Prayer and healing: A medical and scientific perspective on randomized controlled trials.
Religious traditions across the world display beliefs in healing through prayer. The healing powers of prayer have been examined in triple-blind, randomized controlled trials. We illustrate randomized controlled trials on prayer and healing, with one study in each of different categories of outcome. We provide a critical analysis of the scientific and philosophical dimensions of such research. Prayer has been reported to improve outcomes in human as well as nonhuman species, to have no effect on outcomes, to worsen outcomes and to have retrospective healing effects. For a multitude of reasons, research on the healing effects of prayer is riddled with assumptions, challenges and contradictions that make the subject a scientific and religious minefield. We believe that the research has led nowhere, and that future research, if any, will forever be constrained by the scientific limitations that we outline.


Differentiation of Chiari malformation type 1 and spontaneous intracranial hypotension using objective measurements of midbrain sagging.
Chiari malformation type 1 (CM-1) and spontaneous intracranial hypotension (SIH) are causes of headache in which cerebellar tonsillar ectopia (TE) may be present. An accurate method for differentiating these conditions on imaging is needed to avoid diagnostic confusion. Here, the authors sought to determine whether objective measurements of midbrain morphology could distinguish CM-1 from SIH on brain MRI. This is a retrospective case-control series comparing neuroimaging in consecutive adult subjects with CM-1 and SIH. Measurements obtained from brain MRI included previously reported measures of brain sagging: TE, slope of the third ventricular floor (3VF), pontomesencephalic angle (PMA), mamillopontine distance, lateral ventricular angle, internal cerebral vein-vein of Galen angle, and displacement of iter (DOI). Clivus length (CL), an indicator of posterior fossa size, was also measured. Measurements for the CM-1 group were compared to those for the entire SIH population (SIHall) as well as a subgroup of SIH patients with > 5 mm of TE (SIHTE subgroup). Highly significant differences were observed between SIHall and CM-1 groups in the following measures: TE (mean ± standard deviation, 3.1 ± 5.7 vs 9.3 ± 3.5 mm), 3VF (-16.8° ± 11.2° vs -2.1° ± 4.6°), PMA (44.8° ± 13.1° vs 62.7° ± 9.8°), DOI (0.2 ± 4.1 vs 3.8 ± 1.6 mm), and CL (38.3 ± 4.5 vs 44.0 ± 3.3 mm; all p < 0.0001). Eight (16%) of 50 SIH subjects had TE > 5 mm; in this subgroup (SIHTE), a cutoff value of < -15° for 3VF and < 45° for PMA perfectly discriminated SIH from CM-1 (sensitivity and specificity = 1.0). DOI showed perfect specificity (1.0) in detecting SIH among both groups. No subjects with SIH had isolated TE without other concurrent findings of midbrain sagging. Measures of midbrain sagging, including cutoff values for 3VF and PMA, discriminate CM-1 from SIH and may help to prevent misdiagnosis and unnecessary surgery.


Insulin receptor substrate 1 gene expression is strongly up-regulated by HSPB8 silencing in U87 glioma cells.
Objective. The aim of the present investigation was to study the expression of genes encoding IRS1 (insulin receptor substrate 1) and some other functionally active proteins in U87 glioma cells under silencing of polyfunctional chaperone HSPB8 for evaluation of the possible significance of this protein in intergenic interactions.Methods. Silencing of HSPB8 mRNA was introduced by HSPB8 specific siRNA. The expression level of HSPB8, IRS1, HK2, GLO1, HOMER3, MYL9, NAMPT, PER2, PERP, GADD45A, and DEK genes was studied in U87 glioma cells by quantitative polymerase chain reaction.Results. It was shown that silencing of HSPB8 mRNA by specific to HSPB8 siRNA led to a strong down-regulation of this mRNA and significant modification of the expression of IRS1 and many other genes in glioma cells: strong up-regulated of HOMER3, GLO1, and PERP and down-regulated of MYL9, NAMPT, PER2, GADD45A, and DEK gene expressions. At the same time, no significant changes were detected in the expression of HK2 gene in glioma cells treated by siRNA, specific to HSPB8. Moreover, the silencing of HSPB8 mRNA enhanced the glioma cells proliferation rate.Conclusions. Results of this investigation demonstrated that silencing of HSPB8 mRNA affected the expression of IRS1 gene as well as many other genes encoding tumor growth related proteins. It is possible that the dysregulation of most of the studied genes in glioma cells after silencing of HSPB8 is reflected by a complex of intergenic interactions and that this polyfunctional chaperone is an important factor for the stability of genome function and regulatory mechanisms contributing to the tumorigenesis control.


The influence of primary health care organizational models on patients' experience of care in different chronic disease situations.
To examine the extent to which experience of care varies across chronic diseases, and to analyze the relationship of primary health care (PHC) organizational models with the experience of care reported by patients in different chronic disease situations. We linked a population survey and a PHC organizational survey conducted in two regions of Quebec. We identified five groups of chronic diseases and contrasted these with a no-chronic-disease group. Accessibility of care is low for all chronic conditions and shows little variation across diseases. The contact and the coordination-integrated models are the most accessible, whereas the single-provider model is the least. Process and outcome indices of care experience are much higher than accessibility for all conditions and vary across diseases, with the highest being for cardiovascular-risk-factors and the lowest for respiratory diseases (for people aged 44 and under). However, as we move from risk factors to more severe chronic conditions, the coordination-integrated and community models are more likely to generate better process of care, highlighting the greater potential of these two models to meet the needs of more severely chronically ill individuals within the Canadian health care system.


[Impact of photochromotherapy on functional potential of neutrophil granules and adaptive status in children with complicated hemangioma].
Adaptive status was assessed in 50 children. Lysosomal-cationic test was carried out in healthy children and 20 patients with complicated hemangioma. Photochromotherapy was followed by enhanced functional potential of neutrophil granules. That was indicated by greater values of lysosomal-cationic test results as well as by higher counts of high-concentration cationic proteins. Elevated non-specific resistance was accounted for by antistressor reactions.


Modulation of the human gut microbiota by dietary fibres occurs at the species level.
Dietary intake of specific non-digestible carbohydrates (including prebiotics) is increasingly seen as a highly effective approach for manipulating the composition and activities of the human gut microbiota to benefit health. Nevertheless, surprisingly little is known about the global response of the microbial community to particular carbohydrates. Recent in vivo dietary studies have demonstrated that the species composition of the human faecal microbiota is influenced by dietary intake. There is now potential to gain insights into the mechanisms involved by using in vitro systems that produce highly controlled conditions of pH and substrate supply. We supplied two alternative non-digestible polysaccharides as energy sources to three different human gut microbial communities in anaerobic, pH-controlled continuous-flow fermentors. Community analysis showed that supply of apple pectin or inulin resulted in the highly specific enrichment of particular bacterial operational taxonomic units (OTUs; based on 16S rRNA gene sequences). Of the eight most abundant Bacteroides OTUs detected, two were promoted specifically by inulin and six by pectin. Among the Firmicutes, Eubacterium eligens in particular was strongly promoted by pectin, while several species were stimulated by inulin. Responses were influenced by pH, which was stepped up, and down, between 5.5, 6.0, 6.4 and 6.9 in parallel vessels within each experiment. In particular, several experiments involving downshifts to pH 5.5 resulted in Faecalibacterium prausnitzii replacing Bacteroides spp. as the dominant sequences observed. Community diversity was greater in the pectin-fed than in the inulin-fed fermentors, presumably reflecting the differing complexity of the two substrates. We have shown that particular non-digestible dietary carbohydrates have enormous potential for modifying the gut microbiota, but these modifications occur at the level of individual strains and species and are not easily predicted a priori. Furthermore, the gut environment, especially pH, plays a key role in determining the outcome of interspecies competition. This makes it crucial to put greater effort into identifying the range of bacteria that may be stimulated by a given prebiotic approach. Both for reasons of efficacy and of safety, the development of prebiotics intended to benefit human health has to take account of the highly individual species profiles that may result.


Absolute temperature imaging using intermolecular multiple quantum MRI.
A review of MRI temperature imaging methods based on intermolecular multiple quantum coherences (iMQCs) is presented. Temperature imaging based on iMQCs can provide absolute temperature maps that circumvent the artefacts that other proton frequency shift techniques suffer from such as distortions to the detected temperature due to susceptibility changes and magnetic field inhomogeneities. Thermometry based on iMQCs is promising in high-fat tissues such as the breast, since it relies on the fat signal as an internal reference. This review covers the theoretical background of iMQCs, and the necessary adaptations for temperature imaging using iMQCs. Data is presented from several papers on iMQC temperature imaging. These studies were done at 7T in both phantoms and in vivo. Results from phantoms of cream (homogeneous mixture of water and fat) are presented as well as in vivo temperature maps in obese mice. Thermometry based on iMQCs offers the potential to provide temperature maps which are free of artefacts due to susceptibility and magnetic field inhomogeneities, and detect temperature on an absolute scale. The data presented in the papers reviewed highlights the promise of iMQC-based temperature imaging in fatty tissues such as the breast. The change in susceptibility of fat with temperature makes standard proton frequency shift methods (even with fat suppression) challenging and iMQC-based imaging offers an alternative approach.


