Ninety-day inhalation study in rats, comparing smoke from cigarettes that heat tobacco with those that burn tobacco.
Eight groups of 30 male and 30 female rats were exposed 1 hr per day, 5 days per week for 13 weeks, to smoke from reference (tobacco burned) or test (tobacco only heated) cigarettes, at nicotine concentrations of 5, 15, or 30 micrograms/liter of air. Similar smoke concentrations of wet total particulate matter and carbon monoxide were produced in each of the test/reference comparisons. There was a pronounced depression of minute ventilation of animals in the reference groups, but not in the test animals. Blood carboxyhemoglobin concentrations were similar in animals exposed to smoke from test and reference cigarettes. Plasma concentrations of nicotine and cotinine in the test groups were higher than in the reference groups. There were no differences between the smoke-exposed groups in terms of body weight or feed consumption. At necropsy, an increase in heart weight was noted in both high exposure groups. There were notable differences in histopathology, with fewer and less-pronounced changes in the test groups than in the reference groups. Many of the histopathological responses induced in the reference groups were absent in the test groups. Overall, the study demonstrated a substantial reduction in the biological activity of smoke from the test cigarette when compared with the reference.


Monoclonal antibodies to an interferon-induced Mr 68,000 protein and their use for the detection of double-stranded RNA-dependent protein kinase in human cells.
Extracts from interferon-treated human cells show an enhanced level of a double-stranded RNA-dependent protein kinase activity that is manifested by the phosphorylation of an endogenous Mr 69,000-72,000 protein in its phosphate-saturated state. By using a highly purified protein kinase fraction from interferon-treated human Daudi cells, we can now describe the preparation of murine monoclonal antibodies directed against this phosphoprotein, the Mr of which in its native state is found to be 68,000. These monoclonal antibodies (class IgG1) can identify the electrophoresed protein (p68) in polyacrylamide gels by the electrophoretic transfer blotting technique. Immunoprecipitates formed after incubation of extracts from interferon-treated human cells with the monoclonal antibodies can be conveniently recovered by protein A-Sepharose. Such immune complex preparations have associated protein kinase activity--i.e., addition of [gamma-32P]ATP results in the phosphorylation of p68 and added substrates, calf thymus histone, and eukaryotic initiation factor 2. Immune complex preparations from [35S]methionine-labeled extracts show the specific immunoprecipitation of p68. In addition, several other [35S]methionine-labeled proteins are bound unspecifically in these immune complexes prepared under similar experimental conditions as for the assay of protein kinase activity. These unspecifically bound proteins can be washed out by using a buffer containing detergents or high concentrations of KCl and magnesium acetate. Immune complex preparations washed similarly with these buffers still retain p68 but lose their capacity to phosphorylate p68 or exogenous substrates. These results indicate that p68 by itself has no protein kinase activity. The induction of [35S]methionine-labeled p68 in Daudi cells occurs with as little as 1 unit of human alpha interferon, with maximal synthesis between 6 to 9 hr after the addition of interferon. Actinomycin D blocks this induction.


Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos.
Estrogen regulates numerous developmental and physiological processes. Most effects are mediated by estrogen receptors (ERs), which function as ligand-regulated transcription factors. Estrogen also regulates the activity of GPR30, a membrane-associated G protein-coupled receptor. Many different types of environmental contaminants can activate ERs; some can bind GPR30 as well. There is growing concern that exposure to some of these compounds, termed xenoestrogens, is interfering with the behavior and reproductive potential of numerous wildlife species, as well as affecting human health. Here, we investigated how two common, environmentally pervasive chemicals affect the in vivo expression of a known estrogen target gene in the brain of developing zebrafish embryos, aromatase AroB, which converts androgens to estrogens. We confirm that, like estrogen, the well-studied xenoestrogen bisphenol A (BPA, a plastics monomer), induces strong brain-specific overexpression of aromatase. Experiments using ER- and GPR30-selective modulators argue that this induction is largely through nuclear ERs. BPA induces dramatic overexpression of AroB RNA in the same subregions of the developing brain as estrogen. The antibacterial triclocarban (TCC) by itself stimulates AroB expression only slightly, but TCC strongly enhances the overexpression of AroB that is induced by exogenous estrogen. Thus, both BPA and TCC have the potential to elevate levels of aromatase and, thereby, levels of endogenous estrogens in the developing brain. In contrast to estrogen, BPA-induced AroB overexpression was suppressed by TCC. These results indicate that exposures to combinations of certain hormonally active pollutants can have outcomes that are not easily predicted from their individual effects.


On Myelinated Axon Plasticity and Neuronal Circuit Formation and Function.
Studies of activity-driven nervous system plasticity have primarily focused on the gray matter. However, MRI-based imaging studies have shown that white matter, primarily composed of myelinated axons, can also be dynamically regulated by activity of the healthy brain. Myelination in the CNS is an ongoing process that starts around birth and continues throughout life. Myelin in the CNS is generated by oligodendrocytes and recent evidence has shown that many aspects of oligodendrocyte development and myelination can be modulated by extrinsic signals including neuronal activity. Because modulation of myelin can, in turn, affect several aspects of conduction, the concept has emerged that activity-regulated myelination represents an important form of nervous system plasticity. Here we review our increasing understanding of how neuronal activity regulates oligodendrocytes and myelinated axons in vivo, with a focus on the timing of relevant processes. We highlight the observations that neuronal activity can rapidly tune axonal diameter, promote re-entry of oligodendrocyte progenitor cells into the cell cycle, or drive their direct differentiation into oligodendrocytes. We suggest that activity-regulated myelin formation and remodeling that significantly change axonal conduction properties are most likely to occur over timescales of days to weeks. Finally, we propose that precise fine-tuning of conduction along already-myelinated axons may also be mediated by alterations to the axon itself. We conclude that future studies need to analyze activity-driven adaptations to both axons and their myelin sheaths to fully understand how myelinated axon plasticity contributes to neuronal circuit formation and function.


The inositol monophosphatase All2917 (IMPA1) is involved in osmotic adaptation in Anabaena sp. PCC7120.
Inositol monophosphatase (IMPase; EC 220.127.116.11) acts at the last step in the inositol biosynthesis pathway by hydrolysing inositol-1-phosphate into inositol. In this study, an IMPase encoding gene, all2917 from Anabaena sp. PCC7120, was characterized. We found that All2917 exhibits a specific activity on inositol-1-phosphate, in a typical Mg(2+) -dependent, Li(+) -sensitive manner. The deletion of all2917 in Anabaena made the cells more sensitive to osmotic stress caused by sucrose or sorbitol, while its overexpression led to an increased resistance to such stress. Consistent with these phenotypes, the transcription of all2917 was significantly upregulated upon the sucrose-mediated osmotic stress. Phylogenic analysis using 134 IMPase homologues from 36 cyanobacterial strains shows that members of IMPase family form three major distinct clades, suggesting that multiple copies of IMPase family proteins have been maintained in Cyanobacteria during a long history of evolution, and they may play important roles in cyanobacterial physiology.


Assessing the clinical utility of combined movement examination in symptomatic degenerative lumbar spondylosis.
The aim of this study is to report the development and validation of a low back computer-aided combined movement examination protocol in normal individuals and record treatment outcomes of cases with symptomatic degenerative lumbar spondylosis. Test-retest, following intervention. Self-report assessments and combined movement examination were used to record composite spinal motion, before and following neurosurgical and pain medicine interventions. 151 normal individuals aged from 20 years to 69 years were assessed using combined movement examination between L1 and S1 spinal levels to establish a reference range. Cases with degenerative low back pain and sciatica were assessed before and after therapeutic interventions with combined movement examination and a battery of self-report pain and disability questionnaires. Change scores for combined movement examination and all outcome measures were derived. Computer-aided combined movement examination validation and intraclass correlation coefficient with 95% confidence interval and least significant change scores indicated acceptable reliability of combined movement examination when recording lumbar movement in normal subjects. In both clinical cases lumbar spine movement restrictions corresponded with self-report scores for pain and disability. Post-intervention outcomes all showed significant improvement, particularly in the most restricted combined movement examination direction. This study provides normative reference data for combined movement examination that may inform future clinical studies of the technique as a convenient objective surrogate for important clinical outcomes in lumbar degenerative spondylosis. It can be used with good reliability, may be well tolerated by individuals in pain and appears to change in concert with validated measures of lumbar spinal pain, functional limitation and quality of life.


Influenza as a model system for studying the cross-species transfer and evolution of the SARS coronavirus.
Severe acute respiratory syndrome coronavirus (SARS-CoV) moved into humans from a reservoir species and subsequently caused an epidemic in its new host. We know little about the processes that allowed the cross-species transfer of this previously unknown virus. I discuss what we have learned about the movement of viruses into humans from studies of influenza A, both how it crossed from birds to humans and how it subsequently evolved within the human population. Starting with a brief review of severe acute respiratory syndrome to highlight the kinds of problems we face in learning about this viral disease, I then turn to influenza A, focusing on three topics. First, I present a reanalysis of data used to test the hypothesis that swine served as a "mixing vessel" or intermediate host in the transmission of avian influenza to humans during the 1918 "Spanish flu" pandemic. Second, I review studies of archived viruses from the three recent influenza pandemics. Third, I discuss current limitations in using molecular data to study the evolution of infectious disease. Although influenza A and SARS-CoV differ in many ways, our knowledge of influenza A may provide important clues about what limits or favours cross-species transfers and subsequent epidemics of newly emerging pathogens.


Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs.
Patients undergoing solid-organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (HCT) are at increased risk for infectious complications. Community-acquired respiratory viruses (CARVs) pose a particular challenge due to the frequent exposure pre-, peri-, and posttransplantation. Although influenza A and B viruses have a top priority regarding prevention and treatment, recent molecular diagnostic tests detecting an array of other CARVs in real time have dramatically expanded our knowledge about the epidemiology, diversity, and impact of CARV infections in the general population and in allogeneic HCT and SOT patients. These data have demonstrated that non-influenza CARVs independently contribute to morbidity and mortality of transplant patients. However, effective vaccination and antiviral treatment is only emerging for non-influenza CARVs, placing emphasis on infection control and supportive measures. Here, we review the current knowledge about CARVs in SOT and allogeneic HCT patients to better define the magnitude of this unmet clinical need and to discuss some of the lessons learned from human influenza virus, respiratory syncytial virus, parainfluenzavirus, rhinovirus, coronavirus, adenovirus, and bocavirus regarding diagnosis, prevention, and treatment.


