TL;DR: The genus Xanthomonas is a diverse and economically important group of bacterial phytopathogens, belonging to the γ-subdivision of the Proteobacteria, and several groups of strain-specific genes are identified and proposed mechanisms that may explain the differing host specificities and pathogenic processes are proposed.
Abstract: The genus Xanthomonas is a diverse and economically important group of bacterial phytopathogens, belonging to the gamma-subdivision of the Proteobacteria. Xanthomonas axonopodis pv. citri (Xac) causes citrus canker, which affects most commercial citrus cultivars, resulting in significant losses worldwide. Symptoms include canker lesions, leading to abscission of fruit and leaves and general tree decline. Xanthomonas campestris pv. campestris (Xcc) causes black rot, which affects crucifers such as Brassica and Arabidopsis. Symptoms include marginal leaf chlorosis and darkening of vascular tissue, accompanied by extensive wilting and necrosis. Xanthomonas campestris pv. campestris is grown commercially to produce the exopolysaccharide xanthan gum, which is used as a viscosifying and stabilizing agent in many industries. Here we report and compare the complete genome sequences of Xac and Xcc. Their distinct disease phenotypes and host ranges belie a high degree of similarity at the genomic level. More than 80% of genes are shared, and gene order is conserved along most of their respective chromosomes. We identified several groups of strain-specific genes, and on the basis of these groups we propose mechanisms that may explain the differing host specificities and pathogenic processes.
TL;DR: Qualitative research offers a variety of methods for identifying what really matters to patients and carers, detecting obstacles to changing performance, and explaining why improvement does or does not occur, which could lead to a better understanding of how to improve quality.
Abstract: There are no easy solutions to the problem of improving the quality of care. Research has shown how difficult it can be, but has failed to provide reliable and effective ways to change services and professional performance for the better. Much depends on the perspectives of users and the attitudes and behaviours of professionals in the context of their organisations and healthcare teams. Qualitative research offers a variety of methods for identifying what really matters to patients and carers, detecting obstacles to changing performance, and explaining why improvement does or does not occur. The use of such methods in future studies could lead to a better understanding of how to improve quality.
TL;DR: Funnel plot asymmetry tended to be greater in meta-analyses that included smaller number of primary studies, and there was a general lack of consideration of appropriate literature searching to minimize publication bias in reviews of diagnostic accuracy.
Abstract: Background Despite the great possibility of publication bias in studies of diagnostic test research, empirical studies about publication bias have mainly focused on studies of treatment effect. Methods A sample of 28 meta-analyses of diagnostic accuracy was selected from the Database of Abstracts of Reviews of Effectiveness (DARE). Methods used to deal with publication and related biases in these meta-analyses were examined. Asymmetry of funnel plot of estimated test accuracy against corresponding precision for each meta-analysis was assessed by three statistical methods: rank correlation method, regression analysis, and Trim and Fill method. Results In reviews of diagnostic accuracy, there was a general lack of consideration of appropriate literature searching to minimize publication bias, and the impact of possible publication bias has not been systematically assessed. The results of the three different statistical methods consistently showed that in a large proportion of the 28 meta-analyses evaluated, the smaller studies were associated with a greater diagnostic accuracy. Exploratory analyses found that the fewer the literature databases searched, the greater the funnel plot asymmetry in meta-analyses. Funnel plot asymmetry tended to be greater in meta-analyses that included smaller number of primary studies. Our data revealed no consistent relationship between funnel plot asymmetry and language restriction in reviews. Conclusions Further research is required to explain why smaller studies tended to report greater test accuracy in a large proportion of meta-analyses of diagnostic tests. In systematic reviews of diagnostic studies, literature search should be sufficiently comprehensive and possible impact of publication bias should be assessed.
TL;DR: In this article, a simple method to measure synchronization and time-delay patterns between signals is proposed, based on the relative timings of events in the time series, defined, e.g., as local maxima.
Abstract: We propose a simple method to measure synchronization and time-delay patterns between signals. It is based on the relative timings of events in the time series, defined, e.g., as local maxima. The degree of synchronization is obtained from the number of quasisimultaneous appearances of events, and the delay is calculated from the precedence of events in one signal with respect to the other. Moreover, we can easily visualize the time evolution of the delay and synchronization level with an excellent resolution. We apply the algorithm to short rat electroencephalogram (EEG) signals, some of them containing spikes. We also apply it to an intracranial human EEG recording containing an epileptic seizure, and we propose that the method might be useful for the detection of epileptic foci. It can be easily extended to other types of data and it is very simple and fast, thus being suitable for on-line implementations.
