Participation in clinical trials among women living with HIV in Canada. Canadian Women's HIV Study Group.
To describe participation in clinical trials among HIV-positive women enrolled since 1993 in the Canadian Women's HIV Study, a prospective open cohort study. All HIV-positive women being followed at hospital-based or community-based clinics at 28 sites in 11 Canadian cities were eligible to participate in the Canadian Women's HIV Study. Baseline and follow-up information was collected for 413 women every 6 months by study nurses using standardized questionnaires. Data included sociodemographic variables, HIV exposure group, CD4 count, disease classification, use of antiretroviral therapies and participation in clinical trials. At study intake 15.0% (62/413) of the women had participated in a clinical trial; an additional 8.5% (35/413) participated during a median follow-up of 18 months. Multivariate analysis revealed that the following factors were independently associated with participation in a clinical trial: white race (adjusted odds ratio [OR] 3.38, p = 0.001), current use of antiretroviral therapy (adjusted OR 2.01, p = 0.008), completion of secondary school (adjusted OR 1.97, p = 0.024) and residence in the Prairies or Atlantic provinces (adjusted OR 1.98, p = 0.043). Although the overall clinical trial participation rate of 23.5% was relatively high among HIV-positive women, injection drug users were underrepresented in this study population, and non-white women, women who did not complete high school and women not receiving antiretroviral therapy were less likely than white women, women of higher education and women receiving antiretroviral therapy to participate in clinical trials in Canada. Because of the importance of trial participants being representative of the population for which therapeutic agents are intended, HIV clinical trials must recruit women with lower literacy levels, non-white women, women not receiving antiretroviral therapy and women who are injection drug users to ensure generalizability of research findings. Further study is needed to assess factors that act as barriers and motivators to women's participation in HIV clinical trials.


Non-metal sensory electrode design and protocol of DNA-nucleobases in living cells exposed to oxidative stresses.
Sensory protocols for evaluation of DNA distortion due to exposure to various harmful chemicals and environments in living cells are needed for research and clinical investigations. Here, a design of non-metal sensory (NMS) electrode was built by using boron-doped carbon spherules for detection of DNA nucleobases, namely, guanine (Gu), adenine (Ad), and thymine (Th) in living cells. The key-electrode based nanoscale NMS structures lead to voids with a facile diffusion, and strong binding events of the DNA nucleobases. Furthermore, the NMS geometric structures would significantly create electrode surfaces with numerous centrally active sites, curvature topographies, and anisotropic spherules. The NMS shows potential as sensitive protocol for DNA-nucleobases in living cells exposed to oxidative stresses. In one-step signaling assay, NMS shows high signaling transduction of Gu-, Ad-, and Th-DNA nucleobases targets with ultra-sensitive and low detection limits of 3.0, 0.36, and 0.34 nM, respectively, and a wide linear range of up to 1 μM. The NMS design and protocol show evidence of the role of surface construction features and B-atoms incorporated into the graphitic carbon network for creating abundant active sites with facile electron diffusion and heavily target loads along with within-/out-plane circular spheres. Indeed NMS, with spherule-rich interstitial surfaces can be used for sensitive and selective evaluation of damaged-DNA to various dysfunctional metabolism in the human body.


The killing fields of inequality.
The article presents a multidimensional analysis of inequality, in a global perspective, distinguishing vital, existential, and material resources inequality. These dimensions are interrelated and interacting, but irreducible to each other, and have had different historical trajectories, within and between nations. Over the last half-century, the contrast between advances of existential equalization, on one hand, and persistent, even increasing, vital inequality of life expectancy and health is striking. Inequalities are produced by specific mechanisms, of which distanciation, exclusion, hierarchization, and exploitation are the most important. They have each their corresponding mechanism of equality, of rapprochement or approximation, of inclusion, of organizational flattening or de-hierarchization, and of redistribution, rehabilitation, and recompensation. The mechanisms and their results are illustrated empirically in a systematic global overview.


The One-Sample PARAFAC Approach Reveals Molecular Size Distributions of Fluorescent Components in Dissolved Organic Matter.
Molecular size plays an important role in dissolved organic matter (DOM) biogeochemistry, but its relationship with the fluorescent fraction of DOM (FDOM) remains poorly resolved. Here high-performance size exclusion chromatography (HPSEC) was coupled to fluorescence emission-excitation (EEM) spectroscopy in full spectral (60 emission and 34 excitation wavelengths) and chromatographic resolution (<1 Hz), to enable the mathematical decomposition of fluorescence on an individual sample basis by parallel factor analysis (PARAFAC). The approach allowed cross-system comparisons of molecular size distributions for individual fluorescence components obtained from independent data sets. Spectra extracted from allochthonous DOM were highly similar. Allochthonous and autochthonous DOM shared some spectra, but included unique components. In agreement with the supramolecular assembly hypothesis, molecular size distributions of the fluorescence fractions were broad and chromatographically unresolved, possibly representing reoccurring fluorophores forming noncovalently bound assemblies of varying molecular size. Samples shared underlying fluorescence components that differed in their size distributions but not their spectral properties. Thus, in contrast to absorption measurements, bulk fluorescence is unlikely to reliably indicate the average molecular size of DOM. The one-sample approach enables robust and independent cross-site comparisons without large-scale sampling efforts and introduces new analytical opportunities for elucidating the origins and biogeochemical properties of FDOM.


Is female sex an independent risk factor for early mortality in isolated coronary artery bypass graft? A propensity-matched analysis.
Despite several studies reporting a higher mortality rate for women undergoing isolated coronary artery bypass graft (CABG) surgery, this issue has not been completely clarified. The aim of the current study was to determine if sex differences in CABG surgery affect adjusted operative results and operative mortality. Between January 2005 and December 2012, 3756 consecutive patients (3009 men and 747 women) underwent isolated CABG at our institution. Women presented with older age, smaller BSA and higher rate of preoperative comorbidities. The propensity score methodology was used to obtain risk-adjusted outcome comparisons between the two groups. The distribution of preoperative variables among matched pairs (553 patients in both groups) was, on average, equal. Propensity-matched women received a similar number of distal anastomoses (P = 0.56), had similar rate of left internal thoracic artery (LITA) graft (P = 0.73) and comparable extracorporeal circulation (P = 0.61) and aortic cross-clamp (P = 0.39) time as men. Postoperative complications were comparable in the two study groups with the exception of postoperative transfusion rate which was significantly higher in women (P = 0.01). However, operative mortality (3.8 vs. 2.7%; P = 0.20), perioperative acute myocardial infarction (P = 0.50) and stroke (P = 0.75) were not significantly different between the two groups. Interestingly, after adjustment for the other baseline characteristics, female patients with diabetes (P = 0.03), preoperative renal dysfunction (P = 0.07) and obesity (P = 0.07) exhibited a greater operative mortality rate compared with men with the same comorbidities. After adjustment for preoperative variables, female sex seems not to be an independent risk factor for early mortality in isolated CABG surgery. However, renal impairment, diabetes and obesity seem to play an important role in the operative risk profile of women undergoing isolated CABG.


Stress, PTSD, and dementia.
The physiological consequences of acute and chronic stress on a range of organ systems have been well documented after the pioneering work of Hans Selye more than 70 years ago. More recently, an association between exposure to stressful life events and the development of later-life cognitive dysfunction has been proposed. Several plausible neurohormonal pathways and genetic mechanisms exist to support such an association. However, many logistical and methodological barriers must be overcome before a defined causal linkage can be firmly established. Here the authors review recent studies of the long-term cognitive consequences of exposures to cumulative ordinary life stressors as well as extraordinary traumatic events leading to posttraumatic stress disorder. Suggestive effects have been demonstrated for the role of life stress in general, and posttraumatic stress disorder in particular, on a range of negative cognitive outcomes, including worse than normal changes with aging, Alzheimer's disease, and vascular dementia. However, given the magnitude of the issue, well-controlled studies are relatively few in number, and the effects they have revealed are modest in size. Moreover, the effects have typically only been demonstrated on a selective subset of measures and outcomes. Potentially confounding factors abound and complicate causal relationships despite efforts to contain them. More well-controlled, carefully executed longitudinal studies are needed to confirm the apparent association between stress and dementia, clarify causal relationships, develop reliable antemortem markers, and delineate distinct patterns of risk in subsets of individuals.


Unweaving tangled mortality and antibiotic consumption data to detect disease outbreaks - Peaks, growths, and foresight in swine production.
As our capacity to collect and store health data is increasing, a new challenge of transforming data into meaningful information for disease monitoring and surveillance has arisen. The aim of this study was to explore the potential of using livestock mortality and antibiotic consumption data as a proxy for detecting disease outbreaks at herd level. Changes in the monthly records of mortality and antibiotic consumption were monitored in Danish swine herds that became positive for porcine reproductive and respiratory syndrome (PRRS) and porcine pleuropneumonia. Laboratory serological results were used to identify herds that changed from a negative to a positive status for the diseases. A dynamic linear model with a linear growth component was used to model the data. Alarms about state changes were raised based on forecast errors, changes in the growth component, and the values of the retrospectively smoothed values of the growth component. In all cases, the alarms were defined based on credible intervals and assessed prior and after herds got a positive disease status. The number of herds with alarms based on mortality increased by 3% in the 3 months prior to laboratory confirmation of PRRS-positive herds (Se = 0.47). A 22% rise in the number of weaner herds with alarms based on the consumption of antibiotics for respiratory diseases was found 1 month prior to these herds becoming PRRS-positive (Se = 0.22). For porcine pleuropneumonia-positive herds, a 10% increase in antibiotic consumption for respiratory diseases in sow herds was seen 1 month prior to a positive result (Se = 0.5). Monitoring changes in mortality data and antibiotic consumption showed changes at herd level prior to and in the same month as confirmation from diagnostic tests. These results also show a potential value for using these data streams as part of surveillance strategies.


