The draft genome sequence of a desert tree Populus pruinosa.
Populus pruinosa is a large tree that grows in deserts and shows distinct differences in both morphology and adaptation compared to its sister species, P. euphratica. Here we present a draft genome sequence for P. pruinosa and examine genomic variations between the 2 species. A total of 60 Gb of clean reads from whole-genome sequencing of a P. pruinosa individual were generated using the Illumina HiSeq2000 platform. The assembled genome is 479.3 Mb in length, with an N50 contig size of 14.0 kb and a scaffold size of 698.5 kb; 45.47% of the genome is composed of repetitive elements. We predicted 35 131 protein-coding genes, of which 88.06% were functionally annotated. Gene family clustering revealed 224 unique and 640 expanded gene families in the P. pruinosa genome. Further evolutionary analysis identified numerous genes with elevated values for pairwise genetic differentiation between P. pruinosa and P. euphratica. We provide the genome sequence and gene annotation for P. pruinosa. A large number of genetic variations were recovered by comparison of the genomes between P. pruinosa and P. euphratica. These variations will provide a valuable resource for studying the genetic bases for the phenotypic and adaptive divergence of the 2 sister species.


Expression of interleukin-1 beta, tumor necrosis factor alpha, interleukins-6, -10 and -4, and metalloproteases by freshly isolated mononuclear cells from early never-treated and non-acute treated rheumatoid arthritis patients.
To determine IL-1 beta, TNF alpha, IL-6, IL-4, IL-10, MMP-1, MMP-3 and MMP-13 expression by freshly isolated peripheral blood (PBMC) and synovial fluid mononuclear cells (SFMC) in early, never-treated (ENT-RA) and non-acute, treated rheumatoid arthritis (NAT-RA) patients. To elucidate whether excessive or inadequate interleukin (IL) and metalloprotease (MMP) expression is influenced by the disease duration. Fourteen RA patients, 7 with early RA (< 1 year of evolution) never treated with corticosteroids or disease-modifying antirheumatic drugs, and 7 patients with non-acute RA (> 2 years of evolution) treated with disease-modifying antirheumatic drugs, were studied by ELISA and quantitative and semiquantitative RT-PCR. A group of 14 healthy subjects matched for sex and age was included. No statistically significant difference in the protein or transcript levels for the cytokines of interest was found between the ENT-RA and NAT-RA groups. The cytokine mRNA expression by freshly isolated PBMC and SFMC in both groups was as follows: IL-1 beta > TNF alpha > IL-10 > IL-6, with no mRNA IL-4 expression. In contrast, cytokine serum levels in ENT-RA and NAT-RA patients were detected in inverse order as follows: IL-6 > IL-10, while IL-1 beta, TNF alpha and IL-4 were undetectable. MMP-3 mRNA expression by the PBMC of NAT-RA patients was statistically different to that in ENT-RA patients. Similar levels of mRNA expression of MMP-1, MMP-3 and MMP-13 by the PBMC and SFMC in both RA groups were observed. A close equilibrium between MMP and pro/anti-inflammatory cytokine production is observed in ENT-RA and NAT-RA patients. This balance is apparently not influenced by the length of the disease. Highly sensitive methods such as quantitative RT-PCR and ELISA, and even studying freshly isolated MC, showed sustained cytokine secretion at the local level (synovial fluid/SFMC) and scarce translation at the peripheral level (serum/PBMC). Expression of MMP mRNA needs to be further evaluated in order to know whether their peripheral expression reflects their local activity in RA patients.


[Cellular and molecular mechanisms in focal epileptogenesis].
In the review, it is presented an analysis of experimental data about cellular and molecular mechanisms of focal epileptogenesis. Basic principals of synchronized burst activity development in epileptogenic focus are considered. The roles of synaptic activities and extrasynaptic membrane excitability for epileptiform activity development are discussed. The various pathways of Ca2+ entry into neurones as well as an involvement of Ca2+/calmodulin-dependent protein phosphorylation in mechanisms of epileptogenesis are analyzed. In vitro and in vivo experimental models of epileptogenesis (especially, kindling and audiogenic seizures) allowing to study the predisposition of neuronal circuit to epileptiform activity development are discussed.


Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine.
The purpose of this pharmacokinetic study was to investigate the dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine, fluvoxamine and paroxetine. The study was carried out as an in vivo single-dose study including 24 young, healthy men. All volunteers had been identified as sparteine- and mephenytoin-extensive metabolisers. The volunteers received in randomised order, at weekly intervals, increasing single oral doses of one of the four SSRIs, followed 3 h later by sparteine (CYP2D6), mephenytoin (CYP2C19) and caffeine (CYP1A2) tests. Fluoxetine was given at 3-week intervals because of the long half-life of fluoxetine and its metabolite norfluoxetine. Citalopram, fluoxetine and paroxetine were given in doses of 10, 20, 40 and 80 mg and fluvoxamine was given in doses of 25, 50, 100 and 200 mg. With increasing doses, there was a statistically significant increase in the sparteine metabolic ratio (MR) (P < 0.01, Page's test for trend) for all four SSRIs. The increase was modest after intake of citalopram and fluvoxamine, while the increase was more pronounced after fluoxetine intake, although no volunteers changed phenotype from extensive metabolisers to poor metabolisers. Three of the six volunteers changed phenotype from extensive metabolisers to poor metabolisers after intake of 40 or 80 mg paroxetine. There was a statistically significant increase in the mephenytoin S/R ratio (P < 0.01, Page's test for trend) with increasing doses of fluoxetine and fluvoxamine, but not after citalopram and paroxetine. However, no volunteers changed phenotype from extensive to poor metabolisers of S-mephenytoin. After intake of fluvoxamine, the urinary excretion of the metabolites related to N3 demethylation of caffeine were below the limit of quantification, whereas there were no significant changes in the urinary caffeine metabolic ratios after intake of the other three SSRIs. This investigation confirms that paroxetine and fluoxetine are potent inhibitors of CYP2D6, that fluvoxamine and fluoxetine are moderate inhibitors of CYP2C19 and that fluvoxamine is a potent inhibitor of CYP1A2 in humans in vivo. The clinical prediction of interaction from single-dose experiments may have to take the degree of accumulation during steady-state after multiple doses into account.


[Late results of treatment of megaesophagus].
Heller's operation remains the best operation but pneumatic dilatation, which has replaced other methods, gives equivalent results. Our report may be completed by better assessment of the physiopathology, new methods of exploration and more precise knowledge of the complications and failures of myotomy. Finally, the chapter, cancer and megaoesophagus, is the most important to be added.


TEACHER TRAINING: How to Produce Better Math and Science Teachers.
Two National Research Council panels have released new reports on improving science and math education in the United States. One panel says that the best way to improve teacher education is to make it a continuum, with school districts taking more responsibility for the initial preparation of new teachers and university faculty playing a bigger role in ongoing professional development. The other panel says that more recent science Ph.D.s would be willing to teach high school science and math if the government helped with the transition, if the certification process were compressed, and if they could retain ties to research.


The post-humanist embryo: genetic manipulation, assisted reproductive technologies and the Principle of Procreative Beneficence.
Drawing from Julian Savulescu's argument for the obligation to use technological interventions for the enhancement human life, the Principle of Procreative Beneficence (PPB) states that parents have a moral obligation to use available reproductive technologies, including techniques of genetic manipulation, to create children who have the best chance of enjoying the best possible life. The aim of this study is to analyse the extent to which the possibility of using genetic manipulation to promote specific personality traits and thereby enhance human life is actually supported by current scientific knowledge and to determine whether the techniques employed in embryo selection comply with the PPB. In light of this analysis, the importance of involving the scientific community in the enhancement debate will be made clear. Moreover, when current knowledge of genetic and epigenetic processes and evidence of the risks of assisted reproductive technologies are taken into account, we find sufficient reason - even when guided by the PPB - to abstain from the use of current techniques of genetic manipulation and embryonic selection.


Persistence and titer changes of rubella virus antibodies in primiparous women who had been vaccinated with strain RA 27/3 in junior high school.
Taiwan's rubella vaccination program was launched in 1986; each schoolgirl in the third grade of junior high school received one dose of rubella (RA 27/3) vaccine. We reviewed the results of 14,090 prenatal rubella tests for primiparas from three areas of Taiwan during 2002 to 2008 to investigate seronegativity rates and titer changes. In all primiparous women, the average rubella virus seronegativity rate was 6.5% (95% confidence interval [95% CI], 6.1 to 6.9%), and the average rubella virus antibody titer was 65.9 IU/ml (95% CI, 64.7 to 67.1 IU/ml). There were 1,220 women (8.7%) with weakly positive antibody titers (10 to 20 IU/ml). The rubella virus seronegativity rates, which ranged from 5.4 to 9.7%, did not exhibit a linear trend from 9 to 22 years after vaccination (P = 0.201); in contrast, a significant trend appeared in the average rubella virus IgG titer (P = 0.003), dropping from 69.9 IU/ml in the 9th year after vaccination to 54.8 IU/ml in the 22nd year. The mean annual antibody decay rate was -0.77 IU/ml. This study reveals that the level of rubella virus antibodies declined slowly in women of childbearing age who were vaccinated with RA 27/3 at junior high school age. The number of women who were seronegative or had weakly positive antibody titers was still high (15.2%). Therefore, in countries that implement a single-dose regimen in children or teenagers, it should remain an important policy to encourage voluntary immunization in seronegative women and to immunize all postpartum women who are susceptible to rubella virus infection before they leave the hospital.