TL;DR: The age and geochemical data confirm that the West Siberian Basin basalts are part of the Siberian Traps and at least double the confirmed area of the volcanic province as a whole, which strengthens the link between the volcanism and the end-Permian mass extinction.
Abstract: Widespread basaltic volcanism occurred in the region of the West Siberian Basin in central Russia during Permo-Triassic times. New 40 Ar/ 39 Ar age determinations on plagioclase grains from deep boreholes in the basin reveal that the basalts were erupted 249.4 ± 0.5 million years ago. This is synchronous with the bulk of the Siberian Traps, erupted further east on the Siberian Platform. The age and geochemical data confirm that the West Siberian Basin basalts are part of the Siberian Traps and at least double the confirmed area of the volcanic province as a whole. The larger area of volcanism strengthens the link between the volcanism and the end-Permian mass extinction.
TL;DR: In this article, the authors investigated the ages of Indian basalts using Ar-40/Ar-39 incremental-heating experiments on whole rocks and concluded that the Rajmahal basalts, Jharkhand basalts and alkalic basalts in the Bengal Basin were emplaced at similar to118 Ma.
Abstract: During the mid-Cretaceous, extensive magmatism occurred in the Indian Ocean to form volcanic portions of the southern and central Kerguelen Plateau, Elan Bank and Broken Ridge. Basalt was erupted also along the rifted margin of eastern India (Rajmahal). We investigated the ages of these Indian basalts using Ar-40/Ar-39 incremental-heating experiments on whole rocks. Our results are consistent with the hypothesis that the lava pile of similar to230 m thickness in the Rajmahal Hills, Jharkhand, and alkalic basalts in the Bengal Basin were emplaced at similar to118 Ma. Dykes intruded to the SW of the Rajmahal Hills appear to be 2-3 Myr younger than these lavas. Magmatic activity in eastern India therefore was contemporaneous with the final stage of volcanism at Ocean Drilling Program Site 1136 on the Southern Kerguelen Plateau (119-118 Ma), but older than final magmatism at Sites 749 and 750 on the Southern Kerguelen Plateau (112-110 Ma), Site 1137 on Elan Bank (108 Ma) and Site 1138 on the Central Kerguelen Plateau (100 Ma). By combining these age data with plate reconstructions that take into account the motion of hotspots in a convecting mantle, we suggest that eruption of the Rajmahal basalts, formation of the Southern Kerguelen Plateau, and Elan Bank's separation from India are best explained by the presence of the Kerguelen hotspot close to the eastern Indian margin just after 120 Ma.
TL;DR: The novelty of the method is that it can handle in LMI form the situation ranging from no Markov state observation to complete state observation, and when the state observation is complete, the optimal H"2-norm solution is retrieved.
Abstract: The H"2-norm control problem of discrete-time Markov jump linear systems is addressed in this paper when part of, or the total of the Markov states is not accessible to the controller. The non-observed part of the Markov states is grouped in a number of clusters of observations; the case with a single cluster retrieves the situation when no Markov state is observed. The control action is provided in linear feedback form, which is invariant on each cluster, and this restricted complexity setting is adopted, aiming at computable solutions. We explore a recent result by de Oliveira, Bernussou, and Geromel (Systems Control Lett. 37 (1999) 261) involving an LMI characterization to establish a H"2 solution that is stabilizing in the mean square sense. The novelty of the method is that it can handle in LMI form the situation ranging from no Markov state observation to complete state observation. In addition, when the state observation is complete, the optimal H"2-norm solution is retrieved.
TL;DR: The results showed that denture replacement and denture hygiene improvement were useful for DS resolution, particularly types I and II, however, oral and dentures hygiene must be continuous, inasmuch as salivary Candida counts remained high and it is considered an important pre-disposing factor for DS.