Potential function for the ROS-generating activity of TRACP.
TRACP is an enzyme with unknown biological function. It is expressed primarily in bone-resorbing osteoclasts and activated macrophages. In addition to its phosphatase activity, TRACP is capable of generating reactive oxygen species (ROS). In resorbing osteoclasts, TRACP is localized in transcytotic vesicles transporting bone matrix degradation products from the resorption lacuna to a functional secretory domain in the basolateral membrane. ROS generated by TRACP are capable of destroying organic bone matrix components, suggesting that they may be targeted to further destroy initial matrix degradation products in the transcytotic vesicles. The transcytotic route of osteoclasts is analogous with the antigen presentation route of macrophages transporting endocytosed foreign material into cell surface for presentation to other cells of the immune system. Macrophages overexpressing TRACP have elevated levels of intracellular ROS. In alveolar macrophages, TRACP is colocalized with endocytosed Staphylococcus aureus, a pathogen whose clearance is reduced in TRACP-deficient mice, suggesting that ROS generated by TRACP may be targeted to destroy foreign material in the antigen presentation route of macrophages. These data suggest that the ROS generating activity of TRACP may have an important role both in bone resorption and in the immune defense system.


Endovascular treatment of basilar tip aneurysms using electrolytically detachable coils.
Preliminary experience using electrolytically detachable coils to treat basilar tip aneurysms in 33 patients is described. The most frequent presentation was subarachnoid hemorrhage (SAH) in 23 patients. All patients were referred after neurosurgical assessment and exclusion as candidates for surgical clipping of their aneurysms. At the time of initial treatment complete aneurysm occlusion was achieved in seven (21.2%) of 33 patients. In 17 of the patients (51.5%), greater than 90% but less than 100% aneurysm occlusion was achieved. Angiographic follow up (mean 11.7 months) was available in 19 patients. At follow- up angiography four (21%) of 19 aneurysms were 100% occluded and 12 (63.2%) of 19 were more than 90% but less than 100% occluded. The mean clinical follow-up time in treated patients surviving beyond the initial treatment period is 15 months. One patient suffered major permanent morbidity from thrombosis of the basilar tip region a few hours after coil placement. One patient treated following SAH experienced further hemorrhage 6 months later. No other patient suffered direct or indirect permanent morbidity as a consequence of this method of treatment. The authors believe that this technique is a reasonable alternative for patients who are not candidates for conventional surgical treatment or in whom such treatment has failed. This study's follow-up period is brief and greater experience with long-term follow-up study is mandatory.


Association of Preoperative Renal-Resistive Index With Long-term Renal and Cardiovascular Outcomes After Cardiac Surgery.
To investigate the association of elevated preoperative renal-resistive index (RRI) with persistent renal dysfunction, major adverse kidney events (MAKE), and major adverse cardiovascular events (MACE) after cardiac surgery. Observational cohort study. University hospital. Ninety-six adult patients undergoing cardiac surgery. RRI measurement the day before surgery. Fifty-eight patients (60%) had elevated RRI ≥0.70. Five years after surgery, persistent renal dysfunction (sustained decline in estimated glomerular filtration rate ≥25%) had occurred in 25 patients (26%), MAKE (persistent renal dysfunction, renal replacement therapy, or death) in 34 (35%), and MACE (myocardial infarction, unstable angina, decompensated heart failure, stroke, or cardiovascular death) in 28 (29%). RRI was higher in patients who developed persistent renal dysfunction (median, 0.78 [IQR, 0.74-0.82] v 0.70 [0.66-0.77], p = 0.001), MAKE (0.77 [0.72-0.81] v 0.68 [0.65-0.76], p = 0.002), and MACE (0.77 [0.72-0.81] v 0.70 [0.66-0.77], p = 0.006). Patients with elevated RRI had a significantly higher cumulative incidence of all long-term outcomes. After adjustment for baseline renal function and heart failure, elevated RRI was associated with persistent renal dysfunction (hazard ratio [HR], 5.82 [95% CI, 1.71-19.9]), MAKE (HR, 4.21 [1.59-11.1]), and MACE (HR, 2.81 [1.03-7.65]). Elevated preoperative RRI is associated with persistent renal dysfunction, MAKE, and MACE after cardiac surgery. Preoperative RRI may be used for long-term risk assessment in patients undergoing cardiac surgery.


Size and shape in the evolution of ant worker morphology.
Morphological evolution in ants has been traditionally thought as being strongly influenced by selection for colony ergonomic efficiency. Although many studies have focused on the evolution of social characteristics in ants, little is known about the evolution of worker morphology at a macroevolutionary scale. In this study, we investigate the tempo and mode of the evolution of worker morphology, focusing on changes in size and shape. Our datasets included a large sample of species from different ant genera, as well as variation within the hyperdiverse genus Pheidole, for a total of 1650 measurements. The rate of size evolution was at least five times faster than the rate of shape evolution. The fit of alternative models of morphological evolution indicated statistically significant phylogenetic signal in both size and shape and in all datasets. Finally, tests of rate heterogeneity in phenotypic evolution among lineages identified several shifts in rates of evolution in both datasets, although the timing of shifts in size and shape was usually not concordant.


Predictive accuracy of novel risk factors and markers: A simulation study of the sensitivity of different performance measures for the Cox proportional hazards regression model.
Predicting outcomes that occur over time is important in clinical, population health, and health services research. We compared changes in different measures of performance when a novel risk factor or marker was added to an existing Cox proportional hazards regression model. We performed Monte Carlo simulations for common measures of performance: concordance indices ( c, including various extensions to survival outcomes), Royston's D index, R2-type measures, and Chambless' adaptation of the integrated discrimination improvement to survival outcomes. We found that the increase in performance due to the inclusion of a risk factor tended to decrease as the performance of the reference model increased. Moreover, the increase in performance increased as the hazard ratio or the prevalence of a binary risk factor increased. Finally, for the concordance indices and R2-type measures, the absolute increase in predictive accuracy due to the inclusion of a risk factor was greater when the observed event rate was higher (low censoring). Amongst the different concordance indices, Chambless and Diao's c-statistic exhibited the greatest increase in predictive accuracy when a novel risk factor was added to an existing model. Amongst the different R2-type measures, O'Quigley et al.'s modification of Nagelkerke's R2 index and Kent and O'Quigley's [Formula: see text] displayed the greatest sensitivity to the addition of a novel risk factor or marker. These methods were then applied to a cohort of 8635 patients hospitalized with heart failure to examine the added benefit of a point-based scoring system for predicting mortality after initial adjustment with patient age alone.


Barbiturates: active form and site of action at node of Ranvier sodium channels.
Barbiturate sodium channel block was investigated in the voltage-clamped amphibian node of Ranvier. Internal pH was manipulated by diffusion of buffers from the cut internodes. Like local anesthetics and volatile general anesthetics, barbiturates shift the voltage dependence of inactivation in the hyperpolarizing direction. A barbiturate anion, 5-phenyl barbituric acid, blocks sodium channels when applied externally or internally. On external application, block is of very slow onset. The barbiturate anion, like the local anesthetic cation, thus appears to bind to a receptor site on the axoplasmic side of the membrane. Unlike local anesthetics, however, phenobarbital exerts a frequency-dependent block which is modified by changes in internal pH and is not affected by changes in external pH. In addition, barbiturate frequency dependence is apparently more exclusively involved with channel inactivation. The results suggest a barbiturate sodium channel binding site closer to the axoplasm than the local anesthetic binding site is and also suggest that there is a proton barrier between the two sites.


A survey of factor prophylaxis in the Canadian haemophilia A population.
High-dose factor prophylaxis, defined as the infusion of 25-40 factor (F) VIII International Units (IU) kg bodyweight (bw)(-1)> or = x 3 per week, started at age 1-2 years of life in boys with severe haemophilia A prevents the development of significant bleed-related arthropathy. However, programmes of prophylaxis are very expensive and venous access is a challenge. To ascertain patterns of prophylaxis in Canada during the period of a global shortage of recombinant FVIII concentrate a survey was conducted in 2001. The response rate was 83% and the survey identified 247 inhibitor-negative haemophilia A cases receiving prophylaxis, defined as the regular administration of FVIII at least once weekly, from 14 Canadian haemophilia treatment centres. The median age of the group identified was 13 years (range: 1-65) and 95% of cases had severe haemophilia A defined by a circulating factor level of <1%. The median FVIII infusion dose was 26 (range: 16-33) IU kg(-1); infusions were administered > or = x 3 per week in 67% of cases. High-dose factor prophylaxis was used most frequently in boys <5 years of age (23 of 28 cases, 82%) as compared with 56% (56 of 100), 66% (40 of 61) and 62% (36 of 58) of males ages 5-12, 13-18 and >18 years. Prophylaxis accounted for 50% of the annual Canadian FVIII consumption and was a major driving force in the 10% increase (=19.3 million FVIII IU) in the FVIII consumption in Canada in the 4-year period 1999-2003. Given the economic implications of increased use of prophylaxis prospective studies are warranted to better define optimal prophylaxis regimens in the haemophilia A population.


Mydriatic effectiveness of hydroxyamphetamine.
For routine mydriasis, many clinicians prefer to utilize a combination of adrenergic and anticholinergic agents. Some clinicians, however, omit the adrenergic agent because of a real or perceived fear of inducing adverse systemic side effects. The agent most often implicated in causing side effects is 10% phenylephrine. Although the 2 1/2% concentration rarely results in adverse systemic side effects when applied topically for pupillary dilation, we undertook this study to determine whether another adrenergic agent, 1% hydroxyamphetamine, which lacks the notoriety of phenylephrine, would be equally effective in producing mydriasis.


