Search

The article deals with challenges faced by the geriatric populations while on MDR treatment. Risk factors like tobacco use, low socio-economic status, previous disease, longer delays in seeking treatment and reduced mobility are some of the challenges while initiating MDR treatment. Other issues like drug-related adverse events and increased co-morbidity pose a major challenge while treating patients. Susceptibility among the geriatric age group includes various anatomical and physiological changes including nutritional deficiencies and co morbidities.

The parallelization, design and scalability of the PolGrawAllSky code to search for periodic gravitational waves from rotating neutron stars is discussed. The code is based on an efficient implementation of the F -statistic using the Fast Fourier Transform algorithm. To perform an analysis of data from the advanced LIGO and Virgo gravitational wave detectors’ network, which will start operating in 2015, hundreds of millions of CPU hours will be required—the code utilizing the potential of massively parallel supercomputers is therefore mandatory. We have parallelized the code using the Message Passing Interface standard, implemented a mechanism for combining the searches at different sky-positions and frequency bands into one extremely scalable program. The parallel I/O interface is used to escape bottlenecks, when writing the generated data into file system. This allowed to develop a highly scalable computation code, which would enable the data analysis at large scales on acceptable time scales. Benchmarking of the code on a Cray XE6 system was performed to show efficiency of our parallelization concept and to demonstrate scaling up to 50 thousand cores in parallel. Program summary Program title: parallel PolGrawAllSky Catalogue identifier: AEUX_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEUX_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 163747 No. of bytes in distributed program, including test data, etc.: 28989030 Distribution format: tar.gz Programming language: C. Computer: Any parallel computing platform supporting MPI standard. Operating system: Linux as well any other supporting MPI standard. Has the code been vectorized or parallelized?: Yes, using MPI. Tested with up to 50208 processors RAM: 1 Gigabyte per parallel task Classification: 1.5. External routines: MPI v.2 or newer, FFTW v.3 or newer Nature of problem: Search for periodic gravitational waves from rotating neutron stars. Solution method: The F -statistic method using the Fast Fourier Transform algorithm. Running time: The example provided takes approximately 30 mins with 256 processors. [ABSTRACT FROM AUTHOR]

ABSTRACTThe objective of the current study was to systematically evaluate the existing evidence in relation to the safety, quality, productivity or cost-benefit, and patient satisfaction of the procedures performed by the different groups of dental providers. Due to the diversity of the procedures performed and the outcomes measured, it was not possible to create pooled estimates in a meaningful manner. Therefore, summary results of individual studies are presented and critically evaluated.

Systemic nicotine stimulates dopamine (DA) release in the nucleus accumbens (NAcc), and N-methyl-D-aspartate (NMDA) receptors in the ventral tegmental area (VTA) appear to be involved. However, it is not known whether the secretion of DA elicited by nicotine depends on the tonic and/or phasic activation of NMDA receptors by glutamate (Glu). To clarify this, in vivo microdialysis was conducted in freely moving, alert rats to measure DA and Glu overflows in the NAcc and Glu in the VTA. Nicotine (0.065, 0.09, or 0.135 mg/kg delivered i.v. at 0.09 mg/kg/60 s via a jugular cannula) dose dependently stimulated NAcc DA secretion (P <.05). However, 0.065 mg/kg nicotine failed to stimulate Glu release in the VTA, whereas higher doses of nicotine (> or =0.09 mg/kg) were effective (P <.05). Administering the competitive NMDA receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP-5; 1 mM) or 0.2 mM cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) through the VTA probe, abolished NAcc DA release after 0.065 mg/kg nicotine (P <.01) and reduced the response to 0.09 mg/kg nicotine. Therefore, the NAcc DA response to a relatively low dose of nicotine depends on the tonic activation of NMDA receptors in the VTA. In contrast, infusing 1 mM 2-amino-5-phosphonopentanoic acid or 1 mM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, into the NAcc through the microdialysis probe had no effect on NAcc DA secretion in response to 0.09 mg/kg nicotine. These findings, coupled with data showing that Glu secretion in the VTA was stimulated only by higher doses of nicotine, indicate that the phasic release of VTA Glu is involved in the NAcc DA response to higher doses of nicotine (> or =0.09 mg/kg).