Abstract: Denture stomatitis (DS) is frequently associated with high levels of Candida in saliva and deficient denture hygiene. In order to analyse the incidence of DS and its pre-disposing factors, we evaluated 77 edentulous patients before and 6 months after the placement of new complete dentures. Denture stomatitis was observed in 50.6 and 18.2% of the patients at the first and second evaluation, respectively. Salivary flow, Candida counts in saliva and Candida species were similar in both evaluations. Denture stomatitis and Candida in saliva were more common in females. Our results showed that denture replacement and denture hygiene improvement were useful for DS resolution, particularly types I and II. However, oral and denture hygiene must be continuous, inasmuch as salivary Candida counts remained high and it is considered an important pre-disposing factor for DS.
TL;DR: A detailed X-ray spectral analysis of Cas A using a deep exposure from the EPIC-MOS cameras on board XMM-Newton was performed on a 1515 grid of 20 00 20 00 pixels using a two component non-equilibrium ionisation model (NEI) giving maps of ionisation age, temperature, interstellar column density, abundances for Ne, Mg, Si, S, Ca, Fe and Ni and Doppler velocities for the bright Si-K, S-K and Fe-K line complexes as mentioned in this paper.
Abstract: We present a detailed X-ray spectral analysis of Cas A using a deep exposure from the EPIC-MOS cameras on-board XMM-Newton. Spectral tting was performed on a 1515 grid of 20 00 20 00 pixels using a two component non-equilibrium ionisation model (NEI) giving maps of ionisation age, temperature, interstellar column density, abundances for Ne, Mg, Si, S, Ca, Fe and Ni and Doppler velocities for the bright Si-K, S-K and Fe-K line complexes. The abundance maps of Si, S, Ar and Ca are strongly correlated. The correlation is particularly tight between Si and S. The measured abundance ratios are consistent with the nucleosynthesis yield from the collapse of a progenitor star of 12 M at the time of explosion. The distributions of the abundance ratios Ne/Si, Mg/Si, Fe/Si and Ni/Si are very variable and distinctly dierent from S/Si, Ar/Si and Ca/Si. This is also expected from the current models of explosive nucleosynthesis. The ionisation age and temperature of both the hot and cool NEI components varies considerably over the remnant. Accurate determination of these parameters has enabled us to extract reliable Doppler velocities for the hot and cold components. The combination of radial positions in the plane of the sky and velocities along the line of sight have been used to measure the dynamics of the X-ray emitting plasma. The data are consistent with a linear radial velocity eld for the plasma within the remnant with vs = 2600 km s 1 at rs = 153 arcsec implying a primary shock velocity of 4000 500 km s 1 at this shock radius. The Si-K and S-K line emission from the cool plasma component is conned to a relatively narrow shell with radius 100{150 arcsec. This component is almost certainly ejecta material which has been heated by a combination of the reverse shock and heating of ejecta clumps as they plough through the medium which has been pre-heated by the primary shock. The Fe-K line emission is expanding somewhat faster and spans a radius range 110{170 arcsec. The bulk of the Fe emission is conned to two large clumps and it is likely that these too are the result of ablation from ejecta bullets rather than swept up circumstellar medium.
TL;DR: Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations.
Abstract: PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.
TL;DR: It is concluded that pollination by resin‐collecting bees arose independently in Clusiella and the Clusioideae, and the aquatic family Podostemaceae is nested inside Clusiaceae as the sister group of subfamily Hypericoideae or tribe Hypericeae.
Abstract: Phylogenetic models of the Clusiaceae have so far been based on morphological data only. As an additional source of phylogenetic information, the chloroplast gene rbcL was sequenced for 26 species, representing all available genera of Clusiaceae. The DNA data were analyzed cladistically together with previously published sequences. The results show that the aquatic family Podostemaceae is nested inside Clusiaceae as the sister group of subfamily Hypericoideae or tribe Hypericeae. The subfamilies Kielmeyeroideae and Clusioideae, as delimited in recent morphology‐based classifications, are largely supported as monophyletic. The sole exception is Clusiella, which links with Kielmeyeroideae rather than with Clusioideae. We conclude that pollination by resin‐collecting bees arose independently in Clusiella and the Clusioideae: Clusieae.
