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In vitro interactions between endogenous polyamines and superoxide anion.
Endogenous polyamines with anti-inflammatory activity scavenge superoxide and possibly other oxy-radicals produced by xanthine oxidase or from stimulated polymorphonuclear leucocytes. Polyamines incubated with stimulated cells are in part metabolised. Putrescine is converted to metabolites tentatively identified as gamma-aminobutyraldehyde, delta'-pyrolline and gamma-aminobutyric acid. The metabolism of spermidine, spermine and cadaverine was not as extensively studied but metabolites were formed that gave positive reaction to Schiffs reagent on tlc plates. The possible relevance of the results to the anti-inflammatory action of polyamines is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Organ donation as gift exchange.
Organ donation, considered by sociologists as a type of gift exchange, involves moral, social, psychological, religious and legal issues. This gift exchange paradigm can be used as a framework to understand donor and recipient issues, cadaveric organ donation and the importance of the role of nurses during organ procurement. | {
"pile_set_name": "PubMed Abstracts"
} |
The influence of out-of-plane geometry on pulsatile flow within a distal end-to-side anastomosis.
We present an experimental and computational investigation of time-varying flow in an idealized fully occluded 45 degrees distal end-to-side anastomosis. Two geometric configurations are assessed, one where the centerlines of host and bypass vessels lie within a plane, and one where the bypass vessel is deformed out of the plane of symmetry, respectively, termed planar and non-planar. Flow experiments were conducted by magnetic resonance imaging in rigid wall models and computations were performed using a high order spectral/hp algorithm. Results indicate a significant change in the spatial distribution of wall shear stress and a reduction of the time-averaged peak wall shear stress magnitude by 10% in the non-planar model as compared to the planar configuration. In the planar geometry the stagnation point follows a straight-line path along the host artery bed with a path length of 0.8 diameters. By contrast in the non-planar case the stagnation point oscillates about a center that is located off the symmetry plane intersection with the host artery bed wall, and follows a parabolic path with a 0.7 diameter longitudinal and 0.5 diameter transverse excursion. A definition of the oscillatory shear index (OSI) is introduced that varies between 0 and 0.5 and that accounts for a continuous range of wall shear stress vector angles. In both models, regions of elevated oscillatory shear were spatially associated with regions of separated or oscillating stagnation point flow. The mean oscillatory shear magnitude (considering sites where OSI>0.1) in the non-planar geometry was reduced by 22% as compared to the planar configuration. These changes in the dynamic behavior of the stagnation point and the oscillatory shear distribution introduced by out-of-plane graft curvature may influence the localization of vessel wall sites exposed to physiologically unfavorable flow conditions. | {
"pile_set_name": "PubMed Abstracts"
} |
Distributed strain measurements using fiber Bragg gratings in small-diameter optical fiber and low-coherence reflectometry.
Optical low coherence reflectometry and fiber Bragg gratings written in small diameter (50 micrometer) optical fibers were used for measurements of non-homogenous internal strain fields inside an epoxy specimen with sub-grating length resolution. The results were compared with measurements using Fiber Bragg gratings in standard size (125 micrometer) single mode fibers and show that smaller fibers are less intrusive at stress heterogeneities. | {
"pile_set_name": "PubMed Abstracts"
} |
Hypoparathyroidism.
Hypoparathyroidism is a disease characterized by inadequately low circulating concentrations of parathyroid hormone (PTH) resulting in low calcium levels and increased phosphate levels in the blood. Symptoms of the disease result from increased neuromuscular irritability caused by hypocalcaemia and include tingling, muscle cramps and seizures. The most common cause of the disease is inadvertent removal of, or injury to, the parathyroid glands during neck surgery, followed by genetic, idiopathic and autoimmune aetiologies. Conventional treatment includes activated vitamin D and/or calcium supplements, but this treatment does not fully replace the functions of PTH and can lead to short-term problems (such as hypocalcaemia, hypercalcaemia and increased urinary calcium excretion) and long-term complications (which include nephrocalcinosis, kidney stones and brain calcifications). PTH replacement has emerged as a new treatment option. Clinical trials using human PTH(1-34) and PTH(1-84) showed that this treatment was safe and effective in studies lasting up to 6 years. Recombinant human PTH(1-84) has been approved in the United States and Europe for the management of hypoparathyroidism; however, its effect on long-term complications is still being evaluated. Clinical practice guidelines, which describe the consensus of experts in the field, have been published and recognize the need for more research to optimize care. In this Primer, we summarize current knowledge of the prevalence, pathophysiology, clinical presentation and management of hypoparathyroidism. | {
"pile_set_name": "PubMed Abstracts"
} |
Role of echocardiography in takotsubo cardiomyopathy.
Takotsubo cardiomyopathy (TTC) is characterized by transient and reversible left ventricular (LV) systolic dysfunction due to extended myocardial stunning. Despite a good long term prognosis, approximately one-third of patients with TTC experience life-threatening complications during the acute phase. Echocardiography is the first imaging modality for an early evaluation of LV systolic and diastolic function in patients with TTC. Moreover, echocardiography allows the detection of specific findings associated with TTC, such as LV outflow tract obstruction, mitral regurgitation, and right ventricular involvement, providing crucial information for clinical management and therapy and for monitoring myocardial function recovery during the follow-up. | {
"pile_set_name": "PubMed Abstracts"
} |
Monostephanostomum georgianum n. sp. (Digenea: Acanthocolpidae) from Arripis georgianus Valenciennes) Perciformes: Arripidae off Kangaroo Island, South Australia, with comments on Monostephanostomum Kruse, 1979 and Stephanostomum Looss, 1899.
Monostephanostomum georgianum n. sp. is described from Arripis georgianus off Kangaroo Island, South Australia. It differs from its congeners by the presence of a short second row of oral spines. M. manteri Kruse, 1979 is reported from A. georgianus off southern Western Australia and Kangaroo Island, South Australia and A. trutta off northern Tasmania. It is considered that the other two species, M. yamagutii Ramadan, 1984 and M. krusei Reimer, 1983, should probably be removed from this genus. Two new combinations are formed, M. gazzae (Shen, 1990) n. comb. (from Stephanostomum) and M. mesospinosum (Madhavi, 1976) n. comb. (from Stephanostomum). A key to the four recognised species of Monostephanostomum is given. | {
"pile_set_name": "PubMed Abstracts"
} |
Overweight and obesity: key components of cardiometabolic risk.
The current obesity epidemic is a major public health concern worldwide, in both developed and developing countries, and in adults and children alike. Obesity confers physical stress on multiple biologic processes and is associated with an increased risk of developing cardiovascular disease, type 2 diabetes mellitus, osteoarthritis, and certain forms of cancer, among other serious diseases. Therefore, it is essential that all health care providers take an active role in addressing the issue of obesity with their patients to reduce their cardiometabolic risks. Indeed, there is a 3-fold increase in the odds that a patient will attempt weight loss if it is recommended by a trusted health care professional. A reduction of only 5% to 10% of body weight improves lipid profiles, insulin sensitivity, and endothelial function, and reduces thrombosis and inflammatory markers. There is evidence, however, that humans are highly sensitive to the availability and nature of food in the environment, which presents a formidable obstacle to achieving lasting weight loss. The National Heart, Lung, and Blood Institute of the National Institutes of Health recommends lifestyle modification as the primary intervention. For individuals who do not respond or for those who also have a weight-related illness, a weight loss medication may need to be added to their treatment plan. While there are few medical options currently available, new compounds for the treatment of obesity are under investigation. | {
"pile_set_name": "PubMed Abstracts"
} |
Pathogenesis of steatohepatitis: insights from the study of animal models.
Non-alcoholic steatohepatitis (NASH) is a disease of expanded clinical importance. Its pathogenesis remains poorly understood. Tools to identify patients at risk and targeted treatments are lacking. The aim of this work was to analyse potential pathogenic mechanisms for inflammatory recruitment and fibrogenesis in NASH, using animal models. We demonstrated that oxidative stress, invariably associated with NASH, is a primary and necessary event for disease progression. Inhibition of stress-activated transcription factor NF-chiB prevents NASH. NF-chiB therefore appears as a pathogenic link between oxidative stress and NASH. Increased lipid beta-oxidation in NASH could generate oxidative stress. We used a potent inducer of PPAR-alpha to stimulate beta-oxidation in a model of steatohepatitis. Such treatment induced a complete clearance of steatosis together with a significant reduction of oxidative stress and oxidative injuries and prevention of inflammation and fibrosis. Thus in a situation of steatosis, stimulation of lipid combustion depletes the substrates for lipid peroxidation and thereby decreases oxidative stress. This effect is sufficiently powerful to prevent the development of steatohepatitis. We demonstrated that leptin is a pro-fibrogenic adipocytokine and is implicated in the regulation of liver regeneration. Leptin plays this crucial physiological role in hepatic wound healing by controlling the production and the activation of cytokines. The insulin sensitising drugs thiazolidinediones have antiinflammatory and anti-fibrotic properties in rats. We demonstrated that such drugs are poorly effective in the treatment of preestablished hepatic fibrosis in rats and unable to prevent fibrogenesis in vitro as well as in vivo in mice. Direct anti-fibrotic effect of such substances remains to be demonstrated in humans. In conclusion, our work demonstrates the importance of oxidative stress in the pathogenesis of NASH, the role of intrahepatic lipid overload and underlies the links between adipose tissue and the liver. | {
"pile_set_name": "PubMed Abstracts"
} |
Modelling audiovisual integration of affect from videos and music.
Two experiments examined how affective values from visual and auditory modalities are integrated. Experiment 1 paired music and videos drawn from three levels of valence while holding arousal constant. Experiment 2 included a parallel combination of three levels of arousal while holding valence constant. In each experiment, participants rated their affective states after unimodal and multimodal presentations. Experiment 1 revealed a congruency effect in which stimulus combinations of the same extreme valence resulted in more extreme state ratings than component stimuli presented in isolation. An interaction between music and video valence reflected the greater influence of negative affect. Video valence was found to have a significantly greater effect on combined ratings than music valence. The pattern of data was explained by a five parameter differential weight averaging model that attributed greater weight to the visual modality and increased weight with decreasing values of valence. Experiment 2 revealed a congruency effect only for high arousal combinations and no interaction effects. This pattern was explained by a three parameter constant weight averaging model with greater weight for the auditory modality and a very low arousal value for the initial state. These results demonstrate key differences in audiovisual integration between valence and arousal. | {
"pile_set_name": "PubMed Abstracts"
} |
Respirable dust concentrations in equine stables. Part 2: the benefits of soaking hay and optimising the environment in a neighbouring stable.
The effect of soaking hay to minimise equine breathing zone respirable dust concentration (RDC) is unknown, as is the duration of soaking required. Additionally, the influence of the bedding and forage used in one stable on the mean and maximum RDC in a neighbouring stable within a common airspace is unknown. Consequently, in the management of equine environmental respiratory disease uncertainty remains about the necessity for optimising conditions in neighbouring stables. Investigations using a real-time continuous particle monitor revealed that when feeding hay, horses' mean breathing zone RDC was significantly reduced if the hay was immersed or soaked for a prolonged time, prior to feeding. There was no advantage in soaking for an extended time period. Implementing management changes in one stable (changing from straw bedding and hay feeding to wood shavings bedding and haylage feeding) significantly reduced mean and maximum background RDC in a neighbouring stable within a common airspace. | {
"pile_set_name": "PubMed Abstracts"
} |
Risk factors in the development of cesarean section infection.
Fifty consecutive patients undergoing cesarean section were evaluated prospectively. A data collection form was developed and 113 variables relating to demographic features, antepartum care, intrapartum events and postpartum course were evaluated. All of the patients were seen and evaluated within 24 hours of delivery and all forms were completed when the patients were discharged from the hospital. Twenty-five of the 50 patients had postpartum febrile morbidity develop. There were 14 instances of endometritis; five, wound infections; two, urinary tract infections; two, upper respiratory tract infections; three pulmonary infections; one patient with phlebitis, and two with febrile morbidity and no apparent source. Factors significantly associated with an increased risk of developing febrile morbidity included antepartum infections, resident staff as primary surgeon, extension of the uterine incision and positive endometrial culture at the time of the operation. Patients undergoing elective repeat cesarean section had less febrile morbidity than others (p less than 0.025). Statistically significant differences between the two groups were not found for the variables obesity, anemia, rupture of membranes, number of pelvic examinations, fetal monitoring, fetal tachycardia, general anesthesia and skin preparation. Operative blood loss was greater in the patients having febrile morbidity develop, but this difference was not statistically significant. | {
"pile_set_name": "PubMed Abstracts"
} |
Process-independent quantitative assessment of residual biological contamination of medical devices reprocessed in washer-disinfectors.
A method based on measuring a soil-induced fluorescence intensity response of 1,8-anilinonaphthalene sulfonate at two fixed wavelengths (460 and 510 nm) was used for determining residual contamination on test soil carriers simulating medical devices after passage through a hospital washer-disinfector. The fluorescence response can be satisfactorily calibrated to soil levels as low as approximately 1 microg/L. Practical tests were performed in two hospitals with washer-disinfectors of 3 types and with several chemical or enzymic cleansers-disinfectants. In combination with the previously developed system of standardized test soil carriers simulating both easily and poorly accessible parts of soiled medical devices, the liver-lactose-oil test soil and an efficient sonication procedure for stripping the residual soil off the carriers, this soil detection method permits the detection of very low contamination levels. | {
"pile_set_name": "PubMed Abstracts"
} |
Substitute laryngeal voice sources after partial laryngectomies.
The larynx is a highly adjustable organ, preserving at least some of its functions even when severely damaged. Partial surgical excision (trauma) of the larynx creates new anatomical and functional conditions for the production of voice. Depending on the type and extent of the excision, functional closure of the glottis is compromised, usually resulting in a hyperkinetic pattern of voice production. The glottal voice source is jeopardized, which can result in the creation of substitute laryngeal voice sources. Their capacity for voice production is limited, and therefore these mechanisms have considerable clinical significance. In this paper, the incidence of substitute laryngeal voice sources after partial laryngectomies and its clinical implications are analyzed. | {
"pile_set_name": "PubMed Abstracts"
} |
The Big Data Revolution: Opportunities for Chief Nurse Executives.
