Foetal-to-adult transitions in fibroblast phenotype: their possible relevance to the pathogenesis of cancer.
We have previously shown that the migration of foetal, adult and transformed fibroblasts into three-dimensional collagen gels is differentially affected by plating cell density. We now present data indicating that the migration of these fibroblasts is also differentially affected by local cell density in microdomains of the gel surface. In this article we discuss the possible biochemical and behavioural mechanisms that may contribute to the different migratory phenotypes expressed by foetal, adult and transformed fibroblasts; these include: (1) cell-induced alterations in the orientation and or packing density of collagen fibres in the gel; (2) deposition of specific matrix macromolecules by the fibroblasts; (3) social interactions between the cells; and (4) secretion of soluble factors affecting cell migration. We show that foetal fibroblasts secrete a migration stimulating factor (MSF) not produced by adult cells. Incubation of adult fibroblasts in the presence of MSF induces these cells to express a foetal-like migratory phenotype. Foetal fibroblasts undergo a spontaneous foetal-to-adult transition in migratory phenotype after prolonged passage in vitro; this transition is accompanied by a cessation in MSF production. MSF appears to promote fibroblast migration at high cell density by stimulating the deposition of hyaluronic acid in the extracellular matrix. Recent studies have indicated that skin fibroblasts from cancer patients display certain behavioural abnormalities characteristic of transformed and/or foetal cells. In this regard, we have shown that skin fibroblasts from cancer patients commonly express a foetal-like phenotype with respect to migratory behaviour and secretion of MSF: it is of interest to note that these cancer patient fibroblasts are indistinguishable from normal adult cells in other respects, such as morphology in confluent culture. On the basis of these observations, we suggest that: (1) fibroblasts in certain individuals fail to undergo normal foetal-to-adult transitions in a number of phenotypic characteristics; and that (2) the disruption in epithelial-mesenchymal interactions caused by the continued presence of these foetal-like fibroblasts in the adult significantly increases the risk of cancer development.


Conservative and radical oncoplastic approches in the surgical treatment of breast cancer.
In the attempt to optimise the balance between the risk of local recurrence and the cosmetic outcomes in breast surgery, new surgical procedures, so-called oncoplastic techniques, have been introduced in recent years. The term oncoplastic surgery refers to surgery on the basis of oncological principles during which the techniques of plastic surgery are used, mostly for reconstructive and cosmetic reasons. The advantage of the oncoplastic surgery for breast cancer is the possibility of performing a wider excision of the tumour with a good cosmetic result. Oncoplastic surgery is a broad concept that can be used for several different combinations of oncological surgery and plastic surgery: excision of the tumour by reduction mammoplasty, tumour excision followed by remodelling mammoplasty, mastectomy with immediate reconstruction of the breast and partial mastectomy with reconstruction. Careful patient selection and preoperative planning are key components for the success of any oncoplastic operation for breast cancer. Accurate preoperative evaluation of the clinical and biological features of the tumour as well as of the morphological aspects of the breast allow the surgeon to make a decision if a conservative or radical approach is preferable and select the most effective oncoplastic surgical technique. In this review we summarise the indications, advantages and limitations of several oncoplastic procedures.


Y-chromosome analysis reveals genetic divergence and new founding native lineages in Athapaskan- and Eskimoan-speaking populations.
For decades, the peopling of the Americas has been explored through the analysis of uniparentally inherited genetic systems in Native American populations and the comparison of these genetic data with current linguistic groupings. In northern North America, two language families predominate: Eskimo-Aleut and Na-Dene. Although the genetic evidence from nuclear and mtDNA loci suggest that speakers of these language families share a distinct biological origin, this model has not been examined using data from paternally inherited Y chromosomes. To test this hypothesis and elucidate the migration histories of Eskimoan- and Athapaskan-speaking populations, we analyzed Y-chromosomal data from Inuvialuit, Gwich'in, and Tłįch populations living in the Northwest Territories of Canada. Over 100 biallelic markers and 19 chromosome short tandem repeats (STRs) were genotyped to produce a high-resolution dataset of Y chromosomes from these groups. Among these markers is an SNP discovered in the Inuvialuit that differentiates them from other Aboriginal and Native American populations. The data suggest that Canadian Eskimoan- and Athapaskan-speaking populations are genetically distinct from one another and that the formation of these groups was the result of two population expansions that occurred after the initial movement of people into the Americas. In addition, the population history of Athapaskan speakers is complex, with the Tłįch being distinct from other Athapaskan groups. The high-resolution biallelic data also make clear that Y-chromosomal diversity among the first Native Americans was greater than previously recognized.


Relationship between Testicular Volume and Conventional or Nonconventional Sperm Parameters.
Background. Reduced testicular volume (TV) (<12 cm(3)) is associated with lower testicular function. Several studies explored the conventional sperm parameters (concentration, motility, and morphology) and the endocrine function (gonadotropins and testosterone serum concentrations) in the patients with reduction of TV. No other parameters have been examined. Aim. This study aims at evaluating some biofunctional sperm parameters by flow cytometry in the semen of men with reduced TV compared with that of subjects with normal TV. Methods. 78 patients without primary scrotal disease were submitted to ultrasound evaluation of the testis. They were divided into two groups according to testicular volume: A Group, including 40 patients with normal testicular volume (TV > 15 cm(3)) and B Group, including 38 patients with reduced testicular volume (TV ≤ 12 cm(3)). All patients underwent serum hormone concentration, conventional and biofunctional (flow cytometry) sperm parameters evaluation. Results. With regard to biofunctional sperm parameters, all values (mitochondrial membrane potential, phosphatidylserine externalization, chromatin compactness, and DNA fragmentation) were strongly negatively correlated with testicular volume (P < 0.0001). Conclusions. This study for the first time in the literature states that the biofunctional sperm parameters worsen and with near linear correlation, with decreasing testicular volume.


