Knowledge and attitudes to prescription charges in New Zealand and England.
Prescription charge regimes vary between countries but there is little research on how much people know about these or support values underlying them. To explore, in New Zealand (NZ) and England, the public's knowledge of, and attitudes to, charges and whether knowledge and attitudes varied by demographic characteristics or by values about entitlement to public goods. A questionnaire was developed and administered to people over 18 recruited in public places in NZ and England. 451 people in NZ and 300 people in England participated. Less than half in each country knew the current prescription charge. In each country 62% of people were unaware of arrangements to protect people from excessive annual charges. Support for free or lower cost medicines for children, people over 65, people on low incomes, people on benefits, and people with chronic health problems was higher in England than in NZ. Support varied by participants' demographic characteristics and, in the case of people on low incomes and people on benefits, by values about universal entitlements. Gaps in knowledge, particularly about mechanisms to protect people from high costs, are concerning and may lead to people paying excessive charges. There was consensus about the elderly, children and the chronically ill being "deserving" of lower prescription charges, but people who did not believe in universal access to public goods appeared to see people on low incomes or benefits as less "deserving". In general, public views resembled those underlying the prescription charge regime in their country.


Dispositional risk factors for smoking-stage transitions: a social influences program as an effect modifier.
A cognitive-developmental model postulates three predominant adolescent dispositions (self-definition, social compliance, and affect regulation) which may impede or facilitate transitions in stages of smoking. The purpose of the present prospective study was to build on the findings supporting this model. One hundred schools were randomly assigned to either receive or not receive a social influences smoking prevention program. A baseline survey, including smoking behavior and dispositional items, was administered in the sixth grade in 1990, interventions were delivered in the sixth and seventh grades, and a survey was administered following the seventh grade intervention. Principal component patterns, based on dispositional items, were very similar for grades 6 and 7, did not vary by gender, and the components (rebelliousness, rejection of adult authority, personal dissatisfaction, and peer approval) were correlated. All smoking-stage transitions were positively related to rebelliousness for boys. The relationship of the dispositional scores with smoking-stage transitions was more complex for girls. Receiving the program modified the effects of the dispositional risk scores, particularly for girls.


Onset of white striping and progression into wooden breast as defined by myopathic changes underlying Pectoralis major growth. Estimation of growth parameters as predictors for stage of myopathy progression.
The broiler industry has incurred significant economic losses due to two muscle myopathies, white striping (WS) and wooden breast (WB), affecting the Pectoralis major (P. major) of commercial broilers. The present study documented macroscopic changes occurring with age/growth in the P. major and P. minor muscles of commercial broilers from day 2 through day 46 (n = 27/day). Distinct myopathic aberrations observed in both breast muscles corresponded to the onset of WB. These distinct morphological changes were used as determinants in developing a ranking system, defining the ontogeny of WB as the following four stages: (1) WS, (2) petechial epimysium haemorrhages, (3) intramuscular haemorrhages and (4) ischaemia. A cumulative logit proportional odds model was used to relate the rank probabilities with the following growth parameters: body weight, P. major and P. minor weight/yield/length/width/depth. The best-fit model included P. major length/width/depth, P. minor width, P. major and P. minor yield as predictors for rank. Increasing P. major depth, P. minor width and P. major yield increased the odds of falling into higher ranks (more severe myopathy). Conversely, increasing P. major length, P. major width and P. minor yield increased the odds of falling into smaller ranks (less severe myopathy). This study describes the macroscopic changes associated with WB ontogeny in the development of a ranking system and the contribution of growth parameters in the determination of rank (WB severity). Results suggest that physical measurements inherent to selection for high-yielding broiler genotypes are contributing to the occurrence and severity of WS and WB.


Dynamical aspects of quantum entanglement for weakly coupled kicked tops.
We investigate how the dynamical production of quantum entanglement for weakly coupled, composite quantum systems is influenced by the chaotic dynamics of the corresponding classical system, using coupled kicked tops. The linear entropy for the subsystem (a kicked top) is employed as a measure of entanglement. A perturbative formula for the entanglement production rate is derived. The formula contains a correlation function that can be evaluated only from the information of uncoupled tops. Using this expression and the assumption that the correlation function decays exponentially which is plausible for chaotic tops, it is shown that the increment in the strength of chaos does not enhance the production rate of entanglement when the coupling is weak enough and the subsystems (kicked tops) are strongly chaotic. The result is confirmed by numerical experiments. The perturbative approach is also applied to a weakly chaotic region, where tori and chaotic sea coexist in the corresponding classical phase space, to reexamine a recent numerical study that suggests an intimate relationship between the linear stability of the corresponding classical trajectory and the entanglement production rate.


Glucocorticoid-induced tumor necrosis factor receptor is a p21Cip1/WAF1 transcriptional target conferring resistance of keratinocytes to UV light-induced apoptosis.
Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a member of the tumor necrosis factor receptor superfamily, is expressed in T lymphocytes, and exerts an anti-apoptotic function in these cells. We reported that GITR is also highly expressed in the skin, specifically in keratinocytes, and that it is under negative transcriptional control of p21(Cip1/WAF1), independently from the cell cycle. Although GITR expression is higher in p21-deficient keratinocytes and skin, it is down-modulated with differentiation and in response to UVB. The combined analysis of keratinocytes with increased GITR expression versus normal keratinocytes and skin of mice with a disruption of the GITR gene indicates that this protein protects keratinocytes from UVB-induced apoptosis both in vitro and in vivo.


Hypermethylation of BRM promoter plays oncogenic roles in development of clear cell renal cell carcinoma.
Although the inactivation of BRM plays oncogenic roles in tumorigenesis, regulation mechanism is rarely studied in clear cell renal cell carcinoma (RCC). Thus, we aimed to investigate the mechanism of BRM inactivation and explore the tumor suppressing roles of BRM in the development of clear cell RCC. We verified that hypermethylation of the BRM promoter was correlated with decreased expression of BRM by multi-omics analysis based on the TCGA database. This result was further confirmed in our own tumor tissues. Moreover, BRM inhibited the ability of proliferation and invasion of RCC cells in vitro. Consistent with this, BRM overexpressing virtually inhibited the xenograft tumor growth of ACHN cells in vivo. Finally we found that BRM promoted cell apoptosis and cellular cycle arrest in G2/M. In conclusion, our study confirms that the hypermethylation of BRM promoters plays oncogenic roles by the transcription inhibition of BRM in RCC, and the tumor suppressor gene BRM inhibits RCC cell vitality in vitro and in vivo.


Inference of Capillary Nonperfusion Progression on Widefield OCT Angiography in Diabetic Retinopathy.
The purpose of this study was to explore the spatial patterns of the nonperfusion areas (NPAs) on widefield optical coherence tomography angiography (OCTA) images in diabetic retinopathy (DR) and to investigate their associations with NPA progression and DR severity. We prospectively enrolled 201 eyes from 158 patients with DR. Widefield images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of 20-mm (1614 pixels) en face images. Nonperfusion squares (NPSs) were defined as 10 × 10-pixel squares without retinal vessels. Eyes with high-dimensional spatial data were mapped onto a two-dimensional space using the uniform manifold approximation and projection algorithm and divided by clustering. The patterns of NPA distribution were statistically compared between clusters. All eyes were mapped onto a two-dimensional space and divided into six clusters based on the similarity of NPA distribution. Eyes in clusters 1 and 2 had minimal and small NPAs, respectively. Eyes in clusters 3 and 4 exhibited NPAs in the temporal and inferotemporal regions, respectively. Eyes in cluster 5 displayed NPAs in both superonasal and inferonasal areas. The unique NPA distributions in each cluster encouraged us to propose eight possible pathways of NPA progression. DR severity was not equal between clusters (P < 0.001), for example, 8 (15.7%) of 51 eyes and 15 (65.2%) of 23 eyes had PDR in clusters 1 and 5, respectively. Dimensionality reduction and subsequent clustering based on the NPA distribution on widefield OCTA enabled the inference of possible NPA progression in DR.


Antimicrobial peptide action on parasites.
Diseases caused by protozoan parasites can pose a severe thread to human health and are behind some serious neglected tropical diseases like malaria and leishmaniasis. Though several different drugs have been developed in order to eradicate these diseases, a successful candidate has not yet been discovered. Among the most active compounds tested, antimicrobial peptides (AMPs) are particularly appealing because of their wide spectrum of action. AMPs have been described to perturb protozoan homeostasis by disrupting the cellular membranes but also by interfering with key processes in the parasite metabolism. In this review we describe the diverse mechanisms of action of AMPs on protozoan targets and how they can be exploited to treat diseases. Moreover, we describe with detail the antimicrobial action of AMPs on two major parasitical infections: leishmaniasis and malaria. All the features reviewed here show that AMPs are promising drugs to target protozoan parasites and that further understanding of the mechanism of action of these compounds will lead to improved drugs that could be worth to test in a clinical phase.


A Comparison of Health Visualization Evaluation Techniques with Older Adults.
Aging-associated changes in visual acuity, cognition, and motor control in addition to attitudinal and affective perceptions of technology impact the design of information systems for older adults. Although design guidelines and cognitive theories on information visualization exist, they are often understudied for use with older adults. In an effort to evaluate interactive health visualizations with older adults, the authors applied and compared a benchmark evaluation, an insight-based evaluation, and a subjective usability questionnaire. They were unable to identify statistically significant differences between visualizations using the benchmark evaluation, but found moderate differences with the perceived usability scale and more granular differences through the insight evaluation.


Alcohol-associated bowel disease: new insights into pathogenesis.
Excessive alcohol drinking can cause pathological changes including carcinogenesis in the digestive tract from mouth to large intestine, but the underlying mechanisms are not fully understood. In this review, we discuss the effects of alcohol on small and large intestinal functions, such as leaky gut, dysbiosis and alterations of intestinal epithelium and gut immune dysfunctions, commonly referred to as alcohol-associated bowel disease (ABD). To date, detailed mechanistic insights into ABD are lacking. Accumulating evidence suggests a pathogenic role of ethanol metabolism in dysfunctions of the intestinal tract. Ethanol metabolism generates acetaldehyde and acetate, which could potentially promote functional disruptions of microbial and host components of the intestinal barrier along the gastrointestinal tract. The potential involvement of acetaldehyde and acetate in the pathogenesis of the underlying ABD, including cancer, is discussed. We also highlight some gaps in knowledge existing in the field of ABD. Finally, we discuss future directions in exploring the role of acetaldehyde and acetate generated during chronic alcohol intake in various pathologies affecting different sites of the intestinal tract.