Functional characterization of a TerC family protein of Riemerella anatipestifer in manganese detoxification and virulence.
Riemerella anatipestifer is a notorious bacterial pathogen of ducks and other birds. In R. anatipestifer, the genes involved in manganese efflux have not been completely identified, although MetA and MetB have been identified as two manganese exporters. Additionally, the function of TerC family proteins in manganese efflux is controversial. Here, we demonstrated that a TerC family protein helps prevent Mn(II) intoxication in R. anatipestifer and that the ability of TerC to export manganese is intermediate compared to that of MetA and MetB. Sequence analysis and mutagenesis studies showed that the conserved key amino sites of TerC are Glu116, Asp122, Glu245, Asp248, and Asp254. The transcription of terC was regulated by manganese excess and iron limitation. Finally, we show that TerC plays a role in the virulence of R. anatipestifer due to the increased sensitivity to duck serum, rather than the increased sensitivity to manganese. Taken together, these results expand our understanding of manganese efflux and the pathogenic mechanisms of R. anatipestifer.


Increased IgM and IgM immune complex-like material in the circulation of renal transplant recipients with primary cytomegalovirus infections.
Twelve of 60 consecutive adult recipients of cadaver kidney transplants had increased polyethyleneglycol (PEG) precipitable IgM immune complex-like material in their circulation in the first 4 months after transplantation. All 10 recipients with primary CMV and two of four with secondary CMV infections had significant elevations in PEG precipitable IgM that coincided with rises in their CMV antibody titres. Ultracentrifuge analysis demonstrated two peaks of PEG precipitable material with sedimentation rates of about 20S and 40S. Total IgM immunoglobulin levels also were increased in transplant recipients with CMV infections, but this was less specific and occurred in patients without CMV infections. The Clq binding assay, which is more sensitive for IgG than IgM containing complexes, was positive in only three of 10 patients with primary CMV and none of four with secondary CMV. Granular deposits of IgM, but not IgG, were detected in the glomeruli of six of seven transplants biopsied during CMV infection. The PEG-IgM assay was not influenced by rejection or prednisone therapy. Thus, transplant patients, who develop primary CMV infections, produce elevated levels of circulating IgM and IgM immune complex-like material. These findings may help to differentiate CMV infection from transplant rejection as well as to increase our understanding of the special pathogenic properties of CMV in transplant recipients.


Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia.
In a single-blind, crossover, completely randomized study, the effects of oral treatment with pantethine or placebo on fatty acid composition of plasma and platelet phospholipids were investigated in 10 IIa hyperlipoproteinemic patients. A significant decrease of total cholesterol and total phospholipids was observed both in plasma and in platelets after a twenty-eight-day treatment. In plasma, pantethine induced a decrease of the ratio sphingomyelin/phosphatidylcholine. Moreover, a relative increase of n3-polyunsaturated fatty acids both in plasma and in platelet phospholipids and a decrease of arachidonic acid in plasma phospholipids were observed. These results indicate that pantethine can affect plasma and platelet lipid composition with possibly favorable influences on the determinants of cell membrane fluidity.


Optimal Modality Selection for Cooperative Human-Robot Task Completion.
Human-robot cooperation in complex environments must be fast, accurate, and resilient. This requires efficient communication channels where robots need to assimilate information using a plethora of verbal and nonverbal modalities such as hand gestures, speech, and gaze. However, even though hybrid human-robot communication frameworks and multimodal communication have been studied, a systematic methodology for designing multimodal interfaces does not exist. This paper addresses the gap by proposing a novel methodology to generate multimodal lexicons which maximizes multiple performance metrics over a wide range of communication modalities (i.e., lexicons). The metrics are obtained through a mixture of simulation and real-world experiments. The methodology is tested in a surgical setting where a robot cooperates with a surgeon to complete a mock abdominal incision and closure task by delivering surgical instruments. Experimental results show that predicted optimal lexicons significantly outperform predicted suboptimal lexicons (p <; 0.05) in all metrics validating the predictability of the methodology. The methodology is validated in two scenarios (with and without modeling the risk of a human-robot collision) and the differences in the lexicons are analyzed.


Cis and trans regulation of hepcidin expression by upstream stimulatory factor.
Hepcidin is the presumed negative regulator of systemic iron levels; its expression is induced in iron overload, infection, and inflammation, and by cytokines, but is suppressed in hypoxia and anemia. Although the gene is exquisitely sensitive to changes in iron status in vivo, its mRNA is devoid of prototypical iron-response elements, and it is therefore not obvious how it may be regulated by iron flux. The multiplicity of effectors of its expression also suggests that the transcriptional circuitry controlling the gene may be very complex indeed. In delineating enhancer elements within both the human and mouse hepcidin gene promoters, we show here that members of the basic helix-loop-helix leucine zipper (bHLH-ZIP) family of transcriptional regulators control hepcidin expression. The upstream stimulatory factor 2 (USF2), previously linked to hepcidin through gene ablation in inbred mice, appears to exert a polar or cis-acting effect, while USF1 may act in trans to control hepcidin expression. In mice, we found variation in expression of both hepcidin genes, driven by these transcription factors. In addition, c-Myc and Max synergize to control the expression of this hormone, supporting previous findings for the role of this couple in regulating iron metabolism. Transcriptional activation by both USF1/USF2 and c-Myc/Max heterodimers occurs through E-boxes within the promoter. Site-directed mutagenesis of these elements rendered the promoter unresponsive to USF1/USF2 or c-Myc/Max. Dominant-negative mutants of USF1 and USF2 reciprocally attenuated promoter transactivation by both wild-type USF1 and USF2. Promoter occupancy by the transcription factors was confirmed by DNA-binding and chromatin immunoprecipitation assays. Taken together, it would appear that synergy between these members of the bHLH-ZIP family of transcriptional regulators may subserve an important role in iron metabolism as well as other pathways in which hepcidin may be involved.


Ion structure controls ionic liquid near-surface and interfacial nanostructure.
A unique, but unifying, feature of ionic liquids (ILs) is that they are nanostructured on the length scale of the ions; in many ILs well-defined polar and apolar domains exist and may percolate through the liquid. Near a surface the isotropic symmetry of the bulk structure is broken, resulting in different nanostructures which, until now, have only been studied indirectly. In this paper, in situ amplitude modulated atomic force microscopy (AM-AFM) has been used to resolve the 3-dimensional nanostructure of five protic ILs at and near the surface of mica. The surface and near surface structures are distinct and remarkably well-defined, but are very different from previously accepted descriptions. Interfacial nanostructure is strongly influenced by the registry between cations and the mica surface charge sites, whereas near surface nanostructure is sensitive to both cation and anion structure. Together these ILs reveal how interfacial nanostructure can be tuned through ion structure, informing "bottom-up" design and optimisation of ILs for diverse technologies including heterogeneous catalysis, lubrication, electrochemical processes, and nanofluids.


The effect of the trabecular microstructure on the pullout strength of suture anchors.
This study investigates how the microstructural properties of trabecular bone affect suture anchor performance. Seven fresh-frozen humeri were tested for pullout strength with a 5mm Arthrex Corkscrew in the greater tuberosity, lesser tuberosity, and humeral head. Micro-computed tomography analysis was performed in the three regions of interest directly adjacent to individual pullout experiments. The morphometric properties of bone mineral density (BMD), structural model index (SMI), trabecular thickness (TbTh), trabecular spacing (TbS), trabecular number (TbN), and connectivity density were compared against suture anchor pullout strength. BMD (r=0.64), SMI (r=-0.81), and TbTh (r=0.71) showed linear correlations to the pullout strength of the suture anchor with p-values<0.0001. A predictive model was developed to explain the variances in the individual BMD, SMI, and TbTh correlations. The multi-variant model of pullout strength showed a stronger relationship (r=0.86) compared to the individual experimental results. This study helps confirm BMD is a major influence on the pullout strength of suture anchors, but also illustrates the importance of local microstructure in pullout resistance of suture anchors.


Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.
Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer's disease. Therefore, it is our primary goal to determine whether spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of spermidine intake on other neuropsychological, behavioral, and physiological parameters. The SmartAge trial is a monocentric, randomized, double-blind, placebo-controlled phase IIb trial. The study will investigate 12 months of intervention with spermidine-based nutritional supplementation (target intervention) compared with 12 months of placebo intake (control intervention). We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Participants will be allocated to one of the two study arms using blockwise randomization stratified by age and sex with a 1:1 allocation ratio. The primary outcome is the change in memory performance between baseline and post-intervention visits (12 months after baseline). Secondary outcomes include the change in memory performance from baseline to follow-up assessment (18 months after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention. The SmartAge trial aims to provide evidence of the impact of spermidine supplementation on memory performance in older individuals with SCD. In addition, we will identify possible neurophysiological mechanisms of action underlying the anticipated cognitive benefits. Overall, this trial will contribute to the establishment of nutrition intervention in the prevention of Alzheimer's disease. ClinicalTrials.gov, NCT03094546 . Registered 29 March 2017-retrospectively registered. Based on EA1/250/16 version 1.5.


Association of dietary antioxidants on the severity of gastritis in a high risk population.
PURPOSE: This study is to examine the role of dietary antioxidant intake on the severity of gastritis at the baseline in an intervention study, Chemoprevention of Gastric Dysplasia.METHODS: The Chemoprevention of Gastric Dysplasia is an intervention study conducted in the towns of Pasto and Tuquerres, Colombia. A 79-item food frequency questionnaire was administered to 1,219 subjects at baseline. Endoscopic screening for precancerous gastric lesions was performed in all subjects by biopsy and histologic diagnosis. Subjects without adequate diagnostic material (n = 18) and subjects identified as histologically normal (n = 12) or with gastric cancer (n = 4) were excluded from these analyses. Analysis of Variance on logarithm-transformed data was conducted on dietary antioxidants and the stages of gastritis (atrophic gastritis, intestinal metaplasia, and gastric dysplasia).RESULTS: After adjusting for age, body mass index, smoking status, year of education, total calorie intake, and H-pylori infection status, dietary vitamin C and vitamin E were found to be inversely associated with the severity of gastritis (p < 0.05). Decreased dietary alpha-carotene was found to be marginally associated with gastric dysplasia. Data were then stratified by town where subjects were recruited. The trends for the observed associations were apparent for dietary alpha-carotene, vitamin C and E. However, the association was significant only for vitamin C in Pasto. Compared to subjects with atrophic gastritis, subjects diagnosed with gastric dysplasia have an approximately 15% lower intake of vitamin C.CONCLUSIONS: This study confirmed the protective effect of specific dietary antioxidants on the severity of gastritis. Dietary vitamin C, and to a lesser extent, dietary vitamin E are potentially important for the prevention of gastric cancer.