Breast-Specific Gamma Imaging with [99mTc]Tc-Sestamibi: An In Vivo Analysis for Early Identification of Breast Cancer Lesions Expressing Bone Biomarkers.
The main purpose of this pilot investigation was to evaluate the possible relationship among [99mTc]Tc-Sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of molecules involved in bone metabolism, such as estrogen receptor, bone morphogenetic proteins-2, and PTX3. To this end, forty consecutive breast cancer patients who underwent both breast-specific gamma imaging with [99mTc]Tc-Sestamibi and breast bioptic procedure were retrospectively enrolled. From each diagnostic paraffin block collected in the study, histological diagnosis, immunohistochemical investigations, and energy dispersive X-ray microanalysis were performed. Our data highlight the possible use of breast-specific gamma imaging with [99mTc]Tc-Sestamibi for the early detection of breast cancer lesions expressing bone biomarkers in the presence of breast osteoblast-like cells. Specifically, we show a linear association among sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of estrogen receptor, bone morphogenetics proteins-2, and PTX3. Notably, we also observed an increase of [99mTc]Tc-Sestamibi in breast cancer lesions with magnesium-substituted hydroxyapatite. In conclusion, in this pilot study we evaluated data from the nuclear medicine unit and anatomic pathology department on breast cancer osteotropism, identifying a new possible interpretation of Breast Specific Gamma Imaging with [99mTc]Tc-Sestamibi analysis.


Vitamin D reduces falls and hip fractures in vascular Parkinsonism but not in Parkinson's disease.
Vitamin D supplementation is suggested to reduce the risk of falls in older institutionalized or ambulatory individuals by 20%. The present study was undertaken to address the reduced risk, by vitamin D supplementation, of falls and hip fractures in patients with vascular Parkinsonism (VP) and Parkinson's disease (PD). In the open-label-study, 94 elderly patients with VP and 92 age-matched patients with PD were followed for 2 years. All patients received 1200 IU ergocalciferol daily. The number of falls per person and incidence of hip fractures were compared between the two groups. At baseline, serum 25-hydroxyvitamin D (25-OHD) levels were in the deficient range (<25 nmol/L) in all patients, and vitamin D treatment enhanced serum 25-OHD and 1,25-dihydroxyvitamin D levels in both groups. Improved muscle strength of lower extremities was observed in both groups. There was significant difference between the two groups in the number of falls per subject during the 2 years (1.9 ± 0.5 in the PD group and 0.8 ± 0.4 in the VP group, P < 0.001). Hip fractures occurred in seven of 88 in the PD group and one in 90 of the VP group during the 2-year study period (P = 0.035). It is suggested that vitamin D decreases falls and hip fractures in VP by increasing muscle strength but not in PD.


[Stringent responsibilities of the physician in pregnancy termination. The decision of the 28 May 1993 federal court mandates new guidelines].
In declaring abortion during the first 12 weeks of pregnancy fundamentally illegal but not punishable, the Federal Constitutional Court wants to guarantee the constitutionally necessary protection of the embryo by intensifying counselling and help for the pregnant woman. The physician to whom the woman has turned to have an abortion is thus included in the procedure. He is, however, obliged by professional ethics and law to use all his influence basically for the preservation of human life--including unborn human life. His obligation to counsel and inform is thus extended. In his counselling he is to include the woman's conflicting views about abortion beyond the pure medical aspect. He is to ascertain the reasons why the woman demands abortion. He is to try to find out about the deeper reasons (e.g. the influence of the family and of the social environment) and is thus to point out the dangers of subsequent psychological disorders.


pH Tunable Patterning of Quantum Dots.
Patterning of quantum dots (QDs) is essential for many, especially high-tech, applications. Here, pH tunable assembly of QDs over functional patterns prepared by electrohydrodynamic jet printing of poly(2-vinylpyridine) is presented. The selective adsorption of QDs from water dispersions is mediated by the electrostatic interaction between the ligand composed of 3-mercaptopropionic acid and patterned poly(2-vinylpyridine). The pH of the dispersion provides tunability at two levels. First, the adsorption density of QDs and fluorescence from the patterns can be modulated for pH > ≈4. Second, patterned features show unique type of disintegration resulting in randomly positioned features within areas defined by the printing for pH ≤ ≈4. The first capability is useful for deterministic patterning of QDs, whereas the second one enables hierarchically structured encoding of information by generating stochastic features of QDs within areas defined by the printing. This second capability is exploited for generating addressable security labels based on unclonable features. Through image analysis and feature matching algorithms, it is demonstrated that such patterns are unclonable in nature and provide a suitable platform for anti-counterfeiting applications. Collectively, the presented approach not only enables effective patterning of QDs, but also establishes key guidelines for addressable assembly of colloidal nanomaterials.


The role of newer macrolides in the treatment of community-acquired respiratory tract infection. A review of experimental and clinical data.
The macrolide class of antibiotics is well established and often recommended for use in the treatment of community-acquired respiratory tract infection (RTI). The newer agents clarithromycin and azithromycin are frequently prescribed as first- or second-line therapy, and have been considered as superior to erythromycin in microbiological activity and clinical efficacy. In-vitro data show that clarithromycin and azithromycin have good activity (MIC < or = 0.5 microg/ml) against certain RTI pathogens. However the activity of both compounds is intrinsically low against Haemophilus influenzae whilst several other important RTI pathogens - notably Streptococcus pneumoniae and Streptococcus pyogenes - exhibit a high prevalence of resistance to them. In many countries, the prevalence of resistance to clarithromycin and azithromycin is still rising with cross resistance with erythromycin. Maximum serum concentrations of clarithromycin and azithromycin are lower than the MIC90s for these agents against H. influenzae and S. pneumoniae. Concentrations in tissues have been reported to be much higher than those in serum. However, the high concentrations observed in tissues are largely a reflection of high concentrations inside cells. Concentrations of clarithromycin and azithromycin in extracellular tissue fluids, where Haemophilus and streptococci are located, are in equilibrium with concentrations in the serum, and remain low. It has been suggested that phagocytes deliver azithromycin to infection sites in a targeted fashion, but the evidence in support of this hypothesis is weak. Recent clinical experience with clarithromycin and azithromycin is consistent with preclinical results, and suggests that these agents have limited efficacy against certain respiratory infections. Clarithromycin and azithromycin are the first choice treatment of atypical infections caused by intracellular pathogens. For community-acquired RTIs, where H. influenzae and S. pneumoniae are present, they may no longer be an appropriate choice for first-line therapy. Indeed, in areas where levels of drug resistant S. pneumoniae are high, their use may be questionable as second-line therapy.


Semi-occlusive dressing versus surgery in fingertip injuries: A randomized controlled trial.
No gold-standard treatment has been established for the management of distal digital amputation in Ishikawa zones II and III. The objective of this study was to compare the results of management of fingertip amputation by semi-occlusive dressing versus surgery. The principal hypothesis was that a semi-occlusive dressing results in better recovery of sensory function than a digital flap. We conducted a prospective, randomized, multicenter study of 44 patients: 23 managed conservatively with semi-occlusive dressing, and 21 surgically with digital flap. Mean follow-up was 12 months. Mean healing time was 4.9 weeks in the semi-occlusive dressing group and 3.6 weeks in the surgery group. There was no significant difference between groups for sensory recovery of fine touch (p = 0.198) or 2-point discrimination (p = 0.961). No infections were reported in either group. Hook-nail deformity was more frequent in the semi-occlusive dressing group, particularly in case of amputation in zone III. Semi-occlusive dressing enabled satisfactory healing and sensitivity recovery without increasing the risk of infection. However, in zone III amputation, we advocate surgical treatment with a digital flap, due to poor trophicity and the frequency of hook-nail deformity seen with conservative management. II.


Cellular ions in hypertension, insulin resistance, obesity, and diabetes: a unifying theme.
The clinical linkage of hypertensive cardiovascular disease, left ventricular hypertrophy, and accelerated atherosclerosis with a spectrum of metabolic disturbances including peripheral insulin resistance, hyperinsulinemia, obesity, and frank non-insulin dependent diabetes mellitus, has been increasingly appreciated. However, the underlying biologic basis mediating this clinical association remains unclear. Nuclear magnetic resonance techniques have been used to measure various intracellular ion species in human erythrocytes and have found that common, shared intracellular abnormalities of cytosolic free calcium, free magnesium, and pH occur in each of these clinical syndromes. Specifically, essential hypertension is characterized by higher fasting free cytosolic calcium concentrations and reciprocally lower intracellular free magnesium and pH levels compared with those of normotensive control subjects. Furthermore, for all subjects, free calcium and free magnesium levels were closely related both to the left ventricular mass and to the degree of insulin resistance present. Moreover, these same intracellular ionic lesions were found in normotensive obese and/or non-insulin diabetic individuals. Last, evidence has recently been provided that the cardiovascular consequences of increased dietary sugar and salt intake may well be determined by their concurrent influence on cellular ion metabolism. These data led to a hypothesis for a central role for altered cellular ion homeostasis in mediating the clinical linkage of cardiovascular and metabolic disease. According to this ionic hypothesis, essential hypertension, non-insulin dependent diabetes, and their frequently associated features of obesity, left ventricular hypertrophy, and accelerated atherosclerosis all derive from and reflect different clinical manifestations of the same underlying cellular lesion, characterized at least in part by elevated cytosolic free calcium and suppressed free magnesium levels.


Differential virological and immunological outcome of severe acute respiratory syndrome coronavirus infection in susceptible and resistant transgenic mice expressing human angiotensin-converting enzyme 2.
We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8(+) T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.


ENDOCRINE DILEMMA: Managing menopausal symptoms after breast cancer.
Managing the symptoms of menopause after a diagnosis of breast cancer offers some unique clinical challenges. For some women, vasomotor symptoms can be severe and debilitating, and hormone therapy is at least relatively contraindicated. Non-oestrogen therapies for hot flushes include SSRIs, clonidine, gabapentin and perhaps black cohosh extracts. Vulvovaginal atrophy can usually be alleviated by simple moisturizers, although some may need specialized physiotherapy such as vaginal dilators. In a small number, topical oestrogens may be the only treatment that works. The CO2 laser may be a novel, non-oestrogen therapy to alleviate this unpleasant symptom. Bone loss can be accelerated in some patients on AIs or those who had early menopause induced by chemotherapy.