Informatics competency adoption is a recognized issue across nursing roles in digital health practice settings. Further, it has been suggested that the health system's inability to reap the promised benefits of electronic health/patient records is, in part, a manifestation of inadequate development of informatics competency by chief nurse executives (CNEs) and other clinicians (Amendola 2008; Simpson 2013). This paper will focus on CNE informatics competency and nursing knowledge development as it pertains to the Big Data revolution. With the paper's aim of showing how CNEs armed with informatics competency can harness the full potential of Big Data offering new opportunities for nursing knowledge development in their clinical transformation roles as eHealth project sponsors. It is proposed that informatics-savvy CNEs are the new transformational leaders of the digital age who will have the advantage to successfully advocate for nurses in leading 21st-century health systems. Also, transformational CNEs armed with informatics competency will position nurses and the nursing profession to achieve its future vision, where nurses are perceived by patients and professionals alike as knowledge workers, providing the leadership essential for safe, quality care and demonstrating nursing's unique contributions to fiscal health through clinically relevant, evidence-based practices (McBride 2005b). | {
"pile_set_name": "PubMed Abstracts"
} |
Sex-specific promoters regulate Dnmt3L expression in mouse germ cells.
Dnmt3L, a member of the DNA methyltransferase 3 family, lacks enzymatic activity but is required for de-novo methylation of imprinted genes in oocytes and for transposon repression in male germ cells. We used northern blots, RT-PCR, 5' rapid amplification of complementary DNA (cDNA) ends (RACE), RNase H mapping, real-time/quantitative RT-PCR and in situ hybridization to identify and characterize Dnmt3L transcripts produced during germ cell development. Mouse Dnmt3L uses three sex-specific promoters, not the single promoter previously thought. A promoter active in prospermatogonia drives transcription of an mRNA encoding the full-length protein in perinatal testis, where de-novo methylation occurs. Late pachytene spermatocytes activate a second promoter in intron 9 of the Dnmt3L gene. After this stage, the predominant transcripts are three truncated mRNAs, which appear to be non-coding. We could also detect similar adult testis transcripts in humans. In the mouse ovary, an oocyte-specific promoter located in an intron of the neighbouring autoimmune regulator (Aire) gene produces a transcript with the full open reading frame (ORF). This is the only Dnmt3L transcript found in growing oocytes and is absent in the oocytes of Dnmt3L-/- females. Sex-specific promoters control Dnmt3L expression in the mouse germ line, mirroring the situation at the Dnmt1 and Dnmt3A loci. | {
"pile_set_name": "PubMed Abstracts"
} |
The use of CSF pressure recordings in acute purulent meningitis.
Non-fluid displacing pressure transducers can be applied to a spinal needle at LP and direct CSF pressure recordings obtained routinely. The method is particularly applicable to children with suspected meningitis and is both a safer and a more accurate estimate of CSF pressure. Children with acute purulent meningitis frequently have raised intracranial pressure on presentation and Mannitol infusion during the LP recording is useful in returning the pressure to normal. | {
"pile_set_name": "PubMed Abstracts"
} |
On a possible growth mechanism for polycyclic aromatic hydrocarbon di-cations: C(7)H(6)(2+) + C(2)H(2).
The mechanism of the bond-forming reaction between C(7)H(6) (2+) and C(2)H(2) to yield C(9) entities has been investigated by density functional theory calculations with close comparison with experimental data. It is shown that the reaction produces the C(9)H(6) (2+) and C(9)H(7) (2+) di-cations with geometries most probably derived from the indene skeleton. In comparison, the formation of linear structures of di-cations is much more energy-demanding and therefore appears improbable. | {
"pile_set_name": "PubMed Abstracts"
} |
Antibacterial cathelicidin peptide CAP11 inhibits the lipopolysaccharide (LPS)-induced suppression of neutrophil apoptosis by blocking the binding of LPS to target cells.
The action of antibacterial cathelicidin CAP11 (cationic antibacterial polypeptide of 11 kDa) on the lipopolysaccharide (LPS)-induced suppression of neutrophil apoptosis was evaluated in vitro. Human neutrophils (10(6) cells/ml) were incubated alone or with mononuclear cells (6 x 10(5) cells/ml) in the presence of LPS (10 ng/ml) and CAP 11 (0.1 approximately 10 microg/ml), and neutrophil apoptosis was determined. LPS suppressed neutrophil apoptosis, accompanied with the activation of NF-kappaB, phosphorylation of extracellular signal-related protein kinase (ERK), expression of Bcl-XL (an anti-apoptotic protein) and inhibition of caspase 3 activity. Interestingly, CAP11 (> 1 microg/ml) reversed the actions of LPS to trigger these changes, and induced neutrophil apoptosis (p < 0.0001). Moreover, neutralizing antibodies against Mac-1 (CD11b/CD18) and Toll-like receptor (TLR) 4 completely blocked the LPS-induced suppression of neutrophil apoptosis (p < 0.0001), suggesting a major role of Mac-1 and TLR4 in the LPS-mediated neutrophil activation. In addition, LPS activated monocytes to produce proinflammatory cytokines (IL-1beta, TNF-alpha and IL-8) and inhibited neutrophil apoptosis. Importantly, CAP11 (> 1 microg/ml) reduced the cytokine production, thereby inducing neutrophil apoptosis (p < 0.0001). Finally, CAP11 (> 1 microg/ml) strongly suppressed the LPS-binding to neutrophils and monocytes (p < 0.01). CAP11 is able to block the LPS-induced survival of neutrophils via the suppression of anti-apoptotic signaling in neutrophils and cytokine production from monocytes by inhibiting the binding of LPS to target cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Neutrophil-to-lymphocyte ratio as a quick and reliable predictive marker to diagnose the severity of diabetic retinopathy.
Diabetic retinopathy (DR) is the most common complication and cause of visual impairment in diabetes patients. The pathogenesis is not fully understood, but several studies have suggested that inflammation plays an important role. The neutrophil-to-lymphocyte ratio (NLR) was defined as a novel potential marker to determine inflammation. We aimed to evaluate the relationship between DR and inflammation by using NLR. The study was included 58 patients diagnosed with type 2 diabetes mellitus. Twenty-four of them had DR. The control group was composed of 52 age- and sex-matched healthy subjects. Retinopathy was graded using the International Clinical Diabetic Retinopathy Disease Severity Scale. NLR values of the diabetes patients were significantly higher than those of the healthy control group (P<0.001), and NLR levels of the patients with DR were higher than those of the patients without DR (P<0.001). In addition, NLR values were correlated with the presence of DR and DR grades (r=0.466, P<0.001; and r=0.630, P<0.001, respectively). According to our knowledge, this is the first study investigating the relationship between NLR, which is an inflammatory marker, and DR and its severity. Our results suggest that while evaluating diabetes patients in terms of DR, higher NLR values may be a remarkable marker. | {
"pile_set_name": "PubMed Abstracts"
} |
Ponicidin and oridonin are responsible for the antiangiogenic activity of Rabdosia rubescens, a constituent of the herbal supplement PC SPES.
Antiangiogenic activity has been identified in an aqueous EtOH extract of Rabdosia rubescens, a component of the dietary supplement PC SPES. Bioassay-guided fractionation using a novel in vitro human endothelial cell-based assay for angiogenesis afforded the diterpenoids ponicidin (1) and oridonin (2), with significant antiangiogenic activity at subcytotoxic concentrations, suggesting that these constituents may strongly contribute to the demonstrated clinical efficacy of PC SPES as a treatment for advanced prostate cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
A phase II study of bortezomib in the treatment of metastatic malignant melanoma.
Bortezomib is a proteasome inhibitor with manageable clinical toxicity and laboratory evidence of anti-melanoma activity. Therefore, it was considered for clinical testing in patients with metastatic melanoma. Patients with metastatic melanoma and adequate hematologic, renal, and hepatic function were treated with bortezomib (a 1.5-mg/m2 intravenous bolus twice weekly for 2 of every 3 weeks). Eligible patients were age > or = 18 years with an Eastern Cooperative Oncology Group performance status of 0-1. The primary goal of the current study was to evaluate the 18-week disease progression-free survival rate and tolerability of bortezomib in these patients. The current study was intended to treat 45 patients. It was closed at the planned interim analysis due to early evidence of insufficient clinical efficacy. Twenty-seven patients with a median age of 56 years (range, 32-77 years)were accrued. There were no major clinical responses to treatment. Only 6 patients (22%) achieved stable disease. Of these 6 patients, 4 were still stable after 4 cycles of treatment, but were removed from the study due to toxicity. The median time to disease progression was 1.5 months (95% confidence interval [95% CI], 1.4-1.6) with a median overall survival of 14.5 months (95% CI, 9-22). Having failed bortezomib, most patients proceeded to other clinical trials. Twenty-six patients were evaluable for toxicity. One patient was removed from the study for other reasons and could not return for the cycle evaluation and thus was never evaluated. Of the 26 patients, no Grade 4/5 treatment-related toxicities (using the National Cancer Institute Common Toxicity Criteria [version 2.0]) were reported. Eleven patients (42%) had Grade 3 toxicities (believed to be at least possibly related to treatment), including sensory neuropathy, thrombocytopenia, constipation, fatigue, ileus, abdominal pain, and infection without neutropenia. The median number of treatment cycles patients received was two (range, one to six treatment cycles). Two patients (7%) had 1 dose delay and 6 patients (22%) had dose reductions during 1 treatment cycle due to adverse events. Single-agent bortezomib, administered twice weekly x 2 weeks, every 3 weeks at a dose of 1.5 mg/m2, was not found to be effective in the treatment of patients with metastatic melanoma. | {
"pile_set_name": "PubMed Abstracts"
} |
[Functional results after replantation/revascularization of major parts of the extremities].
Twenty-five patients who were submitted to replantation or revascularization of a total of 11 upper arms, 11 forearms, one wrist and three feet were followed-up with the object of assessing the functional status. 85% of the replantated/revascularized parts survived. The follow-up examination included assessment of the level of amputation, mechanism of the injury, duration of ischaemia and the age of the patient in relation to the joint mobility achieved, strength, sensibility, cosmetic inconveniences and the return to previous employment. Out of 19 surviving upper limbs and three feet, the results were classified as excellent and good after Tamai's and Chen's methods. The best results were found after sharp lesions but the investigation revealed that even in severe avulsion lesions, it proved possible to obtain good results. It is thus not possible to establish definite directives for the indications for replantation. The final decision concerning reconstruction cannot be made until after contact with one of the departments in which replantation can be undertaken. | {
"pile_set_name": "PubMed Abstracts"
} |
The B1 subunit of the H+ATPase is a PDZ domain-binding protein. Colocalization with NHE-RF in renal B-intercalated cells.
The 56-kDa B1 subunit of the vacuolar H(+)ATPase has a C-terminal DTAL amino acid motif typical of PDZ-binding proteins that associate with the PDZ protein, NHE-RF (Na(+)/H(+) exchanger regulatory factor). This B1 isoform is amplified in renal intercalated cells, which play a role in distal urinary acid-base transport. In contrast, proximal tubules express the B2 isoform that lacks the C-terminal PDZ-binding motif. Both the B1 56-kDa subunit and the 31-kDa (E) subunit of the H(+)ATPase are pulled down by glutathione S-transferase NHE-RF bound to GSH-Sepharose beads. These subunits associate in vivo as part of the cytoplasmic V1 portion of the H(+)ATPase, and the E subunit was co-immunoprecipitated from rat kidney cytosol with NHE-RF antibodies. The interaction of H(+)ATPase subunits with NHE-RF was inhibited by a peptide derived from the C terminus of the B1 but not the B2 isoform. NHE-RF colocalized with H(+)ATPase in either the apical or the basolateral region of B-type intercalated cells, whereas NHE-RF staining was undetectable in A-intercalated cells. In proximal tubules, NHE-RF was located in the apical brush border. In contrast, H(+)ATPase was concentrated in a distinct membrane domain at the base of the brush border, from which NHE-RF was absent, consistent with the expression of the truncated B2 subunit isoform in this tubule segment. The colocalization of NHE-RF and H(+)ATPase in B- but not A-intercalated cells suggests a role in generating, maintaining, or modulating the variable H(+)ATPase polarity that characterizes the B-cell phenotype. | {
"pile_set_name": "PubMed Abstracts"
} |
Autonomic dysfunction in systemic lupus erythematosus.
The objectives were to study the frequency and pattern of autonomic dysfunction in systemic lupus erythematosus (SLE). Fifty-one patients of SLE and 30 age- and sex-matched healthy controls were studied prospectively using a standard battery of noninvasive tests. Autonomic symptoms were seen in 37% patients. On laboratory testing incipient dysfunction was seen in 9 (18%) cases and 1 (3%) control, while atypical involvement was seen in 11 (21%) cases and 6 (20%) controls. Autonomic dysfunction did not correlate with disease duration, lupus activity, disease damage, any particular organ involvement or the presence/absence of peripheral neuropathy. Autonomic neuropathy is not uncommon in lupus and may exist independent of peripheral neuropathy. There are no specific clinical predictors. The clinical significance of autonomic dysfunction detected by laboratory testing warrants longitudinal studies. | {
"pile_set_name": "PubMed Abstracts"
} |
Antimicrobial, antioxidant, and antimutagenic activities of selected marine natural products and tobacco cembranoids.
Multidrug resistance (MDR) in microorganisms is a cause of major concern for clinicians and pharmaceutical industries. Continuous development of new antimicrobial drugs with multiple targets and potentials is expected to efficiently combat MDR in these microorganisms. In a continued exploration of new antimicrobial drug leads, 11 marine natural products, semisynthetic, or related synthetic analogs (1-11) and two tobacco cembranoids (12 and 13) were screened for their antimicrobial, antioxidant, and antimutagenic activities. Eight compounds showed varying levels of both antibacterial and antifungal activities. Compounds such as 17-O-methyllatrunculin-A, verongiaquinol, (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol), and manzamine-A showed a broad spectrum of activity, inhibiting six of seven tested bacteria with zone of inhibition diameter from 9 to 30 mm. Four of these active compounds also showed antifungal activity. The findings of the in vitro time-kill assay of the most active compound, verongiaquinol, against Staphylococcus aureus indicated its subinhibitory effect at the level lower than the minimal inhibitory concentration (MIC) values (i.e., 2 and 4 µg/mL). At the MIC (8 µg/mL), bacterial cells were completely killed within 18 hours of incubation. DPPH free radical scavenging activity was demonstrated by five compounds in the range of 89.65-36.19% decolorization. Further, four compounds evaluated for their antimutagenic activity against the directly acting mutagens, methyl methanesulfonate and sodium azide, in Salmonella typhimurium strains, interestingly, showed no sign of mutagenicity. Verongiaquinol and manzamine A, in fact, reduced the mutagenicity by 50-75% at a dose of 5 µg/plate in different test strains. Our study seems to provide some novel antimicrobial leads with strong antioxidant potential and the associated ability of antimutagenicity. | {
"pile_set_name": "PubMed Abstracts"
} |
JAZing up jasmonate signaling.