TL;DR: In this paper, a comparative study of butterfly communities in 15 urban/suburban remnants of tropical semideciduous forest in Campinas (Sao Paulo state, SE Brazil; 24°S, 47°W), with areas from 1.0 to 252 ha and widely varying histories and environments, shows that the most significant factors, besides area and sampling time, distinguishing the sites and influencing their diversity (80−702 species) and composition are connectivity, permanent water, vegetation, flowers, and human impact (negative, including pollution).
Abstract: A comparative study of butterfly communities in 15 urban/suburban remnants of tropical semideciduous forest in Campinas (Sao Paulo state, SE Brazil; 24°S, 47°W), with areas from 1.0 to 252 ha and widely varying histories and environments, shows that the most significant factors, besides area and sampling time, distinguishing the sites and influencing their diversity (80–702 species) and composition are connectivity, permanent water, vegetation, flowers, and human impact (negative, including pollution). The diversified Nymphalidae butterflies (38–213 species) and especially two fermented-bait-attracted groups (Satyrinae, 2–30 species, and Biblidini, 9–44 species), are among the more useful indicators of the quality and diversity of the environments in these fragments. Effective conservation of butterfly communities in tropical cities may be achieved by maintenance of arboreal green corridors along streets and watercourses between moderately large (>10 ha) humid areas, not near to the most built-up or polluted city centre(s), and the inclusion within these areas of ponds or streams, diversified native forest, and open vegetation including abundant nectar-rich flowers.
TL;DR: Tunneling of optical pulses at 1.5 microm wavelength through double-barrier periodic fiber Bragg gratings is experimentally investigated and provides experimental evidence of the analogous phenomenon in quantum mechanics of nonresonant superluminal tunneling of particles across two successive potential barriers.
Abstract: Tunneling of optical pulses at $1.5 \ensuremath{\mu}\mathrm{m}$ wavelength through double-barrier periodic fiber Bragg gratings is experimentally investigated in this paper. Tunneling time measurements as a function of the barrier distance show that, far from resonances of the structure, the transit time is paradoxically short\char22{}implying superluminal propagation\char22{}and almost independent of the barrier distance. This result is in agreement with theoretical predictions based on phase-time analysis and provides, in the optical context, an experimental evidence of the analogous phenomenon in quantum mechanics of nonresonant superluminal tunneling of particles across two successive potential barriers.
TL;DR: In this article, the distribution of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma (PCG) was determined by using SSCP and direct sequencing of PCR fragments.
Abstract: PURPOSE. To determine the distribution of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma (PCG). METHODS. PCG diagnosis was established by presence of buphthalmos in at least one affected eye and associated high intraocular pressures before the age of 3 years. CYP1B1 mutation screening of 52 patients with PCG was performed by SSCP and direct sequencing of PCR fragments. RESULTS. Eleven mutations, four of which are novel, were observed in 26 (50%) individuals. A new frameshift mutation (4340delG) was observed in 20.2% of all individuals screened. These individuals had early-onset, bilateral glaucoma that necessitated multiple surgical interventions. CYP1B1 mutations were twice as frequent in affected individuals of European descent as in individuals of African descent. Analysis of six intragenic single nucleotide polymorphisms (SNPs) established 5-C-C-G-G-T-A-3 as the most common haplotype among the affected Brazilian individuals. A nonsense mutation (W57X) previously reported in an individual with Peters anomaly (compound heterozygote) was also observed in two individuals with PCG but combined with different mutations. A newly developed SSCP assay enabled us to detect all DNA mutations and polymorphisms previously detected by direct sequencing. CONCLUSIONS. Our results indicate that CYP1B1 mutations may be responsible for half of cases of PCG in the Brazilian population. The SNP haplotype 5-C-C-G-G-T-A-3 was associated with the majority of CYP1B1 mutations. This haplotype harbors the high-activity V432 allele, which is emerging as a putative susceptibility factor in several cancers. (Invest Ophthalmol Vis Sci. 2002;43:1820 –1827)
TL;DR: Structural differences between these two cytokines, revealed by the crystallographic studies, clearly indicate that, while a homodimer of IL-10 is required for signaling, hIL-22 most probably interacts with its receptor as a monomer.