Predictable surface emission patterns in terahertz photonic-crystal quantum cascade lasers.
We demonstrate a framework to understand and predict the far-field emission in terahertz frequency photonic-crystal quantum cascade lasers. The devices, which employ a high-performance three-well active region, are lithographically tunable and emit in the 104-120 microm wavelength range. A peak output power of 7 mW in pulsed mode is obtained at 10 K, and the typical device maximum operating temperature is 136 K. We identify the photonic-crystal band-edge states involved in the lasing process as originating from the hexapole and monopole modes at the G point of the photonic band structure, as designed. The theoretical far-field patterns, obtained via finite-difference time-domain simulations, are in excellent agreement with experiment. Polarization measurements further support the theory, and the role of the bonding wires in the emission process is elucidated.


[Chemo-irradiation therapy of non-organ malignant tumors of abdominal cavity and retroperitoneal space].
There are presented the results of treatment of 76 patients with nonorganic malignant tumor of abdominal cavity and retroperitoneal space, to whom surgical treatment (radical or palliative one with partial excision of tumor) was not conducted due to various reasons. In 25 patients special treatment was not conducted, in 14--was performed chemotherapy only, in 17--radiation therapy only and in 17--the treatment using radiation plus chemotherapy. Application of special method of treatment have permitted to increase the patients life span, to improve its quality. An advantage of endolymphatic method of chemotherapy in comparison with conventional methods of chemopreparations administration was noted.


Inflammation impairs eNOS activation by HDL in patients with acute coronary syndrome.
The aim of the present study was to evaluate the high-density lipoprotein (HDL) structure and endothelial NO synthase (eNOS) activation capacity in ST-elevation myocardial infarction (STEMI) patients with different acute-phase inflammatory response (APR). Forty-five STEMI patients were stratified in quartiles according to the delta CRP level, calculated by subtracting the CRP value at admission from the CRP peak value (APR peak). The HDL structure and HDL capacity to stimulate NO production were evaluated at admission and at APR peak. STEMI patients with a low APR had a completely preserved HDL structure and HDL ability to activate eNOS and promote NO production, which did not change during STEMI. On the contrary, HDL from STEMI patients developing a significant APR had compromised ability to stimulate eNOS and promote NO production, and underwent a significant particle remodelling during STEMI. The defective capacity to stimulate NO production of HDL isolated from STEMI patients with high APR was explained, at least in part, by the reduced PON-1 and S1P content. The HDL ability to promote cell cholesterol efflux through different pathways was preserved in ACS patients independently of the inflammatory response. The present results extend previous studies reporting an impaired eNOS-activating capacity of HDL from ACS patients, showing that only a subset of patients undergoing STEMI, and in particular those developing an important inflammatory response, have circulating HDL defective in stimulating endothelial eNOS and NO production.


Resilience, Hope, and Subjective Happiness Among the Turkish Population: Fear of COVID-19 as a Mediator.
Psychology deals with not only mental disorders but also psychological strengths within individuals. Psychological strengths will play an important role in struggling with the global novel coronavirus 2019 (COVID-19) pandemic. The present study tested a model concerning the relationship between resilience, hope, and subjective happiness using structural equation modeling to identify the mediating role of fear of COVID-19. A cross-sectional survey was conducted among a convenience sample of 971 Turkish individuals (aged 18 to 74 years) from 75 of 81 cities in Turkey. The survey included the Subjective Happiness Scale, Fear of COVID-19 Scale, Brief Resilience Scale, and the Dispositional Hope Scale, and data were analyzed using structural equation modeling (SEM). The SEM demonstrated an association between resilience-hope and subjective happiness was mediated by fear of COVID-19 (CMIN/df = 2.664, CFI = 0.994, NFI = 0.984, TLI = 0.984, GFI = 0.994, RMSEA = 0.044, SRMR = 0.024, AIC = 81.334, ECVI = 0.084). Resilience had a direct effect and an indirect effect on subjective happiness via fear of COVID-19. Hope also had a direct effect and an indirect effect on subjective happiness via fear of COVID-19. Consequently, in the fight against COVID-19, individuals who are resistant to stress and have a belief that they can find a way to cope can help prevent the fear of COVID-19 and so enhance good mental health.


Loss-of-Huntingtin in Medial and Lateral Ganglionic Lineages Differentially Disrupts Regional Interneuron and Projection Neuron Subtypes and Promotes Huntington's Disease-Associated Behavioral, Cellular, and Pathological Hallmarks.
Emerging studies are providing compelling evidence that the pathogenesis of Huntington's disease (HD), a neurodegenerative disorder with frequent midlife onset, encompasses developmental components. Moreover, our previous studies using a hypomorphic model targeting huntingtin during the neurodevelopmental period indicated that loss-of-function mechanisms account for this pathogenic developmental component (Arteaga-Bracho et al., 2016). In the present study, we specifically ascertained the roles of subpallial lineage species in eliciting the previously observed HD-like phenotypes. Accordingly, we used the Cre-loxP system to conditionally ablate the murine huntingtin gene (Httflx) in cells expressing the subpallial patterning markers Gsx2 (Gsx2-Cre) or Nkx2.1 (Nkx2.1-Cre) in Httflx mice of both sexes. These genetic manipulations elicited anxiety-like behaviors, hyperkinetic locomotion, age-dependent motor deficits, and weight loss in both Httflx;Gsx2-Cre and Httflx;Nkx2.1-Cre mice. In addition, these strains displayed unique but complementary spatial patterns of basal ganglia degeneration that are strikingly reminiscent of those seen in human cases of HD. Furthermore, we observed early deficits of somatostatin-positive and Reelin-positive interneurons in both Htt subpallial null strains, as well as early increases of cholinergic interneurons, Foxp2+ arkypallidal neurons, and incipient deficits with age-dependent loss of parvalbumin-positive neurons in Httflx;Nkx2.1-Cre mice. Overall, our findings indicate that selective loss-of-huntingtin function in subpallial lineages differentially disrupts the number, complement, and survival of forebrain interneurons and globus pallidus GABAergic neurons, thereby leading to the development of key neurological hallmarks of HD during adult life. Our findings have important implications for the establishment and deployment of neural circuitries and the integrity of network reserve in health and disease.SIGNIFICANCE STATEMENT Huntington's disease (HD) is a progressive degenerative disorder caused by aberrant trinucleotide expansion in the huntingtin gene. Mechanistically, this mutation involves both loss- and gain-of-function mechanisms affecting a broad array of cellular and molecular processes. Although huntingtin is widely expressed during adult life, the mutant protein only causes the demise of selective neuronal subtypes. The mechanisms accounting for this differential vulnerability remain elusive. In this study, we have demonstrated that loss-of-huntingtin function in subpallial lineages not only differentially disrupts distinct interneuron species early in life, but also leads to a pattern of neurological deficits that are reminiscent of HD. This work suggests that early disruption of selective neuronal subtypes may account for the profiles of enhanced regional cellular vulnerability to death in HD.


Mitogen-activated protein kinase signaling pathways are involved in regulating α7 nicotinic acetylcholine receptor-mediated amyloid-β uptake in SH-SY5Y cells.
Intraneuronal accumulation of beta-amyloid protein (Aβ) is an early pathological change in Alzheimer's disease (AD). Recent studies demonstrate that α7 nicotinic acetylcholine receptor (α7nAChR) binds to soluble Aβ with a high affinity. In vitro and in vivo experiments also show that Aβ activates p38 MAPK and ERK1/2 signaling pathways via the α7nAChR. Interestingly, it has been reported that p38 MAPK and ERK1/2 signaling pathways affect the regulation of receptor-mediated endocytosis. These data suggest that MAPK signaling pathways maybe involved in the regulation of α7nAChR-mediated Aβ uptake. However, the evidence for this hypothesis is lacking. In the present study, we examined whether Aβ1-42 oligomers activate MAPK signaling pathways via α7nAChR, and assessed the role of MAPK signaling pathways in the regulation of Aβ1-42 uptake by α7nAChR. We confirm that undifferentiated SH-SY5Y cells are capable of taking up extracellular Aβ1-42. The internalization of Aβ1-42 accumulates in the endosomes/lysosomes and mitochondria. MAPK signaling pathways are activated by Aβ1-42 via α7nAChR. Aβ1-42 and α7nAChR are co-localized in SH-SY5Y cells and the expression of α7nAChR involves in Aβ1-42 uptake and accumulation in SH-SY5Y cells. Our data demonstrate that Aβ1-42 induces an α7nAChR-dependent pathway that relates to the activation of p38 MAPK and ERK1/2, resulting in internalization of Aβ1-42. Our findings suggest that α7nAChR and MAPK signaling pathways play an important role in the uptake and accumulation of Aβ1-42 in SH-SY5Y cells. Blockade of α7nAChR may have a beneficial effect by limiting intracellular accumulation of amyloid in AD brain and serves a potential therapeutic target for AD.


Friendship Experiences and Anxiety Among Children: A Genetically Informed Study.
This study examined (a) whether, in line with a gene-environment correlation (rGE), a genetic disposition for anxiety puts children at risk of having anxious friends or having no reciprocal friends; (b) to what extent these friendship experiences are related to anxiety symptoms, when controlling for sex and genetic disposition for this trait; and (c) the additive and interactive predictive links of the reciprocal best friend's anxiety symptoms and of friendship quality with children's anxiety symptoms. Using a genetically informed design based on 521 monozygotic and ic twins (264 girls; 87% of European descent) assessed in Grade 4 (M age = 10.04 years, SD = .26), anxiety symptoms and perceived friendship quality were measured with self-report questionnaires. Results indicated that, in line with rGE, children with a strong genetic disposition for anxiety were more likely to have anxious friends than nonanxious friends. Moreover, controlling for their genetic risk for anxiety, children with anxious friends showed higher levels of anxiety symptoms than children with nonanxious friends but did not differ from those without reciprocal friends. Additional analyses suggested a possible contagion of anxiety symptoms between reciprocal best friends when perceived negative features of friendship were high. These results underline the importance of teaching strategies such as problem solving that enhance friendship quality to limit the potential social contagion of anxiety symptoms.