Recent discoveries show that jasmonate ZIM-domain (JAZ) transcriptional repressors are key regulators of jasmonate hormonal response. Jasmonate promotes interaction between JAZ proteins and the SCF(COI1) ubiquitin ligase, leading to JAZ degradation via the 26S proteasome in Arabidopsis thaliana. Elimination of JAZ repressors then frees the MYC2 transcription factor to stimulate jasmonate-dependent gene expression. Although jasmonic acid and methyl jasmonate were thought to be key regulators of jasmonate responses, they were ineffective in promoting SCF(COI1)-JAZ interaction and it is the isoleucine conjugate of jasmonic acid that acts in this signal transduction pathway. The discovery of JAZ transcriptional regulators greatly advances our understanding of how jasmonate signaling regulates plant growth and response to the environment. | {
"pile_set_name": "PubMed Abstracts"
} |
Use of buserelin to induce ovulation in the cyclic mare.
Inducing ovulation in a cyclic mare is often necessary. For this purpose, hCG has been used commonly, but the response can be reduced after successive administrations. The aims of this study were to test the effectiveness of buserelin in hastening ovulation in estrus mares, and its influence on fertility; and to investigate the effect of treatment on LH secretion. Five crossover trials were designed to compare the effect of two treatments: buserelin (40 microg in 4 doses i.v. at 12 h intervals) vs placebo (Experiments 1 and 2); buserelin 40 microg (in 4 doses i.v.) vs 20 microg (Experiment 3); buserelin (4 doses of 20 microg i.v.) vs hCG (1 dose of 2,500 IU i.v.) (Experiment 4); or buserelin (3 doses of 13.3 microg at 6 h interval) vs hCG (Experiment 5). In Experiment 2, blood samples were taken hourly until ovulation, for LH measurements. In Experiment 1, buserelin treatment significantly hastened ovulation. Reduction of the dose by half (Experiment 3) did not alter the effectiveness. In Experiments 4 and 5, buserelin was as effective as hCG in inducing ovulation between 24 and 48 h after initiation of treatment. Buserelin treatment induced a rise in LH concentration during the 48 h period of the experiment, and LH concentrations before ovulation were significantly higher in buserelin treated cycles than in placebo cycles. These experiments demonstrated the usefulness of two new protocols of administration of buserelin, as an alternative to hCG for induction of ovulation. One hypothesis explaining the mechanism of action is that the persistant rise in LH concentration could modify the ratio of biological/immunological LH, as it occurs physiologically, thereby hastening ovulation. | {
"pile_set_name": "PubMed Abstracts"
} |
A systematic review of the effectiveness of communication interventions for health care providers caring for patients in residential care settings.
This systematic review will describe the theoretical grounding, components, duration, mode of delivery, and outcomes of communication interventions for health care providers delivering care in residential care settings and will evaluate the effectiveness of these interventions. We conducted a comprehensive literature search of multiple databases published from January 1985 to the first week of December 2007, supplemented by a hand search of the references in all relevant articles, to find studies that met the inclusion criteria. Intervention details were extracted, and the studies' validity was evaluated independently by two researchers using a standardized data collection form based on Cooper and Hedges' (1994) approach to quality assessment. Of the six studies that met the inclusion criteria (three randomized controlled trials, three quasi-experimental designs), three used a theoretical framework to guide intervention design. Across the six studies, the most commonly used components were (1) cognitive (to teach staff about communication), (2) behavioral (including practice at the bedside), and (3) psychological (involving individualized feedback). Despite the studies' variability in methodological quality, their results indicated that communication interventions have a positive effect on staffs' knowledge and communication skills and on residents' agitation and challenging behaviors. However, none of the studies provided sufficient information on the duration of the intervention and on determining which interventions were most effective. This made it difficult to draw conclusions about the effectiveness of the interventions' different components. Although communication training has been shown to have positive effects on staffs' communication knowledge and skills as well as on resident outcomes, future controlled intervention research is needed to assess the effectiveness of individual intervention components. | {
"pile_set_name": "PubMed Abstracts"
} |
An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development.
The renin-angiotensin system is associated with a variety of pathophysiological processes in many organ systems, and is known to be involved in the normal regulation of blood pressure and in the pathogenesis of renovascular hypertension. Angiotensin II is a multifunctional hormone that manifests its properties by interacting with two major subtypes of cell surface receptors (AT1 and AT2). Angiotensin converting enzyme (ACE) inhibitors are able to modify the actions of the renin-angiotensin system, and are indicated for the treatment of hypertension and heart disease. The antihypertensive effects of ACE inhibiting drugs are related to their ability to block the conversion of the decapeptide, angiotensin I, to the potent pressor octapeptide, angiotensin II. ACE inhibitors have been implicated in fetopathies in humans and perinatal mortality in rats, rabbits, sheep and baboons. Human fetopathies were seen when ACE inhibitors were given around the 26th week of gestation. The major adverse effects in babies include: oligohydramnios, renal tubular dysgenesis, neonatal anuria, calvarial and pulmonary hypoplasia, mild to severe intrauterine growth retardation, persistent patent ductus arteriosus and fetal or neonatal death. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the fetal renin-angiotensin system and partly due to the ischemia resulting from maternal hypotension and decreases in fetal-placental blood flow and oxygen/nutrient delivery to the fetus. The purpose of this review is to briefly discuss the pathophysiological role of the renin-angiotensin system, the therapeutic uses of ACE inhibitors in pregnant patients and to focus primarily on the major fetotoxic effects of ACE inhibitors encountered in humans and animal models. I will also review our recent data which show that capozide (captopril + hydrochlorothiazide) not only produces oligohydramnios but also disturbs the balance of glucose and NaCl in the maternal plasma and amniotic fluid of the rat. | {
"pile_set_name": "PubMed Abstracts"
} |
Trends in epilepsy admissions in children, 1981-2013: population-based observational study using the Scottish national hospital discharge database.
To examine trends in epilepsy admissions in children from 1981 to 2013. Repeated cross-sectional, population-based study. Scotland. We identified admissions among children between 1981 and 2013 inclusive. Epilepsy admissions were identified from the Scottish national hospital discharge database by using relevant diagnostic codes. Primary epilepsy admissions (PEAs) were those with epilepsy as the primary discharge diagnosis, or convulsions as the primary diagnosis but with epilepsy as secondary diagnosis. All other epilepsy admissions were secondary epilepsy admissions (SEAs). Trends in annual epilepsy and non-epilepsy admission rates, as well as sociodemographic, clinical characteristics, length of stay and readmissions of epilepsy admissions. 57 031 epilepsy and 3 863 809 non-epilepsy admissions were available for analysis. Overall, epilepsy and non-epilepsy admissions increased, with a greater increase in epilepsy admissions (interaction Χ2 test statistic 252, p<0.00001). Elective epilepsy admissions, unlike elective non-epilepsy admissions, continually increased, but emergency epilepsy admissions increased until 2000 and showed only minor fluctuations thereafter. Increase in SEAs was more marked than PEAs (interaction Χ2 test statistic 627, p<0.0001). 48% of epilepsy admissions were to children's hospitals. No substantial trends were apparent in age, gender or deprivation distribution of epilepsy admissions. There was a clear trend towards shorter length of stay. Childhood epilepsy admissions are increasing, at a faster rate than non-epilepsy admissions, and have changed towards shorter, more elective admissions. Many will not be to children's hospitals, and the primary reason will often not be because of epilepsy/convulsions. More, not less, epilepsy resources are needed. | {
"pile_set_name": "PubMed Abstracts"
} |
Dynamics of interacting edge defects in copolymer lamellae.
It is known that terraces at the air-polymer interface of lamella-forming diblock copolymers do not make discontinuous jumps in height. Despite the underlying discretized structure, the height profiles are smoothly varying. The width of a transition region of a terrace edge in isolation is typically several hundreds of nanometres, resulting from a balance between surface tension, chain stretching penalties, and the enthalpy of mixing. What is less well known in these systems is what happens when two transition regions interact with one another. In this study, we investigate the dynamics of the interactions between copolymer lamellar edges. We find that the data can be well described by a model that assumes a repulsion between adjacent edges. While the model is simplistic, and does not include molecular level details, its agreement with the data suggests that some of the the underlying assumptions provide insight into the complex interplay between defects. | {
"pile_set_name": "PubMed Abstracts"
} |
CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue.
Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that are characterized by chronic intestinal inflammation and a constant influx of leukocytes mediated by pro-inflammatory cytokines and chemokines. The intestinal expression of the CXCR1-binding chemokines IL-8/CXCL8 and GCP-2/CXCL6 and the participation of immunocompetent cells in IBD were evaluated. IL-8 production by peripheral blood mononuclear cells (PBMC) from IBD patients, stimulated with endotoxin, plant lectin or double-stranded RNA, was significantly lowered in patients with CD, but not in UC patients or healthy subjects. The reduced chemokine production by PBMC from IBD patients was both IL-8 and CD specific, but not inducer dependent. In serum, most chemokines remained undetectable, while the levels of those that were measurable remained unaltered in IBD patients. GCP-2, but not ENA-78/CXCL5, nor IL-8, were highly expressed by endothelial cells in inflamed intestinal tissue of IBD patients. In contrast, stimulated endothelial cell cultures produced more IL-8 than GCP-2. The selective GCP-2 staining of endothelial cells at sites of ulcerations suggests that GCP-2, despite its low production capacity in vitro, plays a role in IBD that is different from that of structurally (ENA-78) and functionally (IL-8) related ELR(+) CXC chemokines. Thus, the chemokine network shows complementarity rather than redundancy. | {
"pile_set_name": "PubMed Abstracts"
} |
Short stature in patients with 45,X/46,XY mosaicism: report of three cases.
Chromosomal analysis is routinely considered in all girls--but not boys-of short stature to screen for Turner syndrome. We report three patients of short stature (body height < 3rd percentile) with 45,X/46,XY mosaicism karyotype. They were brought to our outpatient department at the ages of 10, 13, and 18 years, respectively. Two of them had some stigmata of Turner syndrome. Two were treated with growth hormone. In the first patient, body height increased by 20 cm in 3 years 7 months. The second case increased by 6.5 cm in 8 months. We suggest that boys with unexplained short stature should be screened with chromosomal analysis, and growth hormone treatment should be offered to boys of short stature and 45,X/46,XY mosaicism before the epiphyseal plates close. | {
"pile_set_name": "PubMed Abstracts"
} |
Sex differences in social stress-induced pressor and behavioral responses in normotensive and prehypertensive rats.
This study investigated sex differences in chronic social stress-induced pressor and behavioral responses in normotensive and prehypertensive rats. Adult Wistar and borderline hypertensive (BH) rats (offspring of Wistar dams and spontaneously hypertensive sires) of both sexes were exposed to crowding stress (200 cm²/rat, 5 rats/cage) for 6 weeks. Controls were kept 4 rats/cage (480 cm²/rat). Blood pressure (BP) and open field activity were determined before experiment and after 1, 3 and 6 weeks of stress. Basal BP of BH rats was higher than in Wistar (p < 0.001) in both males and females. Horizontal and vertical activity of BH males and females was elevated vs. Wistar (p < 0.01) and females in both phenotypes were more active than the respective males (p < 0.01). Crowding resulted in delayed between-session habituation and significant elevation of BP only in BH males (143 ± 2 vs. 134 ± 3 mmHg in controls after 6-week crowding). No changes of BP were observed in crowded females of both phenotypes regardless of their delayed between-session habituation. Thus chronic social stress produced by crowding seems to represent a significant risk factor for development of stress-related hypertension only in males with genetic predisposition to high blood pressure while females of both phenotypes responded to stress by impaired between-session habituation. | {
"pile_set_name": "PubMed Abstracts"
} |
Cohort variation in happiness: some hypotheses and exploratory analyses.
Research on historical and age differences in well-being suggests that cohort factors explain at least part of the variation in adults' reports of well-being. Theoretical arguments suggest that it is the bases of people's evaluations of their well-being that reflect the characteristic socializing influences of their cohort. Portraits of two cohorts of older adults are drawn from historical and sociological sources and hypotheses about cohort-specific values are tested with data collected by Veroff and his colleagues in 1957 and 1976. Findings do not support the idea that happiness among the adults who produced the post-World War II baby boom is uniquely linked to concerns with marriage and children. Results do provide partial support for the view that adults born before 1900 are distinctive from other cohorts in that their happiness levels are more closely linked with survival needs and more firmly wedded to Protestant ethic values. | {
"pile_set_name": "PubMed Abstracts"
} |
IFNγ potentiates TNFα/TNFR1 signaling to induce FAT10 expression in macrophages.
The tight regulation of the cytokine network during macrophage activation is of prime importance to enable a fast and potent innate immune response against exogenous pathogens. The inflammation mediating ubiquitin-like protein HLA-F adjacent transcript number 10 (FAT10) was shown to be transcriptionally regulated by and also regulate the nuclear factor-κB (NFκB) signaling pathway. However, very little is known about the regulation of FAT10 gene expression during macrophage activation. RNA sequencing of interferon (IFN)γ-stimulated mouse peritoneal macrophages analyzed by ingenuity pathway analysis revealed significant involvement of tumor necrosis factor receptor 1 (TNFR1) signaling in addition to IFNγ signaling. Subsequently, IFNγ robustly upregulated FAT10 expression compared to a milder induction seen with TNFα or lipopolysaccharide (LPS) stimulation. While low dose IFNγ with TNFα synergistically elevated FAT10 expression, preincubation of macrophages with IFNγ strongly augmented TNFα-induced FAT10 expression. Moreover, a short preincubation with IFNγ, which did not elevate FAT10, was sufficient to potentiate the induction of FAT10 by TNFα. A double augmentation mechanism of TNFα signaling was demonstrated, where IFNγ rapidly induced the expression of TNFα and TNFR1, which further augmented the induction of TNFα and TNFR1 expression by TNFα. Importantly, the induction of FAT10 by IFNγ in macrophages from TNFα-deficient or TNFR1-deficient mice was completely inhibited compared to macrophages from wild type (WT) mice. Finally, we show that TNFα-induced FAT10 expression is dependent on NFκB signaling. IFNγ potentiates the TNFα/TNFR1 signaling pathway to induce FAT10 expression in mouse macrophages, mediated through NFκB network. | {
"pile_set_name": "PubMed Abstracts"
} |
Immunogenicity of a recombinant MVA and a DNA vaccine for Japanese encephalitis virus in swine.