Internal structure of dendrimers in the melt under shear: a molecular dynamics study.
The molecular structure of fluids composed of dendrimers of different generations is studied using nonequilibrium molecular dynamics (NEMD). NEMD results for dendrimer melts undergoing planar Couette flow are reported and analyzed with particular attention paid to the shear-induced changes in the internal structure of dendrimers. The radii of gyration, pair distribution functions and the fractal dimensionality of the dendrimers are determined at different strain rates. The location of the terminal groups is analyzed and found to be uniformly distributed throughout the space occupied by the molecules. The fractal dimension as a function of strain rate displays crossover behavior analogous to the Newtonian/non-Newtonian transition of shear viscosity.


Long-term survival and prognosis associated with conversion surgery in patients with metastatic gastric cancer.
In gastric cancer, primary systemic chemotherapy is the standard approach for the management of patients with initially unresectable metastasis, and it occasionally leads to a reduction in the size of the lesion, which facilitates surgical resection. The aim of this study was to examine the prognosis of patients who were able to undergo complete resection following chemotherapy. A total of 10 patients who underwent radical surgery for stage IV primary gastric cancer after chemotherapy between 2009 and 2015 at the Department of Surgery of Hokkaido Social Work Association Obihiro Hospital (Obihiro, Japan) were retrospectively investigated. Three regimens were used (S-1, n=1; S-1 + cisplatin, n=8; and S-1 + docetaxel, n=1). The mean time from chemotherapy to surgery was 210 days. One total gastrectomy + splenectomy + colectomy, one total gastrectomy + splenectomy, four total gastrectomies and three distal gastrectomies were performed. There were two cases of pancreatic fistula formation postoperatively. All the patients survived for >1 year. Of the 10 patients, 5 survived without recurrence. The median survival time was 871.1 days after diagnosis. Therefore, curative resection after chemotherapy is associated with a better prognosis in stage IV gastric cancer patients.


Segregation of keratinocyte colony-forming cells in the bulge of the rat vibrissa.
The epidermis and its related appendages such as the hair follicle constitute the epithelial compartment of the skin. The exact location and distribution of the keratinocyte colony-forming cells within the epidermis or its appendages are unknown. We report that in the rat vibrissa, keratinocyte colony-forming cells are highly clustered in the bulge-containing region. Approximately 95% of the total colonies formed in culture from fractionated vibrissae were in this location and fewer than 4% were located in the matrix area of the follicle. Finer dissection of the bulge-containing region located the colony-forming cells in the small part containing the bulge itself. The segregation of keratinocyte colony-forming cells in the bulge confirms the hypothesis that the bulge is the reservoir of the stem cells responsible for the long-term growth of the hair follicle and perhaps of the epidermis as well.


Amenorrhea in ballet dancers in the Netherlands.
The prevalence of amenorrhea was studied among 113 professional and student ballet dancers in the Netherlands (mean age 23.3 yr, SD 4.8). Sixty-one dancers not on oral contraceptives were included in the subsequent analyses. Six cases (prevalence 9.8 percent, 95 percent confidence interval: 2.4-17.2) with secondary amenorrhea (< or = 4 cycles per year; previous menstruation > or = 3 months prior to the study; menarche > or = 1 yr prior to the study) were found. Two dancers had primary amenorrhea (no menarche at the age of > or = 16). There was a negative correlation between the age of menarche and the number of menstrual cycles during the 12 months preceding the study (r = -0.46, P = 0.001). Body composition (four-compartment model), amount of dancing (recorded), resting energy expenditure (ventilated hood), dietary intake (recorded), and indices of eating disorders (Eating Disorders Inventory, EDI) were studied in 15 of the dancers, 5 amenorrheic and 10 eumenorrheic. No significant differences were found between the amenorrheic and eumenorrheic dancers. An explanation for the lower prevalence of amenorrhea in ballet dancers in the Netherlands, compared with U.S. dancers, was not obvious. Relatively low EDI scores (25.8, SD 14.5) in a subsample of 24 dancers could indicate less rigid emphasis on leanness and dieting.


Prevalence of Vitamin D Deficiency and Calcium Homeostasis in Saudi Children.
Vitamin D deficiency (VDD) and vitamin D insufficiency (VDI) are significant health problems all over the world. The aim of this study was to determine the prevalence of VDD and VDI in children and adolescents residing in 8 provinces in the Kingdom of Saudi Arabia and to also investigate calcium homeostasis in these subjects. A cross-sectional study was conducted in 2110 participants aged between 6 and 15 years. Information on socio-demographic status, anthropometric measurements, knowledge about vitamin D, color of the skin, dietary intake, sun exposure experience, smoking, and physical activity were collected through a questionnaire given to the parents of all subjects. The subjects were divided into three groups as vitamin D deficient, vitamin D insufficient, and vitamin sufficient according to their blood level of vitamin D [VDD ≤25 nmol/L (25 hydroxy vitamin D), VDI >25-50 nmol/L, and VDS >50 nmol/L]. VDD was highly prevalent in this group of children. 95.3 of the subjects had either VDD (45.5%) or VDI (49.9%). The prevalence rate of VDD combined with VDI was higher in females (97.8%) compared to males (92.8%) (p<0.001). Only 1.6% had significant hypocalcaemia. Children with dark skin had lower concentrations of vitamin D and higher concentrations of parathormone. A positive correlation was observed between 25 hydroxy vitamin D level and serum calcium, inorganic phosphate, and alkaline phosphatase concentrations. onclusion: The results showed a high prevalence of VDD and VDI in Saudi children with significantly higher prevalence in girls. These findings necessitate the set-up of a national program for vitamin D supplementation and health education for this vulnerable group.


[Personal Telemonitoring: Perspectives of Development in Arhythmology and Cardiology].
Sudden cardiac death (SCD) persists as one of challenging problems in cardiology and cardiac surgery, only in Russia costing more than 350,000 deaths annually. Arrhythmias and ischemic heart disease (IHD) prevail as SCD immediate direct mechanisms. Unfortunately, timely diagnostics of heart diseases is far below the satisfactory level. On the other hand, the number of patients to be followed up is increasing faster than the healthcare capacity. To close the gap, new approaches to diagnostics and prophylaxis of cardiovascular diseases are needed, involving innovative medical technologies. Implantable and external devices for heart arrhythmia and CAD early diagnostics are extensively used in modern cardiologic praxis. Impetuous development of this technique in combination with information and telecommunication technologies during last decade led to origination of completely new medical service based on mobile remote monitoring of patients. Relying on the experience in remote patient monitoring with implantable devices for recording heart electrical activity, Russian Scientific Society.


Tunable mid-infrared (6.3-12 μm)optical vortex pulse generation.
We demonstrated widely tunable mid-infrared (6.3-12 μm) optical vortex pulse generation from a ZGP difference frequency generator pumped by a 2 μm optical vortex laser with a cascaded KTP geometry. The mid-infrared vortex output carried the same topological charge as that of the 1 μm pump output without any destruction. A pulse energy of >135 μJ was obtained in the wavelength region of 6.3-7.0 μm.


[A present view on ivabradine in the therapy of cardiovascular diseases].
Cardiovascular illnesses belong to diseases with the highest prevalence. They are also the most predominant reason of death in the vast majority of European countries. Hence, the offer of effective treatment of these dis-eases is absolutely crucial. This text focuses on the current therapeutical use of ivabradine in its approved indications - chronic stable angina pectoris and chronic heart failure - in the context of so far published relevant clinical trials.Key words: angina pectoris - bradines - heart failure - If current - ischemic heart disease - ivabradine.


Purification and some properties of malarial pigment.
Malarial pigment from erythrocytes infected with Plasmodium berghei was purified by treatment with sodium dodecyl sulphate solution, followed by incubation with Pancreatin. The purified pigment retained the apparently crystalline form of pigment within the parasite, rotated polarised light and had the same solubility characterisation as crude malarial pigment. It contained about 1% iron, all of which could be accounted for in terms of haemin. The iron of the pigment molecule is oxidised by the parasite to the ferric state.


Determination of peripapillary vessel density in optic disc drusen using EDI-OCT and OCT angiography.
Optical coherence tomography angiography (OCTA) is a rapidly developing technique which generates angiographic images non-invasively. This study proposes a method to determine the vessel density in OCTA scans in general and especially the local peripapillary vessel density. The method produces vessel density heatmaps that contain information about the local vessel density. We apply the method in a small study to demonstrate its applicability and its potential to investigate the influence of local conditions on the vessel density. In the study, we combine information from enhanced depth imaging optical coherence tomography (EDI-OCT) about the location of optic disc drusen (ODD) with information from OCTA about the vessel density. We see a reduction in local peripapillary vessel density in peripapillary sections with a large volume of ODD.


A Multimodal Spectroscopic Imaging Method To Characterize the Metal and Macromolecular Content of Proteinaceous Aggregates ("Amyloid Plaques").
Alzheimer's disease (AD) is a major international health and economic concern. A key pathological feature of AD is so-called "amyloid-β-plaques", or "Aβ-plaques", which are deposits of aggregated protein, enriched with the Aβ fragment of amyloid precursor protein. Despite their name, the deposits are not pure Aβ and have a heterogeneous, chemically complex composition that can include multiple proteins, lipids, and metal ions (Fe, Cu, or Zn). Despite extensive research, it is still uncertain whether Aβ-plaques are a cause or a consequence of AD pathology. Further characterization of the elemental and biochemical composition within and surrounding Aβ-plaques, and knowledge of how composition varies with disease state or progression, may provide important insight into the relationship between Aβ-plaques and AD pathology. With this aim in mind, herein we demonstrate a multimodal spectroscopic imaging workflow to better characterize the complex composition of Aβ-plaques. Our approach incorporates several spectroscopic imaging techniques, such as Fourier transform infrared spectroscopic imaging (FTIR), Raman microscopy, and X-ray fluorescence microscopy (XFM). While FTIR, Raman, and XFM have been used previously, mostly in isolation, to study Aβ-plaques, application of all three techniques, in combination with histology and fluorescence microscopy, has not been reported previously. We demonstrate that a multimodal workflow, incorporating all three methods on adjacent or serial tissue sections, can reveal substantial complementary information about the biochemical and elemental composition of Aβ-plaques. Information revealed by the method includes the relative content and distribution of aggregated protein, total lipid, lipid esters, cholesterol, and metals (Fe, Cu, or Zn).