Lipids of Ankistrodesmus braunii.
Ankistrodesmus braunii wasgrown to stationary phase on a chemically defined medium and its cellular lipids were analyzed. The lipid content was found to vary from 18 to 73 percent of dry weight for cultures of different age and method of analysis. The pigments of the nonsaponifiable fraction were separated by adsorption chromatography and counter-current extraction and tentatively identified. The fatty acid fraction was converted to the corresponding methyl esters and analyzed by gas chromatography. The principal fatty acids present were: palmitic, oleic, and linolenic acids. Traces were detected of caprylic, capric, lauric, and palmitoleic acids.


Diagnosis of type 2 diabetes at an older age: effect on mortality in men and women.
To compare the mortality of people who were diagnosed with type 2 diabetes over 65 years of age with that of nondiabetic individuals. Using a population-based diabetes information system for an observational cohort study in Tayside, Scotland, people who were diagnosed with type 2 diabetes over the age of 65 years between 1993 and 2002 were identified. Nondiabetic comparators, matched for age and sex, were identified from the nondiabetic population. The two cohorts were followed up for mortality and cardiovascular mortality according to death certification records. There were 3,594 people with type 2 diabetes (48% male) and 7,188 matched comparators identified in the study. Over a mean follow-up period of 4.6 +/- 2.9 years for 3,594 people with type 2 diabetes and 7,188 comparators, 909 (25.3%) patients in the diabetic cohort and 1,651 (23.0%) in the nondiabetic cohort died. The adjusted relative risk for mortality in the diabetic cohort compared with the nondiabetic cohort was 1.06 (95% CI 0.94-1.19) for men and 1.29 (1.15-1.45) for women. Cardiovascular deaths accounted for 49.4% of the deaths in people with and 45.2% in those without diabetes (adjusted relative risk 1.01 [0.93-1.10]). Men diagnosed with type 2 diabetes over the age of 65 years have no excess mortality compared with their nondiabetic counterparts, a finding that was not replicated for women.


Between the genotype and the phenotype lies the microbiome: symbiosis and the making of 'postgenomic' knowledge.
Emphatic claims of a "microbiome revolution" aside, the study of the gut microbiota and its role in organismal development and evolution is a central feature of so-called postgenomics; namely, a conceptual and/or practical turn in contemporary life sciences, which departs from genetic determinism and reductionism to explore holism, emergentism and complexity in biological knowledge-production. This paper analyses the making of postgenomic knowledge about developmental symbiosis in Drosophila melanogaster by a specific group of microbiome scientists. Drawing from both practical philosophy of science and Science and Technology Studies, the paper documents epistemological questions of artefactuality and representativeness of model organisms as they emerge in the day-to-day labour producing and being produced by the "microbiome revolution." Specifically, the paper builds on all the written and editorial exchanges involved in the troubled publication of a research paper studying the symbiotic role of the microbiota in the flies' development. These written materials permit us to delimit the network of justifications, evidence, standards of knowledge-production, trust in the tools and research designs that make up the conditions of possibility of a postgenomic fact. More than reframing the organism as a radically novel multiplicity of reactive genomes, we conclude, doing postgenomic research on the microbiota and symbiosis means producing a story that deviates from the scripts embedded into the sociotechnical experimental systems of post-Human Genome Project life sciences.


First report of an idiopathic partial tail myonecrosis in European brown shrimp Crangon crangon caught in the North Sea.
The European brown shrimp Crangon crangon is an abundant and commercially important species in the North Sea. Currently, there is interest in landing live shrimp to provide fresh animals for a growing market in live brown shrimp. During 4 survival studies between 2014 and 2016, shrimp were collected from commercial trawlers and maintained alive in off-shore facilities. From Day 1 onwards, a minority of shrimp (~2.24%) developed a white discoloration of the abdominal muscles and a depigmentation of the distal part of the abdomen, along with paralysis of the affected tissues and appendages. As the symptoms progressed, a circumferential blackish delineation appeared, creating a distinct boundary between healthy and necrotic tissue. Affected shrimp survived up to 3 wk, although in several animals the distal part of the tail was completely lost. Histological and electron microscopical examination confirmed the myonecrosis. A secondary bacterial invasion of the necrotic muscle was observed in some animals. RT-PCR for infectious myonecrosis virus was negative. The condition appears not to be contagious, based on the feeding of healthy shrimp with necrotic tissue of affected shrimp. Based on these observations, a mechanical cause inflicted during the catching process is proposed.


Interdependence of amyloid formation in yeast: implications for polyglutamine disorders and biological functions.
In eukaryotic cells amyloid aggregates may incorporate various functionally unrelated proteins. In mammalian diseases this may cause amyloid toxicity, while in yeast this could contribute to prion phenotypes. Insolubility of amyloids in the presence of strong ionic detergents, such as SDS or sarcosyl, allows discrimination between amorphous and amyloid aggregates. Here, we used this property of amyloids to study the interdependence of their formation in yeast. We observed that SDS-resistant polymers of proteins with extended polyglutamine domains caused the appearance of SDS or sarcosyl-insoluble polymers of three tested chromosomally-encoded Q/N-rich proteins, Sup35, Rnq1 and Pub1. These polymers were non-heritable, since they could not propagate in the absence of polyglutamine polymers. Sup35 prion polymers caused the appearance of non-heritable sarcosyl-resistant polymers of Pub1. Since eukaryotic genomes encode hundreds of proteins with long Q/N-rich regions, polymer interdependence suggests that conversion of a single protein into polymer form may significantly affect cell physiology by causing partial transfer of other Q/N-rich proteins into a non-functional polymer state.


The feasibility of a Comprehensive Resilience-building psychosocial Intervention (CREST) for people with dementia in the community: protocol for a non-randomised feasibility study.
A dementia diagnosis can prevent people from participating in society, leading to a further decline in cognitive, social and physical health. However, it may be possible for people with dementia to continue to live meaningful lives and continue to participate actively in society if a supportive psychosocial environment exists. Resilience theory, which focuses on strengthening personal attributes and external assets in the face of serious challenges, may provide a scaffold on which an inclusive multifaceted psychosocial supportive environment can be built. This protocol paper describes a study to determine the feasibility of conducting a multifaceted complex resilience building psychosocial intervention for people with dementia and their caregivers living in the community. This is a non-randomised feasibility study. Ten participants with dementia and their primary caregivers living in the community will be recruited and receive the CREST intervention. The intervention provides (a) a 7-week cognitive stimulation programme followed by an 8-week physical exercise programme for people with dementia and (b) a 6-week educational programme for caregivers. Members of the wider community will be invited to a dementia awareness programme and GP practices to a dementia training workshop. Trained professionals will deliver all intervention components. Outcomes will assess the feasibility and acceptability of all study processes. The feasibility and acceptability of a range of outcomes to be collected in a future definitive trial, including economic measurements, will also be explored. Finally, social marketing will be used to map a route toward stigma change in dementia for use in a subsequent trial. Quantitative feasibility outcome assessments will be completed at baseline and after completion of the 15-week intervention while qualitative data will be collected at recruitment, baseline, during and post-intervention delivery. This feasibility study will provide evidence regarding the feasibility and acceptability of a comprehensive multifaceted psychosocial intervention programme for people with dementia and their caregivers (CREST). The results will be used to inform the development and implementation of a subsequent RCT, should the findings support feasibility. ISRCTN25294519 Retrospectively registered 07.10.2019.


[Development of a computerized system using standard nursing language for creation of a nursing minimum data set].
The aim of a nursing data set is to provide useful information for assessing the level of care and the state of health of the population. Currently, both in Italy and in other countries, this data is incomplete due to the lack of a structured nursing documentation , making it indispensible to develop a Nursing Minimum Data Set (NMDS) using standard nursing language to evaluate care, costs and health requirements. The aim of the project described , is to create a computer system using standard nursing terms with a dedicated software which will aid the decision-making process and provide the relative documentation. This will make it possible to monitor nursing activity and costs and their impact on patients' health : adequate training and involvement of nursing staff will play a fundamental role.


Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling.
Early detection is the only promising approach to significantly improve the survival of patients with pancreatic cancer (PCa). Noninvasive tools for the diagnosis, prognosis, and monitoring of this disease are of urgent need. The purpose of this study was to identify and validate new biomarkers in PCa patient serum samples. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry has been applied to analyze serum protein alterations associated with PCa and to identify sets of potential biomarkers indicative for this disease. A cohort of 96 serum samples from patients undergoing PCa surgery was compared with sera from 96 healthy volunteers as controls. The sera were fractionated by anion exchange chromatography, and 3 of 6 fractions were analyzed onto 2 different chromatographic arrays. Data analysis revealed 24 differentially expressed protein peaks (P < 0.001), of which 21 were downregulated in the PCa samples. The best single marker can predict 92% of the controls and 89% of the cancer samples correctly. In addition, multivariate pattern analysis was performed. The best pattern model using a set of 3 markers was obtained using fraction 6 on immobilized metal affinity capture, loaded with Cu-Cu arrays. With this pattern model, a sensitivity of 100% and a specificity of 98% for the training data set and a sensitivity of 83% and specificity of 77% for the test data set were achieved with the PCa group set as true positive. Several of protein peaks, including the best single marker at 17.27 kd and other proteins from the pattern models, were purified and identified by peptide mapping and postsource decay-matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Apolipoprotein A-II, transthyretin, and apolipoprotein A-I were identified as markers, and these identified proteins were decreased at least 2-fold in PCa serum when compared with the control group. PCa is associated with a specific decrease of distinct serum proteins, which allows a reliable differentiation between pancreatic cancer and healthy controls.


Endovascular repair with bifurcated stent-grafts under local anaesthesia to improve outcome of ruptured aortoiliac aneurysms.
acute haemodynamic changes and/or loss of abdominal muscle tone can occur during induction of general anaesthesia and may be the Achilles' tendon in endovascular aneurysm repair (EVAR) of ruptured aortoiliac aneurysms (rAIA). The purpose of this study was to evaluate the use of local anaesthesia (LA) for EVAR to overcome these limitations. twenty-one consecutive patients with rAIA are included in this study. Twenty patients underwent EVAR under LA, and 1 patient was treated under general anaesthesia. Haemodynamics were stabilised during assessment of EVAR feasibility by CT-scan and during the procedure itself by controlled hypotension (MAP 50-60 mmHg) and moderate fluid resuscitation. median procedure time was 120 min. Haemodynamics remained stable in all but 3 patients who required transfemoral balloon occlusion of the supra-renal aorta. Perioperative intubation was necessary in 5 patients because of respiratory distress (n=3), or retroperitoneal access (n=2). Temporary deterioration of renal function occurred in 6 patients, with 2 requiring hemofiltration. CT-scan confirmed sealing of the rAIA in all patients at discharge. 30-day mortality was 9.5% (2 deaths). In the median follow-up of 19 months, there were no deaths, but 3 endovascularre-interventions, 1 crossover femoro-femoral bypass, and 1 open surgical graft repair. our series is the first to show that EVAR for rAIA can be safely performed under LA. This approach allows implantation of commercially available bifurcated SG and improves patient outcome.