We previously reported that mice immunized with recombinant modified vaccinia virus Ankara (MVA) encoding Japanese encephalitis virus (JEV) prM and E genes were completely protected against JEV challenge (Nam, J.H., Wyatt, L.S., Chae, S.L., Cho, H.W., Park, Y.K., Moss, B. Vaccine 1999,17: 261-268). In this study, we examined the immunogenicity in swine of this recombinant MVA (vJH9) or a DNA vaccine (pcJH-1) expressing the same JEV genes. Although the booster effect in mice with a combination of vJH9, pcJH-1 and inactivated JEV commercial vaccine was not apparent by measuring JEV antibodies, the recombinant MVA vaccine (vJH9) and the DNA vaccine (pcJH-l) efficiently produced neutralizing antibodies in swine and 2 doses of each showed a booster effect in mice and swine. Therefore, both vJH9 and pcJH-1 are good candidates for a second generation JEV vaccine. | {
"pile_set_name": "PubMed Abstracts"
} |
Physical function and gait speed in patients with chronic kidney disease.
Patients with chronic kidney disease (CKD) who are treated with dialysis have impaired physical functioning that is associated with poor outcomes. Gait speed is an important measure of mobility that predicts adverse events and mortality in older people. Gait speed is low in patients with CKD, and those treated with hemodialysis average below cut-points known to indicate increased risk of reduced survival and adverse health events. Measurement of gait speed in patients with CKD may be valuable in identifying those at risk for adverse events, including disability and mortality. | {
"pile_set_name": "PubMed Abstracts"
} |
Changes in red blood cell transfusion practice during the past quarter century: a retrospective analysis of pediatric patients undergoing elective scoliosis surgery using the Mayo database.
Previous studies have demonstrated significant changes in red blood cell (RBC) transfusion practice over several decades. The purpose of the present study was to ascertain changes in transfusion practice during a 25-year study epoch and determine whether these changes had any impact on the frequency of perioperative morbidity and mortality in pediatric patients undergoing major spine surgery. Retrospective chart review. Pediatric patients undergoing elective scoliosis surgery. Impact of RBC transfusion on perioperative morbidity and mortality. Pediatric patients undergoing elective scoliosis surgery were stratified into one of two transfusion-related groups: 1975 to 1985 (ie, pre-human immunodeficiency virus screening, early practice group, n=177) or 1990 to 2000 (ie, recent practice group, n=192). Transfusion and perioperative outcome data were obtained from medical records. Red blood cell use was analyzed as a continuous variable and compared between groups using the Wilcoxon rank sum test, as were preoperative, postoperative, and discharge hemoglobin concentration. Age-adjusted data were compared between groups using chi-square or Fisher exact tests. Patients in the recent practice group had significantly worse comorbid disease and more complex procedures compared with those in the early practice group. The percentage of patients in the recent practice group receiving allogeneic RBC transfusions was significantly less than the early group (37.5% vs. 89.8%, p<.001). Utilization of autologous RBC and intraoperative autotransfusion was significantly greater in the recent practice group (5.1% vs. 47.4% and 20.9% vs. 95.8%, respectively). Hemoglobin concentrations were significantly lower for all time periods in the recent practice group. There were no differences in major morbidity or mortality between groups. In this retrospective review, we report a significant change in blood management strategies in pediatric patients undergoing elective scoliosis surgery. We demonstrated a shift from utilization of allogeneic RBC transfusion toward preoperative donation and intraoperative autotransfusion. Although transfusion triggers were significantly lower in the recent practice group, we were unable to demonstrate a difference in major morbidity or mortality. Utilization of autologous RBC transfusion was safe and effective in reducing allogeneic RBC transfusions in this study. The advantages of autologous blood transfusion may be in preserving a relatively scarce resource (ie, allogeneic blood), rather than mitigating transfusion-related complications. | {
"pile_set_name": "PubMed Abstracts"
} |
Near-edge conduction band electronic states in SiGe alloys
Spatially resolved electron energy loss spectroscopy (EELS) measurements in GeSi alloys illustrate the relationship of atomic structure to local electronic structure. Extending earlier measurements, where electronic structure was found to be controlled by composition in relaxed alloys, measurements in anisotropically strained alloys show splitting of normally degenerate band edges into two components. In a strained Si quantum well, this allows the engineered band offset to be followed from the GeSi substrate through the well to the alloy-capping layer. In the high-mobility conduction channel, the band edge is found to be very sharp, in spite of obvious composition roughness. Near a misfit dislocation under the Si well, the band edge can shift by as much as 0.25 eV due to local strain. Within the core of the defect, however, strictly local behavior dominates the observations. Local conduction band splitting and in-gap states are both observed. | {
"pile_set_name": "PubMed Abstracts"
} |
Referral bias among health workers in studies using hospitalization as a proxy measure of the underlying incidence rate.
Contacts with health services like hospitals or general practitioners are usually the only available proxy measure of incidence of disease in studies based on secondary data and differential referrals or care-seeking behavior often bias such proxy measures. In former analyses based on the Occupational Hospitalization Register in Denmark assisting nurses had high Standardized Hospitalization Ratios for many diseases. It was, however, suspected that it fully or partly was due to a referral bias or self-selection to hospital treatment rather than exposures to occupational hazards. The aim of the present study is to evaluate the referral bias hypothesis by comparing hospitalization and mortality data for health workers for a disease category with a high mortality. Cohorts of all gainfully employed 20- to 59-year-old Danes were formed in order to compare Standardized Mortality Ratios and Standardized Hospitalization Ratios of ischemic heart disease (IHD) in occupational groups. The follow-up period was 10 years. For most of the investigated occupational groups a similar disease pattern was found whether hospitalization or death was used as the outcome measure. In "nurse assistants" a statistically significant higher risk was, however, found using hospitalization due to IHD as the end point rather than mortality. Additional analysis did not support the hypothesis that the finding could be explained by differentiated hospitalization due to social factors. The true incidence rates of the disease need not be equally well described by proxy measures such as hospitalization diagnosis or death diagnosis in all occupational groups. Differential access to medical treatment in some groups may lead to bias when hospital data are used as proxy measures for the underlying incidence rates. | {
"pile_set_name": "PubMed Abstracts"
} |
Limbal cell autograft transplantation for severe ocular surface disorders.
Limbal cell transplantation may improve the visual outcome after chemical trauma and ocular surface diseases. Nine eyes of nine consecutive patients (eight males and one female, age 9-60 years), underwent limbal autograft transplantation (LAUT). In five cases LAUT was done for severe chemical burns in the acute stage (group 1). In four patients with old chemical trauma LAUT was performed years after the trauma (group 2). Penetrating keratoplasty (PKP) was carried out within 6 months after LAUT in three patients of group 2. Preoperatively, the visual acuity in all the patients except one was counting fingers. Postoperatively, patients were treated with topical antibiotics, topical corticosteroids and oral steroids. Oral cyclosporin was used after penetrating keratoplasty. No complications were observed during the surgical procedure. Postoperatively, the epithelialization was complete between days 7 and 12. The inflammatory response subsided within 3 months and the stromal neovascularization decreased. Visual acuity improved in all the nine cases, ranging from 6/6 to 6/30. The decreased visual acuity was due to corneal haze, scars and vascularization. Following PKP, the three grafts remained clear with intact epithelium. No complications were observed during the follow-up period from 7 to 60 months. Limbal cell transplantation is an efficacious procedure for rehabilitation of visual acuity after severe chemical trauma. | {
"pile_set_name": "PubMed Abstracts"
} |
A generalized role of interhemispheric interaction under attentionally demanding conditions: evidence from the auditory and tactile modality.
The present study investigated whether dividing critical information across the hemispheres in the auditory and tactile modalities aids performance more for computationally complex rather than computationally simpler task-a pattern previously observed in the visual modality [Cortex 26 (1990) 77; Neuropsychology 12 (1998) 380; Neuropsychologia 30 (1992) 923]. We conducted two experiments, one in the auditory and one in the tactile modality, that were analogous to those previously performed in the visual modality. In agreement with previous findings, for both modalities we observed that the performance advantage exhibited for within-hemisphere processing in the computationally simpler condition (that required fewer steps to reach a decision) was diminished in the computationally more complex condition. In the auditory experiment we also manipulated computational complexity by varying the amount of time available for processing information. The within-hemisphere advantage in performance was also significantly reduced when complexity was increased through temporal manipulations. These findings suggest that the brain may use interhemispheric interaction as a general strategy to increase computational resources, independent of sensory modality and the manner in which computational demands are increased. | {
"pile_set_name": "PubMed Abstracts"
} |
In vitro and in vivo stimulation of murine lymphocytes by human respiratory syncytial virus strains.
Respiratory syncytial virus (RSV) strains of subtype A (A2, WV9894, and WV12138) and of subtype B (WV1293, WV4843, and WV6873) are mitogenic in vitro for unprimed BALB/c spleen cells. The virus also triggered splenocytes in vitro to secrete immunoglobulins. Plaque-purified and UV-irradiated materials of both RSV subtypes produced comparable levels of DNA synthesis. Infectious materials of both subtypes also induced pronounced responses. Lymphocyte activation with UV-inactivated RSV strain A2 was dose-dependent and maximal responses occurred after 4-5 days of incubation. The virus preparations were mitogenic for spleen cells depleted of T lymphocytes by treatment with anti-Thy 1.2 and complement and for lymphocytes of congenitally athymic mice (nu-nu). They were also mitogenic for highly purified T lymphocytes separated by panning of spleen cells on anti-mouse Ig-coated Petri dishes, suggesting that both B and T lymphocytes respond to the mitogenic activity of RSV. Moreover, mice infected intranasally with RSV strain A2 generated local as well as peripheral cellular and humoral responses. | {
"pile_set_name": "PubMed Abstracts"
} |
Overexpression of SNORA21 suppresses tumorgenesis of gallbladder cancer in vitro and in vivo.
Gallbladder cancer (GBC) ranks fifth in the most common malignancy of the gastrointestinal tract worldwide. It is reported many small nucleolar RNAs (SNORNs) could regulate the progression of GBC. To identify potential therapeutic targets for GBC, we conducted microarray analysis in GBC tissues and adjacent normal tissues. We found that SNORA21 was downregulated most in gallbladder tumor samples. Therefore, this research aimed to investigate the role of SNORA21 during the tumorigenesis of GBC. The differential expression of SNORNs between GBC tissues and para-carcinoma tissues were examined by microarray analysis and that were confirmed by qRT-PCR. Cell proliferation was tested by CCK-8 and immunofluorescence. Cell apoptosis and cell cycle in GBC were detected by flow cytometry. Expression of proteins in GBC cells was measured by Western-blot. Transwell assay was used for testing the cell migration and invasion. Xenograft tumor model was established to verify the effect of SNORA21 overexpression on GBC in vivo. The results revealed that SNORA21 overexpression inhibited the proliferation, migration and invasion of GBC cells. Moreover, overexpression of SNORA21 significantly increased the expression of E-cadherin and decreased the levels of N-cadherin and vimentin. Meanwhile, overexpression of SNORA21 significantly induced apoptosis and G1 arrest of GBC cells. Finally, SNORA21 overexpression significantly suppressed the growth of gallbladder tumors in vivo. Overexpression of SNORA21 significantly suppressed the tumorigenesis of GBC in vitro and in vivo, which may serve as a potential novel target for the treatment of GBC. | {
"pile_set_name": "PubMed Abstracts"
} |
Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide.
Pyrazinamide (PZA) is an important front-line anti-tuberculosis drug that is active only at acid pH. However, acid pH causes significant difficulty for PZA susceptibility testing. A common problem in PZA testing is false resistance caused by large bacterial inocula. This study investigated the relationship of false resistance to numbers of bacilli, pH and other factors that potentially affect susceptibility to PZA. Large inocula (10(7-8) bacilli/ml) of M. tuberculosis H37Ra caused significant increase in medium pH from 5.5 towards neutrality, and thus produced false resistance results. The increase in medium pH was determined to be a function of live bacilli; heat-killed bacilli had little or no effect. Susceptibility to PZA and its active derivative pyrazinoic acid (POA) was comparable on 7H11 agar medium, but POA was less active than PZA in liquid medium containing bovine serum albumin (BSA), suggesting that susceptibility to PZA or POA was reduced in the presence of BSA, because of its neutralising effect on medium pH and significant POA binding. A 3-month-old H37Ra culture was shown to be more susceptible to PZA exposure than a 4-day log-phase culture, suggesting that PZA is more active for non-growing bacilli. Finally, reserpine, an inhibitor of POA efflux pump, increased susceptibility to PZA even near neutral pH 6.8, with an MIC of 400 mg/L compared with 1,000 mg/L without reserpine. These findings should have implications for understanding the mode of action of PZA and for PZA susceptibility testing. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical features of idiopathic portal hypertension in China: A retrospective study of 338 patients and literature review.
Idiopathic portal hypertension (IPH) refers to a relatively rare condition characterized by intrahepatic portal hypertension in the absence of underlying disease such as liver cirrhosis. We retrospectively reviewed 338 patients with IPH that were diagnosed at the pathological consultation center of our hospital. The ratio of male to female patients was 1:1. Mean age at onset was 35.1 ± 16.5 years; male patients on average were 12 years younger than female patients at onset. The median duration from onset to IPH diagnosis was 12 months. In 50 patients, medication use may have been an etiological factor. The most common clinical manifestations were splenomegaly (91.3%) and hypersplenism (68.9%); 57.0% patients presented varicosis, while 25.1% patients had a history of variceal bleeding. Nodular regenerative hyperplasia was found in 22.2% liver biopsies. Among patients for whom laboratory data were available, 65.0%, 50.3%, and 71.4% patients presented leukopenia, anemia, and thrombocytopenia due to hypersplenism. Liver function was mostly in the compensated stage. Female patients showed worse leukopenia and anemia, while male patients were more likely to have abnormal serum transaminase and bilirubin levels. Sixty-seven patients received surgical or interventional treatment. High-quality liver biopsy, detailed clinical information, and expert pathologist are necessary for diagnosis of IPH. IPH can occur concurrently with other liver disease such as hepatitis and drug-induced liver injury. Medication appears to be an important etiological factor for IPH in China. Management approach was largely focused on treatment of portal hypertension and its complications. | {
"pile_set_name": "PubMed Abstracts"
} |
Image analysis to quantify the browning in fresh cut tender jackfruit slices.