Previous studies have shown that nicotinic receptors (NAChRs) accessible from the cerebral aqueduct of the brainstem mediate the hippocampal norepinephrine (NE) release induced by i.v. nicotine. The present study was designed to investigate the role of hippocampal NAChRs in this process. Nicotinic antagonists were microinjected or microdialyzed into the hippocampus (HP) before administering nicotine (0.09 mg/kg over 60 s, i.v.) to freely moving rats. alpha-Bungarotoxin (0.3 nmol by microinjection) blocked nicotine-induced hippocampal NE release by 47% (p <.05) and abolished the effect of 0.065 mg/kg nicotine. Methyllycaconitine (1.4-5.6 mM in the dialysate) inhibited the stimulatory effect of nicotine 0.09 mg/kg by 48 to 75% (p <.05). In contrast, mecamylamine (2.9-5.8 mM) and dihydro-beta-erythroidine (7-14 mM) were completely ineffective. The role of hippocampal NAChRs was demonstrated further by selectively desensitizing these receptors before the systemic infusion of nicotine. To do so, the HP was pretreated with nicotine (0.1 mM) delivered through the microdialysis probe; this concentration was calculated to yield tissue concentrations similar to those produced by the systemic infusions of nicotine. Dialyzing this concentration of nicotine into the HP inhibited the NE response to i.v. nicotine by 34% (p <.05), and 1.0 mM nicotine reduced the response by 40%. These studies indicate that alpha-bungarotoxin-sensitive hippocampal NAChRs, probably containing alpha7 subunits, modulate hippocampal NE release because of systemic nicotine.

Nicotine is a potent secretagogue for the release of adrenocorticotropin (ACTH) from the anterior pituitary in vivo. However, the location of its action is unknown; knowledge of this is essential for elucidating its mechanism. Our studies show that cytisine, a peripherally acting nicotinic cholinergic agonist, given i.v. at doses equimolar or greater than nicotine, failed to elevate plasma ACTH levels, whereas nicotine (0.01 and 0.03 mg/kg b.wt.) had significant effects. Nicotine (10(-7)-10(-4) M) had no effect on the secretion of beta-endorphin by anterior pituicytes in vitro, nor did it potentiate the action of corticotropin-releasing factor (10(-9) or 10(-8) M). Intracerebroventricular injection of nicotine (1-20 micrograms) significantly elevated ACTH levels. Moreover, ACTH responses to nicotine delivered into the hypothalamic region of the third ventricle were significantly greater than those elicited by injection into the upper region. Additional studies were conducted to determine the earliest age at which nicotine stimulates ACTH. The response to i.p. nicotine (1 or 2 mg/kg b.wt.) was present but diminished during the postnatal period, whereas maximal responses comparable to mature rats were attained by day 15. To establish whether nicotine has a central effect in younger animals, nicotinic antagonists were tested. Hexamethonium (2 mg/kg b.wt.), a peripherally acting antagonist, was ineffective against nicotine (0.025 and 2.0 mg/kg b.wt.), whereas mecamylamine (2 mg/kg b.wt.), inhibitory at both peripheral and central sites, blocked the ACTH response. Thus, whether administered peripherally or centrally, nicotine activates central mechanisms mediating the release of ACTH; it appears that the target(s) for nicotine are within the hypothalamus or brainstem.