Impact of HIV testing and counseling (HTC) knowledge on HIV prevention practices among traditional birth attendants in Nigeria.
Nigeria is second in the world for the number of people with HIV and has a high rate of mother-to-child transmission (MTCT). Over 60% of births in Nigeria occur outside of health care facilities, and because of this, Traditional Birth Attendants (TBAs) play a significant role in maternal and child health. It is important that TBAs be knowledgeable about HIV prevention. The purpose of this study was to determine the impact of HIV testing and counseling (HTC) knowledge on the HIV prevention practices among TBAs in Nigeria. Five hundred TBAs were surveyed. Chi-square and logistic regression were used to assess differences in HIV prevention practices between TBAs with and without HTC knowledge. TBAs with HTC knowledge are significantly more likely to engage in HIV prevention practices than TBAs without HTC. Prevention practices included: wearing gloves during delivery (p < 0.01), sterilization of delivery equipment (p < 0.01), participation in blood safety training (p < 0.01), and disposal of sharps (p < 0.01). As long as a high percent of births occur outside health care facilities in Nigeria, there will be a need for TBAs. Providing TBAs with HTC training increases HIV prevention practices and can be a key to improve maternal and child health.


Neural network-based adaptive controller design of robotic manipulators with an observer.
A neural network (NN)-based adaptive controller with an observer is proposed for the trajectory tracking of robotic manipulators with unknown dynamics nonlinearities. It is assumed that the robotic manipulator has only joint angle position measurements. A linear observer is used to estimate the robot joint angle velocity, while NNs are employed to further improve the control performance of the controlled system through approximating the modified robot dynamics function. The adaptive controller for robots with an observer can guarantee the uniform ultimate bounds of the tracking errors and the observer errors as well as the bounds of the NN weights. For performance comparisons, the conventional adaptive algorithm with an observer using linearity in parameters of the robot dynamics is also developed in the same control framework as the NN approach for online approximating unknown nonlinearities of the robot dynamics. Main theoretical results for designing such an observer-based adaptive controller with the NN approach using multilayer NNs with sigmoidal activation functions, as well as with the conventional adaptive approach using linearity in parameters of the robot dynamics are given. The performance comparisons between the NN approach and the conventional adaptation approach with an observer is carried out to show the advantages of the proposed control approaches through simulation studies.


Inhibition of fos-jun-DNA complex formation by dihydroguaiaretic acid and in vitro cytotoxic effects on cancer cells.
The effect of dihydroguaiaretic acid (DHGA), isolated from the aryls of Myristica fragrans, on the transcription factor (fos-jun dimer) action was investigated via in vitro assay. DHGA showed an inhibitory effect against the complex formation of the fos-jun dimer and the DNA consensus sequence with an IC50 value of 0.21 micromol. Nordihydroguaiaretic acid (NDGA) and curcumin also inhibited fos-jun dimer action showing IC50 values of 7.9 and 6.9 nmol, respectively. DHGA and NDGA suppressed leukemia, lung cancer and colon cancer in an in vitro bioassay. The in vitro experiment suggested that inhibition of fos-jun-DNA complex formation could be due to the direct interference of fos-jun dimer binding onto the DNA consensus sequence by NDGA and curcumin.


A Novel Intronic Pathogenic Variant in STAR With a Dominant Negative Mechanism Causes Attenuated Lipoid Congenital Adrenal Hyperplasia.
Lipoid congenital adrenal hyperplasia (LCAH) is typically inherited as an autosomal recessive condition. There are 3 reports of individuals with a dominantly acting heterozygous variant leading to a clinically significant phenotype. We report a 46,XY child with a novel heterozygous intronic variant in STAR resulting in LCAH with an attenuated genital phenotype. The patient presented with neonatal hypoglycemia and had descended testes with a fused scrotum and small phallus. Evaluation revealed primary adrenal insufficiency with deficiencies of cortisol, aldosterone, and androgens. He was found to have a de novo heterozygous novel variant in STAR: c.65-2A>C. We report a case of a novel variant and review of other dominant mutations at the same position in the literature. Clinicians should be aware of the possibility of attenuated genital phenotypes of LCAH and the contribution of de novo variants in STAR at c.65-2 to the pathogenesis of that phenotype.


Interrelationships among postprandial satiety, glucose and insulin responses and changes in subsequent food intake.
The aim of this study was to investigate whether postprandial glucose and insulin responses were related to concurrent changes in satiety. Thirty-eight common foods, grouped into six food categories, were tested in total. Each food category was fed to a separate group of subjects. A within-subjects repeated-measures design was used such that within each food category each subject consumed all of the test foods in random order. The study was conducted at the Human Nutrition Research Unit, Sydney University. Separate groups of 11-13 healthy young subjects, who were unrestrained eaters, were recruited for each of the six food categories. Isoenergetic 1000 kJ (240 kcal) portions of the test foods were fed to fasting subjects. Fingerprick blood samples and satiety ratings were obtained every 15 min over 120 min after which a standard meal was presented and ad libitum food intake was recorded. A glycaemic score, insulin index and satiety index score was calculated for each food by dividing the area under the 120 min response curve (AUC) for the test food by the AUC for white bread and multiplying by 100. Expressing the results of the test foods relative to those for white bread minimised the confounding influence of inherent differences between the subjects. Among the 38 test foods, there were no significant relationships between satiety and plasma glucose or insulin responses. However, a negative correlation was found between insulin AUC responses and ad libitum food intake at 120 min which suggests that test foods producing a higher insulin response within 120 min were associated with less food intake and thus indirectly greater satiety. This result is consistent with previous findings that carbohydrate-rich foods are more satiating than fat-rich foods. Thus, total carbohydrate content appears to have been a stronger determinant of short-term satiety, in conjunction with the foods structural characteristics, than the foods glycaemic impact. The total amount of carbohydrate consumed at a meal and subsequent insulinaemia may partly determine the degree of hunger arising within the next 2 h.


Participation of Brahma-related gene 1 (BRG1)-associated factor 57 and BRG1-containing chromatin remodeling complexes in thyroid hormone-dependent gene activation during vertebrate development.
Multiple cofactors and chromatin remodeling complexes have been identified to contribute to the transcriptional activation regulated by thyroid hormone receptors (TRs) in vitro. However, their role and function during development in vivo remains to be elucidated. The total dependence of amphibian metamorphosis on thyroid hormone T3 provides a unique vertebrate model for studying the molecular mechanism of TR function in vivo. In this study, we show that the expression of Brahma-related gene 1 (BRG1), a chromatin-remodeling enzyme, is up-regulated at the climax of Xenopus laevis metamorphosis, whereas BRG1-associated factor 57 (BAF57), a BRG1-binding protein in BRG1-containing chromatin remodeling complexes, is constitutively expressed during development. Consistently, T3 treatment of premetamorphic tadpoles led to up-regulation of the expression of BRG1 but not BAF57. Studies using a reconstituted T3-dependent Xenopus oocyte transcription system, where we could study TR function in the context of chromatin, revealed that BRG1 enhances the transcriptional activation by ligand-bound TRs in a dose-dependent manner, whereas a remodeling-defective BRG1 mutant inhibited the activation, suggesting that this process relies on chromatin remodeling. Additional studies showed that BAF57 interacted with BRG1 in oocytes and enhanced gene activation by TR cooperatively with BRG1 in vivo. Chromatin immunoprecipitation revealed that BAF57 was recruited to the TR-regulated promoter in the presence of TR and T3. Together, these findings suggest a role of BRG1/BAF57-containing chromatin remodeling complexes in TR-regulated gene expression during postembryonic development.


Early but not late allograft nephrectomy reduces allosensitization after transplant failure.
Allosensitization is a significant obstacle to retransplantation for patients with primary renal graft failure. We assessed the impact of allograft nephrectomy (Group I) and weaning of immunosuppression (Group II) on percent panel reactive antibody (%PRA) at various time points after graft failure in 132 patients with a median follow-up of 47 months. Of these, 68% had allograft nephrectomy while 32% were placed on the waiting list and were either taken off immunosuppression, left on prednisone or on low-dose immunosuppressive therapy. When groups were stratified into early (<6 months) and late (>6 months) graft failure, patients who had transplant nephrectomy for early failure demonstrated a decline in %PRA from 46% at time of graft failure to 27% at last follow-up (p = 0.02); conversely, %PRA continued to rise in Group II experiencing early allograft failure. Both Groups I and II patients with late graft failure maintained elevated %PRA at last follow-up. Allograft nephrectomy may play a role in limiting allosensitization in patients with early but not late graft failures.


Cd, Pb, and Zn mobility and (bio)availability in contaminated soils from a former smelting site amended with biochar.
Biochar is a potential candidate for the remediation of metal(loid)-contaminated soils. However, the mechanisms of contaminant-biochar retention and release depend on the amount of soil contaminants and physicochemical characteristics, as well as the durability of the biochar contaminant complex, which may be related to the pyrolysis process parameters. The objective of the present study was to evaluate, in a former contaminated smelting site, the impact of two doses of wood biochar (2 and 5% w/w) on metal immobilization and/or phytoavailability and their effectiveness in promoting plant growth in mesocosm experiments. Different soil mixtures were investigated. The main physicochemical parameters and the Cd, Pb, and Zn contents were determined in soil and in soil pore water. Additionally, the growth, dry weight, and metal concentrations were analyzed in the different dwarf bean plant (Phaseolus vulgaris L.) organs tested. Results showed that the addition of biochar at two doses (2 and 5%) improved soil conditions by increasing soil pH, electrical conductivity, and water holding capacity. Furthermore, the application of biochar (5%) to metal-contaminated soil reduced Cd, Pb, and Zn mobility and availability, and hence their accumulation in the different P. vulgaris L. organs. In conclusion, the data clearly demonstrated that biochar application can be effectively used for Cd, Pb, and Zn immobilization, thereby reducing their bioavailability and phytotoxicity.