Changes in physicochemical properties of fresh cut tender jackfruit during storage is depend on its colour. Colorimeter measurements are best for the samples with homogeneous colour. However, for samples with non-homogenous colors or large sizes (like fruits and vegetables), the colorimeters are inappropriate and inaccurate. The aim for this study is to quantify the amount of browning in fresh cut tender jackfruit slices by using image analysis technique and justify the results by comparing them with existing techniques like sensory examination, enzyme activity, and colorimeter. It can be concluded from the results that browning in fresh cut tender jackfruit slices increase rapidly in control and normally packed samples. Correlation coefficient as high as 0.963, represent that image analysis system is an accurate and highly consistent method to quantify the colour of fruits and vegetables. | {
"pile_set_name": "PubMed Abstracts"
} |
A forgotten cause of wide complex tachycardia.
Wide complex tachycardia secondary to an acute overdose from TCA's is a well-documented phenomenon. In this case we present a wide complex tachycardia after clear documentation of no acute overdose, which responded to standard treatment for TCA toxicity. These findings combined with chronic electrocardiographic abnormalities were suggestive of an acute on chronic TCA toxicity. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis of isocoumarin derivatives via the copper-catalyzed tandem sequential cyclization of 2-halo-N-phenyl benzamides and acyclic 1,3-diketones.
A facile and rapid synthesis of isocoumarin derivatives using a copper-catalyzed tandem C-C/C-O coupling strategy from readily available substrates is described. The reactions of a wide range of 2-iodo-N-phenyl benzamides and acyclic diketones as starting materials were investigated. | {
"pile_set_name": "PubMed Abstracts"
} |
MR imaging of a false carotid aneurysm.
Two months after a gunshot wound to the head of a 12-year-old boy, MR imaging outlined an asymptomatic false aneurysm of the carotid artery. The scan's ability to image in multiple planes with noninvasive visualization of pulsatile vessel flow suggests its use for follow-up examinations of traumatic injuries to the head or neck. | {
"pile_set_name": "PubMed Abstracts"
} |
Substrate Elastic Modulus Regulates the Morphology, Focal Adhesions, and α-Smooth Muscle Actin Expression of Retinal Müller Cells.
The stiffness of the extracellular matrix has been shown to regulate cell adhesion, migration, and transdifferentiation in fibrotic processes. Retinal Müller cells have been shown to be mechanosensitive; they are involved in fibrotic vitreoretinal diseases. Since fibrosis increases the rigidity of the extracellular matrix, our aim was to develop an in vitro model for studying Müller cell morphology and differentiation state in relation to matrix stiffness. A spontaneously immortalized human Müller cell line (MIO-M1) was cultured on type I collagen-coated polyacrylamide gels with Young's moduli ranging from 2 to 92 kPa. Cell surface area, focal adhesion, and the expression and morphology of α-smooth muscle actin induced by transforming growth factor β (TGF-β [10 ng/mL for 48 hours]) were analyzed by immunocytology. The images were documented by using fluorescence microscopy and confocal scanning laser microscopy. MIO-M1 cells cultured on stiff substrates exhibited a significant increase in cell surface area, stress fiber, and mature focal adhesion formation. Furthermore, Müller cells treated with TGF-β1 and TGF-β2 and cultured on stiff substrates showed an increased incorporation of α-smooth muscle actin into stress fibers when compared to those grown on soft surfaces. Compliance of the surrounding matrix seems to influence the morphology and contraction of retinal Müller cells in fibrotic conditions. Development of an in vitro model simulating both the normally compliant retinal tissue and the rigid retinal fibrotic tissue helps fill the gap between the results of petri-dish cell culture with rigid surfaces and in vivo findings. | {
"pile_set_name": "PubMed Abstracts"
} |
The equine rhabdomyolysis syndrome in the United Kingdom: epidemiological and clinical descriptive information.
The paper provides some basic epidemiological and clinical descriptive information for the equine rhabdomyolysis syndrome (ERS) in the United Kingdom. Information was obtained retrospectively from laboratory submission data as well as cases investigated by the author via their veterinary surgeon. Sex appeared to be a significant variable, with females being more likely than males to suffer from ERS compared to other conditions (P less than 0.01). More samples were submitted in the period November-February than at other times of the year (P less than 0.01). The condition appeared to be found in many breeds/types. Most episodes occurred whilst animals were being worked, although 38% occurred after exercise. In the majority of instances the affected animal was still able to walk. A clinical description of a very mild, mild, moderately severe and severe case of ERS is given. Utilizing all the information the syndrome was divided into five grades according to the severity of the stiffness and the presence or absence of auxiliary signs such as sweating and discoloured urine. | {
"pile_set_name": "PubMed Abstracts"
} |
New jobs.
■ Kate Billingham will become assistant chief nursing officer at the Department of Health, responsible for developing and leading the implementation of the strategic action programme in public health nursing and primary care, later this month. Ms Billingham is currently senior research fellow in the Institute of General Practice and Primary Care at the University of Sheffield. | {
"pile_set_name": "PubMed Abstracts"
} |
The shark HoxN cluster is homologous to the human HoxD cluster.
The statistical analysis of phylogenetic footprints in the two known horn shark Hox clusters and the four mammalian clusters shows that the shark HoxN cluster is HoxD-like. This finding implies that the most recent common ancestor of jawed vertebrates had at least four Hox clusters, including those which are orthologous to the four mammalian Hox clusters. | {
"pile_set_name": "PubMed Abstracts"
} |
A telematic tool to predict the risk of colorectal cancer in white men and women: ColoRectal Cancer Alert (CRCA).
Colorectal cancer is an important disease because of its severity and also since it affects much of the population. Nothing helps patients and doctors to determine the risk of suffering from colorectal cancer during their lives, except for medical tests such as the colonoscopy. There have been several studies and research to try to estimate the relative risks of colorectal cancer based on various factors and the applications to calculate the risk of this cancer, but these are not within everyone's research. This project offers a multilingual Web tool, called ColoRectal Cancer Alert (CRCA), to calculate the risk of colorectal cancer for life in men and women of white race. With this application, doctors can carry out research in a few minutes to explore this risk when they are seeing a patient. The platform is designed in such a way that anyone can use it. It is easy to use and intuitive. We should keep in mind that this tool does not replace diagnostic tests such as the colonoscopy or the sigmoidoscopy. It is designed so that users with the assistance of their doctor know the risk and act accordingly (for example, having more checkups on the disease in case of high risk). To access the tool a computer with Internet connection will be required. Currently, 250 users of white race under the supervision of a specialist have completed the questionnaire. | {
"pile_set_name": "PubMed Abstracts"
} |
[Frequency and prognostic features of rheumatoid patients with remission-inducing agents--a comparison of different kinds of medication].
Recently, the disease activity has been believed to be effectively controlled by remission inducing agents such as gold salt and D-penicillamine in rheumatoid arthritis. However, there remain some doubts whether the prognosis of RA has been improved by these drugs or not. The frequency of complete remission in RA patients and their special features were studied to know the real state of the remission of RA under the present treatments. The subjects under investigation were 466 RA patients who were treated with remission-inducing agents for one to eight years. There were 90 male and 376 female patients diagnosed as definite or classical RA. Complete remission according to ARA criteria (Pinals R.S. et al. 1981) was noted in 33 (7.1%) of the 466 patients. However, relapse of the disease activity was observed in five patients during an observation period of two years on average. The followings were noted as the clinical and laboratory features of 26 cases with complete remission which could be observed for more than six months. A breakdown on sex revealed that the remission rate was 13.3% in male patients, compared to 5.6% in female patients. Duration of the disease for these complete remission cases was shorter for males than for females. Clinical examination of the cases with complete remission revealed that the most of them had no family history of RA, as well as no rheumatoid nodule or hip contracture.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Syntheses and characterization of copper complexes with the ligand 2-aminoethyl(2-pyridylmethyl)-1,2-ethanediamine (apme).
Copper(I)/(II) complexes with the ligand 2-aminoethyl(2-pyridylmethyl)1,2-ethanediamine (apme, abbreviated as PDT in the literature as well) were prepared and characterized. Crystal structures of the copper(I) complexes, [Cu2(apme)2]X2 (1, 2; X=ClO4, CF3SO3), showed that they are dinuclear, in contrast to the trigonal bipyramidal copper(II) complexes [Cu(apme)Cl]BPh4 (3) and [Cu(apme)(DMF)](BPh4)2 (4). 1 and 2 could be investigated in solution by NMR spectroscopy and 3 and 4 by cyclovoltammetry. From the results of these studies it is clear that in solution equilibria between the dinuclear complexes 1/2 and another species exist, most likely the monomeric [Cu(apme)CH3CN]+. Time-resolved UV/vis spectra at low temperatures allowed the spectroscopic detection of dioxygen adduct complexes as reactive intermediates during the oxidation of 1/2 with dioxygen that seem to play an important role in copper enzymes such as peptidylglycine-alpha-hydroxylating monooxygenase (PHM). | {
"pile_set_name": "PubMed Abstracts"
} |
Unusual presentation of Amsler's sign in Fuchs' heterochromic uveitis.
Hyphema occurring after ocular paracentesis has been described as a classic feature of Fuchs' heterochromic uveitis (FHU) (Amsler's sign). We describe a case of hyphema occurring after peribulbar anesthesia in a patient with FHU. The bleeding occurred before the surgery began. Although the occurrence of this phenomenon does not preclude successful surgical outcomes, topical anesthesia may lower the risk preoperatively. | {
"pile_set_name": "PubMed Abstracts"
} |
Combined effect of vitamin E and insulin on cataracts of diabetic rats fed a high cholesterol diet.
In the present study we investigated the effects of a long-term treatment with vitamin E, an antioxidant vitamin, insulin or their combination on cataracts of streptozotocin (STZ)-induced diabetic rats fed a high cholesterol diet. Each rat was checked for cataracts at 0, 1, 2, 4, 8, 12 and 15 weeks after STZ injection. Cataracts were observed from 8 weeks in the control diabetic rats and their incidence of catarats increased to 100% by 12 weeks. The incidence of cataracts in rats treated with vitamin E, insulin and their combination was first seen at 12 weeks and 56%, 20% and 10%, respectively, at 12 weeks and 78%, 50% and 20%, respectively, at 15 weeks. The preventive effects of either agent alone and their combination on the cataracts were in agreement with those obtained by histopathological evaluation of eyeballs. The combined treatment with both agents markedly improved hyperglycemia, hyperlipidemia and increased serum lipid peroxide levels. These results indicate that the combined treatment with vitamin E and insulin is useful in preventing the development and progression of diabetic cataracts. | {
"pile_set_name": "PubMed Abstracts"
} |
The costs of diabetes and its complications.
Diabetes mellitus is a disease with major long-term implications, not only for the health and well-being of affected individuals, but also for costs to the National Health Service. Treatment of the disease and its complications takes up 4-5% of total health care expenditure in the U.K. These costs are dominated by in-patient care for the complications arising from diabetes. This paper presents a review of studies which have been carried out on the costs of diabetes and its complications. For such a chronic and potentially disabling disease with numerous complications it is surprising that costs have not been more extensively researched. A large amount of data are available about the implications of diabetes in terms of incidence and prevalence, but few costs have been collected, particularly indirect and marginal costs. Both insulin dependent (IDDM) and non-insulin dependent (NIDDM) diabetic patients exhibit similar complications so that the cost of treatment may be comparable, but further studies are needed to establish this. In addition, few studies have included diabetes as a secondary diagnosis. The studies which are available have tended to focus on direct costs, for example, the costs of hospital care, consultations and drugs, because they are the easiest to measure. Fewer studies have included indirect costs, such as the effect of time lost from work, early retirement and premature death, because of the difficulties in assigning monetary values to these factors. The most important contributors to the costs of diabetes are those of treating complications such as eye and limb disease, heart disease, neuropathy and nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Cloning and expression of low temperature active endoglucanase EG5C from Paenibacillus sp. IHB B 3084.
The endoglucanase gene designated as EG5C encoding cold active endoglucanase produced by Paenibacillus sp. IHB B 3084 was cloned and expressed in Escherichia coli BL21(DE3). The gene consisting of 1719bp open reading frame encoded a protein of 573 amino acids with a predicted molecular weight of 63.5kDa. The presence of N-terminal catalytic domain of the glycosyl hydrolase family 5 (GH5) and C-terminal carbohydrate binding X2 domain suggested the modular nature of the enzyme. The native signal peptide of EG5C was capable of efficiently secreting the enzyme with near equal activities in the cytoplasmic and extracellular fractions. The recombinant enzyme purified 9.46 fold to homogeneity with 22.33% yield gave 7.758IU/mg specific activity. The enzyme was stable over the broad pH range of 4-12 with more than 50% residual activity. The optimal activity was at 40°C with 70% relative activity at 5°C. The low temperature activity despite the shorter linker region suggested a novel cold adaptation mechanism by the enzyme. The enzyme displayed higher activity on carboxymethylcellulose than avicel which is useful in maintaining the tensile strength of fiber. The efficient secretion and low temperature activity offer prospect for large-scale production and industrial application of the endoglucanase. | {
"pile_set_name": "PubMed Abstracts"
} |
Molecular mechanisms contributing to the protective effect of levosimendan in liver ischemia-reperfusion injury.
Ischemia-reperfusion injury (IRI) is an important cause of liver damage in many clinical situations. Levosimendan is a promising therapy for prevention of IRI. The present work investigated the possible contribution of nitric oxide (NO), cyclooxygenase (COX) enzymes, and adenosine triphosphate sensitive potassium channel (K-ATP) in the protective effect of levosimendan in liver IRI in rats. Rats were divided into 7 groups. Sham-operated group (negative control group); IR-nontreated group (positive control group), levosimendan-treated group (treated with levosimendan); indomethacin, nonselective COX inhibitor,+levosimendan group (cotreated with indomethacin+levosimendan); celecoxib (selective COX-2 inhibitor)+levosimendan group; L-NNA (Nitro- ω-L-arginine, nonselective NO synthase inhibitor)+levosimendan group; and glibenclamide (K-ATP blocker)+levosimendan group. Liver injury was evaluated biochemically (by serum level of alanine aminotransferase (ALT)) as well as by histopathology. Hepatic tissue content of oxidative stress markers, tumor necrosis factor-alpha (TNF-α), along with immunohistochemical expression of induced NO synthase (iNOS), endothelial NO synthase (eNOS), and caspase-3 in hepatic tissue were assayed. The study showed that levosimendan attenuated liver IRI as evidenced by a decrease in serum ALT level and confirmed by histopathology. The protective effect of levosimendan was associated with modulation of oxidative stress, TNF-α, iNOS, eNOS, and caspase-3. The hepatoprotective effect of levosimendan was partially attenuated by pretreatment by either nonselective COX inhibitor, NOS inhibitor, or K-ATP channel blocker; indicating that the hepatoprotective effect of levosimendan was attributed, at least in part to activation of COX-1, modulation of NO, and opening of K-ATP channel. | {
"pile_set_name": "PubMed Abstracts"
} |
A microfluidic device for quantitative investigation of zebrafish larvae's rheotaxis.