BRAF(V600E) mutation in Turkish patients with papillary thyroid cancer: strong correlation with indicators of tumor aggressiveness.
Papillary thyroid cancer (PTC) constitutes more than 90% of the thyroid cancers. MAP kinase/ERK pathway plays an important role in the development of several cancers. BRAF which is a member of Raf-kinase family activates this way. BRAF gene activating mutations lead to neoplastic transformation in thyroid follicle cells. In PTC, this mutation itself is a poor prognostic sign independent of other clinicopathological characteristics. We evaluated BRAF(V600E) mutation and clinical-pathological characteristics in Turkish population with PTC. We assessed 109 patients with PTC (88 female, 21 male). The average age was 38.7 ± 9.9 (17-71). BRAF(V600E) mutation was detected using polymerase chain reaction and fluorescent melting curve analysis. The results show that BRAF(V600E) mutation rate was found in 39.45% of our patients. We observed that BRAF(V600E) mutation was significantly higher in men, in tumors larger than 1 cm in size, and in patients with classical PTC. Moreover, statistically significant correlations of BRAF(V600E) with indicators of tumor aggressiveness such as thyroid capsular invasion, multifocality, lymph node metastasis, and extrathyroidal spread were found. Patient groups below and over the age of 45 did not differ in mutation frequency. Patients with micro-PTC were evaluated separately, it was found that BRAF(V600E) mutation was more frequent in the classic type and that lymph node metastasis rate significantly increased when the mutation was present. We concluded that BRAF(V600E) was correlated with indicators of tumor aggressiveness in our study population. This fact is taken into consideration in treatment and follow-up of our patients with PTC and positive BRAF(V600E) mutation.


Quasi-interpolating spline models for hexagonally-sampled data.
The reconstruction of a continuous-domain representation from sampled data is an essential element of many image processing tasks, in particular, image resampling. Until today, most image data have been available on Cartesian lattices, despite the many theoretical advantages of hexagonal sampling. In this paper, we propose new reconstruction methods for hexagonally sampled data that use the intrinsically 2-D nature of the lattice, and that at the same time remain practical and efficient. To that aim, we deploy box-spline and hex-spline models, which are notably well adapted to hexagonal lattices. We also rely on the quasi-interpolation paradigm to design compelling prefilters; that is, the optimal filter for a prescribed design is found using recent results from approximation theory. The feasibility and efficiency of the proposed methods are illustrated and compared for a hexagonal to Cartesian grid conversion problem.


A one pot, one step method for the preparation of clickable hydrogels by photoinitiated polymerization.
Current preparation methods for hydrogels based on redox or photopolymerization of water soluble monomers are simple to use, and flexible, but have the drawback of requiring additional modification steps for tuning or introducing properties for specific purposes. We have devised a simple and rapid synthetic strategy to prepare hydrogels possessing reactive sites to incorporate any molecules of interest by "Click Chemistry". The strategy is based on the use of propargyl acrylamide (PAm) as comonomer together with acrylamide (AAm) and N,N'-methylene bisacrylamide (BAAm) as crosslinker in photoinitiated polymerization. With the selective reactivity of photochemically generated free radicals towards acrylic function of PAm, hydrogels with clickable acetylene groups can be prepared in one pot, one step manner. Based on the acetylene functionality, any molecule possessing azide groups can be conjugated onto hydrogel by "Click Chemistry" as demonstrated on the example of fluoroscent azide functional pyrene.


Traditional and novel tools to probe the mitochondrial metabolism in health and disease.
Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α-ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl-CoA, iron-sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer. Therefore, there is great interest in understanding mitochondrial metabolism and the complex relationship it has with other cellular processes. A large number of studies on mitochondrial metabolism have been conducted in the last 50 years, taking a broad range of approaches. In this review, we summarize and discuss the most commonly used tools that have been used to study different aspects of the metabolism of mitochondria: ranging from dyes that monitor changes in the mitochondrial membrane potential and pharmacological tools to study respiration or ATP synthesis, to more modern tools such as genetically encoded biosensors and trans-omic approaches enabled by recent advances in mass spectrometry, computation, and other technologies. These tools have allowed the large number of studies that have shaped our current understanding of mitochondrial metabolism. WIREs Syst Biol Med 2017, 9:e1373. doi: 10.1002/wsbm.1373 For further resources related to this article, please visit the WIREs website.


Health status of people who have provided informal care or support to an adult with chronic disease in the last 5 years: results from a population-based cross-sectional survey in South Australia.
Objective The aim of the present study was to compare the health status of South Australians with recent experience of caring for an adult with chronic disease with non-carers drawn from the same population. Methods Data were collected via the South Australian Health Omnibus, an annual population-based, cross-sectional survey. Respondents were asked whether they had provided care or support in the last 5 years to someone with cancer, heart disease, respiratory disease, mental illness, neurological disease or dementia. Health status was measured using the Short Form-12 version 1 (SF-12) physical and mental component scale summary scores (PCS and MCS respectively), with poor health status defined as ≥0.5 standard deviation below the normative mean. Logistic regression explored characteristics associated with poor health status. Results Of 3033 respondents analysed, 987 (32.5%) reported caring experience. Poor PCS and MCS were associated with carer status, lower-than-degree-level education, employment status other than employed and annual household income less than A$60000. Being Australian born was a protective factor for PCS, whereas factors protective for MCS were being married or in a de facto relationship and age ≥65 years. Conclusions Providing care or support in the last 5 years is independently associated with poorer health status, but not with the magnitude found in studies of current carers. Future research should explore health status recovery after completion of the caring role, and investigate whether relationships between health and socioeconomic status differ for carers versus non-carers. What is known about the topic? Population-based survey studies in Australia and overseas have consistently found that informal carers have worse health status than non-carers. What does this paper add? Including recent as well as current carers in a population-based sample was associated with less effect on health status compared with studies focused on current carers only. This finding is consistent with the possibility that health status recovers during the 5 years after caring. What are the implications for practitioners? Support for Australian carers is warranted to ensure their continuing contributions to society and return to productivity after their caring role is completed.