Modeling new immunoregulatory therapeutics as antimicrobial alternatives for treating Clostridium difficile infection.
The current treatment paradigm in Clostridium difficile infection is the administration of antibiotics contributing to the high rates of recurrent infections. Recent alternative strategies, such as fecal microbiome transplantation and anti-toxin antibodies, have shown similar efficacy in the treatment of C. difficile associated disease (CDAD). However, barriers exist for either treatment or other novel treatments to displace antibiotics as the standard of care. To aid in the comparison of these and future treatments in CDAD, we developed an in silico pipeline to predict clinical efficacy with nonclinical results. The pipeline combines an ordinary differential equation (ODE)-based model, describing the immunological and microbial interactions in the gastrointestinal (GI) mucosa, with machine learning algorithms to translate simulated output quantities (i.e. time of clearance, quantity of commensal bacteria, T cell ratios) into clinical predictions based on prior preclinical, translational and clinical trial data. As a use case, we compare the efficacy of lanthionine synthetase C-like 2 (LANCL2), a novel immunoregulatory target with promising efficacy in inflammatory bowel disease (IBD), activation with antibiotics, fecal microbiome transplantation and anti-toxin antibodies in the treatment of CDAD. We further validate the potential of LANCL2 pathway activation, in a mouse model of C. difficile infection in which it displays an ability to decrease weight loss and inflammatory cell types while protecting against mortality. The computational pipeline can serve as an important resource in the development of new treatment modalities.


Anatomy of the Canine Skull in Low-grade Otocephaly.
An inherited low-grade otocephaly in a strain of Beagles was studied. All cases were "mild" with partial agnathia a constant feature in the adult animal. One case of high-grade otocephaly with aprosopus was recorded in an outcrossed animal. Neonatal mortalities in the low-grade type were associated with gross patency of the parietal fontanelle and hydrocephaly. Enlarged lateral ventricles were found in adult dogs, associated with incomplete union of the cranial sutures and occasional membranous-like paietal bone replacement over the patent fontanelle. Partial agnathia was not obvious in the neonate, but became apparent during postnatal skeletal development. The major anatomical differences in the skulls of these dogs were compared with normal Beagles. Malocclusion of the lower mandible and teeth against the upper jaw during development may have resulted in changes in length and width of the upper jaw and certain cranial structures. It was thought that the maloccluding lower jaw acted as a wedge against the upper jaw during mastication and these abnormal pressures, transmitted in an upward, forward, and outward direction, caused lengthening and widening of the palatine and temporal bones, and lengthening of the premaxilla and nasal bones. The nasopharyngeal meatus and palatine fissures were narrower and elongated. The pterygoid processes were pulled into a more horizontal position. It was suggested that a primary inherited abnormality may cause secondary changes in contiguous structures during development, and differentiation between primary (genetic) and secondary (acquired) anatomical abnormalities should be considered.


Adaptive introgression as a resource for management and genetic conservation in a changing climate.
Current rates of climate change require organisms to respond through migration, phenotypic plasticity, or genetic changes via adaptation. We focused on questions regarding species' and populations' ability to respond to climate change through adaptation. Specifically, the role adaptive introgression, movement of genetic material from the genome of 1 species into the genome of another through repeated interbreeding, may play in increasing species' ability to respond to a changing climate. Such interspecific gene flow may mediate extinction risk or consequences of limited adaptive potential that result from standing genetic variation and mutation alone, enabling a quicker demographic recovery in response to changing environments. Despite the near dismissal of the potential benefits of hybridization by conservation practitioners, we examined a number of case studies across different taxa that suggest gene flow between sympatric or parapatric sister species or within species that exhibit strong ecotypic differentiation may represent an underutilized management option to conserve evolutionary potential in a changing environment. This will be particularly true where advanced-generation hybrids exhibit adaptive traits outside the parental phenotypic range, a phenomenon known as transgressive segregation. The ideas presented in this essay are meant to provoke discussion regarding how we maintain evolutionary potential, the conservation value of natural hybrid zones, and consideration of their important role in adaptation to climate.


Detection and monitoring toxigenicity of cyanobacteria by application of molecular methods.
The aim of this study was early genetic identification of microcystin-producing cyanobacteria and monitoring their toxigenicity by determining toxin concentrations in three Polish lakes throughout the summer of 2004. The assessment of cyanobacterial blooms was carried out in shallow, eutrophic water bodies: Lake Jeziorak, Lake Bninskie, and Sulejow Reservoir. Samples for DNA, phycological, and toxin analyses were collected from July till October. Molecular analysis of the 16S rRNA region was used to detect cyanobacteria in water samples. The microscopic analysis was performed to investigate seasonal variation of phytoplankton. Cyanobacteria, with domination by Microcystis, Planktothrix, and Planktolyngbya were detected during the whole monitoring period in Sulejow Reservoir, Lake Bninskie, and Lake Jeziorak, respectively. The presence and identification of toxic strains in water bodies was studied by PCR amplification of mcy genes in the microcystis synthesis pathway. The presence of the mcyA, mcyB, mcyD, and mcyE genes in water samples indicated the genetic potential to produce microcystins. Toxicity of water samples and microcystin concentrations were established by PPIA and HPLC, respectively. The maximum concentration of microcystins was 11.13 microg/L and 4.67 microg/L in samples dominated by P. agardhii and M. aeruginosa, respectively. Molecular analysis showed that toxigenic strains of cyanobacteria occurred in the three lakes throughout the summer season.


Flexible regression models over river networks.
Many statistical models are available for spatial data but the vast majority of these assume that spatial separation can be measured by Euclidean distance. Data which are collected over river networks constitute a notable and commonly occurring exception, where distance must be measured along complex paths and, in addition, account must be taken of the relative flows of water into and out of confluences. Suitable models for this type of data have been constructed based on covariance functions. The aim of the paper is to place the focus on underlying spatial trends by adopting a regression formulation and using methods which allow smooth but flexible patterns. Specifically, kernel methods and penalized splines are investigated, with the latter proving more suitable from both computational and modelling perspectives. In addition to their use in a purely spatial setting, penalized splines also offer a convenient route to the construction of spatiotemporal models, where data are available over time as well as over space. Models which include main effects and spatiotemporal interactions, as well as seasonal terms and interactions, are constructed for data on nitrate pollution in the River Tweed. The results give valuable insight into the changes in water quality in both space and time.


Clarifying the mechanics of DNA strand exchange in meiotic recombination.
During meiosis, accurate separation of maternal and paternal chromosomes requires that they first be connected to one another through homologous recombination. Meiotic recombination has many intriguing but poorly understood features that distinguish it from recombination in mitotically dividing cells, and several of these features depend on the meiosis-specific DNA strand exchange protein Dmc1 (disrupted meiotic cDNA1). Many questions about this protein have arisen since its discovery more than a decade ago, but recent genetic and biochemical breakthroughs promise to shed light on the unique behaviours and functions of this central player in the remarkable chromosome dynamics of meiosis.


Figure drawing as an expression of self-esteem.
Figure drawings were obtained from 97 preadolescent males who differed in self and behavioral assessments of self-esteem. These subjects had been selected from a much larger sample and represented five different types of self-esteem. The figure drawings were scored for 15 variables, dealing with formal characteristics, content, and global-interpretations of the total drawings. Five significant differences were obtained, with the content and global-interpretative categories proving more differentiating between self-esteem groups than did the formal characteristics. Behavioral expressions of self-esteem were more associated with figure drawing characteristics than were subjective evaluations. Discussion focuses on the nature of self-concept and self-esteem in children as a sensorimotor rather than symbolic expression.


In vitro crevice corrosion behavior of implant materials.
The crevice corrosion susceptibility of cold-worked Type 316LVM stainless steel, cast Co-Cr-Mo, wrought Co-Cr-W-Ni, non-nitrided and nitrided Ti-6Al-4V ELI, and c.p. Ti, Grades 1 and 4, was studied in vitro by means of a crevice cell. Occlusion was created by interfacing a disc specimen and a Teflon bar. Specimens were mechanically prepared through 2-4 micron Al2O3 and passivated in 30% HNO3, followed by steam sterilization. Tests were performed in a deaerated Ringer's solution, maintained at pH = 7 and 37 degrees C. Anodic polarization was conducted potentiostatically at pre-selected levels, and resultant currents were monitored: stainless steel, 50 and 100 mV (S.C.E.), 450 min; non-stainless materials, 600 mV, 1000 min. Results for the stainless steel demonstrated that a HNO3 passivation treatment reduced its crevice corrosion susceptibility. For the non-stainless steel materials, no crevice corrosion susceptibility was observed, although a dulling and discoloration of c.p. Ti was evident. Recognizing that 600 mV is in excess of the O2 reduction potential in vivo, it was concluded that, in the absence of fretting, implants of these non-stainless steel materials would not experience significant corrosion loss under crevice conditions.


The research agenda on oral health inequalities: the IADR-GOHIRA initiative.
The World Health Organization asserts that oral health is a basic human right, yet this is a right enjoyed by few. Oral disease is a major problem in high-income countries, where the cost of treating oral diseases often exceeds that for major non-communicable diseases. In low-to-middle income countries, oral diseases are a severe and growing public health problem. Furthermore, major inequalities exist both within and between countries in terms of disease severity and prevalence, and major social gradients exist in the prevalence of oral disease. The International Association for Dental Research (IADR) has responded to the challenge of poor oral health and oral health inequalities through the Global Oral Health Inequalities: the Research Agenda (GOHIRA) initiative. In a Call to Action it has set out the priorities for research that can lead to a reduction in oral health inequalities. Three key challenges have been identified, namely gaps in knowledge and an insufficient focus on social policy, the separation of oral health from general health, and inadequate evidence-based data. Ten key research priorities have been identified with due regard to the differing needs of the variety of global health care systems, and a set of prioritized outcomes and a timeline for implementation have been defined. In the wider context of the proposals set out above, five immediate priorities for action have been proposed.