Zebrafish is a model organism for various sensory-motor biological studies. Rheotaxis, or the ability of zebrafish to orient and swim against the water stream, is a common behavior that involves multiple sensory-motor processes such as their lateral line and visual systems. Due to the lack of a controllable and easy-to-use assay, zebrafish rheotaxis at larval stages is not well-understood. In this paper, we report a microfluidic device that can be used to apply the flow stimulus precisely and repeatedly along the longitudinal axis of individual zebrafish larvae to study their coaxial rheotaxis. We quantified rheotaxis in terms of the response rate and location along the channel at various flow velocities (9.5-38 mm.sec-1). The larvae effectively exhibited a similarly high rheotactic response at low and medium velocities (9.5 and 19 mm.sec-1); however, at high velocity of 38 mm.sec-1, despite sensing the flow, their rheotactic response decreased significantly. The flow velocity also affected the response location along the channel. At 9.5 mm.sec-1, responses were distributed evenly along the channel length while, at 19 and 38 mm.sec-1, the larvae demonstrated higher rheotaxis responses at the anterior and posterior ends of the channel, respectively. This result shows that although the response is similarly high at low and medium flow velocities, zebrafish larvae become more sensitive to the flow at medium velocity, demonstrating a modulated rheotactic behavior. Employing our device, further investigations can be conducted to study the sensory-motor systems involved in rheotaxis of zebrafish larvae and other fish species. | {
"pile_set_name": "PubMed Abstracts"
} |
Mammalian design and rate of living.
Terrestrial placental mammals are physiologically and biochemically similar. However, though some of their design and life history characteristics vary in a uniform way with body mass across the mammalian class (e.g. basal metabolic rate, body length, liver or adrenal mass, etc.), others follow less uniform "laws" with apparent differences among the various orders (e.g. brain mass, life span, etc.). Based on data from 38 species, it is shown that despite the absence of a uniform law describing body mass, my, of young at birth, or litter size, n, their product, i.e. total body mass of litter at birth, m lambda, does follow such a law: It appears that, like basal metabolic rate, m lambda is proportional to the 3/4-power of body mass of the mother; no inter-order differences are apparent. Nevertheless, despite their remarkably similar metabolic apparatus, mammals cannot be functional scale models of each other, i.e. the metabolic machinery has to be set at a lower level as body size increases, leading to reduced heart rate, developmental rate, and "rate of living"--and thus prolonged life span. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparative effects of lipid-lowering therapies.
The pharmacologic regulation of lipid metabolism in patients with dyslipidemia is unequivocally associated with significant reductions in risk for cardiovascular morbidity and mortality. A number of therapeutic drug classes have been developed in an effort to ever more precisely and intensively modulate lipid metabolism. Statins, fibrates, ezetimibe, and niacin exert their effects via different mechanisms and afford physicians the opportunity to beneficially impact multiple pathways in patients. When used alone or in combination, these drugs decrease risk for the development and progression of atherosclerotic disease. There are strong clinical trial data to support of the use of lipid-lowering therapies in the settings of both primary and secondary prevention. This article (1) discusses the mechanisms of action of antilipidemic medications, (2) reviews dosing regimens and the pharmacokinetic differences among drugs of the same class, (3) assesses risk for drug interactions, and (4) reviews the clinical trial evidence used to support the use of particular antilipidemic medications in specific physiologic settings. The incidence of dyslipidemia is rising worldwide. This trend portends an ever-growing need for the aggressive and judicious use of different antilipidemic medication(s) in patients at risk for all forms of atherosclerotic vascular disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Marine anti-biofouling efficacy of amphiphilic poly(coacrylate) grafted PDMSe: effect of graft molecular weight.
There is currently strong motivation due to ecological concerns to develop effective anti-biofouling coatings that are environmentally benign, durable, and stable for use by the maritime industry. The antifouling (AF) and fouling-release (FR) efficacy of amphiphilic, charged copolymers composed of ~52% acrylamide, ~34% acrylic acid, and ~14% methyl acrylate grafted to poly(dimethyl siloxane) (PDMSe) surfaces were tested against zoospores of the green alga Ulva linza and the diatom Navicula incerta. The biofouling response to molecular weight variation was analyzed for grafts ranging from ~100 to 1,400 kg mol-1, The amphiphilic coatings showed a marked improvement in the FR response, with a 55% increase in the percentage removal of diatoms and increased AF efficacy, with 92% reduction in initial attachment density of zoospores, compared to PDMSe controls. However, graft molecular weight, in the range tested, was statistically insignificant. Grafting copolymers to PDMSe embossed with the Sharklet™ microtopography did not produce enhanced AF efficacy. | {
"pile_set_name": "PubMed Abstracts"
} |
Bacterial food-borne zoonoses.
In many countries of the world, bacterial food-borne zoonotic infections are the most common cause of human intestinal disease. Salmonella and Campylobacter account for over 90% of all reported cases of bacteria-related food poisoning world-wide. Poultry and poultry products have been incriminated in the majority of traceable food-borne illnesses caused by these bacteria, although all domestic livestock are reservoirs of infection. In contrast to the enzootic nature of most Salmonella and Campylobacter infections, Salmonella Enteritidis caused a pandemic in both poultry and humans during the latter half of the 20th Century. Salmonella Typhimurium and Campylobacter appear to be more ubiquitous in the environment, colonising a greater variety of hosts and environmental niches. Verocytotoxin-producing Escherichia coli O157 (VTEC O157) also emerged as a major food-borne zoonotic pathogen in the 1980s and 1990s. Although infection is relatively rare in humans, clinical disease is often severe, with a significant mortality rate among the young and elderly. The epidemiology of VTEC O157 is poorly understood, although ruminants, especially cattle and sheep, appear to be the major source of infection. The dissemination of S. Enteritidis along the food chain is fairly well understood, and control programmes have been developed to target key areas of poultry meat and egg production. Recent evidence indicates that these control programmes have been associated with an overall reduction of S. Enteritidis along the food chain. Unfortunately, existing controls do not appear to reduce the levels of Campylobacter and VTEC O157 infections. Future control strategies need to consider variations in the epidemiologies of food-borne zoonotic infections, and apply a quantitative risk analysis approach to ensure that the most cost-effective programmes are developed. | {
"pile_set_name": "PubMed Abstracts"
} |
The prevalence of the 235delC GJB2 mutation in a Chinese deaf population.
Mutations in the GJB2 gene are the most frequently found mutations in patients with nonsyndromic hearing impairment in populations studied to date. However, the prevalence of mutations varies among different ethnic groups. In most areas of China, genetic testing for nonsyndromic hearing impairment is currently not available because of the lack of information regarding the molecular cause of nonsyndromic hearing impairment. The purpose of this study is to determine the prevalence of a common GJB2 mutation, 235delC, in Chinese deaf children. We collected DNA specimens from 3004 patients with nonsyndromic hearing impairment from 26 regions of China; 368 Han Chinese and 98 Uigur controls, and screened for the 235delC mutation. The coding exon of the GJB2 gene was polymerase chain reaction amplified, followed by restriction enzyme digestion with ApaI and analysis by agarose gel. Overall, 488 patients (16.3%) were determined to carry at least one 235delC mutant allele, with 233 (7.8%) homozygotes and 255 (8.5%) heterozygotes. Therefore, within the subpopulations examined, the frequency varies from 0% to 14.7% for 235delC homozygotes and from 1.7% to 16.1% for heterozygotes. On the basis of this survey of the patient cohort as stated, Chinese patients with nonsyndromic hearing impairment appear to have a relatively higher 235delC frequency than that of other Asian populations. These results demonstrate that an easy and fast genetic testing method for this well-known GJB2 gene mutation can be made available for at least 2 million Chinese patients and family members with nonsyndromic hearing impairment. By screening for the common GJB2 235delC mutation, the molecular cause in as high as 15% of patients with nonsyndromic hearing impairment in certain regions of China can be identified. In addition, patients who are negative for the 235delC mutation would be candidates for further mutational analysis of GJB2 or other deafness-related genes. | {
"pile_set_name": "PubMed Abstracts"
} |
Atropinic (anticholinergic) burden in antipsychotic-treated patients.
Antipsychotic drugs possess side atropinic (anticholinergic) properties that may induce several adverse drug reactions (ADRs), such as memory loss or cognitive impairment. The aim of this study was to investigate anticholinergic burden in patients treated with antipsychotic drugs. All ADR reports including at least one antipsychotic and registered between 2000 and 2015 in the Midi-Pyrénées PharmacoVigilance Database were extracted and analyzed using the Anticholinergic Duran's list. The primary objective of this cross-sectional study was to calculate anticholinergic burden in antipsychotic-treated patients; the secondary one was to investigate associated factors. Among the 1948 reports, the average number of atropinic drugs per report was 2.4 ± 1.4. At least one atropinic drug was found in 59.4% of reports (1158), in addition to antipsychotic drugs. The mean anticholinergic burden per report was 3.9 ± 2.9. A value ≥3 was found in 61.7% of the reports. A significant association between anticholinergic burden, age, and male gender of patients was found. The mean value of anticholinergic burden remained stable during the study period. This study showed high values of anticholinergic burden in patients receiving antipsychotics. Thus, considering the potential noxious clinical impact of atropinic properties on cognitive functions, an appropriate approach should be used to reduce prescription of antipsychotics with a high anticholinergic burden but also coprescription of other frequently associated atropinic drugs, such as antiparkinsonians, H1 antihistamines, or imipraminic antidepressants in these patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Current concepts in validity and reliability for psychometric instruments: theory and application.
Validity and reliability relate to the interpretation of scores from psychometric instruments (eg, symptom scales, questionnaires, education tests, and observer ratings) used in clinical practice, research, education, and administration. Emerging paradigms replace prior distinctions of face, content, and criterion validity with the unitary concept "construct validity," the degree to which a score can be interpreted as representing the intended underlying construct. Evidence to support the validity argument is collected from 5 sources: Do instrument items completely represent the construct? The relationship between the intended construct and the thought processes of subjects or observers. Acceptable reliability and factor structure. Correlation with scores from another instrument assessing the same construct. Do scores really make a difference? Evidence should be sought from a variety of sources to support a given interpretation. Reliable scores are necessary, but not sufficient, for valid interpretation. Increased attention to the systematic collection of validity evidence for scores from psychometric instruments will improve assessments in research, patient care, and education. | {
"pile_set_name": "PubMed Abstracts"
} |
SELDI-TOF plasma profiles distinguish individuals in a protein C-deficient family with thrombotic episodes occurring before age 40.
We tested the hypothesis that differences in the low-molecular-weight (500-20,000 Da) proteomic profile of plasma may be detectable between members of a protein C-deficient family who have suffered thrombotic events before age 40 compared to family members without a history of venous thrombosis. Unfractionated plasma samples from members of a previously described large thrombophilic kindred with type I protein C deficiency were applied to ProteinChip weak cation exchange interaction arrays (WCX2; Ciphergen Biosystems, Fremont, CA, USA) and subjected to SELDI-TOF (surface-enhanced laser desorption/ionization time-of-flight) mass spectrometry using the Ciphergen PBSII ProteinChip System (Ciphergen Biosystems). Profiles were analyzed by a boosted decision-tree algorithm. When individuals who had presented with deep venous thrombosis (DVT) before the age of 40 (n = 21) were compared to age-matched, healthy family members (n = 50), the proteomic patterns defined by the decision-tree analysis could classify the entity of DVT before age 40 with 67% sensitivity, at a specificity of 86%. When a small group of cases with history of superficial venous thrombosis (n = 6) was added to the case group, the sensitivity was 87.5% at a specificity of 80%. These data support the hypothesis that members of the protein C deficient Vermont kindred II who suffer a thrombotic event before age 40 display significant differences in low-molecular-weight proteomics profile compared to those who remain disease-free. This is the first study to apply SELDI-TOF technology in conjunction with a bioinformatics tool to analyze low-molecular-weight proteomic patterns in patients with venous thrombosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Induced and controlled dietary ketosis as a regulator of obesity and metabolic syndrome pathologies.
A worsening epidemic of diabetes and its precursor, metabolic syndrome (MetS) is engulfing America. A healthy individual, with proper glucose regulation has an ability to switch between burning fat and carbohydrates. It has been suggested that signaling errors within this homeostatic system, characterized by impaired switching of substrate oxidation from glucose to fat in response to insulin, can contribute to the etiology of metabolic syndrome and occurs before the development of type II diabetes. Glucose regulation with restored insulin sensitivity facilitated through clinically regulated, benign dietary ketosis (BDK), may significantly reduce, regulate and reverse the adverse pathologies common to MetS and obesity. The study assessed if prolonged maintenance of induced and controlled physiological, dietary ketosis, would reverse pathological processes induced by MetS including a reduction in fasting triglycerides, BMI (body mass index) and body fat mass (BFM), weight, a significant decrease and/or normalization of hemoglobin A1c (HgA1c) and an increase in resting metabolic rate (RMR) and blood ketones. A group of 30 adults, previously diagnosed with MetS by their primary care physician, were randomly prescribed to one of three groups: a sustained ketogenic diet with no exercise, standard American diet (SAD) with no exercise or SAD with 3-5 days per week of exercise (30 min.). The results demonstrated that the change over time from week 0 to week 10 was significant (p=0.001) in the ketogenic group for weight, body fat percentage, BMI, HgA1c and ketones. All variables for the ketogenic group out-performed those of the exercise and non-exercise groups, with five of the seven demonstrating statistical significance. | {
"pile_set_name": "PubMed Abstracts"
} |
Amylase release from rat parotid glands. II. Calcium kinetics.
The kinetics of 45Ca2+ uptake, efflux, and calcium potentiation of amylase release by slices of rat parotid glands were examined. Pretreatment of the tissue with 11.25 mM 45Ca2+ medium increased the total tissue 45calcium content. Lanthanum (1 mM) decreased tissue uptake, blocked the slow components of exchange and appeared to inhibit transcellular calcium movement. Neither dibutyryl cyclic AMP nor caffeine caused consistently significant effects on 45Ca2+ kinetics, or total 45calcium content. Carbamylcholine increased the initial rate of 45Ca2+ uptake, but had no effect on total uptake. Elevation of the extracellular Ca2+ concentration to 11.25 mM during stimulation of amylase release resulted in an initial decrease in the rate of amylase release followed by a potentiation of release which developed slowly, requiring 40--50 min to reach the maximal response. The inability to detect release-related changes in either calcium influx or mobilization, and the lengthy times and high Ca2+ concentrations required to achieve calcium potentiation suggests that calcium does not couple amylase release. | {
"pile_set_name": "PubMed Abstracts"
} |
Noradrenergic responses of neurones in the mediolateral part of the lateral septum: alpha1-adrenergic depolarization and rhythmic bursting activities, and alpha2-adrenergic hyperpolarization from guinea pig brain slices.