How to express tumor markers in bronchoalveolar lavage.
Bronchoalveolar lavage (BAL) is a fundamental technique in the diagnosis of different respiratory diseases including lung cancer. Tumor marker values can be determined in the BAL fluid, but controversy still exists about how to express the results. The aim of this study was to determine the best method of expressing tumor markers in BAL, either referring to total proteins or volume of fluid recovered. A prospective, randomized, non-blind study was carried out. Seventy-six patients (72 men and 4 women) diagnosed with lung cancer and 17 subjects without respiratory disease were included. BAL was performed in all patients and the fluid retrieved was divided into two fractions: a bronchiolar fraction (F0) and an alveolar fraction (F1). Five tumor markers: cytokeratin fragment 19 (CYFRA 21-1), squamous cell carcinoma antigen (SCC), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and neuron-specific enolase (NSE) as well as total protein were measured in both fractions. The concentrations were expressed in relation to the volume of BAL fluid recovered (ng or mU/mL) and in milligrams of total protein of lavage fluid (ng or mU/mg TP). The SPSS 11.01 software was used for statistical analysis. Mann-Whitney U test and ROC curves were developed when significant differences were found. We found significant differences in the CYFRA 21-1 values in the two BAL fractions and in both ways of expressing its concentration; in SCC in F1 expressed in ng/mg TP; in TPA in F0 expressed in mU/mg TP; in TPS in both fractions expressed in mU/mg TP, and in NSE in both fractions in ng/mg TP. The markers that best differentiated tumors from controls (ROC curves) were CYFRA 21-1 in F0 and NSE in both fractions in ng/mg TP. Our study demonstrates that the concentrations of tumor markers in BAL expressed in relation to total protein were more effective than if expressed in mL of BAL fluid collected.


Psychopathology in children and adolescents with autism compared to young people with intellectual disability.
Autism is a neurodevelopmental disorder with a specific pattern of behavioural, communication and social problems. Additional mental health problems are often poorly understood and undetected. This study investigates the level and pattern of emotional and behavioural problems in young people with autism compared with children with intellectual disability (ID). Subjects were 381 young people with autism and a representative group of 581 Australian young people with ID aged 4-18 years. Parents/carers provided details of the emotional and behavioural problems of their child using the Developmental Behaviour Checklist (DBC-P). Young people with autism were found to suffer from significantly higher levels of psychopathology than young people with ID. The implications of this finding are discussed.


Biomagnetic signals recorded during transcranial magnetic stimulation (TMS)-evoked peripheral muscular activity.
Transcranial magnetic stimulation (TMS) has widespread clinical applications from diagnosis to treatment. We combined TMS with non-contact magnetic detection of TMS-evoked muscle activity in peripheral limbs to explore a new diagnostic modality that enhances the utility of TMS as a clinical tool by leveraging technological advances in magnetometry. We recorded measurements in a regular hospital room using an array of optically pumped magnetometers (OPMs) inside a portable shield that encloses only the forearm and hand of the subject. We present magnetomyograms (MMG)s of TMS-evoked movement in a human hand, together with a simultaneous surface electromyograph (EMG) data. The biomagnetic signals recorded in the MMG provides detailed spatial and temporal information that is complementary to that of the electric signal channels. Moreover, we identify features in the magnetic recording beyond that of the EMG. This system demonstrates the value of biomagnetic signals in TMS-based clinical approaches and widens its availability and practical potential.


Exploring the Relationship Between Attribute Discrepancy and Avatar Embodiment in Immersive Social Virtual Reality.
Social virtual reality (VR) is an emerging set of platforms where users interact while embodying avatars. Given that VR headsets track real physical movements and map them onto one's avatar body, the nature of one's digital representation is an important aspect of social VR. However, little is known about how the visual proximity of an avatar to the self shapes user experience in naturalistic, social VR environments. In this article, we use this context to explore how embodiment is influenced by the perceived differences between the physical attributes of a user and the virtual attributes of their avatar. We selected a number of attributes for this measure that have been shown to be important for customization and representation in VR. Participants created an avatar, spent time in social VR, and reported on their experience in a questionnaire. Our results demonstrate a significant negative association between attribute discrepancy and avatar embodiment, the psychological experience of one's virtual body as their own body. We discuss implications for theories of self-representation and suggest urgency on the part of games and VR designers to improve the methods of creating avatars.


The effect of lithium on platelet monoamine oxidase activity in bipolar and schizoaffective disorders.
Platelet monoamine oxidase (MAO) activity was studied in 33 in-patients with bipolar and schizoaffective disorder who were treated with lithium. Platelet MAO activity was found to increase following 10-41 dys of lithium treatment compared to a prior drug free period, and the increase was positively correlated with the duration of lithium treatment. The increase in platelet MAO activity was not correlated wtih clinical improvement as measured by the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment Scale (GAS). The number of platelets per unit of blood was also significantly correlated with the number of days of lithium treatment. However, the increase in the number of platelets in lithium-treated patients was not correlated with the increase in MAO activity and thus appears not to account for it. These results indicate that studies relating platelet MAO activity to psychiatric diagnosis should be interpreted cautiously if patients are receiving lithium carbonate.


Comparative investigation of DNA from mouse and Ehrlich ascites tumor cells.
Mouse DNA and DNA of Ehrlich ascites tumor have been comparatively studied in the search for changes in DNA during tumor progression. No differences were found in kinetics of homologous (mouse X mouse) and heterologous (mouse X tumor) DNA reassociation; in thermal stability of homologous and heterologous duplexes of repeated, unique and satellite DNA; in percentage of hybridization with mouse liver heterogenous nuclear RNA; in thermal stability of the RNA.DNA hybrids. The negative results suggest that the considerable evolution of transplantable tumors (both in biological properties and in karyotype) has not been accompanied by alterations of the genome which could be detected by the now available methods of molecular hybridization for studying DNA divergence. In the light of the results obtained the functions ascribed to the mouse satellite DNA are discussed.


Impact of time-variant turbulence behavior on prediction for adaptive optics systems.
For high-contrast imaging systems, the time delay is one of the major limiting factors for the performance of the extreme adaptive optics (AO) sub-system and, in turn, the final contrast. The time delay is due to the finite time needed to measure the incoming disturbance and then apply the correction. By predicting the behavior of the atmospheric disturbance over the time delay we can in principle achieve a better AO performance. Atmospheric turbulence parameters, which determine wavefront phase fluctuations, have time-varying behavior. We present a stochastic model for wind speed and model time-variant atmospheric turbulence effects using varying wind speeds. We test a low-order, data-driven predictor, the linear minimum mean square error predictor, for a near-infrared AO system under varying conditions. Our results show varying wind can have a significant impact on the performance of wavefront prediction, preventing it from reaching optimal performance. The impact depends on the strength of wind fluctuations with the greatest loss in expected performance being for high wind speeds.


Heavy Metals Induce Decline of Derivatives of 5-Methycytosine in Both DNA and RNA of Stem Cells.
Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Here, we established a chemical labeling strategy in combination with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) analysis for highly sensitive detection of eight modified cytidines in DNA and RNA. The developed method allowed simultaneous detection of all eight modified cytidines with improved detection sensitivities of 128-443-fold. Using this method, we demonstrated that the levels of 5-hmC, 5-foC, and 5-caC significantly decreased in both the DNA and RNA of mouse embryonic stem (ES) cells while exposed to arsenic (As), cadmium (Cd), chromium (Cr), and antimony (Sb). In addition, we found that treatments by heavy metals induced a decrease of the activities of 10-11 translocation (Tet) proteins. Furthermore, we revealed that a content change of metabolites occurring in the tricarboxylic acid cycle may be responsible for the decline of the derivatives of 5-mC. Our study shed light on the epigenetic effects of heavy metals, especially for the induced decline of the derivatives of 5-mC in both DNA and RNA.


Design and synthesis of molecular probes for the determination of the target of the anthelmintic drug praziquantel.
Schistosomiasis is a highly prevalent neglected tropical disease caused by blood-dwelling helminths of the genus Schistosoma. Praziquantel (PZQ) is the only drug available widely for the treatment of this disease and is administered in racemic form, even though only the (R)-isomer has significant anthelmintic activity. Progress towards the development of a second generation of anthelmintics is hampered by a lack of understanding of the mechanism of action of PZQ. In this Letter, we report an efficient protocol for the small-scale separation of enantiomers of 2 (hydrolyzed PZQ) using supercritical fluid chromatography (SFC). The enantiopure 2 was then used to develop several molecular probes, which can potentially be used to help identify the protein target of PZQ and study its mode of action.


Label-free antibody detection using band edge fringes in SOI planar photonic crystal waveguides in the slow-light regime.
We report experimental results of label-free anti-bovine serum albumin (anti-BSA) antibody detection using a SOI planar photonic crystal waveguide previously bio-functionalized with complementary BSA antigen probes. Sharp fringes appearing in the slow-light regime near the edge of the guided band are used to perform the sensing. We have modeled the presence of these band edge fringes and demonstrated the possibility of using them for sensing purposes by performing refractive index variations detection, achieving a sensitivity of 174.8 nm/RIU. Then, label-free anti-BSA biosensing experiments have been carried out, estimating a surface mass density detection limit below 2.1 pg/mm2 and a total mass detection limit below 0.2 fg.


Experimental and Computational Approaches to Measure Telomere Length: Recent Advances and Future Directions.
The length of telomeres, protective structures at the chromosome ends, is a well-established biomarker for pathological conditions including multisystemic syndromes called telomere biology disorders. Approaches to measure telomere length (TL) differ on whether they estimate average, distribution, or chromosome-specific TL, and each presents their own advantages and limitations. The development of long-read sequencing and publication of the telomere-to-telomere human genome reference has allowed for scalable and high-resolution TL estimation in pre-existing sequencing datasets but is still impractical as a dedicated TL test. As sequencing costs continue to fall and strategies for selectively enriching telomere regions prior to sequencing improve, these approaches may become a promising alternative to classic methods. Measurement methods rely on probe hybridization, qPCR or more recently, computational methods using sequencing data. Refinements of existing techniques and new approaches have been recently developed but a test that is accurate, simple, and scalable is still lacking.