Beyond the Baby Bump: Subtle Discrimination Against Working Mothers In the Hiring Process.
Despite a large proportion of working mothers in the American workforce, research suggests that negative stereotypes and discrimination against working mothers continue to exist. In a set of two experimental studies, the current paper examined subtle discrimination against non-pregnant, working mothers in different hiring settings. In Study 1, using a between-subject field experiment and applying for geographically dispersed jobs with manipulated resumes, we found evidence for subtle discrimination, such that mothers received more negativity in callback messages than women without children, men without children, and fathers. They were also rejected more quickly than women without children and fathers. In Study 2, using a more controlled experimental paradigm, we tested our hypothesis in a hypothetical interview evaluation setting. We found that mothers faced more interpersonal hostility across different job types as compared to women without children. Together, these studies highlight the presence of subtle discrimination against working mothers at different stages of the hiring process.


Use of computational fluid dynamics models for dosimetry of inhaled gases in the nasal passages.
Computational fluid dynamics (CFD) models of the nasal passages of a rat, monkey, and human are being used (1) to determine important factors affecting nasal uptake, (2) to make interspecies dosimetric comparisons, (3) to provide detailed anatomical information for the rat, monkey, and human nasal passages, and (4) to provide estimates of regional air-phase mass transport coefficients (a measure of the resistance to gas transport from inhaled air to airway walls) in the nasal passages of all three species. For many inhaled materials, lesion location in the nose follows patterns that are both site and species specific. For reactive, water-soluble (Category 1) gases, regional uptake can be a major factor in determining lesion location. Since direct measurement of airflow and uptake is experimentally difficult, CFD models are used here to predict uptake patterns quantitatively in three-dimensional reconstructions of the F344 rat, rhesus monkey, and human nasal passages. In formaldehyde uptake simulations, absorption processes were assumed to be as rapid as possible, and regional flux (transport rate) of inhaled formaldehyde to airway walls was calculated for rats, primates, and humans. For uptake of gases like vinyl acetate and acrylic acid vapors, physiologically based pharmacokinetic uptake models incorporating anatomical and physical information from the CFD models were developed to estimate nasal tissue dose in animals and humans. The use of biologically based models in risk assessment makes sources of uncertainty explicit and, in doing so, allows quantification of uncertainty through sensitivity analyses. Limited resources can then be focused on reduction of important sources of uncertainty to make risk estimates more accurate.


Murine glomerular transcriptome links endothelial cell-specific molecule-1 deficiency with susceptibility to diabetic nephropathy.
Diabetic nephropathy (DN) is the leading cause of kidney disease; however, there are no early biomarkers and no cure. Thus, there is a large unmet need to predict which individuals will develop nephropathy and to understand the molecular mechanisms that govern this susceptibility. We compared the glomerular transcriptome from mice with distinct susceptibilities to DN at four weeks after induction of diabetes, but before histologic injury, and identified differential regulation of genes that modulate inflammation. From these genes, we identified endothelial cell specific molecule-1 (Esm-1), as a glomerular-enriched determinant of resistance to DN. Glomerular Esm-1 mRNA and protein were lower in DN-susceptible, DBA/2, compared to DN-resistant, C57BL/6, mice. We demonstrated higher Esm-1 secretion from primary glomerular cultures of diabetic mice, and high glucose was sufficient to increase Esm-1 mRNA and protein secretion in both strains of mice. However, induction was significantly attenuated in DN-susceptible mice. Urine Esm-1 was also significantly higher only in DN-resistant mice. Moreover, using intravital microscopy and a biomimetic microfluidic assay, we showed that Esm-1 inhibited rolling and transmigration in a dose-dependent manner. For the first time we have uncovered glomerular-derived Esm-1 as a potential non-invasive biomarker of DN. Esm-1 inversely correlates with disease susceptibility and inhibits leukocyte infiltration, a critical factor in protecting the kidney from DN.


Zernike polynomials as a basis for wave-front fitting in lateral shearing interferometry.
A new method for handling Zernike polynomials is presented. Owing to its efficiency, this method enables the use of Zernike polynomials as a basis for wave-front fitting in shearography systems. An excerpt of a C(++) class is presented to show how the polynomials are calculated and represented in computer memory.


The role of biologics in the treatment of moderate-to-severe plaque psoriasis.
Psoriasis is a chronic, relapsing, inflammatory skin disease requiring long-term treatment and in many cases involving a reduction in the quality of life. Treatment with biologics is indicated in patients with moderate-to-severe psoriasis who do not respond or cannot be treated with conventional systemic drugs, and the therapeutic goal is an improvement of 90% (or at least 75%) with respect to baseline PASi at the end of the induction phase, which should be maintained long-term in the mainternance phase of treatment. Before starting treatment with a biological agent it is necessary to review the contraindications and precautions, rule out latent tuberculosis infection and complete the pending immunizations. Biological agents have a more favorable safety profile than classical systemic treatments; the most common side effects are mild and rarely involve the discontinuation of treatment. The treatment decision will be based on individual characteristics and patient preferences, functional limitation, expected speed of onset of effect, adverse reactions, availability and cost of treatment.


A proposed technique for the morphometric analysis of arteriolar smooth muscle cells from scanning electron microscopic preparations.
Morphometric methods are developed which allow the determination of smooth muscle cell (SMC) features from microvasculature prepared for scanning electron microscopy (SEM). In vessels so prepared, the SMCs are visible as either tapered ends (T) or complete wraps (CW) around the visible vessel. Formulas were developed so that these features could be used to determine the number of cells (C) in a vessel segment and the number of times the smooth muscle cells wrap around the vessel (W/C). Models were constructed to simulate such vessel preparations to test these formulas. From the two pieces of data (C and W/C) so determined, other SMC parameters could be calculated such as: SMC density along the vessel, SMC length and vessel surface area covered by a SMC. Therefore, it is evident that SMC data can be determined from microvessels prepared for SEM. This data would allow a more complete understanding of SMCs and their changes in normal and diseased states.


Narcolepsy-cataplexy. I. Clinical and electrophysiologic characteristics.
The development, clinical course, and electrophysiologic characteristics of narcolepsy were evaluated in 50 adults who had a current complaint of sleep attacks and cataplexy. In most of the patients, the first symptoms, usually excessive daytime sleepiness and sleep attacks, developed during childhood or adolescence. The condition was invariably chronic. Patients frequently had family histories of some disorder of excessive daytime sleepiness. In nocturnal sleep or daytime nap recordings, all but three of the patients demonstrated a rapid-eye-movement (REM) period at sleep onset. Sleep apnea was found in only one patient. Our findings indicate that sleep laboratory recordings to detect a sleep-on-set REM period are of little diagnostic value when the narcoleptic patient has cataplexy. Furthermore, narcoleptic patients require sleep laboratory evaluation for sleep apnea only when the presence of apnea is suggested by the sleep history.


Physical Demands of Multimodal Training Competitions and Their Relationship to Measures of Performance.
Jagim, AR, Rader, O, Jones, MT, and Oliver, JM. Physical demands of multimodal training competitions and their relationship to measures of performance. J Strength Cond Res 31(5): 1212-1220, 2017-The purpose of this study was to identify the physical demands of multimodal training (MMT) competitions and to determine the extent of their relationship to select measures of performance. Eighteen (>1.5 years of strength training experience) men (n = 10) and women (n = 8) (mean ± SD; age: 37.8 ± 10.6 years, height: 172.8 ± 8 cm, weight: 77.4 ± 13.2 kg, 16.6 ± 6% body fat) with experience performing MMT participated in a simulated MMT competition. All participants were assessed for body composition, countermovement vertical jump, and aerobic capacity during baseline testing. All participants then participated in a simulated MMT-style competition on a separate day within 10 days of baseline testing. The simulated MMT-style competition consisted of 3 events with 90 minutes of recovery allowed in between events. During the events, changes in blood lactate (La), heart rate (HR), and estimated V[Combining Dot Above]O2 were recorded. Bivariate (Pearson) correlations were computed to determine if a relationship existed between traditional measures of performance and those of the MMT-style competition. Significance was set at p ≤ 0.05. Mean change in La ranged between 9 and 12 mmol·L during the events. Mean HR and estimated V[Combining Dot Above]O2 values ranged from 145 to 172 b·min and 24 to 35 ml·kg·min, respectively, during the events. A strong correlation was observed (r = -0.722; p < 0.001) between aerobic capacity and time to completion for event 1. There was a strong correlation between lean body mass and lower-body strength performance (r = 0.882; p < 0.001) and time to completion for event 3 (r = -0.792; p < 0.001). A strong correlation was observed between lower-body power and time to completion for event 1 (r = -0.755; p < 0.001) and event 3 (r = -0.818; p < 0.001). Based on the results of this study, MMT-style competitions appear to be physically demanding activities performed at a high intensity with a great involvement of the anaerobic energy system and that some measures of aerobic capacity and power correlate with performance. When training for MMT-style competitions, it may be beneficial to focus on improving lower-body power and/or aerobic capacity.