In search of America's best hospitals. The promise and reality of quality assessment.
"America's Best Hospitals," by US News & World Report, is a sophisticated and influential appraisal of hospital care. Using measures of health care structure, process, and outcome, the report identifies outstanding hospitals in 16 medical specialties through an overall "index of hospital quality." This strong conceptual design, however, has not been adequately implemented because national data sources for all 3 components are severely limited. Most importantly, since there are no national data on process of care, a reputation survey has been used to measure this component of quality. One consequence of reliance on reputation is that a small group of prominent hospitals in each specialty receives such high scores that they automatically rise to the top of the rankings, regardless of structure or outcome score. "America's Best Hospitals" identifies America's best regarded hospitals, but provides limited additional insight into quality. Adequate surveillance and protection of quality in an era of managed care requires measurement systems beyond the scope of existing data and methods.


Effect of low-level laser stimulation on EEG.
Conventional laser stimulation at the acupoint can induce significant brain activation, and the activation is theoretically conveyed by the sensory afferents. Whether the insensible low-level Laser stimulation outside the acupoint could also evoke electroencephalographic (EEG) changes is not known. We designed a low-level laser array stimulator (6 pcs laser diode, wavelength 830 nm, output power 7 mW, and operation frequency 10 Hz) to deliver insensible laser stimulations to the palm. EEG activities before, during, and after the laser stimulation were collected. The amplitude powers of each EEG frequency band were analyzed. We found that the low-level laser stimulation was able to increase the power of alpha rhythms and theta waves, mainly in the posterior head regions. These effects lasted at least 15 minutes after cessation of the laser stimulation. The amplitude power of beta activities in the anterior head regions decreased after laser stimulation. We thought these EEG changes comparable to those in meditation.


Cholinergic nerves mediate stress-induced intestinal transport abnormalities in Wistar-Kyoto rats.
We have previously reported that acute stress alters intestinal transport physiology in Wistar-Kyoto rats, a stress-susceptible strain. In this study, we tested the hypothesis that the abnormalities in these rats are due to cholinergic mechanisms. Atropine- or saline-treated rats were exposed to acute restraint stress, and, subsequently, electrophysiological parameters of excised jejunal segments were assessed in Ussing chambers. Compared with the parent Wistar rat strain, Wistar-Kyoto rats demonstrated significantly greater stress-induced changes in ion secretion and permeability. The activity of cholinesterase in intestinal mucosal homogenates was significantly less in Wistar-Kyoto than in Wistar rats. Atropine pretreatment of rats before stress corrected the epithelial pathophysiology. Our results suggest that stress stimulated the release of acetylcholine, resulting in altered epithelial function in these genetically predisposed rats.


Influence of Dynamic Neuromuscular Stabilization Approach on Maximum Kayak Paddling Force.
The purpose of this study was to examine the effect of Dynamic Neuromuscular Stabilization (DNS) exercise on maximum paddling force (PF) and self-reported pain perception in the shoulder girdle area in flatwater kayakers. Twenty male flatwater kayakers from a local club (age = 21.9 ± 2.4 years, body height = 185.1 ± 7.9 cm, body mass = 83.9 ± 9.1 kg) were randomly assigned to the intervention or control groups. During the 6-week study, subjects from both groups performed standard off-season training. Additionally, the intervention group engaged in a DNS-based core stabilization exercise program (quadruped exercise, side sitting exercise, sitting exercise and squat exercise) after each standard training session. Using a kayak ergometer, the maximum PF stroke was measured four times during the six weeks. All subjects completed the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire before and after the 6-week interval to evaluate subjective pain perception in the shoulder girdle area. Initially, no significant differences in maximum PF and the DASH questionnaire were identified between the two groups. Repeated measures analysis of variance indicated that the experimental group improved significantly compared to the control group on maximum PF (p = .004; Cohen's d = .85), but not on the DASH questionnaire score (p = .731) during the study. Integration of DNS with traditional flatwater kayak training may significantly increase maximum PF, but may not affect pain perception to the same extent.


Membranous Nephropathy: Approaches to Treatment.
Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. This review focuses on mechanisms involved in the pathogenesis of MN and approaches to treatment of this disease. Our understanding of the pathogenesis of primary MN has advanced greatly with the identification of M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A as target antigens whose antibodies serve as biomarkers of this disease. Additional research, including investigations into the roles of complement and melanocortin receptors on the podocyte, may further improve our understanding of how best to treat this condition. Immunosuppressive therapies, including corticosteroids alternating with alkylating agents, and calcineurin inhibitors are partially successful in reducing proteinuria in MN, but their use may be associated with significant adverse effects and a high relapse rate. Novel interventions, including targeting B cells with rituximab as well as treatment with adrenocorticotropic hormone (ACTH), are being investigated. Key Messages: The understanding of treatment targets and availability of new biomarkers has facilitated diagnosis and improved risk stratification for MN and may also be useful for individualizing treatment with a wider range of therapeutic options for patients with MN. Considerable evidence supports the use of B-cell depletion as initial therapy in nephrotic patients with MN. ACTH should be considered for patients who do not respond to traditional therapies such as alkylating agents and calcineurin inhibitors.


Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area.
In this study we investigated the effects of the injection into the supraoptic nucleus (SON) of non-peptide AT1- and AT2-angiotensin II (ANG II) receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP) receptor antagonist d(CH2)5-Tyr(Me)-AVP, on water and 3% NaCl intake induced by the injection of ANG II into the medial septal area (MSA). The effects on water or 3% NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 microliter over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65%, N = 10, P < 0.01) and sodium intake (81%, N = 8, P < 0.01) induced by the injection of ANG II (10 nmol) into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. On the other hand, while there was a decrease in water intake (45%, N = 9, P < 0.01), ANG II-induced sodium intake was significantly increased (70%, N = 8, P < 0.01) following injection of the V1-type vasopressin antagonist d(CH2)5-Tyr(Me)-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses.


The Gram-Positive Bacterial Cell Wall.
The chapter about the Gram-positive bacterial cell wall gives a brief historical background on the discovery of Gram-positive cell walls and their constituents and microscopic methods applied for studying the Gram-positive cell envelope. Followed by the description of the different chemical building blocks of peptidoglycan and the biosynthesis of the peptidoglycan layers and high turnover of peptidoglycan during bacterial growth. Lipoteichoic acids and wall teichoic acids are highlighted as major components of the cell wall. Characterization of capsules and the formation of extracellular vesicles by Gram-positive bacteria close the section on cell envelopes which have a high impact on bacterial pathogenesis. In addition, the specialized complex and unusual cell wall of mycobacteria is introduced thereafter. Next a short back view is given on the development of electron microscopic examinations for studying bacterial cell walls. Different electron microscopic techniques and methods applied to examine bacterial cell envelopes are discussed in the view that most of the illustrated methods should be available in a well-equipped life sciences orientated electron microscopic laboratory. In addition, newly developed and mostly well-established cryo-methods like high-pressure freezing and freeze-substitution (HPF-FS) and cryo-sections of hydrated vitrified bacteria (CEMOVIS, Cryo-electron microscopy of vitreous sections) are described. At last, modern cryo-methods like cryo-electron tomography (CET) and cryo-FIB-SEM milling (focus ion beam-scanning electron microscopy) are introduced which are available only in specialized institutions, but at present represent the best available methods and techniques to study Gram-positive cell walls under close-to-nature conditions in great detail and at high resolution.


Conversion of solar energy into electricity by using duckweed in Direct Photosynthetic Plant Fuel Cell.
In the present study we demonstrate for the first time the possibility for conversion of solar energy into electricity on the principles of Direct Photosynthetic Plant Fuel Cell (DPPFC) technology by using aquatic higher plants. Lemna minuta duckweed was grown autotrophically in specially constructed fuel cells under sunlight irradiation and laboratory lighting. Current and power density up to 1.62±0.10 A.m(-2) and 380±19 mW.m(-2), respectively, were achieved under sunlight conditions. The influence of the temperature, light intensity and day/night sequencing on the current generation was investigated. The importance of the light intensity was demonstrated by the higher values of generated current (at permanently connected resistance) during daytime than those through the nights, indicating the participation of light-dependent photosynthetic processes. The obtained DPPFC outputs in the night show the contribution of light-independent reactions (respiration). The electron transfer in the examined DPPFCs is associated with a production of endogenous mediator, secreted by the duckweed. The plants' adaptive response to the applied polarization is also connected with an enhanced metabolism resulting in an increase of the protein and carbohydrate intracellular content. Further investigations aiming at improvement of the DPPFC outputs and elucidation of the electron transfer mechanism are required for practical application.


The perceived impact of COVID-19 and associated restrictions on young people with epilepsy in the UK: Young people and caregiver survey.
To garner the views of young people with epilepsy and caregivers regarding the impact of COVID-19 and subsequent restrictions in the UK. An online survey was used to explore the views of young people with epilepsy (n = 71) and caregivers (n = 130) in June 2020. It included questions on the impact of the pandemic and associated restrictions on the child's epilepsy and on child and parental wellbeing. One in three young people and 29 % of caregivers reported that the young person's seizures had increased during the pandemic (only 10 % of young people and 8% of caregivers reported a decrease). Half of young people reported that they were more reluctant to go to hospital. Thirty-one percent of young people and 20 % of parents reported difficulties getting epilepsy medication whilst a significant minority of young people (18 %) and caregivers (25 %) reported that the young person had investigations/assessments cancelled by their hospital. The majority of young people reported their sleep (72 %), mood (64 %) and levels of physical activity (53 %) had deteriorated. Caregivers experienced increases in stress (55 %) and anxiety (52 %). Epilepsy nurses were seen as the most helpful support CONCLUSIONS: Results indicate that the pandemic and associated restrictions have had a negative impact on young people with epilepsy. Perceived increases in seizures, reluctance to go to hospital and cancelled investigations are likely to impact on epilepsy management. The wider psychosocial impact is also likely to be significant with increases in child and caregiver mental health problems in an already vulnerable group.


Genetic analysis of complement factor H related 5, CFHR5, in patients with age-related macular degeneration.
To investigate the complement factor H related 5 (CFHR5) gene, encoding a member of the complement factor H family, for the presence of genetic polymorphisms or mutations associated with age-related macular degeneration (AMD). We screened 639 unrelated patients with AMD and 663 age-matched normal controls using direct genomic sequencing of the ten coding exons, along with the immediately flanking intronic DNA. The pathologic impact of the identified sequence variants were analyzed by computational methods using PolyPhen and PMut algorithms. We identified five heterozygous sequence changes in CFHR5. Asp169Asp had a minor allele frequency of 0.001% in patients and 0.014% in controls (p<0.0001), while Arg356His had a minor allele frequency of 0.016% in patients and 0.007% in controls. Val379Leu, Met514Arg, and Cys568Ter were found only in normal controls. In silico analysis predicted Arg356His and Val379Leu to be neutral and benign. Met514Arg was predicted to be pathological and damaging to the function of the CFHR5 protein. No definitive pathogenic CFHR5 mutations have been found in any of 639 unrelated patients with AMD, indicating that sequence variations in CFHR5 do not play a major role in determining AMD susceptibility. However, our findings suggest a possible protective role for Asp169Asp. Further studies of different and larger populations of patient and control samples will be required to address this observation.