Bath application of noradrenaline on neurones of class A, B and C within the mediolateral part of the lateral septum from guinea pig brain slices elicited depolarization (through alpha1-adrenoceptors) or hyperpolarization (through alpha2-adrenoceptors) and rhythmic bursting activities (through alpha1-adrenoceptors). A co-existence of these two types of adrenoceptors (alpha1 and alpha2) mediating opposite effects on membrane excitability was sometimes observed on the same neurone. Three types (I, II and III) of neurones were identified on the basis of their bursting properties during noradrenaline application. With the bursting activities persisting under tetrodotoxin and their frequency being sensitive to changes in membrane potential, these neurones could be considered as conditional bursters. An afterdepolarizing potential could promote burst initiation in the three types of neurones. Neuronal input resistance decreased at the afterdepolarizing potential peak. Application of low-Na+ medium blocked the generation of bursts and afterdepolarizing potentials induced by noradrenaline in the three types of neurones. Furthermore, the bursts were dependent on the presence of Ca(2+) in the medium in a subpopulation of neurones. We conclude that afterdepolarizing potentials and bursts induced by noradrenaline are generated by a cationic conductance largely permeable to Na+ in neurones of the mediolateral part of the lateral septum. | {
"pile_set_name": "PubMed Abstracts"
} |
Continuing education requirements to maintain occupational therapy licensure.
Different states use a variety of regulatory mechanisms to monitor the quality of practice in occupational therapy. The requirement for mandatory continuing education has been adopted by fewer than half of American states, but there is reason to predict that this trend will increase. This study investigates the patterns linking licensure to continuing education and recommends actions to ensure uniformity and accountability. | {
"pile_set_name": "PubMed Abstracts"
} |
[Colorectal carcinogenesis. 2. Underlying epigenetic and genetic alterations and molecular classification of colorectal cancers].
Gene alterations which have been implicated in colorectal carcinogenesis are characterized by three major mechanisms: chromosomal instability, microsatellite instability, and epigenetic mechanisms (i.e., CpG island hypermethylation). Progress in understanding of these genetic and epigenetic instabilities has led to advances in the individualization and characterization of more homogeneous sub-groups of colorectal tumors with regard to progression, prognosis and response to therapy. | {
"pile_set_name": "PubMed Abstracts"
} |
Vaccination against congenital toxoplasmosis.
Different types of Toxoplasma gondii vaccines were evaluated using parasitological and histopathological means to induce immunity in Swiss pregnant mice and their pups against the challenge with virulent RH strain. Immunization was performed before mating by using live cyst vaccines (LCV), LCV-IL-2 combination, irradiated cyst vaccine (ICV) and ICV-IL-2 combination. It was demonstrated that pre-immunization with the current vaccines offered significant protection of both dams and pups. The highest level of protection was noticed in mice which received LCV-IL-2, followed by ICV-IL-2, then LCV and the least protection was elicited in dams immunized with ICV alone. The results threw light on the possibility of applying such vaccines not only in mice but also in other mammalian hosts including human. | {
"pile_set_name": "PubMed Abstracts"
} |
Drug use in French children: a population-based study.
To provide an overview of drug use in outpatient children in France, a population-based study using a national reimbursement claims database representative of 90% of the French population was conducted. Cross-sectional study performed between January and December 2011 using the EGB database (Echantillon Généraliste de Bénéficiaires), a 1/97th sample of the national healthcare insurance system beneficiaries. Drug use in children <18 years old was estimated through reimbursements for prescribed drugs excluding vaccines. Prevalences of use were calculated for different levels of the Anatomical Therapeutic Chemical classification by considering as users children who had at least one reimbursement during the study period. In 2011, 133,800 children were included in the study. The overall prevalence of drug use was 84% and the median number of different drugs per child was 5. Drug use was greatest in children aged <2 years. The most widely used drugs were paracetamol, systemic anti-infectives, nasal corticosteroids and decongestants, and anti-histamines. 21% children <2 years received domperidone. There is widespread use of medicines that are unlikely to be effective and may have significant toxicity in French children. Irrational use of medicines appears to be greatest in children aged 5 years and under. | {
"pile_set_name": "PubMed Abstracts"
} |
Is treatment of type 1 diabetes mellitus (insulin therapy, metabolic control) optimal for preventing cardiovascular autonomic neuropathy?
Long-term poor metabolic control promotes the occurrence of microvascular complications, such as cardiovascular autonomic neuropathy (CAN) and atherogenic hyperlipidaemia, which translates into increased mortality in patients with type 1 diabetes mellitus (T1DM). The aim of the study was to assess the prevalence of CAN in patients with T1DM in relation to treatment method (continuous subcutaneous insulin infusion, CSII, versus multiple daily injections using pens, MDI) and metabolic control. The study group comprised 93 adults (60 women, 33 men), mean age 31 years, with T1DM being treated at a local clinical centre from 2011 to 2015. The presence of CAN, the results of laboratory tests, and anthropometric data were analysed. The subjects were divided into two groups according to treatment method (CSII, MDI). The median duration of diabetes was 16 years. 61% of the subjects used MDI and 39% used CSII. 41% of the subjects presented with CAN (confirmed with the Ewing test using ProSciCard apparatus), with a significantly lower prevalence in the group of patients treated with CSII (15.4% vs. 60.4%; p < 0.001). The mean HbA1c level in the CSII-treated group was noticeably lower (7.44 ± 1.67% vs.8.55 ± 1.1%, p < 0.001), and these patients also had lower triglyceride levels (0.71 vs. 1.32 mmol/L, p < 0.001). Regardless of the treatment method, 72% of all patients under 40 years of age achieved their therapeutic target of LDL cholesterol level < 2.6 mmol/L, whereas only 13% of all those over 40 years old achieved an LDL cholesterol level < 1.8 mmol/L. The presented results draw attention to the high prevalence of CAN among T1DM patients. The study reveals the need for more intensive monitoring and treatment of hyperlipidaemia, despite good glycaemic control, especially in those over the age of 40 years. | {
"pile_set_name": "PubMed Abstracts"
} |
Light gradient partitioning by tropical tree seedlings in the absence of canopy gaps.
To explore the importance of light availability for seedling growth in low light environments, we examined light-dependent growth, biomass allocation and mortality of tree seedlings growing in sites with 0.2-6.5% full sun, the range of light commonly encountered in the understory of closed canopy, lowland tropical forests. We transplanted seedlings of the canopy tree species, Dipteryx panamensis, Virola koschnyii, and Brosimum alicastrum into second-growth forest and native tree plantations at La Selva Biological Station, Costa Rica. We assessed seedling survival, growth, and seedling light environments bimonthly for 14 months. Plants were harvested at the end of the study to assess leaf area, total biomass, biomass partitioning and root growth. Survivorship of all species exceeded 60% across all microsites, although both D. panamensis and B. alicastrum had lower probabilities of survival in the darkest microsites. All species showed a strong positive relationship between light availability and growth, increasing in total biomass as light increased. However, the strength of the growth response differed among species causing a change in the rank order of species growth rates as light availability increased. Although D. panamensis showed the lowest growth rates in the darkest microsites, a strong response to increasing light led to a cross-over in performance, such that D. panamensis had the highest growth rate at the highest light levels studied. These data suggest that resource gradient partitioning could occur even in low light environments (0.2-6.5%). Given the limited range of light regimes sampled (i.e., non-gap microsites), our data demonstrate that growth of tropical tree seedlings beneath closed canopies is highly sensitive to light availability and that shade-tolerant species vary in these responses. Our results show that understory light heterogeneity, in the absence of canopy gaps, can significantly affect recruitment processes for shade-tolerant tree species. | {
"pile_set_name": "PubMed Abstracts"
} |
A Mutation in CTSK Gene in an Autosomal Recessive Pycnodysostosis Family of Chinese Origin.
Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures, and skull deformities. Mutation in the gene encoding cathepsin K (CTSK), which is a lysosomal cysteine protease, has been found to be responsible for this disease. Here we reported a consanguineous Chinese family with 1 affected individual demonstrating autosomal recessive pycnodysostosis with recurrent kidney stone, a new clinical manifestation which has not been reported in patients of pycnodysostosis before. To identify the pathogenic mutation, we evaluated the patient clinically, biochemically, and radiographically. To screen for mutations in the CTSK gene of the patient and his family members, all of its exons and exon-intron junctions were PCR amplified from genomic DNA and sequenced. Sequence analysis of the patient's CTSK gene revealed homozygosity for a missense mutation (c.746T>C) in exon 6, which leads to amino change (p.Ile249Thr) in the mature CTSK protein. This mutation was firstly reported by Michela Donnarumma and his colleagues in 2007 in a Spanish family. Our study strengthens the role of this particular mutation in the pathogenesis of pycnodysostosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Obesity associated with type 2 diabetes mellitus is linked to decreased PC1/3 mRNA expression in the Jejunum.
Bariatric surgery is the most effective therapeutic option for obesity and its complications, especially in type 2 diabetes. The aim of this study was to investigate the messenger RNA (mRNA) gene expression of proglucagon, glucose-dependent insulinotropic peptide (GIP), prohormone convertase 1/3 (PC1/3), and dipeptidyl peptidase-IV (DPP-IV) in jejunum cells of the morbidly obese (OB) non type 2 diabetes mellitus (NDM2) and type 2 diabetes mellitus (T2DM), to determine the molecular basis of incretin secretion after bariatric surgery. Samples of jejunal mucosa were obtained from 20 NDM2 patients: removal of a section of the jejunum about 60 cm distal to the ligament of Treitz and 18 T2DM patients: removal of a section of the jejunum about 100 cm distal to the ligament of Treitz. Total RNA was extracted using TRIzol. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was carried out. Samples were sequenced to PC1/3 by ACTGene Análises Moleculares Ltd. Immuno content was quantified with a fluorescence microscope. T2DM showed decreased PC1/3 mRNA expression in the primers tested (primer a, p=0.014; primer b, p=0.048). Many patients (36.5 %) did not express PC1/3 mRNA. NDM2 and T2DM subjects showed nonsignificantly different proglucagon, GIP, and DPP-IV mRNA expression. The immuno contents of glucagon-like peptide-1 and GIP decreased in T2DM jejunum, but incubation with high glucose stimulated the immuno contents. The results suggest that bioactivation of pro-GIP and proglucagon could be impaired by the lower expression of PC1/3 mRNA in jejunum cells of obese patients with T2DM. However, after surgery, food could activate this system and improve glucose levels in these patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Chronic tubulointerstitial nephritis and renal insufficiency associated with long-term "subtherapeutic" gentamicin.
To determine whether long-term "subtherapeutic" concentrations of aminoglycoside produce chronic tubulointerstitial nephropathy, Fisher rats were given gentamicin, 20 mg/kg/day, for up to 6 months via indwelling osmotic infusion pumps. Studies included renal histology, autoradiographic quantitation of renal cell tritiated thymidine uptake, renal function and renal cortical gentamicin assay. Acute proximal tubular injury, without tubular necrosis, followed by recovery, occurred during the first month. Subsequently only mild, nonprogressive tubulointerstitial changes and a twofold increase in tubular cell turnover were observed. Inulin clearance fell more than 50% during the 6 months of treatment compared with 10% in age-matched controls. Serum creatinine and creatinine clearance overestimated glomerular filtration rate during treatment and did not distinguish treated animals from controls. During the month after 6 months of gentamicin, tubular microcystic changes and active tubulointerstitial nephritis developed, with a continued fall in inulin clearance. In summary, gentamicin, in "subtherapeutic" doses, produces mild chronic tubulointerstitial nephritis with progressive renal failure. Cessation of treatment is associated with microcystic and inflammatory changes, suggesting that the renal response to tubular injury can be dissociated from the amount of toxin in the renal cortex. Keeping serum aminoglycoside levels below accepted therapeutic range for 6 months did not preclude nephrotoxicity. | {
"pile_set_name": "PubMed Abstracts"
} |
Difference in stair negotiation ability based on TKA surgical approach.
Several surgical approaches for total knee arthroplasty (TKA) have been developed to minimize soft-tissue trauma and expedite functional recovery. A group of 61 subjects undergoing computer-navigated, minimally invasive TKA were randomized to receive a mini-parapatellar, standard parapatellar, mini-midvastus (MV), or mini-subvastus approach. Before and after treatment, subjects were asked to negotiate stairs in a self-selected manner. This study used the manner of stair negotiation (i.e., use of handrail, step-over-step, step-by-step) as a proxy for functional ability. Subjects who received TKA through a mini-MV approach demonstrated a significantly lower level of function at 2 and 4 months. If early functional recovery is a goal of TKA, surgeons should be cautious when considering the mini-MV approach, which was found to be inferior to other approaches in this study. | {
"pile_set_name": "PubMed Abstracts"
} |
A novel hydrogen sulfide-releasing donor, HA-ADT, suppresses the growth of human breast cancer cells through inhibiting the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling pathways.
Breast cancer is one of the most frequent cancers among women worldwide. Hyaluronic acid (HA) is one of the best biopolymers in terms of safety issues and has been widely used in drug delivery and tissue engineering. 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH) is a commonly used H2S donor. In this study, we designed and synthesized a conjugate, HA-ADT, by connecting HA with ADT-OH through chemical reactions. Our results indicated that HA-ADT could produce more H2S than NaHS and GYY4137. HA-ADT exerted more potent inhibitory effects than NaHS and GYY4137 in the proliferation, viability, migration, and invasion of human breast cancer cells. Similar trends were observed in the apoptosis and the protein levels of phospho (p)-PI3K, p-AKT, p-mTOR, H-RAS, p-RAF, p-MEK, and p-ERK in human breast cancer cells. Furthermore, HA-ADT exhibited more powerful inhibitory effects on the growth of human breast cancer xenograft tumors in nude mice. In conclusion, HA-ADT could suppress the growth of human breast cancer cells through the inhibition of the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK signaling pathways. HA-ADT and its derivatives might be of great potential in the treatment of different types of cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Nonkin in older adults' personal networks: more important among later cohorts?