Abstract: Interleukin-22 (IL-10-related T cell-derived inducible factor/IL-TIF/IL-22) is a novel cytokine belonging to the IL-10 family. Recombinant human IL-22 (hIL-22) was found to activate the signal transducers and activators of transcription factors 1 and 3 as well as acute phase reactants in several hepatoma cell lines, suggesting its involvement in the inflammatory response. The crystallographic structure of recombinant hIL-22 has been solved at 2.0 A resolution using the SIRAS method. Contrary to IL-10, the hIL-22 dimer does not present an interpenetration of the secondary-structure elements belonging to the two distinct polypeptide chains but results from interface interactions between monomers. Structural differences between these two cytokines, revealed by the crystallographic studies, clearly indicate that, while a homodimer of IL-10 is required for signaling, hIL-22 most probably interacts with its receptor as a monomer.
TL;DR: The results indicate that the reduced capacity of CBA/Ca mice to induce rapid TNF activity within the airways following infection with S. pneumoniae may be a factor in their elevated susceptibility to pneumococcal pneumonia.
Abstract: Variations in the host response during pneumonia caused by Streptococcus pneumoniae in susceptible (CBA/Ca) and resistant (BALB/c) inbred mouse strains were investigated. Significant differences were detected in survival time, core body temperature, lung-associated and systemic bacterial loads, mast cell numbers, magnitude and location of cytokine production, lung disruption, and ability of isolated lung cells to release the cytokine tumor necrosis factor (TNF) alpha in vitro. Overall, the results indicate that the reduced capacity of CBA/Ca mice to induce rapid TNF activity within the airways following infection with S. pneumoniae may be a factor in their elevated susceptibility to pneumococcal pneumonia.
TL;DR: The first known polynomial-time approximation scheme (PTAS), based on linear programming, is presented and is based on a new approach to the single-objective knapsack problem using a partition of the profit space into intervals of exponentially increasing length.
Abstract: For multiobjective optimization problems, it is meaningful to compute a set of solutions covering all possible trade-offs between the different objectives. The multiobjective knapsack problem is a generalization of the classical knapsack problem in which each item has several profit values. For this problem, efficient algorithms for computing a provably good approximation to the set of all nondominated feasible solutions, the Pareto frontier, are studied.For the multiobjective one-dimensional knapsack problem, a practical fully polynomial-time approximation scheme (FPTAS) is derived. It is based on a new approach to the single-objective knapsack problem using a partition of the profit space into intervals of exponentially increasing length. For the multiobjectivem-dimensional knapsack problem, the first known polynomial-time approximation scheme (PTAS), based on linear programming, is presented.
TL;DR: This work confirms that mouse ESTR loci are very sensitive to ionizing radiation and establishes that induced germline mutation results from radiation-induced mutant alleles being present in sperm, rather than from unrepaired sperm DNA lesions that subsequently lead to the appearance of mutants in the early embryo.
Abstract: Expanded simple tandem repeat (ESTR) loci include some of the most unstable DNA in the mouse genome and have been extensively used in pedigree studies of germline mutation. We now show that repeat DNA instability at the mouse ESTR locus Ms6-hm can also be monitored by single molecule PCR analysis of genomic DNA. Unlike unstable human minisatellites which mutate almost exclusively in the germline by a meiotic recombination-based process, mouse Ms6-hm shows repeat instability both in germinal (sperm) DNA and in somatic (spleen, brain) DNA. There is no significant variation in mutation frequency between mice of the same inbred strain. However, significant variation occurs between tissues, with mice showing the highest mutation frequency in sperm. The size spectra of somatic and sperm mutants are indistinguishable and heavily biased towards gains and losses of only a few repeat units, suggesting repeat turnover by a mitotic replication slippage process operating both in the soma and in the germline. Analysis of male mice following acute pre-meiotic exposure to X-rays showed a significant increase in sperm but not somatic mutation frequency, though no change in the size spectrum of mutants. The level of radiation-induced mutation at Ms6-hm was indistinguishable from that established by conventional pedigree analysis following paternal irradiation. This confirms that mouse ESTR loci are very sensitive to ionizing radiation and establishes that induced germline mutation results from radiation-induced mutant alleles being present in sperm, rather than from unrepaired sperm DNA lesions that subsequently lead to the appearance of mutants in the early embryo. This single molecule monitoring system has the potential to substantially reduce the number of mice needed for germline mutation monitoring, and can be used to study not only germline mutation but also somatic mutation in vivo and in cell culture.