Surgical considerations in aortitis with special emphasis on Takayasu's arteritis.
Aortitis may result in an injury to the aorta or its branches. The inflammatory process that occurs in response to the injury may ultimately result in stenosis or occlusion from fibrosis and dilatation or aneurysm formation from destruction and weakening of the arterial wall. As a result of antibiotics, some diseases known to cause arteritis have declined over the years (most notably syphilis and rheumatic fever). Other systemic diseases not initially thought to have vascular involvement have also been found to be associated with widespread arteritis. All forms of this entity are capable of producing dilatation or aneurysm formation, but only Takayasu's arteritis can produce narrowing or occlusion of the aorta or its branches, with the rare exception of stenosing arteritis, which sometimes follows radiation therapy in childhood. In Takayasu's arteritis, any segment of the aorta, as well as the pulmonary arteries, may be affected. This disease is divided into four types, depending on the location and extent of the arteritis. In Type I, the disease is limited to the aortic arch and its branches. In Type II, the vascular lesions are confined to the descending thoracic and abdominal aorta without involvement of the aortic arch. Type III is mixed, containing features of Types I and II. Type IV is characterized by dilatation and aneurysm formation in the affected vessels and may have pulmonary artery involvement. The four types are described, with their clinical manifestations, diagnosis, and surgical treatment.


Comparison of DXA and water measurements of body fat following gastric bypass surgery and a physiological model of body water, fat, and muscle composition.
Measurement of body composition changes following bariatric surgery is complicated because of the difficulty of measuring body fat in highly obese individuals that have increased photon absorption and are too large for the standard dual-energy X-ray absorptiometry (DXA) table. We reproducibly measured body composition from half-body DXA scans and compared the values of total body fat estimated from total body water (TBW) and DXA measurements before and after Roux-en-Y gastric bypass surgery (RYGB). DXA, TBW (deuterium dilution), extracellular water (ECW; bromide dilution), and intracellular water (ICW) measurement (by subtraction) were made before surgery and at 2 wk, 6 wk, 6 mo, and 12 mo after surgery. Twenty individuals completed baseline and at least four follow-up visits. DXA appeared to underestimate the fat and bone mass in extreme obesity (before surgery), whereas at 6 and 12 mo after surgery, the DXA and TBW fat measurements were similar. The ECW-to-ICW ratio was increased in obese individuals and increased slightly more after surgery. We describe a new model that explains this abnormal water composition in terms of the normal physiological changes that occur in body composition in obesity and weight loss. This model is also used to predict the muscle mass loss following RYGB.


Can patellar tape reduce the patellar malalignment and pain associated with patellofemoral osteoarthritis?
Patellar taping is a conservative treatment that may reduce patellar malalignment and pain in people with patellofemoral joint osteoarthritis (OA). This study aimed to compare patellar alignment in people with and without patellofemoral joint OA and to evaluate immediate effects of patellar taping on patellar alignment and pain in people with patellofemoral joint OA. Patellar malalignment was measured from magnetic resonance imaging (MRI; 15 degrees knee flexion) in 28 individuals (14 with patellofemoral joint OA and 14 asymptomatic, age-matched controls). In the patellofemoral joint OA group, MRI data were collected in 2 randomly allocated conditions (tape and no tape). Patellar alignment indices were measured from deidentified axial scans by 1 examiner. Pain during squatting was recorded in the 2 conditions (tape and no tape). People with patellofemoral joint OA exhibited greater lateral displacement and bisect offset compared with controls (P < 0.001). Lateral patellar tilt angle did not differ between groups. In the patellofemoral joint OA group, patellar tape resulted in a significant lessening of lateral alignment, with reduced lateral displacement (P = 0.028) and increased lateral patellar tilt angle (P < 0.001). Mean pain during squatting decreased with patellar tape by 15 mm on a 100-mm scale (P = 0.045). Patellar tape may reduce malalignment and pain associated with patellofemoral joint OA.


A summary of computational resources for protein phosphorylation.
Protein phosphorylation is the most ubiquitous post-translational modification (PTM), and plays important roles in most of biological processes. Identification of site-specific phosphorylated substrates is fundamental for understanding the molecular mechanisms of phosphorylation. Besides experimental approaches, prediction of potential candidates with computational methods has also attracted great attention for its convenience, fast-speed and low-cost. In this review, we present a comprehensive but brief summarization of computational resources of protein phosphorylation, including phosphorylation databases, prediction of non-specific or organism-specific phosphorylation sites, prediction of kinase-specific phosphorylation sites or phospho-binding motifs, and other tools. The latest compendium of computational resources for protein phosphorylation is available at: http://gps.biocuckoo.org/links.php.


Clinical presentations of chronic obstructive pulmonary disease.
The diagnosis of chronic obstructive pulmonary disease covers a wide range of lung problems that have as their base the partial blockage of the smooth movement of air from the lungs during expiration. Asthma, simple bronchitis, chronic obstructive bronchitis, and emphysema are the diseases usually considered as chronic obstructive disease. Many of their multiple presentations are quite common in clinical medicine but are sometimes difficult to recognize. Once the inciting event is identified, it is often reversible.


Non-functional plastid ndh gene fragments are present in the nuclear genome of Norway spruce (Picea abies L. Karsch): insights from in silico analysis of nuclear and organellar genomes.
Many genes have been lost from the prokaryote plastidial genome during the early events of endosymbiosis in eukaryotes. Some of them were definitively lost, but others were relocated and functionally integrated to the host nuclear genomes through serial events of gene transfer during plant evolution. In gymnosperms, plastid genome sequencing has revealed the loss of ndh genes from several species of Gnetales and Pinaceae, including Norway spruce (Picea abies). This study aims to trace the ndh genes in the nuclear and organellar Norway spruce genomes. The plastid genomes of higher plants contain 11 ndh genes which are homologues of mitochondrial genes encoding subunits of the proton-pumping NADH-dehydrogenase (nicotinamide adenine dinucleotide dehydrogenase) or complex I (electron transport chain). Ndh genes encode 11 NDH polypeptides forming the Ndh complex (analogous to complex I) which seems to be primarily involved in chloro-respiration processes. We considered ndh genes from the plastidial genome of four gymnosperms (Cryptomeria japonica, Cycas revoluta, Ginkgo biloba, Podocarpus totara) and a single angiosperm species (Arabidopsis thaliana) to trace putative homologs in the nuclear and organellar Norway spruce genomes using tBLASTn to assess the evolutionary fate of ndh genes in Norway spruce and to address their genomic location(s), structure, integrity and functionality. The results obtained from tBLASTn were subsequently analyzed by performing homology search for finding ndh specific conserved domains using conserved domain search. We report the presence of non-functional plastid ndh gene fragments, excepting ndhE and ndhG genes, in the nuclear genome of Norway spruce. Regulatory transcriptional elements like promoters, TATA boxes and enhancers were detected in the upstream regions of some ndh fragments. We also found transposable elements in the flanking regions of few ndh fragments suggesting nuclear rearrangements in those regions. These evidences support the hypothesis that, at least in Picea, ndh translocations from the plastid to the nuclear genome have occurred, and that there might have been a functional machinery at some time during evolution to accommodate them within a nuclear-encoded environment, or attempts to form it.


Use of intravitreal rituximab and methotrexate in vitreoretinal lymphoma.
A 64-year-old Caucasian woman was referred to our hospital after referring vision loss; she had been previously diagnosed with systemic diffuse large B-cell lymphoma. Retinal and optic nerve involvement were found in her right eye, and iris and vitreous involvement were found in her left eye. Vitreoretinal lymphomas (VRL) are rare in medical literature, hence there is a lack of standardised studies regarding therapeutic options in these patients. In our patient, we decided to add intravitreal injections of rituximab and methotrexate to systemic chemotherapy, and to perform pars plana vitrectomy.


Healthcare providers' perceptions about the unmet needs of their patients with cancer across healthcare systems: results of the International Psycho-Oncology Society survivorship survey.
Systematic understanding of patients' unmet needs is essential for providing effective supportive care. This study sought to compare the unmet needs of patients with cancer identified by health care providers (HCPs) among four major healthcare systems. HCPs (n = 247) participated in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey, evaluating their patients' unmet needs. The country of HCPs was grouped into four major healthcare systems: Beveridge model, Bismarck model, National Health Insurance model, and out-of-pocket model. Most HCPs were from countries with the Bismarck model. Substantial levels (> 50%) of unmet needs in all domains are reported across the four healthcare systems. Pediatric patients/survivors living in countries under out-of-pocket healthcare model were evaluated to have less unmet needs for managing decline in physical or cognitive functioning and insomnia/sleep difficulty/fatigue, than those in countries under Beveridge, Bismarck, and National Health Insurance models. Moreover, middle-aged patients/survivors under Beveridge and National Health Insurance models were likely to have greater unmet needs for dealing with cancer-related financial concerns than those under Bismarck model. This study provides valuable insights into the unmet needs of patients with cancer in different healthcare systems, highlighting the significance of targeted interventions to address the unique needs of patients across diverse healthcare systems. Further investigation is warranted to identify the system factors associated with patients' unmet needs, enabling the development of effective healthcare policies and interventions to comprehensively address the multifaceted needs of patients with cancer.