Residual recombination in Neurospora crassa spo11 deletion homozygotes occurs during meiosis.
Spo11 is considered responsible for initiation of meiotic recombination in higher organisms, but previous analysis using spo11 (RIP) mutants suggests that the his-3 region of Neurospora crassa experiences spo11-independent recombination. However, despite possessing several stop codons, it is conceivable that the mutants are not completely null. Also, since lack of spo11 interferes with chromosomal pairing and proper segregation at Meiosis I, spores can be partially diploid for a period after meiosis. Thus, it is possible that the recombination observed could be an abnormal event, occurring during the period of aneuploidy rather than during meiosis. To test the former hypothesis, we generated spo11 deletion homozygotes. Using crosses heteroallelic for his-3 mutations, we showed that His(+) progeny are generated in spo11 deletion homozygotes at a frequency at least as high as in wild type and, as in the spo11 (RIP) mutants, local crossing over is not reduced. To test the latter hypothesis, we utilised mutations in either end of a histone H1-GFP fusion gene, inserted between the recombination hotspot cog and his-3, in which GFP(+) spores arise as a result of recombination in a cross between the two GFP alleles. In a control cross homozygous for spo11 (+), the frequency at which GFP(+) spores arise is comparable to the frequency of His(+) spores and glowing nuclei first appear during prophase, prior to metaphase I, as expected for a product of meiotic recombination. Similarly in spo11 deletion homozygotes, GFP(+) spores arise at high frequency and glowing nuclei are first seen before metaphase, indicating that allelic recombination occurs during meiosis in the absence of spo11. We have therefore shown that spo11 is not essential for either his-3 allelic recombination or crossing over in the vicinity of his-3, and that spo11-independent allelic recombination is meiotic, indicating that there is a spo11-independent mechanism for initiation of recombination in Neurospora.


[Issues of provision of the safety of laserwares in the use of nanotechnologies].
Current technologies, including nanotechnologies, cannot be introduced, without applying laser equipment. For provision of the safety in the manufacture and use of up-to-date laser equipment that is characterized by new, previously unused wavelengths and exposure levels, it is necessary to develop the hygienic regulation of the arrangement and maintenance of lasers, to improve approaches to making their sanitary-and-epidemiological examination and manufacturing inspection, to design measuring instruments that permit an objective assessment of new types of laser exposures, and to develop the current means for protecting the organ of vision in service personnel.


Endoscopic technique for subfascial perforating vein interruption.
Surgical treatment of incompetent perforating veins of the lower leg performed openly carries considerable morbidity associated with wound healing. Newer minimally invasive techniques offer an effective treatment alternative that avoids the lengthy incisions of the classical subfascial ligation techniques. The authors report a simple and quick two-port endoscopic method for clipping incompetent perforating veins of the lower leg using commonly available endoscopic instrumentation. The technique is unique in its use of a balloon dissector to rapidly establish the subfascial working space.


Persistent tachypnea in children: keep pulmonary embolism in mind.
Tachypnea in children is associated with respiratory disorders and nonrespiratory disorders such as cardiac disease, metabolic acidosis, fever, pain, and anxiety. Pulmonary embolism is seldom considered by pediatricians as a cause of tachypnea. Three children of various ages with persistent tachypnea are described: a girl after orthopedic surgery for kyphoscoliosis, a boy with nephrotic syndrome, and a neonate with Hirschsprung disease. Other causes of tachypnea were diagnosed and treated before pulmonary embolism was considered. Ventilation-perfusion scanning appeared to be highly probable for pulmonary embolism in these patients. Anticoagulant therapy was started. Pulmonary embolism should be kept in mind in children with tachypnea, especially when other risk factors for venous thromboembolism are present, to avoid delay in anticoagulant treatment and a fatal outcome.


MAIN ETHICAL BREACHES IN MULTICENTER CLINICAL TRIALS REGULATIONS OF TURKEY.
Turkey has been a growing market for multicenter clinical trials for the last ten years and is considered among the top ten countries in terms of potential study subject populations. The objective of increasing the share of Turkey in multicenter clinical trials is strongly supported. This ambitious goal of Turkey raises the need to have regulations in compliance with other leading countries conducting clinical trials. The latest published Turkish regulations on clinical trials are structured in compliance with the International Conference on Harmonization (ICH) Guidelines and in harmony with the regulations of other leading countries in clinical research, such as the US. There are still flaws in Turkish regulation with the risk of violating human subjects' rights and issues with responsible conduct of research. The aim of this article is to compare Turkish clinical trials regulations with those of the US, to determine if there exists any incompatibility between the countries' regulations and, if so, how to ameliorate these. The main flaws in Turkish clinical trials regulations are identified as follows: lack of definition of the term "human subject; absence of explicit referral to the unacceptability of Conflict of Interest (COI) and taking measures to avoid it; exiguity of emphasis on plurality of the IRB members; nonexistence of a clear expression that this is research; and clinical equipoise, regarding the treatment of the existing clinical problem and lack of integration with international accreditation systems for Institutional Review Boards.


Interaction of protein percent with caloric density and protein source for lactating cows.
Experiment 1 was to test effect of three ratios of energy to protein in complete mixed diets for 36 lactating cows in three, 28-d periods. Energy was varied with cottonseed hulls, pelleted ground corrugated boxes, and a mixture of the two. Crude protein was varied with soybean meal to give energy:crude protein of 5.7, 5.0, and 4.6 for each energy amount. Cottonseed meal was compared with soybean meal in corrugated box diets. Feed intake was much higher with cottonseed hulls, and appreciable feedlot bloat resulted from pelleted ground corrugated box diets. Data adjusted to equal feed intake showed significant effect of energy to crude protein ratio on milk yield and improved digestion of organic matter with soybean meal vs. cottonseed meal. Experiment 2 tested the hypothesis that lactating cows consuming high-protein alfalfa may benefit from supplemental protein. Diets were 50% forage. Six diets were 14 or 18% crude protein in three ratios of alfalfa hay to corn silage (0:100, 50:50, 100:0). Additional corn silage diets were to compare: 14 versus 18% protein from distiller's dried grains with solubles only and with .5 or .9% urea (four diets); two 14% protein diets compared .6% added potassium chloride with or without .5% urea. Thirty-six Holstein cows in early lactation received one of the 12 diets in each of three 28-d periods. Distiller's grains with solubles markedly depressed milk yield (2.2 kg/d) and milk protein (.22%); heat damage of distiller's grains was evident. Protein interacted with alfalfa so gain in milk from 18 versus 14% increased from .55 to 1.36 to 2.66 kg/d as alfalfa changed from 0 to 50 to 100%. Thus, crude protein of alfalfa was not as effective as that from soybean meal in supporting milk yield.


Expanding HIV Testing in African American Communities Through Community-Based Distribution of Home-Test Vouchers.
We investigated the implementation feasibility and effectiveness of community-based HIV home-test voucher distribution in three Indianapolis African American communities. Community-based organizations augmented traditional outreach methods to distribute vouchers for home HIV tests redeemable at three pharmacies during three distribution waves from February to April 30, 2015. Voucher redemption served as a proxy indicator of intent to test for HIV. 315 vouchers were distributed and 47 vouchers were redeemed for a 14.9% redemption rate. Distribution was 46% of plan. Vouchers were redeemed at all three pharmacies, and 21% of visits involved redemption of more than one voucher. The original team of seven distributors in three organizations reduced to a remaining five distributors in two organizations by wave 2. This study suggests that outreach organizations could implement HIV home test voucher distribution, and that people would redeem the vouchers at a pharmacy for an HIV test. Future studies should explore how voucher distribution can expand the current HIV testing system.


Use of a prohibition order after a large outbreak of gastroenteritis caused by norovirus among function attendees.
In May 2011, an outbreak of acute gastroenteritis occurred among guests attending two functions (Function A and B) at a local function centre in Sydney, Australia. The Sydney South West Public Health Unit and the New South Wales (NSW) Food Authority sought to determine the cause of the outbreak and implement control measures. A retrospective cohort study was planned. A complete guest list was unavailable, so guests who could be contacted were asked to provide details of other guests. Attendee demographics, symptom profile and food histories were obtained using a standard response questionnaire. Stool samples were requested from symptomatic guests. The NSW Food Authority conducted a site inspection. Of those interviewed, 73% of Function A guests and 62% of Function B guests were ill, with mean incubation times of 27 and 23 hours respectively. Diarrhoea was the most common symptom. Three stool samples and four environmental swabs were positive for norovirus. One food handler reported feeling ill before and during the functions. A prohibition order was used to stop food handlers implicated in the outbreak from preparing food. This outbreak strongly suggests transmission of norovirus, possibly caused by an infected food handler. Regulatory measures such as prohibition orders can be effective in enforcing infection control standards and minimising ongoing public health risk.


Postdischarge quality of care: do age disparities exist among Department of Veterans Affairs ischemic stroke patients?
This study examined whether age disparities existed across postdischarge quality indicators (QIs) for veterans with ischemic stroke who received care at Department of Veterans Affairs medical centers (VAMCs). This retrospective cohort included a national sample of 3,196 veterans who were diagnosed with ischemic stroke and received acute and postdischarge stroke care at 127 VAMCs in fiscal year 2007 (10/1/06 through 9/30/07). Data included an assessment of postdischarge stroke QIs in the outpatient setting during the 6 mo postdischarge. The QIs included measurement of and goal achievement for (1) blood pressure, (2) serum international normalized ratio (INR) for all patients discharged on warfarin, (3) cholesterol (low-density lipoprotein [LDL]) levels, (4) serum glycosylated hemoglobin, and (5) depression treatment. The mean age for the 3,196 veterans included in this study was 67.2 +/- 11.3 yr. Before risk adjustment, there were age differences in (1) depression screening/treatment, (2) blood pressure goals, and (3) LDL levels. After we adjusted for patient sociodemographic, clinical, and facility-level characteristics by using hierarchical linear mixed modeling, none of these differences remained significant but INR goals for patients discharged on warfarin differed significantly by age. After we adjusted for patient and facility characteristics, fewer age differences were found in the postdischarge stroke QIs. Clinical trial registration was not required.


tRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming.
tRFs and tiRNAs (tRNA-derived fragments) are an emerging class of small noncoding RNAs produced by the precise shearing of tRNAs in response to specific stimuli. They have been reported to regulate the pathological processes of numerous human cancers. However, the biofunction of tRFs and tiRNAs in the development and progression of papillary thyroid cancer (PTC) has not been reported yet. In this study, we aimed to explore the biological roles of tRFs and tiRNAs in PTC and discovered that a novel 5'tRNA-derived fragment called tRF-1:30-Gly-CCC-3 (tRF-30) was markedly down-regulated in PTC tissues and cell lines. Functionally, tRF-30 inhibited the proliferation and invasion of PTC cells. Mechanistically, tRF-30 directly bound to the biotin-dependent enzyme pyruvate carboxylase (PC), downregulated its protein level, interfered with the TCA cycle intermediate anaplerosis, and thus affected metabolic reprogramming and PTC progression. These findings revealed a novel regulatory mechanism for tRFs and a potential therapeutic target for PTC.