Synchrotron Photoionization Study of Furan and 2-Methylfuran Reactions with Methylidyne Radical (CH) at 298 K.
The reactions of furan and 2-methylfuran with methylidyne CH (X2Π) radical were investigated at 298 K using synchrotron radiation produced at the Advanced Light Source of the Lawrence Berkeley National Laboratory. Reaction products were observed by multiplexed photoionization mass spectrometry and characterized based on their photoionization spectra and kinetic time traces. Primary products observed in furan + CH are 2,4-cyclopentadien-1-one (m/z = 80), 2-penten-4-ynal (m/z = 80), and vinylacetylene (m/z = 52). From 2-methylfuran + CH, 2-4-cyclopentadien-1-carbaldehyde (m/z = 94), 2,3,4-hexatrienal (m/z = 94), 1,3 cyclopentadiene (m/z = 66), 3-penten-1-yne (Z) (m/z = 66), and vinylacetylene (m/z = 52) are the primary products observed. Using potential energy surface scans, thermodynamically favorable reaction pathways are proposed. CH addition to the π-bonds in furan and 2-methylfuran rings was found to be the entrance channel that led to formation of all identified primary products. Both reactions follow patterns of H loss and CHO loss, as well as formation of cyclic and acyclic isomers.


Pattern formation in the limbs of Drosophila: bric à brac is expressed in both a gradient and a wave-like pattern and is required for specification and proper segmentation of the tarsus.
We have identified the gene bric à brac and show that it is required for pattern formation along the proximal-distal axis of the leg and antenna of Drosophila. In bric à brac mutant legs, the bristle pattern of the three central tarsal segments is transformed towards the pattern of the most proximal tarsal segment. In addition, bric à brac mutant legs and antennae have segmentation defects. bric à brac encodes a nuclear protein that shares a highly conserved domain with two transcription factors from Drosophila. bric à brac function is dosage dependent and is required in a graded manner for the specification of tarsal segments. The graded requirement for bric à brac correlates with its graded expression pattern, suggesting that the concentration of BRIC A BRAC protein specifies segment identity in the tarsus.


Acute nicotine interactions with nicotinic and muscarinic antagonists: working and reference memory effects in the 16-arm radial maze.
In the 8-arm radial maze and other tests, acute nicotine administration has been found to improve memory performance significantly, whereas acute administration of the nicotinic antagonist mecamylamine has been found to impair memory performance. However, questions remain concerning the behavioral and pharmacological nature of acute nicotine effects on memory. In the current studies, we examined acute nicotine effects on working and reference memory in a 16-arm radial maze. In the first study, nicotine caused a significant improvement in working memory but not in reference memory. The muscarinic antagonist scopolamine caused significant deficits in working memory but not in reference memory. Nicotine did not significantly attenuate the scopolamine-induced deficit. In the second study, with rats trained to near-perfect performance, a low dose of mecamylamine (1.25 mg/kg) caused a significant working memory impairment in the 16-arm maze. This deficit was significantly attenuated by concurrent acute administration of nicotine. These studies show that acute nicotine, like chronic nicotine, preferentially improves working compared with reference memory in the radial-arm maze. Mecamylamine can impair working memory performance in the 16-arm maze at low doses which are less likely to have effects at N-methyl-D-aspartate receptors. Nicotine can selectively reverse mecamylamine-induced deficits.


Hurdles and delays in access to anti-cancer drugs in Europe.
Demographic changes in the world population will cause a significant increase in the number of new cases of cancer. To handle this challenge, societies will need to adapt how they approach cancer prevention and treatment, with changes to the development and uptake of innovative anticancer drugs playing an important role. However, there are obstacles to implementing innovative drugs in clinical practice. Prior to being incorporated into daily practice, the drug must obtain regulatory and reimbursement approval, succeed in changing the prescription habits of physicians, and ultimately gain the compliance of individual patients. Developing an anticancer drug and bringing it into clinical practice is, therefore, a lengthy and complex process involving multiple partners in several areas. To optimize patient treatment and increase the likelihood of implementing health innovation, it is essential to have an overview of the full process. This review aims to describe the process and discuss the hurdles arising at each step.


A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 × 10(-6)) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 × 10(-7)), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 × 10(-7)) and PLCL1 genes (p = 4.1 × 10(-6)) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p ≤ 10(-4)) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 × 10(-3), 3 × 10(-6)), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.


Deciphering antibody-mediated rejection: new insights into mechanisms and treatment.
To outline recent studies describing the mechanisms of antibody-mediated rejection (AMR) and new clinical protocols aimed at prevention and/or treatment of this difficult clinical entity. The natural history of acute AMR after positive cross-match kidney transplantation involves an acute rise in donor-specific alloantibody (DSA) in the first few weeks after transplantation. Whereas the exact cellular mechanisms responsible for AMR are not known, it seems likely that both pre-existing plasma cells and the conversion of memory B cells to new plasma cells play a role in the increased DSA production. One recent study suggested that combination therapy with plasmapheresis, high-dose IVIG and rituximab was more effective treatment for AMR than high-dose intravenous immunoglobulin (IVIG) alone, but the role of anti-CD20 antibody is still unclear. Two new promising approaches to AMR focus on depletion of plasma cells with the proteasome inhibitor, bortezomib, and the inhibition of terminal complement activation with a humanized, anti-C5 antibody, eculizumab. The pathogenesis of AMR in several different clinical settings is becoming clearer and more effective treatments are being developed. Whether the prevention or successful treatment of AMR will decrease the prevalence of chronic injury and improved long-term graft survival will require longer-term studies.


Primitive reflexes and early motor development.
To investigate the relationship between primitive reflexes and typical early motor development, 156 full-term infants with normal 18-month developmental outcomes were assessed using a modified Primitive Reflex Profile (PRP) and the Alberta Infant Motor Scale (AIMS) at 6 weeks and 3 and 5 months. No significant positive or negative correlations were obtained between the scores of the PRP and the AIMS at any of the ages assessed. Similarly, PRP scores did not differ between infants scoring above and below the 50th percentile on the AIMS. Primitive reflexes were unrelated to motor development. If this finding is maintained among infants at risk for motor disability, observational assessment of spontaneously generated movement, rather than isolated testing of primitive reflexes, might yield more valuable information on the child's overall level of maturation. Intervention for children with identified motor delays or neurological impairments might not need to be focused on either suppression or enhancement of these motor functions.


The intrinsic GTPase activity of the Gtr1 protein from Saccharomyces cerevisiae.
The Gtr1 protein of Saccharomyces cerevisiae is a member of the RagA subfamily of the Ras-like small GTPase superfamily. Gtr1 has been implicated in various cellular processes. Particularly, the Switch regions in the GTPase domain of Gtr1 are essential for TORC1 activation and amino acid signaling. Therefore, knowledge about the biochemical activity of Gtr1 is required to understand its mode of action and regulation. By employing tryptophan fluorescence analysis and radioactive GTPase assays, we demonstrate that Gtr1 can adopt two distinct GDP- and GTP-bound conformations, and that it hydrolyses GTP much slower than Ras proteins. Using cysteine mutagenesis of Arginine-37 and Valine-67, residues at the Switch I and II regions, respectively, we show altered GTPase activity and associated conformational changes as compared to the wild type protein and the cysteine-less mutant. The extremely low intrinsic GTPase activity of Gtr1 implies requirement for interaction with activating proteins to support its physiological function. These findings as well as the altered properties obtained by mutagenesis in the Switch regions provide insights into the function of Gtr1 and its homologues in yeast and mammals.


Subordinate performance appraisal: what nurses really want in their managers.
This project describes a process used to identify the important job behaviors of nursing managers as seen by their staff nurses. A questionnaire developed for this purpose was administered to thirty-nine staff nurses at the Tom Baker Cancer Centre in Calgary, Alberta. The questionnaire included behaviors of managers which were categorized as either contributing to "structure" or "consideration". Staff nurses were found to favor both high structure and high consideration behaviors in a nurse manager. Behaviors found in the questionnaire to be most valued became content items on the subordinate appraisal form developed as a result of this project. The Landy-Farr Model of Performance Appraisal guided the project development. Health care organizations in their efforts to improve productivity and the quality of work life for nurses should consider alternate methods of performance appraisal for nurse managers.


Gaze position corrective eye movements in normal subjects and in patients with vestibular deficits.
Eye movements in response to high-acceleration head rotations (thrusts) in the horizontal plane from patients with unilateral (UVD) or bilateral vestibular loss (BVD) were recorded. The rapid, gaze-position corrections (GPCs) that appeared when vestibulo-ocular reflex (VOR) slow phases were undercompensatory were characterized. For comparison, eye movements from normal subjects who were asked to generate saccades in the direction opposite head rotation (in the same direction as slow phases) were recorded. This normal-subject model produced responses with spatial and temporal characteristics similar to those from GPCs in patients as follows: When head rotations were generated actively, compared with passively, gaze-position errors and corresponding GPCs were smaller and occurred earlier. During passively generated head thrusts, GPCs still occurred when head rotations were made in total darkness, though their accuracy decreased as the requirement for maintaining gaze on a specific location in space was relaxed. Time of onset of GPCs was not rigidly tied to head kinematics (peak velocity or peak acceleration). Speeds of GPCs, however, were lower than speeds of similar-sized, head-fixed saccades. Finally, during passive and active head thrusts in patients, sustained, high-frequency (20 to 30 Hz) oscillations that appeared as tiny saccades were occasionally observed, one immediately following the other, resembling a compensatory slow-phase response. Taken together, the results suggest that one strategy for overcoming a VOR deficit is to enlist the saccadic system to produce an oculomotor response that is required to compensate for head rotation. This response may come in the form of high-velocity GPCs or smaller-amplitude oscillations.


