Patients' perspective on self-management in the recovery from depression.
Self-management appears to be a promising approach in the case of depression, which helps to stimulate patients' autonomy. However, a good and systematic description of the concept self-management from the patients' perspective, to our knowledge, has not yet been performed. To determine: (i) what strategies patients think they can use themselves to recover from depression, (ii) which main themes of self-management strategies can be detected, and (iii) which of these strategies patients perceive as being most helpful. We used concept mapping to explore the experiences of patients who recently recovered from a depressive episode. Patients generated self-management strategies in focus group discussions. The strategies were clustered on a two-dimensional concept map by a hierarchical cluster analysis. Patients generated 50 strategies that formed eight clusters: (i) proactive attitude towards depression and treatment, (ii) daily life strategies and rules, (iii) explanation of disease to others, (iv) remaining socially engaged, (v) engaging in activities, (vi) structured attention to oneself, (vii) contact with fellow sufferers, and (viii) other. Behavioural and cognitive strategies and a proactive attitude towards treatment were considered as the most helpful. From the patients' perspective, there is a wide range of self-management strategies that they can use - and perceive as helpful- to contribute to their own recovery. Professionals could encourage patients to take an active role in achieving recovery. Further research could open new roads to improve patients' active contributions to current treatments for depression.


Nanoparticles in Clinical Translation for Cancer Therapy.
The advent of cancer therapeutics brought a paradigm shift from conventional therapy to precision medicine. The new therapeutic modalities accomplished through the properties of nanomaterials have extended their scope in cancer therapy beyond conventional drug delivery. Nanoparticles can be channeled in cancer therapy to encapsulate active pharmaceutical ingredients and deliver them to the tumor site in a more efficient manner. This review enumerates various types of nanoparticles that have entered clinical trials for cancer treatment. The obstacles in the journey of nanodrug from clinic to market are reviewed. Furthermore, the latest developments in using nanoparticles in cancer therapy are also highlighted.


Concussion and the autonomic nervous system: An introduction to the field and the results of a systematic review.
Recent evidence suggests that autonomic nervous dysfunction may be one of many potential factors contributing to persisting post-concussion symptoms. This is the first systematic review to explore the impact of concussion on multiple aspects of autonomic nervous system functioning. The methods employed are in compliance with the American Academy of Neurology (AAN) and PRISMA standards. Embase, MEDLINE, PsychINFO, and Science Citation Index literature searches were performed using relevant indexing terms for articles published prior to the end of December 2016. Data extraction was performed by two independent groups, including study quality indicators to determine potential risk for bias according to the 4-tiered classification scheme of the AAN. Thirty-six articles qualified for inclusion in the analysis. Only three studies (one Class II and two Class IV) did not identify anomalies in measures of ANS functioning in concussed populations. The evidence supports the conclusion that it is likely that concussion causes autonomic nervous system anomalies. An awareness of this relationship increases our understanding of the physical impact of concussion, partially explains the overlap of concussion symptoms with other medical conditions, presents opportunities for further research, and has the potential to powerfully inform treatment decisions.


Annual and regional variation in mercury concentrations in wood stork nestlings.
Mercury concentrations were measured in blood, down, and feathers from approximately 300 wood stork nestlings in one South Carolina, USA, and four Georgia, USA, colonies from 1996 to 1999. Coastal nestlings generally had lower mercury concentrations than those from inland colonies. Inter-year differences were also apparent, particularly for coastal colonies, where nestling mercury concentrations were higher in 1998 than in 1997 or 1999. In 1998, a wet winter followed by a dry spring and summer produced ideal freshwater foraging conditions and mercury concentrations in coastal nestlings were higher than during the two dry years. There was little inter-year variation in mercury concentrations in nestlings from inland colonies, as parent storks from these colonies forage exclusively in freshwater habitats regardless of rainfall patterns. These results suggest that greater risk of mercury exposure to nestlings is associated with use of freshwater foraging habitats.


p73 is required for survival and maintenance of CNS neurons.
Here, we show that the p53 family member, p73, is necessary for survival and long-term maintenance of CNS neurons, including postnatal cortical neurons. In p73-/- animals, cortical neuron number is normal at birth but decreases significantly by postnatal day 14 (P14)-P16 because of enhanced apoptosis. This decrease continues into adulthood, when p73-/- animals have approximately one-half as many cortical cells as their wild-type littermates. Cortical neurons express the DeltaNp73alpha protein, and overexpression of DeltaNp73 isoforms rescues cortical neurons from diverse apoptotic stimuli. Thus, DeltaNp73 isoforms are survival proteins in cortical neurons, and their deletion causes a gradual loss of cortical neurons in the weeks and months after birth. This decrease in CNS neuron number in p73-/- animals is not limited to the cortex; facial motor neuron number is decreased, and postnatal development of the olfactory bulb is greatly perturbed. These findings, together with our previous work showing that DeltaNp73 is essential for survival of peripheral sympathetic neurons (Pozniak et al., 2000), indicate that p73 isoforms are essential survival proteins in CNS as well as PNS neurons, and that they likely play a role not only during developmental cell death but also in the long-term maintenance of at least some adult neurons.


Constitutive mutations of the OccR regulatory protein affect DNA bending in response to metabolites released from plant tumors.
OccR is a LysR-type transcriptional regulator of Agrobacterium tumefaciens that positively regulates the octopine catabolism operon of the Ti plasmid and is also an autorepressor. Positive control of the occ genes occurs in response to octopine, a nutrient released from crown gall tumors. OccR binds to a site upstream of the occQ promoter in the presence and absence of octopine. Octopine causes prebound OccR to undergo a conformational change at the DNA binding site that causes changes in footprint length and DNA bending. To determine the roles of these conformational changes in transcriptional activation, we isolated 22 OccR mutants that were able to activate the occQ promoter in the absence of octopine. Thirteen of these mutants contained single amino acid substitutions, and nine contained two base pair changes resulting in two amino acid substitutions, which in most cases acted synergistically. These mutations spanned the entire length of the protein. Most of these mutant proteins in the absence of octopine displayed DNA binding and bending properties characteristic of transcriptionally active OccR-octopine complexes.


Pharmacokinetic and pharmacodynamic analysis of combined chemotherapy with carboplatin and paclitaxel for patients with ovarian cancer.
This study was conducted to assess the utility of pharmacokinetic and pharmacodynamic analyses of carboplatin (CBDCA) and paclitaxel (TAX) employed for chemotherapy in ovarian cancer patients. The pharmacokinetics and pharmacodynamics of chemotherapy with CBDCA and TAX were analyzed in 13 patients with ovarian cancers. The pharmacodynamic model, based on myelosuppression, was assessed in terms of concentrations of free platinum (free-Pt) and TAX in blood samples. TAX (175 mg/m2) was administered intravenously (i.v.) over 3 h, and CBDCA (target area under the concentration curve [AUC], 5 mg/ml x min) over 1 h. Free-Pt and TAX concentrations in blood samples were measured at several time points after administration. The nadirs of both the leukocyte and neutrophil counts correlated significantly with the TAX AUC (AUCtax) and serum albumin level, and the percentage decrease in platelet count (pd-Plt) correlated significantly with AUCtax, free-Pt AUC (AUCpt), and the serum albumin level. A pharmacodynamic model corresponding to the nadirs of leukocytes and neutrophils and to pd-Plt was thus generated. This pharmacodynamic model may allow the ready prediction, from AUCtax, AUCpt, and the serum albumin value, of the degree of myelosuppression with combined CBDCA and TAX chemotherapy.


Resource usage and outcomes in a facilitated discharge service in Christchurch, New Zealand.
To describe the type and level of support provided by a facilitated discharge team to frail older patients discharging from a 113-bed elderly rehabilitation hospital and the outcomes achieved. Prospective data detailing reasons for referral, services provided and retrospective data on outcomes, were obtained to 90 days post discharge on visits to new patients during 21/2/08 to 15/7/08. Seventy-four patients (mean age 82, 58% female) were included. The mean duration of intervention was 19 days with the most common reasons for referral being poor mobility/falls risk, poor cognition, hygiene concerns. The average number of contacts was 6.5. Patients with the highest number of contacts were those referred with patient anxiety/low confidence (7.4), and family concern (8.4). The most common interventions were family contact and management of carer stress, liaison with medical staff. Unplanned readmission (within 90 days) occurred in 32% whereas 12% and 8% were in residential care or had died respectively. Managing the transition from hospital to home for older people requires a large range of interventions, particularly in this highly selected group. Unplanned readmission occurred in a third of this very frail elderly group, yet only 12% needed residential care, suggesting the reasons for readmission could be resolved. Patient or family anxiety resulted in more follow-up visits to patients, and inpatient teams should be mindful of this when planning discharges.


Proton beam writing of Nd:GGG crystals as new waveguide laser sources.
Focused proton beam writing has been utilized to fabricate optical channel waveguides in Nd:GGG crystals. The 1 MeV proton beam irradiation creates a local modified region with positive refractive index changes at the end of the proton trajectory, in which the channel waveguide could confine the light field in a symmetric way. Room-temperature laser emission has been achieved at 1063.7 nm, with absorbed pump power of 61 mW (at 808 nm). The obtained slope efficiency of the Nd:GGG waveguide laser system is as high as 66%, which is, to our best knowledge, the highest value for integrated lasers from ion beam processed channel waveguide systems.


Crystallization and preliminary X-ray diffraction analysis of the fructofuranosidase from Schwanniomyces occidentalis.
Schwanniomyces occidentalis invertase is an extracellular enzyme that releases beta-fructose from the nonreducing termini of various beta-d-fructofuranoside substrates. Its ability to produce 6-kestose by transglycosylation makes this enzyme an interesting research target for applications in industrial biotechnology. The enzyme has been expressed in Saccharomyces cerevisiae. Recombinant and wildtype forms, which showed different glycosylation patterns, were crystallized by vapour-diffusion methods. Although crystallization trials were conducted on both forms of the protein, crystals suitable for X-ray crystallographic analyses were only obtained from the wild-type enzyme. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 105.78, b = 119.49, c = 137.68 angstrom. A diffraction data set was collected using a synchrotron source. Self-rotation function and sedimentation-velocity experiments suggested that the enzyme was dimeric with twofold symmetry.