Home-based chlamydia and gonorrhoea screening: a systematic review of strategies and outcomes.
In many countries, low Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) screening rates among young people in primary-care have encouraged screening programs outside of clinics. Nucleic acid amplification tests (NAATs) make it possible to screen people in homes with self-collected specimens. We systematically reviewed the strategies and outcomes of home-based CT/NG screening programs. Electronic databases were searched for home-based CT and/or NG screening studies published since January 2005. Screening information (e.g. target group, recruitment and specimen-collection method) and quantitative outcomes (e.g. number of participants, tests and positivity) were extracted. The screening programs were classified into seven groups on the basis of strategies used. We found 29 eligible papers describing 32 home-based screening programs. In seven outreach programs, people were approached in their homes: a median of 97% participants provided specimens and 76% were tested overall (13717 tests). In seven programs, people were invited to receive postal test-kits (PTKs) at their homes: a median of 37% accepted PTKs, 79% returned specimens and 19% were tested (46225 tests). PTKs were sent along with invitation letters in five programs: a median of 33% returned specimens and 29% of those invited were tested (15126 tests). PTKs were requested through the internet or phone without invitations in four programs and a median of 32% returned specimens (2666 tests). Four programs involved study personnel directly inviting people to receive PTKs: a median of 46% accepted PTKs, 21% returned specimens and 9.1% were tested (341 tests). PTKs were picked-up from designated locations in three programs: a total of 6765 kits were picked-up and 1167 (17%) specimens were returned for screening. Two programs used a combination of above strategies (2395 tests) but the outcomes were not reported separately. The overall median CT positivity was 3.6% (inter-quartile range: 1.7-7.3%). A variety of strategies have been used in home-based CT/NG screening programs. The screening strategies and their feasibility in the local context need to be carefully considered to maximize the effectiveness of home-based screening programs.


Optogenetic evidence for inhibitory signaling from orexin to MCH neurons via local microcircuits.
The lateral hypothalamus (LH) is a key regulator of multiple vital behaviors. The firing of brain-wide-projecting LH neurons releases neuropeptides promoting wakefulness (orexin/hypocretin; OH), or sleep (melanin-concentrating hormone; MCH). OH neurons, which coexpress glutamate and dynorphin, have been proposed to excite their neighbors, including MCH neurons, suggesting that LH may sometimes coengage its antagonistic outputs. However, it remains unclear if, when, and how OH actions promote temporal separation of the sleep and wake signals, a process that fails in narcolepsy caused by OH loss. To explore this directly, we paired optogenetic stimulation of OH cells (at rates that promoted awakening in vivo) with electrical monitoring of MCH cells in mouse brain slices. Membrane potential recordings showed that OH cell firing inhibited action potential firing in most MCH neurons, an effect that required GABAA but not dynorphin receptors. Membrane current analysis showed that OH cell firing increased the frequency of fast GABAergic currents in MCH cells, an effect blocked by antagonists of OH but not dynorphin or glutamate receptors, and mimicked by bath-applied OH peptide. In turn, neural network imaging with a calcium indicator genetically targeted to MCH neurons showed that excitation by bath-applied OH peptides occurs in a minority of MCH cells. Collectively, our data provide functional microcircuit evidence that intra-LH feedforward loops may facilitate appropriate switching between sleep and wake signals, potentially preventing sleep disorders.


A comparison of deconvolution techniques for the ultrasonic nondestructive evaluation of materials.
Several major deconvolution techniques commonly used for seismic applications are studied and adapted for ultrasonic NDE (nondestructive evaluation) applications. Comparisons of the relative merits of these techniques are presented based on a complete set of simulations on some real ultrasonic pulse echoes. Methods that rely largely on a reflection seismic model, such as one-at-a-time L(1) spike extraction and MVD (minimum variance deconvolution), are not suitable for the NDE applications discussed here because they are limited by their underlying model. L(2) and Wiener filtering, on the other hand, do not assume such a model and are, therefore, more flexible and suitable for these applications. The L(2) solutions, however, are often noisy due to numerical ill conditions. This problem is partially solved in Wiener filtering, simply by adding a constant desensitizing factor q. The computational complexities of these Wiener filtering-based techniques are relatively moderate and are, therefore, more suitable for potential real-time implementations.


Does attention play a role in dynamic receptive field adaptation to changing acoustic salience in A1?
Acoustic filter properties of A1 neurons can dynamically adapt to stimulus statistics, classical conditioning, instrumental learning and the changing auditory attentional focus. We have recently developed an experimental paradigm that allows us to view cortical receptive field plasticity on-line as the animal meets different behavioral challenges by attending to salient acoustic cues and changing its cortical filters to enhance performance. We propose that attention is the key trigger that initiates a cascade of events leading to the dynamic receptive field changes that we observe. In our paradigm, ferrets were initially trained, using conditioned avoidance training techniques, to discriminate between background noise stimuli (temporally orthogonal ripple combinations) and foreground tonal target stimuli. They learned to generalize the task for a wide variety of distinct background and foreground target stimuli. We recorded cortical activity in the awake behaving animal and computed on-line spectrotemporal receptive fields (STRFs) of single neurons in A1. We observed clear, predictable task-related changes in STRF shape while the animal performed spectral tasks (including single tone and multi-tone detection, and two-tone discrimination) with different tonal targets. A different set of task-related changes occurred when the animal performed temporal tasks (including gap detection and click-rate discrimination). Distinctive cortical STRF changes may constitute a "task-specific signature". These spectral and temporal changes in cortical filters occur quite rapidly, within 2min of task onset, and fade just as quickly after task completion, or in some cases, persisted for hours. The same cell could multiplex by differentially changing its receptive field in different task conditions. On-line dynamic task-related changes, as well as persistent plastic changes, were observed at a single-unit, multi-unit and population level. Auditory attention is likely to be pivotal in mediating these task-related changes since the magnitude of STRF changes correlated with behavioral performance on tasks with novel targets. Overall, these results suggest the presence of an attention-triggered plasticity algorithm in A1 that can swiftly change STRF shape by transforming receptive fields to enhance figure/ground separation, by using a contrast matched filter to filter out the background, while simultaneously enhancing the salient acoustic target in the foreground. These results favor the view of a nimble, dynamic, attentive and adaptive brain that can quickly reshape its sensory filter properties and sensori-motor links on a moment-to-moment basis, depending upon the current challenges the animal faces. In this review, we summarize our results in the context of a broader survey of the field of auditory attention, and then consider neuronal networks that could give rise to this phenomenon of attention-driven receptive field plasticity in A1.


Are Implant Choice and Surgical Approach Associated With Biceps Tenodesis Construct Strength? A Systematic Review and Meta-regression.
Despite the increasing use of biceps tenodesis, there is a lack of consensus regarding optimal implant choice (suture anchor vs interference screw) and implant placement (suprapectoral vs subpectoral). The purpose was to determine the associations of procedural parameters with the biomechanical performance of biceps tenodesis constructs. The authors hypothesized that ultimate failure load (UFL) would not differ between sub- and suprapectoral repairs or between interference screw and suture anchor constructs and that the number of implants and number of sutures would be positively associated with construct strength. Meta-analysis. The authors conducted a systematic literature search for studies that measured the biomechanical performance of biceps tenodesis repairs in human cadaveric specimens. Two independent reviewers extracted data from studies that met the inclusion criteria. Meta-regression was then performed on the pooled data set. Outcome variables were UFL and mode of failure. Procedural parameters (fixation type, fixation site, implant diameter, and numbers of implants and sutures used) were included as covariates. Twenty-five biomechanical studies, representing 494 cadaveric specimens, met the inclusion criteria. The use of interference screws (vs suture anchors) was associated with a mean 86 N-greater UFL (95% CI, 34-138 N; P = .002). Each additional suture used to attach the tendon to the implant was associated with a mean 53 N-greater UFL (95% CI, 24-81 N; P = .001). Multivariate analysis found no significant association between fixation site and UFL. Finally, the use of suture anchors and fewer number of sutures were both independently associated with lower odds of native tissue failure as opposed to implant pullout. These findings suggest that fixation with interference screws, rather than suture anchors, and the use of more sutures are associated with greater biceps tenodesis strength, as well as higher odds of native tissue failure versus implant pullout. Although constructs with suture anchors show inferior UFL compared with those with interference screws, incorporation of additional sutures may increase the strength of suture anchor constructs. Supra- and subpectoral repairs provide equivalent biomechanical strength when controlling for potential confounders.


Late gadolinium enhancement on CMR and sustained ventricular tachycardia predict severe cardiac inflammation.
Early diagnosis of severe inflammatory forms of non-ischaemic cardiomyopathy (NICM), e.g. cardiac sarcoidosis (CS) or giant cell myocarditis (GCM), may enable unique treatment. However, there is limited information on how to identify CS or GCM in unselected patients with suspected NICM. We studied the clinical and imaging predictors of severe cardiac inflammation at the era of late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). In this observational cohort study, we enrolled 86 consecutive patients referred for LGE-CMR due to suspected NICM. Patients were extensively examined for underlying aetiology and followed up for at least two years to assure the final diagnosis. Ischaemic cardiomyopathy was excluded. During follow-up, 11(13%) patients were diagnosed with CS (n = 8) or GCM (n = 3). At baseline, sustained ventriculartachycardia (OR = 20.8, P = 0.001) and the volume of left ventricular LGE (OR = 1.06 for each 1% increase in LGE, P = 0.001) were significant adjusted predictors of CS or GCM. Palpitation, a disease course less than 3 months, septal abnormality in echocardiography, reduced stroke volume and atrioventricular block were other unadjusted predictors of CS or GCM. Multifocal LGE, affecting several myocardial layers and not confined to coronary artery perfusion territories, was useful in identifying CS or GCM, with 52-fold unadjusted OR (P < 0.001), sensitivity of 91% and specificity of 84%. In addition, positron emission tomography detected mediastinal lymph node biopsy targets in CS. In consecutive patients suspected for NICM, LGE volume and sustained ventricular tachycardia predict independently CS or GCM. Multifocal LGE is useful in identifying severe cardiac inflammation.