Preparation and Characteristics of High-Performance, Low-Density Metallo-Ceramics Composite.
By applying the physical vapour deposition method, hollow ceramic microspheres were coated with titanium, and subsequently, they were sintered using the spark plasma sintering technique to create a porous ceramic material that is lightweight and devoid of a matrix. The sintering process was carried out at temperatures ranging from 1050 to 1200 °C, with a holding time of 2 min. The samples were subjected to conventional thermal analyses (differential scanning calorimetry, thermogravimetry, dilatometry), oxidation resistance tests, and thermal diffusivity measurements. Phase analysis of the samples was performed using the XRD and the microstructure of the prepared specimens was examined using electron microscopy. The titanium coating on the microspheres increased the compressive strength and density of the resulting ceramic material as the sintering temperature increased. The morphology of the samples was carefully examined, and phase transitions were also identified during the analysis of the samples.


Egg yolk antibodies for passive immunity.
The avian egg contains all of the necessary nutrients and growth factors required for the developing embryo, including antibodies that are transported from the blood of the hen into the egg yolk to provide immunity to the chick. Since the discovery of egg yolk antibodies, now called immunoglobulin Y (IgY), in the late 1800s, this process has been harnessed to produce antigen-specific yolk antibodies for numerous applications in the medical and research fields, including in areas such as diagnostics and proteomics. However, one of the most valuable and promising areas of IgY research is its use for passive immunization to treat and prevent human and animal diseases. The following review covers the key features and advantages of IgY and the production and purification of IgY from the egg yolk, as well as highlights some of the most promising applications of egg yolk antibodies in human and veterinary medicine.


Anemia in hospitalized patients with pulmonary tuberculosis.
To describe the prevalence of anemia and of its types in hospitalized patients with pulmonary tuberculosis. This was a descriptive, longitudinal study involving pulmonary tuberculosis inpatients at one of two tuberculosis referral hospitals in the city of Rio de Janeiro, Brazil. We evaluated body mass index (BMI), triceps skinfold thickness (TST), arm muscle area (AMA), ESR, mean corpuscular volume, and red blood cell distribution width (RDW), as well as the levels of C-reactive protein, hemoglobin, transferrin, and ferritin. We included 166 patients, 126 (75.9%) of whom were male. The mean age was 39.0 ± 10.7 years. Not all data were available for all patients: 18.7% were HIV positive; 64.7% were alcoholic; the prevalences of anemia of chronic disease and iron deficiency anemia were, respectively, 75.9% and 2.4%; and 68.7% had low body weight (mean BMI = 18.21 kg/m2). On the basis of TST and AMA, 126 (78.7%) of 160 patients and 138 (87.9%) of 157 patients, respectively, were considered malnourished. Anemia was found to be associated with the following: male gender (p = 0.03); low weight (p = 0.0004); low mean corpuscular volume (p = 0.03);high RDW (p = 0; 0003); high ferritin (p = 0.0005); and high ESR (p = 0.004). We also found significant differences between anemic and non-anemic patients in terms of BMI (p = 0.04), DCT (p = 0.003), and ESR (p < 0.001). In this sample, high proportions of pulmonary tuberculosis patients were classified as underweight and malnourished, and there was a high prevalence of anemia of chronic disease. In addition, anemia was associated with high ESR and malnutrition.


Deoxyribonucleic acid synthesis in mammalian nuclei. Incorporation of deoxyribonucleotides and chain-terminating nucleotide analogues.
The properties of a nuclear preparation from rat liver and thymus are described. (1) Nearest-neighbour analysis after incorporation of (32)P-labelled nucleotide residues from dATP, dCTP, dGTP, dTTP and arabinofuranosyl analogues of CTP and ATP shows template-dependent DNA synthesis. (2) Where primer termini are limiting, incorporation of arabinofuranosyl analogues of AMP and CMP residues proceeds to a limit indicating that both of these analogues are DNA chain terminators. (3) No large differences have been found between the priming potentialities or the intrinsic DNA polymerase activities of nuclei from resting or regenerating liver and the relationship of this DNA synthesis in vitro to DNA replication or repair in vivo is briefly discussed.


Angiotensin II plays a role in acute murine experimental autoimmune cystitis.
To investigate whether angiotensin II (AII) receptor antagonism decreases the inflammation and oedema in acute murine experimental autoimmune cystitis (EAC), as interstitial cystitis (IC) might have an autoimmune component and AII has been implicated in autoimmune-mediated vascular congestion, oedema and scarring. Female Balb/cAN mice were divided into three treatment groups (eight in each group) that were autoimmunized with bladder homogenate to induce EAC. One group received an AII type 1 receptor (AT(1)) antagonist, one group an AII type 2 receptor (AT(2)) antagonist, and one group remained untreated (EAC). A control and sham-injected group were also included. After 10 weeks, bladders were removed, sectioned, and stained with haematoxylin and eosin. Grossly, there was no thickening or adhesions in the bladders of the control or sham-injected mice. In five of seven surviving EAC bladders, there were dense adhesions to surrounding peritoneal structures. There were also adhesions and bladder thickening in all of the AT(2) antagonist-treated mice (though in a milder form) but in only two of seven surviving AT(1) antagonist-treated mice. There was no inflammation or oedema in the sham and control groups. All the EAC bladders were inflamed, with submucosal oedema and urothelial detachment from the lamina propria. In the AT(1) antagonist-treated mice there was no inflammation or oedema. By contrast, all AT(2) antagonist-treated mice had moderate inflammation and minor detachment of the urothelium from the lamina propria. AT(1) receptor blockade ameliorated the inflammatory infiltration, submucosal oedema, and urothelial detachment associated with EAC in mice. This was achieved to a lesser extent by AT(2) receptor blockade. If some patients with IC have a pathophysiology similar to that of EAC mice, there might be potential benefit from AII receptor blockade.


Bone marrow aspirations in oncological patients: experience from an in-house standard in paediatrics.
Nearly all paediatric patients require deep sedation when undergoing bone marrow aspiration (BMA). We analyzed the data from our protocols documented in a standardised procedure for bone marrow puncture over a period of 2 years. Our standard included the documentation of personal data as well as vital parameters. In addition, we documented all medications administered, potential complications and required intervention measures, as necessary. A total of 107 protocols were available for the evaluation. Our standard covered the usage of midazolam and S‑ketamine and resulted in complications in just 9 patients, which could be remedied using simple measures. For both active substances, the dosage necessary to reach sufficient deep analgosedation was significantly higher for patients under 24 months of age. Our standard for BMA provides a practical and feasible procedure. In addition to good examination conditions, our standard also helps ensure the safety of our patients.


Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease).
The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were produced from one normal and one affected animal, and cDNA clones homologous to human HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at position +39 of the putative coding region results in a frame shift and a stop codon at base +191. This disease-related deletion was consistently detected by sequencing of cloned polymerase chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and two additional affected animals. The defect was further demonstrated using single-strand conformational polymorphism analysis of the polymerase chain reaction products. In addition, alternative splicing of both normal and affected messenger RNAs was demonstrated. These results should facilitate the use of this animal model to assess gene therapy.


Prevalence of hepatitis B and C in pregnant women who are infected with human immunodeficiency virus.
The purpose of this study was to evaluate the prevalence of hepatitis B and hepatitis C virus co-infection among pregnant women who are infected by human immunodeficiency virus and who attend an obstetric complications prenatal clinic. A de-identified research obstetric human immunodeficiency virus database was reviewed regarding patient demographic characteristics, risk factors for infection, history of sexually transmitted diseases, and initial CD4 count. Four hundred fifty-five women who are infected with human immunodeficiency virus with 572 pregnancies were delivered over 11 years. The overall prevalence of human immunodeficiency virus and hepatitis B or C virus co-infection in our population was 6.3%. More specifically, 1.5% was co-infected with hepatitis B virus, and 4.9% was co-infected with hepatitis C virus. Patients with hepatitis virus were more likely to use intravenous drugs (52% vs 18%; P < .01) and alcohol (38% vs 5%; P < .01). Co-infected patients were older (28 vs 25.6 years; P=.04), but there were no racial differences. Median baseline CD4 counts in hepatitis B virus co-infected patients were significantly lower (310 cells/mm3) than those in either hepatitis C virus co-infected patients (453 cells/mm3) or patients who were not co-infected with human immunodeficiency virus (414 cells/mm3). One of 16 pregnant women who were infected with human immunodeficiency virus was co-infected with hepatitis B or hepatitis C virus. Hepatitis B co-infections appear to be associated with more compromised immune status in our cohort.


Free-radical chemistry of sulfite.
The free-radical chemistry of sulfite oxidation is reviewed. Chemical transformations of organic and biological molecules induced by sulfite oxidation are summarized. The kinetics of the free-radical oxidations of sulfite are discussed, as are the kinetics of the reactions of the sulfite-derived radicals SO3 and the peroxy derivative SO5 with organic compounds.


Systemic endotoxin activity correlates with clot formation: an observational study in patients with early systemic inflammation and sepsis.
Inflammation and coagulation are closely linked, and both can be triggered by endotoxin. Thrombelastometry and impedance aggregometry are of diagnostic and predictive value in critically ill patients. In this observational study we investigated the correlation of endotoxin activity with thrombelasometric and aggregometric variables in patients with systemic inflammation. Based on a daily screening on a tertiary academic surgical ICU, patients, as soon as they fulfilled two or more criteria for systemic inflammatory response syndrome (SIRS), were included. In whole blood we performed endotoxin activity (EA) assay, thrombelastometry (ROTEM®) and impendance aggregometry (Multiplate®). In total, 49 patients were included with a broad spread of EA levels of (median (minimum to maximum)) 0.27 (0.01 to 0.72), allowing expedient correlative analysis. Clot formation time (CFT) (263 s (60 to 1,438 s)) and clotting time (CT) (1,008 s (53 to 1,481 s)) showed a significant negative correlation with EA level (r = -0.38 (P < 0.005) and r = -0.29 (P < 0.05)). Positive correlations were found for alpha-angle (50° (17 to 78°), r = 0.40 (P < 0.005)) and maximum clot firmness (MCF) (55 mm (5/76), r = 0.27 (P < 0.05)). No significant correlations were found between Lysis Index at 60 minutes (LI60) and EA levels. There was no correlation between EA level and aggregometric values, or classical coagulation parameters. In patients with systemic inflammation, increasing endotoxin concentrations correlate with increased clot formation.