Metabolic and clinical studies on patients with acromegaly treated with bromocriptine over 22 months.
In twenty-two patients with active acromegaly who were untreated or unsuccessfully operated or irradiated (mean growth hormone (GH) values greater than 4 ng/ml) the following investigations were performed: routine laboratory tests, tomography of pituitary fossa, oral glucose tolerance tests, TRH and other pituitary function tests and GH profiles over 5-10 h before and during bromocriptine treatment with daily doses between 7.5 and 50 mg. In seventeen patients GH was suppressed to less than 50% by bromocriptine, in thirteen of them it was normalized on at least one occasion. A TRH induced GH release was observed in all but two responders to bromocriptine before therapy. This effect of TRH was not blunted during treatment with bromocriptine and also in the two patients with negative tests before therapy a significant GH increase was observed. In no non-responder to bromocriptine was a significant increase of GH after TRH observed. One patient showed a secondary resistance to bromocriptine during a period of treatment with griseofulvin. In the remaining sixteen patients the GH suppression has been consistent for between 3 and 22 months. A single dose of pimozide abolished the bromocriptine effect on GH totally in one patient; in others a slight or no significant effect was observed. Tissue swelling and sweating decreased in all bromocriptine responders and glucose tolerance improved in five patients. In four diabetic patients a partial or full remission of diabetes occurred. Apart from postural hypotension after the first administration in two patients no other severe side effects have been observed. Sella size and the other pituitary functions did not change during the time of the study. It seems that a high percentage of acromegalics may be successfully treated with bromocriptine.


Association of nuts and unhealthy snacks with subclinical atherosclerosis among children and adolescents with overweight and obesity.
The process of atherosclerosis begins early in childhood and usually remains asymptomatic until later in life. Carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis could identify early vascular alterations. Unhealthy snacks consumption is associated with obesity and other CVD risk factors in children and adolescents. The aim of this study is to investigate the association of different snack substitution and cIMT among overweight and obesity children and adolescents. A total of 339 participants aged 6 to 13 years with the body mass index Z score ≥ 1 based on WHO criteria enrolled in this study. We measured food intakes of participants by validate and reliable food frequency questionnaire (FFQ). Carotid intima media thickness was measured in the common carotid artery with high-resolution ultrasonography. After controlling for confounders, intake of nuts had a negative relationship with cIMT (β = 0.135 mm P value = 0.009). Moreover, participants in the last tertile of nuts intake had 59% lower risk of high cIMT in comparison with those who consumed less than 0.64 serving/wk./1000Kcal of nuts (P for trend = 0.010). Substituted of nuts intake with sweet unhealthy snacks had a negative relationship with cIMT (β = 0.15 mm). There was no other significant association between energy-dense nutrient-poor solid snacks and cIMT. Our findings emphasize the impact of nuts consumption as a healthy snack on subclinical stages atherosclerosis. Clinical trial studies could examine the effect of different kinds of nuts consumption on cIMT and complications of CVD risk factors.


[Lymphatic involvement in postphlebitic disease].
Veins and lymph ducts are closely linked anatomically, embryologically and physiologically. It is therefore not surprising that such a close relationship should reemerge in the pathology of each. Post-phlebitic disorders provide a classic example of this. Microlymphography, using fluorescence, and isotopic phlebolymphography produce positive, unequivocable arguments for the contribution of lymph to the genesis of post-phlebitic disorders; these methods are better than direct lymphology which is technically difficult and not altogether without its dangers. These findings should, of course, have bearing on therapy.


Carbon nanotube photo-thermo-mechanical actuator.
Carbon nanotubes show a remarkable tendency for direct (rapid) temperature increase of the order of hundreds of degrees when exposed to near infra-red light. The reason is local confinement of the heat wave in their 1D structure which generates rapid temperature rise. Here we demonstrate that these high temperatures can be exploited to generate large deformation and force output by anchoring the nanotubes to a substrate. We report energy density (i.e., work done per unit mass) of the nanotube actuator as approximately 4268 J/Kg which is significantly larger than piezoceramic (approximately 4.25 J/Kg), magnetostrictive (approximately 21.6 J/Kg), lead-zinc-niobate/lead-titanate single-crystals (approximately 131 J/Kg), polyvinylidene fluoride trifluoro-ethylene copolymers (approximately 160 J/Kg) and shape memory alloys (approximately 1337 J/Kg).


Expression of the neuroprotective protein aryl hydrocarbon receptor nuclear translocator 2 correlates with neuronal stress and disability in models of multiple sclerosis.
Axonal degeneration and neuronal loss have been described as the major causes of irreversible clinical disability in multiple sclerosis (MS). The aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) protein has been associated with neuroprotection in models of ischemia and neuronal responses to stressors. To characterize its potential to influence inflammatory neurodegeneration, we examined ARNT2 expression in the experimental autoimmune encephalomyelitis (EAE) model of MS and characterized mediators that influence ARNT2 expression as well as plausible partners and targets. Arnt2 message and protein levels dropped significantly in EAE spinal cords as disease developed and were lowest at peak disability. ARNT2 expression is prominent in neuronal cell bodies within the gray matter with some staining in glial fibrillary acidic protein (GFAP)+ astrocytes in healthy animals. At peak disease, ARNT2 expression is reduced by 20-50% in gray matter neurons compared to healthy controls. ARNT2 intensity in neurons throughout the EAE spinal cord correlated inversely with the degree of immune cell infiltration (r = - 0.5085, p < 0.01) and axonal damage identified with SMI32 staining (r = - 0.376, p = 0.032). To understand the relationship between ARNT2 expression and neuronal health, we exposed enriched cortical cultures of neurons to hydrogen peroxide (H2O2) to mimic oxidative stress. H2O2 at lower doses rapidly increased ARNT2 protein levels which returned to baseline within 3-4 h. Exposure to higher doses of H2O2) dropped ARNT2 levels below baseline, preceding cytotoxicity measured by morphological changes and lactate dehydrogenase release from cells. Decreases in ARNT2 secondary to staurosporine and H2O2 preceded increases in cleaved caspase 3 and associated apoptosis. We also examined expression of neuronal pas 4 (Npas4), whose heterodimerization with ARNT2 drives expression of the neurotrophic factor brain-derived neurotrophic factor (Bdnf). Like ARNT2, Npas4 levels also decline at the onset of EAE and are linked to decreases in Bdnf. In vitro, H2O2 exposure drives Npas4 expression that is tied to increases in Bdnf. Our data support ARNT2 as a neuronal transcription factor whose sustained expression is linked to neuronal and axonal health, protection that may primarily be driven through its partnering with Npas4 to influence BDNF expression.


(Metallo)porphyrins for potential materials science applications.
The bottom-up approach to replace existing devices by molecular-based systems is a subject that attracts permanently increasing interest. Molecular-based devices offer not only to miniaturize the device further, but also to benefit from advanced functionalities of deposited molecules. Furthermore, the molecules itself can be tailored to allow via their self-assembly the potential fabrication of devices with an application potential, which is still unforeseeable at this time. Herein, we review efforts to use discrete (metallo)porphyrins for the formation of (sub)monolayers by surface-confined polymerization, of monolayers formed by supramolecular recognition and of thin films formed by sublimation techniques. Selected physical properties of these systems are reported as well. The application potential of those ensembles of (metallo)porphyrins in materials science is discussed.


Stress and coping on the home front: guard and reserve spouses searching for a new normal.
During deployment of National Guard or reserve troops to Iraq or Afghanistan, spouses on the home front have been largely invisible to our collective consciousness. A total of 18 spouses living in rural Wisconsin were interviewed to identify sources of stress and coping strategies. Stressors varied from predeployment through postdeployment, as did coping responses. During predeployment, spouses articulated that the primary stressor was their lives being "on hold." During deployment, five stressors summarize the experience: worrying, waiting, going it alone, pulling double duty, and loneliness. Communication technology made it possible for most spouses to stay in touch using telephone, e-mail, or even Webcam. Keeping busy-managing personal, family, and household responsibilities-was the most commonly identified coping strategy. Postdeployment was a period of adjustment while couples searched for a new normal. Throughout all deployment phases, skilled and astute nurses can assist families toward health and healing.


The effects of sildenafil in maternal and fetal outcomes in pregnancy: A systematic review and meta-analysis.
The number of studies associating the use of sildenafil in gestation is increasing. This drug inhibits phosphodiesterase type 5 (PDE5), an enzyme responsible for degradation of nitric oxide, and its efficacy is greater in the placental territory, as the maternal side of the placenta have more PDE5 than other sites. For this reason, promising results have been observed related to the prevention of preeclampsia and intrauterine growth restriction and to improvement of maternal-fetal morbidity in cases of placental insufficiency. To evaluate the benefits of using sildenafil in pregnancy. MEDLINE, ClinicalTrials.gov, Embase, LILACS and Cochrane databases were searched through September 2018. There was no restriction in language or year of publication. This study was registered in PROSPERO (CRD42017060288). Randomized clinical trials which used sildenafil for treatment or prevention of obstetric diseases compared with placebo were selected. The results were obtained using the inverse variance method for continuous variables and Man-Whitney for categorical variables. Among a population of 598 pregnant women from the seven clinical trials included, 139 had pre-eclampsia, 275 had intrauterine growth restriction, and 184 had oligohydramnios. A significant increase of 222.58 grams [27.75 to 417.41] was observed in the fetal weight at birth of patients taking sildenafil. The other outcomes did not show any statistical significance. This may be due to the small number of patients used in each study and the great heterogeneity between the groups. Sildenafil could be associated with increasing fetal weight at birth in placental insufficiency despite the limitations of this meta-analysis, even though more studies in this field are needed to introduce this drug into obstetric clinical practice.


5'-untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder.
Recently the molecular genetic basis of attention-deficit hyperactivity disorder (ADHD) has been the focus of a number of studies with the majority of these investigating the role of dopamine system genes. A great deal of attention has been focused on the possible involvement of the dopamine D4 receptor gene (DRD4) following a report of an association of ADHD with the allele containing seven copies of the 48-bp repeat in the third exon. In this paper we extended the search for the molecular explanation for the observed association by testing three polymorphisms in the region 5' to the dopamine receptor D4 gene transcription start site for linkage to ADHD. We specifically targeted polymorphisms in the region 5' to the start site of transcription as DNA variants in this region could alter the transcription level of the gene and hence the phenotype. We did not observe significant evidence for biased transmission of any of the alleles at these three polymorphisms to ADHD probands using the transmission disequilibrium test. We conclude that these three polymorphisms are not related to the ADHD phenotype.


Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention.
Parkinson's disease (PD) is the second most common neurodegenerative disease, after Alzheimer's disease. The potential causes of PD remain uncertain, but recent studies suggest neuroinflammation and microglia activation play important roles in PD pathogenesis. Major unanswered questions include whether protein aggregates cause the selective loss of dopaminergic neurons in the substantia nigra that underlies the clinical symptoms and whether neuroinflammation is a consequence or a cause of nigral cell loss. Within the microenvironment of the brain, glial cells play a critical role in homeostatic mechanisms that promote neuronal survival. Microglia have a specialized immune surveillance role and mediate innate immune responses to invading pathogens by secreting a myriad of factors that include, cytokines, chemokines, prostaglandins, reactive oxygen and nitrogen species, and growth factors. Some of these factors have neuroprotective and trophic activities and aid in brain repair processes; while others enhance oxidative stress and trigger apoptotic cascades in neurons. Therefore, pro- and anti-inflammatory responses must be in balance to prevent the potential detrimental effects of prolonged or unregulated inflammation-induced oxidative stress on vulnerable neuronal populations. In this review, we discuss potential triggers of neuroinflammation and review the strongest direct evidence that chronic neuroinflammation may have a more important role to play in PD versus other neurodegenerative diseases. Alternatively, we propose that genetic deficiency is not the only way to reduce protective factors in the brain which may function to keep microglial responses in check or regulate the sensitivity of DA neurons. If chronic inflammation can be shown to decrease the levels of neuroprotective factors in the midbrain, in essence genetic haploinsufficiency of protective factors such as Parkin or RGS10 may result from purely environmental triggers (aging, chronic systemic disease, etc.), increasing the vulnerability to inflammation-induced nigral DA neuron death and predisposing an individual to development of PD. Lastly, we review the latest epidemiological and experimental evidence supporting the potential use of anti-inflammatory and immunomodulatory drugs as neuroprotective agents to delay the progressive nigrostriatal degeneration that leads to motor dysfunction in PD.


Principal component analysis-based imaging angle determination for 3D motion monitoring using single-slice on-board imaging.
Through-plane motion introduces uncertainty in three-dimensional (3D) motion monitoring when using single-slice on-board imaging (OBI) modalities such as cine MRI. We propose a principal component analysis (PCA)-based framework to determine the optimal imaging plane to minimize the through-plane motion for single-slice imaging-based motion monitoring. Four-dimensional computed tomography (4DCT) images of eight thoracic cancer patients were retrospectively analyzed. The target volumes were manually delineated at different respiratory phases of 4DCT. We performed automated image registration to establish the 4D respiratory target motion trajectories for all patients. PCA was conducted using the motion information to define the three principal components of the respiratory motion trajectories. Two imaging planes were determined perpendicular to the second and third principal component, respectively, to avoid imaging with the primary principal component of the through-plane motion. Single-slice images were reconstructed from 4DCT in the PCA-derived orthogonal imaging planes and were compared against the traditional AP/Lateral image pairs on through-plane motion, residual error in motion monitoring, absolute motion amplitude error and the similarity between target segmentations at different phases. We evaluated the significance of the proposed motion monitoring improvement using paired t test analysis. The PCA-determined imaging planes had overall less through-plane motion compared against the AP/Lateral image pairs. For all patients, the average through-plane motion was 3.6 mm (range: 1.6-5.6 mm) for the AP view and 1.7 mm (range: 0.6-2.7 mm) for the Lateral view. With PCA optimization, the average through-plane motion was 2.5 mm (range: 1.3-3.9 mm) and 0.6 mm (range: 0.2-1.5 mm) for the two imaging planes, respectively. The absolute residual error of the reconstructed max-exhale-to-inhale motion averaged 0.7 mm (range: 0.4-1.3 mm, 95% CI: 0.4-1.1 mm) using optimized imaging planes, averaged 0.5 mm (range: 0.3-1.0 mm, 95% CI: 0.2-0.8 mm) using an imaging plane perpendicular to the minimal motion component only and averaged 1.3 mm (range: 0.4-2.8 mm, 95% CI: 0.4-2.3 mm) in AP/Lateral orthogonal image pairs. The root-mean-square error of reconstructed displacement was 0.8 mm for optimized imaging planes, 0.6 mm for imaging plane perpendicular to the minimal motion component only, and 1.6 mm for AP/Lateral orthogonal image pairs. When using the optimized imaging planes for motion monitoring, there was no significant absolute amplitude error of the reconstructed motion (P = 0.0988), while AP/Lateral images had significant error (P = 0.0097) with a paired t test. The average surface distance (ASD) between overlaid two-dimensional (2D) tumor segmentation at end-of-inhale and end-of-exhale for all eight patients was 0.6 ± 0.2 mm in optimized imaging planes and 1.4 ± 0.8 mm in AP/Lateral images. The Dice similarity coefficient (DSC) between overlaid 2D tumor segmentation at end-of-inhale and end-of-exhale for all eight patients was 0.96 ± 0.03 in optimized imaging planes and 0.89 ± 0.05 in AP/Lateral images. Both ASD (P = 0.034) and DSC (P = 0.022) were significantly improved in the optimized imaging planes. Motion monitoring using imaging planes determined by the proposed PCA-based framework had significantly improved performance. Single-slice image-based motion tracking can be used for clinical implementations such as MR image-guided radiation therapy (MR-IGRT).


Comparing Multiple Paths to Mastery: What is Learned?
Contemporary theories of learning postulate one or at most a small number of different learning mechanisms. However, people are capable of mastering a given task through qualitatively different learning paths such as learning by instruction and learning by doing. We hypothesize that the knowledge acquired through such alternative paths differs with respect to the level of abstraction and the balance between declarative and procedural knowledge. In a laboratory experiment we investigated what was learned about patterned letter sequences via either direct instruction in the relevant patterns or practice in solving letter-sequence extrapolation problems. Results showed that both types of learning led to mastery of the target task as measured by accuracy performance. However, behavioral differences emerged in how participants applied their knowledge. Participants given instruction showed more variability in the types of strategies they used to articulate their knowledge as well as longer solution times for generating the action implications of that knowledge as compared to the participants given practice. Results are discussed regarding the implications for transfer, generalization, and procedural application. Learning theories that claim generality should be tested against cross-scenario phenomena, not just parametric variations of a single learning scenario.


Multicellular redox regulation: integrating organismal biology and redox chemistry.
Early in the 20th century, Charles Manning Child attributed organismal gradients in metabolism to interactions among groups of cells. Metabolic gradients are now firmly grounded in redox chemistry, yet modern work on metabolic signaling has consistently focused on the cellular level. Multicellular redox regulation, however, may occur when redox state is determined by the behavior of a group of cells. For instance, typically an abundance of substrate will shift the redox state of mitochondria in the direction of reduction, leading to increased reactive oxygen species (ROS). These ROS, in turn, may modify the conformation and activity of proteins involved in signaling pathways, resulting in phenotypic changes. In contrast, if substrate triggers the contractions of a muscular structure comprising mitochondrion-rich cells, the resulting metabolic demand may shift the redox state in the direction of oxidation, with a corresponding decrease of ROS and different phenotypic effects. Indeed, colonial hydroids exemplify this process. Parallel examples may occur whenever mitochondria are concentrated in cells of structures that can respond to environmental perturbations with increased metabolic demand. In these circumstances, predicting the direction of metabolic signaling may require an understanding of events at the organismal level.


Human intestinal alphabeta IEL clones in celiac disease show reduced IL-10 synthesis and enhanced IL-2 production.
Celiac disease is a gluten-induced T-cell mediated autoimmune process that results in the destruction of the intestinal mucosa and is associated with an expansion of CD8(+) CD103(+) TCRalphabeta intraepithelial lymphocytes (IELs) in the damaged epithelium. The role of this IEL population in the pathology is unknown. The aim of this work was to compare the cytokine profile and the cytotoxicity pattern from CD8(+) IEL clones isolated from celiac (CD) and non-celiac (NCD) biopsies. We report that the number of IL-10 producing CD clones was significantly lower (26%) than that obtained from the NCD sample (62%). Instead, IL-2 was produced by more CD (44%) than NCD clones (26%). Cytotoxicity patterns against intestinal epithelial cell lines suggest different functional subsets of CD8(+) IELs. CD clones capable of high cytotoxicity produced IL-2 whereas most cytotoxic NCD IELs produced IL-10. This clonal analysis indicates that an impaired immune regulation in celiac mucosa may be partially attributed to the low generation of regulatory CD8(+) IELs that produce IL-10.


Cellular schwannoma. A clinicopathologic study of 57 patients and 58 tumors.
The cellular schwannoma is a variety of schwannoma with a predominantly cellular growth but no Verocay bodies. Because doubt has been raised about the original assessment of this tumor as benign, the clinical and pathologic characteristics of 58 cellular schwannomas from 57 patients were reviewed. The patients were most often middle aged (63% were female), and their tumors most commonly were painless masses with a predilection for the paravertebral region of the retroperitoneum, pelvis, and mediastinum. Most tumors were solitary and encapsulated, and an associated nerve was identified for 43% of the cases. Electron microscopic and immunohistochemistry studies confirmed the tumor's Schwann cell nature. Worrisome features such as bone erosion, hypercellularity, foci of necrosis (four tumors), hyperchromasia, nuclear pleomorphism, and the presence of mitotic figures led to a malignant diagnosis for 28% of the cases. Treatment in all but one case was surgical excision. Two patients also received radiation therapy and chemotherapy. Follow-up of from 1 year to 24 years, 7 months (median of 6 years and mean of 7 years) for 61% (35 cases) of the cases reveals three patients with a local recurrence but no cases in which the tumor metastasized or the patient died of the tumor. Awareness of this tumor type is important so that the surgeon will avoid unnecessary sacrifice of functionally important nerves attached to these tumors and so that needless adjuvant radiation and chemotherapy will not be instituted.