Perspectives of older women with early breast cancer on telemedicine during post-primary treatment.
Telemedicine has the potential to lessen healthcare burden of older patients due to frequent appointments, physical disabilities, and reliance on caretakers. To benefit from telemedicine, patients must have the capacity and willingness to engage with technology. This study aimed to better understand the telemedicine experiences of older women with non-metastatic breast cancer regarding visit convenience, completeness, and interpersonal satisfaction. Semi-structured interviews were conducted in a convenience sample of women age 65+, post-primary treatment for stage I-III breast cancer, who had received in-person outpatient care at a cancer center in urban North Carolina before a telemedicine appointment occurring after March 2020. Patients were interviewed about their perceptions of telemedicine (telephone, video) as compared to in-person visits. Audio files of interviews were transcribed and analyzed for themes and subthemes established a priori in the interview protocol. Fifteen patients (telephone = 5, video = 10) were consented and interviewed July-October 2021, mean age 74. Thirteen participants reported they preferred a hybrid care model that included telemedicine care over in-person care alone. COVID-19, physical disability, and transportation burden were the most common factors for telemedicine preference. Comfort with familiar face-to-face interactions and having a physical exam were common factors for in-person appointment preference. In-person appointment was favored early in the post-primary treatment phase; telemedicine was more acceptable when relationships were well-established and patients were farther out from diagnosis. Patient-provider discussions about appointment modality should take into account newness of diagnosis, patient familiarity with the care team, travel burden, and necessity of physical exam.


Antitumor effect and pharmacokinetics of intraperitoneal NK105, a nanomicellar paclitaxel formulation for peritoneal dissemination.
The intraperitoneal administration of paclitaxel has been shown to be a promising treatment strategy for peritoneal malignancy. The present study evaluated the effects of intraperitoneal administration of NK105, a paclitaxel-incorporating micellar nanoparticle, which has been shown to have a remarkable effect in a mouse model of gastric cancer. Intraperitoneal NK105 significantly reduced peritoneal tumors in vivo compared with the conventional paclitaxel formulation of paclitaxel solubilized in Cremophor EL and ethanol (PTX-Cre). Moreover, intraperitoneal NK105 significantly reduced the size of subcutaneously inoculated tumors, whereas no such effect was seen with PTX-Cre. Similar systemic toxic effects were observed following the intraperitoneal administration of both NK105 and PTX-Cre. Although NK105 disappeared rapidly almost within a day from the peritoneal cavity, the paclitaxel concentration in peritoneal nodules 4 h after intraperitoneal administration was significantly higher in the NK105 group than in the PTX-Cre group (P < 0.05), whereas there were no significant differences in liver paclitaxel concentrations between the two groups. We also evaluated the pharmacokinetics following intraperitoneal administration of NK105 and PTX-Cre. Serum paclitaxel concentrations 6, 12, 24, and 48 h after the intraperitoneal administration of the drugs were significantly higher in the NK105 than the PTX-Cre group. Furthermore, the peak serum concentration was higher in the NK105 than PTX-Cre group (24 100 ± 3560 vs 108 ± 25 ng/mL, respectively; P < 0.001), as was the area under the concentration-time curve from 0 to 48 h (191 000 ± 32 100 vs 1500 ± 108 ng·h/mL, respectively; P < 0.001). Therefore, intraperitoneal chemotherapy with nanoparticulate paclitaxel NK105 may offer a novel treatment strategy for improving drug delivery in gastric cancer with peritoneal dissemination because of enhanced drug penetration into peritoneal nodules and its prolonged presence in the systemic circulation.


The relative importance of metacognitive skills, emotional status, and executive function in psychosocial adjustment following acquired brain injury.
To examine the interrelationships between metacognitive skills and measures of emotional status and executive function following acquired brain injury (ABI), and examine their relative importance to psychosocial outcomes. A cross-sectional multicentre study employing correlational and multiple regression analyses. Sixty-seven adults with ABI living in the community, on average 4.4 years (SD = 4.7) postinjury. Sydney Psychosocial Reintegration Scale, Self-Awareness of Deficits Interview, Self-Regulation Skills Interview, Hospital Anxiety Depression Scale, Beck Hopelessness Scale, and standardized measures of executive function. Metacognitive skills correlated with level of hopelessness and executive measures of idea generation and error self-regulation. The best predictor of psychosocial outcome was depressive symptoms, with specific outcomes additionally related to error self-regulation and intellectual awareness. The findings highlight the need to evaluate interventions targeting depression and metacognitive skills to improve psychosocial outcomes.


Tactile localization on digits and hand: structure and development.
Localization of tactile stimuli to the hand and digits is fundamental to somatosensory perception. However, little is known about the development or genetic bases of this ability in humans. We examined tactile localization in normally developing children, adolescents, and adults and in people with Williams syndrome (WS), a genetic disorder resulting in a wide range of severe visual-spatial deficits. Normally developing 4-year-olds made large stimulus-localization errors, sometimes across digits, but nevertheless their errors revealed a structured internal representation of the hand. In normally developing individuals, errors became exponentially smaller over age, reaching the adult level by adolescence. In contrast, people with WS showed large localization errors regardless of age and a significant proportion of cross-digit errors, a profile similar to that of normally developing 4-year-olds. Thus, tactile localization reflects internal organization of the hand even early in normal development, undergoes substantial development in normal children, and is susceptible to developmental, but not organizational, impairment under genetic deficit.


Reassessment of the classification of Bryopsidales (Chlorophyta) based on chloroplast phylogenomic analyses.
The Bryopsidales is a morphologically diverse group of mainly marine green macroalgae characterized by a siphonous structure. The order is composed of three suborders - Ostreobineae, Bryopsidineae, and Halimedineae. While previous studies improved the higher-level classification of the order, the taxonomic placement of some genera in Bryopsidineae (Pseudobryopsis and Lambia) as well as the relationships between the families of Halimedineae remains uncertain. In this study, we re-assess the phylogeny of the order with datasets derived from chloroplast genomes, drastically increasing the taxon sampling by sequencing 32 new chloroplast genomes. The phylogenies presented here provided good support for the major lineages (suborders and most families) in Bryopsidales. In Bryopsidineae, Pseudobryopsis hainanensis was inferred as a distinct lineage from the three established families allowing us to establish the family Pseudobryopsidaceae. The Antarctic species Lambia antarctica was shown to be an early-branching lineage in the family Bryopsidaceae. In Halimedineae, we revealed several inconsistent phylogenetic positions of macroscopic taxa, and several entirely new lineages of microscopic species. A new classification scheme is proposed, which includes the merger of the families Pseudocodiaceae, Rhipiliaceae and Udoteaceae into a more broadly circumscribed Halimedaceae, and the establishment of tribes for the different lineages found therein. In addition, the deep-water genus Johnson-sea-linkia, currently placed in Rhipiliopsis, was reinstated based on our phylogeny.


Mutations in the carcinoembryonic antigen gene in colorectal cancer patients: implications on liver metastasis.
Carcinoembryonic antigen (CEA) expression is used clinically to monitor patients with colorectal and other cancers. A subset of patients have extraordinarily high CEA levels that cannot be attributed solely to tumor load. We have shown mutations in the region of CEA (PELPK motif) responsible for its hepatic clearance in three of eight patients with high CEA levels. We used denaturing high-performance liquid chromatography to provide evidence of polymorphism in these patients. These mutations were scored by DNA cycle sequencing and shown to be heterozygous. The patients with mutations in the PELPK motif showed remarkably reduced circulatory clearance rates in an animal model. A patient without mutation in the region showed normal clearance rates. Mutations in PELPK may affect structural stability and binding affinity to the Kupffer cell receptor in the liver. These studies have implications for the role of CEA as a facilitator of hepatic metastasis.


Leaf shape evolution has a similar genetic architecture in three edaphic specialists within the Mimulus guttatus species complex.
The genetic basis of leaf shape has long interested botanists because leaf shape varies extensively across the plant kingdom and this variation is probably adaptive. However, knowledge of the genetic architecture of leaf shape variation in natural populations remains limited. This study examined the genetic architecture of leaf shape diversification among three edaphic specialists in the Mimulus guttatus species complex. Lobed and narrow leaves have evolved from the entire, round leaves of M. guttatus in M. laciniatus, M. nudatus and a polymorphic serpentine M. guttatus population (M2L). Bulk segregant analysis and next-generation sequencing were used to map quantitative trait loci (QTLs) that underlie leaf shape in an M. laciniatus × M. guttatus F2 population. To determine whether the same QTLs contribute to leaf shape variation in M. nudatus and M2L, F2s from M. guttatus × M. nudatus and lobed M2L × unlobed M. guttatus crosses were genotyped at QTLs from the bulk segregant analysis. Narrow and lobed leaf shapes in M. laciniatus, M. nudatus and M. guttatus are controlled by overlapping genetic regions. Several promising leaf shape candidate genes were found under each QTL. The evolution of divergent leaf shape has taken place multiple times in the M. guttatus species complex and is associated with the occupation of dry, rocky environments. The genetic architecture of elongated and lobed leaves is similar across three species in this group. This may indicate that parallel genetic evolution from standing variation or new mutations is responsible for the putatively adaptive leaf shape variation in Mimulus.


Examining the effects of paper type, pen type, writing pressure and angle of intersection on white and dark dominance in ESDA impressions of sequenced strokes--an application of the likelihood ratio.
Questioned document casework can occasionally involve the sequencing of impressions. Although some conclusions can be drawn from looking at ESDA traces of intersections there is currently no way of assessing the strength of the observations made in any given case. Using a range of paper and pen types this work examines points of intersection and evaluates the results statistically in order judge the value of the results obtained.