Research on age-related changes in personal networks has found compelling evidence for socioemotional selectivity theory and exchange theory holding that older adults experience a decline in less emotionally close nonkin relations as they age. However, recent societal developments are likely to have increased the salience of nonkin relations. We hypothesize that age-related decline in the proportion of nonkin in personal networks has been delayed or is slower in late birth cohorts of older adults compared with earlier cohorts. Seven observations by the Longitudinal Aging Study Amsterdam covering a time span of 17 years since 1992 were analyzed using multilevel regression analysis. The sample had 12,949 person-year observations from 3,516 respondents born between 1908 and 1937. Age-related decline in the proportion of nonkin is absent for cohorts born after 1922 and large for cohorts born in 1922 and before. Mediating variables for health and other resources did not explain cohort differences in age-related change. The salience of nonkin relationships is likely to have increased due to societal changes, resulting in absence or delay of decline in later cohorts. The findings raise the need for a reevaluation of old age and the creation of new theoretical perspectives. | {
"pile_set_name": "PubMed Abstracts"
} |
Embryonic human leukocyte antigen-G expression: possible implications for human preimplantation development.
To investigate further the association between human leukocyte antigen G (HLA-G) expression in human embryos and other factors known to influence IVF pregnancy outcome. A university-based tertiary referral center (The Toronto Hospital). Nontransferred embryos at the two- to four-cell stage were obtained from patients undergoing IVF and were cultured in Ham's F-10 medium supplemented with 10% human sera or cocultured with ovarian cancer cells in the same medium. Embryos that reached blastocyst stage (n = 148) were analyzed by reverse transcriptase-polymerase chain reaction for HLA-G and beta 2 microglobulin (beta 2m) expression. Statistical analysis was performed to identify possible factors associated with variability of expression. Approximately 40% of studied blastocysts had detectable expression of both HLA-G and beta 2m messenger RNA. In 46% of blastocysts, beta 2m alone was observed. Interestingly, sibling embryos from patients that became pregnant were significantly more likely to express HLA-G than embryos from patients that did not conceive as a result of their IVF cycles. No association was found between HLA-G expression and culture conditions, patients age, or infertility diagnosis. The population of embryos obtained through IVF is heterogeneous in expression of HLA-G and beta 2m, which may reflect overall health of the embryos. Blastocysts showing positive HLA-G expression may have increased viability and implantation potential, although the underlying mechanisms remain to be elucidated. | {
"pile_set_name": "PubMed Abstracts"
} |
Pocket mobile smartphone system for the point-of-care submandibular ultrasonography.
Focused ultrasonography of the airway may be useful in the prediction of difficult intubation. The wider use of sonography in quantitative airway assessment may depend on the availability of highly portable, inexpensive, and accurate ultrasound systems. Pocket-sized ultrasound devices are emerging as a useful tool for point-of-care ultrasonography. The aim of this study was to evaluate the suprahyoid airway of healthy volunteers using a smartphone-based ultrasound imaging system in comparison with a platform-based machine. Mobisante MobiUS SP1 system with 2 mechanical sector (3.5 and 7.5 MHz) probes was used to acquire images of the tongue and measure the diameter of the hyomental muscle in the mouth floor. In the same group of subjects, imaging and measurements were repeated using BK Medical Flex Focus 400 ultrasound system with linear (18 MHz ) and curved 5 (MHz) transducers. The MobiUS system was also used to image plastic cylinders and procedure needles embedded in tofu bars. Outside diameters of cylinders were measured using digital calipers and sonography. The mean diameter of the hyomental muscle in 10 healthy volunteers was 7.22 ± 1.6 mm using BK 18 MHz probe, 7.11 ± 1.7 mm using MobiUS 7.5 MHz probe, and 7.84 ± 2 mm using MobiUS 3.5 MHz probe. These means were not statistically different (BK vs Mo 7.5, P = .74, and BK vs Mo 3.5, P = .13). The mean outside diameter of plastic cylinders measured with digital calipers was 10.1 ± 0.2 mm (n = 5) vs 9.8 ± 0.3 mm and 10.2 ± 0.2 mm using 3.5 and 7.5 MHz probes, respectively. These means were not statistically different (calipers vs Mo 3.5, P = .16 and calipers vs Mo 7.5, P = .39). Mobisante MobiUS system was able to acquire clinically useful images of the suprahyoid airway and muscular architecture in the mouth floor and allowed accurate measurements of linear distances. | {
"pile_set_name": "PubMed Abstracts"
} |
Aberrant hippocampal spine morphology and impaired memory formation in neuronal platelet-derived growth factor β-receptor lacking mice.
The physiological role of platelet-derived growth factor (PDGF) in the central nervous system (CNS) synaptic function remains uncharacterized. Here we identify physiological roles of PDGF receptor-β (PDGFR-β) in the CNS by conditional knockout of the gene encoding it. In the hippocampus, PDGFR-β colocalized immunohistochemically with both presynaptic synaptophysin and postsynaptic density-95 (PSD-95). In the hippocampal CA1 region, expression levels of postsynaptic proteins, including spinophilin, drebrin, and PSD-95, were significantly decreased in PDGFR-β knockout mice, although presynaptic synaptophysin levels remained comparable to controls. Interestingly, in hippocampal CA1 pyramidal neurons, dendritic spine density in PDGFR-β knockout mice was significantly decreased compared with that seen in wild-type mice, although spine length and number of dendritic branches remained unchanged. Consistent with these findings, impairment in hippocampal long-term potentiation (LTP) and in hippocampus-dependent memory formation were seen in PDGFR-β knockout mice. These results suggest PDGFR-β plays critical roles in spine morphology and memory formation in mouse brain. | {
"pile_set_name": "PubMed Abstracts"
} |
Universal magnetic structure of the half-magnetization phase in Cr-based spinels.
Using an elastic neutron scattering technique under a pulsed magnetic field up to 30 T, we determined the magnetic structure in the half-magnetization plateau phase in the spinel CdCr2O4. The magnetic structure has a cubic P4{3}32 symmetry, which is the same as that observed in HgCr2O4. This suggests that despite their different zero-field ground states a universal field-induced spin-lattice coupling mechanism is at work in the Cr-based spinels. | {
"pile_set_name": "PubMed Abstracts"
} |
Surgical defect coverage in oral submucous fibrosis patients with single-stage extended nasolabial flap.
Long standing oral submucous fibrosis (OSMF) is associated with involvement of the oral submucosa and the muscles of mastication leading to difficulty in mouth opening. Various surgical modalities are mentioned for release but each has its own limitations. The aim of the study was to evaluate the postoperative mouth opening in patients of OSMF after excision of fibrous bands followed by coronoidotomy and surgical defect coverage by extended nasolabial flap. We evaluated the use of extended nasolabial flaps and coronoidectomy in the management of 11 randomly selected patients with histologically confirmed oral submucous fibrosis. They all had interincisal opening of less than 25 mm and were treated by bilateral release of fibrous bands, coronoidectomy or coronoidotomy, and extended grafting with a nasolabial flap. Their interincisal opening improved significantly from a mean of 8.68±7 mm to a mean of 36.75±4.05 mm at 6-month follow-up. The procedure was effective in the management of patients with oral submucous fibrosis, the main disadvantage being the extraoral scars. | {
"pile_set_name": "PubMed Abstracts"
} |
Glycine stimulation of glutamate binding to chick retinal pigment epithelium.
The effect of glycine (Gly) and taurine (Tau) on the biochemical and pharmacological properties of [3H]L-glutamate ([3H] Glu) binding to membranes from primary cultures of chick retinal pigment epithelium (RPE), as well as from intact tissue during development was studied. Gly and Tau increase Bmax of [3H]Glu binding to a high affinity site (KB = 300 nM) in membranes from 16 days in vitro (immature) cultures; additionally, Gly discloses a low affinity Glu-binding site (KB = 970 nM) at this stage. In membranes from 25 days in vitro (mature) cultures, the high affinity site is no longer present and Tau has no effect on Glu-binding; Gly still stimulates binding to the low affinity site by four fold, with an EC50 = 200 microM. Pharmacological profile using specific excitatory amino acid (EAA) receptor agonists and antagonists suggests that at 16 days in vitro Glu binds preferentially to metabotropic Glu receptors (mGluRs), and at 25 days in vitro to ionotropic receptors different from neuronal ones. The stimulatory effect of Gly and Tau was also observed in intact RPE, and decreased with increasing embryonic age. Glu binding was also stimulated in membranes from chick retina, but not in those from rat brain. Results support the possibility of EAA participation in several aspects of RPE physiology, including phagocytosis and cell division. | {
"pile_set_name": "PubMed Abstracts"
} |
Radiotherapy for metastatic brain tumors.
Radiation therapy has been the most important treatment for patients with brain metastases. With the development of stereotactic irradiation, conventional radiotherapy is being employed less often. However, whole-brain radiation therapy (WBRT) is still the mainstay of treatment for multiple brain metastases. This article reviews the results of conventional radiotherapy for brain metastases, and discusses optimal treatment, including fractionation schedules and combination with stereotactic irradiation, and the effects on neurocognitive functions. The authors conclude that WBRT with 30 Gy in ten fractions is no longer optimal for every patient with multiple brain metastases. WBRT employing appropriate fractionation schedules with or without stereotactic boost should be considered, depending on the patient's condition, disease status, and expected period of life. | {
"pile_set_name": "PubMed Abstracts"
} |
pH difference across the outer mitochondrial membrane measured with a green fluorescent protein mutant.
In this study we have generated a EYFP targeted to the mitochondrial intermembrane space (MIMS-EYFP) to determine for the first time the pH within this compartment. The fragment encoding HAI-tagged EYFP was fused with the C-terminus of glycerol-phosphate dehydrogenase, an integral protein of the inner mitochondrial membrane. Human ECV304 cells transiently transfected with MIMS-EYFP showed the typical mitochondrial network, co-localized with MitoTracker Red. Following the calibration procedure, an estimation of the pH value in the intermembrane space was obtained. This value (6.88+/-0.09) was significantly lower than that determined in the cytosol after transfection with a cytosolic EYFP (7.59+/-0.01). Further, the pH of the mitochondrial matrix, determined with a EYFP targeted to this subcompartment, was 0.9 pH units higher than that in the intermembrane space. In conclusion, MIMS-EYFP represents a novel powerful tool to monitor pH changes in the mitochondrial intermembrane space of live cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Relaxin and the progression of kidney disease.
Relaxin is a peptide hormone named for its ability to soften the birth canal in preparation for parturition. Not surprisingly, therefore, subsequent attention has focused on its role in remodeling connective tissue in other organs, especially in circumstances of pathological fibrosis and scarring. This review discusses the renoprotective and therapeutic potential of relaxin in the kidney, which has highlighted its relevance in human pathophysiology. Growing evidence suggests that the kidney is both a therapeutic target and potential source of relaxin. Although the expression of renal relaxin is low, endogenous relaxin appears to play an important role in connective tissue homeostasis within the kidney, whereas exogenous relaxin has been shown to consistently and rapidly abrogate renal fibrosis at many levels, primarily through an ability to interfere with the actions of transforming growth factor beta-1. Furthermore, the vasodilatory and angiogenic properties of relaxin, in addition to its ability to improve renal function in humans, have contributed to its therapeutic significance in renal disease. Accumulating evidence from studies at the preclinical and clinical level has demonstrated a potential antifibrotic and regenerative capacity of relaxin, directly relevant to the kidney. | {
"pile_set_name": "PubMed Abstracts"
} |
Temporal summation in hearing-impaired listeners.
A study was conducted to explore variations in auditory temporal summation in listeners with normal hearing, and impairment due to otosclerosis, sensori-neural hearing loss and acoustic neuroma. Using a two-interval forced-choice procedure the detection threshold was measured for one-third octave noise bands centered at either 1000 or 4000 Hz, in combination with eight signal durations (2.5, 5, 10, 20, 40, 80, 160, and 640 ms). The results indicated that for normal listeners: (1) the slope of the function relating the detection threshold and the signal duration varied inversely with the frequency tested, and (2) the variability in the detection threshold was greater for 4000 Hz than for 1000 Hz. A comparison of performance across groups showed that the magnitude of the slope of the temporal integration function decreased as the site of lesion moved from middle ear to eighth nerve. For listeners with normal hearing and those with otosclerosis, temporal integration appeared to be incomplete at 640 ms. | {
"pile_set_name": "PubMed Abstracts"
} |
Student-led co-curricular medical Spanish training in a pharmacy professional program.
This paper describes a student-led co-curricular training program to increase pharmacy student proficiency with medical Spanish terminology. Western University of Health Sciences (WesternU) pharmacy students frequently can interact with Spanish-speaking patients in experiential rotations. Moreover, the clear majority of program graduates remain in California, a state with a high Spanish-speaking population. Developing foundational knowledge of medical Spanish terminology can enhance communication with Spanish-speaking patients, who may have limited English proficiency and experience a lack of language concordance when interacting with the healthcare system. Providing training in medical terminology in another language is important because communication barriers have been associated with adverse medical outcomes, such as poor medication adherence. The development of the training logistics and materials are described for replication of the process, whether with medical Spanish or other languages. Students in the pharmacy program developed the medical Spanish training that is now a robust co-curricular activity with over 100 students participating in the training each semester. An important aspect of the WesternU co-curricular activity is that students develop materials, create learning activities, and facilitate training. | {
"pile_set_name": "PubMed Abstracts"
} |
How do English-speaking Cancer Patients Conceptualise Personhood?
Understanding personhood or "what makes you, you" is pivotal to the provision of person-centred care. Yet the manner that personhood is conceived amongst patients varies significantly. This study aims to investigate conceptions of personhood in a multiracial, multicultural, multireligious setting. A mixed-methods study was conducted at National Cancer Centre Singapore, from January 2013 to April 2013. We used a validated questionnaire where English-speaking oncology patients rated the importance of 26 features of "personhood" on a 10-point Likert scale from 0 to 9, with 9-points being extremely important. This was followed by a semi-structured interview. Analysis of transcripts using the Grounded Theory revealed original data that inspired novel ideas about the nature of personhood, which precipitated a further study in April 2014. Our initial study of 100 patients revealed that personhood is conceived in a unique and novel manner. To study this, we interviewed a further 40 patients using a supplemental question to our original questionnaire. Our data affirmed our initial findings and evidenced a change in conceptions of personhood. Our evidence supports the Ring Theory of Personhood, which suggests that personhood is defined by innate, individual, relational, societal elements. It also evidences that personhood is temporally and contextually sensitive allowing for better appreciation of the evolving goals of care that frequently occur at end-of- life. Most importantly, this study reminds healthcare professionals on the importance of "treating persons" and looking beyond familial interests in maintaining the interests and dignity of the patient. | {
"pile_set_name": "PubMed Abstracts"
} |
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