Coat colour in dogs: identification of the merle locus in the Australian shepherd breed.
Coat colours in canines have many natural phenotypic variants. Some of the genes and alleles involved also cause genetic developmental defects, which are also observed in humans and mice. We studied the genetic bases of the merle phenotype in dogs to shed light on the pigmentation mechanisms and to identify genes involved in these complex pathways. The merle phenotype includes a lack of eumelanic pigmentation and developmental defects, hearing impairments and microphthalmia. It is similar to that observed in microphthalmia mouse mutants. Taking advantage of the dog as a powerful genetic model and using recently available genomic resources, we investigated the segregation of the merle phenotype in a five-generation pedigree, comprising 96 sampled Australian shepherd dogs. Genetic linkage analysis allowed us to identify a locus for the merle phenotype, spanning 5.5 megabases, at the centromeric tip of canine chromosome 10 (CFA10). This locus was supported by a Lod score of 15.65 at a recombination fraction theta = 0. Linkage analysis in three other breeds revealed that the same region is linked to the merle phenotype. This region, which is orthologous to human chromosome 12 (HSA12 q13-q14), belongs to a conserved ordered segment in the human and mouse genome and comprises several genes potentially involved in pigmentation and development. This study has identified the locus for the merle coat colour in dogs to be at the centromeric end of CFA10. Genetic studies on other breeds segregating the merle phenotype should allow the locus to be defined more accurately with the aim of identifying the gene. This work shows the power of the canine system to search for the genetic bases of mammalian pigmentation and developmental pathways.


Intolerance of profligacy: an aptamer concentration gradient-tailored unicellular array for high-throughput biologics-mediated phenotyping.
In aptamer-based assay schemes, aptamer probes not labeled with biomarkers have to be eliminated before testing, which may lead to a tremendous waste of precious probes. We herein propose a microfluidics system integrating an aptamer concentration gradient generator (Apt-CGG) and a dual single-cell culturing array (D-SCA), termed Mi-Apt-SCA. This facilitates the precise construction of a nanoscale-gradient microenvironment and the high-throughput profiling of single-cell growth/phenotypes in situ with the minimal consumption of Apt-probe. Unlike previous snakelike mixers, the choreographed winding-ravined aptamer dual-spiral micromixer (Apt-WD-mixer) in Apt-CGG could allow thorough blending to generate linear concentration gradients of aptamer (quasi-non-Newtonian fluid) under the action of continuous fluidic wiggles and bidirectional Dean flow. In contrast to other trap-like systems, the mild vortex allows single-cell growth in an ultra-tender fluidic microenvironment using triple-jarless single-cell culture capsules (TriJ-SCCs) in D-SCA (shear stress: 3.43 × 10-5 dynes per cm2). The minimum dosage of aptamer probe required for exploring PDL1 protein expression in two hepatoma cell lines is only one-900th of that required by conventional protocols. In addition, this approach facilitated the profiling of ITF-β/cisplatin-mediated single-cell/cell-cluster phenotypes.


Impact of previous inguinal hernia repair on transperitoneal robotic prostatectomy.
Several investigators have noted that previous inguinal hernia repair with or without the use of prosthetic mesh might be a relative contraindication for open or laparoscopic radical prostatectomy due to the presence of adhesions and the difficulty of tissue dissection. We aimed to evaluate the impact of previous hernia repair on the performance and feasibility of robotic prostatectomy. We performed a retrospective analysis of 354 patients who underwent robotic prostatectomy at our institution. The three patient groups were: 292 patients who had no prior hernia repair (group 1), 50 patients who had prior inguinal herniorrhaphy without the use of prosthetic mesh (group 2), and 12 patients who had prior inguinal herniorrhaphy with the use of prosthetic mesh. We compared operative time (surgeon console time), estimated blood loss, and operative complications (bladder, bowel, and/or vascular injuries) in the three groups. Patients with no prior herniorrhaphy (group 1), prior herniorrhaphy without mesh (group 2), and prior herniorrhaphy with mesh (group 3), had similar mean operating times (126.9 minutes, 129.3 minutes and 145.6 minutes, respectively) and similar mean estimated blood loss (152.5 ml, 140.6 ml, and 141.6 ml, respectively) during radical prostatectomy. However, compared to the group of patients who had no prior hernia repair, the group who had prior herniorrhaphy with the use of mesh had a significantly longer mean console operating time (145.6 versus 126.9 minutes, p = .012). Previous hernia surgery, with or without the use of prosthetic mesh, did not represent a significant barrier to the performance of transperitoneal robotic prostatectomy.


Learned digital lens enabled single optics achromatic imaging.
High-quality imaging with reduced optical complexity has been extensively investigated owing to its promising future in academic and industrial research. However, the practical performance of most imaging systems has encountered a bottleneck posed by optics rather than electronics. Here, we propose a digital lens (DL) to compensate for the chromatic aberration induced by physical optical elements, while the residual wavelength-independent degradation is tackled through a self-designed neural network. By transforming physical aberration correction to an algorithm-based computational imaging task, the proposed DL enables our framework to reduce optical complexity and achieve achromatic imaging in the analog domain. Real experiments have been conducted with an off-the-shelf single lens and recovered images show up to 14.62 dB higher peak signal-to-noise ratio (PSNR) than the original chromatic input. Furthermore, we run a comprehensive ablation study to highlight the contribution of embedding the proposed DL, which shows a 4.83 dB PSNR improvement compared with the methods without DL. Technically, the proposed method can be an alternative for future applications that require both simple optics and high-fidelity visualization.


Localization of Hidden Insulinomas with ⁶⁸Ga-DOTA-Exendin-4 PET/CT: A Pilot Study.
(111)In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle(14),Lys(40)(Ahx-DOTA-(68)Ga)NH2]exendin-4 ((68)Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. (68)Ga-DOTA-exendin-4 PET/CT and (111)In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive (68)Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. (68)Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas (111)In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. These preliminary data suggest that the use of (68)Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.


Preliminary results with modified techniques of balloon kyphoplasty for vertebra plana, traumatic fractures and neoplasms.
Percutaneous vertebroplasty and balloon kyphoplasty are less invasive treatment options than open surgery for patients with vertebral compression fractures. With balloon kyphoplasty, the injection of bone cement is preceded by inflation and removal of bone tamps (balloons) inside the fractured vertebral body. This allows for the creation of a void, where viscous cement is delivered resulting in a lower risk for cement leakage than with vertebroplasty. Another advantage of the balloon inflation is the potential to correct the deformity and restore sagittal alignment. The percutaneous techniques normally require intact pedicles and intact posterior elements. We found that modifying the technique made it suitable for the management of vertebra plana, traumatic fractures, and neoplasms. Our study documents the different modified techniques and the clinical results obtained within the first 21 patients.


[Diagnosis and treatment of thyroid cancer in children in the multicenter analysis in Poland for PPGGL].
Differentiated thyroid carcinoma (DTC) in children presents different biological behavior in comparison to adults. Authors presents preliminary results of multicenter analysis concerning incidence, diagnostics and treatment of DTC in children. The study is a retrospective analysis of 107 pediatric patients from 14 academic centers based on the data from 2000 to 2005 obtained by questionnaire in hospitals involved in the treatment of DTC in children. Papillary thyroid cancer was diagnosed in 83 children, follicular thyroid cancer in 10 children and medullary thyroid cancer in 14 children. Incidence of DTC in children was estimated between 18 and 23 cases per year. The biggest group of patients consisted of children between 11 and 15 years of age, with girls to boys ratio 3.3 : 1. Clinically DTC in children presented most often as solitary thyroid nodule. Cervical lymphadenopathy was observed in 42% of patients. Intraoperative verification indicated metastatic nodes in 50% of children. Low stage DTC predominated (T1 in 36% and T2 in 26% of children). One step surgery was performed in 65% of children with DTC, two step surgery in 25% of patients. I131 therapy was undertaken in 80% of children. Lung metastases were indicated in post therapeutic studies in 14% of children with DTC. Prophylactic thyroidectomies were performed in 79% of children in the group of patients with MTC and RET gene mutations. The necessity of introduction of unified therapeutic standard in children with DTC in Poland is underlined.


Interrupted aortic arch in an adolescent male.
Interrupted aortic arch (IAA) is an uncommon and usually lethal congenital malformation. The present report describes an unusual case of IAA, an aneurysmal ascending aorta and a bicuspid aorta in a 15-year-old boy. He presented with general malaise, weakness of his legs, headache and hypertension that began six months earlier. He had suffered from effort intolerance since childhood. A three-dimensional gadolinium contrast-enhanced magnetic resonance angiogram demonstrated IAA and a markedly developed collateral circulation. IAA is an uncommon disease that is rarely encountered in an adolescent patient with nonspecific symptoms or hypertension. The present case also shows the clinical value of three-dimensional gadolinium contrast-enhanced magnetic resonance angiography for noninvasive assessment of the aortic arch, and magnetic resonance angiography can replace angiography in the assessment of aortic arch anomalies and visualization of well-developed collaterals.


Isolation of genomic DNA using magnetic nanoparticles as a solid-phase support.
In recent years, techniques employing magnetizable solid-phase supports (MSPS) have found application in numerous biological fields. This magnetic separation procedure offers several advantages in terms of subjecting the analyte to very little mechanical stress compared to other methods. Secondly, these methods are non-laborious, cheap, and often highly scalable. The current paper details a genomic DNA isolation method optimized in our laboratory using magnetic nanoparticles as a solid-phase support. The quality and yields of the isolated DNA from all the samples using magnetic nanoparticles were higher or equivalent to the traditional DNA extraction procedures. Additionally, the magnetic method takes less than 15 min to extract polymerase chain reaction (PCR) ready genomic DNA as against several hours taken by traditional phenol-chloroform extraction protocols. Moreover, the isolated DNA was found to be compatible in PCR amplification and restriction endonuclease digestion. The developed procedure is quick, inexpensive, robust, and it does not require the use of organic solvents or sophisticated instruments, which makes it more amenable to automation and miniaturization.


Ontogenetic and spatial variation in size-selective mortality of a marine fish.
Although body size can affect individual fitness, ontogenetic and spatial variation in the ecology of an organism may determine the relative advantages of size and growth. During an 8-year field study in the Bahamas, we examined selective mortality on size and growth throughout the entire reef-associated life phase of a common coral-reef fish, Stegastes partitus (the bicolour damselfish). On average, faster-growing juveniles experienced greater mortality, though as adults, larger individuals had higher survival. Comparing patterns of selection observed at four separate populations revealed that greater population density was associated with stronger selection for larger adult size. Large adults may be favoured because they are superior competitors and less susceptible to gape-limited predators. Laboratory experiments suggested that selective mortality of fast-growing juveniles was likely because of risk-prone foraging behaviour. These patterns suggest that variation in ecological interactions may lead to complex patterns of lifetime selection on body size.


