[Effect of radiation on calcium-dependent pathway of nitroglycerin-evoked relaxation of rat aorta].
The effects of nitroglycerine (NG, 10(-7)-10(-4) M) on contractile force and intracellular calcium concentration ([Ca2+]i) in deendotelized thoracic aorta smooth muscles (SM) precontracted with high K+ in control and gamma-irradiated rats (6 Gy) were investigated. NG-induced activation of soluble guanylate cyclase (sGC) as dominating pathway of NG-induced SM relaxation without related decrease in [Ca2+]i level is demonstrated. Radiation was without effect on this sGC-dependent and [Ca2+]i -independent NG-induced relaxation of vascular smooth muscle but decreased the basal levels of[Ca2+]i by (28.4 +/- 11.9)% (6 Gy, 9th-day).


Dilated cardiomyopathy and sensorineural hearing loss: a heritable syndrome that maps to 6q23-24.
Dilated cardiomyopathy (DCM) and sensorineural hearing loss (SNHL) are prevalent disorders that occur alone or as components of complex multisystem syndromes. Multiple genetic loci have been identified that, when mutated, cause DCM or SNHL. However, the isolated coinheritance of these phenotypes has not been previously recognized. Clinical evaluations of 2 kindreds demonstrated autosomal-dominant transmission and age-related penetrance of both SNHL and DCM in the absence of other disorders. Moderate-to-severe hearing loss was evident by late adolescence, whereas ventricular dysfunction produced progressive congestive heart failure after the fourth decade. DNA samples from the larger kindred (29 individuals) were used to perform a genome-wide linkage study. Polymorphic loci on chromosome 6q23 to 24 were coinherited with the disease (maximum logarithm of odds score, 4.88 at locus D6S2411). The disease locus must lie within a 2.8 cM interval between loci D6S975 and D6S292, a location that overlaps an SNHL disease locus (DFNA10). However, DFNA10 does not cause cardiomyopathy. The epicardin gene, which encodes a transcription factor expressed in the myocardium and cochlea, was assessed as a candidate gene by nucleotide sequence analysis; no mutations were identified. A syndrome of juvenile-onset SNHL and adult-onset DCM is caused by a mutation at 6q23 to 24 (locus designated CMD1J). Recognition of this cardioauditory disorder allows for the identification of young adults at risk for serious heart disease, thereby enabling early intervention. Definition of the molecular cause of this syndrome may provide new information about important cell physiology common to both the ear and heart.


PEX14 is required for microtubule-based peroxisome motility in human cells.
We have established a procedure for isolating native peroxisomal membrane protein complexes from cultured human cells. Protein-A-tagged peroxin 14 (PEX14), a central component of the peroxisomal protein translocation machinery was genomically expressed in Flp-In-293 cells and purified from digitonin-solubilized membranes. Size-exclusion chromatography revealed the existence of distinct multimeric PEX14 assemblies at the peroxisomal membrane. Using mass spectrometric analysis, almost all known human peroxins involved in protein import were identified as constituents of the PEX14 complexes. Unexpectedly, tubulin was discovered to be the major PEX14-associated protein, and direct binding of the proteins was demonstrated. Accordingly, peroxisomal remnants in PEX14-deficient cells have lost their ability to move along microtubules. In vivo and in vitro analyses indicate that the physical binding to tubulin is mediated by the conserved N-terminal domain of PEX14. Thus, human PEX14 is a multi-tasking protein that not only facilitates peroxisomal protein import but is also required for peroxisome motility by serving as membrane anchor for microtubules.


Nonequilibrium phase transitions in systems with long-range interactions.
We introduce a generalized Hamiltonian mean field model-an XY model with both linear and quadratic coupling between spins and explicit Hamiltonian dynamics. In addition to the usual paramagnetic and ferromagnetic phases, this model also possesses a nematic phase. The generalized Hamiltonian mean field model can be solved explicitly using Boltzmann-Gibbs statistical mechanics, in both canonical and microcanonical ensembles. However, when the resulting microcanonical phase diagram is compared with the one obtained using molecular dynamics simulations, it is found that the two are very different. We will present a dynamical theory which allows us to explicitly calculate the phase diagram obtained using molecular dynamics simulations without any adjustable parameters. The model illustrates the fundamental role played by dynamics as well the inadequacy of Boltzmann-Gibbs statistics for systems with long-range forces in the thermodynamic limit.


Towards the Personalized Treatment of Glioblastoma: Integrating Patient-Specific Clinical Data in a Continuous Mechanical Model.
Glioblastoma multiforme (GBM) is the most aggressive and malignant among brain tumors. In addition to uncontrolled proliferation and genetic instability, GBM is characterized by a diffuse infiltration, developing long protrusions that penetrate deeply along the fibers of the white matter. These features, combined with the underestimation of the invading GBM area by available imaging techniques, make a definitive treatment of GBM particularly difficult. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of GBM evolution in every single patient throughout his/her oncological history, in order to target therapeutic weapons in a patient-specific manner. In this work, we propose a continuous mechanical model and we perform numerical simulations of GBM invasion combining the main mechano-biological characteristics of GBM with the micro-structural information extracted from radiological images, i.e. by elaborating patient-specific Diffusion Tensor Imaging (DTI) data. The numerical simulations highlight the influence of the different biological parameters on tumor progression and they demonstrate the fundamental importance of including anisotropic and heterogeneous patient-specific DTI data in order to obtain a more accurate prediction of GBM evolution. The results of the proposed mathematical model have the potential to provide a relevant benefit for clinicians involved in the treatment of this particularly aggressive disease and, more importantly, they might drive progress towards improving tumor control and patient's prognosis.


A tyrosine residue in the small nuclear inclusion protein of tobacco vein mottling virus links the VPg to the viral RNA.
The identity of the amino acid residue that links the VPg of the potyvirus tobacco vein mottling virus (TVMV) to the viral RNA was determined. 32P-labeled TVMV RNA was digested with RNase A and micrococcal nuclease. The resulting 32P-labeled VPg was isolated and partially hydrolyzed with 6 N HCl at 110 degrees C for 2 h. Analysis by thin-layer electrophoresis revealed the presence of [32P]phosphotyrosine but not [32P]phosphoserine or [32P]phosphothreonine. Another preparation of TVMV RNA was treated with endoproteinase Lys-C, and the resulting peptide-RNA was purified by sodium dodecyl sulfate-sucrose gradient centrifugation. The sequence of the N-terminal 15 amino acid residues of the peptide, when compared with the RNA-derived amino acid sequence of the TVMV polyprotein, demonstrated that the peptide occurs in the small nuclear inclusion protein. These data suggest that Tyr-1860 of the polyprotein is the amino acid residue that links the TVMV VPg to the viral RNA.


The use of basic parameters for monitoring the haemodynamic effects of midazolam and ketamine as opposed to propofol during cardiac catheterization.
Our aim is to compare the haemodynamic and adverse effects of propofol versus the mixture of midazolam and ketamine as used in sedation for cardiac catheterization in children. In a prospective randomized trial, we divided patients needing sedation into 72 receiving a mixture of midazolam and ketamine and 42 receiving propofol. Their ages ranged from 6 months to 12 years, and 1 year to 16 years, respectively. We collected data relative to heart rate, mean arterial pressure, respiratory rate, peripheral saturations of oxygen, and adverse effects. We assessed cyanotic patients to establish any relationship between the haemodynamic data and peripheral arterial saturations of oxygen. Demographic data, including age, gender, and weight, was not statistically different between the groups. In those receiving midazolam and ketamine, mean systemic arterial pressures before, and 30 minutes after, sedation were 64.3, with standard deviation of 9.8, and 62.5, with standard deviation of 10.2, millimetre of mercury (p equals to 0.237). Heart rates were 131.3, with standard deviation of 13.5, and 109.2, with standard deviation of 17.3 beats per minute, (p less than 0.001) whereas in those given propofol the comparable values were 71.2, with standard deviation of 14.4, and 53.6 with standard deviation of 9.7 millimetres of mercury (p less than 0.001), and 115.2, with standard deviation of 13.6, and 100.5 with standard deviation of 20.1 beats per minute (p less than 0.01), respectively. Mean systemic arterial pressures in the subgroups of cyanotic patients before and 30 minutes after sedation were 74.8, with standard deviation of 14.6, and 72.7, with standard deviation of 12.4 millimetres of mercury for those receiving midazolam and ketamine (p equals to 0.544), and heart rates were 119.3, with standard deviation of 12.2, and 104.6 with standard deviation of 16.1 beats per minute (p equals to 0.001). In those given propofol, the comparable values were 71.1 with deviation of 15.5 and 53.9 with deviation of 9.2 millimetres of mercury (p equals to 0.001), and 126.7 with deviation of 20.8 and 107.2 with deviation of 13.5 beats per minute (p equals to 0.001), respectively. In cyanotic children, propofol used as a sedative agent during cardiac catheterization causes a decrease in mean arterial pressure and arterial desaturation. Ketamine produces more stable haemodynamic data in children with congenitally malformed hearts.


Physiotherapy in upper limb lymphedema after breast cancer treatment: a randomized study.
Our aim was to compare the responses of physical treatment with or without manual lymphatic drainage (MLD) in lymphedema after breast cancer treatment in a Brazilian population. This was a controlled clinical trial with lymphedema secondary to breast cancer treatment patients that were randomized into either: Group 1 consisting of MLD, skin care, bandaging and remedial exercises; or Group 2 using skin care, bandaging and remedial exercises. Sixty-six patients were randomized and 9 were excluded during the first phase, resulting in a total of 57 patients eligible for analyzes with 28 in Group 1 and 29 in Group 2. The first phase of treatment had an average duration of 24 days (+/- 12.38) and final volume excess average (VE) between limbs was 494.51 ml, corresponding to 29.18% of the initial volume. Volume reduction was highly significant, independent of the intervention (p < 0.001), and both treatments led to an average of percentage volume excess reduction (PVER) of 15.02%. Patients with incomplete range of motion and lymphatic-related fibrotic tissues showed a statistically significant reduction in the percentage of volume excess (p = 0.010; p = 0.009). The presence of arm paresthesia was associated with the lowest therapeutic response (p = 0.024). Both treatment groups demonstrated absolute and relative reductions of excess limb volume, and the addition of MLD did not significantly increase the therapeutic response in women with lymphedema after breast cancer.