A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers.
Studies indicate that higher sun exposure, especially in the recent past, is associated with reduced risk of non-Hodgkin lymphoma (NHL). Ultraviolet radiation-derived vitamin D may be protective against lymphomagenesis. We examined the relationship between prediagnostic serum 25-hydroxyvitamin D (25(OH)D) and lymphoid cancer risk in a case-control study nested within the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort (1985-2002) of 29,133 Finnish male smokers (ages 50-69). We identified 270 incident lymphoid cancer cases and matched them individually with 538 controls by birth-year and month of fasting blood draw at baseline. In conditional logistic regression models for 10 nmol/L increments or tertile comparisons, serum 25(OH)D was not associated with the risk of overall lymphoid cancers, NHL (n = 208) or multiple myeloma (n = 41). Odds ratios (OR) for NHL for higher tertiles were 0.75 (95% confidence interval (CI), 0.50, 1.14) and 0.82 (95% CI, 0.53, 1.26). The 25(OH)D-NHL association, however, differed by follow-up duration at diagnosis. Cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest vs. lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17). The inverse association found for close exposure to diagnosis was not confounded by other risk factors for lymphoma or correlates of 25(OH)D. Although our findings suggest that circulating 25(OH)D is not likely associated with overall lymphoid cancer, they indicate a potentially protective effect on short-term risk of NHL.


Effects of continuous use of Entonox in comparison with intermittent method on obstetric outcomes: a randomized clinical trial.
Entonox (N2O2) which is an inhalational gas for relieving labor pain is commonly used intermittently; however some women are interested in continuous breathing in face mask. So we decided to compare the complications induced by two methods to find out whether it is safe to permit the mothers to use Entonox continuously or not. This randomized clinical trial was performed in Mobini Hospital, Sabzevar, Iran. 50 parturients used Entonox intermittently and 50 cases used it continuously during labor. Then obstetrical outcomes were analyzed in two groups by spss 17 software, t-test, and Chi(2) while P < 0.05 was considered significant. This study showed the mean duration of second stage of labor had no significant difference (P = 0.3). Perineal laceration was less in continuous group significantly (P = 0.04). Assisted vaginal birth was not different significantly (P = 0.4). Uterine atony had no significant difference in two groups (P = 0.2). Maternal collaboration in pushing and satisfaction were higher in continuous group significantly (P = 0.03), (P < 0.0001). Apgar score of neonates at first and fifth minute was acceptable and not different significantly in two groups (P = 0.3). Our study demonstrated continuous method is also safe. So, it seems reasonable to set mothers free to choose the desired method of Entonox usage.


Construction of Isocytosine Scaffolds via DNA-Compatible Biginelli-like Reaction.
Herein we report a DNA-compatible Biginelli reaction to construct isocytosine scaffolds. This reaction utilizes a one-pot reaction of DNA-conjugated guanidines with aldehydes and methyl cyanoacetates to give isocytosine derivatives, and the method is well compatible with different types of substrates. This is the first report on the synthesis of an isocytosine backbone in the field of DNA-compatible organic synthesis. The successful development of this reaction can widen the chemical space of DELs.


Long-Range RNA Structural Information via a Paramagnetically Tagged Reporter Protein.
NMR has provided a wealth of structural and dynamical information for RNA molecules of up to ∼50 nucleotides, but its application to larger RNAs has been hampered in part by difficulties establishing global structural features. A potential solution involves measurement of NMR perturbations after site-specific paramagnetic labeling. Although the approach works well for proteins, the inability to place the label at specific sites has prevented its application to larger RNAs transcribed in vitro. Here, we present a strategy in which RNA loop residues are modified to promote binding to a paramagnetically tagged reporter protein. Lanthanide-induced pseudocontact shifts are demonstrated for a 232-nucleotide RNA bound to tagged derivatives of the spliceosomal U1A RNA-binding domain. Further, the method is validated with a 36-nucleotide RNA for which measured NMR values agreed with predictions based on the previously known protein and RNA structures. The ability to readily insert U1A binding sites into ubiquitous hairpin and/or loop structures should make this approach broadly applicable for the atomic-level study of large RNAs.


Separation of parental genomes in human blood and bone marrow cells and its implications.
The linear order of genes is apparently interrupted at chromosomal ends. Our observations on human blood and bone marrow cells indicate that the chromosomes of each of the two parental sets maintain coherence, perhaps in tandem, forming a ring. Two such rings in a diploid cell join building a larger ring, which folds up to form the interphase nucleus. The linear order of genes thus extends beyond the chromosomal ends. These observations become especially significant when seen in the light of cell biologic findings on interaction of chromosomes or chromatin and centrioles in different cell cycle phases, in polymorphonuclear cells and during the zygotic developments. They may explain how the genomic order and the sequential continuity of the genes are maintained and why such order remains often cryptic.


Calculated chemical shifts as a fine tool of conformational analysis: an unambiguous solution for haouamine alkaloids.
In this study, for the first time, conformational analysis by calculated chemical shifts (CCS) deals with a real conformational problem of a large biomolecule. This new methodology is applied to haouamine A, which is much more stereodynamically puzzled than the small models used to validate previous CCS-based conformational studies. Thorough NMR experiments by Zubia et al. on this exotic polyfunctional paracyclophane alkaloid could not determine which experimentally detected interconversion of this compound occurs in solution, rotation or N-inversion. The present study uses CCS to locate the lowest energy conformers and thus to identify the observed stereodynamic process. Molecular mechanics calculations were used to explore the conformational space of this polycyclic system, and then the geometry of located conformers was refined by ab initio calculations at the B3LYP/6-31G(d,p) level; an implicit model for acetone solution was employed. Calculated relative energies are considered too inaccurate to identify the lowest energy (i.e., those detectable by NMR) conformers. Instead, rational regression analysis of CCS for carbon atoms using B3LYP/6-31+G(d)//GIAO-based calculations singled out two conformers from a large set of alternative low energy structures, although solvation shell was not explicitly included in the model. For only these two conformers, the differences in CCS (Delta delta) for selected pairs of carbons are very similar to the experimental Delta delta values. Thus, the conformers monitored by NMR have now been identified; their piperideine ring is of (1)Sf and Sf 1 (sofa-shaped) geometry. This azacycle appears to be flexible despite the presence of the ethylenebiphenylene bridge in haouamines. Interconversion between the conformers probably occurs via a concerted process of inversion of the piperideine ring, N-inversion coupled with rotation around the C-N bond, and rotation around two C-C bonds in the ethylenebiphenylene bridge. This CCS method of conformational analysis is sufficiently simple and reliable that if chemical shifts for a pair of the same carbons are sufficiently different in routine (13)C NMR spectra of stereoisomers (ca. > or = 2 ppm), the "resolving power" of the CCS technique may rival that of NMR techniques.


Plasma catecholamines in long-term diabetes.
To investigate a possible defect in sympathetic innervation of the blood vessels in diabetics, 18 normals, 13 normotensive juvenile diabetics without complications and 13 normotensive juvenile diabetics with complications were first treated with an increasing infusion of norepinephrine (NE) and subsequently given a two minutes' exercise with a 150 Watt load. Plasma catecholamines were measured under both conditions. In the infusion experiments diabetics were found to have higher NE levels than normals. In normals NE fells to starting levels 5 min. after completion of the work load. In diabetics this fall-back rate was slower. The reduction in the fall-back rate was correlated with the duration of the diabetes.


Biological embedding in mental health: an epigenomic perspective.
Human epidemiological studies and studies of animal models provide many examples by which early life experiences influence health in a long-term manner, a concept known as biological embedding. Such experiences can have profound impacts during periods of high plasticity in prenatal and early postnatal life. Epigenetic mechanisms influence gene function in the absence of changes in gene sequence. In contrast to the relative stability of gene sequences, epigenetic mechanisms appear, at least to some extent, responsive to environmental signals. To date, a few examples appear to clearly link early social experiences to epigenetic changes in pathways relevant for mental health in adulthood. Our recent work using high-throughput epigenomic techniques points to large-scale changes in gene pathways in addition to candidate genes involved in the response to psychosocial stress and neuroplasticity. Elucidation of which pathways are epigenetically labile under what conditions will enable a more complete understanding of how the epigenome can mediate environmental interactions with the genome that are relevant for mental health. In this mini-review, we provide examples of nascent research into the influence of early life experience on mental health outcomes, discuss evidence of epigenetic mechanisms that may underlie these effects, and describe challenges for research in this area.


Antigen-specific suppressor cell activity in patients with scleroderma.
Antigen-specific suppressor cell activity (SCA) of peripheral blood mononuclear cells was investigated in 22 patients with scleroderma (PSS) and 22 age and sex matched healthy controls. SCA was induced by priming peripheral blood mononuclear cells with high dose antigen (ovalbumin). Antigen-specific SCA was measured by determining the ability of the primed cells to suppress an optimal ovalbumin specific plaque forming cell (PFC) response in an autologous target culture. The in vitro PFC response and suppressor cell activity of the PSS patients was not different from that of the normal controls. Antigen dose-response curves of the priming phase of the assay were similar in both the patient and control groups.


