 |
pubmed_576_18923 | Angiotensin-converting enzyme (ACE) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity (M). However, the evidence for the latter effect does not stand close scrutiny. We have assessed the effect of the ACE inhibitor trandolapril on M in 16 patients (mean +/- SD age, 58 +/- 10.6 yr) with mild-to-moderate essential hypertension (initial blood pressure, 173 +/- 14.5/93 +/- 8.0 mm Hg), obesity (body mass index, 30 +/- 5.4 kg/m2), and impaired glucose intolerance (n = 4) or type 2 diabetes (n = 12) in a double-blind, placebo-controlled crossover design. All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies (soluble insulin, 1.5 mU/kg x min) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg trandolapril or placebo (2-week washout). M (mean +/- SD) did not change with trandolapril: placebo (run-in), 5.2 +/- 1.98 mg/kg x min; placebo, 5.3 +/- 1.70 mg/kg x min; trandolapril, 5.1 +/- 1.65 mg/kg x min; P = 0.58; 95% confidence intervals, -0.74, 0.43 (trandolapril vs. placebo); 95% power to exclude an 8% increase in M. In conclusion, trandolapril had no clinically relevant effect on M in patients with hypertension and type 2 diabetes. Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and/or use of surrogate measures of M. | 10.1210/jcem.85.5.6599 |
pubmed_349_21007 | Interferon-γ-inducible protein 10 (IP-10), also known as chemokine C-X-C motif ligand (CXCL) 10, is closely associated with antiviral immunity and the progression of chronic hepatitis B (CHB). However, the value of baseline serological and histological IP-10 expression levels in predicting the efficacy of the antiviral response to nucleoside/nucleotide analogues (NAs) is still unknown. In our research, intrahepatic and peripheral IP-10 expression levels were systemically examined before and after treatment with entecavir (ETV). Baseline serological and histological IP-10 expression levels were significantly increased in patients with CHB, particularly in patients with higher degrees of liver inflammation and liver fibrosis. Moreover, higher baseline intrahepatic IP-10 levels indicated better prognoses in patients with CHB after entecavir therapy. The baseline IP-10 level was also positively associated with several clinical parameters, including baseline levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus (HBV) DNA, and hepatitis B surface antigen (HBsAg), and with the decrease in HBsAg levels after treatment. In addition, monocyte-derived IP-10 was expressed at higher levels in patients with CHB than in patients with liver cirrhosis (LC) and healthy controls (HC). According to the results of our in vitro experiments, IP-10 directly promoted hepatocyte apoptosis. Based on these findings, baseline serological and histological IP-10 levels might predict CHB severity and the decrease in HBsAg levels after entecavir therapy. | 10.14348/molcells.2017.0051 |
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