SNP discovery performance of two second-generation sequencing platforms in the NOD2 gene region.
A potentially important application of second generation sequencing technologies is to identify disease-associated variation. For comparison of the performance in SNP detection, the Crohn's disease (CD)-associated NOD2 gene was subjected to targeted resequencing using two different second-generation sequencing technologies. Eleven CD patients were selected based on their haplotype background at the NOD2 locus. The 40-kb large NOD2 gene region was amplified using long-range PCR (LR-PCR), and sequenced with the Roche 454/FLX system, an Applied Biosystems SOLiD mate-pair library (2 x 25 bp), and a SOLiD fragment (50 bp) library. The entire NOD2 region was also sequenced using conventional Sanger technology. Four-hundred forty-two single nucleotide polymorphisms (SNPs) were discovered with the SOLiD mate-pair library, 454 with the fragment library, and 441 with the 454/FLX. For the homozygous SNPs, 98% were confirmed by Sanger for the mate-pair library, 100% for the fragment library and 99% for the 454/FLX. Ninety-six percent of the heterozygous SNPs detected with the SOLiD mate-pair library, 91% with the fragment library and 96% with the 454/FLX were confirmed by Sanger. In a simulation, the SNP detection performance fell rapidly when the achieved coverage was below 40 x. Due to uneven representation of the target region when using LR-PCR, oversequencing of other regions is necessary.


Gender-specific secondary prevention? Differential psychosocial risk factors for major cardiovascular events.
To explore the psychosocial determinants and interhospital variability on a major acute cardiovascular event (MACE), during follow-up of a multicenter cohort of patients hospitalised with heart disease, participating in a nurse-led secondary prevention programme. Outcome data were retrospectively analysed from 602 cardiac inpatients randomised to postdischarge standard care (n=296), or home-based intervention (n=306), with prolonged follow-up of individualised multidisciplinary support. Baseline psychosocial profiling comprised depressive status, health-related quality of life (HRQoL), social isolation and mild cognitive impairment (MCI). Multivariate analyses examined the independent correlates of a composite 2-year MACE rate of all-cause mortality and unplanned cardiovascular-related hospitalisation, according to gender. Participants were aged 70±10 years, 431 (72%) were men and 377 (63%) had coronary artery disease. During 2-year follow-up, 165 (27%) participants (114 men, 51 women; p=0.431) experienced a MACE. Independent correlates of a MACE in men were depressive status (OR 1.95, 95% CI 1.06 to 3.58; p=0.032), low physical HRQoL (OR 0.98, 95% CI 0.96 to 1.00; p=0.027) and increasing comorbidity (OR 1.14, 95% CI 1.04 to 1.25; p=0.004). In women, age (OR 1.06, 95% CI 1.02 to 1.12; p=0.008), MCI (OR 2.38, 95% CI 1.09 to 5.18; p=0.029) and hospital site predicted a MACE (OR 2.32, 95% CI 1.09 to 4.93; p=0.029). Psychological determinants, cognitive impairment and responses to secondary prevention are different for men and women with heart disease and appear to modulate cardiovascular-specific outcomes. Early detection of psychosocial factors through routine screening and gender-specific secondary prevention is encouraged. 12608000014358.


Audio-visuomotor processing in the musician's brain: an ERP study on professional violinists and clarinetists.
The temporal dynamics of brain activation during visual and auditory perception of congruent vs. incongruent musical video clips was investigated in 12 musicians from the Milan Conservatory of music and 12 controls. 368 videos of a clarinetist and a violinist playing the same score with their instruments were presented. The sounds were similar in pitch, intensity, rhythm and duration. To produce an audiovisual discrepancy, in half of the trials, the visual information was incongruent with the soundtrack in pitch. ERPs were recorded from 128 sites. Only in musicians for their own instruments was a N400-like negative deflection elicited due to the incongruent audiovisual information. SwLORETA applied to the N400 response identified the areas mediating multimodal motor processing: the prefrontal cortex, the right superior and middle temporal gyrus, the premotor cortex, the inferior frontal and inferior parietal areas, the EBA, somatosensory cortex, cerebellum and SMA. The data indicate the existence of audiomotor mirror neurons responding to incongruent visual and auditory information, thus suggesting that they may encode multimodal representations of musical gestures and sounds. These systems may underlie the ability to learn how to play a musical instrument.


Cascade reactions in multicompartmentalized polymersomes.
Enzyme-filled polystyrene-b-poly(3-(isocyano-L-alanyl-aminoethyl)thiophene) (PS-b-PIAT) nanoreactors are encapsulated together with free enzymes and substrates in a larger polybutadiene-b-poly(ethylene oxide) (PB-b-PEO) polymersome, forming a multicompartmentalized structure, which shows structural resemblance to the cell and its organelles. An original cofactor-dependent three-enzyme cascade reaction is performed, using either compatible or incompatible enzymes, which takes place across multiple compartments.


Psychometric Testing of a Religious Belief Scale.
Nurses account for a significant percentage of staff in the healthcare system. The religious beliefs of nurses may affect their competence to provide spiritual care to patients. No reliable and valid instruments are currently available to measure the religious beliefs of nurses in Taiwan. The aims of this study were to develop a religious belief scale (RBS) for Taiwanese nurses and to evaluate the psychometric properties of this scale. A cross-sectional study design was used, and 24 RBS items were generated from in-depth interviews, a literature review, and expert recommendations. The RBS self-administered questionnaire was provided to 619 clinical nurses, who were recruited from two medical centers and one local hospital in Taiwan during 2011-2012. A calibration sample was used to explore the factor structure, whereas a validation sample was used to validate the factor structure that was constructed by the calibration sample. Known-group validity and criterion-related validity were also assessed. An exploratory factor analysis resulted in an 18-item RBS with four factors, including "religious effects," "divine," "religious query," and "religious stress." A confirmatory factor analysis recommended the deletion of one item, resulting in a final RBS of 17 items. The convergent validity and discriminate validity of the RBS were acceptable. The RBS correlated positively with spiritual health and supported concurrent validity. The known-group validity was supported by showing that the mean RBS between nurses with or without religious affiliation was significant. The 17-item RBS developed in this study is a reliable, valid, and useful scale for measuring the religious beliefs of nurses in Taiwan. This scale may help measure the religious beliefs of nurses and elicit the relationship between these beliefs and spirituality.


A basal dinosaur from the dawn of the dinosaur era in southwestern Pangaea.
Upper Triassic rocks in northwestern Argentina preserve the most complete record of dinosaurs before their rise to dominance in the Early Jurassic. Here, we describe a previously unidentified basal theropod, reassess its contemporary Eoraptor as a basal sauropodomorph, divide the faunal record of the Ischigualasto Formation with biozones, and bracket the formation with (40)Ar/(39)Ar ages. Some 230 million years ago in the Late Triassic (mid Carnian), the earliest dinosaurs were the dominant terrestrial carnivores and small herbivores in southwestern Pangaea. The extinction of nondinosaurian herbivores is sequential and is not linked to an increase in dinosaurian diversity, which weakens the predominant scenario for dinosaurian ascendancy as opportunistic replacement.


Negative symptoms in temporal lobe epilepsy.
This study examined the frequency of negative and positive symptoms in nonpsychotic patients with temporal lobe epilepsy and the relationship of negative and positive symptoms to cognition, quantitative magnetic resonance imaging (MRI) volumetrics, and depression. Eighty-four patients with temporal lobe epilepsy and 74 healthy comparison subjects were evaluated for negative and positive symptoms and underwent comprehensive neuropsychological evaluation, quantitative MRI volumetrics, and assessment of mood state and depression. Negative symptoms were significantly more prevalent in the patients with temporal lobe epilepsy (31%) than in the comparison subjects (8%). There was no difference between groups in the rate of positive symptoms. Although the epilepsy patients as a group exhibited generalized cognitive impairment relative to the comparison subjects, the epilepsy patients with negative symptoms performed significantly worse than patients without negative symptoms and comparison subjects across measures of nonverbal intelligence, visuoperception, speeded visuomotor processing, and memory. The epilepsy patients with negative symptoms exhibited significantly greater diffuse atrophy than the healthy comparison subjects and higher CSF volumes than the epilepsy patients without negative symptoms. The epilepsy patients with and without negative symptoms had statistically equivalent Beck Depression Inventory scores and lifetime history of mood disorders, including major depression. Negative but not positive symptoms were more prevalent in temporal lobe epilepsy patients than in healthy comparison subjects. Negative symptoms were independent of current and past depression and were associated with neuropsychological deficits exceeding the general cognitive morbidity associated with temporal lobe epilepsy and with quantitative MRI indices suggesting greater cerebral atrophy.