Comparative genetico-mathematic analysis of essential hypertension and coronary heart disease mode of inheritance: a study using direct methods testing.
Essential hypertension (EH) and coronary heart disease (CHD) very often exhibit familial recurrence pattern, which are estimated in the Bulgarian population at 63.11% for EH and at 48.90% for CHD. The author made comparative genetico-mathematical analysis of the inheritance patterns of the two diseases. Examining the pedigrees from a large number of families two data sets were formed and analyzed separately: a subgroup of families of probands with phenotypically unaffected parents, in which the genealogical pattern was most often consistent with a recessive model of inheritance and a subgroup of families of probands with one or both parents affected, in which the pedigree analysis resembled that of a disease with a monogenic dominant model of inheritance. The segregation coefficients obtained in the subgroup of families with two healthy parents most often varied from 0.298 to 0.362--results that consistently reject the hypothesis of recessive inheritance; the respective coefficients obtained by the same direct methods in the subgroup of families with one or both parents affected showed values from 0.279 to 0.468--findings rejecting the hypothesis of dominant model of inheritance. The author pointed out the identical relationships exhibited by genetico-mathematical testing of EH and CHD, a fact demonstrating the significant genetic proximity between the two diseases. Conclusions are made about the complex and specific relationships between genetic and environmental risk factors in the two diseases.


[Cryosurgery for nose basal cell carcinoma. Series of 17 tumors].
Basal cell carcinoma (BCC) is the most common malignant tumour of the skin frequently located on the head and chiefly on the nose. Cryosurgery is one of the methods to treat BCC. To determine the efficacy of cryosurgery of 17 BCC of the nose in terms of recurrence rates and cosmetic results. 15 patients were included with a median age of 73 years and a photo type III or IV in 86% of cases. Mean size of tumours was 12 mm. Lesions were chiefly located on the alae nasi (70.5%). Complications were few and minor. After an average follow-up of 13.5 months, recurrence rate was about 5.8% (one case). Cosmetic results were good or excellent in 14 cases/17; only one patient had developed a notch of the nose. Cryosurgery is a rapid, of a low cost technique and chiefly with good oncological and cosmetic results.


Influenza M2 virus-like particle vaccination enhances protection in combination with avian influenza HA VLPs.
Despite the ability to induce a broad range of cross protection, M2e5x virus-like particles (VLPs) alone provide limited vaccine efficacy and confer low efficacy of protection against highly pathogenic avian influenza virus (HPAIV) infection in chickens. Avian influenza hemagglutinin (HA) has been a major antigenic target that enhances humoral immunity, but the efficacy of avian HA-based vaccines against HPAIV needs to be further improved. In this study, we evaluated the vaccine efficacy induced by combination of conserved tandem repeat M2e5x VLPs and HA VLPs against an avian influenza virus. We found that combinatorial vaccine elicited higher levels of reassortant H5N1 (rgH5N1) virus-specific IgG, IgG1, IgG2a and IgA antibody responses compared to M2e5x VLPs in sera and lungs of mice. Combinatorial VLPs vaccination induced higher levels of CD8+ T cell and germinal center B cell responses in lung and spleen compared to M2e5x VLPs. Combinatorial VLPs vaccination showed significantly reduced inflammatory responses and lung viral loads upon rgH5N1 virus challenge infection, resulting in less body weight loss compared to M2e5x VLPs alone. These results indicate that immune responses to both M2e and HA might provide a strategy of vaccination inducing enhanced protection against avian influenza virus.


A retrospective review of Mohs micrographic surgery trends over more than 10 years in Saudi Arabia.
To review Mohs micrographic surgery (MMS) trends in Saudi Arabia.Mohs micrographic surgery is a precise surgical technique that has been proven to have the highest cure rate with maximum normal tissue preservation. It is the treatment of choice for non-melanoma skin cancer (NMSC), especially the aggressive histopathological forms, and tumors located in high-risk regions or where tissue preservation is a mandate. A multicentric retrospective study was performed on patients who underwent MMS between January 2010 and September 2022. The information was extracted from the database of King Saud University Medical City and Prince Sultan Military Medical City in Saudi Arabia. A total of 70 participants were enrolled in this study. Two-thirds (67%) of the tumors that were treated using MMS were basal-cell carcinomas (BCC), 18.6% were squamous cell carcinomas (SCC), 5.7% were sebaceous carcinoma, 4.3% were dermatofibrosarcoma protuberans (DFSP), and 1.4% were rare tumors such as primary mucinous carcinoma. The most common type of reconstruction used to repair post-MMS defect was primary closure in more than half of the patients followed by secondary intention healing (20%). There were no side effects apart from a hematoma in one patient and wound infection in two patients. Although MMS is still generally underutilized in Saudi Arabia, its use has increased in the last decade.


Post-menopausal bleeding.
PMB is a common symptom, which is associated with approximately a 20% incidence of malignancy in the genital tract. Every effort, therefore, needs to be made to exclude adenocarcinoma of the uterus, a condition with a good prognosis if an early diagnosis is made. In most other patients the cause of PMB is minor and can readily be controlled.


Feeding the machine: Challenges to reproducible predictive modeling in resting-state connectomics.
In this critical review, we examine the application of predictive models, for example, classifiers, trained using machine learning (ML) to assist in interpretation of functional neuroimaging data. Our primary goal is to summarize how ML is being applied and critically assess common practices. Our review covers 250 studies published using ML and resting-state functional MRI (fMRI) to infer various dimensions of the human functional connectome. Results for holdout ("lockbox") performance was, on average, ∼13% less accurate than performance measured through cross-validation alone, highlighting the importance of lockbox data, which was included in only 16% of the studies. There was also a concerning lack of transparency across the key steps in training and evaluating predictive models. The summary of this literature underscores the importance of the use of a lockbox and highlights several methodological pitfalls that can be addressed by the imaging community. We argue that, ideally, studies are motivated both by the reproducibility and generalizability of findings as well as the potential clinical significance of the insights. We offer recommendations for principled integration of machine learning into the clinical neurosciences with the goal of advancing imaging biomarkers of brain disorders, understanding causative determinants for health risks, and parsing heterogeneous patient outcomes.


[Local immunity factors in the reproductive system of women with Chlamydia infection].
A total of 50 healthy women and 184 women of reproductive age with Chlamidia infection, complicated by candidiasis, mycoplasmosis and bacterial vaginosis were under examination. The local infectious immunity indices of cervical mucous were detected. The investigation of cell-mediated and humoral factors of cervical secretions revealed the dysfunction of local infectious protection in women with Chlamydia infection.


[Progressive multifocal encephalopathy in neurological practice].
Progressive multifocal leukoencephalopathy (PML) is considered so far as a rare rapidly progressive demyelinating CNS disease caused by the JC virus activation. Current data suggest that PML developed in people with impaired immunity. However, in some cases PML developed in the absence of severe immunological deficit. In clinical practice, the early diagnosis of PML is difficult because symptoms are mild and, therefore, the physician should be familiar with diagnostic criteria of this disease to make the correct diagnosis and start the symptomatic therapy as soon as possible. This will help to improve patient's state though there is no effective treatment of PML so far. Up to the present moment, antiviral medications, cytostatic drugs, serotonin receptor antagonists, plasmapheresis are widely used. These methods can be used only if the causes of PML have been identified while the patient needs urgent help. Thus, the schemes of pathogenetic treatment with the drugs with pleiotropic effects should be used.


Optimizing therapy of seizures in patients with renal or hepatic dysfunction.
Patients with epilepsy may suffer from renal or hepatic diseases that interfere with their antiepileptic drug (AED) treatment. Furthermore, such diseases may themselves cause seizures. Reduced renal function and hypoalbuminemia lead to accumulation of renally excreted AEDs, such as gabapentin, vigabatrin, topiramate, levetiracetam, and phenytoin. Valproate, lamotrigine, and benzodiazepines are less affected. Low protein-bound AEDs are extensively removed by hemodialysis and supplemental doses are required for dialysis patients. Uremia and related conditions, including intracranial hemorrhage, glucose and electrolyte imbalances, and concomitant drug use, can cause seizures, as can dialysis encephalopathy, primary cerebral lymphoma, fungal infections, and immunosuppressant toxicity in renal transplant recipients. Hepatic dysfunction reduces enzymatic metabolism of AEDs and causes hypoalbuminemia. Gabapentin, topiramate, and levetiracetam are preferred in these conditions, whereas conversely valproate and felbamate are potentially hepatotoxic and should be avoided. Seizures related to hepatic encephalopathy are controlled by oral lactulose or neomycin. Porphyria sufferers may benefit from gabapentin, oxcarbazepine, or levetiracetam. Seizures in Wilson's disease may derive from d-penicillamine-induced pyridoxine deficiency. Effective treatment of seizures in renal and hepatic diseases requires attention to changes in AED pharmacokinetics and adequate care of the underlying illnesses. Monitoring of free drug concentrations is a valuable aid to therapy.


Management of hypertension and diabetes mellitus by cardiovascular and endocrine physicians: a China registry.
We investigated hypertension and diabetes mellitus in two management settings, namely cardiology and endocrinology, and their associations with albuminuria while accounting for the management of these two diseases. Our multicentre registry included patients (≥20 years) seen for hypertension in cardiology or for diabetes mellitus in endocrinology. We administered a questionnaire and measured blood pressure, glycosylated haemoglobin A1c and albuminuria. Presence of both hypertension and diabetes was observed in 32.9% of hypertensive patients in cardiology (n = 1291) and 58.9% of diabetic patients in endocrinology (n = 1168). When both diseases were present, the use of combination antihypertensive therapy [odds ratio (OR) 0.31, P < 0.0001] and inhibitors of the renin-angiotensin system (OR 0.66, P = 0.0009) was less frequent in endocrinology than cardiology, and the use of combination antidiabetic therapy (OR 0.16, P < 0.0001) was less frequent in cardiology than endocrinology. The control of hypertension and diabetes, however, was not different between the two management settings (P ≥ 0.21), regardless of the therapeutic target (SBP/DBP < 140/90 or 130/80 mmHg and glycosylated haemoglobin A1c <7.0 or 6.5%). The prevalence of albuminuria was higher (P ≤ 0.02) in the presence of both diseases (23.3%) than those with either hypertension (12.6%) or diabetes alone (15.9%). Hypertension and diabetes mellitus were often jointly present, especially in the setting of endocrinology. The management was insufficient on the use of combination antihypertensive therapy and inhibitors of the renin-angiotensin system in endocrinology and for combination antidiabetic therapy in cardiology, indicating a need for more intensive management and better control of both clinical conditions.