MicroRNA expression profiling of elongated cloned and in vitro-fertilized bovine embryos.
The objective of this study was to identify microRNAs (miRNAs) expressed in bovine (Bos Taurus) cloned embryos at Day 17 of development (Day 0=day of nucleus transfer or in vitro fertilization) during elongation. Day 7 bovine expanded blastocysts produced by hand made cloning (HMC) or in vitro fertilization were bulk-transferred to synchronized recipient cattle (48 HMC embryos to 10 recipients and 28 in vitro-produced embryos to four recipients). Elongated embryos were retrieved at Day 17; miRNAs were isolated and subjected to microarray screening using custom composite slides spotted with human, mouse, and rat and in silico-predicted miRNAs. An initial profile of expressed miRNAs was determined in cloned embryos and somatic donor cells; this profile changed after somatic cell nucleus transfer, identifying differentially expressed miRNAs between cloned and in vitro-produced bovine embryos. Furthermore, microarray data were validated using a miRNA-specific quantitative reverse transcription-polymerase chain reaction (qRT-PCR) approach (miR-Q). There was an 83% correlation (P=0.01) between microarray and qPCR data. Based on qRT-PCR, correct reprogramming of some miRNAs from the donor cells was confirmed in cloned bovine embryos, whereas other somatic miRNAs were not appropriately reprogrammed. Some of the miRNAs that were equally reprogrammed clustered on the same chromosomal location in the bovine genome. In conclusion, reprogramming of miRNAs seemed to occur in cloned bovine embryos. This could have profound implications for elucidating nuclear reprogramming in somatic cloning, as well as for the role of miRNAs in preimplantation mammalian development.


Ultrasound-guided percutaneous microwave ablation versus surgery for papillary thyroid microcarcinoma.
Papillary thyroid microcarcinoma (PTMC) has high incidence and low disease-specific mortality. However, active surveillance is not accepted by most patients owing to high physical or psychological pressures. The emergence of ablation technologies is supplanting traditional surgery. Our goal was to compare the clinical outcomes of microwave ablation (MWA) and surgery for T1aN0M0 PTMC. A total of 92 consecutive patients with T1aN0M0 PTMC were studied retrospectively. Forty-six patients had been treated with MWA, and the other 46 had undergone surgery. MWA was performed using extensive ablation extending from the nodule's lower pole to the upper pole. Surgery was performed by total thyroidectomy or thyroid lobectomy. We compared the two groups in terms of mean length of stay, cost, mean blood loss, surgical incision, operating room (OR) time, quality of life (QOL) assessment, complications, and therapeutic efficacy over a follow-up period of 42 months. The mean length of stay, cost, mean blood loss, surgical incisions, OR time, and complications in the MWA group were significantly lower than those of the surgery group. The QOL after MWA was higher than it was after surgery. The nodule volume decreased significantly from 53.61 ± 48.43 mm3 to 4.84 ± 6.55 mm3 (p < .001) at the 42-month follow-up, exhibiting a percentage volume reduction of 81.33 ± 36.87%. No recurrence or metastasis occurred in either group during the follow-up period. MWA may be considered a minimally invasive alternative to surgery for solitary T1aN0M0 PTMC with low incidence of complications and good therapeutic effect.


Screening for multiple endocrine neoplasia type 1 in patients with recognized pituitary adenoma.
A total of 79 consecutive patients with pituitary tumours were screened for multiple endocrine neoplasia type 1 (MEN-1). The 79 patients included 21 patients with acromegaly, nine with Cushing's disease, 18 with prolactinomas, three with mixed pituitary adenomas (GH and PRL), and 28 patients with no detectable hypersecretion of hormones. The screening consisted of: (1) a family history, (2) a uniform medical history of the patient using a standard questionnaire, and (3) hormonal evaluation including measurements of the serum levels of insulin, gastrin, glucagon, somatostatin, vasoactive intestinal polypeptide and pancreatic polypeptide. Ionized calcium and glucose concentration in serum were also measured. We found no patients with the MEN-1 syndrome. In one patient, we found a transient elevation of serum concentrations of pancreatic polypeptide for which we have no explanation. In another patient, the serum gastrin concentration was elevated secondary to achlorhydria. No other endocrine disorders were found, and no patients had relatives with recognized endocrine pancreatic tumours, primary hyperparathyroidism (HPT), or pituitary adenomas.


Innovative Head-Mounted System Based on Inertial Sensors and Magnetometer for Detecting Falling Movements.
This work presents a fall detection system that is worn on the head, where the acceleration and posture are stable such that everyday movement can be identified without disturbing the wearer. Falling movements are recognized by comparing the acceleration and orientation of a wearer's head using prespecified thresholds. The proposed system consists of a triaxial accelerometer, gyroscope, and magnetometer; as such, a Madgwick's filter is adopted to improve the accuracy of the estimation of orientation. Moreover, with its integrated Wi-Fi module, the proposed system can notify an emergency contact in a timely manner to provide help for the falling person. Based on experimental results concerning falling movements and activities of daily living, the proposed system achieved a sensitivity of 96.67% in fall detection, with a specificity of 98.27%, and, therefore, is suitable for detecting falling movements in daily life.


Robust incision of Benoz[a]pyrene-7,8-dihyrodiol-9,10-epoxide-DNA adducts by a recombinant thermoresistant interspecies combination UvrABC endonuclease system.
Prokaryotic DNA repair nucleases are useful reagents for detecting DNA lesions. UvrABC endonuclease, encoded by the UvrA, UvrB, and UvrC genes can incise DNA containing bulky nucleotide adducts and intrastrand cross-links. UvrA, UvrB, and UvrC were cloned from Bacillus caldotenax (Bca)and UvrC from Thermatoga maritima (Tma), and recombinant proteins were overexpressed in and purified from Escherichia coli. Incision activities of UvrABC composed of all Bca-derived subunits (UvrABC(Bca)) and an interspecies combination UvrABC composed of Bca-derived UvrA and UvrB and Tma-derived UvrC (UvrABC(Tma)) were compared on benoz[a]pyrene-7,8-dihyrodiol-9,10-epoxide (BPDE)-adducted substrates. Both UvrABC(Bca) and UvrABC(Tma) specifically incised both BPDE-adducted plasmid DNAs and site-specifically modified 50-bp oligonucleotides containing a single (+)-trans- or (+)-cis-BPDE adduct. Incision activity was maximal at 55-60 degrees C. However, UvrABC(Tma) was more robust than UvrABC(Bca) with 4-fold greater incision activity on BPDE-adducted oligonucleotides and 1.5-fold greater on [(3)H]BPDE-adducted plasmid DNAs. Remarkably, UvrABC(Bca) incised only at the eighth phosphodiester bond 5' to the BPDE-modified guanosine. In contrast, UvrABC(Tma) performed dual incision, cutting at both the fifth phosphodiester bond 3' and eighth phosphodiester bond 5' from BPDE-modified guanosine. BPDE adduct stereochemistry influenced incision activity, and cis adducts on oligonucleotide substrates were incised more efficiently than trans adducts by both UvrABC(Bca) and UvrABC(Tma). UvrAB-DNA complex formation was similar with (+)-trans- and (+)-cis-BPDE-adducted substrates, suggesting that UvrAB binds both adducts equally and that adduct configuration modifies UvrC recognition of the UvrAB-DNA complex. The dual incision capabilities and higher incision activity of UvrABC(Tma) make it a robust tool for DNA adduct studies.


Vanillic acid in Panax ginseng root extract inhibits melanogenesis in B16F10 cells via inhibition of the NO/PKG signaling pathway.
Panax ginseng C. A. Meyer has been widely used in skin care. Our previous study showed that the phenolic acids in ginseng root extract (GRE) impart inhibitory effects on melanogenesis. In this study, we found that as the most abundant component of phenolic acids in GRE, vanillic acid decreased tyrosinase activity and melanin levels with or without α-MSH stimulation and suppressed the expression of microphthalmia-associated transcription factor (MITF) and melanogenic enzymes in B16F10 cells. Furthermore, vanillic acid downregulated NOS activity, nitric oxide (NO) content, cGMP level, guanylate cyclase (GC) and protein kinase G (PKG) activity, and the phosphorylation of cAMP-response element-binding protein (CREB), whereas arbutin had no effect on the NO/PKG pathway. These findings indicate that vanillic acid in GRE suppressed melanogenesis by inhibiting the NO/PKG signaling pathways. This study provides a potential mechanism underlying the inhibitory effect of ginseng on melanogenesis.


Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women.
A role for matrix metalloproteinase polymorphisms in breast cancer development and progression was proposed, but with inconclusive results. We assessed the relation of matrix metalloproteinase-2 variants with breast cancer and related phenotypes in Tunisians. This case-control retrospective study involved 430 women with breast cancer and 498 healthy controls. Genotyping of matrix metalloproteinase-2 rs243866, rs243865, rs243864, and rs2285053 was analyzed by allelic exclusion. The minor allele frequency of rs2285053 was significantly lower in women with breast cancer cases as compared to control women; minor allele frequencies of the remaining single-nucleotide polymorphisms were similar between cases and control women. The distribution of rs243865 and rs2285053 genotypes was significantly different between breast cancer patients and control subjects. This persisted when key covariates were controlled for. None of the matrix metalloproteinase-2 variants were associated with estrogen receptor positivity, progesterone receptor positivity, or with double estrogen receptor-progesterone receptor positivity in breast cancer patients. Matrix metalloproteinase-2 rs243866, rs243865, and rs243864 were positively associated with menstrual irregularity and histological type, while rs243866 and rs2285053 were negatively associated with menarche and nodal status. In addition, rs2285053 was negatively associated with triple negativity, tumor size, distance metastasis, molecular type, and chemotherapy. Haploview analysis revealed high linkage disequilibrium between matrix metalloproteinase-2 variants. Four-locus Haploview analysis identified haplotypes GCTT and GTTC to be negatively associated with breast cancer, which remained statistically after controlling for key covariates. Matrix metalloproteinase-2 alleles and genotypes, along with four-locus haplotypes, are related to reduced susceptibility to breast cancer in Tunisian women, suggesting a protective effect.