Zr-Based Metal-Organic Frameworks with Intrinsic Peroxidase-Like Activity for Ultradeep Oxidative Desulfurization: Mechanism of H2O2 Decomposition.
The restriction of sulfur content in fuels has become increasingly stringent as a result of the growing environmental concerns. Although several MOF-derived materials like POM@MOF composites have shown the ability to catalyze oxidative desulfurization (ODS), their catalytic activities inevitably obstructed by the encapsulated catalytic sites like POM due to the blockage of cavities. Therefore, MOFs with intrinsic and accessible catalytic sites are highly desirable for their applications in ultradeep ODS. Herein, four representative Zr-based MOFs (Zr-MOFs), namely, UiO-66, UiO-67, NU-1000, and MOF-808, were assessed for catalytic ODS. These MOFs were confirmed that they have peroxidase-like activity and can catalyze ODS with H2O2 as oxidant. Among them, MOF-808 showed the highest catalytic activity and it can fully desulfurize dibenzothiophene (DBT) in a model gasoline with a S concentration of 1000 ppm under 40 °C within 5 min. An extremely low apparent Arrhenius activation energy (22.0 KJ·mol-1) and an extraordinarily high TOF value (42.7 h-1) were obtained, ranking MOF-808 among the best catalysts for the catalytic DBT oxidation. Further studies confirmed that the excellent catalytic activity is mainly responsible for the high concentration of the accessible Zr-OH(H2O) catalytic sites decorated in MOF-808. The superoxide radicals (•O2-) and hydroxyl radicals (•OH) were identified and were proved to involve in the DBT oxidation. Besides, the effects of Brönsted and lewis acidity to the catalytic efficiency were also discussed. Based on the experimental results, a plausible mechanism concerning on Zr-OH(H2O) groups promoting the H2O2 decomposion in to both •O2- and •OH was first proposed. Moreover, MOF-808 can be facilely reused for at least eight runs without significant loss of its catalytic activity. By the integration of facile synthesis, high catalytic efficiency, and good stability, MOF-808 thus represents a new benchmark catalyst for catalytic oxidative desulfurization.


Pathology of experimental Babesia microti infection in the Syrian hamster.
Pathologic changes produced after 4 weeks of infection by Babesia microti in Syrian hamsters are described and compared to babesiosis of humans. Following intraperitoneal inoculation, both intravascular and extravascular hemolysis developed. Up to 70% of red blood cells were parasitized. The principal morphologic abnormalities were an increase in extramedullary hematopoiesis and hyperplasia of the mononuclear phagocytic cells of the red pulp manifested grossly as splenomegaly, marked renal tubular hemosiderosis and hypertrophy of Kupffer cells. The disease was not fatal to any hamsters during the 4 week study. The clinical signs and lesions were less severe than fatal babesiosis of asplenic humans and similar to severe, but nonfatal disease in spleen intact humans. The hamster may serve as an animal model for the studying the pathophysiology of human babesiosis and for studying potential chemotherapeutic agents.


Time perception in boys with attention-deficit/hyperactivity disorder according to time duration, distraction and mode of presentation.
In a recent theoretical model of attention-deficit/hyperactivity disorder (ADHD), Barkley (1997a) predicted that ADHD children experience impairments in their psychological sense of time. This was demonstrated in a series of experiments by Barkley, Koplowicz, Anderson, and McMurray (1997). The present study sought to investigate the effects of ADHD subtype, stimulus duration, mode of presentation (visual versus auditory) and distractors on the performance of a simple time reproduction task. Data were obtained from 44 ADHD children (14 predominantly inattentive and 30 combined type) and 44 age-matched Controls using the Time Perception Application version 1.0 (Barkley, University of Massachusetts Medical Center, 1998). Results revealed that the ADHD children made significantly larger errors on Visual time reproduction tasks than the Controls, regardless of ADHD subtype or the presence of distractors. Furthermore, ADHD children were more likely to overestimate the shorter time intervals (0.5 and 2 s) and underestimate the longer time intervals (3, 4 and 6 s) relative to Controls. No group differences were observed on the auditory time reproduction task, with both ADHD and Control groups consistently underestimating the durations to be reproduced. The results of this study provide further support for the prediction that children with ADHD have an impaired sense of time.


Detection of endotoxins and other pyrogens using human whole blood.
When cells of the immune system, i.e. primarily blood monocytes and macrophages, come into contact with pyrogens (fever-inducing contaminations) they release mediators transmitting the fever reaction through the organism to the thermoregulatory centres of the brain. The new test discussed here exploits this reaction for the detection of pyrogens: human whole blood taken from healthy volunteers is incubated in the presence of the test sample. If there is pyrogen contamination, the endogenous pyrogen interleukin-1 is released, which is then determined by ELISA. According to the pharmacopoeia, the rabbit pyrogen test determines the fever reaction following injection of a test sample. In comparison, the new whole blood assay is more sensitive, less expensive and determines the reaction of the targeted species. Compared to the well established in vitro alternative, i.e. the limulus amebocyte lysate assay (LAL), the new blood assay is not restricted to endotoxins of gram-negative bacteria, it is not affected by endotoxin-binding blood proteins and it reflects the potency of different endotoxin preparations in mammals. Here, interim results of the ongoing optimization and pre-validation are reported and the present state of the evaluation for biological and pharmaceutical drugs are presented.


Electrical stimulation of hyoid muscles in post-stroke dysphagia.
The purpose of this study was to evaluate swallowing changes in post-stroke patients with dysphagia after four weeks of suprahyoid muscles electrical stimulation. This was a prospective randomized study of early stage stroke patients with dysphagia. Electrical stimulation of suprahyoid muscles was given to a group of 54 patients (26 men, average age 70 years) for 20 minutes a day, 5 days a week. Standard orofacial rehabilitation without electrical stimulation was carried out on a control group of 54 patients (31 men, average age 69 years). Swallowing was evaluated at the beginning of the study and at the end, by videofluoroscopy - measuring the time for oral and pharyngeal phases. The difference in duration of oral transit time (OTT) after the therapy between the study group (average: 0.55 ± 0.01) and the control group (average: 0.29 ± 0.03) was statistically significant (P=0.01). Difference in duration of the pharyngeal transit time (PTT) after the therapy between the study group (average: 0.37 ± 0.02) and control group (average: 0.15 ± 0.02) was also statistically significant (P=0.009). Electrical stimulation of suprahyoid muscles significantly reduced the duration of the oral and pharyngeal phases: in the post-stroke patients with dysphagia used in this study. The result is improved swallowing. This is a recently recommended approach and your study confirms its efficacy.


Heroin maintenance for chronic heroin dependents.
Dependent heroin users are characterised by the persistence of use in spite of the difficulties they experience with health, law, social achievements and personal relationships. The present review will consider maintenance treatment in which the patients enter programs of pharmacological administration tailored to achieve patient stabilisation. Many medications have been used for this purpose such as: Methadone, Buprenorphine and LAAM. The present review will focus on maintenance treatment through the prescription of heroin. To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning. The Cochrane Central Register of Trials (CENTRAL) issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000 and CINAHL till 2000 were searched. There was no language or publication year restrictions. Many researchers were contacted for information. Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments. The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity. 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies included could not be analysed cumulatively because of heterogeneity of interventions and outcomes considered. Two studies compared injected heroin to oral methadone for 1 year (270 patients) but considered different outcomes; one study compared injected heroin and methadone to oral methadone for 6 months (51 patients); and one compared inhaled heroin and methadone to oral methadone for 1 year (235 patients). Retention in treatment: in two studies there was no statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI 1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90) in favour of methadone. Relapse to illegal heroin use, based on self report: in one study the proportion of people still using heroin were 64% in the heroin group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72) in favour of heroin. The remaining studies did not provide the data. Criminal offence: one of the two studies which provided details about this showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome did not show statistical difference between intervention groups. The two most recent studies considered criminal offence and social functioning as part of a multidomain outcome measure and showed higher improvement among those treated with heroin plus methadone over those on methadone only. No definitive conclusions about the overall effectiveness of heroin prescription is possible because of non-comparability of the experimental studies available to be included in this review. Results favouring heroin treatment come from studies conducted in countries where the treatment system is comprehensive and easy accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments.


Effect of antisense oligonucleotides to nuclear factor-kappaB on the survival of LPS-induced ARDS in mouse.
Because nuclear factor (NF)-kappaB-regulated cytokines, including tumor necrosis factor-alpha (TNF-alpha), from monocytes and macrophages have been implicated in the pathogenesis and development of septic shock and acute respiratory distress syndrome (ARDS), the effect of the antisense oligonucleotide to the p65 subunit of NF-kappaB on the survival of lipopolysaccharide (LPS)-induced ARDS in BALB/c mice was examined. None and 70% of the animals died of diffuse hemorrhagic lung edema 1 to 2.5 days after intraperitoneal administration of 10 and 20 mg/kg LPS alone, respectively. Intravenously administered antisense oligonucleotide alone did not produce any significant changes in the behavior or lung histology. After intravenous administration of the anti-sense oligonucleotide, both peripheral blood monocytes and alveolar macrophages in bronchoalveolar lavage fluid were confirmed to contain sufficiently large amounts of intracellular antisense oligonucleotides for their function usingfluorescein isothiocyanate (FTCC)-labeled microscopy. The antisense oligonucleotide administered 6 hours before the intraperitoneal administration of LPS significantly decreased the survival rate with the progress of hemorrhagic edema in lung histology; 90% and 100% of animals treated with the antisense oligonuleotide died 0.5 to 1.5 days after the administration of 10 and 20 mg/kg LPS, respectively. These findings suggest that the suppression of cytokines and mediators in monocytes and alveolar macrophages by the antisense oligonucleotide to the p65 subunit of NF-kappaB worsens the survival of LPS-induced ARDS in mice with the progress of hemorrhagic lung edema.


[Carbogen therapy in high myopia in children].
Forty-eight patients, aged 7 to 15, with the diagnosis of high developed myopia complicated by chorioretinal peripheral dystrophy were investigated. A total of 1500 examinations were made. The patients were shared between the main and control groups. Sex, age and the clinical pattern were compatible. The main-group patients received the carbogene therapy and routine neurotrophic treatment, while the controls received only the latter. The treatment course lasted for as long as 10 days (10 inhalations). There were no any complications during and after the carbogene inhalations. The conclusion, based on the data obtained, can be that the carbogene inhalations, when added to the neurotrophic treatment scheme, enhance the therapy efficiency in case of high, complicated and developed myopia in children.


Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.
To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.