TL;DR: Assessment of the small amounts of urinary albumin excretion has become an integrated marker of cardiovascular and/or renal risk in both diabetic and non-diabetic elderly populations and in essential hypertension measurement of microalbuminuria has increased.
Abstract: Over the last few years, assessment of the small amounts of urinary albumin excretion, the so-called microalbuminuria, has become an integrated marker of cardiovascular and/or renal risk in both diabetic [1] and non-diabetic elderly populations [2]. In essential hypertension, measurement of microalbuminuria has increased despite the scarce evidence supporting any prognostic value [3] and the absence of evidence bolstering the contention that a reduction in microalbuminuria is followed by a decrease in risk.
TL;DR: A 5‐year‐and‐11‐month‐old‐boy who had started cyanosis at age 4 years and 11 months, and did not have any other pulmonary or cardiac signs or symptoms was concluded to have HPS caused by Abernethy malformation, the first case described in the literature with this form of presentation.
Abstract: Hepatopulmonary syndrome (HPS) is the clinical relationship between hepatic disease and the existence of pulmonary vascular dilatations, which can result in a range of arterial oxygenation abnormalities. It is probably caused by an alteration in the synthesis or metabolism of vasoactive pulmonary substances at a hepatic level, leading to vasodilatation of pulmonary vessels and diffusion perfusion defects. The Abernethy malformation is characterized by the congenital diversion of portal blood away from the liver, by either end-to-side or side-to-side shunt. Here, we report on a 5-year-and-11-month-old-boy who had started cyanosis at age 4 years and 11 months, and did not have any other pulmonary or cardiac signs or symptoms. In the investigation, arterial blood gases revealed a PaO(2) of 41.4 mm Hg. The chest x-ray film and echo Doppler cardiography were normal. Nuclear scanning with Technetium 99m-labeled macroaggregated albumin showed the presence of arteriovenous shunt, at 47%. Abdominal echography revealed Abernethy malformation with an absence of portal vein. We concluded that the patient had HPS caused by Abernethy malformation. The possible mechanism is that in this malformation, there is a deviation in the blood that comes from the spleen to the vena cava without passing through the liver, so there is no metabolism of some substances which can be responsible for the imbalance between the vasodilatation and the vasoconstriction of the pulmonary circulation. Abernethy malformation must be included as one of the etiologies of hepatopulmonary syndrome. This is the first case described in the literature with this form of presentation.
TL;DR: Solitaire composite resin presented the smoothest surfaces when polished with Poli I and II aluminum oxide pastes, Ultralap diamond paste, Politip finishing points and 30-blade tungsten carbide burs.
Abstract: Purpose To evaluate the surface roughness of two packable composites after finishing and polishing with six different systems. Materials and methods Solitaire and Alert composite samples were prepared and polished with Poli I and Poli II aluminum oxide pastes, Ultralap diamond paste, Enhance finishing points, Politip rubber polishers, fine and extra fine diamond burs, and 30-blade tungsten carbide burs according to the manufacturers' instructions. The polished surfaces were then evaluated with a profilometer and a scanning electron microscope. Results Solitaire composite resin presented the smoothest surfaces when polished with Poli I and II aluminum oxide pastes, Ultralap diamond paste, Politip finishing points and 30-blade tungsten carbide burs. The smoothest surfaces for Alert composite were evident with the 30-blade tungsten carbide burs.
TL;DR: The use of ventilation tubes (grommets) in secretory otitis media (SOM) remains controversial with conflicting data on developmental outcome and quality of life in young children as mentioned in this paper.
Abstract: Upper respiratory tract infections are common and important. Although rarely fatal, they are a source of significant morbidity and carry a considerable economic burden. Numerous therapies for the common cold have no effect on symptoms or outcome. Complications such as cough are not improved by over-the-counter preparations, while labelling cough alone as a symptom of asthma may result in unnecessary use of inhaled steroid treatment. Clinical presentation of sore throat does not accurately predict whether the infection is viral or bacterial, while throat culture and rapid antigen tests do not significantly change prescribing practice. Antibiotics have only a limited place in the management of recurrent sore throat due to group A beta-haemolytic streptococcal infection. Routine use of antibiotics in upper respiratory infection enhances parent belief in their effectiveness and increases the likelihood of future consultation in primary care for minor self-limiting illness. Respiratory viruses play a major role in the aetiology of acute otitis media (AOM); prevention includes the use of influenza or RSV vaccination, in addition to reducing other risk factors such as early exposure to respiratory viruses in day-care settings and to environmental tobacco smoke. The use of ventilation tubes (grommets) in secretory otitis media (SOM) remains controversial with conflicting data on developmental outcome and quality of life in young children. New conjugate pneumococcal vaccines appear safe in young children and prevent 6-7% of clinically diagnosed AOM.