Rubber Tree (Hevea brasiliensis) Bark Necrosis Syndrome III: A Physiological Disease Linked to Impaired Cyanide Metabolism.
First attempts to discriminate between tapping panel dryness (TPD) and bark necrosis (BN), two Hevea sp. bark diseases leading to the cessation of latex production, showed differences in latex biochemical characteristics (1). Further, contrary to TPD, BN is characterized by inner phloem necrosis starting at the rootstock/scion junction (RS/S) and spreading upward to the tapping cut. Recent etiological (3) and epidemiological studies did not provide evidence of a causative pathogen for BN, but showed that BN is favored by a combination of various stresses (2). Searching for molecular markers of BN using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses highlighted differential expression of some proteins in the latex and bark, especially a 67-kDa protein, which accumulates in the inner phloem of the BN trees. This protein was identified by peptide microsequencing as a linamarase (cyanogenic β-glucosidase). This led to the suspicion of the involvement of cyanogenesis in the spread of the syndrome inside the inner bark. The cDNAs of enzymes involved in cyanide (CN) metabolism (linamarase, hydroxynitrile lyase, and cyanoalanine synthase) were cloned from our Hevea sp. phloem specific cDNA library. In addition, the most BN-susceptible rubber clones were shown to exhibit higher cyanide potentions in the leaves and bark, together with low cyanoalanine synthase (CAS) gene expression and activity. Furthermore, linamarine (the cyanogene glucoside substrate of linamarase) was shown to accumulate in the phloem at the base of the trunk, especially above the rootstock/scion junction. The results of biochemical and gene expression studies associated with recent ecophysiological advances (2) strongly suggest a possible cell decompartmentalization near the RS/S junction, resulting in a local release of toxic concentration of highly diffusive CN. This, combined with a lethal imbalance between cyanogenic and CN-detoxifying activities (CAS) in the phloem of BN trees, could lead to poisoning of neighboring cells and to the spread of tissue necrosis toward the tapping cut. In conclusion, after providing evidence of exogenous factors favoring BN (2), this report highlights endogenous disorders that may be at the origin of this physiological disease leading to BN. References: (1) D. Nandris et al. Eur. J. For. Pathol. 21:325, 1991. (2) D. Nandris et al. Plant Dis. 88:1047, 2004.


Monitoring strategies in children with asthma: a randomised controlled trial.
Asthma guidelines recommend monitoring of asthma control. However, in a substantial proportion of children, asthma is poorly controlled and the best monitoring strategy is not known. We studied two monitoring strategies for their ability to improve asthma outcomes in comparison with standard care (SC): web-based monthly monitoring with the (Childhood) Asthma Control Test (ACT or C-ACT) and 4-monthly monitoring of FENO. In this randomised controlled, partly blinded, parallel group multicentre trial with a 1-year follow-up, children aged 4-18 with a doctor's diagnosis of asthma treated in seven hospitals were randomised to one of the three groups. In the web group, treatment was adapted according to ACT obtained via a website at 1-month intervals; in the FENO group according to ACT and FENO, and in the SC group according to the ACT at 4-monthly visits. The primary endpoint was the change from baseline in the proportion of symptom-free days (SFD). Two-hundred and eighty children (mean age 10.4 years, 66% boys) were included; 268 completed the study. Mean changes from baseline in SFD were similar between the groups: -2.1% (web group, n=90), +8.9% (FENO group, n=91) versus 0.15% (SC, n=87), p=0.15 and p=0.78. Daily dose of inhaled corticosteroids (ICS) decreased more in the web-based group compared with both other groups (-200 μg/day, p<0.01), while ACT and SFD remained similar. The change from baseline in SFD did not differ between monitoring strategies. With web-based ACT monitoring, ICS could be reduced substantially while control was maintained. NTR 1995.


Prostate cancer after initial high-grade prostatic intraepithelial neoplasia and benign prostate biopsy.
Limited data exist on long term pathological outcomes in patients with initial prostate biopsies showing either high-grade intraepithelial neoplasia (HGPIN) or benign findings, who are subsequently diagnosed with prostate cancer. Preoperative characteristics of patients showing either HGPIN or benign initial prostate biopsies were investigated and compared in patients with and without a subsequent diagnosis of prostate cancer. We also compared the biopsy and prostatectomy findings in patients with prostate cancer in both groups. We evaluated 161 and 85 patients with initial HGPIN and benign prostate biopsies, respectively, who underwent a subsequent biopsy. After a median follow up of 11 years, prostate cancer was detected in 26.7% patients after HGPIN and in 22.3% patients after initial benign biopsy. Ninety-eight percent of positive biopsies after initial HGPIN demonstrated either Gleason score (GS) 3 + 3 (86%) or GS 3 + 4 (12%). In the benign group, 100% of patients demonstrated prostate cancer on biopsy with either GS 3 + 3 (58%) or GS 3 + 4 (42%). Of 35 patients who underwent prostatectomy (22 after initial HGPIN biopsy and 13 after initial benign biopsy), all had node negative, organ-confined disease; 86% and 54% patients had GS6 disease, with = 5% tumor volume found in 91% and 62% of the HGPIN and benign group, respectively. Patients with initial HGPIN or benign biopsies preceding a diagnosis of prostate cancer usually show favourable pathology on positive biopsy and prostatectomy, most commonly exhibiting low volume and low grade disease. These findings may help clinicians risk-stratify patients who may benefit from conservative management options.