Nutrient Status and perceptions of energy and macronutrient intake in a Group of Collegiate Female Lacrosse Athletes.
The purpose of this study was to compare nutritional intakes against recommended values as well as between the perceived intake and needs of female lacrosse players. Twenty female NCAA Division II lacrosse players (20.0 ± 1.7 yrs., 169.7 ± 6.4 cm; 69.9 ± 10.7 kg; 27.5 ± 3.3% fat) completed a four-day monitoring period during in-season. Athletes were outfitted with an activity monitor over four consecutive days and completed four-day food records to assess total daily energy expenditure (TDEE) and dietary intake. Body composition was assessed and used to calculate recommended dietary intakes. Actual intake was self-reported using a commercially available food tracking program (MyFitnessPal©, USA). Daily average values were calculated for total and relative energy, protein, carbohydrate, and fat intake. These values were then compared to published nutritional recommendations established by the International Society of Sports Nutrition. Appropriate pairwise comparisons were made depending on the normality of the distribution. Athletes ate significantly less than recommended values for energy, carbohydrates and protein. (p < 0.001). Significant discrepancies (p < 0.001) were also observed between perceptions of intake versus actual intake. Athletes significantly underestimated perceived intake of dietary fat and carbohydrate when compared to perceived needs. Massive standard deviations and ranges were observed, suggesting that some athletes lack a basic understanding of their daily needs. Results from this data suggest that collegiate athletes lack appropriate understanding of basic nutrition needs and could benefit from basic nutrition education as it pertains to their health and performance.


Lineage-specific regulation of the neural differentiation gene MASH1.
Mash1 is a transcription factor required during embryogenesis for the development of multiple neural lineages. It is expressed in restricted domains at specific stages in the developing central and peripheral nervous systems and in the developing olfactory epithelium. We have investigated the regulation of Mash1 expression during embryogenesis using transgenic mice containing Mash1/lacZ reporter constructs. Cis-acting regulatory elements controlling Mash1 expression in the central nervous system are located within an 8-kb sequence upstream of the Mash1 coding region. This 8-kb sequence does not contain elements directing expression to the peripheral nervous system, olfactory epithelium, or retina. Sequences outside this 8 kb but within 36 kb of the Mash1 locus contain elements responsible for expression in the autonomic division of the peripheral nervous system. However, transgene expression in embryos containing the 36-kb sequence was never detected in the olfactory epithelium and retina. Thus, regulatory elements driving expression in these lineages may be at even greater distances from the Mash1 coding region. These data provide evidence for complex regulation of Mash1 expression in which multiple lineage-specific cis-acting regulatory regions span greater than 36 kb of the Mash1 locus. Further characterization of these regions will facilitate the study of factors that regulate the temporal and spatial expression of Mash1 during development. In addition, the regulatory sequences identified here can direct expression of heterologous genes to developing neural lineages that normally express Mash1, thus providing an important tool for examining the function of candidate regulatory genes in mammalian nervous system development.


Disseminated Lyme disease presenting with nonsexual acute genital ulcers.
Nonsexual acute genital ulceration (NAGU) is a rare vulvar skin condition typically affecting girls and young women, characterized by acute onset of singular or multiple painful vaginal ulcers. The etiology of this ulcerative dermatosis has not been identified, although it has been associated with systemic infections. To our knowledge, this is the first report of an association with Lyme disease. A case of a woman with early disseminated Lyme disease presenting with NAGU is reported. A thorough workup ruled out other causes of genital ulceration, and the ulcers completely resolved after treatment with topical steroids and oral doxycycline. Although the etiology of NAGU is unknown, the vulvar ulcers may result from an exuberant immune response to infection. Most patients with NAGU exhibit nonspecific symptoms such as myalgias and fever, suggesting an infectious agent, but the majority have no identifiable pathogen. In addition to previously reported associations with systemic infection, which are reviewed herein, Lyme disease should be considered in women presenting with acute-onset genital ulcers.


High Levels of Syndemics and Their Association with Adherence, Viral Non-suppression, and Biobehavioral Transmission Risk in Miami, a U.S. City with an HIV/AIDS Epidemic.
Miami is a Southeastern United States (U.S.) city with high health, mental health, and economic disparities, high ethnic/racial diversity, low resources, and the highest HIV incidence and prevalence in the country. Syndemic theory proposes that multiple, psychosocial comorbidities synergistically fuel the HIV/AIDS epidemic. People living with HIV/AIDS in Miami may be particularly affected by this due to the unique socioeconomic context. From April 2017 to October 2018, 800 persons living with HIV/AIDS in a public HIV clinic in Miami completed an interviewer-administered behavioral and chart-review cross-sectional assessment to examine the prevalence and association of number of syndemics (unstable housing, low education, depression, anxiety, binge drinking, drug use, violence, HIV-related stigma) with poor ART adherence, unsuppressed HIV viral load (≥ 200 copies/mL), and biobehavioral transmission risk (condomless sex in the context of unsuppressed viral load). Overall, the sample had high prevalence of syndemics (M = 3.8), with almost everyone (99%) endorsing at least one. Each syndemic endorsed was associated with greater odds of: less than 80% ART adherence (aOR 1.64, 95% CI 1.38, 1.98); having unsuppressed viral load (aOR 1.16, 95% CI 1.01, 1.33); and engaging in condomless sex in the context of unsuppressed viral load (1.78, 95% CI 1.30, 2.46). The complex syndemic of HIV threatens to undermine the benefits of HIV care and are important to consider in comprehensive efforts to address the disproportionate burden of HIV/AIDS in the Southern U.S. Achieving the 90-90-90 UNAIDS and the recent U.S. "ending the epidemic" targets will require efforts addressing the structural, social, and other syndemic determinants of HIV treatment and prevention.


Thermoperiodic responses in insects and mites simulated with the double circadian oscillator clock.
The "double circadian oscillator model" for the photoperiodic clock has been used to simulate thermoperiodic responses in insects and mites. Two assumptions have been made: (1) the clock measures cryophase in a similar way to scotophase, and (2) temperature cycles are able to entrain the clock in a similar way to LD cycles. Simulations showed that Assumption 1 causes the "critical cryophase" to be of about equal duration as the critical night length. Assumption 2 is not always needed if diapause incidences in DD are high at low temperatures but low or zero at high temperatures. The latter assumption is needed, however, if high diapause occurs in thermoperiodic cycles in DD, whereas nondiapause occurs in DD with both high and low constant temperatures. The model accounts for the observation that the amplitude of the temperature cycle is important in some insects, whereas the temperature of the cryophase is crucial in others.


Gestational diabetes exacerbates maternal immune activation effects in the developing brain.
Maternal inflammation and diabetes increase the risk for psychiatric disorders in offspring. We hypothesized that these co-occurring risk factors may potentiate each other. To test this, we maternally exposed developing mice in utero to gestational diabetes mellitus (GDM) and/or maternal immune activation (MIA). Fetal mouse brains were exposed to either vehicle, GDM, MIA or GDM+MIA. At gestational day (GD) 12.5, GDM produced a hyperglycemic, hyperleptinemic maternal state, whereas MIA produced significant increases in proinflammatory cytokines and chemokines. Each condition alone resulted in an altered, inflammatory and neurodevelopmental transcriptome profile. In addition, GDM+MIA heightened the maternal inflammatory state and gave rise to a new, specific transcriptional response. This exacerbated response was associated with pathways implicated in psychiatric disorders, including dopamine neuron differentiation and innate immune response. Based on these data, we hypothesize that children born to GDM mothers and exposed to midgestation infections have an increased vulnerability to psychiatric disorder later in life, and this should be tested in follow-up epidemiological studies.


Multicentre study of the molecular epidemiology, serotypes and antimicrobial susceptibility patterns of invasive Streptococcus pneumoniae invasive isolated from children in the Ille de France area.
Between January 1997 and April 2002, 73 consecutive invasive strains of Streptococcus pneumoniae were isolated from children under 16 years of age in four hospitals in suburban Paris. Their genetic diversity was investigated by serotyping and analysis of pulsed-field gel electrophoresis restriction patterns. Antibiotic susceptibility patterns were analysed by disk susceptibility testing and determination of minimal inhibitory concentrations. The genetic basis of macrolide resistance was investigated by polymerase chain reaction. Studies of penicillin and vancomycin tolerance were performed for each strain. Despite the high prevalence (45.2%) of penicillin-nonsusceptible Streptococcus pneumoniae, resistance to amoxicillin (1.4%) was rare, and no strain was resistant to cefotaxime. Overall, 4.1% of pneumococcal strains were resistant to penicillin. Penicillin or vancomycin tolerance was not detected in any of the 73 strains studied. Of the erythromycin-resistant strains (48%), all but one carried the ermB gene. No strains showing a decreased susceptibility to ciprofloxacin (MIC, >4 mg/l) or overexpressing an efflux pump inhibited by reserpine were isolated. The serotypes found, in order of frequency, were as follows: 18C, 14, 6B, 19F, 19A, 9V, 23F, 1, 7F, 9A, 38. Strains of penicillin-nonsusceptible Streptococcus pneumoniae belonged predominantly to serotypes 14, 6B, 9V, 9A, 23F, 19F and 19A. The seven-valent conjugated vaccine covered 85.5% of the serogroups isolated in children under 2 years of age and 65.6% of the serogroups identified in children over 2 years of age. The genetic analysis showed a high identity for some serotypes, such as 14/9V, 6B and 23F. The use of the seven-valent conjugated vaccine is a critical measure to prevent invasive pneumococci infections in children in the Ille de France area.


Glucose-dependent insulinotropic polypeptide regulates body weight and food intake via GABAergic neurons in mice.
The development of single-molecule co-agonists for the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) is considered a breakthrough in the treatment of obesity and type 2 diabetes. But although GIPR-GLP-1R co-agonism decreases body weight with superior efficacy relative to GLP-1R agonism alone in preclinical1-3 and clinical studies4,5, the role of GIP in regulating energy metabolism remains enigmatic. Increasing evidence suggests that long-acting GIPR agonists act in the brain to decrease body weight through the inhibition of food intake3,6-8; however, the mechanisms and neuronal populations through which GIP affects metabolism remain to be identified. Here, we report that long-acting GIPR agonists and GIPR-GLP-1R co-agonists decrease body weight and food intake via inhibitory GABAergic neurons. We show that acyl-GIP decreases body weight and food intake in male diet-induced obese wild-type mice, but not in mice with deletion of Gipr in Vgat(also known as Slc32a1)-expressing GABAergic neurons (Vgat-Gipr knockout). Whereas the GIPR-GLP-1R co-agonist MAR709 leads, in male diet-induced obese wild-type mice, to greater weight loss and further inhibition of food intake relative to a pharmacokinetically matched acyl-GLP-1 control, this superiority over GLP-1 vanishes in Vgat-Gipr knockout mice. Our data demonstrate that long-acting GIPR agonists crucially depend on GIPR signaling in inhibitory GABAergic neurons to decrease body weight and food intake.