TL;DR: It is concluded that CYP3A4 is the only P450 of those tested that converts tamoxifen to alpha-hydroxytamox ifen and the only one that results in appreciable levels of irreversible binding of tamoxIFen to DNA.
Abstract: This study investigates which CYP forms are responsible for the conversion of tamoxifen to its putative active metabolite α-hydroxytamoxifen and irreversible binding to DNA. We have used eight different baculovirus expressed recombinant human CYP forms and liquid chromatography-mass spectrometry to show that only CYP3A4 is responsible for the NADPH-dependent αhydroxylation of tamoxifen. Surprisingly, this CYP did not catalyse the formation of 4-hydroxytamoxifen. We demonstrate for the first time, by means of accelerator mass spectrometry, that CYP3A4 also catalysed the activation of [ 14 C]tamoxifen to intermediates that irreversibly bind to exogenous DNA. Incubation of [ 14 C]tamoxifen (20.6 kBq,
TL;DR: Doxycycline penetrated atherosclerotic plaques with acceptable tissue levels and resulted in a reduction in MMP-1 concentration because of decreased expression, which was due to decreased expression.
Abstract: Background and Purpose— Elevated levels of matrix metalloproteinases (MMPs), particularly MMP-1 and MMP-9, have been implicated in plaque rupture. It has been suggested that inhibition of MMPs may stabilize vulnerable atherosclerotic plaques and improve clinical outcome. The aim of the study was to investigate the ability of doxycycline, a nonspecific MMP inhibitor, to reduce MMP concentration in carotid atheroma. Methods— The study design was a prospective, double-blind randomized trial. One hundred patients requiring carotid endarterectomy were randomized to receive 200 mg/d doxycycline or placebo for 2 to 8 weeks before surgery. During endarterectomy, carotid plaques were retrieved. The concentrations of MMPs and doxycycline were determined in the atherosclerotic tissue by enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. Clinical events were recorded, as was the rate of preoperative embolization (transcranial Doppler). Results— Analysis of endarterectomized sp...
TL;DR: It is shown that mitochondrial PTP formation is involved in the signaling pathway by which NO induces apoptosis in cultured Citrus cells, and SNP caused loss of the mitochondrial membrane electrical potential.
Abstract: In the present study, we investigated the involvement of the mitochondrial permeability transition pore (PTP) in nitric oxide (NO)-induced plant cell death. NO donors such as sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine inhibited growth and caused death in suspension-cultured cells of Citrus sinensis. Cells treated with SNP showed chromatin condensation and fragmentation, characteristic of apoptosis. SNP caused loss of the mitochondrial membrane electrical potential, which was prevented by cyclosporin A (CsA), a specific inhibitor of PTP formation. CsA also prevented the nuclear apoptosis and subsequent Citrus cell death induced by NO. These findings indicate that mitochondrial PTP formation is involved in the signaling pathway by which NO induces apoptosis in cultured Citrus cells.
TL;DR: The behavioural consequences of a single neurotoxic dose of MDMA can be demonstrated over 2 months after administration of the compound, thereby indicating that long-term adaptive changes occur within the brain following the neurodegeneration of 5-HT neurones produced by this recreationally used drug.