Molecular simulation study of CO2 and N2 absorption in a phosphonium based organic ionic plastic crystal.
An organic ionic plastic crystal (OIPC), methyl(diethyl)isobutylphosphonium hexafluorophosphate [P122i4][PF6], was investigated for CO2 and N2 absorption using molecular simulations. Ab initio calculations showed that both the cation and anion exhibit larger binding energy for CO2 compared with N2. The CO2 absorption, as calculated from classical molecular dynamics simulations, increased by a factor of 7.5 from 275 K to 325 K, while that of N2 showed low absorption at both temperatures. The simulations suggest that the significant increase in CO2 absorption at 325 K is attributed to a higher degree of disorder and increase in the free volume due to the gas/solid interfaces. While the ab initio calculations were helpful in identifying specific interaction sites on the constituent ions, the classical MD simulations elucidated the importance of interfaces in gas absorption studies in this material. The results show that the OIPC can be a promising material for CO2 separations from CO2/N2 mixture.


[Pharmacological correction of the psycho-emotional status in breast cancer patients in the postoperative period].
It was established the presence of psychological disorders in 120 breast cancer patients in postoperative chemotherapy and considered the need for correction of revealed changes in the psychoemotional sphere to improve the quality of life of patients. The use of psychotropic drugs to correct the mental and emotional status in 80 women has improved their status, had a positive effect on the postoperative course, and helped to create the installation for continued treatment.


The Campaign for Universal Free Lunch in New York City: Lessons Learned.
The New York City (NYC) Department of Education is the largest public school system in the United States, with an enrollment of >1.1 million students. Students who participate in school meal programs can have higher dietary quality than nonparticipating students. Historically, family income documentation qualifying students in the NYC Department of Education for free or reduced-price meals reimbursed by the National School Lunch Program perpetuated poverty stigma. Additionally, National School Lunch Program qualification paperwork was a deterrent to many vulnerable families to participate and impeded all eligible children's access to nutritious meals, potentially magnifying food insecurity. The Healthy, Hunger-Free Kids Act of 2010 provided a viable option for schools to serve free meals to all students, regardless of income status, as a universal free lunch (UFL) through a Community Eligibility Provision if ≥40% of students already participated in another means-based program, such as the Supplemental Nutrition Assistance Program. In this case study, we describe the processes of (1) strategic coalition building of the Lunch 4 Learning campaign (a coalition of students, parents, school-based unions, teachers, pediatricians, community leaders, and children's advocacy organizations) to bring UFL to all NYC public schools, (2) building political support, (3) developing a media strategy, and (4) using an evidence-based strategy to overcome political, administrative, and procedural challenges. The Lunch 4 Learning campaign successfully brought UFL to all NYC public schools in 2017. This case study informs further advocacy efforts to expand UFL in other school districts across the country and national UFL advocacy.


[Effect of vasodilator agents on the electrolyte balance and the transmural potential difference in the wall of blood vessels].
It has been shown in experiments on adult cats that chronic treatment of normotensive animals with vasodilators leads to inconsistent changes in the transmural potential difference and electrolyte balance of the wall of blood vessels. A permanent correlation has been revealed to exist between vasodilation and increased electronegativity of the intima with regard to advention. Euphylline gives rise to potassium accumulation by the wall of blood vessels, whereas sodium nitrite produces no appreciable action on the electrolyte balance in the vascular wall. Angiotrophin and no-spa do not alter arterial pressure and transmural potential difference.


Delays in inactivation development and activation kinetics in myxicola giant axons.
Na inactivation was studied in Myxicola (two-pulse procedure, 6-ms gap between conditioning and test pulses). Inactivation developed with an initial delay (range 130-817 microseconds) followed by a simple exponential decline (time constant tau c). Delays (deviations from a simple exponential) are seen only for brief conditioning pulses were gNa is slightly activated. Hodgkin-Huxley kinetics with series resistance, Rs, predict deviations from a simple exponential only for conditioning pulses that substantially activate gNa. Reducing INa fivefold (Tris substitution) had no effect on either tau c or delay. Delay in not generated by Rs or by contamination from activation development. The slowest time constant in Na tails is approximately 1 ms (Goldman and Hahin, 1978) and the gap was 6 ms. Shortening the gap to 2 ms had no effect on either tau c or delay. Delay is a true property of the channel. Delay decreased with more positive conditioning potentials, and also decreased approximately proportionally with time to peak gNa during the conditioning pulse, as expected for sequentially coupled activation and inactivation. In a few cases the difference between Na current values for brief conditioning pulses and the tau c exponential could be measured. Difference values decayed exponentially with time constant tau m. The inactivation time course is described by a model that assumes a process with the kinetics of gNa activation as a precursor to inactivation.


Effect of ivermectin on the ovarian development of Aedes aegypti (Diptera: Culicidae).
The effect of ivermectin (0.1 microgram/ml) on blood digestion, ovarian development, and ovipositional attributes of Aedes aegypti was studied using standard morphological and histological techniques. Uncoordinated movements and paralysis were observed in most ivermectin-treated females within 1 h after ingestion of blood containing the chemical. Eight days after the blood meal, 23.5% of the treated females had died, whereas no mortality occurred in controls. Formation of the peritrophic membrane and digestion of the blood meal were delayed in the surviving treated mosquitoes. The most striking effect of ivermectin on Ae. aegypti at this dosage was on ovarian development. Changes observed among ivermectin-treated mosquitoes included: blood digestion without development of ovarian follicles; degeneration of primary follicles and formation of ovarian dilatations within 24 h after ingestion of the chemical; significant reduction in the rate of vitellogenesis and follicle development; decreased egg production; reduced egg hatching; abnormal egg size and shape; and increased percentages of unhatched embryonated and sterile eggs. Although the precise action of ivermectin on Ae. aegypti is unknown, our studies indicate that the chemical directly or indirectly affects at least three major organ systems (nervous, digestive, and reproductive).


[First epidemiological description of visceral leishmaniasis in Campo Grande, State of Mato Grosso do Sul].
An epidemiological study was conducted on cases of visceral leishmaniasis that were notified in Campo Grande between 2001 and 2006, using data from the Brazilian information system for notifiable diseases (Sistema de Informação de Agravos de Notificação, SINAN). In 2001, 577 cases were notified, giving an incidence of 1.47 cases/100,000. This rose to 20.98 cases/100,000 in 2006. From 2002 onwards, new cases were notified every month. Children up to nine years of age accounted for 40% of the cases. Males accounted for 64% of the cases and females, 36%. The death rate ranged from 5 to 11%, with a mean of 8%. Among the 44 deaths, 33 (75%) were male cases and 11 (25%) were female cases. Although elderly people accounted for 9% of the cases, mortality among them reached 39%. There were 27 cases of Leishmania /HIV coinfection (5%), with a mortality rate of 15%, mostly among men aged 20 to 49 years. A process of disease endemization with a high rate of incidence was observed.


The blood oxygen level-dependent functional MR imaging signal can be used to identify brain tumors and distinguish them from normal tissue.
In neuro-oncology, a major problem is clear identification of tumor from the surrounding normal tissue. We hypothesized that we could use the blood oxygen level-dependent functional MR imaging (BOLD fMRI) signals from tumors and normal brain to identify the tumors and distinguish them from the surrounding brain. Fourteen patients with meningiomas, gliomas, and metastatic tumors were scanned before surgery. All subjects performed a motor task; 2 subjects were also scanned while in a resting state. The BOLD signals were taken from selected points within the tumor and from the surrounding normal brain and were analyzed by using correlation analysis to determine how closely they were related. The BOLD signals from all of the tumors were significantly different from those in the surrounding normal tissue. In meningiomas and gliomas, selection of a voxel in the tumor for signal-intensity analysis highlighted the entire tumor mass while excluding the normal tissue. The BOLD signal intensity was the same whether the subjects were motionless or finger tapping. Analysis of the BOLD signal intensity provides a relatively simple and straightforward method for identifying brain tumors and distinguishing them from normal tissue. This approach may be of use in neurosurgery.


Safety and efficacy of intra-articular injection of the hip.
The aim of the present study was twofold: a) to establish the therapeutic efficacy of the hip injection with marcaine and steroid; (b) to establish the safety of the procedure with respect to possible bacterial contamination at the time of passage of needle into the hip joint. Thirty-five patients with osteoarthritis of the hip were injected. All patients were admitted as day cases and the procedure was performed in a laminar flow theatre under full aseptic conditions. The hip was aspirated before injection. Aspirate and injecting needles were sent for microbiological examination. Both aerobic and anaerobic cultures were performed. All patients were followed up for three months after hip injection. Microbiology results were not revealed to reviewing clinicians. All patients were reviewed at two weeks and at twelve weeks. Thirty-three patients (94.3%) had no growth in the samples. Two cases out of thirty-five hips had a positive culture but none of the patients went on to develop clinical sepsis. Patient response for pain in the hip was graded using a 10 point visual analogue scale (VAS) with 10 point as maximum pain and 0 points as no pain. Pre-injection the patient VAS for pain was a mean value of 6.4 0.77 (median, 6). The mean value of VAS score at 2 weeks dropped to 2.6 2.7 with median of 2. This difference was highly significant (p=0.003). At 12 weeks mean VAS score was 2.7 2.5 with median value of 2 (p=001). Three patients were worse after the injection. We found the hip injection to be safe. The risk of bacterial contamination is low provided a strict aseptic protocol is observed. In this study, one third of the patients had excellent pain relief for 3 months after the injection but in two thirds of cases it failed to provide complete, long-term pain relief (> 3 months). (Hip International 2002; 4: 378-82).