Sample size computation in phase II designs combining the A'Hern design and the Sargent and Goldberg design.
This work focuses on the modification of two classical phase II trials designs, the A'Hern design, a single-arm single-stage design, and the Sargent and Goldberg design introduced in the context of flexible screening designs. In the first part of the paper, we have proposed a drift-adjusted A'Hern design, a hybrid design combining the A'Hern design and the Sargent and Goldberg design. Indeed, classical single-arm phase II designs such as the A'Hern design are still widely used in oncology. Conducting randomized comparative phase II trials may be challenging in many settings due to the increased sample size and this despite larger type 1 errors. Randomized non-comparative phase II designs first introduced by Herson and Carter include a simultaneous randomized standard-treatment reference arm to detect any drift in the reference arm assumption, but the trial is analyzed against historical controls as if it were a single-arm study. However, not incorporating at all an internal control arm in the trial design has been criticized in the literature. Our new design takes into account the observed response rate in a non-comparative reference arm to reduce the trial's risk of a false-positive conclusion. In the second part, we have proposed an alternative strategy to determining the sample size of the screened selection design. The latter, introduced in recent years by Yap et al. and Wu et al., extended the Sargent and Goldberg design to include a comparison to a historical control. However, their sample size computations may have potential weaknesses, which motivated us to revisit the existing approaches. A detailed simulation study has been carried out to evaluate the operating characteristics of the drift-adjusted A'Hern design and the different sample size strategies of the screened selection designs.


EphA4 Regulates the Balance between Self-Renewal and Differentiation of Radial Glial Cells and Intermediate Neuronal Precursors in Cooperation with FGF Signaling.
In mouse cerebral corticogenesis, neurons are generated from radial glial cells (RGCs) or from their immediate progeny, intermediate neuronal precursors (INPs). The balance between self-renewal of these neuronal precursors and specification of cell fate is critical for proper cortical development, but the signaling mechanisms that regulate this progression are poorly understood. EphA4, a member of the receptor tyrosine kinase superfamily, is expressed in RGCs during embryogenesis. To illuminate the function of EphA4 in RGC cell fate determination during early corticogenesis, we deleted Epha4 in cortical cells at E11.5 or E13.5. Loss of EphA4 at both stages led to precocious in vivo RGC differentiation toward neurogenesis. Cortical cells isolated at E14.5 and E15.5 from both deletion mutants showed reduced capacity for neurosphere formation with greater differentiation toward neurons. They also exhibited lower phosphorylation of ERK and FRS2α in the presence of FGF. The size of the cerebral cortex at P0 was smaller than that of controls when Epha4 was deleted at E11.5 but not when it was deleted at E13.5, although the cortical layers were formed normally in both mutants. The number of PAX6-positive RGCs decreased at later developmental stages only in the E11.5 Epha4 deletion mutant. These results suggest that EphA4, in cooperation with an FGF signal, contributes to the maintenance of RGC self-renewal and repression of RGC differentiation through the neuronal lineage. This function of EphA4 is especially critical and uncompensated in early stages of corticogenesis, and thus deletion at E11.5 reduces the size of the neonatal cortex.


The burden of responsibility: duty, depression, and nervios in Andean Ecuador.
Saraguro Indian women possess relatively high status in their community. Nevertheless, they experience high rates of the culturally interpreted illness nervios. This syndrome produces symptoms characteristic of stress-induced depression and is identified by Saraguros as the product of suffering and misfortune. Descriptive and quantitative interview data indicate that episodes of nervios correlate with experiences of gender role failure, and the condition is identified as a coping mechanism for excessive responsibility and unrealistic social expectation. This syndrome also appears to serve as an effective strategy for enhancing power and social status.


Impact and relevance of alcohol dehydrogenase enantioselectivities on biotechnological applications.
Alcohol dehydrogenases (ADHs) catalyze the reversible reduction of a carbonyl group to its corresponding alcohol. ADHs are widely employed for organic synthesis due to their lack of harm to the environment, broad substrate acceptance, and high enantioselectivity. This review focuses on the impact and relevance of ADH enantioselectivities on their biotechnological application. Stereoselective ADHs are beneficial to reduce challenging ketones such as ketones owning two bulky substituents or similar-sized substituents to the carbonyl carbon. Meanwhile, in cascade reactions, non-stereoselective ADHs can be utilized for the quantitative oxidation of racemic alcohol to ketone and dynamic kinetic resolution.


Characterization of monofloral honeys with multivariate analysis of their chemical profile and antioxidant activity.
Various bioactive chemical constituents were quantified for 21 honey samples obtained at Rio de Janeiro and Minas Gerais, Brazil. To evaluate their antioxidant activity, 3 different methods were used: the ferric reducing antioxidant power, the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity, and the 2,2'-azinobis (3-ethylbenzothiazolin)-6-sulfonate (ABTS) assays. Correlations between the parameters were statistically significant (-0.6684 ≤ r ≤-0.8410, P < 0.05). Principal component analysis showed that honey samples from the same floral origins had more similar profiles, which made it possible to group the eucalyptus, morrão de candeia, and cambara honey samples in 3 distinct areas, while cluster analysis could separate the artificial honey from the floral honeys. This research might aid in the discrimination of honey floral origin, by using simple analytical methods in association with multivariate analysis, which could also show a great difference among floral honeys and artificial honey, indicating a possible way to help with the identification of artificial honeys.


Comparative analysis of the Lang Stereopad in a non-clinic population.
Aim: New methods of measurement require testing to evaluate test validity. This study compares stereoacuity results of the Lang Stereopad to other common clinical stereoacuity assessments in a normal vision population. Methods: A prospective cross-sectional study was conducted comparing the Lang Stereopad stereoacuity results to results from the Lang II, Frisby, and TNO stereo tests. Mean stereoacuity values and their correlation with inter-ocular visual acuity difference were compared for each stereo test. Results: 98 subjects (mean age of 33.5 years, SD 14.1; 39 males and 59 females) with normal parameters of visual function underwent multiple stereotest assessments. Median stereoacuity values were the lowest (i.e. more detailed stereoacuity) when using the Frisby stereotest (median 40"; 20-170" [minimum-maximum]) and TNO stereotest (median 60"; 15-480"). In comparison, medians were about double at 100" (50-800") for the Lang Stereopad and greater at 200" (200-200") for the Lang II stereotest. There was no correlation for each stereotest with interocular visual acuity differences. Conclusions: The Lang Stereopad test is easy to administer and it has certain advantages such as no requirement for additional test glasses. It is a useful assessment to add to the clinical armamentarium for binocular assessment of stereopsis. The Lang Stereopad does not agree well with other stereo tests such as the TNO and Frisby but provides a greater stereoacuity test range than the Lang II. The Lang Stereopad now requires testing in a clinical population in which stereoacuity is a pre-requisite part of the assessment.


Vascular evaluation and arterial reconstruction of the diabetic foot.
Findings of diminished or absent pulses, pallor on elevation, redness of the foot on lowering of the leg, sluggish refilling of the toe capillaries, and thickened nails or absence of toe hair are consistent with impaired arterial perfusion to the foot. When ischemia is recognized as contributing to pedal ulceration and infection in the diabetic foot, quantitation of its severity may be difficult. Standard clinical evaluation of trophic changes is limited in an infected foot with its accompanying swelling, edema, and erythema. A palpable pedal pulse does not preclude the possibility of the presence of limb-threatening ischemia. Additional non-invasive vascular studies should be undertaken for these patients. Management of the diabetic foot is often a complex clinical problem. However, the principles of care are simple, including correction of systemic factors, such as blood glucose control, cardiovascular risk factor management, and smoking, as well as local factor correction, such as debridement, pressure relief, infection control, and revascularization when indicated. When a patient presents with evidence of infection, adequate drainage and antibiotic therapy are mandatory. The next step should be performed to differentiate the more common neuropathic ulcerations from the truly ischemic ulceration. Symptoms of rest pain or claudication are not often helpful because many of these patients are asymptomatic as a result of the presence of their neuropathy and inactivity. If an infected foot requires debridement or open partial forefoot amputation, observing the wound on a daily base is also important. Once infection is eradicated, there should be prompt signs of healing, including the development of wound granulation within several days. If wounds are not showing signs of prompt healing, arteriography is necessary. Early aggressive drainage, debridement, and local foot amputations combined with liberal use of revascularization results in cumulative limb salvage of 74% at 5 years in high-risk groups. Others report that pedal bypass to the ischemic infected foot is effective and safe as long as infection adequately controlled. These studies strongly suggest that early recognition and aggressive surgical drainage of pedal sepsis followed by surgical revascularization is critical to achieving maximal limb salvage in the high-risk population. Patients who have diabetes present a unique challenge in lower extremity revascularization because of the distal origination of many bypasses, distal distribution of the occlusive disease, and the frequently calcified arterial wall. An aggressive multidisciplinary approach to foot disease associated with diabetes involving the primary care provider, medical specialists, interventional radiology, and podiatric, plastic, and vascular surgeons will provide optimal medical and surgical care. Peripheral vascular disease is highly treatable if intervention is instituted in a timely and collegial fashion.