The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.
We analysed the serum C-reactive protein level, synovial fluid obtained by joint aspiration and five synovial biopsies from 145 knee replacements prior to revision to assess the value of these parameters in diagnosing late peri-prosthetic infection. Five further synovial biopsies were used for histological analysis. Samples were also obtained during the revision and incubated and analysed in an identical manner for 14 days. A total of 40 total knee replacements were found to be infected (prevalence 27.6%). The aspiration technique had a sensitivity of 72.5% (95% confidence interval (CI) 58.7 to 86.3), a specificity of 95.2% (95% CI 91.2 to 99.2), a positive predictive value of 85.3% (95% CI 73.4 to 100), a negative predictive value of 90.1% (95% CI 84.5 to 95.7) and an accuracy of 89%. The biopsy technique had a sensitivity of 100%, a specificity of 98.1% (95% CI 95.5 to 100), a positive predictive value of 95.2% (95% CI 88.8 to 100), a negative predictive value of 100% and an accuracy of 98.6%. C-reactive protein with a cut-off-point of 13.5 mg/l had a sensitivity of 72.5% (95% CI 58.7 to 86.3), a specificity of 80.9% (95% CI 73.4 to 88.4), a positive predictive value of 59.2% (95% CI 45.4 to 73.0), a negative predictive value of 88.5% (95% 81.0 to 96.0 CI) and an accuracy of 78.1%. We found that biopsy was superior to joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.


Diabetic retinopathy in pregnancy.
The records of 23 insulin-dependent diabetics who had serial ophthalmological examinations during pregnancy and afterwards were reviewed. Fourteen pregnancies occurred in 10 patients with no retinopathy; 30% of these patients had obstetric complications. The mean birthweight was 3.5 kg. Ophthalmological status was unchanged in this group. In eight patients with background retinopathy during 10 pregnancies the obstetric complication rate was 70% and mean birthweight 3.3 kg. During pregnancy there was no evidence of progression of retinopathy. One patient developed proliferative retinopathy 4 years later. Five patients had proliferative retinopathy. The mean age (32 years) and duration of diabetes at index pregnancy (18 years) was greater than for the other groups. All patients developed pre-eclampsia and mean birthweight was 2.8 kg. Four of these patients required argon laser photocoagulation in association with pregnancy for progressive retinopathy; one died subsequently from end-stage diabetic nephropathy; the other four have maintained their pre-pregnancy visual acuity from 4 to 10 years.


Factors associated with organ donation in Filipino Americans: results from Hawai'i's Bayanihan Project.
Results from mailed surveys (n = 424) showed that 28% of adult Filipinos were a designated organ donor on their driver's license. In logistic regression analyses respondents who were born in the United States were 3.5 times more likely to be a designated donor compared with foreign-born Filipinos. Future programs should emphasize the need for Filipinos, especially immigrants, to become organ donors.


Ixodid ticks on feral swine in Florida.
More than 99% of the 645 feral swine (Sus scrofa L.) in southern Florida harbored ixodid ticks. Dermacentor variabilis (American dog tick) was present on 99.6% of the swine and comprised 82.5% of the ticks collected. Amblyomma maculatum (Gulf Coast tick) occurred on 85.9% of the hosts and 17.4% of the collections were of this species. Amblyomma americanum (Lone Star tick) and Ixodes scapularis (Black-legged tick) were found infrequently and together constituted less than 0.1% of the ticks. Pigs were infested by 7-22 days of age and 95% carried ticks by 6 wk of age. Only adult ticks were found on swine from southern Florida, but immature stages of A. americanum were present from a small sample of swine from northern Florida. Each species had a different pattern of distribution on the feral swine. No Ornithodoros species were found among the 36,616 ticks collected from feral swine during this survey.


Developmental expression of high-mobility group box 1 (HMGB1) in the mouse cochlea.
The expression changes of high-mobility group box 1 (HMGB1) in the mouse cochlea have recently been implicated in noise-induced hearing loss, suggesting that HMGB1 participates in regulating cochlear function. However, the precise role of HMGB1 in the auditory system remains largely unclear. This study aimed to investigate its function in the developing mouse cochlea by examining the expression pattern of HMGB1 in the mouse cochlea from embryonic day (E) 18.5 to postnatal day (P) 28 using double immunofluorescence on frozen sections. Our findings revealed that HMGB1 was extensively expressed in the cell nucleus across various regions of the mouse cochlea, including the organ of Corti. Furthermore, its expression underwent developmental regulation during mouse cochlear development. Specifically, HMGB1 was found to be localized in the tympanic border cells at each developmental stage, coinciding with the gradual anatomical in this region during development. In addition, HMGB1 was expressed in the greater epithelial ridge (GER) and supporting cells of the organ of Corti, as validated by the supporting cell marker Sox2 at P1 and P8. However, at P14, the expression of HMGB1 disappeared from the GER, coinciding with the degeneration of the GER into the inner sulcus cells. Moreover, we observed that HMGB1 co-localized with Ki-67-positive proliferating cells in several cochlear regions during late embryonic and early postnatal stages, including the GER, the tympanic border cells, cochlear lateral wall, and cochlear nerves. Furthermore, by dual-staining Ki-67 with neuronal marker TUJ1 and glial marker Sox10, we determined the expression of Ki-67 in the neonatal glial cells. Our spatial-temporal analysis demonstrated that HMGB1 exhibited distinct expression patterns during mouse cochlear development. The co-localization of HMGB1 with Ki-67-positive proliferating cells suggested that HMGB1 may play a role in cochlear development.


Association between intrauterine mild hyperglycemia and post-natal high-fat diet with adiponectin and AMPK pathway genes.
To investigate the mechanisms of maternal-fetal interactions in the setting of gestational diabetes mellitus. We investigated the long-term effects of intrauterine mild hyperglycemia and a postnatal high-fat diet on the glucose metabolism of adult offspring, and explored the role of adiponectin on hepatic gluconeogenesis. Twenty-one pregnant Wistar rats were randomly divided into an intrauterine hyperglycemia group (group D, n = 14) and a control group (group C, n = 7). Offspring were divided into four groups according to intrauterine blood glucose level and post-weaning dietary patterns (high-fat diet groups: DF and CF or normal diet groups: DN and CN, n = 8 per group). The average birth weights of group D offspring were higher than for group C. In the DF rats, low adiponectin mRNA expression in perirenal and epididymal fat was significantly positively correlated with low hepatic AdipoR1 mRNA expression and significantly correlated with high hepatic PEPCK, G-6-Pase, and PGC-1α mRNA levels. In DF rats, hepatic P-AMPK was cytoplasmically located and its level was decreased; in these rats, hepatic CRTC2 was expressed in the nucleus and its level was significantly increased. Our study shows that the dietary structure of offspring has a large influence on the incidence of abnormal glucose tolerance.


Fenton-Chemistry-Mediated Radical Polymerization.
In this review, the power of a classical chemical reaction, the Fenton reaction for initiating radical polymerizations, is demonstrated. The reaction between the Fenton reagents (i.e., Fe2+ and H2 O2 ) generates highly reactive hydroxyl radicals, which can act as radical initiators for the polymerization of vinyl monomers. Since the Fenton reaction is fast, easy to set up, cheap, and biocompatible, this unique chemistry is widely employed in various polymer synthesis studies via free radical polymerization or reversible addition-fragmentation chain transfer polymerization, and is utilized in a wide range of applications, such as the fabrication of biomaterials, hydrogels, and core-shell particles. Biologically activated Fenton-mediated radical polymerization, which can be performed in aerobic environments, are particularly useful for applications in biomedical systems.


Mild cognitive impairment in medical inpatients: the Mini-Mental State Examination is a promising screening tool.
To assess the prevalence of mild cognitive impairment (MCI) in medical inpatients aged 55-85 years without known cognitive deficits, and how often ward physicians mentioned MCI in their discharge notes. Moreover, we aimed to identify variables associated with MCI and to assess the sensitivity and specificity of the Mini-Mental State Examination (MMSE) for MCI. Two neuropsychologists administered a 60-min battery of validated tests to evaluate different cognitive domains. The diagnosis of MCI was based on a prespecified algorithm. The sensitivity and specificity of the MMSE for MCI were calculated. Fifteen patients showed a normal cognitive profile (21.4%), while 55 patients (78.6%) showed MCI. Ward physicians, blinded to the results of the neuropsychological evaluation, did not mention MCI in their discharge notes of any of the evaluated patients. The only variable independently associated with MCI was the MMSE. A MMSE score of < or =28 showed a sensitivity of 85.5% and a specificity of 66.7% for MCI. MCI is frequent albeit overlooked in elderly medical inpatients without previously known cognitive deficits. In view of therapies preventing the progression of MCI to dementia, MCI screening will be crucial. The MMSE represents a promising screening tool for MCI in medical inpatients.


In situ electrical resistivity measurements of vanadium thin films performed in vacuum during different annealing cycles.
The present study describes a sputtering and in situ vacuum electrical resistivity setup that allows a more efficient sputtering-oxidation coupling process for the fabrication of oxide compounds like vanadium dioxide, VO2. After the sputtering deposition of pure V thin films, the proposed setup enables the sample holder to be transferred from the sputtering to the in situ annealing + resistivity chamber without venting the whole system. The thermal oxidation of the V films was studied by implementing two different temperature cycles up to 550 °C, both in air (using a different resistivity setup) and vacuum conditions. Main results show that the proposed system is able to accurately follow the different temperature setpoints, presenting clean and low-noise resistivity curves. Furthermore, it is possible to identify the formation of different vanadium oxide phases in air, taking into account the distinct temperature cycles used. The metallic-like electrical properties of the annealed coatings are maintained in vacuum whereas those heated in air produce a vanadium oxide phase mixture.


The potential role of iron chelators in the treatment of Parkinson's disease and related neurological disorders.
Neurodegeneration is characterized by a marked accumulation of iron in the affected brain regions. The reason for this is still unknown. In this article we review the available data on the possible involvement of iron and mediated oxidative stress in the aetiology of Parkinson's disease and related disorders. Iron chelators, if they effectively prevent radical formation, have great therapeutic potential against ischaemia/reperfusion, rheumatoid arthritis, and anthracycline toxicity, which are most likely free radical-mediated. The efficacy of the best established chelating drug desferal in neurodegenerative disease is limited due to its high cerebro- and oculotoxicity. New bioactive chelating agents are currently being developed, among them are oxidative stress activatable iron chelators which are most likely less toxic and can flexibly respond to an increase of free radical formation in the cell.