Internalising health-economic impacts of air pollution into climate policy: a global modelling study.
Climate change and air pollution are two major societal problems. Their complex interplay calls for an advanced evaluation framework that can support decision making. Previous assessments have looked at the co-benefits of climate policies for air pollution, but few have optimised air pollution benefits. In our study, we lay out a modelling framework that internalises air pollution's economic impacts on human mortality, while considering climate constraints and aerosol feedback. We developed a modelling framework based on an integrated assessment model (World Induced Technical Change Hybrid [WITCH]) designed to assess optimal climate change mitigation policies. We included structural and end-of-pipe measures in a detailed process integrated assessment model, that is hard-linked to air pollution and climate models. We analysed a large set of baseline scenarios, including five shared socioeconomic pathways (SSPs). SSP scenarios were also tested with three different levels of value per statistical life, and were combined with the Paris Agreement temperature targets (TTs), focusing on the 2°C and 1·5°C TTs by the end of the century. We found that, in the baseline scenarios, where no policies are applied, the number of annual premature deaths grew before declining slightly to 4·45 (range 3·86-6·11) million annual premature deaths by 2050. Reaching the Paris Agreement TT decreases mortality by approximately 0·47 million premature deaths by 2050 (up to 1·28 million premature deaths in SSP3 -1·5°C) with respect to the baseline. We showed that welfare-maximising policies accounting for air pollution benefits reduces premature mortality by 1·62 million deaths annually. This is three times greater than the co-benefits of climate policies. China is the region where most of the avoided mortality is possible, whereas the reforming economies (ie, non-EU eastern European countries, including Russia) region has the greatest welfare benefits. We find that global and regional welfare increases when air pollution impacts are internalised, with no negative repercussions on global inequality. Air pollution control strategies are found to be an important complement to structural emission reductions. Accounting for air pollution impacts reduces climate mitigation costs and inequality and increases global and regional welfare. Results are robust to a broad set of scenarios and assumptions, including debated normative choices on how to value improved health. EU Commission projects: INNOPATHS, NAVIGATE, ENGAGE, and COMMIT.


On the socio-economic determinants of antenatal care utilization in Azerbaijan: evidence and policy implications for reforms.
Azerbaijan is a country with one of the highest child mortality rates in the regions of Eastern Europe and the former Soviet Union. Drawing on the nationally representative Demographic and Health Survey, this study examines the utilization of antenatal care in Azerbaijan to identify the socio-economic determinants of the usage, and its frequency, timing and quality. Consequently, binomial logit, two ordered logit and negative binomial regression models are specified to estimate the effect of various socio-economic characteristics on the likelihood of utilization. Place of living is an important determinant of antenatal healthcare utilization in Azerbaijan. It is important in determining the likelihood of utilization, its timing and quality of care received, whereas it is not significant in the model predicting the frequency of antenatal utilization. Women's education is also significant in three models out of four. Education is important in explaining the frequency and timing of utilization as well as the quality of services received, but it is not significant in predicting the likelihood of utilization. Wealth gradient is another important determinant of antenatal care utilization in Azerbaijan inasmuch as it is significant in explaining the likelihood of prenatal care utilization and its frequency. In addition, two variables, birth order and desirability of the last child or current pregnancy, are significant only in explaining the likelihood of utilization. Therefore, we confirm the findings of previous studies, which reported that the utilization of prenatal health care is a multistage process in which decisions are sequential. Although the same set of factors may affect decision-making at all stages, the effect of these factors is different at different stages. Implications for reforms in the healthcare sector to improve antenatal care utilization in Azerbaijan are provided and discussed.


Trends in Cannabis and Cigarette Use Among Parents With Children at Home: 2002 to 2015.
In this study, we investigated trends in cannabis use among parents with children at home in the United States and estimated changes in prevalence of any cannabis use and daily cannabis use among parents who identified as cigarette smokers and nonsmokers with children in the home from 2002 to 2015. The National Survey on Drug Use and Health is an annual, nationally representative, cross-sectional study conducted in the United States. Using logistic regression models, associations between cigarette smoking and any past-month and daily past-month cannabis use among parents with children in the home from 2002 to 2015 were estimated. Moderation of these associations by demographics and trends over time was examined. Past-month cannabis use among parents with children in the home increased from 4.9% in 2002 to 6.8% in 2015, whereas cigarette smoking declined from 27.6% to 20.2%. Cannabis use increased from 11.0% in 2002 to 17.4% in 2015 among cigarette-smoking parents and from 2.4% to 4.0% among non-cigarette-smoking parents (P value for trends <.0001). Cannabis use was nearly 4 times more common among cigarette smokers versus nonsmokers (17.4% vs 4.0%; adjusted odds ratio = 3.88 [3.16-4.75]), as was daily cannabis use (4.6% vs 0.8%; adjusted odds ratio = 3.70 [2.46-5.55]). The overall percentage of parents who used either cigarettes and/or cannabis decreased from 29.7% in 2002 to 23.5% in 2015. Efforts to decrease secondhand smoke exposure via cigarette smoking cessation may be complicated by increases in cannabis use. Educating parents about secondhand cannabis smoke exposure should be integrated into public education programs on secondhand tobacco smoke exposure.


Alleviation of hippocampal necroptosis and neuroinflammation by NecroX-7 treatment after acute seizures.
Temporal lobe epilepsy (TLE) is one of the most common neurological disorders, but still one-third of patients cannot be properly treated by current medication. Thus, we investigated the therapeutic effects of a novel small molecule, NecroX-7, in TLE using both a low [Mg2+]o-induced epileptiform activity model and a mouse model of pilocarpine-induced status epilepticus (SE). NecroX-7 post-treatment enhanced the viability of primary hippocampal neurons exposed to low [Mg2+]o compared to controls in an MTT assay. Application of NecroX-7 after pilocarpine-induced SE also reduced the number of degenerating neurons labelled with Fluoro-Jade B. Immunocytochemistry and immunohistochemistry showed that NecroX-7 post-treatment significantly alleviated ionized calcium-binding adaptor molecule 1 (Iba1) intensity and immunoreactive area, while the attenuation of reactive astrocytosis by glial fibrillary acidic protein (GFAP) staining was observed in cultured hippocampal neurons. However, NecroX-7-mediated morphologic changes of astrocytes were seen in both in vitro and in vivo models of TLE. Finally, western blot analysis demonstrated that NecroX-7 post-treatment after acute seizures could decrease the expression of mixed lineage kinase domain-like pseudokinase (MLKL) and phosphorylated MLKL (p-MLKL), markers for necroptosis. Taken all together, NecroX-7 has potential as a novel medication for TLE with its neuroprotective, anti-inflammatory, and anti-necroptotic effects.


Rational design of lanthanide nano periodic mesoporous organosilicas (Ln-nano-PMOs) for near-infrared emission.
We present three Periodic Mesoporous Organosilica (PMO) materials: a PMO material functionalized with pyridine dicarboxamide (DPA-PMO) and two amine functionalized PMO materials (Am-PMO and Am-ePMO). The pyridine dicarboxamide ligands in the DPA-PMO material provide the tethering sites for Ln3+-coordination. A Schiff base reaction was carried out on the amine functionalized PMOs to introduce similar lanthanide coordination sites. The Nd and Yb modified nano-PMOs are evaluated as near-infrared (NIR) emitting luminescent materials. The DPA-PMO and Am-ePMO materials can act as good platforms for NIR luminescence. A significant enhancement in the decay time can be observed upon grafting an Yb(hfa)3 complex to the PMO materials instead of YbCl3. All of the DPA-PMO@Ln(hfa)3 and Am-ePMO@Ln(hfa)3 materials show characteristic NIR emission performance both in the solid state and in aqueous suspension.


Effect of nutritional intervention on nutritional status among children with disorders of amino acid and nitrogen metabolism (AANMDs): A scoping review.
Disorders of amino acid and nitrogen metabolism (AANMDs) occur due to an enzyme deficiency in a normal biochemical pathway. Nutritional intervention is recognized as the mainstay of treatment for children diagnosed with AANMD. Hence, this scoping review aimed to identify the nutritional interventions available in managing AANMD disorders and their effects on nutritional status. A systematic search using PRISMA Extension for Scoping Reviews (PRISMA-ScR) method was conducted across 4 databases: PubMed, ScienceDirect (Elsevier), EBSCOhost and Cochrane Central Register of Controlled Trials (CENTRAL). Inclusion criteria for the study to be selected are: subjects aged less than 18-year-old, article published in English, utilized an experimental design and published within the past 20 years. A total of 22 articles were included in this review. The majority of the subjects are boys (55.6%) and employed a randomized controlled trial (RCT) study design (45.4%). Nutritional interventions were categorized into 4 categories which are: "protein substitute" (n = 5), "protein substitute with modified composition" (n = 6), "nutrient supplementation (n=8)", and "distribution and dosage of protein substitute (n = 3)". The most frequently assessed outcomes were biochemical parameters that gauge the effectiveness of metabolic control (68.2%). Overall, "protein substitute enriched with inhibitive amino acids", "long-chain polyunsaturated fatty acids supplementation", and "evenly distributed protein substitute" demonstrated beneficial effects towards the nutritional status, especially in terms of biochemical parameters. In summary, nutritional intervention plays a significant role in improving the nutritional status of AANMD patients. Further investigations of nutritional intervention among AANMD children using a meta-analysis approach are necessary for better comprehension of their impact in management of AANMD disorders.