Responding to inflammatory challenges is less costly for a successful avian invader, the house sparrow (Passer domesticus), than its less-invasive congener.
When introduced into new regions, invading organisms leave many native pathogens behind and also encounter evolutionarily novel disease threats. In the presence of predominantly novel pathogens that have not co-evolved to avoid inducing a strong host immune response, costly and potentially dangerous defenses such as the systemic inflammatory response could become more harmful than protective to the host. We therefore hypothesized that introduced populations exhibiting dampened inflammatory responses will tend to be more invasive. To provide initial data to assess this hypothesis, we measured metabolic, locomotor, and reproductive responses to inflammatory challenges in North American populations of the highly invasive house sparrow (Passer domesticus) and its less-invasive relative, the tree sparrow (Passer montanus). In the house sparrow, there was no effect of phytohemagglutinin (PHA) challenge on metabolic rate, and there were no detectable differences in locomotor activity between lipopolysaccharide (LPS)-injected birds and saline-injected controls. In contrast, tree sparrows injected with PHA had metabolic rates 20-25% lower than controls, and LPS injection resulted in a 35% drop in locomotor activity. In a common garden captive breeding experiment, there was no effect of killed-bacteria injections on reproduction in the house sparrow, while tree sparrows challenged with bacteria decreased egg production by 40% compared to saline-injected controls. These results provide some of the first data correlating variation in immune defenses with invasion success in introduced-vertebrate populations.


Hydraulic Conductivity Fields: Gaussian or Not?
Hydraulic conductivity (K) fields are used to parameterize groundwater flow and transport models. Numerical simulations require a detailed representation of the K field, synthesized to interpolate between available data. Several recent studies introduced high resolution K data (HRK) at the Macro Dispersion Experiment (MADE) site, and used ground-penetrating radar (GPR) to delineate the main structural features of the aquifer. This paper describes a statistical analysis of these data, and the implications for K field modeling in alluvial aquifers. Two striking observations have emerged from this analysis. The first is that a simple fractional difference filter can have a profound effect on data histograms, organizing non-Gaussian ln K data into a coherent distribution. The second is that using GPR facies allows us to reproduce the significantly non-Gaussian shape seen in real HRK data profiles, using a simulated Gaussian ln K field in each facies. This illuminates a current controversy in the literature, between those who favor Gaussian ln K models, and those who observe non-Gaussian ln K fields. Both camps are correct, but at different scales.


Recent developments in suicide prevention among the Indigenous peoples of Australia.
Suicide is an Aboriginal and Torres Strait Islander (hereafter 'Indigenous') population health issue. Over 2015-2016, the Aboriginal and Torres Strait Islander Suicide Prevention Project (ATSISPEP) aimed to identify success factors in Indigenous suicide prevention. For non-Indigenous practitioners working with indigenous clients at risk of suicide, ATSISPEP identified important considerations to make treatment more effective. The start is acknowledging the differences in the historical, cultural, political, social and economic experiences of Indigenous peoples, and their greater exposure to trauma, psychological distress and risks to mental health. These mental health difficulties are specific and more prevalent amongst Indigenous peoples and communities due to the ongoing impacts of colonisation in Australia including a range of social determinants impacting on the well-being of Indigenous peoples today. Working effectively with Indigenous clients also includes being able to establish culturally safe work environments, and the ability of non-Indigenous practitioners to work in a culturally competent and trauma-informed manner. There are also considerations regarding time protocols and client follow-up. Further, postvention responses might be required. Supporting selective suicide prevention activity among younger people (and other groups at increased risk) and community-level work is an important complement to working with Indigenous individuals at risk of suicide.


The human brain: rewired and running hot.
The past two decades have witnessed tremendous advances in noninvasive and postmortem neuroscientific techniques, advances that have made it possible, for the first time, to compare in detail the organization of the human brain to that of other primates. Studies comparing humans to chimpanzees and other great apes reveal that human brain evolution was not merely a matter of enlargement, but involved changes at all levels of organization that have been examined. These include the cellular and laminar organization of cortical areas; the higher order organization of the cortex, as reflected in the expansion of association cortex (in absolute terms, as well as relative to primary areas); the distribution of long-distance cortical connections; and hemispheric asymmetry. Additionally, genetic differences between humans and other primates have proven to be more extensive than previously thought, raising the possibility that human brain evolution involved significant modifications of neurophysiology and cerebral energy metabolism.


Biofouling in membrane bioreactors: nexus between polyacrylonitrile surface charge and community composition.
The influence of membrane surface charge on biofouling community composition during activated sludge filtration in a membrane bioreactor was investigated in this study using polyacrylonitrile-based membranes. Membranes with different surface properties were synthesized by phase inversion followed by a layer-by-layer modification. Various characterization results showed that the membranes differed only in their surface chemical composition and charge, ie two of them were negative, one neutral and one positive. Membrane fouling experiments were performed for 40 days and the biofouling communities were analyzed. PCR-DGGE fingerprinting indicated selective enrichment of bacterial populations from the sludge suspension within the biofilms at any time point. The biofilm community composition seemed to change with time. However, no difference was observed between the biofilm community of differently charged membranes at specific time points. It could be concluded that membrane charges do not play a decisive role in the long-term selection of the key bacterial foulants.


Tracking a dynamic set of feature points.
We address the problems of tracking a set of feature points over a long sequence of monocular images as well as how to include and track new feature points detected in successive frames. Due to the 3-D movement of the camera, different parts of the images exhibit different image motion. Tracking discrete features can therefore be decomposed into several independent and local problems. Accordingly, we propose a localized feature tracking algorithm. The trajectory of each feature point is described by a 2-D kinematic model. Then to track a feature point, an interframe motion estimation scheme is designed to obtain the estimates of interframe motion parameters. Subsequently, using the estimates of motion parameters, corresponding points are identified to subpixel accuracy. Afterwards, the temporal information is processed to facilitate the tracking scheme. Since different feature points are tracked independently, the algorithm is able to handle the image motion arising from general 3-D camera movements. On the other hand, in addition to tracking feature points detected at the beginning, an efficient way to dynamically include new points extracted in subsequent frames is devised so that the information in a sequence is preserved. Experimental results for several image sequences are also reported.


Applications of generalizability theory and their relations to classical test theory and structural equation modeling.
Although widely recognized as a comprehensive framework for representing score reliability, generalizability theory (G-theory), despite its potential benefits, has been used sparingly in reporting of results for measures of individual differences. In this article, we highlight many valuable ways that G-theory can be used to quantify, evaluate, and improve psychometric properties of scores. Our illustrations encompass assessment of overall reliability, percentages of score variation accounted for by individual sources of measurement error, dependability of cut-scores for decision making, estimation of reliability and dependability for changes made to measurement procedures, disattenuation of validity coefficients for measurement error, and linkages of G-theory with classical test theory and structural equation modeling. We also identify computer packages for performing G-theory analyses, most of which can be obtained free of charge, and describe how they compare with regard to data input requirements, ease of use, complexity of designs supported, and output produced. (PsycINFO Database Record


Tobacco Dependence Treatment in Oncology: Initial Patient Clinical Characteristics and Outcomes from Roswell Park Comprehensive Cancer Center.
Despite the importance of smoking cessation to cancer care treatment, historically, few cancer centers have provided treatment for tobacco dependence. To address this gap, the National Cancer Institute (NCI) launched the Cancer Center Cessation Initiative (C3i). As part of this effort, this study examined implementation outcomes in a cohort of cancer survivors (CSs) who smoked cigarettes in the first year of an ongoing process to develop and implement a robust Tobacco Treatment Service at Roswell Park Comprehensive Cancer Center. We provide a comprehensive description of the new tobacco use assessment and referral process, and of the characteristics of cancer survivors who agreed to treatment including traditional tobacco-related psychosocial and cancer treatment-related characteristics and novel characteristics such as delay discounting rates. We also examine characteristic differences among those who agreed to treatment between those who attended and those who did not attend treatment. As the new tobacco assessment was implemented, the number of referrals increased dramatically. The mean number of treatment sessions attended was 4.45 (SD = 2.98) and the six-month point prevalence intention to treat abstinence rate among those who attended was 22.7%. However, only 6.4% agreed to treatment and 4% attended at least one treatment session. A large proportion of cancer survivors who agreed to treatment were women, of older age, of lower socioeconomic status (SES), and who had high levels of depressive symptomology. The findings demonstrate that the implementation of system changes can significantly improve the identification of cancer survivors who use tobacco and are referred to tobacco use treatment. Among those who attend, treatment is effective. However, the findings also suggest that a systematic assessment of barriers to engagement is needed and that cancer survivors may benefit from additional treatment tailoring. We present plans to address these implementation challenges. Systematic electronic medical record (EMR)-sourced referral to tobacco treatment is a powerful tool for reaching cancer survivors who smoke, but more research is needed to determine how to enhance engagement and tailor treatment processes.


Retinal nerve fiber hypertrophy in ataxia of Charlevoix-Saguenay patients.
To present full ophthalmologic examination and retinal nerve fiber layer (RNFL) photographs of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) patients showing significant increases in RNFL thickness compared to healthy subjects, but without myelinated retinal fibers. The study design was observational case series. Ten eyes of five patients with molecular confirmation of ARSACS underwent a full ophthalmologic examination that included clinical history, visual acuity, biomicroscopy of the anterior segment, gonioscopy, Goldmann applanation tonometry, central corneal ultrasonic pachymetry, ophthalmoscopy of the posterior segment, standard automatic perimetry (Humphrey field), simultaneous stereophotographs of the optic disc after mydriasis, a series of five red-free digital fundus photographs for RNFL evaluation, topographic analysis of the optic disc using the Heidelberg retina tomography, and measurement of peripapillary RNFL thickness with Cirrus optical coherence tomography. All patients showed abnormal visual fields, normal optic discs with a mild to strikingly increased visibility of RNFL in color stereophotographs, normal Heidelberg tomography, and moderate to markedly increased RNFL thickness in Cirrus tomography (average thickness ranging from 119 μm to 220 μm). We found evidence of RNFL hypertrophy in ARSACS patients that may have been interpreted as hypermyelinated retinal fibers in previous reports. A revision of ARSACS diagnostic criteria, particularly with regard to retinal alterations, is necessary.