Cumulative, additive benefits of memantine-donepezil combination over component monotherapies in moderate to severe Alzheimer's dementia: a pooled area under the curve analysis.
Treatment in moderate or severe Alzheimer's disease (AD) often involves adding memantine to a cholinesterase-inhibitor (ChEI: donepezil, galantamine, rivastigmine). Evidence from six-month randomized trials and long-term observational studies supports superiority of memantine-ChEI combination to ChEI monotherapy. We utilized area-under-the-curve (AUC) analysis to assess six-month cumulative treatment efficacy of memantine-donepezil combination versus component monotherapies on individual clinical domains and on a composite index. Data were pooled from 1,408 individuals with moderate to severe AD from four six-month randomized trials of memantine monotherapy (n = 570) or add-on therapy (donepezil-only subset: n = 847). AUC changes from baseline on measures of cognition (SIB), function (ADCS-ADL19), behavior (NPI), global status (CIBIC-Plus), and a composite index (4D-CI: equally weighted composite of four domain measures) were calculated using the trapezoidal rule and evaluated via analysis of covariance (ANCOVA) (2-sided-α = 0.05). AUC results were contrasted with visit-by-visit changes from baseline ("snapshot analysis"), performed using a mixed-effects model with repeated measures (MMRM). Over the entire six-month period, placebo-only treatment was associated with significant cumulative worsening on all outcomes. Memantine-donepezil combination showed significantly greater AUC improvements (point x week) on the SIB, NPI, and CIBIC-Plus than placebo-donepezil (SIB: 68.4 versus 32.0, P = 0.019; NPI: -74.3 versus -28.2, P = 0.003; CIBIC-Plus: -2.5 versus 1.4, P = 0.006) and memantine-only monotherapies (SIB: 68.4 versus 12.0, P <0.001; NPI: -74.3 versus -7.4, P <0.001; CIBIC-Plus: -2.5 versus 2.7, P <0.001), whereas these comparisons were not significant for the ADCS-ADL19 (memantine-donepezil (1.4) versus placebo-donepezil (-0.9), P = 0.407; versus memantine-only (-12.2), P = 0.310). Composite index analysis demonstrated significant cumulative advantages of memantine-donepezil combination (630.0) over placebo-donepezil (344.7, P <0.001) and memantine-only (152.1, P <0.001) treatments. Combining memantine and donepezil had an additive effect. Compared with AUC analysis, baseline-to-endpoint change-score analysis underestimated effects of combination therapy, monotherapies, or both. This large pooled area-under-the-curve analysis of randomized-trial data in moderate to severe AD provides ecologically valid support that adding memantine to stable donepezil results in overall clinical benefits that are additive compared with individual monotherapies, continue to accumulate through six-month treatment, and are at least 50% greater than those of monotherapies.


Web based diabetes care planning - sociotechnical barriers to implementation in general practice.
This research explored the sociotechnical barriers in the implementation of web based diabetes care plans in general practice from the perspective of implementing stakeholders. A qualitative case study design was use to explore the sociotechnical barriers. Twenty-one stakeholders were purposely recruited and interviewed. Technological barriers included rudimentary IT applications in general practice; standardisation and interoperability issues; and 'bugs' in the system. The role of practice managers as gatekeepers influenced the uptake of the technology. General practitioners were noted to be time poor, while practice nurses preferred to stick with paper based ways of doing care plans. The relationship between allied health professionals and GPs also influenced the adoption process. Implementers had significant insight into the sociotechnical barriers to diabetes web based care planning in general practice. Future research should examine the roles of the stakeholders involved in determining standards and the interoperability of systems.


[Clinical polymorphism of anorectal lymphogranuloma venereum in Buenos Aires City].
From 2003 to date there has been a rising number of reports from developed countries on cases of lymphogranuloma venereum with anorectal localization in HIV-infected men who have sex with men. This localization differs from the classical inguinal abscesses which are typical of the disease in the tropics. The objective of this work is to document the presence of anorectal lymphogranuloma venereum in Buenos Aires and to describe its varied clinical manifestations. In the context of a systematic survey of rectal chlamydial infection, in just one trimester, eight cases of lymphogranuloma venereum caused by Chlamydia trachomatis biovar LGV were identified in HIV-infected men who have sex with men. The most frequent anorectal manifestations were pus, tenesmus, rectal urgency, and mucous or haemopurulent discharge. The proctitis was mostly mild or moderate and, in some cases, it was accompanied by perianal lesions. Given the great polymorphism and unspecificity of the clinical manifestations of the disease, we warn on the presence of this form of rectal lymphogranuloma venereum in our setting. If Chlamydia trachomatis is detected, it should be genotyped, not only for the correct diagnosis and treatment but also for epidemiological surveillance. Where genotyping is not available, the disease must be considered as caused by the LGV biovar and treated accordingly.


Adenomyomatosis of the gallbladder. A premalignant lesion?
Gallbladder cancer is the most common malignant tumor of the biliary tract, but its early diagnosis is uncommon. The use of ultrasonography has increased the detection of benign gallbladder tumors, and the premalignant potential of gallbladder adenomas is now undisputed. Adenomyomatosis of the gallbladder has recently been suggested to have malignant potential, and we report a case of adenocarcinoma of the gallbladder occurring in localized adenomyomatosis that was successfully treated by radical curative surgery. The more rigorous use of ultrasonography and a more aggressive approach to "benign" polypoid lesions of the gallbladder may represent the best way of achieving early diagnosis and cure in gallbladder cancer.


Public health preparedness: a systems-level approach.
Public health and emergency preparedness have become central concepts in the current restructuring of various regional-, national- and global-level public health and emergency management agencies and systems. In this article, a glossary of the most important terms and concepts currently pertaining to public health preparedness is provided with a focus on systems-level and organisational issues.


Global analysis of dauer gene expression in Caenorhabditis elegans.
The dauer is a developmental stage in C. elegans that exhibits increased longevity, stress resistance, nictation and altered metabolism compared with normal worms. We have used DNA microarrays to profile gene expression differences during the transition from the dauer state to the non-dauer state and after feeding of starved L1 animals, and have identified 1984 genes that show significant expression changes. This analysis includes genes that encode transcription factors and components of signaling pathways that could regulate the entry to and exit from the dauer state, and genes that encode components of metabolic pathways important for dauer survival and longevity. Homologs of C. elegans dauer-enriched genes may be involved in the disease process in parasitic nematodes.


[Ex vitro sentinel lymph node mapping in colorectal carcinoma].
To investigate the feasibility of ex vitro sentinel lymph node (SLN) mapping with methylene blue staining and its clinical value of predicting regional lymph node metastasis in colorectal cancer. Methylene blue (1 ml) was injected submucosally around the tumor immediately after resection. After 2-5 minutes, the first blue-dyed lymph nodes, sentinel lymph nodes (SLNs), were harvested for pathological examination, and compared with the pathological results of other lymph nodes. Of the total 32 patients, 57 SLNs were successfully identified in 30 patients with an average of 1.9 nodes per person. The successful labeling rate was 93.8% (30/32). Among the 13 patients with positive SLNs, there were 5 patients with positive non-SLNs and 8 patients with negative Non-SLNs. Among the 17 patients with negative SLNs, there were 15 patients with negative non-SLNs and 2 patients with positive Non-SLNs. The accuracy of SLNs for regional lymph node metastasis was 93.3% (28/30), the false negative rate was 11.8% (2/17), and the specificity was 100% (13/13). Ex vitro sentinel lymph node mapping with methylene blue staining in colorectal carcinoma is technically feasible and can effectively reflect the metastatic situation of regional lymph nodes.


NAIP-deletion analysis in Malaysian patients with spinal muscular atrophy.
Spinal Muscular Atrophy (SMA) is an autosomal recessive disease, which is characterized by degeneration of the anterior horn cells of the spinal cord. SMA is classified into 3 clinical subtypes, type I (severe), type II (intermediate), and type III (mild). Two genes, SMN1 and NAIP, have been identified as SMA-related genes. The SMN1 gene is now recognized as a responsible gene for the disease because it is deleted or mutated in most SMA patients. However, the role of the NAIP gene in SMA has not been fully clarified. To clarify the contribution of NAIP to the disease severity of SMA, we studied the relationship between NAIP-deletion and clinical phenotype in Malaysian patients. A total of 39 patients lacking SMN1 (12 type I, 19 type II, and 8 type III patients) were enrolled into this study. Seven out of 12 patients with type I SMA (approximately 60%) showed NAIP deletion. On the contrary, only 2 out of 20 type II patients and none of type III patients showed NAIP deletion. There was a statistically significant difference in NAIP-deletion frequency among the clinical subtypes (Fisher's exact probability test, p value = 0.014). In conclusion, according to our data that NAIP deletion was more frequent in type I SMA than in type II-III SMA, the NAIP gene may be a modifying factor for disease severity of SMA.


Recent Progress of Toxic Gas Sensors Based on 3D Graphene Frameworks.
Air pollution is becoming an increasingly important global issue. Toxic gases such as ammonia, nitrogen dioxide, and volatile organic compounds (VOCs) like phenol are very common air pollutants. To date, various sensing methods have been proposed to detect these toxic gases. Researchers are trying their best to build sensors with the lowest detection limit, the highest sensitivity, and the best selectivity. As a 2D material, graphene is very sensitive to many gases and so can be used for gas sensors. Recent studies have shown that graphene with a 3D structure can increase the gas sensitivity of the sensors. The limit of detection (LOD) of the sensors can be upgraded from ppm level to several ppb level. In this review, the recent progress of the gas sensors based on 3D graphene frameworks in the detection of harmful gases is summarized and discussed.


Activation of the alpha7 nAChR reduces acid-induced acute lung injury in mice and rats.
New evidence indicates that neural mechanisms can down-regulate acute inflammation. In these studies, we tested the potential role of the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) in a rodent model of acid-induced acute lung injury. We first determined that the alpha7 nAChR was expressed by alveolar macrophages and lung epithelial cells. Then, using an acid-induced acute lung injury mouse model, we found that nicotine, choline, and PNU-282,987 (a specific alpha7 nAChR agonist) decreased excess lung water and lung vascular permeability, and reduced protein concentration in the bronchoalveolar lavage (BAL). Deficiency of alpha7 nAChR resulted in a 2-fold increase in excess lung water and lung vascular permeability. The reduction of proinflammatory cytokines (macrophage inflammatory protein-2 and TNF-alpha) in the BAL with nicotine probably resulted from the suppression of NF-kappaB activation in alveolar macrophages. The beneficial effect of nicotine was also tested in rat model of acid-induced acute lung injury in which BAL protein and receptor for advanced glycation end products (RAGE), a marker of type I cell injury, were reduced by nicotine treatment. These results indicate that activation of alpha7 nAChR may provide a new therapeutic pathway for the treatment of acute lung injury.