Temperature response of CO2 exchange in three tropical tree species.
Tropical forests play a critical role in the global carbon cycle, but our limited understanding of the physiological sensitivity of tropical forest trees to environmental factors complicates predictions of tropical carbon fluxes in a changing climate. We determined the short-term temperature response of leaf photosynthesis and respiration of seedlings of three tropical tree species from Panama. For one of the species net CO2 exchange was also measured in situ. Dark respiration of all species increased linearly - not exponentially - over a ~30°C temperature range. The early-successional species Ficus insipida Willd. and Ochroma pyramidale (Cav. ex Lam.) Urb. had higher temperature optima for photosynthesis (Topt) and higher photosynthesis rates at Topt than the late-successional species Calophyllum longifolium Willd. The decrease in photosynthesis above Topt could be assigned, in part, to observed temperature-stimulated photorespiration and decreasing stomatal conductance (gS), with unmeasured processes such as respiration in the light, Rubisco deactivation, and changing membrane properties probably playing important additional roles, particularly at very high temperatures. As temperature increased above Topt, gS of laboratory-measured leaves first decreased, followed by an increase at temperatures >40-45°C. In contrast, gS of canopy leaves of F. insipida in the field continued to decrease with increasing temperature, causing complete suppression of photosynthesis at ~45°C, whereas photosynthesis in the laboratory did not reach zero until leaf temperature was ~50°C. Models parameterised with laboratory-derived data should be validated against field observations when they are used to predict tropical forest carbon fluxes.


Aerial ultrasonic micro Doppler sonar detection range in outdoor environments.
Current research demonstrates that micro Doppler sonar has the capability to uniquely identify the presence of a moving human, making it an attractive component in surveillance systems for border security applications. Primary environmental factors that limit sonar performance are two-way spreading losses, ultrasonic absorption, and backscattered energy from the ground that appears at zero Doppler shift in the sonar signal processor. Spectral leakage from the backscatter component has a significant effect on sonar performance for slow moving targets. Sonar performance is shown to rapidly decay as the sensor is moved closer to the ground due to increasing surface backscatter levels.


The small introns of antisense genes are better explained by selection for rapid transcription than by "genomic design".
Several models have been proposed to explain why expression parameters of a gene might be related to the size of the gene's introns. These include the idea that an energetic cost of transcription should favor smaller introns in highly expressed genes (the "economy selection" argument) and that tissue-specific genes reside in genomic locations with complex chromatin level control requiring large amounts of noncoding DNA (the "genomic design" hypothesis). We recently proposed a modification of the economy model arguing that, for some genes, the time that expression takes is more important than the energetic cost, such that some weakly but rapidly expressed genes might also have small introns. We suggested that antisense genes might be such a class and showed that the data appear to be consistent with this. We now reexamine this model to ask (a) whether the effects described were owing solely to the fact that antisense genes are often noncoding RNA and (b) whether we can confidently reject the "genomic design" model as an explanation for the facts. We show that the effects are not specific to noncoding RNAs and that the predictions of the "genomic design" model for the most part are not upheld.


Placental passage of antiepileptic drugs at delivery and neonatal outcomes.
Children of women treated with antiepileptic drugs (AEDs) are at increased risk of adverse outcomes detectable in the neonatal period, which may be associated with the amount of AEDs in the fetal circulation. Placental passage of AEDs can be measured by calculating the ratio of umbilical cord to maternal AED concentrations collected at delivery. The aims of this study were to determine the umbilical cord concentrations and umbilical-to-maternal ratios for AEDs, and whether higher cord concentrations are associated with increased risk of neonatal complications. AED cord and maternal blood concentrations from 70 mother-newborn dyads and neonatal complications were recorded. Logistic regressions were performed to determine the association between AED concentrations and complications. Mean umbilical-to-maternal ratios for total concentrations ranged from 0.79 for carbamazepine to 1.20 for valproic acid, and mean umbilical-to-maternal ratios for free concentrations ranged from 0.86 for valproic acid to 1.42 for carbamazepine, indicating complete placental passage. Neither umbilical cord concentrations nor umbilical-to-maternal ratios were associated with adverse neonatal outcomes. Additional investigations are warranted to delineate the relationship between quantified fetal AED exposure and neonatal complications.


Electric-field-assisted assembly of perpendicularly oriented nanorod superlattices.
We observe the assembly of CdS nanorod superlattices by the combination of a DC electric field and solvent evaporation. In each electric-field (1 V/microm) assisted assembly, CdS nanorods (5 nm x 30 nm) suspended initially in toluene were observed to align perpendicular to the substrate. Azimuthal alignment along the nanorod crystal faces and the presence of stacking faults indicate that both 2D and 3D assemblies were formed by a process of controlled super crystal growth.


Effects of Culturing on the Stability of the Putative Murine Adipose Derived Stem Cells Markers.
Mesenchymal stem cells have generated much interest because of their potential use in regenerative medicine. The major draw back in the application of these cells is that there is no single marker or markers that have been established to identify and aid in isolating the cells from a variety of other cell types. The commonly expressed mesenchymal stem cell surface antigens include CD44, CD73, CD90.2, CD105, and CD146. In the present study we examined the stability of these surface antigens in culture and their potential application in identifying and isolating murine derived adipose derived stem cells. The data showed that the expression of these markers increased with culturing and appeared to stabilize by passage 8; the cells were sorted positively for the surface markers at this passage. Each subset was maintained in culture and evaluated for differentiation toward osteogenic lineage in vitro and in vivo. The CD73 and CD105 positive cell subsets demonstrated robust differentiation toward osteogenic lineage in vitro; the CD90.2+ cell subset exhibited the least differentiation toward osteogenic lineage. Assessment of the cell subpopulations for in vivo differentiation demonstrated that all the cell subsets exhibited potential to differentiate into osteoblasts. Taken together, these data suggest that this panel of markers although useful in identifying cells with potential to differentiate toward osteogenic lineage, cannot prospectively be used for enriching for ADSC from a variety of other cell types.


Low-Cost 3-D Flow Estimation of Blood With Clutter.
Volumetric flow rate estimation is an important ultrasound medical imaging modality that is used for diagnosing cardiovascular diseases. Flow rates are obtained by integrating velocity estimates over a cross-sectional plane. Speckle tracking is a promising approach that overcomes the angle dependency of traditional Doppler methods, but suffers from poor lateral resolution. Recent work improves lateral velocity estimation accuracy by reconstructing a synthetic lateral phase (SLP) signal. However, the estimation accuracy of such approaches is compromised by the presence of clutter. Eigen-based clutter filtering has been shown to be effective in removing the clutter signal; but it is computationally expensive, precluding its use at high volume rates. In this paper, we propose low-complexity schemes for both velocity estimation and clutter filtering. We use a two-tiered motion estimation scheme to combine the low complexity sum-of-absolute-difference and SLP methods to achieve subpixel lateral accuracy. We reduce the complexity of eigen-based clutter filtering by processing in subgroups and replacing singular value decomposition with less compute-intensive power iteration and subspace iteration methods. Finally, to improve flow rate estimation accuracy, we use kernel power weighting when integrating the velocity estimates. We evaluate our method for fast- and slow-moving clutter for beam-to-flow angles of 90° and 60° using Field II simulations, demonstrating high estimation accuracy across scenarios. For instance, for a beam-to-flow angle of 90° and fast-moving clutter, our estimation method provides a bias of -8.8% and standard deviation of 3.1% relative to the actual flow rate.


Loss of spinal cord monitoring signals in children during thoracic kyphosis correction with spinal osteotomy: why does it occur and what should you do?
A retrospective review of pediatric kyphosis patients undergoing a spinal cord-level osteotomy for correction. To evaluate the prevalence, etiology, timing, and intervention related to loss of spinal cord monitoring data during surgical correction of pediatric kyphosis in the spinal cord region. Although much has been written regarding the risks inherent to scoliosis surgery, there is less literature available regarding the neurologic outcomes of pediatric kyphosis surgery. As more surgeons contemplate posterior-only kyphosis correction with spinal cord-level osteotomies, the importance of maintaining spinal cord neurologic function is paramount. Forty-two patients with pediatric kyphosis undergoing a posterior-only spinal reconstruction with a spinal cord level osteotomy or posterior-based vertebral column resection performed were reviewed. Patients were categorized by diagnosis, type and incidence of osteotomies, and loss of neurogenic mixed-evoked potential (NMEP) data. Interventions required to regain data and postoperative neurologic outcomes were also reviewed. Of the 42 patients, 9 (21.4%) demonstrated a complete loss of NMEP data sometime during surgery while concomitant somatosensory sensory-evoked potentials (SSEP) remained within acceptable limits of baseline values. All 9 patients had intraoperative intervention including: blood pressure elevation (n = 1), release of corrective forces (n = 2), blood pressure elevation and correction release (n = 3), malalignment/subluxation adjustment (n = 1), further bony decompression (n = 1), or restoration of anterior column height via a titanium cage along with further posterior decompression (n = 1). In all cases, SSEPs were unchanged and NMEPs returned varying from 8 to 20 minutes after loss, with all patients having a normal wake-up test intraoperatively and a normal neurologic examination after surgery. Intraoperative multimodality monitoring with some form of motor tract assessment is a fundamental component of kyphosis correction surgery in the spinal cord region in order to create a safer, optimal environment and to minimize neurologic deficit. The surgeon must be able to trust the information monitoring provides and act on it accordingly.