Optical solitons and wave-particle duality.
We investigate the propagation of optical solitons interacting with linear defects in the medium. We show that solitons exhibit a wave-particle dualism versus power, i.e., depending on the relative size of soliton and defect, responsible for a soliton trajectory dependent on its waist.


Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis.
In the last few years, significant progress has been made in understanding the pathogenic mechanisms and in defining the role of relevant cells and molecules in the pathophysiology of rheumatoid arthritis (RA). Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1]) and small molecule inhibitors have been explored for the treatment of RA. To date, no single signaling pathway inhibitor as wide acting as the corticosteroids, is known. However, treatment with corticosteroids is also associated with allied side effects. Despite a lot of efforts in the category of small molecule inhibitors, no inhibitor is available to deal with RA at both fronts (inflammation and tissue damage), without causing immense side effects. This present review explores the role of spleen tyrosine kinase (Syk) in the pathogenesis of RA and also discusses how it may meet the present day therapeutic requirements for the treatment of RA. This review gives an in-depth discussion on the role of Syk signaling in RA, the possibilities of using Syk as a target and also discusses the possible side effects that could be associated with its inhibition. We propose Syk inhibition as a potential therapeutic approach for the treatment of RA.


World Health Organization (WHO) infant and young child feeding indicators: associations with growth measures in 14 low-income countries.
Eight World Health Organization (WHO) feeding indicators (FIs) and Demographic and Health Survey data for children <24 months were used to assess the relationship of child feeding with stunting and underweight in 14 poor countries. Also assessed were the correlations of FI with country gross national income (GNI). Prevalence of underweight and stunting increased with age and ≥ 50% of 12-23-month children were stunted. About 66% of babies received solids by sixth to eighth months; 91% were still breastfeeding through months 12-15. Approximately half of the children were fed with complementary foods at the recommended daily frequency, but <25% met food diversity recommendations. GNI was negatively correlated with a breastfeeding index (P < 0.01) but not with other age-appropriate FI. Regression modelling indicated a significant association between early initiation of breastfeeding and a reduction in risk of underweight (P < 0.05), but a higher risk of underweight for continued breastfeeding at 12-15 months (P < 0.001). For infants 6-8 months, consumption of solid foods was associated with significantly lower risk of both stunting and underweight (P < 0.001), as was meeting WHO guidance for minimum acceptable diet, iron-rich foods (IRF) and dietary diversity (P < 0.001); desired feeding frequency was only associated with lower risk of underweight (P < 0.05). Timely solid food introduction, dietary diversity and IRF were associated with reduced probability of underweight and stunting that was further associated with maternal education (P < 0.001). These results identify FI associated with growth and reinforce maternal education as a variable to reduce risk of underweight and stunting in poor countries.


Renal excretion of magnesium in a freshwater teleost, Salmo gairdneri.
Infusion of magnesium salts into the body cavity of freshwater-adapted rainbow trout led to elevated plasma magnesium concentrations and to stimulation of renal tubular secretion of magnesium. The majority of the infused load was excreted renally, no net branchial excretion being detected. Magnesium sulphate infusion led to increased tubular secretion of sulphate. Magnesium chloride infusion led to reduced tubular reabsorption of chloride. Magnesium could either be reabsorbed or secreted in control freshwater-adapted trout, apparently as a function of nutritional status. Fish could switch from reabsorption to secretion in response to magnesium loading. It is suggested that freshwater fish eliminate excess dietary magnesium renally.


RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest.
RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.


Effect of kaolin impregnated with calico plant extract on properties of starch films.
Starch film has poor tensile properties and poor water resistance. We aimed to improve these properties by adding kaolin impregnated with calico plant extract (CP-Kaolin). UV-Vis spectrophotometry showed that the calico plant extract (CPE) contained 4867.52 mg/L of total phenolic compounds and betacyanins were the predominant constituents. CP-Kaolin was characterized by Fourier transform infrared spectroscopy (FTIR), zeta potential, scanning electron microscopy (SEM) and x-ray diffraction (XRD) analysis. FTIR analysis showed that betacyanins were adsorbed on kaolin via hydrogen bonding. Zeta potential analysis confirmed the adsorption of betacyanins on kaolin. The intercalation of betacyanins between kaolin platelets was observed by XRD. SEM revealed that CP-Kaolin was well dispersed and embedded within the starch matrix. It was found that the addition of 10 wt% of CP-Kaolin increased the water resistance, tensile strength and thermal stability of starch film. Moreover, starch film containing 10 wt% of CP-Kaolin was sensitive to the change in pH of the fish during storage. Therefore, the addition of CP-Kaolin improved the properties of starch film and starch film composite with CP-Kaolin could be applied as a smart packaging in the food industry.


Screening of mortality in transplant patients using an assay for immune function.
So far, the ImmuKnow Immune Cell Function Assay (Cylex, Inc., Columbia, MD, USA) has been used to assess risks of infection and rejection in transplant patients. We hypothesized that the ImmuKnow assay might be used for mortality screening in transplant patients overall. In the period of February 2007 to December 2009, at the Uppsala University Hospital, 362 patients who received either kidney, kidney+pancreas, kidney+islet cells, liver or liver+kidney allografts were randomly screened using the ImmuKnow assay. All causes of mortality were compared between two groups: patients with at least one ImmuKnow assay below 175ng/mL and patients with all ImmuKnow assays from 175ng/mL and above. Subsequently, the frequency of rejection within thirty days of the ImmuKnow assay was compared between these two groups. The study included 1031 ImmuKnow assays obtained from the 362 patients. A total of 111 patients had at least one ImmuKnow below 175ng/mL and 251 patients had all their ImmuKnow assays from 175ng/mL and above. By January 31st 2010, 16 of 111 patients (14.4%) with at least one ImmuKnow assay below 175ng/mL were deceased, compared to 13 of 251 patients (5.2%) with all ImmuKnow assays from 175ng/mL and above (p=0.0053, Fisher's exact test). There was no difference in the frequency of rejection between the two groups (19.8% versus 17.5%, p=0.66). In addition to assessing relative risks of infection and rejection in transplant patients, the ImmuKnow assay may be used to identify patients with increased risk of short-term mortality. Transplant patients being highly overimmunosuppressed as assessed by the ImmuKnow assay do not seem to have a lower risk of short-term rejection.


Managing magnets: An audit of introduction of the Royal College of Emergency Medicine Best Practice Guideline.
To evaluate management of children and young people presenting to the Emergency Department (ED) with magnet ingestion before and after new guidance. In May 2021, a National Patient Safety Agency and Royal College of Emergency Medicine (RCEM) Best Practice Guideline about management of ingested magnets was published. This was implemented in our department. Children and young people presenting after magnet ingestion were identified from SNOMED (coded routinely collected data) and X-ray requests between January 2016 and March 2022. Management was compared to national guidance. There were 138 patient episodes of magnet ingestion, with a rising incidence over the 5-year period. Following introduction of the guideline, there was a higher incidence of admission (36% vs. 20%) and operative intervention (15.7% vs. 8%). Use of follow-up X-ray increased from 56% to 90%. There was substantial variation in the management prior to guidance which reduced after introduction of the RCEM guidance. Management of magnet ingestion has become more standardised since introduction of the National RCEM Best Practice Guideline, but there is still room for improvement.


Unusual gastric band migration outcome: distal small bowel obstruction and coming out per-rectum.
We describe a case of unusual gastric band migration outcome. A 54 years old female was submitted to laparoscopic adjustable gastric band in September 2001. In September 2009 she developed access-port infection which needed drainage and access-port removal. Three months later in December 2009 the patient was investigated due to abdominal pain and abdominal distention. X-rays and Abdomen CT revealed migrated gastric band which is completely intraluminal with its connecting tube, causing transient distal small bowel obstruction and subsequently comes out per-rectum. Band erosion and intragastric migration is a late complication that frequently needs surgical removal. There are few reported cases in the literature of migrated gastric band removal by endoscopy. However according to my knowledge, this is the first reported case of migrated gastric band coming out per rectum without need for surgical or enoscoipic removal.


Interventions for adult family carers of people who have had a stroke: a systematic review.
A systematic review of the effectiveness of interventions for adult family carers of people with stroke, and an exploratory examination of the relationship between the conceptual basis of these interventions and their effectiveness. Seventeen electronic databases and grey literature sources were searched, including ASSIA, BNI, Cochrane Library, CINAHL, EMBASE, MEDLINE, PsycINFO, Social Science Citation Index and the Science Citation Index, HMIC and the National Research Register. Authors of unpublished material were contacted for data and additional publications. Reference and citation tracking was performed on included publications. randomized controlled trials of interventions aimed primarily at adult family carers of people post stroke; carers were the primary sample; primary outcomes reported were for carers. Two independent reviewers screened titles and abstracts to identify publications and extract data. Quality assessment was performed to weight study findings. Eight papers were found reporting on six complex, generally heterogeneous, interventions: caregiver training; education and counselling; social problem-solving partnerships, delivered principally by telephone; a psycho-educational telephone support group; a nurse-led support and education programme; and a support programme, delivered either to groups in hospital or individuals during home visits. Half of the interventions were based on stress-coping theories; the remainder did not identify a conceptual basis for the intervention. Some benefits were reported for all interventions, although trials were generally of low quality, preventing firm conclusions being drawn. The presence of a conceptual basis for interventions does not appear to influence effectiveness.