Rat vitamin D binding protein. Determination of the full-length primary structure from cloned cDNA.
Vitamin D binding protein (DBP) is an abundant serum glycoprotein secreted by the liver which transports vitamin D sterols, binds to actin, and is found on the surface of B-lymphocytes and subpopulations of T-lymphocytes. In the current study, a cDNA to rat DBP mRNA was cloned from a bacteriophage lambda gt 11 rat liver expression library. This DBP cDNA clone was identified by immunoblotting and its identity was confirmed by immunoprecipitation of a 54-kDa protein after hybrid-assisted translation. Northern analysis and primer extension mapping of rat liver mRNA indicated that the full-length DBP mRNA contains 1700 bases. By DNA sequence analysis this 1655-base pair clone contains a single open reading frame encoding the 476-amino acid containing full-length DBP and includes its 16-amino acid signal sequence. Analysis of the sequence reveals about 40% nucleotide and 23% amino acid homology to both albumin and alpha-fetoprotein. The encoded DBP contains a characteristic placement of cysteine residues, identical to that in albumin, suggesting a similar secondary folding structure. Albumin and alpha-fetoprotein are composed of three internally homologous domains. DBP mRNA terminates 122 amino acids before the larger albumin mRNA in the third internal domain, but retains the characteristic homology among the first two domains and the truncated portion of the third domain. These data support the conclusion that DBP is a member of a multigene family which includes albumin and alpha-fetoprotein.


Glucosamine: a review of its use in the management of osteoarthritis.
Glucosamine occurs naturally in all human tissues. It stimulates the synthesis of glycosaminoglycan, proteoglycan and hyaluronic acid, although the precise mechanism of action remains to be established. Formulated as glucosamine sulphate (Dona) and various others), glucosamine has been evaluated for its efficacy in relieving the symptoms of osteoarthritis and its disease-modifying potential. In two large randomised, double-blind, multicentre studies in patients with osteoarthritis, oral or intramuscular glucosamine for 4-6 weeks was associated with a greater decrease in symptom severity (as assessed by the Lequesne index) than placebo. In addition, there was a greater proportion of responders (defined as patients with a >or=3-point reduction in the Lequesne index, along with a positive overall assessment by the investigator) at the end of the treatment period with glucosamine than with placebo. In two large 4-week trials, oral glucosamine produced similar improvements to ibuprofen in the Lequesne index in one study and in articular pain scores in the other study. In a smaller 8-week comparative trial, oral glucosamine therapy achieved a significantly greater improvement in articular pain score than ibuprofen, and the investigators rated treatment efficacy as 'good' in a significantly greater proportion of glucosamine than ibuprofen recipients. In comparison with piroxicam, glucosamine significantly improved arthritic symptoms after 12 weeks of therapy and remained effective 8 weeks after treatment was discontinued. Beneficial effects of long-term oral glucosamine therapy in preventing joint space narrowing and improving symptoms were shown in two 3-year placebo-controlled trials in a total of 414 patients with osteoarthritis. Statistically significant differences favouring glucosamine were noted in the per-protocol and intention-to-treat analyses for the primary endpoints for both joint structural changes and symptom modification. Glucosamine has a tolerability profile similar to that of placebo and is better tolerated than ibuprofen or piroxicam. In particular, glucosamine recipients had a markedly lower incidence of gastrointestinal disturbances than those receiving ibuprofen. Other adverse events reported in both glucosamine and ibuprofen recipients were pruritus or skin reactions, flushing and fatigue. In general, a lower incidence of withdrawal from clinical trials was reported for glucosamine recipients than either ibuprofen or piroxicam recipients. In short-term clinical trials, glucosamine provided effective symptomatic relief for patients with osteoarthritis of the knee. In addition, glucosamine has shown promising results in modifying the progression of arthritis over a 3-year period. Glucosamine may therefore prove to be a useful treatment option for osteoarthritis.


Does Cycling Training Reduce Quality of Functional Movement Motor Patterns and Dynamic Postural Control in Adolescent Cyclists? A Pilot Study.
The aim of this study was to assess whether cycling training may influence quality of functional movement patterns and dynamic postural control. We also sought to determine if the Functional Movement Screen and Lower Quarter Y-balance tests could be predictive of injury risk among adolescent road cyclists. Twenty-three male road cyclists, aged 15-18 years, were involved in the study. Quality of functional movement patterns was assessed using the Functional Movement Screen test (FMS). Dynamic postural control was evaluated using the Lower Quarter Y-balance test (YBT-LQ). Information on injury occurrence was collected through a retrospective survey. The results showed the highest percentage of scores equalling 0 and 1 (>30% in total) in two FMS component tests: the hurdle step and trunk stability push-up. The results also demonstrated a low injury predictive value of the Functional Movement Screen (cut-off <14/21 composite score) and the Lower Quarter Y-balance test (cut-off <94% composite score and >4 cm reach distance asymmetry) in adolescent road cyclists. The most important information obtained from this study is that youth road cyclists may have functional deficits within the lumbo-pelvic-hip complex and the trunk, while neither the FMS nor the YBT-LQ test are not recommended for injury risk screening in cyclists.


Temperature dependence of the structural dimensions of the inverted hexagonal (HII) phase of phosphatidylethanolamine-containing membranes.
The characteristic temperature dependence of the lattice basis vector length d of phospholipid-water systems in the inverted hexagonal (HII) phase has been investigated with X-ray diffraction. For 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), d falls sharply from 78.1 A at 10 degrees C to 62.5 A at 90 degrees C. When used in conjunction with the volume fractions of the constituents, d can be used to determine the dimensions within the lipid and water regions. These data showed that a reduction in the radius of the HII-phase water cylinders Rw accounted for most of the reduction in d. From geometrical relationships between the dimensions in the HII phase, it was shown that both d and Rw are sensitive functions of the thickness of the lipid monolayer dHII. The characteristic shape of d(T) could be parameterized with the small temperature dependence of dHII along with the ratio v/a, which is the ratio of the specific volume to the area per lipid molecule at the polar interface. The ratio v/a was found to be independent of temperature for the fully hydrated HII system. Additional measurements made with a mixture of DOPE and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), mole ratio 5.07:1, produced a similar parameterization of d(T). The larger basis vector lengths for this mixture compared to those for DOPE can be attributed to a smaller ratio of v/a, which was also found to be temperature independent for this mixture. The smaller value of v/a is due to the larger effective headgroup area of DOPC.(ABSTRACT TRUNCATED AT 250 WORDS)


["I say no, she says yes": matrimonial violence according to male speech].
This study aims to analize the violence between couples from the man's point of view. We adopted a qualitative methodology approach having as reference the Social Representation Theory. Ten adult men took part in the survey. They live in the Calafate community, in San Martin, Salvador-BA and had a relationship for at least 2 years. In order to collect the data, a semi-estructured interview was used. As a result, it was observed that the respondents agree directly with the process of men and women's socialization in order to define the way husband and wife behave in a relationship. This is an asymetric and hierarchical perspective, where the masculine tendencies are defined by the society, as well as the women's undefined social role. These two motives are pointed out as the explanation for the violence between couples.


The biocathode of microbial electrochemical systems and microbially-influenced corrosion.
The cathode reaction is one of the most important limiting factors in bioelectrochemical systems even with precious metal catalysts. Since aerobic bacteria have a much higher affinity for oxygen than any known abiotic cathode catalysts, the performance of a microbial fuel cell can be improved through the use of electrochemically-active oxygen-reducing bacteria acting as the cathode catalyst. These consume electrons available from the electrode to reduce the electron acceptors present, probably conserving energy for growth. Anaerobic bacteria reduce protons to hydrogen in microbial electrolysis cells (MECs). These aerobic and anaerobic bacterial activities resemble those catalyzing microbially-influenced corrosion (MIC). Sulfate-reducing bacteria and homoacetogens have been identified in MEC biocathodes. For sustainable operation, microbes in a biocathode should conserve energy during such electron-consuming reactions probably by similar mechanisms as those occurring in MIC. A novel hypothesis is proposed here which explains how energy can be conserved by microbes in MEC biocathodes.


Identifying constituents to participate in a project to control pesticide exposure in children of farmworkers.
Farmers in Washington State use pesticides to control harmful pests that might interfere with the quality of their products. Farmworkers, who are primarily responsible for thinning, harvesting, and other agricultural work, are often exposed to these pesticides and take home pesticide residues on their clothing, shoes, and skin, potentially exposing children in the household to pesticides. We designed a project to reduce children's exposure by using a community organization model. To better understand the community views regarding pesticide exposure, we conducted a qualitative community analysis. Two methods of data gathering were used to collect information. Individual interviews were conducted with some respondents, and small group discussions were held with others. Analysis indicated wide disparity among involved groups in their views on pesticides; however, a number of themes common to the majority of the constituents were identified and discussed with a community planning group. Because of the contention around pesticides, the group recommended every constituent participate in decision making. The group noted it was important to emphasize that the research project could provide scientific information on pesticide exposure to everyone in the Lower Yakima Valley. Our study demonstrates both the widely varying views of different constituents around the issue of pesticide exposure and common themes that can form the basis for collaboration and consensus on approaching the issue.


Successful treatment of urinary incontinence with clozapine in a schizophrenic patient.
There is evidence that urinary incontinence (UI) can develop without any organic aetiology as a direct side effect of typical antipsychotic medication. Clozapine was administered to a chronic schizophrenic patient with UI who was refractory to typical antipsychotic medication. After various laboratory and functional tests, UI was demonstrated to be unrelated to any organic aetiology. UI was monitored throughout the study as frequency (wetting the bed) per day and night. The Brief Psychiatric Rating Scale (BPRS) was also rated. Clozapine (dose-dependently) reduced both the BPRS score and frequency of UI, which were refractory to trifluoperazine and sulpiride. This is the first report of a dramatic resolution of UI in a schizophrenic patient after clozapine treatment. It is suggested that preference should be given to clozapine in such cases, since various other antipsychotic medications were ineffective and in some cases worsened the existing UI.


A moral imperative to improve the quality of work-life for nurses: building inclusive social capital capacity.
The complexity and incessant change in the corporatised health care workplace has influenced nurses' work choices, morale, quality of work-life and the wellbeing of patients. Thus, there is an urgent moral imperative to improve the quality of work-life for nurses. To this end, it is crucial to re-define progress beyond the sole economic markers of success and profit in the health care workplace. This paper argues for the identification of ethical markers and indicators of organisational success based on bridging and linking social capital which could be used to re-organise health care organisations, hence crafting inclusive moral spaces where nurses can safely work and provide quality care for patients. Social and ethical evaluation is well suited to examine current workplace dilemmas from a psychosocial perspective and provide a framework for best practice in building capacity in effective social relations and family friendly, ethical workplaces.