Adverse drug events in hospitalized children at Ethiopian University Hospital: a prospective observational study.
The nature and magnitude of adverse drug events (ADEs) among hospitalized children in low-income countries is not well described. The aim of this study was thus, to assess the incidence and nature of ADEs in hospitalized children at a teaching hospital in Ethiopia. We used prospective observational method to study children that were hospitalized to Jimma University Specialized Hospital between 1 February and 1 May 2011. ADEs were identified using review of treatment charts, interview of patient and care-giver, attendance at ward rounds and/or meetings and voluntary staff reports. Two senior pediatric residents evaluated the severity and preventability of ADEs using preset criteria. Logistic regression analysis was employed to determine predictors of ADEs. There were 634 admissions with 6182 patient-days of hospital stay. There were 2072 written medication orders accounting for 35,117 medication doses. Fifty eight ADEs were identified with an incidence of 9.2 per 100 admissions, 1.7 per 1000 medication doses and 9.4 per 1000 patient-days. One-third of ADEs were preventable; 47% of these were due to errors in the administration stage of medication use process. Regarding the severity of ADEs, 91% caused temporary harms and 9% resulted in permanent harm/death. Anti-infective drugs were the most common medications associated with ADEs. The occurrence of ADEs increased with age, length of hospital stay, and use of CNS, endocrine and antihistamine medicines. ADEs are common in hospitalized children in low-income settings; however, one-third deemed preventable. A strategy to prevent the occurrence and consequences of ADEs including education of nurses/physicians is of paramount importance.


Background music as a risk factor for distraction among young-novice drivers.
There are countless beliefs about the power of music during driving. The last thing one would think about is: how safe is it to listen or sing to music? Unfortunately, collisions linked to music devices have been known for some time; adjusting the radio controls, swapping tape-cassettes and compact-discs, or searching through MP3 files, are all forms of distraction that can result in a near-crash or crash. While the decrement of vehicular performance can also occur from capacity interference to central attention, whether or not music listening is a contributing factor to distraction is relatively unknown. The current study explored the effects of driver-preferred music on driver behavior. 85 young-novice drivers completed six trips in an instrumented Learners Vehicle. The study found that all participants committed at-least 3 driver deficiencies; 27 needed a verbal warning/command and 17 required a steering or braking intervention to prevent an accident. While there were elevated positive moods and enjoyment for trips with driver-preferred music, this background also produced the most frequent severe driver miscalculations and inaccuracies, violations, and aggressive driving. However, trips with music structurally designed to generate moderate levels of perceptual complexity, improved driver behavior and increased driver safety. The study is the first within-subjects on-road high-dose double-exposure clinical-trial investigation of musical stimuli on driver behavior.


A specific amyloid-beta protein assembly in the brain impairs memory.
Memory function often declines with age, and is believed to deteriorate initially because of changes in synaptic function rather than loss of neurons. Some individuals then go on to develop Alzheimer's disease with neurodegeneration. Here we use Tg2576 mice, which express a human amyloid-beta precursor protein (APP) variant linked to Alzheimer's disease, to investigate the cause of memory decline in the absence of neurodegeneration or amyloid-beta protein amyloidosis. Young Tg2576 mice (< 6 months old) have normal memory and lack neuropathology, middle-aged mice (6-14 months old) develop memory deficits without neuronal loss, and old mice (> 14 months old) form abundant neuritic plaques containing amyloid-beta (refs 3-6). We found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta assembly, which we term Abeta*56 (Abeta star 56). Abeta*56 purified from the brains of impaired Tg2576 mice disrupts memory when administered to young rats. We propose that Abeta*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.


A phase I study of concurrent chemotherapy (paclitaxel and carboplatin) and thoracic radiotherapy with swallowed manganese superoxide dismutase plasmid liposome protection in patients with locally advanced stage III non-small-cell lung cancer.
Manganese superoxide dismutase (MnSOD) is a genetically engineered therapeutic DNA/liposome containing the human MnSOD transgene. Preclinical studies in mouse models have demonstrated that the expression of the human MnSOD transgene confers protection of normal tissues from ionizing irradiation damage. This is a phase I study of MnSOD plasmid liposome (PL) in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (carboplatin and paclitaxel) was given weekly (for 7 weeks), concurrently with radiation. MnSOD PL was swallowed twice a week (total 14 doses), at three dose levels: 0.3, 3, and 30 mg. Dose escalation followed a standard phase I design. Esophagoscopy was done at baseline, day 4, and 6 weeks after radiation with biopsies of the squamous lining cells. DNA was extracted and analyzed by PCR for the detection of the MnSOD transgene DNA. Ten patients with AJCC stage IIIA (three) and IIIB (seven) completed the course of therapy. Five had squamous histology, two adenocarcinoma, one large cell, and two not specified. Patients were treated in three cohorts at three dose levels of MnSOD PL: 0.3 (three patients), 3 (three patients), and 30 mg (four patients). The median dose of radiation was 77.7 Gy (range 63-79.10 Gy). Overall response rate for the standard chemoradiation regimen was 70% (n = 10). There were no dose-limiting toxicities reported in all three dosing tiers. It is concluded that the oral administration of MnSOD PL is feasible and safe. The phase II recommended dose is 30 mg.


Microcontroller-driven fluid-injection system for atomic force microscopy.
We present a programmable microcontroller-driven injection system for the exchange of imaging medium during atomic force microscopy. Using this low-noise system, high-resolution imaging can be performed during this process of injection without disturbance. This latter circumstance was exemplified by the online imaging of conformational changes in DNA molecules during the injection of anticancer drug into the fluid chamber.