Previous studies have shown that nicotine stimulates norepinephrine (NE) release in the rat hypothalamic paraventricular nucleus, which in turn activates the hypothalamo-pituitary-adrenal axis. In the present study, nicotine induced NE release in the amygdala (AMYG) and the hippocampus (HP) of the same rat in vivo. Nicotine (0.065-0.135 mg/kg i.v. at a rate of 0.09 mg/kg/60 sec) dose-dependently increased NE release at both sites with similar potencies. To determine whether the site of action of nicotine is in the brainstem, which contains the noradrenergic cell bodies projecting to AMYG and HP, nicotinic cholinergic receptor (NAchR) antagonists were injected into the cerebral aqueduct before i.v. nicotine. Use of the following antagonists enabled partial characterization of the NAchRs mediating NE secretion: mecamylamine (Mec), dihydro-beta-erythroidine (DH beta E), methyllycaconitine (MLA) and alpha-bungarotoxin (alpha-BTX). Mec inhibited 80% of NE release in AMYG and 87% in HP (IC50 = 6 nmol for both regions). DH beta E blocked 62% of NE release in AMYG (IC50 = 8 nmol) and 63% in HP (IC50 = 15 nmol). Similar to DH beta E, MLA inhibited 60% of NE release in AMYG and 66% in HP (IC50 = 5 nmol for both regions). In contrast, alpha-BTX had no effect on NE release in either region. These results indicate that brainstem NAchRs accessible from the fourth ventricle mediate nicotine-stimulated NE secretion in AMYG and HP. Taken together with prior investigations showing the brainstem expression of mRNAs encoding NAchR subtypes and the selectivity of antagonists for NAchR subtypes, the present studies suggest that brainstem alpha-3 subunits may be involved.

Peripherally administered nicotine elevates rat plasma adrenocorticotropic hormone (ACTH) levels, acting at brain regions adjacent to or downstream from the third cerebroventricle. Studies evaluated whether the paraventricular nucleus (PVN) mediates directly the ACTH response to nicotine administered i.v. and if regions adjacent to the fourth ventricle (IV) are involved. Direct involvement of the PVN in the release of ACTH in response to i.v. nicotine (0.03 or 0.01 mg/kg b.wt.) was refuted by studies in which the administration of the nicotinic cholinergic antagonist, mecamylamine (20 or 40 micrograms bilaterally adjacent to the PVN), failed to block ACTH secretion. To activate sites distal to the third ventricle, nicotine (0.25, 0.5, 2.5 or 5.0 micrograms) was injected into the IV; ACTH levels peaked between 3 and 7 min. Nicotine 0.25 micrograms injected into the IV elevated ACTH to levels within the range of those produced by i.v. nicotine (0.03 mg/kg b.wt.). To confirm that sites accessible from the IV are involved, mecamylamine was administered i.v. (0.5 or 1.0 mg/kg b.wt.) or into the IV (4 or 40 micrograms) and nicotine was delivered by the opposite route. Intravenous mecamylamine reduced the plasma ACTH response to 0.25 micrograms of nicotine in the IV. Mecamylamine, administered into the IV before i.v. nicotine (0.03 mg/kg b.wt.) antagonized the effect of nicotine. These results indicate that stimulation of ACTH secretion by nicotine delivered i.v. occurs via structures accessible from the IV. In contrast to prevailing ideas, the PVN does not appear to be the direct site of action of nicotine.

Single cells isolated from rat islets of Langerhans were cultured under conditions that support reassociation into islet-like aggregates. Comparisons were made of enzymatic methods of islet dissociation, rotational or static culture conditions, and culture at basal or stimulatory glucose concentrations. Over a period of 4 days the aggregates progressed through three stages of organization: cell coalescence to cellular chains, rearrangement of chains into small spheroids, and growth of spheroids. The numerical yield of aggregates was optimum after islets were dissociated with dispase. Culture under rotation resulted in the production of more aggregates of significantly larger diameter than under static conditions. Medium glucose concentrations of 4 and 11 mM supported cell reassociation under rotator culture, but no aggregation occurred under static culture at the basal (4 mM) glucose level. Aggregates resulting from 4-day rotator culture exhibited endocrine cell distributions similar to intact islets. Islet aggregates released insulin in response to glucose, but non aggregated cells, maintained in culture, did not. The present comparisons reveal significant variability in the cellular composition, rate of formation, and yield of aggregates, and suggest that the methodology for producing aggregates should be carefully considered in experimental design.