Dosimetry based on EPR spectral analysis of fingernail clippings.
Exposure of fingernails and toenails to ionizing radiation creates radicals that are stable over a relatively long period (days to weeks) and characterized by an isotropic EPR signal at g = 2.003 (so-called radiation-induced signal, RIS). This signal in readily obtained fingernail parings has the potential to be used in screening a population for exposure to radiation and determining individual dose to guide medical treatment. However, the mechanical harvesting of fingernail parings also creates radicals, and their EPR signals (so-called mechanically-induced signals, MIS) overlap the g approximately 2.0 region, interfering with efforts to quantify the RIS and, therefore, the radiation dose. Careful analysis of the time evolution and power-dependence of the EPR spectra of freshly cut fingernail parings has now resolved the MIS into three major components, including one that is described for the first time. It dominates the MIS soon after cutting, but decays within the first hour and consists of a unique doublet that can be resolved from the RIS. The MIS obtained within the first few minutes after cutting is consistent among fingernail samples and provides an opportunity to achieve the two important dosimetry objectives. First, perturbation of the initial MIS by the presence of RIS in fingernails that have received a threshold dose of radiation leads to spectral signatures that can be used for rapid screening. Second, decomposition of the EPR spectra from irradiated fingernails into MIS and RIS components can be used to isolate and thus quantify the RIS for determining individual exposure dose.


Trimolecular Fluorescence Complementation (TriFC) Assay for Visualization of RNA-Protein Interaction in Plants.
RNA-protein interactions play important roles in various eukaryotic biological processes. Molecular imaging of subcellular localization of RNA-protein complexes in plants is critical for understanding these interactions. However, methods to image RNA-protein interactions in living plants have not yet been developed until now. Recently, we have developed a trimolecular fluorescence complementation (TriFC) system for in vivo visualization of RNA-protein interaction by transient expression in tobacco leaves. In this method, we combined conventional bimolecular fluorescence complementation (BiFC) system with the MS2 system (phage MS2 coat protein [MCP] and its binding RNA sequence [MS2 sequence]) to tag lncRNA. Target RNA is tagged with 6xMS2, and MCP and RNA-binding protein are fused with YFP fragments. DNA constructs encoding such fusion RNA and proteins are infiltrated into tobacco leaves with Agrobacterium suspensions. RNA-protein interaction in vivo is observed by confocal microscopy.


The role of pyrophosphate/phosphate homeostasis in terminal differentiation and apoptosis of growth plate chondrocytes.
Extracellular inorganic phosphate (P(i)) concentrations are the highest in the growth plate just before the onset of mineralization. The study reported here demonstrates that P(i) not only is required for hydroxyapatite mineral formation but also modulates terminal differentiation and apoptosis of growth plate chondrocytes. Extracellular P(i) stimulated terminal differentiation marker gene expression, including the progressive ankylosis gene (ank), alkaline phosphatase (APase), matrix metalloproteinase-13 (MMP-13), osteocalcin, and runx2, mineralization, and apoptosis of growth plate chondrocytes. The stimulatory effect of extracellular P(i) on terminal differentiation and apoptosis events of growth plate chondrocytes was dependent on the concentration, the expression levels of type III Na(+)/P(i) cotransporters, and ultimately P(i) uptake. A high extracellular P(i) concentration was required for the stimulation of apoptosis, whereas lower P(i) concentrations were required for the most effective stimulation of terminal differentiation events, including terminal differentiation marker gene expression and mineralization. Suppression of Pit-1 was sufficient to inhibit the stimulatory effects of extracellular P(i) on terminal differentiation events. On the other hand, increasing the local extracellular P(i) concentration by overexpressing ANK, a protein transporting intracellular PP(i) to the extracellular milieu where it is hydrolyzed to P(i) in the presence of APase, resulted in marked increases of hypertrophic and early terminal differentiation marker mRNA levels, including APase, runx2 and type X collagen, and slight increase of MMP-13 mRNA levels, but decreased osteocalcin mRNA level, a late terminal differentiation markers. In the presence of levamisole, a specific APase inhibitor to prevent hydrolysis of extracellular PP(i) to P(i), ANK overexpression of growth plate chondrocytes resulted in decreased mRNA levels of hypertrophic and terminal differentiation markers but increased MMP-13 mRNA levels. In conclusion, with extracellular PP(i) inhibiting and extracellular P(i) stimulating hypertrophic and terminal differentiation events, a precise regulation of PP(i)/P(i) homeostasis is required for the spatial and temporal control of terminal differentiation events of growth plate chondrocytes.


[Solitary hearing and equilibrium damage after vaccinations].
Solitary impairments of hearing and equilibrium after vaccinations are rarely seen. They are usually connected with damage to the central nervous system, thus being combined with further neurological symptoms. In German and English literature 9 cases of isolated statoacoustic nerve lesions due to vaccinations could be found. They are summarized and their similarities and differences are discussed. Information relevant for the evaluation of possible causal relations between vaccinations and solitary 8th cranial nerve disorders is emphasized. Questions concerning the incidence, etiology and differential diagnosis of functional cochleovestibular impairments are highlighted.


Hemolytic-uremic syndrome during recombinant alpha-interferon treatment for hairy cell leukemia.
We report a case of hemolytic uremic syndrome in a patient suffering from hairy cell leukemia during recombinant alpha-interferon treatment. We believe that this is the first report of the occurrence of this peculiar kind of acute renal failure following alpha-interferon therapy. This association may suggest possible speculations regarding side effects of interferon treatment and pathogenesis of hemolytic uremic syndrome.


Cytokine-induced translocation of GRP78 to the plasma membrane triggers a pro-apoptotic feedback loop in pancreatic beta cells.
The 78-kDa glucose-regulated protein (GRP78) is an ubiquitously expressed endoplasmic reticulum chaperone, with a central role in maintaining protein homeostasis. Recently, an alternative role for GRP78 under stress conditions has been proposed, with stress-induced extracellular secretion and translocation of GRP78 to the cell surface where it acts as a multifunctional signaling receptor. Here we demonstrate translocation of GRP78 to the surface of human EndoC-βH1 cells and primary human islets upon cytokine exposure, in analogy to observations in rodent INS-1E and MIN6 beta cell lines. We show that GRP78 is shuttled via the anterograde secretory pathway, through the Golgi complex and secretory granules, and identify the DNAJ homolog subfamily C member 3 (DNAJC3) as a GRP78-interacting protein that facilitates its membrane translocation. Evaluation of downstream signaling pathways, using N- and C-terminal anti-GRP78 blocking antibodies, demonstrates that both GRP78 signaling domains initiate pro-apoptotic signaling cascades in beta cells. Extracellular GRP78 itself is identified as a ligand for cell surface GRP78 (sGRP78), increasing caspase 3/7 activity and cell death upon binding, which is accompanied by enhanced Chop and Bax mRNA expression. These results suggest that inflammatory cytokines induce a self-destructive pro-apoptotic feedback loop through the secretion and membrane translocation of GRP78. This proapoptotic function distinguishes the role of sGRP78 in beta cells from its reported anti-apoptotic and proliferative role in cancer cells, opening the road for the use of compounds that block sGRP78 as potential beta cell-preserving therapies in type 1 diabetes.


A Fast and Efficient Ultrasound-Assisted Extraction of Tocopherols in Cow Milk Followed by HPLC Determination.
A fast HPLC method with fluorescence detector (FD) was developed for the determination of three tocopherols (TOCs) in milk samples from Modicana cattle breed. The ultrasound-assisted procedure was optimized for the extraction of TOCs prior to HPLC/FD analysis, reducing sample preparation time and allowing a fast quantification of α-tocopherol, δ-tocopherol and γ tocopherol. The optimized ultrasonic extraction combines an efficient and simple saponification at room temperature and a rapid HPLC quantification of TOCs in milk. The precision of the full analytical procedure was satisfactory and the recoveries at three spiked levels were between 95.3% and 87.8%. The linear correlations were evaluated (R2 > 0.99) and the relative standard deviation (RSD) values for intra-day and inter-day tests at three spiked levels were below 1% for the retention time and below 5.20% for the area at low level spiking. The proposed procedure, reducing the experimental complexity, allowed accurate extraction and detection of three TOCs in milk samples from Modicana cattle breed.


Ecologic studies of mosquitoes and birds as hosts of Ockelbo virus in Sweden and isolation of Inkoo and Batai viruses from mosquitoes.
Field studies were conducted in central Sweden from 1983 through 1985 to obtain information on the etiologic agent of Ockelbo disease, described in Sweden in the 1960s and probably identical to Pogosta disease in Finland and to Karelian fever in the western USSR. Mosquitoes (63,644) collected during this 3 year period yielded 21 virus strains. Ockelbo virus isolations were from Culiseta morsitans (5 strains), Culex pipiens and/or Cx. torrentium (6 strains), and Aedes cinereus (3 strains). Inkoo (6 strains) and Batai (1 strain) viruses were recovered from Ae. communis. Blood samples collected March-May from migrating birds on the southeast and est coast of Sweden and in July and August from resident birds in east-central Sweden were tested for neutralizing antibody to Ockelbo virus. Antibody was not detected in 328 birds sampled during spring migrations. Two of 58 (3.4%) birds bled in July and 8 of 78 birds (10%) bled in August had antibody to Ockelbo virus. Ockelbo virus circulates in a mosquito-bird-mosquito cycle, with Cs. morsitans and Cx. pipiens and/or Cx. torrentium as enzootic vectors. Antibody was detected in passerine birds. Other classes of birds or other vertebrates were not sampled. Aedes cinereus may serve primarily to transmit virus to people. The role of other mosquito species as vectors for people is unknown.