Stromal p16 Overexpression in Gastric-type Mucinous Carcinoma of the Uterine Cervix.
Gastric-type mucinous carcinoma (MC-G) of the uterine cervix displays distinct morphological features and an aggressive clinical course. The expression status of p16 in the stroma has not been investigated in adenocarcinoma of the uterine cervix. Stromal p16 expression was evaluated in endocervical adenocarcinomas, including usual-type endocervical adenocarcinoma (UEA), intestinal-type mucinous carcinoma (MC-I), and MC-G. Whether stromal p16 expression varied significantly according to the histological subtype and whether the expression status is associated with clinicopathological characteristics of MC-G was also investigated. Immunostaining of p16 was performed for 24, 19, and 18 cases of UEA, MC-I, and MC-G, respectively. UEA and MC-I subtypes exhibited horizontally continuous, strong nuclear p16 immunoreactivity in the tumor cells, whereas none of the MC-G cases showed diffuse and strong nuclear immunoreactivity for p16 in the tumor cells. Instead, 10 (55.6%) cases of MC-G displayed moderately to strongly positive p16 expression in the stroma. Stromal p16 expression of MC-G was significantly higher than that of normal cervix, UEA, and MC-I. Metastatic MC-G had significantly higher stromal p16 expression than primary MC-G. Further, stromal p16 overexpression in MC-G was associated with advanced stage, parametrial invasion, and lymphovascular invasion. Stromal p16 expression of MC-G was significantly higher than that of normal cervix and other histological subtypes of adenocarcinoma and was associated with advanced stage, parametrial invasion, and lymphovascular invasion, reflecting the aggressive behavior of MC-G. Our observations suggest that stromal p16 expression is involved in the development and progression of MC-G.


Role of kinases and phosphatases in the regulation of fluid secretion and Cl-/HCO3- exchange in cholangiocytes.
The role of protein kinase A (PKA), protein kinase C (PKC), and protein phosphatases in the process of secretin stimulation of fluid and bicarbonate secretion from biliary epithelium was examined using a novel isolated bile duct unit (IBDU) model from rat liver. Sp-adenosine 3',5'-cyclic monophosphothiolate (Sp-cAMPS), 100 microM, a PKA-specific agonist, significantly increased secretion during a 30-min perfusion (+61%, P < 0.01). In contrast, preincubation and perfusion of Rp-cAMPS, 100 microM, a specific PKA inhibitor, reduced the ability of secretin to stimulate both fluid secretion (111 vs. 25%; P < 0.01) and Cl-/HCO3- exchanger activity (80 vs. 28%). Neither the PKC agonist phorbol 12-myristate 13-acetate, 10 microM, nor the PKC antagonist staurosporine showed any effect on either basal or secretin-stimulated fluid secretion or Cl-/HCO3- exchange activity in IBDU. Okadaic acid, a specific inhibitor of protein phosphatases 1 and 2A, also had no effect on basal fluid secretion or on the basal activity of the Cl-/HCO3- exchanger. However, okadaic acid resulted in persistence of secretion after removal of secretin, in contrast to the reduction in secretion observed in controls. These findings indicate that PKA but not PKC is involved in the signal transduction of secretin-stimulated fluid secretion and Cl-/HCO3- exchange activity in rat bile duct epithelium, a process inactivated by dephosphorylation by protein phosphatases 1 and/or 2A.


A healthcare integration system for disease assessment and safety monitoring of dementia patients.
Elderly dementia patients often get lost due to lack of a sense of direction. This may put them at risk and cause their families much worry. The goal of this study is to use information technology to enhance the professional judgment of caregivers, strengthen internal safety monitoring at care organizations, and improve the quality of care for dementia patients. An eXtensible-Markup-Language-based dementia assessment system combining program code and assessment content is used to provide caregivers with better flexibility and real-time response ability. Beyond establishing long-term case files, the system can also perform data consistency analysis, strengthen caregivers' continuing education, improve caregivers' case judgment skills, and reduce the incidence of accidents due to neglect. This study also applies radio frequency identification (RFID) technology to the development of an indoor and outdoor active safety monitoring mechanism. The system can automatically remind caregivers whenever an elderly person approaches a dangerous area or strays too far. Apart from the use of different size tags, the realization of the system also employs the tame transformation signatures (TTS) algorithm to encrypt tag IDs and protect personal privacy. Clinical testing of the system showed that the indoor RFID reader has a response time of 0.5 s when sensing 40 tags, while the outdoor reader has a sensing time of approximately 5 s due to the need to save power. In the latter case, the system can ensure that elderly patients stay less than 15 m away from their caregivers. Patients were relatively willing to wear light tags. We also found that irritable patients with strong mobility were less compliant and often removed their own tags. Caregivers must provide active care and adopt various safety measures to protect the type of patients.


Lack of genic variation in the abundant proteins of human kidney.
Abundant proteins of 25 human kidneys were surveyed for genic variation by means of two-dimensional electrophoresis. Eighty-three (83) proteins were scored, and no genic variation was detected. This reduction in genic heterozygosity corroborates results determined with two-dimensional electrophoresis in mice and flies. These results suggest that previous estimates of electrophoretic variation may have been in error because of biased selection of loci.


Structure and magnetic properties of highly oriented LaBaCo2O5+δ films deposited on Si wafers with Pt/Ti buffer layer.
Fabrication of highly crystalline oxide films onto silicon wafers has long been a critical obstacle for integrating multi-functional oxides into silicon-based technology. Herein, Pt/Ti is used as a buffer layer for the integration of highly oriented crystalline LaBaCo2O5+δ (LBCO) thin films onto silicon via pulsed laser deposition. LBCO films are highly (00l) oriented with smooth and sharp LBCO/Pt interfaces. The highly oriented LBCO films exhibit a high magnetic transition temperature (TC) and large coercive field (HC) with superparamagnetism over those deposited on single crystal substrates. What is more, the metallic-like behavior with enhanced magnetoresistance is also observed. The opportunity of using a Pt/Ti buffer layer as the growth template opens an alternative route for integrating functional transition metal oxides with tunable magnetic properties into Si-based technology.


[Effect of the kallikrein-like enzyme salivain on the course of experimental acute parotitis].
Mechanical trauma of rat parotid gland led to an increase in the size of the gland (due to edema) with simultaneous activation of unspecific proteases, which were estimated at pH 7.6 using casein as a substrate. Administration of kallikrein-like salivary enzyme salivain into non-traumatized parotid gland caused also the same alterations. Complex application of two factors (trauma and salivain) resulted in distinct increase of the gland edema and the proteolytic activity. Administration of trasilol (inhibitor of proteases) decreased the pathogenic effects of salivain. After administration of salivain the alkaline phosphatase activity was shown to decrease in the parotid salivary gland.


[The protective action of essentiale, riboxin, and elkar against hemotoxic anemia].
The introduction of phenylhydrazine in rats inhibited the hemopoiesis, decreased the functional activity of immune cells, hepatocytes and myocytes, and reduced the work capacity. The combined administration of essentiale and riboxin decreased the expression of inhibition of the nonspecific resistance and immune reactivity in rats pretreated with phenylhydrazine. The combined use of essentiale and elkar produced a hepatoprotective effect in rats with phenylhydrazine-induced hemotoxic anemia. Elkar in combination with riboxin enhance the physical work capacity in rats poisoned by the hemotropic toxin. The pairwise drug injections did not influence the reduced content of erythrocytes and hemoglobin in the blood caused by phenylhydrazine. However, the combined injection of all the three drugs (essentiale, riboxin and elkar) decreased the expression of hemopoiesis inhibition.


The prevention of leprosy related disability as an integral component of the government health delivery programme in Indonesia: perspectives on implementation.
This paper presents a record of three interviews with groups of Ministry of Health personnel and consultants that took place in Jakarta, Indonesia in May 2012. Those contributing to the first interview were provincial and district supervisors with responsibility for leprosy. Those contributing to the second interview were consultants, three of whom were seconded to the Ministry of Health and one was a WHO consultant. A third interview was conducted with the Head and a technical staff member of the Sub Directorate of Leprosy and Yaws Control Programme, Ministry of Health, Indonesia. Leprosy control in Indonesia had been targeted for further enquiry after it became apparent, through an earlier survey of national programme managers and consultants, that the programme had been relatively successful in integrating POD into the government health delivery programme. The perspectives of significant representatives and actors in the national programme were recorded through the interviews undertaken in Jakarta. Limitations This report does not purport to be a study of integration of leprosy services in Indonesia. The perspectives of representatives and significant actors are offered here to enhance understanding of factors that contributed to POD becoming a routine component of general health care in Indonesia. It is also declared here that no independent verification of statements was undertaken and that the effectiveness of measures taken to integrate leprosy related POD has not been independently evaluated.


Cannabinoids, endocannabinoids, and related analogs in inflammation.
This review covers reports published in the last 5 years on the anti-inflammatory activities of all classes of cannabinoids, including phytocannabinoids such as tetrahydrocannabinol and cannabidiol, synthetic analogs such as ajulemic acid and nabilone, the endogenous cannabinoids anandamide and related compounds, namely, the elmiric acids, and finally, noncannabinoid components of Cannabis that show anti-inflammatory action. It is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation. A possible mechanism for these actions is suggested involving increased production of eicosanoids that promote the resolution of inflammation. This differentiates these cannabinoids from cyclooxygenase-2 inhibitors that suppress the synthesis of eicosanoids that promote the induction of the inflammatory process.