Horseshoe-based Bayesian nonparametric estimation of effective population size trajectories.
Phylodynamics is an area of population genetics that uses genetic sequence data to estimate past population dynamics. Modern state-of-the-art Bayesian nonparametric methods for recovering population size trajectories of unknown form use either change-point models or Gaussian process priors. Change-point models suffer from computational issues when the number of change-points is unknown and needs to be estimated. Gaussian process-based methods lack local adaptivity and cannot accurately recover trajectories that exhibit features such as abrupt changes in trend or varying levels of smoothness. We propose a novel, locally adaptive approach to Bayesian nonparametric phylodynamic inference that has the flexibility to accommodate a large class of functional behaviors. Local adaptivity results from modeling the log-transformed effective population size a priori as a horseshoe Markov random field, a recently proposed statistical model that blends together the best properties of the change-point and Gaussian process modeling paradigms. We use simulated data to assess model performance, and find that our proposed method results in reduced bias and increased precision when compared to contemporary methods. We also use our models to reconstruct past changes in genetic diversity of human hepatitis C virus in Egypt and to estimate population size changes of ancient and modern steppe bison. These analyses show that our new method captures features of the population size trajectories that were missed by the state-of-the-art methods.


[Clinical significance of arrhythmia in patients with hypertension].
Cardiac arrhythmias were studied in patients with essential hypertension in relation to their myocardial function. It was found that the arrhythmias occurring in the early period of the disease (borderline hypertension, Stage I hypertension) were primarily functional and affected the course of the disease and hemodynamics to a small degree. The life-threatening arrhythmias recorded in early hypertension were more commonly caused by mitral prolapse. The duration and severity of hypertension, development of left ventricular myocardial hypertrophy, myocardial fiber distension in relative heart failure play a decisive role in the development of cardiac arrhythmias in patients with Stage II hypertensive disease. It is essential to make comprehensive clinical and instrumental studies to clarify the genesis of the arrhythmic syndrome and to correctly choose the management policy in these patients.


Major ecosystems in China: dynamics and challenges for sustainable management.
Ecosystems, though impacted by global environmental change, can also contribute to the adaptation and mitigation of such large scale changes. Therefore, sustainable ecosystem management is crucial in reaching a sustainable future for the biosphere. Based on the published literature and publicly accessible data, this paper discussed the status and trends of forest, grassland, and wetland ecosystems in China that play important roles in the ecological integrity and human welfare of the nation. Ecological degradation has been observed in these ecosystems at various levels and geographic locations. Biophysical (e.g., climate change) and socioeconomic factors (e.g., intensive human use) are the main reasons for ecosystem degradation with the latter factors serving as the dominant driving forces. The three broad categories of ecosystems in China have partially recovered from degradation thanks to large scale ecological restoration projects implemented in the last few decades. China, as the largest and most populated developing nation, still faces huge challenges regarding ecosystem management in a changing and globalizing world. To further improve ecosystem management in China, four recommendations were proposed, including: (1) advance ecosystem management towards an application-oriented, multidisciplinary science; (2) establish a well-functioning national ecological monitoring and data sharing mechanism; (3) develop impact and effectiveness assessment approaches for policies, plans, and ecological restoration projects; and (4) promote legal and institutional innovations to balance the intrinsic needs of ecological and socioeconomic systems. Any change in China's ecosystem management approach towards a more sustainable one will benefit the whole world. Therefore, international collaborations on ecological and environmental issues need to be expanded.


Model-based traction force microscopy reveals differential tension in cellular actin bundles.
Adherent cells use forces at the cell-substrate interface to sense and respond to the physical properties of their environment. These cell forces can be measured with traction force microscopy which inverts the equations of elasticity theory to calculate them from the deformations of soft polymer substrates. We introduce a new type of traction force microscopy that in contrast to traditional methods uses additional image data for cytoskeleton and adhesion structures and a biophysical model to improve the robustness of the inverse procedure and abolishes the need for regularization. We use this method to demonstrate that ventral stress fibers of U2OS-cells are typically under higher mechanical tension than dorsal stress fibers or transverse arcs.


Prediction of serotonergic treatment efficacy using age of onset and Type A/B typologies of alcoholism.
Previously, we reported that ondansetron was efficacious at treating early-onset (< or =25-years old) but not late-onset (> or =26-years old) alcoholics in a double-blind, randomized, placebo-controlled clinical trial (n = 321 enrolled patients, 271 of them randomized). Randomized participants underwent 11 weeks of treatment with ondansetron (1, 4, or 16 microg/kg twice daily; n = 67, 77, and 71, respectively) or identical placebo (n = 56), plus weekly standardized group cognitive behavioral therapy. For this study, we reanalyzed the original sample to determine whether the Type A/B typological classification predicts ondansetron treatment response. In this comparative analysis, k-means clustering was applied to 19 baseline measures of drinking behavior, psychopathology, and social functioning, similar to those used by Babor in the original typological derivation. A 2-factor solution described robustly 2 groups phenomenologically consistent with Type A/B classification. Subjects were subdivided into early- and late-onset alcoholics. Seventy-two percent of Type B subjects had early-onset alcoholism (EOA); 67% of Type A subjects had late-onset alcoholism (LOA). The A/B typology better discriminated 2 clusters based upon baseline severity of alcoholism. There was a significant effect (p < 0.05) for Type B alcoholics to respond to ondansetron (4 microg/kg); however, Type A alcoholics receiving ondansetron showed no beneficial effect. Early-onset vs. late-onset classification predicted ondansetron response substantially better than Type A/B classification, which did not add to the prediction of treatment outcome. Further analyses showed that ondansetron was effective in the 33% of Type A alcoholics with EOA but ineffective in the 28% of Type B alcoholics with LOA. Type A/B classification best discriminates alcoholic subtypes based upon baseline severity. Early- vs. late-onset classification is, however, a better predictor of response to ondansetron treatment because it might be more closely related to fundamental neurobiological processes associated with the underlying pathophysiology of alcoholism.


[Direct determination of lead in urine with a new micro-method of flame atomic absorption spectroscopy (loop-AAS) (author's transl)].
This paper describes a method for the direct determination of lead in urine using the newly developed loop AAS. In this technique, the sample to be analyzed is dried outside the flame on an electrically heated iridium loop. The loop is introduced into the flame of an AA-spectrometer by a precise transport mechanism. The detection limits of slightly and medium volatile elements are one or two orders of magnitude lower than those of conventional flame-AAS. By using an additional ceramic stagnation tube arranged in the flame, the power of detection is increased once more by about a factor 10. The high chemical resistance of iridium permits the use of strong acids for decomposition of the urine directly on the loop. The relative standard deviation is about 0.04 for a lead concentration of 90 micrograms/l. The detection limits are 3 to 10 micrograms/l depending on the AA-spectrometer used. The accuracy of the method is controlled by the analysis of control urine and by analyzing the same samples by graphite furnace-AAS.


Effects of Vibration on Leg Blood Flow After Intense Exercise and Its Influence on Subsequent Exercise Performance.
This study aimed to determine the effects of vibration on leg blood flow after intense exercise and find out whether or not these effects can influence subsequent maximal exercise performance. Twenty-three participants performed an exercise test-to-exhaustion followed by a recovery period using six 1-minute sets of whole-body vibration (WBV; 25 Hz-4 mm) or a passive control (noWBV; 0 Hz-0 mm) in the seated position on separate days in random order. Blood flow was assessed at baseline and during each 1-minute interset rest periods post-WBV and noWBV. Thereafter, participants performed a cycle-ergometer test, and time to exhaustion and total distance covered (TDC) were recorded. During recovery, a similar trend was observed in both systolic and diastolic peak frequency dynamics in both conditions. The pulsatility index decreased (p < 0.01) from baseline during postbout 1 in both trials and during post-4 and post-5 in the WBV trial. Significant between-group differences were observed during post-4 (p ≤ 0.05) with greater decreases in pulsatility index after WBV compared with noWBV. Time to exhaustion and TDC were higher after WBV compared with noWBV. In conclusion, WBV decreased pulsatility index in the popliteal artery after maximal exercise and was effective to increase performance in a later exercise test-to-exhaustion.


Nanomedicine for Intranasal Delivery to Improve Brain Uptake.
Intranasal drug delivery system provides distinct advantage over conventional drug delivery system for a drug that is pharmacokenetically or biologically unstable. Major concern for the treatment of central nervous system diseases is, low concentration of therapeutically active molecule within brain as blood brain barrier is creating obstacle, where intranasal drug delivery provides direct transport of therapeutically active moiety into brain via olfactory or trigeminal pathway. Nasal mucosa provides distinct advantages like improved bioavailability, law dose and quick onset of action and high patient compliance, and the major disadvantage is residence time of drug and irreversible entrapment of drug. This article provides anatomical and physiological information about nasal route and various factors. Article discusses various types of nanoparticles used intranasally and moreover article also emphasizes patents, formulation under development and some.