Abstract: Rationale: Decreased 5-HT function has been shown to induce behaviour consistent with an "anxiolytic" effect. Administration of a single dose of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy" 12.5 mg/kg IP) to rats results in prolonged damage to central serotonergic nerve terminals. Thus we wished to assess whether an MDMA-induced lesion may have longer-term behavioural consequences. Objective: The study was designed to examine the behaviour of MDMA-pretreated and control animals in the elevated plus-maze and open field at a number of time-points, up to 80 days, after the administration of a single neurotoxic dose of MDMA (12.5 mg/kg IP). Results: MDMA-pretreated Dark Agouti rats demonstrated a statistically significant reduction in anxiety-related behaviour, compared to saline-pretreated control rats, in both the elevated plus-maze and open field when the rats were tested on day 73 (open field) and day 80 (plus maze) after MDMA administration. Conclusions: The behavioural consequences of a single neurotoxic dose of MDMA can be demonstrated over 2 months after administration of the compound, thereby indicating that long-term adaptive changes occur within the brain following the neurodegeneration of 5-HT neurones produced by this recreationally used drug.
TL;DR: The usefulness of DNA genotyping for RBC antigens as a tool for the management of multiply‐transfused patients with sickle cell disease to overcome the limitations of hemagglutination assays was evaluated.
Abstract: BACKGROUND: The usefulness of DNA genotyping for RBC antigens as a tool for the management of multiply-transfused patients with sickle cell disease (SCD) to overcome the limitations of hemagglutination assays was evaluated.
STUDY DESIGN AND METHODS: Blood samples from 40 multiply-transfused SCD patients were studied by hemagglutination and by PCR-RFLP for antigens or genes in the Rh (D, C/c, E/e), Kell, Kidd, and Duffy systems.
RESULTS: Discrepancies were found between hemagglutination and DNA typing test results in six patients: two were discrepant in Rh typing (one was D− by hemagglutination and RhD by DNA, and one was E+e− and RhEe by DNA), two were discrepant in Duffy typing [both were Fy(a+b−) and Fyb/Fyb by DNA], and four were discrepant in Kidd typing [Jk(a+b+) and Jkb/Jkb by DNA; two of these samples were also discrepant in Duffy]. Stored segments from blood units that had been recently transfused to these six recipients were phenotyped, confirming that the transfused RBCs were the source of the discrepancy between genotype and phenotype.
CONCLUSION: DNA typing of blood groups by PCR-RFLP in peripheral blood WBCs contributes to the management of transfusions in SCD patients by allowing a more accurate selection of donor units.
TL;DR: The results suggest that a stressful situation can be a predisposing factor for the increase of VSCs in the mouth air, but the mechanism cannot be simply explained by reduction of the salivary flow.
Abstract: The relationship between stress, salivary flow rate and oral volatile sulfur-containing compounds (VSCs) is not clearly established. Two stressful situations were studied: psychological stress caused by a biochemistry examination (Study I) and psychophysiological stress caused by premenstrual syndrome (PMS) (Study II). Seventy-one undergraduate dental students took part in Study I and VSCs were measured 1 wk before the examination, on the day of examination and 1 wk after. In Study II, 50 women were selected (23 with and 27 without PMS) and the measurements were made during non-menstrual, premenstrual and menstrual stages. Unstimulated salivary flow was determined in the subjects of both studies. On the day of the biochemistry examination, VSCs significantly increased and salivary flow decreased compared with baseline values. Women with PMS showed higher VSC concentrations during the premenstrual stage than those without PMS (P < 0.05), but the salivary flow was not statistically different. A change in VSCs was observed during different stages of the menstrual cycle for the groups of women, but the salivary flow did not change. The results suggest that a stressful situation can be a predisposing factor for the increase of VSCs in the mouth air, but the mechanism cannot be simply explained by reduction of the salivary flow.
TL;DR: In this paper, the authors propose a framework to explain the reasons for adoption of managerial expertise and the reaction of Brazilian companies to it, based on field surveys, they identify the three most typical approaches to t...
Abstract: Executive Overview Emerging economies are drawing increasing attention from investors and foreign businesses. However, doing business within emerging countries can be frustrating. As a case in point, in the largest South American economy there is a saying that goes: ‘Brazil is not for beginners.’ For casual foreign observers, the country may appear to have the same institutions and traits as developed Western nations. But acting on that assumption may well lead to unsuccessful, frustrating experiences. Behind the Brazilian facade lie institutions still under construction and a complex, hybrid, and everchanging business culture. In this article, we seek to contribute to the understanding of the Brazilian business environment. We deal specifically with the importation and adoption of managerial expertise. We propose a framework to explain the reasons for adoption of this expertise and the reaction of Brazilian companies to it. Based on field surveys, we have identified the three most typical approaches to t...