Decreased white matter lesion volume and improved cognitive function after liver transplantation.
Focal T2-weighted white matter lesions (WML) on brain magnetic resonance imaging (MRI), mimicking those seen in cerebrovascular small-vessel disease described in patients with persistent hepatic encephalopathy, decreased in volume with the improvement of hepatic encephalopathy. This outcome has been interpreted as a decrease in the edema that it is proposed to be involved in the pathogenesis of hepatic encephalopathy. We designed a study to further investigate potential changes in focal WML in the brains of patients with cirrhosis following liver transplantation and to study the relationship between these changes and overall cognitive function. We used MRI to measure the volume of supratentorial focal WML and a neuropsychological examination to assess cognitive function before and after liver transplantation in 27 patients with cirrhosis without signs of overt hepatic encephalopathy. Baseline MRI identified focal T2-weighted lesions in 19 patients (70.3%). The presence of WML was associated with older age but not with vascular risk factors, severity of liver function, or psychometric tests. A significant reduction in lesion volume was observed after liver transplantation (from a median of 1.306 cm(3) to 0.671 cm(3), P = 0.001). This decrease correlated with an improvement in an index of global cognitive function (r = -0.663; P < 0.001). This evolution indicates that lesion volume is partially related to a reversible type of tissue damage, which is compatible with brain edema. Focal WML probably induced by age-related microvascular injury can decrease their volume with liver transplantation. The associated improvement of cognitive function supports a relationship between brain edema and minimal hepatic encephalopathy.


Examination of the Influence of Cognitive Behavior Therapy Components, Consumer Satisfaction and Engagement in Mothers Referred for Drug Abuse and Child Neglect on Treatment Outcomes.
Psychological interventions for child maltreatment have predominately been limited to family-supported, multi-component behavioral therapies. Although these comprehensive programs have resulted in positive outcomes, they are relatively costly and there is limited information available as to how the components of these programs influence treatment outcomes. In this study, the CBT components of an evidence-based treatment for child neglect and drug abuse (Family Behavior Therapy) were examined in regards to consumer preferences, consumer engagement and treatment outcomes. Thirty-five mothers identified for child neglect and drug abuse were administered various CBT components successively and cumulatively based on their preferences. Repeated measure ANOVAs indicated that participants chose to receive components that were specific to managing antecedents to drug abuse and child neglect most frequently, followed by parenting skills training, communication skills training, and job/financial skills training. No differences were found in treatment providers' ratings of the participants' engagement across intervention components throughout treatment. Participants rated the intervention components as similarly helpful. Partial correlations revealed that participants' ratings of helpfulness and provider ratings of participants' engagement were not associated with improved drug use outcomes at 6- and 10-months post baseline. Participants' ratings of helpfulness were associated with child maltreatment outcomes at 10-month post baseline, and provider ratings of participants' engagement were associated with child maltreatment outcomes at both 6- and 10-month post baseline. Participants identified for neglect not related to drug exposure in utero improved at a higher percentage than did participants identified for in utero drug exposure, and receiving behavioral intervention components more frequently led to greater percentages of participants improving in both drug use and child maltreatment outcomes.


Docosahexaenoic acid promotes oligodendrocyte differentiation via PPAR-γ signalling and prevents tumor necrosis factor-α-dependent maturational arrest.
Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid known to be neuroprotective in several models of human diseases, including multiple sclerosis. The protective effects of DHA are largely attributed to its ability to interfere with the activity of transcription factors controlling immune and inflammatory responses, including the agonist-dependent transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ). In this study, we used primary oligodendrocyte progenitor (OP) cultures from neonatal rat brain to investigate whether DHA could influence OP maturation and directly promote myelination, as previously reported for selective PPAR-γ agonists. We show that, similarly to the selective PPAR-γ agonist pioglitazone (PGZ), DHA promotes OP maturation and counteracts the maturational arrest induced by TNF-α, used to mimic inflammatory conditions. The PPAR-γ antagonist GW9662 prevented both DHA-induced OP maturation and PPAR-γ nuclear translocation, supporting the hypothesis that DHA acts through the activation of PPAR-γ. In addition, both PGZ and DHA induced the phosphorylation of extracellular signal-regulated-kinase 1-2 (ERK1/2), in a PPAR-γ-dependent manner. ERK1/2 activity is known to regulate the transition from OPs to immature oligodendrocytes and the presence of specific inhibitors of ERK1/2 phosphorylation (U0126 or PD98059) prevented the differentiating effects of both DHA and PGZ. These results indicate that DHA might influence the process of OP maturation through its PPAR-γ agonistic activity and provide novel molecular mechanisms for the action of this dietary fatty acid, further supporting the nutritional intervention in demyelinating diseases such as multiple sclerosis.


Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology.
Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex vivo models that faithfully recapitulate in vivo tumour biology are urgently needed. These may especially benefit the management of pancreatic ductal adenocarcinoma (PDAC), where therapy failure has been ascribed to its high cancer stem cell (CSC) content and high density of stromal cells and extracellular matrix (ECM). To date, these features are only partially reproduced ex vivo using organoid and sphere cultures. We have now developed a more comprehensive and highly tuneable ex vivo model of PDAC based on the 3D co-assembly of peptide amphiphiles (PAs) with custom ECM components (PA-ECM). These cultures maintain patient-specific transcriptional profiles and exhibit CSC functionality, including strong in vivo tumourigenicity. User-defined modification of the system enables control over niche-dependent phenotypes such as epithelial-to-mesenchymal transition and matrix deposition. Indeed, proteomic analysis of these cultures reveals improved matrisome recapitulation compared to organoids. Most importantly, patient-specific in vivo drug responses are better reproduced in self-assembled cultures than in other models. These findings support the use of tuneable self-assembling platforms in cancer research and pave the way for future precision medicine approaches.


Direct continuous-wave measurement of n(2) in various types of telecommunication fiber at 1.55 microm.
A method for measuring the nonlinear refractive index of optical fibers with an error of less than 5% is demonstrated. The technique is based on measuring the nonlinear phase shift experienced by a dual-frequency beat signal, permitting a simple, highly sensitive, accurate, repeatable, and easily automated measurement procedure and sampling. Measurements of the nonlinear coefficient in standard telecommunication, dispersion-shifted, and a number of dispersion-compensated fibers are presented.


The challenging genetics of epilepsy.
The purpose of this chapter is to highlight the clinical, epidemiological, genetic and animal studies that have led us to the conclusion that many forms of epilepsy are clearly inherited on a genetic basis. The genetics of epilepsy are complex. Many forms of epilepsy do not follow simple Mendelian patterns of inheritance and still elude clear genetic explanation. The challenge in these areas is evident, and at the end of this chapter some suggestions based on recent advances in molecular neurobiology are given that might explain some of these complex patterns of inheritance. Hopefully, the synthesis of clinical, epidemiological, genetic and biological studies will provide, in the next decade, a clearer understanding of this complex genetic picture. The challenge raised in the first workshop held in Minnesota in 1980 is being realized in this conference with clear evidence that juvenile myoclonic epilepsy and benign neonatal convulsions are linked to specific chromosomes in man. The challenge for the next decade and the strategies to meet that challenge are what will be outlined in this conference.


High levels of hybridization between molecular forms of Anopheles gambiae from Guinea Bissau.
In the malaria vector Anopheles gambiae Giles sensu stricto, two molecular forms denoted M and S are considered units of incipient speciation within this species. Very low hybrid frequencies and significant genetic differentiation have been found in sympatric M- and S-form populations. We studied the molecular form composition and the degree of genetic differentiation at 15 microsatellites in two samples of An. gambiae collected in two consecutive years from Bissau, Guinea Bissau. High frequencies of M/S hybrids (19-24%) were found in this area. Coincidently, very low levels of genetic differentiation were detected between forms when analysis involved microsatellites mapped at chromosome-3 (mean Fst, 0.000-0.002). The single exception was the X-linked AGXH678, for which high differentiation was measured (Fst, 0.158-0.301). This locus maps near the centromere of chromosome X, a low recombination region in which selection is likely to promote divergence between M and S forms. These results strongly suggest that the degree of isolation between M and S forms, considered the units of incipient speciation within An. gambiae, is not homogenous throughout the species distribution range.


Do anticodons of misacylated tRNAs preferentially mismatch codons coding for the misloaded amino acid?
Accurate amino acid insertion during peptide elongation requires tRNAs loaded by cognate amino acids and that anticodons match codons. However, tRNA misloading does not necessarily cause misinsertions: misinsertion is avoided when anticodons mismatch codons coding for misloaded amino acids. Occasional compensation of misacylation by codon-anticodon mismatch necessarily occurs. Putatively, occasional error compensation may be enhanced beyond the random combination of independent errors in tRNA loading and codon-anticodon interactions: tRNA misacylation might alter potentials for codon-anticodon mismatches, perhaps specifically increasing potentials for mismatching those codons coding for the misacylated non-cognate amino acid. This hypothetical phenomenon is called 'error coordination', in distinction from 'error compensation' that assumes independence between misacylation and mismatch. Eventually, the hypothesis should be tested for each combination of amino acid misacylation and codon-anticodon mismatch, by comparing stabilities or frequencies of mismatched codon-anticodon duplexes formed by tRNAs loaded by their cognate amino acid with stabilities formed by that tRNA when misloaded with the amino acid coded by the mismatched codon. Competitive mismatching experiments between misloaded and correctly loaded tRNAs could also be useful, yet more sophisticated experiments. Detecting error coordination implies estimating error compensation, which also promotes protein synthesis accuracy. Hence even in the absence of evidence for error coordination, experiments would yield very useful insights into misacylation and mismatch processes. In case experiments consider post-transcriptional RNA modifications (especially at wobble positions), results on codon-anticodon mismatches would enable significant improvements and sophistications of secondary structure prediction softwares. Positive results would show that protein translation enhances accuracies of products, not of single steps in the production. Ancient translational machineries putatively optimized error coordination, especially before tRNA editing by tRNA synthetases evolved: few primitive, but functionally versatile tRNA species perhaps executed low accuracy translation. Systems artificially designed/selected for low complexity and high efficiency could make use of this property for anticodons with high levels of error compensation and coordination.