Cannabis Use and Emotional Awareness Difficulties in Adolescents with Co-Occurring Substance Use and Psychiatric Disorders.
Background: Assessing predictors of cannabis use following adolescent substance use treatment may inform essential treatment elements to be emphasized before discharge. Adolescents with low emotional awareness may have limited resources for identifying and overcoming negative emotions, and therefore, use cannabis to regulate emotions. Purpose/objectives: The purpose of this study was to test the hypothesis that emotional awareness difficulties are associated with increased cannabis use across the transition out of substance use treatment. This hypothesis was investigated by applying an autoregressive random-intercept cross-lagged panel-modeling framework to test the fit of alternative models and inform hypotheses about directional associations between cannabis use and emotional awareness difficulties over time. Methods: Participants were 110 adolescents with co-occurring disorders and their families participating in an intensive home-based treatment trial. Adolescents reported on past 7-day cannabis use and difficulties in emotional awareness at baseline and three follow-up assessments across 12 months. Results: At baseline, 54% of the sample reported past-week cannabis use. A directional effect was supported such that difficulties with emotional awareness at 3 months' post-baseline, which corresponded to the approximate end of the treatment program, were associated with increased cannabis use at 6 months' post-baseline, controlling for the stability of cannabis use, and emotional awareness over time. Cannabis use, however, was not associated with subsequent difficulties in emotional awareness (i.e., effects in the opposite direction were not supported). Conclusions/Importance: Emotional awareness difficulties toward the end of a course of intensive outpatient treatment may be associated with increased cannabis use after the completion of treatment.


Fostering IRB collaboration for review of international research.
This article presents a review of the literature, summarizes current initiatives, and provides a heuristic for assessing the effectiveness of a range of institutional review board (IRB) collaborative strategies that can reduce the regulatory burden of ethics review while ensuring protection of human subjects, with a particular focus on international research. Broad adoption of IRB collaborative strategies will reduce regulatory burdens posed by overlapping oversight mechanisms and has the potential to enhance human subjects protections.


The soyabean isoflavone genistein modulates endothelial cell behaviour.
The aim of the present study was to investigate the direct action of the phyto-oestrogen genistein (Gen) on vascular endothelial behaviour, either in the presence or absence of proinflammatory agents. In rat aortic endothelial cell (EC) cultures, 24 h of treatment with Gen significantly increased cell proliferation in a wide range of concentration (0.001-10 nm). This mitogenic action was prevented by the oestrogen receptor (ER) antagonist ICI 182780 or by the presence of the specific NO synthase inhibitor l-nitro-arginine methyl ester. When monocytes adhesion to EC was measured, Gen partially attenuated leucocyte adhesion not only under basal conditions, but also in the presence of bacterial lipopolysaccharides (LPS). The effect of the phyto-oestrogen on the expression of EC adhesion molecules was evaluated. Gen down-regulated the enhancement in mRNA levels of E-selectin, vascular cell adhesion molecule-1 and P-selectin elicited by the proinflammatory agent bacterial LPS. The regulation of EC programmed death induced by the isoflavone was also demonstrated. Incubation with 10 nm Gen prevented DNA fragmentation induced by the apoptosis inductor H2O2. The results presented suggest that Gen would exert a protective effect on vascular endothelium, due to its regulatory action on endothelial proliferation, apoptosis and leucocyte adhesion, events that play a critical role in vascular diseases. The molecular mechanism displayed by the phyto-oestrogen involved the participation of the ER and the activation of the NO pathway.


Dietary intakes and socioeconomic factors are associated with the hemoglobin concentration of Bangladeshi women.
Iron deficiency anemia affects a large number of women in developing countries, especially during child-bearing years. The hemoglobin concentration is useful for identifying iron deficiency anemia. The main objectives of this study were, first, to extend algorithms for calculating bioavailable iron from mixed diets, taking into account the enhancers and inhibitors of iron absorption under alternative assumptions on body iron stores. Second, a comprehensive longitudinal model was developed for the proximate determinants of hemoglobin concentration that included the subjects' dietary intakes, nutritional status, morbidity and socioeconomic factors and the unobserved between-subject differences. The model for hemoglobin concentration was estimated using three repeated observations on 514 free living women in Bangladesh. Socioeconomic factors affecting the iron intake from meat, fish and poultry and from all animal sources were also modeled. The main results were that bioavailable iron, women's height and mid upper arm circumference and intake of iron tablets were significant predictors of hemoglobin concentration. Increases in household incomes were associated with higher intake of iron from meat, fish and poultry and from all animal sources. The algorithms for estimating bioavailable iron showed the importance of assumptions regarding body iron stores and underscored the need to develop suitable algorithms for subjects in developing countries.


The case for using research on trait narcissism as a building block for understanding narcissistic personality disorder.
The empirical literature on narcissistic personality disorder (NPD) is quite sparse with only a small number of studies singularly devoted to this important construct. Of the published articles on NPD, the majority (approximately 80%) are either of a theoretical nature or present data from a case study perspective. There is, however, a thriving and growing literature on trait narcissism. In comparison to NPD, trait narcissism is viewed as a continuous construct in which no attempt is made to make dichotomous decisions of a clinical nature. Recent data suggest that research on trait narcissism is relevant to NPD as self-report scores are substantially correlated with the Diagnostic and Statistical Manual of Mental Disorders (4th ed., American Psychiatric Association, 1994) interviews of NPD and generate a five-factor model personality profile that is congruent with expert ratings of prototypical NPD. We review the literature on trait narcissism in relation to implicit and explicit aspects of self-esteem, self-presentation, decision making, relationships, work performance, and externalizing behavior (e.g., aggression). Ultimately, we argue that this literature might be used as a stepping stone toward the development of a better empirical understanding of NPD and its nomological network.


Response to zinc deficiency of two rice lines with contrasting tolerance is determined by root growth maintenance and organic acid exudation rates, and not by zinc-transporter activity.
*Zinc (Zn)-deficient soils constrain rice (Oryza sativa) production and cause Zn malnutrition. The identification of Zn-deficiency-tolerant rice lines indicates that breeding might overcome these constraints. Here, we seek to identify processes underlying Zn-deficiency tolerance in rice at the physiological and transcriptional levels. *A Zn-deficiency-tolerant line RIL46 acquires Zn more efficiently and produces more biomass than its nontolerant maternal line (IR74) at low [Zn](ext) under field conditions. We tested if this was the result of increased expression of Zn(2+) transporters; increased root exudation of deoxymugineic acid (DMA) or low-molecular-weight organic acids (LMWOAs); and/or increased root production. Experiments were performed in field and controlled environment conditions. *There was little genotypic variation in transcript abundance of Zn-responsive root Zn(2+)-transporters between the RIL46 and IR74. However, root exudation of DMA and LMWOA was greater in RIL46, coinciding with increased root expression of putative ligand-efflux genes. Adventitious root production was maintained in RIL46 at low [Zn](ext), correlating with altered expression of root-specific auxin-responsive genes. *Zinc-deficiency tolerance in RIL46 is most likely the result of maintenance of root growth, increased efflux of Zn ligands, and increased uptake of Zn-ligand complexes at low [Zn](ext); these traits are potential breeding targets.


Identification and characterization of a novel regulatory factor: IgA-inducing protein.
IgA is the predominant Ig isotype in mucosal secretions and thus plays a pivotal role in host defense. The mechanisms by which IgA expression is regulated may differ among species and involve multiple pathways. Various cytokines and costimulators have been identified which regulate expression of this isotype, including IL-10, IL-2, vasoactive intestinal peptide, and TGF-beta. We have tested a wide array of known factors, but only under very limited conditions do these factors mediate substantial IgA production in vitro from bovine B cells. In response to these findings, we generated a cDNA library in a mammalian expression vector from activated cells derived from bovine gut-associated lymphoid tissues (Peyer's patch and mesenteric lymph node cells) as a source of soluble factor(s) that may regulate IgA production. We have identified a novel factor, IgA-inducing protein, which stimulates relatively high levels of IgA production in vitro following CD40 stimulation in coculture with IL-2. Our data suggest that IgA-inducing protein regulates IgA by acting as a switch or differentiation factor and is expressed in a variety of lymphoid and nonlymphoid tissues.


The new hire/preceptor experience: cost-benefit analysis of one retention strategy.
Retention of nurses is central to the strategic planning process of any healthcare organization. The authors discuss a strategy to leverage the relationship between new nurses and their preceptors in an attempt to positively effect nurse retention. The authors present the costs and benefits of this retention strategy.


Mitochondrial metabolic determinants of multiple myeloma growth, survival, and therapy efficacy.
Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the clonal proliferation of antibody producing plasma cells. Despite the use of next generation proteasome inhibitors (PI), immunomodulatory agents (IMiDs) and immunotherapy, the development of therapy refractory disease is common, with approximately 20% of MM patients succumbing to aggressive treatment-refractory disease within 2 years of diagnosis. A large emphasis is placed on understanding inter/intra-tumoral genetic, epigenetic and transcriptomic changes contributing to relapsed/refractory disease, however, the contribution of cellular metabolism and intrinsic/extrinsic metabolites to therapy sensitivity and resistance mechanisms is less well understood. Cancer cells depend on specific metabolites for bioenergetics, duplication of biomass and redox homeostasis for growth, proliferation, and survival. Cancer therapy, importantly, largely relies on targeting cellular growth, proliferation, and survival. Thus, understanding the metabolic changes intersecting with a drug's mechanism of action can inform us of methods to elicit deeper responses and prevent acquired resistance. Knowledge of the Warburg effect and elevated aerobic glycolysis in cancer cells, including MM, has allowed us to capitalize on this phenomenon for diagnostics and prognostics. The demonstration that mitochondria play critical roles in cancer development, progression, and therapy sensitivity despite the inherent preference of cancer cells to engage aerobic glycolysis has re-invigorated deeper inquiry into how mitochondrial metabolism regulates tumor biology and therapy efficacy. Mitochondria are the sole source for coupled respiration mediated ATP synthesis and a key source for the anabolic synthesis of amino acids and reducing equivalents. Beyond their core metabolic activities, mitochondria facilitate apoptotic cell death, impact the activation of the cytosolic integrated response to stress, and through nuclear and cytosolic retrograde crosstalk maintain cell fitness and survival. Here, we hope to shed light on key mitochondrial functions that shape MM development and therapy sensitivity.