[Morphological changes in the oviducts of infertile cows of the zebu breed].
Gross and histologic studies were carried out with a total of 118 Fallopian tubes of 59 slaughtered sterile cows of the Zebu breed originating from the Gamagüey region in Cuba. Morphologically, there were changes in 53 of the animals (89.8 per cent); of these in 29 cases both oviducts were affected, and in 24 of them only one was with lesions. In 6 of the cases (5 per cent) there were signs of acute salpingitis--hyperaemia, serous exudate, infiltration with lymphocytes and neutrophile granulocytes, and desquamation of the epithelium paving the folds. In 15 cases (13 per cent) there was subacute salpingitis--desquamation of the fold epithelium, negligible hyperaemia with oedema of the mucous membrane, and numerous plasmatic cells, fibroblasts, lymphocytes, and neutrophile granulocytes. In 61 cases (51 per cent) there were chronic salpingitis with varying fibrosis, atrophy of the folds, and cysts in the base of the folds. There were also sporadic cases of perisalpingitis.


Fruit quality of sweet pepper as affected by foliar Ca applications to mitigate the supply of saline water under a climate change scenario.
Sweet pepper fruit quality disorders have been related mainly to an unbalanced nutrient supply and non-optimal growth conditions. Increases in the atmospheric CO2 concentration ([CO2 ]) have been associated with a reduction of transpiration, which can affect calcium (Ca) uptake as it is linked closely to water uptake. We investigated whether foliar application of Ca can counterbalance the effects of saline water and elevated [CO2 ]. High CO2 favoured generative growth instead of vegetative growth. Foliar Ca supply did not affect the marketable yield, but reduced the total yield when combined with salinity and 400 µmol mol-1 CO2 . Salinity affected negatively the total yield but this was overcome when CO2 was applied. The B and K concentrations were reduced by foliar Ca application, while Ca and Mn were increased at 400 µmol mol-1 CO2 . Salinity increased the Mn, Cl, and Na concentrations, regardless of the [CO2 ], and decreased K at 800 µmol mol-1 CO2 . The total protein was affected negatively only by elevated [CO2 ], and the total free amino acid concentration was reduced by all treatments. The effect of Ca application differed according to the other treatments applied. This procedure should be optimised to overcome future climate impacts on fruit quality. © 2017 Society of Chemical Industry.


Seizures and Epileptiform Patterns in SAH and Their Relation to Outcomes.
In subarachnoid hemorrhage (SAH), seizures are frequent and occur at different time points, likely reflecting heterogeneous pathophysiology. Young patients, those with more severe SAH (by clot burden or presence of severe mental status changes at onset or focal neurologic deficits at any time), those with associated increased cortical irritation (by infarction or presence of underlying hematoma), and patients undergoing craniotomy are at higher risk. Advanced neurophysiologic monitoring allows for seizure burden quantification, identification of subclinical seizures, and interictal patterns as well as neurovascular complications that may have an independent impact on the outcome in this population. Practice regarding seizure prophylaxis varies widely; its institution is often guided by the risk-benefit ratio of seizures and medication side effects. Newer anticonvulsants seem to be equally effective and may have a more favorable profile. However, questions regarding the association of seizures and vasospasm, the therapeutic dosing, timing, and duration of antiepileptic treatment and the impact of seizures and antiepileptics on the outcome remain unanswered. In this review, we provide a broad overview of the work in this area and offer a diagnostic and therapeutic approach based on our own expert opinion.


Genetics of myeloid malignancies: pathogenetic and clinical implications.
Myeloid malignancies are clonal disorders that are characterized by acquired somatic mutation in hematopoietic progenitors. Recent advances in our understanding of the genetic basis of myeloid malignancies have provided important insights into the pathogenesis of acute myeloid leukemia (AML) and myeloproliferative diseases (MPD) and have led to the development of novel therapeutic approaches. In this review, we describe our current state of understanding of the genetic basis of AML and MPD, with a specific focus on pathogenetic and therapeutic significance. Specific examples discussed include RAS mutations, KIT mutations, FLT3 mutations, and core binding factor rearrangements in AML, and JAK2 mutations in polycythemia vera, essential thrombocytosis, and chronic idiopathic myelofibrosis.


Epidemiology of uraemic itch: New data.
Chronic itch (CI) is a frequent and impairing symptom in haemodialysis (HD) patients. Within the last decades, worldwide variations were reported in the prevalence of itch in HD patients, ranging from 10 to 77%. Regional differences and especially the irregular pattern of itch in HD may explain why CI is still not well perceived and underestimated in HD patients. The pathogenesis is still unclear and therapy is ineffective in the majority of cases. There is a great diversity of prevalence estimates of itch used in different studies as well, as the study population greatly differs, especially when investigating CI in HD. Due to the demographic situation with a rising number of aged patients and increasing survival rates in HD, the number of HD patients will continuously grow, especially in the Western countries. Up to now, representative epidemiological data on CI in HD were missing. GEHIS (German Epidemiological Hemodialysis Itch Study) was established in 2012 as a representative prospective cross-sectional study. Eight hundred and sixty HD patients from a randomly selected cluster sample were included. The primary outcome measures were different prevalence measures of CI. The point prevalence was 25.2%, the 12-month prevalence was 27.2% and the lifetime prevalence of CI was 35.2%. General health status and health-related quality of life (HRQOl) were significantly impaired in those with CI. Due to the comparability of standards in HD quality, these results can be transferred to Western countries. This study demonstrates that CI is a frequent, long-lasting burden in HD patients affecting every fourth HD patient (point prevalence) and more than every third HD patient at some point in their lifetime.


Combination of 595-nm pulsed dye laser, long-pulsed 755-nm alexandrite laser, and microdermabrasion treatment for keratosis pilaris: retrospective analysis of 26 Korean patients.
Keratosis pilaris (KP) has beenpresented as small keratotic follicular papules with or without surrounding erythema. Various treatments with laser or light therapy have been used for the management of KP with various clinical outcomes. In the present study, we investigated the efficacy and safety of a combination therapy for KP. A total of 29 anatomical sites with KP in 26 patients were treated using a 595-nm pulsed dye laser (PDL) with nonpurpuragenic fluences, a long-pulsed 755-nm alexandrite laser, and microdermabrasion. Clinical improvement was assessed by comparing preand posttreatment clinical photographs and patient satisfaction rates. Evaluation of the clinical results three months after the treatments showed that 12 of the 29 anatomical sites (41.4%) demonstrated Grade 3 clinical improvement, ten (34.5%) had Grade 2 clinical improvement, four (13.8%) showed Grade 1 improvement, and three (10.3%) showed Grade 4 improvement. We observed that KP lesions improved not only in erythema and skin texture, but also in brownish dyschromias. Potential adverse events were not observed, except prolonged posttherapy scaling. Our observations demonstrate that combination therapy using a 595-nm PDL, a long-pulsed 755-nm alexandrite laser, and microdermabrasion can have a positive therapeutic effect on KP.


Barriers and facilitators to the use of e-health by older adults: a scoping review.
Limited attention has been paid to how and why older adults choose to engage with technology-facilitated health care (e-health), and the factors that impact on this. This scoping review sought to address this gap. Databases were searched for papers reporting on the use of e-health services by older adults, defined as being aged 60 years or older, with specific reference to barriers and facilitators to e-health use. 14 papers were included and synthesised into five thematic categories and related subthemes. Results are discussed with reference to the Unified Theory of Acceptance and Use of Technology2. The most prevalent barriers to e-health engagement were a lack of self-efficacy, knowledge, support, functionality, and information provision about the benefits of e-health for older adults. Key facilitators were active engagement of the target end users in the design and delivery of e-health programs, support for overcoming concerns privacy and enhancing self-efficacy in the use of technology, and integration of e-health programs across health services to accommodate the multi-morbidity with which older adults typically present. E-health offers a potential solution to overcome the barriers faced by older adults to access timely, effective, and acceptable health care for physical and mental health. However, unless the barriers and facilitators identified in this review are addressed, this potential will not be realised.


Influence of the pneumococcal conjugate vaccines on the temporal variation of pneumococcal carriage and the nasal microbiota in healthy infants: a longitudinal analysis of a case-control study.
Bacterial colonization of the upper airways is a prerequisite for subsequent invasive disease. With the introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13), changes in pneumococcal upper airway colonization have been described. It is, however, less evident whether the vaccines lead to compositional changes of the upper airway microbiota. Here, we performed a case-control study using samples from a longitudinal infant cohort from Switzerland. We compared pneumococcal carriage and the nasal microbiota within the first year of life of healthy infants vaccinated with either PCV7 (n = 20, born in 2010) or PCV13 (n = 21, born between 2011 and 2013). Nasal swabs were collected every second week (n = 763 in total). Pneumococcal carriage was analyzed by quantitative PCR of the pneumococcal-specific lytA gene. Analysis of the bacterial core microbiota was performed based on 16S rRNA sequencing and subsequent oligotyping. We exclusively performed oligotyping of the core microbiota members, which were defined as the five most abundant bacterial families (Moraxellaceae, Streptococcaceae, Staphylococcaceae, Corynebacteriaceae, and Pasteurellaceae). Linear mixed effect (LME) and negative binomial regression models were used for statistical analyses. We found a higher number of samples positive for pneumococcal carriage in PCV7- compared to PCV13-vaccinated infants (LME model; P = 0.01). In contrast, infants vaccinated in the PCV13 era had an increased alpha diversity as measured by the richness and the Shannon Diversity Index (LME model; P = 0.003 and P = 0.01, respectively). Accordingly, the PCV13 era was associated with clusters of a higher diversity than PCV7-associated clusters. Furthermore, infants vaccinated with PCV13 had a higher binary-based within-subject microbiota similarity, as well as a decreased Jensen-Shannon distance over time as compared to PCV7-vaccinated infants, indicating a higher microbiota stability in the PCV13 era (LME model and t test; P = 0.06 and P = 0.03, respectively). We hypothesize that the higher diversity and stability of the upper airway microbiota in the PCV13 era is the result of the lower pneumococcal carriage rate. This seems to indicate that the nasal bacterial microbiota of infants has changed in recent years as compared to the beginning of this study.