Implementation of safety standards of compounded sterile preparations in hospital pharmacies: a multinational cross-sectional study.
To evaluate implementation of safety standards of compounded sterile preparations in different hospitals. This cross-sectional study included 124 hospitals from 19 countries. A survey was developed based on the guidelines and safety practices of the Institute for Safe Medication Practices (ISMP) for sterile preparations compounding, and was sent to the members of the Intravenous and Parenteral Nutrition experts' network (IV PN experts' network) in the Gulf region and beyond using SurveyMonkey software. 124 pharmacists were invited to participate in this study. Only 39 (31.5%) pharmacists from seven countries responded: 16 (41%) of the participants were pharmacy supervisors, and 23 (59%) had >10 years of work experience. However, a majority, 27 (69%), of the respondents were from Saudi Arabia. Written policies and procedures for sterile preparations compounding were available in 37 (95%) hospitals. The concentrated electrolytes were removed from all patient care areas in 28 (72%) hospitals, and 30 (77%) hospitals clearly labelled those as high-alert medications. The use of advanced technologies, such as bar code verification or IV robotics, for compounding sterile preparations were not implemented in 27 (69%) hospitals. Minimum standards and best practice recommendations to ensure safety of sterile preparation compounding were implemented in many hospitals of different countries. However, advanced technologies were not implemented by the majority of the hospitals.


The Mickey Finn defense: involuntary intoxication and insanity.
The legal context of voluntary and involuntary intoxication is delineated. The author reports a case of involuntary intoxication involving scopolamine toxic psychosis or delirium, in which he testified as a psychiatric expert witness. The specific psychological and physiological symptomatology produced by scopolamine intoxication is outlined. The forensic psychiatrist should be alert to the involuntary intoxication defense in these cases and should familiarize himself with the specific toxicity of scopolamine, in view of the significant increase in the number of incidents in which it is utilized as "knockout" drops in certain jurisdictions.


Genome-Wide Association Study of Spot Form of Net Blotch Resistance in the Upper Midwest Barley Breeding Programs.
Pyrenophora teres f. maculata, the causal agent of spot form of net blotch (SFNB), is an emerging pathogen of barley in the United States and Australia. Compared with net form of net blotch (NFNB), less is known in the U.S. Upper Midwest barley breeding programs about host resistance and quantitative trait loci (QTL) associated with SFNB in breeding lines. The main objective of this study was to identify QTL associated with SFNB resistance in the Upper Midwest two-rowed and six-rowed barley breeding programs using a genome-wide association study approach. A total of 376 breeding lines of barley were evaluated for SFNB resistance at the seedling stage in the greenhouse in Fargo in 2009. The lines were genotyped with 3,072 single nucleotide polymorphism (SNP) markers. Phenotypic evaluation showed a wide range of variability among populations from the four breeding programs and the two barley-row types. The two-rowed barley lines were more susceptible to SFNB than the six-rowed lines. Continuous distributions of SFNB severity indicate the quantitative nature of SFNB resistance. The mixed linear model (MLM) analysis, which included both population structure and kinship matrices, was used to identify significant SNP-SFNB associations. Principal component analysis was used to control false marker-trait association. The linkage disequilibrium (LD) estimates varied among chromosomes (10 to 20 cM). The MLM analysis identified 10 potential QTL in barley: SFNB-2H-8-10, SFNB-2H-38.03, SFNB-3H-58.64, SFNB-3H-78.53, SFNB-3H-91.88, SFNB-3H-117.1, SFNB-5H-155.3, SFNB-6H-5.4, SFNB-6H-33.74, and SFNB-7H-34.82. Among them, four QTL (SFNB-2H-8-10, SFNB-2H-38.03 SFNB-3H-78.53, and SFNB-3H-117.1) have not previously been published. Identification of SFNB resistant lines and QTL associated with SFNB resistance in this study will be useful in the development of barley genotypes with better SFNB resistance.


Acoustically evoked auditory change complex in children with auditory neuropathy spectrum disorder: a potential objective tool for identifying cochlear implant candidates.
The overall aim of the study was to evaluate the feasibility of using electrophysiological measures of the auditory change complex (ACC) to identify candidates for cochlear implantation in children with auditory neuropathy spectrum disorder (ANSD). To achieve this overall aim, this study (1) assessed the feasibility of measuring the ACC evoked by temporal gaps in a group of children with ANSD across a wide age range and (2) investigated the association between gap detection thresholds (GDTs) measured by the ACC recordings and open-set speech-perception performance in these subjects. Nineteen children with bilateral ANSD ranging in age between 1.9 and 14.9 years (mean: 7.8 years) participated in this study. Electrophysiological recordings of the auditory event-related potential (ERP), including the onset ERP response and the ACC, were completed in all subjects and open-set speech perception was evaluated for a subgroup of 16 subjects. For the ERP recordings, the stimulus was a Gaussian noise presented through ER-3A insert earphones to the test ear. Two stimulation conditions were used. In the "control condition," the stimulus was an 800-msec Gaussian noise. In the "gapped condition," the stimuli were two noise segments, each being 400 msec in duration, separated by one of five gaps (i.e., 5, 10, 20, 50, or 100 msec). The interstimulation interval was 1200 msec. The aided open-set speech perception ability was assessed using the Phonetically Balanced Kindergarten (PBK) word lists presented at 60 dB SPL using recorded testing material in a sound booth. For speech perception tests, subjects wore their hearing aids at the settings recommended by their clinical audiologists. For a subgroup of five subjects, psychophysical GDTs for the Gaussian noise were also assessed using a three-interval, three-alternative forced-choice procedure. Responses evoked by the onset of the Gaussian noise (i.e., onset responses) were recorded in all stimulation conditions from all subjects tested in this study. The presence/absence, peak latency and amplitude, and response width of the onset response did not correlate with aided PBK word scores. The objective GDTs measured with the ACC recordings from 17 subjects ranged from 10 to 100 msec. The ACC was not recorded from two subjects for any gap durations tested in this study. There was a robust negative correlation between objective GDTs and aided PBK word scores. In general, subjects with prolonged objective GDTs showed low-aided PBK word scores. GDTs measured using electrophysiological recordings of the ACC correlated well with those measured using psychophysical procedures in four of five subjects who were evaluated using both procedures. The clinical application of the onset response in predicting open-set speech-perception ability is relatively limited in children with ANSD. The ACC recordings can be used to objectively evaluate temporal resolution abilities in children with ANSD having no severe comorbidities, and who are older than 1.9 years. The ACC can potentially be used as an objective tool to identify poor performers among children with ANSD using properly fit amplification, and who are thus, cochlear implant candidates.