Community participation: lessons for maternal, newborn, and child health.
Primary health care was ratified as the health policy of WHO member states in 1978.(1) Participation in health care was a key principle in the Alma-Ata Declaration. In developing countries, antenatal, delivery, and postnatal experiences for women usually take place in communities rather than health facilities. Strategies to improve maternal and child health should therefore involve the community as a complement to any facility-based component. The fourth article of the Declaration stated that, "people have the right and duty to participate individually and collectively in the planning and implementation of their health care", and the seventh article stated that primary health care "requires and promotes maximum community and individual self-reliance and participation in the planning, organization, operation and control of primary health care". But is community participation an essential prerequisite for better health outcomes or simply a useful but non-essential companion to the delivery of treatments and preventive health education? Might it be essential only as a transitional strategy: crucial for the poorest and most deprived populations but largely irrelevant once health care systems are established? Or is the failure to incorporate community participation into large-scale primary health care programmes a major reason for why we are failing to achieve Millennium Development Goals (MDGs) 4 and 5 for reduction of maternal and child mortality?


The effectiveness of clear speech as a masker.
It is established that speaking clearly is an effective means of enhancing intelligibility. Because any signal-processing scheme modeled after known acoustic-phonetic features of clear speech will likely affect both target and competing speech, it is important to understand how speech recognition is affected when a competing speech signal is also spoken clearly. In 2 experiments, the authors investigated whether listeners would experience improved intelligibility when both target and nontarget speech were spoken clearly. Listeners' recognition of sentences in competing sounds was examined in 2 experiments. For both experiments, the target speech was spoken in conversational and clear styles. The competing sounds in Experiment 1 included 2-talker maskers spoken in conversational and clear styles of English or Croatian. The competing sounds in Experiment 2 included 1-talker maskers spoken in clear or conversational styles and temporally modulated white noise maskers shaped to mimic the 1-talker maskers. Performance increased for clear versus conversational targets. No significant differences were found between conversational and clear maskers. If it were possible to implement clear speech through a listening device, it appears that listeners would still receive a clear-speech benefit, even if all sounds (including competing sounds) were (inadvertently) processed to be more clear.


The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery.
Drug delivery to brain tumors has been a controversial subject. Some believe the blood-brain barrier is not important, while others believe it is the major obstacle in treatment and have devised innovative approaches to circumvent it. These approaches can be divided into two categories: those that attempt to increase drug delivery of intravascularly administered drugs by manipulating either the drugs or capillary permeability, and those that attempt to increase drug delivery by local administration. Several strategies have been developed to increase the fraction of intravascular drug reaching the tumor, including intra-arterial administration, barrier disruption, new ways of packaging drugs, and, most recently, inhibiting drug efflux from tumor. When given intravascularly, all drugs have a common drawback: the body acts as a sink, and, even in the best situations, only a small fraction of administered drug actually reaches the tumor. A consequence is that systemic toxicity is usually the dose-limiting factor. When given locally, such as into the cerebrospinal fluid or directly into the tumor, 100% of an administered dose is delivered to the target site. However, local delivery is associated with variable and unpredictable spatial distribution and variation in drug concentration. The major dose-limiting factor of most local delivery methods will be neurotoxicity. The relative advantages and disadvantages of the different methods of circumventing the blood-brain barrier are presented in this review, and special attention is given to convection-enhanced delivery, which has particular promise for the local delivery of large therapeutic agents such as monoclonal antibodies, antisense oligonucleotides, or viral vectors.


Impact of synaptic unreliability on the information transmitted by spiking neurons.
The spike generating mechanism of cortical neurons is highly reliable, able to produce spikes with a precision of a few milliseconds or less. The excitatory synapses driving these neurons are by contrast much less reliable, subject both to release failures and quantal fluctuations. This suggests that synapses represent the primary bottleneck limiting the faithful transmission of information through cortical circuitry. How does the capacity of a neuron to convey information depend on the properties of its synaptic drive? We address this question rigorously in an information theoretic framework. We consider a model in which a population of independent unreliable synapses provides the drive to an integrate-and-fire neuron. Within this model, the mutual information between the synaptic drive and the resulting output spike train can be computed exactly from distributions that depend only on a single variable, the interspike interval. The reduction of the calculation to dependence on only a single variable greatly reduces the amount of data required to obtain reliable information estimates. We consider two factors that govern the rate of information transfer: the synaptic reliability and the number of synapses connecting each presynaptic axon to its postsynaptic target (i.e., the connection redundancy, which constitutes a special form of input synchrony). The information rate is a smooth function of both mechanisms; no sharp transition is observed from an "unreliable" to a "reliable" mode. Increased connection redundancy can compensate for synaptic unreliability, but only under the assumption that the fine temporal structure of individual spikes carries information. If only the number of spikes in some relatively long-time window carries information (a "mean rate" code), an increase in the fidelity of synaptic transmission results in a seemingly paradoxical decrease in the information available in the spike train. This suggests that the fine temporal structure of spike trains can be used to maintain reliable transmission with unreliable synapses.


Hybrid surface implants: Influence of residual stress on mechanical behavior, evaluated by finite element analysis and validation by fatigue tests.
To determine the influence of different surface roughness and residual stress of hybrid surface implants on their behavior and mechanical failure. Three types of implants with different surface roughness were used as specimens: smooth, rough, and hybrid. A diffractometer was used to determine the residual stress of the implants according to their different surface treatment. These results were used as an independent variable in a finite element analysis that compared the three specimens to determine the von Mises stress transferred to the implants and supporting bone and the resulting microdeformations. Flexural strength and fatigue behavior tests were performed to compare the results of the three types of implants. Higher residual stress values were found for rough surfaces (p < 0.05, Student's t-test) compared to smooth surfaces, and both types of stress were different for the two types of hybrid implant surfaces. Finite element analysis found different von Mises stress and microdeformation results, both at the level of the implant and the bone, for the three types of implants under study. These results were correlated with the different flexural strength behaviors (lower resistance for hybrids and higher for rough surfaces, p < 0.05) and fatigue behavior (the rough implant had the longest fatigue life, while the hybrid implant exhibited the worst fatigue behavior). The results show a trend toward a less favorable mechanical behavior of the hybrid implants related to the retention of different residual stresses caused by the surface treatment.


Effect of farnesol on Staphylococcus aureus biofilm formation and antimicrobial susceptibility.
Staphylococcus aureus is among the leading pathogens causing bloodstream infections able to form biofilms on host tissue and indwelling medical devices and to persist and cause disease. Infections caused by S. aureus are becoming more difficult to treat because of increasing resistance to antibiotics. In a biofilm environment particularly, microbes exhibit enhanced resistance to antimicrobial agents. Recently, farnesol was described as a quorum-sensing molecule with possible antimicrobial properties. In this study, the effect of farnesol on methicillin-resistant and -susceptible strains of S. aureus was investigated. With viability assays, biofilm formation assessment, and ethidium bromide uptake testing, farnesol was shown to inhibit biofilm formation and compromise cell membrane integrity. The ability of farnesol to sensitize S. aureus to antimicrobials was assessed by agar disk diffusion and broth microdilution methods. For both strains of staphylococci, farnesol was only able to reverse resistance at a high concentration (150 microM). However, it was very successful at enhancing the antimicrobial efficacy of all of the antibiotics to which the strains were somewhat susceptible. Therefore, synergy testing of farnesol and gentamicin was performed with static biofilms exposed to various concentrations of both agents. Plate counts of harvested biofilm cells at 0, 4, and 24 h posttreatment indicated that the combined effect of gentamicin at 2.5 times the MIC and farnesol at 100 microM (22 microg/ml) was able to reduce bacterial populations by more than 2 log units, demonstrating synergy between the two antimicrobial agents. This observed sensitization of resistant strains to antimicrobials and the observed synergistic effect with gentamicin indicate a potential application for farnesol as an adjuvant therapeutic agent for the prevention of biofilm-related infections and promotion of drug resistance reversal.


Investigating the influence of threat appraisals and social support on healthy eating behavior and drive for thinness.
This study examined the relationship between perceived obesity threats, social support, and college students' eating attitudes and behaviors. Results showed that perceived vulnerability to obesity negatively predicted healthy eating behavior. In addition, the perceived severity of obesity-related health problems positively predicted women's drive for thinness. Social support played a significant role in explaining health behaviors. Specifically, appraisal by others indirectly predicted college students' healthy eating behavior through increased self-efficacy. Among women, informational support moderated the relationships between both vulnerability and severity on healthy eating behavior. At low levels of support, vulnerability and severity negatively predicted students' healthy eating behavior. Overall, results suggest that messages designed to increase perceived vulnerability and severity may be detrimental when trying to improve people's dietary habits; however, among women certain types of social support may buffer the defensive responses resulting from obesity threats.


How can the service user voice be best heard at psychiatric meetings?
Service user contributions to mental health conferences are now routine. How effective they are at promoting dialogue is not clear. We report a difficult exchange following a presentation about coercive treatment, with our individual reflections on what we learnt. Suggestions are made to improve both the clinical practice and the dialogue.