Protecting liver sinusoidal endothelial cells suppresses apoptosis in acute liver damage.
Apoptosis is associated with various types of hepatic disorders. We have developed a novel cell-transfer drug delivery system (DDS) using a multifunctional envelope-type nano device that targets liver sinusoidal endothelial cells (LSECs). The purpose of this study was to determine the efficacy of the novel DDS containing siRNA at suppressing apoptosis in LSECs. Bax siRNA was transfected into a sinusoidal endothelial cell line (M1) to suppress apoptosis induced by an anti-Fas antibody and staurosporine. C57BL/6J mice were divided into three groups: (i) a control group, only intravenous saline; (ii) a nonselective group, injections of siRNA sealed in the nonselective DDS; and (iii) an LSEC-transfer efficient group, injections of siRNA sealed in an LSEC-transfer efficient DDS. Hepatic cell apoptosis was induced by an anti-Fas antibody. Bax siRNA had an anti-apoptotic effect on M1 cells. Serum alanine aminotransferase was reduced in the LSEC-transfer efficient group, as were cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive hepatocytes. Silver impregnation staining indicated that the sinusoidal space was maintained in the LSEC-transfer efficient group but not in the other groups. Electron microscopy showed that the LSECs were slightly impaired, although the sinusoidal structure was maintained in the LSEC-transfer efficient group. Hepatocyte apoptosis was reduced by the efficient suppression of LSEC apoptosis with a novel DDS. Protecting the sinusoidal structure by suppressing LSEC damage will be an effective treatment for acute liver failure.


Optimisation of Microwave-Assisted Extraction of Pomegranate (Punica granatum L.) Seed Oil and Evaluation of Its Physicochemical and Bioactive Properties.
Pomegranate seed oil was extracted in a closed-vessel high-pressure microwave system. The characteristics of the obtained oil, such as fatty acid composition, free fatty acidity, total phenolic content, antioxidant activity and colour, were compared to those of the oil obtained by cold solvent extraction. Response surface methodology was applied to optimise extraction conditions: power (176-300 W), time (5-20 min), particle size (d=0.125-0.800 mm) and solvent to sample ratio (2:1, 6:1 and 10:1, by mass). The predicted highest extraction yield (35.19%) was obtained using microwave power of 220 W, particle size in the range of d=0.125-0.450 mm and solvent-to-sample ratio of 10:1 (by mass) in 5 min extraction time. Microwave-assisted solvent extraction (MASE) resulted in higher extraction yield than that of Soxhlet (34.70% in 8 h) or cold (17.50% in 8 h) extraction. The dominant fatty acid of pomegranate seed oil was punicic acid (86%) irrespective of the extraction method. Oil obtained by MASE had better physicochemical properties, total phenolic content and antioxidant activity than the oil obtained by cold solvent extraction.


Role of E-cadherin in epithelial architecture maintenance.
Morphogenesis and architecture of a developing epithelium is controlled by both cell shape and contacts, mediated by spatially and temporally regulated cell adhesion molecules. The authors study if E-cadherin functions as a key factor of epithelial adhesion and epidermal architecture in vivo. They apply whole-mount digital deconvolution microscopy to evaluate three-dimensional (3D) E-cadherin expression during skin morphogenesis of Rhinella arenarum and in a cell adhesion alteration model. Results show morphogenetic changes in the 3D E-cadherin spatiotemporal expression pattern correlated with the increase of E-cadherin and in the number of cells with hexagonal geometry. Alterations in junction-protein phosphorylation showed drastic loss of E-cadherin and beta-catenin in cell-cell contacts and the increase of cytoplasm and nuclear beta-catenin in epidermis, suggesting the activation of the beta-catenin signal pathway. Surprisingly, no changes in cell shape and skin architecture were registered, suggesting that epidermal E-cadherin appears to be involved in signaling rather than cell contact maintenance in vivo.


Refinement of nanoporous copper by dealloying the Al-Cu alloy in NaOH solution containing sodium dodecyl sulfate.
This work reports the refinement of nanoporous copper (NPC) ligaments by introducing the sodium dodecyl sulfate (SDS) surfactant in the dealloying process. The Al80Cu20 (at%) alloy precursor is chemically dealloyed in a mixed solution of NaOH and SDS surfactant, producing NPC with a hierarchical microstructure. Micron-scaled skeletons that build up higher level networks consist of geometrically similar nano-scaled bi-continuous ligament-pore networks at the lower level. It has been found that the size of the ligaments in the lower level networks reduces from ∼32 nm to ∼24 nm with increasing SDS concentration to 1 mM. Further increasing the SDS concentration to 5 mM only leads to a slight ligament size decrease to ∼21 nm. Remarkably, nano-sized cones are formed on the lower level network surface in the dealloying solution containing 1 mM SDS, and the cone number greatly rises when the SDS concentration increases to 5 mM. The surface diffusivity of Cu adatoms is evaluated based on the experimental data, and the refinement of the ligament as well as the formation of cones are associated with the decreased surface diffusivity and the retarded Cu adatom motions with the addition of SDS. Quantum chemical calculations and molecular dynamics simulations are performed to model the adsorption behavior of SDS. It has been found that the SDS-substrate interaction increases with the number of SDS molecules before SDS reaches saturation.


Studies on the enzymatic degradation of beta-casomorphins.
beta-Casomorphins (beta-CMs), although known to be highly resistant to proteolytic enzymes, are demonstrated to be rapidly degraded in bovine or rat plasma. Degradation of these peptides consisting of the amino acid sequence TYR-PRO-PHE-PRO-GLY-PRO-ILE and C-terminally shortened fragments thereof, may be due to an enzyme identical with or similar to the dipeptidyl-peptidase IV (DP IV) which is known to cleave dipeptide fragments from the N-terminus of peptides after proline residues. This assumption is compatible with the finding that beta-casomorphin (beta-CM) analogues in which the proline residue in position two has been replaced by D-alanine, seem to be completely resistant to enzymatic attack in the plasma.


Results obtained with combination therapy of VM-26, natulan and prednisolone in generalized Hodgkin's disease.
By evaluating the results obtained in 50 patients the authors stated that VM-26 given in combination with Natulan and Prednisolone is a drug of value in the therapy of generalized Hodgkin's disease. It cause milder side effects than drugs previously used in combination therapy. Complete or partial remissions were obtained in 84% of patients treated. 75% of the therapy-resistant cases proved to be Hodgkin's sarcoma by the postmortem examination. Remission lasted longer in stage III than in stage IV and the previously untreated patients responded better than the treated one. Definite correlation could not be revealed between histologic type and duration of remission.


Biochar reduces the bioaccumulation of PAHs from soil to carrot (Daucus carota L.) in the rhizosphere: A mechanism study.
The aim of this study was to reveal the mechanisms on how biochar reduces bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) in tuberous vegetables. Corn straw-derived biochar pyrolyzed at 300°C (CB300) or bamboo-derived biochar pyrolyzed at 700°C (BB700) was amended into PAH-contaminated soil planted with carrot (Daucus carota L.). After 150days, 2% CB300 or 2% BB700 amendments significantly reduced the bioaccumulation of PAHs in carrot root (p<0.05), especially for high-molecular-weight PAHs. In the non-rhizosphere, either CB300 or BB700 suppressed PAH dissipation and decreased the bioavailability via adsorption processes. Compared to the control, the total concentration of PAHs in the rhizosphere was higher in the 2% BB700 treatment but the bioavailable concentration was lower. This indicates that BB700 decreased the bioavailability of PAHs primarily via immobilization (adsorption processes). By contrast, the total and bioavailable PAH concentrations were both lower in the 2% CB300 treatment than those in the control. The abundance of bacteria such as Arthrobacter and Flavobacterium and the total number of genes playing important roles in microbial PAH degradation processes increased significantly (p<0.05), which were likely responsible for the rapid dissipation of PAHs in the 2% CB300 treatment in the rhizosphere. These results indicate that CB300 decreased the PAH bioavailability primarily via increasing degradation of PAHs by indigenous microorganisms. The two biochars both showed better effectiveness at reducing the bioavailability of high-molecular-weight PAHs than the low-molecular-weight PAHs in the rhizosphere. Therefore, the mechanisms on how biochar reduces the PAH uptake into carrot are dependent on the type of biochar (e.g., pyrolysis temperature and feedstock) and root presence.


Implication of hypR in the virulence and oxidative stress response of Enterococcus faecalis.
HypR has recently been described as the first transcriptional regulator involved in the oxidative stress response and in the intracellular survival of Enterococcus faecalis within macrophages. In order to characterize the HypR regulon, real-time quantitative RT-PCR experiments were performed. The expression of four genes involved in the oxidative stress response encoding catalase, glutathione reductase, and the two subunits of alkyl hydroperoxide reductase were down regulated in the hypR background under H(2)O(2) condition. These findings show that HypR acts as a transcriptional activator, especially during oxidative stress. In addition, DNAse I footprinting assays allowed us to identify the HypR-protected DNA regions corresponding to the "HypR box" in the hypR promoter. Moreover, the effect of the hypR mutation on the virulence of E. faecalis was evaluated in comparison with the wild-type JH2-2 strain using a mouse peritonitis model. Our results revealed that HypR appears to be an important virulence factor in E. faecalis.