The central mechanism(s) whereby peripherally administered nicotine (N) stimulates prolactin secretion has not been clarified. The current studies showed that an i.c.v. injection of N into the fourth ventricle (IV) produced a significant dose-dependent elevation of plasma prolactin [buffer less than N 0.125 micrograms = N 0.25 micrograms (P less than .05) less than N 0.5 micrograms = N 2.5 micrograms (P less than .01)]. Injecting the nicotinic cholinergic (NAch) antagonist, mecamylamine, into the IV (20 or 40 micrograms) or i.v. (0.5 mg/kg b.wt.) before the administration of N by the alternate route indicated that nicotine was activating NAch receptors accessible from the IV. Because brain stem catecholaminergic cell groups, adjacent to the IV, project to hypothalamic regions involved in modulating prolactin release, the involvement of IV catecholaminergic neurons in N-stimulated prolactin release was investigated. Ablation of central catecholaminergic neurons by 6-hydroxydopamine abolished the prolactin response to N injected i.c.v. (1 or 2.5 micrograms; P less than .05) or i.v. (0.03 or 0.05 mg/kg b.wt.; P less than .05). To assess the role of norepinephrine and epinephrine, LY 10853, an inhibitor of dopamine-beta-hydroxylase, was given i.p. 4 h before i.v. nicotine; the prolactin response was attenuated (P less than .01). Selective inhibitors of epinephrine synthesis, SKF 64139 or 2,3-dichloro-alpha-methylbenzylamine, administered on the same schedule, reduced (P less than .01) the prolactin response to N without altering responsiveness to the dopamine receptor antagonist, domperidone.(ABSTRACT TRUNCATED AT 250 WORDS)

Graphene and AlN are promising materials, interesting to combine together. In this study, we will present first results for direct growth of graphene on bulk AlN and on AlN templates using chemical vapor deposition, including the annealing of these substrates at high temperatures. Atomic force microscopy (AFM) enabled us to study the evolution of the AlN surface morphology after annealing and growth. Few‐layer graphene deposition is demonstrated on the basis of X‐ray photoemission and Raman spectroscopy. AFM view of graphene wrinkles on the N‐face of bulk AlN.

Objective:  We aimed to investigate the reproducibility of vena contracta (VC) in mitral regurgitation (MR) of different etiology between an inexperienced and an experienced echocardiographer. Background: MR is the second most common valvular heart disease in Europe that requires surgery.  Echocardiography is the principal modality of investigation when MR is suspected. In European and American guidelines VC is described as one of the most feasible echocardiographic measurements in the assessment of MR. There is a lack of publications regarding intra-observer variability and studies comparing inexperienced and experienced echocardiographers for the assessment of VC. Method/Material: VC of 55 recorded 2D echocardiograms with known MR of different degree and etiology were analyzed from parasternal long axis view, 4- and 3 chamber view. The mean value of the different plane measurements of each exam was used for statistical analysis. Analyses were made by an inexperienced (A) fellow echocardiographer (<100 studies) and a level 3 experienced (B) echocardiographer. Measurements of VC by the 2 echocardiographers were performed blinded to clinical data. Measurements were performed with at least 2 weeks apart, blinded to the first measurement. Results: Three exams were excluded (feasibility 95%) from statistical analysis because adequate color Doppler images from all tree planes was not available. The inter class correlation (ICC) between the first and second analysis was (r=0.75; 95% CI -1.1 to 1.7mm) for A and (r=0.94; 95% CI -0.76 to 0.84mm) for B. There was good ICC between the 2 echocardiographers (r=0.78; 95% CI -1.5 to 1.3mm). The intra observer variability was 11.1% for A and 6.1% for B. The inter observer variability was 11.7% (p>0.05 for all). Conclusion: Measurement of vena contracta in mitral regurgitation is a feasible semi-quantitative parameter. Good correlation and narrow limits of agreement between a novice and an experienced echocardiographer was demonstrated in our study.