Apraxia of lid opening mimicking ptosis in compound heterozygosity for A467T and W748S POLG1 mutations.
Patients harboring A467T and W748S POLG1 mutations present with a broad variety of neurological phenotypes, including cerebellar ataxia, progressive external ophthalmoplegia (PEO), myoclonus, epilepsy, and peripheral neuropathy. With exception of ataxia and myoclonus, movement disorders are not typical features of POLG1 associated disorders. We report on two affected siblings compound heterozygous for A467T and W748S mutations, one suffering from choreoathetosis and apraxia of lid opening due to focal eyelid dystonia that mimicked progression of ptosis, resulting in functional blindness. So far, focal dystonia has not been reported in POLG1 mutation carriers, and should be considered when investigating patients with PEO and ptosis. Further studies on POLG1 mutations in focal dystonia are warranted.


Smell what you hardly see: Odors assist visual categorization in the human brain.
Visual categorization is the brain ability to rapidly and automatically respond to a certain category of inputs. Whether category-selective neural responses are purely visual or can be influenced by other sensory modalities remains unclear. Here, we test whether odors modulate visual categorization, expecting that odors facilitate the neural categorization of congruent visual objects, especially when the visual category is ambiguous. Scalp electroencephalogram (EEG) was recorded while natural images depicting various objects were displayed in rapid 12-Hz streams (i.e., 12 images / second) and variable exemplars of a target category (either human faces, cars, or facelike objects in dedicated sequences) were interleaved every 9th stimulus to tag category-selective responses at 12/9 = 1.33 Hz in the EEG frequency spectrum. During visual stimulation, participants (N = 26) were implicitly exposed to odor contexts (either body, gasoline or baseline odors) and performed an orthogonal cross-detection task. We identify clear category-selective responses to every category over the occipito-temporal cortex, with the largest response for human faces and the lowest for facelike objects. Critically, body odor boosts the response to the ambiguous facelike objects (i.e., either perceived as nonface objects or faces) over the right hemisphere, especially for participants reporting their presence post-stimulation. By contrast, odors do not significantly modulate other category-selective responses, nor the general visual response recorded at 12 Hz, revealing a specific influence on the categorization of congruent ambiguous stimuli. Overall, these findings support the view that the brain actively uses cues from the different senses to readily categorize visual inputs, and that olfaction, which has long been considered as poorly functional in humans, is well placed to disambiguate visual information.


Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression.
Interferon (IFN)-alpha has been used to study the effects of innate immune cytokines on the brain and behavior in humans. The degree to which peripheral administration of IFN-alpha accesses the brain and is associated with a central nervous system (CNS) inflammatory response is unknown. Moreover, the relationship among IFN-alpha-associated CNS inflammatory responses, neurotransmitter metabolism, and behavior has yet to be established. Twenty-four patients with hepatitis C underwent lumbar puncture and blood sampling after approximately 12 weeks of either no treatment (n = 12) or treatment with pegylated IFN-alpha 2b (n = 12). Cerebrospinal fluid (CSF) and blood samples were analyzed for proinflammatory cytokines and their receptors as well as the chemokine, monocyte chemoattractant protein-1 (MCP-1), and IFN-alpha. Cerebrospinal fluid samples were additionally analyzed for monoamine metabolites and corticotropin releasing hormone. Depressive symptoms were assessed using the Montgomery Asberg Depression Rating Scale. Interferon-alpha was detected in the CSF of all IFN-alpha-treated patients and only one control subject. Despite no increases in plasma IL-6, IFN-alpha-treated patients exhibited significant elevations in CSF IL-6 and MCP-1, both of which were highly correlated with CSF IFN-alpha concentrations. Of the immunologic and neurotransmitter variables, log-transformed CSF concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were the strongest predictor of depressive symptoms. Log-transformed CSF concentrations of IL-6, but not IFN-alpha or MCP-1, were negatively correlated with log-transformed CSF 5-HIAA (r(2) = -.25, p < .05). These data indicate that a peripherally administered cytokine can activate a CNS inflammatory response in humans that interacts with monoamine (serotonin) metabolism, which is associated with depression.


Serious acute coronary thrombosis associated with heparin-induced thrombocytopenia in off-pump coronary artery bypass grafting.
A 72-year-old female underwent off-pump coronary bypass grafting one month after heparin exposure. Immediately after protamine administration, she developed hypotension due to acute graft failure. Grafting to left anterior descending branch was revised under intra-aortic balloon pump insertion and she was transferred to intensive care unit under stable hemodynamic condition. However, she gradually developed low cardiac output syndrome and echocardiography showed new onset of myocardial infarction. Coronary angiography on the first postoperative day revealed diffuse serious coronary thrombosis involving all grafts and grafted native coronary arteries. Emergent percutaneous coronary intervention (PCI) was performed for native vessels. Laboratory examination revealed severe progressive thrombocytopenia and she was clinically diagnosed as heparin-induced thrombocytopenia (HIT). After cessation of all heparins and alternative anticoagulation with argatroban, thrombocytopenia was improved and some of occluded grafts were recanalized. She was discharged on the 51st postoperative day. Acute graft thrombosis, especially caused by HIT, is a serious complication, which sometimes results in mortality. This is a successful case treated by PCI followed by an alternative anticoagulation.


Recovery of pulmonary and skin lesions of sarcoidosis after thymectomy.
Sarcoidosis is a multisystem inflammatory disorder of unknown etiology. It is characterized by the presence of noncaseating granulomas and an inflammatory process in which T lymphocytes, especially type-1 helper T (Th1) cells, macrophages and different cytokines are involved. Different studies have shown the importance of genetic background in addition to environmental exposure in explaining different clinical phenotypes and disease outcome. In addition, potential auto antigens that might lead to the disease have been identified. Here, we present a 53-year-old female patient presenting with subcutaneous nodules and mediastinal hilar lymphadenopathies refractory for corticosteroid treatment. Computed tomography of the thorax revealed a soft-tissue lesion in the thymus location. The lesions due to sarcoidosis resolved after thymectomy. The remission of skin and pulmonary sarcoidosis only after thymectomy does potentially indicate the critical role that the thymus might play in the pathogenesis of this disease in a certain group of patients.


[UV-vis spectroscopic characterization of inclusion compounds of beta-cyclodextrin with lycopene].
Water-soluble inclusion compounds of beta-cyclodextrin with lycopene were prepared by two methods: (1) complexation in solution and (2) complexation by kneading. It was found that UV-Vis spectra of the inclusion complexes in water are different from those of lycopene in water-miscible organic solvents (tetrahydrofuran) and beta-cyclodextrin in water, which confirms the formation of the inclusion complexes. Specific interactions of lycopene and beta-cyclodextrin cause great changes in absorbance maximum (lambdamax) of lycopene. It is considered that the inclusion complexes in water are formed as supermolecular aggregates with nanometer size, after card-pack type lycopene is included by beta-cyclodextrin in molecular level.


[Experiences with a paste used as an anthelmintic in cats].
When the anthelmintic Banminth 'Katze' was administered twice to ninety-two cats, the owners were questioned on the method by which the animals took this paste. Minor, if any, problems were observed in 94.5 per cent of the cats. Major problems occurred in 5.5 per cent of the animals. Significantly more adult than young cats had difficulties in taking the paste.


In vitro and in vivo antioxidative and hepatoprotective activity of aqueous extract of Cortex Dictamni.
To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract (CDAE) in carbon tetrachloride (CCl4)-induced liver damage in rats. The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate (FTC) and thiobarbituric acid (TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAE against CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1 (CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinine oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase catalytic subunit (γ-GCSc) protein expression was measured by Western blot. Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation (P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE (160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes (P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression. CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.


An examination of comorbid asthma and obesity: assessing differences in physical activity, sleep duration, health-related quality of life and parental distress.
Compare youth with comorbid asthma and obesity to youth with obesity only to determine if differences exist in body mass index, dietary intake, levels of physical activity, sleep duration and health-related quality of life. Levels of parent distress were also compared. Participants included 248 children (n = 175 in Obesity group; n = 73 in Asthma + Obesity group) with a BMI ≥ 85th percentile for age and gender, and their participating parent(s) or legal guardian(s). Measures of child height and weight were obtained by study personnel and Z-scores for child body mass index were calculated using age- and gender-specific norms. Child physical activity and sleep duration were measured via accelerometers. Dietary intake, health-related quality of life and parent distress were assessed via self-report. The Asthma + Obesity group evidenced significantly higher body mass index scores, and had lower sleep duration. There was a non-statistically significant trend for lower levels of physical activity among children in the Asthma + Obesity group. Dietary intake, health-related quality of life and parent distress did not differ between groups. Youth with comorbid asthma and obesity are at increased risk for negative health and psychosocial difficulties compared to youth who are overweight or obese only. Professionals providing treatment for youth with asthma are encouraged to assess the implications of weight status on health behaviors and family psychosocial adjustment.


HIV-related Pneumocystis jirovecii pneumonia managed with caspofungin and veno-venous extracorporeal membrane oxygenation rescue therapy.
Patients with pneumocystis pneumonia have a risk of progressing to acute respiratory failure necessitating admission to intensive care. The case described is of a patient with a newly diagnosed HIV infection presenting with pneumocystis pneumonia. Despite initiating the appropriate pharmacological treatment the patient's clinical condition deteriorated, and required both rescue pharmacological therapy with echinocandins as well as respiratory support with extracorporeal membrane oxygenation therapy. The patient recovered well on ventilator and circulatory support despite a long weaning process complicated by sequelae common to pneumocystis pneumonia. Following initialisation of antiretroviral therapy and step-down from an intensive care setting, the patient required further prolonged hospital stay for rehabilitation and mental health support before being discharged. This case reviews the novel pharmacological therapies and respiratory support strategies used in cases of pneumocystis pneumonia, including the clinical and psychological sequelae that may follow.