Anticancer Activities of 9-chloro-6-(piperazin-1-yl)-11H-indeno[1,2-c] quinolin-11-one (SJ10) in Glioblastoma Multiforme (GBM) Chemoradioresistant Cell Cycle-Related Oncogenic Signatures.
Current anticancer treatments are inefficient against glioblastoma multiforme (GBM), which remains one of the most aggressive and lethal cancers. Evidence has shown the presence of glioblastoma stem cells (GSCs), which are chemoradioresistant and associated with high invasive capabilities in normal brain tissues. Moreover, accumulating studies have indicated that radiotherapy contributes to abnormalities in cell cycle checkpoints, including the G1/S and S phases, which may potentially lead to resistance to radiation. Through computational simulations using bioinformatics, we identified several GBM oncogenes that are involved in regulating the cell cycle. Cyclin B1 (CCNB1) is one of the cell cycle-related genes that was found to be upregulated in GBM. Overexpression of CCNB1 was demonstrated to be associated with higher grades, proliferation, and metastasis of GBM. Additionally, increased expression levels of CCNB1 were reported to regulate activation of mitogen-activated protein kinase 7 (MAPK7) in the G2/M phase, which consequently modulates mitosis; additionally, in clinical settings, MAPK7 was demonstrated to promote resistance to temozolomide (TMZ) and poor patient survival. Therefore, MAPK7 is a potential novel drug target due to its dysregulation and association with TMZ resistance in GBM. Herein, we identified MAPK7/extracellular regulated kinase 5 (ERK5) genes as being overexpressed in GBM tumors compared to normal tissues. Moreover, our analysis revealed increased levels of the cell division control protein homolog (CDC42), a protein which is also involved in regulating the cell cycle through the G1 phase in GBM tissues. This therefore suggests crosstalk among CCNB1/CDC42/MAPK7/cluster of differentiation 44 (CD44) oncogenic signatures in GBM through the cell cycle. We further evaluated a newly synthesized small molecule, SJ10, as a potential target agent of the CCNB1/CDC42/MAPK7/CD44 genes through target prediction tools and found that SJ10 was indeed a target compound for the above-mentioned genes; in addition, it displayed inhibitory activities against these oncogenes as observed from molecular docking analysis.


Phenotypic quality influences fertility in Gombe chimpanzees.
1. Fertility is an important fitness component, but is difficult to measure in slowly reproducing, long-lived animals such as chimpanzees (Pan troglodytes). 2. We measured fertility and the effect of measured covariates on fertility in a 43-year sample of birth intervals of chimpanzees from the Gombe National Park, Tanzania using Cox proportional hazards regression with individual-level random effects. 3. The birth hazard declined with mothers' age at a rate of 0·84 per year following age at first reproduction. This value is somewhat stronger than previous estimates. 4. Loss of the infant that opened the birth interval increased the birth hazard 134-fold. 5. Birth intervals following the first complete birth interval were shorter than this first interval, while sex of the previous infant had no significant effect. 6. Maternal dominance rank was significant at the P < 0·1 level when coded as high/middle/low but was highly significant when we simply considered high rank vs. others. 7. Individual heterogeneity had a substantial impact on birth interval duration. We interpret this individual effect as a measure of phenotypic quality, controlling for the measured covariates such as dominance rank. This interpretation is supported by the correlation of individual heterogeneity scores with similar independent measures of body mass.


Secondary Analysis of Existing Data Sets for Developmental Behavioral Pediatrics.
Secondary analysis of existing large, national data sets is a powerful method to address many of the complex, key research questions in developmental behavioral pediatrics (DBP). Major advantages include decreasing the time needed to complete a study and reducing expenses associated with research by eliminating the need to collect primary data. It can also increase the generalizability of research and, with some data sets, provide national estimates that may form the basis for developing policy. However, few resources are available to direct researchers who seek to develop expertise in this area. This study aims to guide investigators with limited experience in this area who wish to improve their skills in performing secondary analysis of existing large data sets. This study provides direction on the steps to perform secondary analysis of existing data sets. It describes where and how data sets can be identified to answer questions of interest to DBP. Finally, it offers an overview of a number of data sets relevant to DBP.


Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-thienyl)pyrazoline derivatives.
In this study, the synthesis of twelve 3-(2-thienyl)pyrazoline derivatives are described. The structures of all compounds were confirmed by UV, IR, (1)H-NMR, mass spectral data, and microanalyses. In the pharmacological studies, antidepressant and anticonvulsant activities of these compounds have been screened. The antidepressant activities of the compounds were investigated by Porsolt's behavioral despair test (forced swimming) on albino mice and compared with tranylcypromine. Among the compounds examined, the compounds 9 and 12 showed significant antidepressant activity. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (metrazol) (scMet.) tests, neurotoxicities were determined by rotarod toxicity test on albino mice. Compound 8 was found to be protective against MES in the range of 30-300 mg/kg dose levels at four hours. None of the synthesized compounds showed neurotoxicity at 30-300 mg/kg dose levels.


Can exercise regulate the circadian system of adolescents? Novel implications for the treatment of delayed sleep-wake phase disorder.
Adolescents are vulnerable to inadequate sleep due to a unique constellation of risk factors. In particular, the puberty-related phase delay in the timing of the circadian system postpones the onset of sleep. Resultantly, disordered sleep is common among teenagers and young adults, with the most common sleep problem being delayed sleep wake-phase disorder (DSWPD). Although current treatments for DSWPD show promise, novel ways to improve our youth's sleep are needed. The purpose of this review is to critically evaluate the evidence for the role of exercise as a method to shift and/or regulate circadian timing, and thus improve sleep, in adolescents and young adults. A growing body of evidence suggests that nocturnal exercise can delay circadian timing. However, exercise administered at different times of the 24-h day may result in phase advances, particularly when the timing of exercise is gradually advanced in small daily increments. The implications of these results for young people's sleep health are discussed and suggestions are provided for ways that exercise could be used clinically, to improve the treatment of DSWPD.


Estimating missing heritability for disease from genome-wide association studies.
Genome-wide association studies are designed to discover SNPs that are associated with a complex trait. Employing strict significance thresholds when testing individual SNPs avoids false positives at the expense of increasing false negatives. Recently, we developed a method for quantitative traits that estimates the variation accounted for when fitting all SNPs simultaneously. Here we develop this method further for case-control studies. We use a linear mixed model for analysis of binary traits and transform the estimates to a liability scale by adjusting both for scale and for ascertainment of the case samples. We show by theory and simulation that the method is unbiased. We apply the method to data from the Wellcome Trust Case Control Consortium and show that a substantial proportion of variation in liability for Crohn disease, bipolar disorder, and type I diabetes is tagged by common SNPs.


[The nature of the luminescence of the heliomycin producer Actinomyces enissus].
Luminescence of Actinomyces enissus synthesizing heliomycin is caused by the action of UV; it is multicoloured, mosaic, and changes in the course of growth. Multicoloured luminescence is due to formation of substances with various colours of luminescence (antibiotics heliomycin and resistoflavin, coproporphyrins I and III, riboflavin, etc.); its mosaic character is caused by the presence in the population of variants with difference in the component composition of luminescent substances and the degree of differentiation of colonies.


Dietary intake of n-3 long-chain polyunsaturated fatty acids and risk of myocardial infarction in coronary artery disease patients with or without diabetes mellitus: a prospective cohort study.
A beneficial effect of a high n-3 long-chain polyunsaturated fatty acid (LCPUFA) intake has been observed in heart failure patients, who are frequently insulin resistant. We investigated the potential influence of impaired glucose metabolism on the relation between dietary intake of n-3 LCPUFAs and risk of acute myocardial infarction (AMI) in patients with coronary artery disease. This prospective cohort study was based on the Western Norway B-Vitamin Intervention Trial and included 2,378 patients with coronary artery disease with available baseline glycosylated hemoglobin (HbA1c) and dietary data. Patients were sub-grouped as having no diabetes (HbA1c <5.7%), pre-diabetes (HbA1c ≥5.7%), or diabetes (previous diabetes, fasting baseline serum glucose ≥7.0, or non-fasting glucose ≥11.1 mmol/L). AMI risk was evaluated by Cox regression (age and sex adjusted), comparing the upper versus lower tertile of daily dietary n-3 LCPUFA intake. The participants (80% males) had a mean age of 62 and follow-up of 4.8 years. A high n-3 LCPUFA intake was associated with reduced risk of AMI (hazard ratio 0.38, 95%CI 0.18, 0.80) in diabetes patients (median HbA1c = 7.2%), whereas no association was observed in pre-diabetes patients. In patients without diabetes a high intake tended to be associated with an increased risk (hazard ratio1.45, 95%CI 0.84, 2.53), which was significant for fatal AMI (hazard ratio 4.79, 95%CI 1.05, 21.90) and associated with lower HbA1c (mean ± standard deviation 4.55 ±0.68 versus 4.92 ±0.60, P = 0.02). No such differences in HbA1c were observed in those with pre-diabetes or diabetes. A high intake of n-3 LCPUFAs was associated with a reduced risk of AMI, independent of HbA1c, in diabetic patients, but with an increased risk of fatal AMI and lower HbA1c among patients without impaired glucose metabolism. Further studies should investigate whether patients with diabetes may benefit from having a high intake of n-3 LCPUFAs and whether patients with normal glucose tolerance should be careful with a very high intake of these fatty acids. This trial is registered at clinicaltrials.gov as NCT00354081.


Stretching vibrational frequencies and pKa differences in H-bond networks of protein environments.
The experimentally measured stretching vibrational frequencies of O-D [νO-D(donor)] and C=O [νC=O(donor)] H-bond donor groups can provide valuable information about the H-bonds in proteins. Here, using a quantum mechanical/molecular mechanical approach, the relationship between these vibrational frequencies and the difference in pKa values between H-bond donor and acceptor groups [ΔpKa(donor … acceptor)] in bacteriorhodopsin and photoactive yellow protein environments was investigated. The results show that νO-D(donor) is correlated with ΔpKa(donor … acceptor), regardless of the specific protein environment. νC=O(donor) is also correlated with ΔpKa(donor … acceptor), although the correlation is weak because the C=O bond does not have a proton. Importantly, the shifts in νO-D(donor) and νC=O(donor) are not caused by changes in pKa(donor) alone, but rather by changes in ΔpKa(donor … acceptor). Specifically, a decrease in ΔpKa(donor … acceptor) can lead to proton release from the H-bond donor group toward the acceptor group, resulting in shifts in the vibrational frequencies of the protein environment. These findings suggest that changes in the stretching vibrational frequencies, in particular νO-D(donor), can be used to monitor proton transfer in protein environments.