A review of anti-IgE monoclonal antibody (omalizumab) as add on therapy for severe allergic (IgE-mediated) asthma.
Bronchial asthma is recognized as a highly prevalent health problem in the developed and developing world with significant social and economic consequences. Increased asthma severity is not only associated with enhanced recurrent hospitalization and mortality but also with higher social costs. The pathogenetic background of allergic-atopic bronchial asthma is characterized by airway inflammation with infiltration of several cells (mast cells, basophils, eosinophils, monocytes, and T-helper (Th)2 lymphocytes). However, in atopic asthma the trigger factors for acute attacks and chronic worsening of bronchial inflammation are aeroallergens released by pollens, dermatophagoides, and pets, which are able to induce an immune response by interaction with IgE antibodies. Currently anti-inflammatory treatments are effective for most asthma patients, but there are asthmatic subjects whose disease is not completely controlled by inhaled or systemic corticosteroids and who account for a significant portion of the healthcare costs of asthma. A novel therapeutic approach to asthma and other allergic respiratory diseases involves interference in the action of IgE, and this antibody has been viewed as a target for novel immunological drug development in asthma. Omalizumab is a humanized recombinant monoclonal anti-IgE antibody approved for treatment of moderate to severe IgE-mediated (allergic) asthma. This non-anaphylactogenic anti-IgE antibody inhibits IgE functions, blocking free serum IgE and inhibiting their binding to cellular receptors. By reducing serum IgE levels and IgE receptor expression on inflammatory cells in the context of allergic cascade, omalizumab represents a new class of mast cells stabilizing drugs; it is a novel approach to the treatment of atopic asthma. Omalizumab therapy is well tolerated and significantly improves symptoms and disease control, reducing asthma exacerbations and the need to use high dosage of inhaled corticosteroids. Moreover, omalizumab improves quality of life of patients with severe persistent allergic asthma which is inadequately controlled by currently available asthma medications. In conclusion omalizumab may fulfil an important need in patients with moderate to severe asthma.


Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment.
Defective copper regulation is implicated as a causative mechanism of organ damage in diabetes. Treatment with trientine, a divalent-copper-selective chelator, improves arterial and renal structure/function in diabetes, wherein it also ameliorates left-ventricular (LV) hypertrophy. However, direct in vivo evidence that trientine can improve cardiac function in heart failure has hitherto been lacking. To determine whether trientine treatment could improve in vivo outcome, we measured cardiac function in groups of trientine-treated diabetic (TETA-DIA), non-drug-treated diabetic (DIA) and sham-treated control (SHAM) rats, by using in vivo high-field cardiac magnetic-resonance imaging (cMRI) and an ex vivo isolated-perfused working heart method. Forty age-matched animals underwent a cMRI scan after which 12 were randomized to the SHAM group and 28 underwent streptozotocin-injection; of these, 25 developed stable diabetes, and 12 were then randomized to receive no treatment for 16 weeks (DIA) and the other 13 to undergo 8-weeks' untreated diabetes followed by 8-weeks' drug treatment (TETA-DIA). Animals were studied again by cMRI at 8 and 16 weeks following disease induction, and finally by measurement of ex vivo cardiac function. After eight weeks diabetes, rats (DIA/TETA-DIA) had developed significant impairment of LV function, as judged by impairment of ejection fraction (LVEF), cardiac output (CO), and LV mass (LVM)/body-mass (all P < 0.001), as well as other functional indexes. LVEF, CO (both P < 0.001) and the other indexes deteriorated further at 16 weeks in DIA, whereas trientine (TETA-DIA) improved cardiac function by elevating LVEF and CO (both P < 0.001), and also partially reversed the increase in LVM/body-mass (P < 0.05). In ex vivo hearts from DIA, the CO response to increasing preload pressure was deficient compared with SHAM (P < 0.001) whereas the preload-CO relationship was significantly improved in TETA-DIA animals (P < 0.001). Trientine treatment significantly improved cardiac function in diabetic rats with substantive LV impairment. These results implicate impaired copper regulation in the pathogenesis of impaired cardiac function caused by diabetic cardiomyopathy, and support ongoing studies of trientine treatment in patients with heart failure.


Low Xanthophylls, Retinol, Lycopene, and Tocopherols in Grey and White Matter of Brains with Alzheimer's Disease.
Oxidative stress contributes to pathogenesis and progression of Alzheimer's disease (AD). Higher levels of the dietary antioxidants- carotenoids and tocopherols- are associated with better cognitive functions and lower risk for AD, and lower levels of multiple carotenoids are found in serum and plasma of patients with AD. Although brains donated by individuals with mild cognitive impairment had significantly lower levels of lutein and beta-carotene, previous investigators found no significant difference in carotenoid levels of brains with AD and cognitively normal brains. This study tested the hypothesis that micronutrients are significantly lower in donor brains with AD than in healthy elderly brains. Samples of donor brains with confirmed AD or verified health were dissected into grey and white matter, extracted with organic solvents and analyzed by HPLC. AD brains had significantly lower levels of lutein, zeaxanthin, anhydrolutein, retinol, lycopene, and alpha-tocopherol, and significantly increased levels of XMiAD, an unidentified xanthophyll metabolite. No meso-zeaxanthin was detected. The overlapping protective roles of xanthophylls, carotenes, α- and γ-tocopherol are discussed. Brains with AD had substantially lower concentrations of some, but not all, xanthophylls, carotenes, and tocopherols, and several-fold higher concentrations of an unidentified xanthophyll metabolite increased in AD (XMiAD).


Evaluation of an oral health education program for nursing personnel in special housing facilities for the elderly. Part II: Clinical aspects.
In Sweden, efforts are being made to create strategies for evaluating realistic dental treatment needs among the elderly, who are retaining more natural teeth. These strategies focus on the importance of maintaining adequate oral hygiene. Elderly in long-term-care facilities often depend on nursing personnel for carrying out daily oral hygiene procedures. Therefore, the nursing personnel's knowledge about and attitudes toward oral health make oral health education for health care professionals an important concern. The purpose of this study was to evaluate the clinical oral health outcome in residents after their caregivers had undergone a one-session, four-hour oral health education program. The study consisted of an intervention with a pre- and a post-test and was carried out in three municipalities in the southwestern part of Sweden. A newly developed oral health screening protocol was carried out for 170 subjects living in long-term-care facilities both before and 3-4 months after nursing personnel had attended an oral health education program. Following the intervention, a statistically significant improvement was recorded for changes in oral mucosal color, a modified plaque index which measured oral hygiene status, and a mucosal index which recorded mucosal inflammation. This study indicated that a limited, one-session, four-hour oral health education, offered to caregivers within long-term-care facilities, had a positive impact on the oral health status of residents.


A deep stop during decompression from 82 fsw (25 m) significantly reduces bubbles and fast tissue gas tensions.
In spite of many modifications to decompression algorithms, the incidence of decompression sickness (DCS) in scuba divers has changed very little. The success of stage, compared to linear ascents, is well described yet theoretical changes in decompression ratios have diminished the importance of fast tissue gas tensions as critical for bubble generation. The most serious signs and symptoms of DCS involve the spinal cord, with a tissue half time of only 12.5 minutes. It is proposed that present decompression schedules do not permit sufficient gas elimination from such fast tissues, resulting in bubble formation. Further, it is hypothesized that introduction of a deep stop will significantly reduce fast tissue bubble formation and neurological DCS risk. A total of 181 dives were made to 82 fsw (25 m) by 22 volunteers. Two dives of 25 min and 20 min were made, with a 3 hr 30 min surface interval and according to 8 different ascent protocols. Ascent rates of 10, 33 or 60 fsw/min (3, 10, 18 m/min) were combined with no stops or a shallow stop at 20 fsw (6 m) or a deep stop at 50 fsw (15 m) and a shallow at 20 fsw (6 m). The highest bubbles scores (8.78/9.97), using the Spencer Scale (SS) and Extended Spencer Scale (ESS) respectively, were with the slowest ascent rate. This also showed the highest 5 min and 10 min tissue loads of 48% and 75%. The lowest bubble scores (1.79/2.50) were with an ascent rate of 33 fsw (10 m/min) and stops for 5 min at 50 fsw (15 m) and 20 fsw (6 m). This also showed the lowest 5 and 10 min tissue loads at 25% and 52% respectively. Thus, introduction of a deep stop significantly reduced Doppler detected bubbles together with tissue gas tensions in the 5 and 10 min tissues, which has implications for reducing the incidence of neurological DCS in divers.


Development and characterization of siRNA lipoplexes: Effect of different lipids, in vitro evaluation in cancerous cell lines and in vivo toxicity study.
Cationic liposomes have long been used as non-viral vectors for small interfering RNA (siRNA) delivery but are associated with high toxicity, less transfection efficiency, and in vivo instability. In this investigation, we have developed siRNA targeted to RRM1 that is responsible for development of resistance to gemcitabine in cancer cells. Effect of different lipid compositions has been evaluated on formation of stable and less toxic lipoplexes. Optimized cationic lipoplex (D2CH) system was comprised of dioleoyl-trimethylammoniumpropane (DOTAP), dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), hydrogenated soya phosphocholine (HSPC), cholesterol, and methoxy(polyethyleneglycol)2000-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG2000-DSPE). D2CH lipoplexes have shown particle size (147.5 ± 2.89 nm) and zeta potential (12.26 ± 0.54 mV) characteristics essential for their in vivo use. In vitro cytotoxicity study has shown low toxicity of developed lipoplexes as compared with lipofectamine-2000 up to N/P ratio as high as 7.5. Cell uptake studies and gene expression studies have confirmed intracellular availability of siRNA. In addition, developed lipoplexes also showed ~3 times less hemolytic potential as compared with DOTAP/DOPE lipoplexes at lipid concentration of 5 mg/mL. Lipoplexes also maintained particle size less than 200 nm on exposure to high electrolyte concentration and showed >70% siRNA retention in presence of serum showing siRNA protection conferred by lipoplexes. Furthermore, in vivo acute toxicity studies in mice showed that formulation was non-toxic up to a dosage of 0.75 mg of siRNA/kg as lipoplexes and 300 mg lipid/kg as blank liposomes indicating tolerability of lipoplexes at a dose much higher than required for therapeutic use. Promising results of this study warrant further investigation of developed siRNA lipoplexes for cancer treatment.