Chaos, patterns, coherent structures, and turbulence: Reflections on nonlinear science.
The paradigms of nonlinear science were succinctly articulated over 25 years ago as deterministic chaos, pattern formation, coherent structures, and adaptation/evolution/learning. For chaos, the main unifying concept was universal routes to chaos in general nonlinear dynamical systems, built upon a framework of bifurcation theory. Pattern formation focused on spatially extended nonlinear systems, taking advantage of symmetry properties to develop highly quantitative amplitude equations of the Ginzburg-Landau type to describe early nonlinear phenomena in the vicinity of critical points. Solitons, mathematically precise localized nonlinear wave states, were generalized to a larger and less precise class of coherent structures such as, for example, concentrated regions of vorticity from laboratory wake flows to the Jovian Great Red Spot. The combination of these three ideas was hoped to provide the tools and concepts for the understanding and characterization of the strongly nonlinear problem of fluid turbulence. Although this early promise has been largely unfulfilled, steady progress has been made using the approaches of nonlinear science. I provide a series of examples of bifurcations and chaos, of one-dimensional and two-dimensional pattern formation, and of turbulence to illustrate both the progress and limitations of the nonlinear science approach. As experimental and computational methods continue to improve, the promise of nonlinear science to elucidate fluid turbulence continues to advance in a steady manner, indicative of the grand challenge nature of strongly nonlinear multi-scale dynamical systems.


Evaluating venepuncture practice on a general children's ward.
To assess the training for, practice of, and effects of venepuncture in children on a general children's ward. To identify approaches that might reduce the adverse physical and psychological effects related to venepuncture. Questionnaire survey of 51 parents, 39 children and 72 junior doctors following venepuncture in the children. Telephone survey of 25 paediatric senior house officers on venous access training. Parents and children assessed venepuncture as extremely distressing. Parents' assessments of the mean number of venepuncture attempts were markedly higher than those of the doctors surveyed. When carrying out venepuncture, doctors used therapeutic measures much less frequently than expected. Only seven of the 25 departments surveyed offered any training in venepuncture. Venepuncture is consistently one of the most distressing aspects of hospital admission for children. Much could be done to alleviate this, but trainir patchy and interventions shown to reduce distress are not uniformly used.


Quercetin acutely relaxes airway smooth muscle and potentiates β-agonist-induced relaxation via dual phosphodiesterase inhibition of PLCβ and PDE4.
Asthma is a disease of the airways with symptoms including exaggerated airway narrowing and airway inflammation. Early asthma therapies used methylxanthines to relieve symptoms, in part, by inhibiting cyclic nucleotide phosphodiesterases (PDEs), the enzyme responsible for degrading cAMP. The classification of tissue-specific PDE subtypes and the clinical introduction of PDE-selective inhibitors for chronic obstructive pulmonary disease (i.e., roflumilast) have reopened the possibility of using PDE inhibition in the treatment of asthma. Quercetin is a naturally derived PDE4-selective inhibitor found in fruits, vegetables, and tea. We hypothesized that quercetin relaxes airway smooth muscle via cAMP-mediated pathways and augments β-agonist relaxation. Tracheal rings from male A/J mice were mounted in myographs and contracted with acetylcholine (ACh). Addition of quercetin (100 nM-1 mM) acutely and concentration-dependently relaxed airway rings precontracted with ACh. In separate studies, pretreatment with quercetin (100 μM) prevented force generation upon exposure to ACh. In additional studies, quercetin (50 μM) significantly potentiated isoproterenol-induced relaxations. In in vitro assays, quercetin directly attenuated phospholipase C activity, decreased inositol phosphate synthesis, and decreased intracellular calcium responses to Gq-coupled agonists (histamine or bradykinin). Finally, nebulization of quercetin (100 μM) in an in vivo model of airway responsiveness significantly attenuated methacholine-induced increases in airway resistance. These novel data show that the natural PDE4-selective inhibitor quercetin may provide therapeutic relief of asthma symptoms and decrease reliance on short-acting β-agonists.


GENETIC EVIDENCE FOR A PLEISTOCENE POPULATION EXPLOSION.
Expansions of population size leave characteristic signatures in mitochondrial "mismatch distributions." Consequently, these distributions can inform us about the history of changes in population size. Here, I study a simple model of population history that assumes that, t generations before the present, a population grows (or shrinks) suddenly from female size N0 to female size N1 . Although this model is simple, it often provides an accurate description of data generated by complex population histories. I develop statistical methods that estimate θ0 = 2uN0 , θ1 = 2uN1 , and τ = 2ut (where u is the mutation rate), and place a confidence region around these estimates. These estimators are well behaved, and insensitive to simplifying assumptions. Finally, I apply these methods to published mitochondrial data, and infer that a major expansion of the human population occurred during the late Pleistocene.


Comparative Analysis of Serum Allergen sIgE Detected by Western Blotting and Fluorescent Enzyme Immunoassay.
Various new methods to diagnose allergens have gradually developed in recent years. The present study aimed to evaluate the diagnostic performance and clinical utility of Allergy-Q detection system (Proteometech Inc., Korea) on serum allergen-specific IgE (sIgE). Immunoblotting (Allergy-Q system) and fluorescent enzyme immunoassay (ImmunoCAP system, Phadia Inc., Sweden) were used to detect serum total IgE and allergen sIgE of 244 cases of allergic diseases, followed by comparative analysis of the results. The study focused on analyzing 15 kinds of common allergens. Comparison of the two methods showed that the diagnostic performance of qualitative results of AllergyQ system for the majority of allergens was satisfactory, with Dermatophagoides farinae having the highest agreement (96.4%) and sensitivity (97.8%) and Dermatophagoides pteronyssinus having the highest specificity (100%), positive predictive value (100%), and Youden's index (J = 0.951). Scatter plots and Spearman's correlation analysis showed correlations between the quantitative results of the two methods, with the highest correlation for Dermatophagoides pteronyssinus (r = 0.875, p < 0.001). For most common allergens, the Allergy-Q system is an effective method for diagnosis. It is safe, convenient, economical, accurate, and efficient in screening multi-allergens. Moreover, it is good for semi-quantitative detection of allergens in the basic hospitals that are unable to carry out the ImmunoCAP detection, and also for patients with fewer samples. However, its clinical application needs to be validated using a number of samples from a variety of countries and regions.


Hot crystals of thermo-responsive particles with temperature dependent diameter in the presence of a temperature gradient.
Structure formation under non-equilibrium steady state conditions is poorly understood. A non-equilibrium steady state can be achieved in a system by maintaining a temperature gradient. A class of cross-linked microgel particles, such as poly-N-iso-propylacrylamide, is reported to increase in size due to the adsorption of water as the temperature decreases. Here, we study thermo-responsive particles with a temperature sensitive diameter in the presence of a temperature gradient, using molecular dynamics simulations with the Langevin thermostat. We find long-ranged structural order using bond order parameters in both cold and hot regions of the system beyond a certain diameter ratio of the cold and hot particles. This is due to an increase in packing and pressure in both regions. Our observations might be useful in understanding ordered structures under extreme conditions of a non-equilibrium steady state.


Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives.
Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.


The pineal gland hormone melatonin improves survival in a rat model of sepsis/shock induced by zymosan A.
Melatonin has demonstrated protective effects in severe sepsis/shock in the animal model. Zymosan A causes inflammation and shock leading to death in rats. We hypothesized that daily afternoon melatonin administration would improve rat survival after an intraperitoneal (IP) zymosan injection. Adult male rats, maintained on a 12L:12D photoperiod, received a single IP injection of either zymosan (500 mg/kg) or paraffin vehicle at 1200 hours. At 1700 hours and daily thereafter, zymosan-injected rats received subcutaneous injections of either melatonin (0.8 mg/kg) or saline (SAL). Any surviving animals were killed on day 10 to obtain wet organ weights. Three independent experiments produced similar results. In each zymosan+SAL group, all animals died by day 4. In the melatonin-treated groups combined, 33/45 rats survived (73.33%, P<.00002). Posthumous body weight was greater in melatonin-treated animals compared with the zymosan+SAL groups (P<.001). Mean splenic weight in the melatonin-treated groups was twice that of the control groups (P<.001). Melatonin administered in the late afternoon after a lethal dose of zymosan significantly improved animal survival. Melatonin has no known adverse effects in humans and may represent a novel treatment for sepsis/shock.


A hermeneutic phenomenological analysis of aging with a childhood onset disability.
In this qualitative study, we combined multiple interviews, field notes, life history review charts, and demographic questions to explore the life course experiences of 25 women, ages 55 to 65 years, who developed impairments due to paralytic polio during childhood. Based on a hermeneutic phenomenological methodology using thematic analysis, multiple themes emerged that traced their lives from childhood to later adulthood. The women described how they pushed their bodies and dismissed their physical decline as long as possible. The women's early experiences combined with the culturally defined role expectations for women to influence their perceptions of how to react to changing physical abilities with age.


A placenta-specific gene ectopically activated in many human cancers is essentially involved in malignant cell processes.
The identification and functional characterization of tumor-specific genes is a prerequisite for the development of targeted cancer therapies. Using an integrated data mining and experimental validation approach for the discovery of new targets for antibody therapy of cancer, we identified PLAC1. PLAC1 is a placenta-specific gene with no detectable expression in any other normal human tissue. However, it is frequently aberrantly activated and highly expressed in a variety of tumor types, in particular breast cancer. RNAi-mediated silencing of PLAC1 in MCF-7 and BT-549 breast cancer cells profoundly impairs motility, migration, and invasion and induces a G1-S cell cycle block with nearly complete abrogation of proliferation. Knockdown of PLAC1 is associated with decreased expression of cyclin D1 and reduced phosphorylation of AKT kinase. Moreover, PLAC1 is localized on the surface of cancer cells and is accessible for antibodies which antagonize biological functions of this molecule. These features, in summary, make PLAC1 an attractive candidate for targeted immunotherapeutic approaches.


Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.
Biologically active cell penetrating peptides (CPPs) are an emerging class of therapeutic agent. The wasp venom peptide mastoparan is an established CPP that modulates mitochondrial activity and triggers caspase-dependent apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP). Mitochondrial depolarisation and activation of the caspase cascade also underpins the action of dithranol, a topical agent for treatment of psoriasis. The effects of a potent mitP analogue on mitochondrial activity were therefore examined to assess its potential as a novel approach for targeting mitochondria for the treatment of psoriasis. In HaCaT keratinocytes treated with the mitP analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10 μmol L-1, MTT activity was less than 30% that observed in untreated cells. Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also dissipated the mitochondrial membrane potential, with a threefold increase in mitochondrial depolarisation levels. However, caspase activity appeared to be reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly-RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity but does not appear to evoke apoptosis in HaCaT keratinocytes.