Reduced surface runoff losses of metolachlor in narrow-row compared to wide-row soybean.
Cultural management practices that reduce the off-site transport of herbicides applied to row crops are needed to protect surface water quality. A soybean [Glycine max (L.) Merr.] field study was conducted near Stoneville, MS on Sharkey clay to evaluate row spacing (50 cm vs. 100 cm) effects on metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(methoxy-1-methylethyl) acetamide] transport. One day after the foliar application of metolachlor to 2.03 m wide by 2.43 m long plots, 60 mm h(-1) of simulated rainfall was applied until 25 min of runoff was generated per plot. The calculated mass of metolachlor intercepted by the soybean foliage was greater in narrow-row than wide-row soybean, 0.39 kg ha(-1) vs. 0.23 kg ha(-1), respectively. Field and laboratory studies indicated that less than 2% of the metolachlor intercepted by the soybean foliage was available for foliar wash-off 1 d after application. Antecedent soil water content at the start of the simulations was lower in narrow-row soybean. In turn, there was a 1.7-fold greater time to runoff on narrow-row plots. The greater time to runoff likely contributed to lower metolachlor concentration in runoff from narrow-row plots. Cumulative metolachlor losses were significantly greater in wide-row than narrow-row soybean, 3.7% vs. 2.2%, respectively. Findings indicate that narrow-row planting systems may reduce metolachlor runoff following a post-emergence application.


Multiple pathways mediate the sex-peptide-regulated switch in female Drosophila reproductive behaviours.
Male-derived sex-peptide (SP) induces profound changes in the behaviour of Drosophila females, resulting in decreased receptivity to further mating and increased egg laying. SP can mediate the switch in female reproductive behaviours via a G protein-coupled receptor, SPR, in neurons expressing fruitless, doublesex and pickpocket. Whether SPR is the sole receptor and whether SP induces the postmating switch in a single pathway has not, to our knowledge been tested. Here we report that the SP response can be induced in the absence of SPR when SP is ectopically expressed in neurons or when SP, transferred by mating, can access neurons through a leaky blood brain barrier. Membrane-tethered SP can induce oviposition via doublesex, but not fruitless and pickpocket neurons in SPR mutant females. Although pickpocket and doublesex neurons rely on G(o) signalling to reduce receptivity and induce oviposition, G(o) signalling in fruitless neurons is required only to induce oviposition, but not to reduce receptivity. Our results show that SP's action in reducing receptivity and inducing oviposition can be separated in fruitless and doublesex neurons. Hence, the SP-induced postmating switch incorporates shared, but also distinct circuitry of fruitless, doublesex and pickpocket neurons and additional receptors.


Tuberculosis-Diagnostic Expert System: an architecture for translating patients information from the web for use in tuberculosis diagnosis.
Over 1.5-2 million tuberculosis deaths occur annually. Medical professionals are faced with a lot of challenges in delivering good health-care with unassisted automation in hospitals where there are several patients who need the doctor's attention. To automate the pre-laboratory screening process against tuberculosis infection to aid diagnosis and make it fast and accessible to the public via the Internet. The expert system we have built is designed to also take care of people who do not have access to medical experts, but would want to check their medical status. A rule-based approach has been used, and unified modeling language and the client-server architecture technique were applied to model the system and to develop it as a web-based expert system for tuberculosis diagnosis. Algorithmic rules in the Tuberculosis-Diagnosis Expert System necessitate decision coverage where tuberculosis is either suspected or not suspected. The architecture consists of a rule base, knowledge base, and patient database. These units interact with the inference engine, which receives patient' data through the Internet via a user interface. We present the architecture of the Tuberculosis-Diagnosis Expert System and its implementation. We evaluated it for usability to determine the level of effectiveness, efficiency and user satisfaction. The result of the usability evaluation reveals that the system has a usability of 4.08 out of a scale of 5. This is an indication of a more-than-average system performance. Several existing expert systems have been developed for the purpose of supporting different medical diagnoses, but none is designed to translate tuberculosis patients' symptomatic data for online pre-laboratory screening. Our Tuberculosis-Diagnosis Expert System is an effective solution for the implementation of the needed web-based expert system diagnosis.


Depression, health-related quality of life, and medical cost outcomes of receiving recommended levels of antidepressant treatment.
We evaluated depression severity, health-related quality of life (HRQL), and medical cost outcomes of primary care patients receiving recommended and less-than-recommended levels of antidepressant treatment. We performed a secondary analysis of clinical trial data from primary care clinics in a staff-model managed care organization. The trial included patients with Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for major depression who were starting antidepressant treatment. The primary outcomes measures used were the 17-item Hamilton Depression Rating Scale (HDRS), Hopkins Symptom Checklist depression scores, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) mental and physical component summary scores, and the total outpatient and inpatient medical costs. Of 358 patients starting antidepressant treatment, 195 (54.5%) received doses recommended by the Agency for Health Care Policy and Research for 90 days or more. Mean HDRS score decreased from 14.1 to 8.8 in patients receiving less-than-recommended treatment and decreased from 13.8 to 8.9 in patients with minimum recommended treatment (P = .761). No significant differences in improvement of HRQL outcomes during 6 months were observed between patients receiving recommended or less-than-recommended antidepressant therapy. Mean total medical costs over 6 months for patients taking the recommended levels of antidepressant treatment were $1872 +/- 140 compared with $2622 +/- 413 for patients taking less-than-recommended treatment (P = .032). The differences in total medical costs were attributable to significantly lower nonmental health-related inpatient costs in the recommended antidepressant treatment group ($104 vs $785, P = .004). Patients receiving minimum recommended levels of antidepressant therapy for 3 months showed improvement in depression severity and HRQL comparable with patients receiving less-than-recommended treatment. Patients receiving minimum recommended treatment had lower total costs and nonmental health-related inpatient costs. Antidepressant treatment in primary care patients may have the greatest impact on the frequency of health care visits and on costs for medical conditions and impairments.


A survey of Brugia malayi infection on the Heugsan Islands, Korea.
Lymphatic filariasis due to Brugia malayi infection was endemic in several areas of South Korea. The infection was controlled, or disappeared, in most areas, with the exception of the remote southwestern islands of Jeonranam-do, including the Heugsan Islands. To discover its current situation, a small-scale survey was performed on the Heugsan Islands in September 2000. A total of 378 people, 151 male and 227 female, living in 8 villages (6 on Daeheugsan-do, 1 on Daejang-do, and 1 on Yeongsan-do) were subjected to a night blood survey for microfilaremia, and physical examination for elephantiasis on the extremities. There were 6 (1.6%) microfilaria positive cases, all in females aged 57-72 years, and from only two villages of the Daeheugsan-do area. There were 4 patients with lower leg elephantiasis, but they showed no microfilaremia. The results show that a low-grade endemicity of filariasis remains on the Daeheugsan-do.


Risk behaviors and self-reported illnesses among Pacific Northwest surfers.
Although surfers have high incidental exposure to marine waters, no studies have investigated if surfer risk behaviors (such as surfing during advisories, near an outfall, during a rain event, or use of personal protective equipment) increase or decrease the risk of acquiring waterborne illnesses. We used a web-based survey to assess the association between risk-based behaviors and self-reported illnesses among Pacific Northwest surfers. Commonly reported illnesses include: ear infection or discharge (38%), sore throat or a cough (28%), diarrhea (16%), fever (10.5%), and vomiting (7%). Surfing often during rain events was associated with an increased likelihood of diarrhea (OR = 2.7; 95% CI: 1.4-5.47), sore throat (OR = 1.26; 95% CI: 1.01-2.05), and ear infection (OR = 1.39; 95% CI: 1.01-2.32). Surfing during a health advisory was associated with increased likelihood of diarrhea (OR = 1.94; 95% CI: 1.03-4.64) and sore throat (OR = 2.32; 95% CI: 1.23-4.40). Other behaviors associated with increased illnesses include body surfing, surfing near an outfall, frequency of surfing, and use of ear plugs. Approximately 40% of surfers were unaware if they had surfed during an active health advisory and 29% knowingly surfed during advisories, suggesting the need to engage this population about potential harm and behaviors that may increase health risk.


Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone.
The effect of long-term administration of analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin on the growth of the growth hormone (GH)- and prolactin (PRL)-secreting rat pituitary GH3 tumor was investigated. Daily administration of [D-Trp6]LH-RH (50 micrograms/day), early after inoculation of the GH3 tumor, inhibited tumor growth by more than 90% as compared to controls. Similarly, in two experiments, a single once-a-month injection of long-acting [D-Trp6]LH-RH microcapsules (in a dose calculated to release about 25 micrograms/day for 30 days) inhibited the growth of GH3 pituitary tumor by more than 50% 6 or 13 wk after transplantation, when the tumors were fully developed. Serum GH and PRL levels also were reduced markedly by treatment with [D-Trp6]LH-RH. On the other hand, the administration of an antagonistic analog of LH-RH, N-Ac-[D-Phe(4Cl)1,2, D-Trp3, D-Arg6, D-Ala10]LH-RH, did not significantly reduce the growth of this tumor, and the treatment with two different analogs of somatostatin, cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr NH2, appeared to enhance it. These results are in agreement with previous findings of growth inhibition of 7315a pituitary tumors with different hormone-secreting characteristics by agonistic analogs of LH-RH. The collective data from experimental work with rat pituitary tumor models support the contention that the use of [D-Trp6]LH-RH might be considered for the treatment of some patients with pituitary tumors who failed to respond to conventional therapy.


Plasmacytoid dendritic cell recruitment by immobilized CXCR3 ligands.
Plasmacytoid dendritic cells (pDCs) recognize microbes, viruses in particular, and provide unique means of innate defense against them. The mechanism of pDC tissue recruitment remained enigmatic because the ligands of CXCR3, the cardinal chemokine receptor on pDCs, have failed to induce in vitro chemotaxis of pDCs in the absence of additional chemokines. In this study, we demonstrate that CXCR3 is sufficient to induce pDC migration, however, by a migratory mechanism that amalgamates the features of haptotaxis and chemorepulsion. To mediate "haptorepulsion" of pDCs, CXCR3 requires the encounter of its cognate ligands immobilized, optimally by heparan sulfate, in a form of a negative gradient. This is the first report of the absolute requirement of chemokine immobilization and presentation for its in vitro promigratory activity. The paradigmatic example of pDC haptorepulsion described here may represent a new pathophysiologically relevant migratory mechanism potentially used by other cells in response to other chemokines.