Rescue forced-suction thrombectomy using the reperfusion catheter of the Penumbra System for thromboembolism during coil embolization of ruptured cerebral aneurysms.
No definite conclusive management has been established in the treatment of thromboembolism during coil embolization of cerebral aneurysms. To date, intravenous heparin, intra-arterial fibrinolytic agent, and intravenous or intra-arterial glycoprotein IIb-IIIa inhibitors have been the mainstay of treatment. However, in practice, 2 major concerns may arise; first, recanalization is not always possible despite every effort of management; second, rehemorrhagic risk is increased if the event occurred during coiling of ruptured cerebral aneurysms. We introduce a new endovascular mechanical thrombectomy technique to overcome the aforementioned concerns. In 4 refractory cases involving conventional pharmaceutical treatment of thromboembolism during coiling, we practiced rescue suction thrombectomy using the reperfusion catheter of the Penumbra System. All 4 of the patients to whom this technique was applied were successfully recanalized; 2 were Thrombolysis In Cerebral Infarction scale of 2b and the other 2 were a scale of 3. Recanalization was confirmed at the follow-up angiography at least 12 hours after the procedure. No complication associated with this technique occurred. Forced-suction thrombectomy is a simple modification of the Penumbra System. Based on our preliminary data, this technique can play a role as an adjuvant management or as a last resort combined with injection of glycoprotein IIb-IIIa inhibitors in thromboembolic events that occur in coil embolization of a ruptured cerebral aneurysm.


The neural basis of executive functioning deficits in adolescents with epilepsy: a resting-state fMRI connectivity study of working memory.
Working memory deficits are common in youth with epilepsy and consistently associated with long-term negative outcomes. Existing research on the neural basis of working memory disruptions in pediatric epilepsy is limited. The question of whether differences in the functional connectivity of neural networks underlie working memory disruptions in pediatric patients with epilepsy remains unanswered. A total of 49 adolescents between the ages of 13-17 years participated in this study. Twenty-nine adolescents had confirmed epilepsy (n = 17 generalized epilepsy, n = 6 localization-related, n = 6 unclassified). The control group included 20 healthy adolescents. A total of 10-min resting state functional magnetic resonance imaging was obtained for all participants. NeuroSynth-derived regions of interest were used as nodes that comprise working memory neural networks. Group differences in resting state functional connectivity were examined between adolescents with epilepsy and controls. Functional connectivity was computed as the temporal correlation of functional magnetic resonance imaging signal fluctuations between any two regions of interest. Compared to controls, adolescents in the epilepsy group demonstrated both hypoconnectivity and hyperconnectivity in cortical areas that map onto fronto-parietal and cingulo-opercular networks, as well as cerebellar regions. Functional connectivity between pairs of regions of interest was also significantly associated with behavioral measures of working memory across epilepsy and control groups. This study demonstrates that the presence of abnormal patterns in resting state neural network connectivity may underlie the working memory disruptions that frequently characterize the neurocognitive profile of youth with epilepsy.


Phylogenetic diversity, polyamine pattern and DNA base composition of members of the order Planctomycetales.
The 16S rDNA sequences of 20 novel isolates of members of the order Planctomycetales were compared to those of the type strains of described planctomycete species and 22 planctomycete isolates for which the 16S rDNA sequences had been previously determined. The novel isolates could be assigned to several phylogenetically broad groups, four of which are defined by the genera Gemmata, Isosphaera, Planctomyces and Pirellula. To evaluate polyamines as a chemotaxonomic marker within this order, the polyamine pool was determined for six planctomycete reference species and for 20 planctomycete isolates. All analysed members of the order Planctomycetales contained significant amounts of polyamines. sym-Homospermidine (HSPD) is present in all strains except Planctomyces limnophilus and related strains, which had high amounts of putrescine (PUT) as the dominant polyamine component. The distribution of PUT, HSPD and spermidine reflects the phylogenetic diversity within the Planctomycetales as closely related representatives of the phylogenetic groups defined by described species and novel isolates exhibit similar polyamine patterns. Determination of the DNA base composition revealed G + C contents of > 60 mol% for members of Gemmata and Isosphaera whereas, except for two isolates, strains which are phylogenetically associated with Planctomyces and Pirellula had G + C contents of 51-57 mol%.


Trends in Store-Level Sales of Sugary Beverages and Water in the U.S., 2006-2015.
Previous research on sugar-sweetened beverage trends has focused on self-reported consumption from surveys. Few studies used objective store sales or explored differences by area-level demographics and store type. The average volume of beverages sold per store per 3-digit zoning improvement plan code from 2006 to 2015 was calculated using national Nielsen Retail Scanner point-of-sale data from 24,240 stores. A multilevel regression model analyzed annual trends, with random intercepts for state and separate models for beverage type (regular soda, no/low-calorie soda, other sugary drinks, 100% fruit juice, bottled water). Differences by store type (convenience, supermarkets, drug stores, mass merchandisers) and area-level demographics (categorized as tertiles) were examined. Data were analyzed in 2019. The model-based estimates indicated that sales of regular soda (-11.8%), no/low-calorie soda (-19.8%), and 100% fruit juice (-31.9%) decreased over time, whereas sales of bottled water (+34.4%) increased and sales of other sugary drinks remained stable (+2.4%). Decreases in sugar-sweetened beverage sales were largely concentrated in supermarkets and larger in areas with high income and education levels and a high percentage of black and Hispanic people. There were also relatively larger increases in bottled water sales in states located in the South and Midwest. The finding that sales of sugar-sweetened beverages decreased over time, whereas sales of bottled water increased is encouraging because sugar-sweetened beverage consumption is linked to obesity and other chronic conditions. This study provides a novel, rigorous assessment of U.S. beverage sales trends and differences by community and store characteristics.


E-health literacy levels of high school students in Turkey: results of a cross-sectional study.
Digital health literacy is defined as the ability to search, find, and understand health information available on electronic resources and to use the information obtained from these resources to address a health problem. This study aimed to identify the digital health literacy levels of high school students and the factors that contribute to its development. This cross-sectional study was conducted with 1250 high school students from 10 high schools. The data were collected using the descriptive characteristics form and e-Health Literacy Scale (eHEALS) for adolescents. The mean age of the students was 15.92 ± 0.95 years and 50.8% of them were girls. The mean score on the eHEALS was 27.52 ± 6.76, which was in the high digital health literacy range (eHEALS ≥ 26). The results indicated the mean digital health literacy scores were high in students who lived in a nuclear family, who understood the importance of good health, who had easy access to the Internet and who had highly educated parents with high income levels. Encouraging the development of digital health literacy through school curricula could offer opportunities for all young people to develop digital health literacy, regardless of socio-economic status or family situation.


Development of surrogate endpoint biomarkers for clinical trials of cancer chemopreventive agents: relationships to fundamental properties of preinvasive (intraepithelial) neoplasia.
The tissue changes offering the greatest immediate potential for development as surrogate endpoint biomarkers (SEBs) to be used in Phase II trials of cancer chemopreventive agents are those derived from the microscopic tissue changes pathologists use to make the diagnosis of preinvasive (intraepithelial) neoplasia. These changes comprise four categories: proliferative index, ploidy, nuclear morphometry (size, shape, texture, and pleomorphism), and nucleolar morphometry (number, size, shape, position, and pleomorphism). Computer-assisted image analysis (CIA) permits dozens of additional morphometric parameters to be developed. Other categories of candidate SEBs are: DNA and chromosomal structural changes associated with genomic instability, activation of oncogenes and inactivation of tumor suppressor genes, structural changes in differentiated molecules, and aberrations of growth factor/receptor structure and function. Self-perpetuating DNA breakage with secondary mutator mutations in genomic stability genes is a major mechanism by which the genomic instability characteristic of neoplasia occurs, and from which stem other basic neoplastic properties, including clonal evolution, along multiple pathways of genetic variation that are stochastically determined, continuously increasing proliferation, rate and extent of phenotypic heterogeneity. SEBs resulting from genomic instability include homogeneously staining regions, double minute chromosomes, micronuclei, dicentrics, gene amplification, loss of heterozygosity, and alterations in chromosome number. Newly developed assays for detecting genomic instability include comparative genomic hybridization using fluorescence in situ hybridization on > 20 micron-thick sections monitored by confocal laser scanning microscopy, assays for microsatellite instability, and restriction landmark genomic scanning. These assays offer promise for detecting the earliest molecular changes of neoplasia in normal-appearing epithelium prior to the onset of the dysplastic phase of intraepithelial neoplasia.


Detailed mapping of the antigenicity of the surface unit glycoprotein of equine infectious anemia virus by using synthetic peptide strategies.
We describe here a detailed analysis of the antigenic determinants of the surface unit glycoprotein (gp90) of equine infectious anemia virus (EIAV), using a comprehensive panel of synthetic peptides in enzyme-linked immunosorbent assays with immune serum from naturally and experimentally infected horses and with a panel of gp90-specific neutralizing and nonneutralizing monoclonal antibodies. The results of these studies identify immunoreactive segments throughout the conserved and variable domains of gp90 but localize immunodominant (100% reactivity) determinants to the amino and carboxyl termini of the glycoprotein molecule. Analysis of peptide reactivities with longitudinal serum samples taken from experimentally infected ponies revealed that antibody responses to conserved B-cell determinants appeared earlier and at higher titers than do antibodies specific for determinants contained in the variable domain of gp90. These observations suggest an evolution of antibody responses in EIAV-infected ponies that may correspond to the establishment of immunological control of virus replication and disease routinely observed in EIAV infections. In addition, the mapping of monoclonal antibody epitopes to peptides of 9 to 12 amino acids demonstrated that all of the neutralizing epitopes are located in the variable domain of gp90. The arrangement of neutralizing epitopes and critical structural considerations suggest that EIAV gp90 contains a principal neutralizing domain similar to the V3 loop of human immunodeficiency virus type 1. These antigenic analyses provide an important foundation for further analyzing the protective immune response generated during persistent EIAV infections and also provide potential peptide substrates for diagnostic assays and for vaccine strategies.