Cystic fibrosis gene variability in two southern Brazilian Amerindian populations: analysis of the deltaF508 mutation and the KM19 and XV2C haplotypes.
The frequencies of the deltaF508 deletion, the most common cystic fibrosis mutation in Europeans and European-derived populations, and the XV2C and KM19 restriction fragment length polymorphisms that are tightly linked to the CFTR locus vary among populations. To determine the distribution of these extragenic markers and of the deltaF508 mutation, we analyzed 326 chromosomes of individuals from two South American Indian populations, the Guarani and the Kaingang. The allele and haplotype frequencies differed greatly between the two populations as well as among Amerindians and normal European Brazilians and European Brazilian cystic fibrosis patients. The absence of the deltaF508 mutation and the B haplotype are in agreement with the hypothesis that the deltaF508 mutation occurred after the divergence of these two populations. This finding is useful for populations containing a large Amerindian component and helps us to understand the origins of the deltaF508 deletion, the most common cystic fibrosis mutation in Europeans and European-derived populations, as well as the different incidences of cystic fibrosis in continental groups.


Contrast-enhanced MR imaging of malignant brain tumors.
Magnetic resonance (MR) imaging was performed before and serially after intravenous injection of 1 mmol/kg gadolinium-DTPA (Schering) in 17 patients with clinical and histologic diagnosis of malignant cerebral tumors. There was a decrease of 1% in T1 and 10% in T2 in normal white matter and a decrease of 8% in T1 and 14% in T2 in normal gray matter. Contrast enhancement was observed in 16 of the 17 tumors. In the region of maximal enhancement a mean decrease of 16% in T1 was observed in low-grade gliomas, a mean decrease in T1 of 29% was seen in high-malignancy gliomas, and a mean decrease in T1 of 33% was observed in metastases. The decreases in T1 persisted for at least 50 min. In one case the central cystic region of the tumor displayed a decrease in T1 and T2. Measurements of signal intensity displayed maximal contrast enhancement with an IR 1500/500/44 sequence, much less with SE 1500/44, and least with SE 1500/80. Edema was observed on precontrast images in 14 cases, but satisfactory definition of the tumor-edema margin was only possible in four cases. After contrast enhancement this margin was defined in 10 cases. In four of the 17 cases areas of apparent "edema" seen before administration of Gd-DTPA displayed significant contrast enhancement and probably represented tumor infiltration. Comparison with CT showed a greater degree of contrast enhancement on MR images in eight cases, an equal degree in eight cases, and greater enhancement on CT in one case.(ABSTRACT TRUNCATED AT 250 WORDS)


Investigating Diagnostic Value of Ultrasonography in Acute Appendicitis.
Acute appendicitis is one of the most commonly diagnosed surgical diseases that its accurate diagnosis is still a problem, and there is no certainty. Ultrasound is recommended for diagnosis of appendicitis as an easy and noninvasive method. Therefore, due to the spread of disease and the urgent need to accurately diagnose in all educational centers, we decided to determine the diagnostic value of this inclusive method in identifying acute appendicitis. This is a descriptive cross-sectional research that was conducted on 540 patients referring to Educational Center of Ayatollah Kashani Hospital. All individuals suspected to appendicitis, and undergone ultrasound was included in the study, and then the result of ultrasound was compared to the obvious pathological results. Data were entered into statistical software of SPSS 20 and were analyzed. According to the ultrasound findings, appendicitis was diagnosed as negative in 351 ones and positive in 189 ones. Ultrasound sensitivity in the diagnosis of appendicitis was 37.1%, while its specificity was 87.2%. The positive predictive value was 96.8% and the negative predictive value was only 11.7%. Considering very low-negative predictive value in educational centers, it is suggested that ultrasound is done for diagnosis of appendicitis only in complicated cases of appendicitis and differential diagnose (kidney stones, and ovarian cysts). In addition, it is recommended that routine ultrasound be avoided for all patients.


Genomic and epigenomic cross-talks in the regulatory landscape of miRNAs in breast cancer.
MicroRNAs (miRNA) are a class of endogenous, small noncoding RNAs found in animals, plants, and viruses that control their target gene expression posttranscriptionally. They are involved in a wide array of biological processes including cell differentiation, development, cell death and homeostasis, and fine-tune the regulation of these pathways. Their aberrant expressions have been associated with different diseases. These small RNAs are also known to function as oncogenes, oncosupressor genes, modulators of metastatic spread, and regulators of cancer stem cells. Their deregulation is a hallmark of different cancers types including breast cancer. Despite the growing evidence for their involvement in breast cancer, understanding the interplay between miRNAs and their targets leading to the disease remains largely unknown. Here, we provide a comprehensive story on miRNA signatures of breast cancer, miRNAs in breast cancer stem cells, metastamirs (i.e., metastasis regulatory miRNAs), circulating miRNAs as invasive blood-based biomarkers, and oncomiRs and oncosupressor miRNAs associated with breast cancer. Furthermore, we provide biological insights on their regulation by various mechanisms including genomic alterations and demonstration of a complicated feedback network between miRNAs and epigenetic regulators forming an epigenetics-miRNA regulatory circuit whose disruption may underlie the cause of breast cancer.


Modulation of scleral DNA synthesis in development of and recovery from induced axial myopia in the tree shrew.
Visually modulated scleral extracellular matrix remodelling is associated with the development of, and recovery from, induced axial myopia in the tree shrew, a commonly used mammalian model of refractive error development. The involvement of scleral cell proliferation in this process was investigated using [3H] thymidine. Tree shrews were monocularly deprived of pattern vision, using translucent occluders, or the retinal image was optically defocused, using negative lenses, over a period of 5 days. A further group was monocularly deprived for 5 days, then allowed 3 days of binocular recovery. A control group of binocularly open animals was employed to establish normal parameters. On the final day of the experimental period, [3H] thymidine was administered by intraperitoneal injection, then optical and biometric measures were taken and tissue samples collected for assay. Incorporation of [3H] thymidine into cellular DNA was measured in proteinase K digests, following precipitation with trichloroacetic acid. After 5 days, significant amounts of myopia were present in the treated eyes of both form-deprived [-7. 0+/-0.7 Dioptres (D), group mean+/-s.e.m.; P<0.01] and lens-defocused animals (-6.2+/-0.9 D;P<0.01). After 3 days of recovery, 50% of the refractive error had been compensated for, predominantly through shortening of the vitreous chamber in the treated eye. Reduced levels of [3H] thymidine incorporation were observed in sclera from both groups of myopic animals (form-deprived, -34.3+/-9.9%;P<0.05 and lens-defocus, -32.8+/-4.5%;P<0.005). Increased levels of [3H] thymidine incorporation were found in the sclera of recovering animals (+144.0+/-43.2%;P<0.05). The results show that changes in regulation of cell proliferation, during the development of myopia, are visually mediated and inversely related to the direction of change in ocular size. This implies that alterations in the scleral fibroblast population are involved in the modulation of scleral matrix turnover during myopia development.


Clinical progression of high-grade cervical intraepithelial neoplasia: estimating the time to preclinical cervical cancer from doubly censored national registry data.
Little is known about the time span of progression from high-grade cervical intraepithelial neoplasia (CIN2/3) to invasive cervical cancer. Estimation of this duration from longitudinal studies is not permitted, as CIN2/3 should be treated when detected. Cross-sectional data on the age-specific incidence of detected CIN2/3 and cervical cancer cases are readily available in national registries, but these data are difficult to interpret because neither the moment of lesion development nor the onset of invasive cancer is observed. We developed a statistical model for estimating the duration of time between CIN2/3 and preclinical cancer using Dutch national registries for the years 2000-2005. Human papillomavirus (HPV) genotype data were used to separate CIN2/3 and cancer incidences to obtain estimates for HPV-16-positive and HPV-16-negative lesions. The median time from CIN2/3 to cancer was estimated to be 23.5 years (95% confidence interval: 20.8, 26.6), and 1.6% of the lesions progressed to cancer within 10 years. The median duration for HPV-16-positive lesions was similar, but 2.4% of the HPV-16-positive lesions progressed to cancer within 10 years, as compared with 0.6% for HPV-16-negative lesions. Estimated durations of time to cancer are essential for reassessment of the optimal screening interval in light of vaccination and novel screening tests.


The tomato Arp2/3 complex is required for resistance to the powdery mildew fungus Oidium neolycopersici.
The actin-related protein 2/3 complex (Arp2/3 complex), a key regulator of actin cytoskeletal dynamics, has been linked to multiple cellular processes, including those associated with response to stress. Herein, the Solanum habrochaites ARPC3 gene, encoding a subunit protein of the Arp2/3 complex, was identified and characterized. ShARPC3 encodes a 174-amino acid protein possessing a conserved P21-Arc domain. Silencing of ShARPC3 resulted in enhanced susceptibility to the powdery mildew pathogen Oidium neolycopersici (On-Lz), demonstrating a role for ShARPC3 in defence signalling. Interestingly, a loss of ShARPC3 coincided with enhanced susceptibility to On-Lz, a process that we hypothesize is the result of a block in the activity of SA-mediated defence signalling. Conversely, overexpression of ShARPC3 in Arabidopsis thaliana, followed by inoculation with On-Lz, showed enhanced resistance, including the rapid induction of hypersensitive cell death and the generation of reactive oxygen. Heterologous expression of ShARPC3 in the arc18 mutant of Saccharomyces cerevisiae (i.e., ∆arc18) resulted in complementation of stress-induced phenotypes, including high-temperature tolerance. Taken together, these data support a role for ShARPC3 in tomato through positive regulation of plant immunity in response to O. neolycopersici pathogenesis.