Determinants of long-term satisfaction after vertical banded gastroplasty.
The long-term usefulness of vertical banded gastroplasty (VBG) in achieving weight loss is controversial, and adverse effects related to the procedure may attenuate patient satisfaction. Our objective was to evaluate patient satisfaction, and to identify parameters that are related to such satisfaction, 3 to10 years after VBG. All consecutive patients who underwent VBG in one surgical ward were invited for a follow-up study 3 to 10 years after surgery. Questions relating to symptoms and quality of life were evaluated in a personal interview using a structured questionnaire. Of the 122 patients who underwent VBG from 1986 to 1992, 75 patients were located and agreed to participate in the follow-up study. The average time since surgery was 5.4 +/- 1.8 years. The average weight loss was 24.9 +/- 12.4%, representing an excess body-weight loss of 58.6 +/- 30.4%. Overall, 65% of the patients were satisfied with the results of surgery while 19% expressed dissatisfaction. Significant improvement was seen in respiratory difficulties, ability to perform physical exercise, and mental status. Successful weight loss and the frequency of respiratory difficulties were the only independent parameters associated with patient satisfaction. Although vomiting, gastroesophageal reflux and difficulty in swallowing occurred in over two-thirds of the patients, their presence was not correlated with patient dissatisfaction. Despite the presence of a multitude of adverse effects, the majority of our patients were satisfied with the long-term results of VBG. Successful weight loss and improvement in respiratory difficulties were the major determinants of patient satisfaction.


Complete chloroplast genome sequence of an orchid model plant candidate: Erycina pusilla apply in tropical Oncidium breeding.
Oncidium is an important ornamental plant but the study of its functional genomics is difficult. Erycina pusilla is a fast-growing Oncidiinae species. Several characteristics including low chromosome number, small genome size, short growth period, and its ability to complete its life cycle in vitro make E. pusilla a good model candidate and parent for hybridization for orchids. Although genetic information remains limited, systematic molecular analysis of its chloroplast genome might provide useful genetic information. By combining bacterial artificial chromosome (BAC) clones and next-generation sequencing (NGS), the chloroplast (cp) genome of E. pusilla was sequenced accurately, efficiently and economically. The cp genome of E. pusilla shares 89 and 84% similarity with Oncidium Gower Ramsey and Phalanopsis aphrodite, respectively. Comparing these 3 cp genomes, 5 regions have been identified as showing diversity. Using PCR analysis of 19 species belonging to the Epidendroideae subfamily, a conserved deletion was found in the rps15-trnN region of the Cymbidieae tribe. Because commercial Oncidium varieties in Taiwan are limited, identification of potential parents using molecular breeding method has become very important. To demonstrate the relationship between taxonomic position and hybrid compatibility of E. pusilla, 4 DNA regions of 36 tropically adapted Oncidiinae varieties have been analyzed. The results indicated that trnF-ndhJ and trnH-psbA were suitable for phylogenetic analysis. E. pusilla proved to be phylogenetically closer to Rodriguezia and Tolumnia than Oncidium, despite its similar floral appearance to Oncidium. These results indicate the hybrid compatibility of E. pusilla, its cp genome providing important information for Oncidium breeding.


Reducing obesity via a school-based interdisciplinary intervention among youth: Planet Health.
To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grades 6 to 8. Randomized, controlled field trial with 5 intervention and 5 control schools. Outcomes were assessed using preintervention (fall 1995) and follow-up measures (spring 1997), including prevalence, incidence, and remission of obesity. A group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities. Students participated in a school-based interdisciplinary intervention over 2 school years. Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education. Sessions focused on decreasing television viewing, decreasing consumption of high-fat foods, increasing fruit and vegetable intake, and increasing moderate and vigorous physical activity. Obesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles. Because schools were randomized, rather than students, the generalized estimating equation method was used to adjust for individual-level covariates under cluster randomization. The prevalence of obesity among girls in intervention schools was reduced compared with controls, controlling for baseline obesity (odds ratio, 0.47; 95% confidence interval, 0.24-0.93; P = .03), with no differences found among boys. There was greater remission of obesity among intervention girls vs. control girls (odds ratio, 2.16; 95% confidence interval, 1.07-4.35; P = .04). The intervention reduced television hours among both girls and boys, and increased fruit and vegetable consumption and resulted in a smaller increment in total energy intake among girls. Reductions in television viewing predicted obesity change and mediated the intervention effect. Among girls, each hour of reduction in television viewing predicted reduced obesity prevalence (odds ratio, 0.85; 95% confidence interval, 0.75-0.97; P = .02). Planet Health decreased obesity among female students, indicating a promising school-based approach to reducing obesity among youth.


Wounding-induced WRKY8 is involved in basal defense in Arabidopsis.
The WRKY family of plant transcription factors controls several types of plant stress responses. Arabidopsis WRKY8, localized to the nucleus, is mainly induced by abscissic acid, H(2)O(2), wounding, Pseudomonas syringae and Botrytis cinerea infection, and aphid and maggot feeding. To determine its biological functions, we isolated loss-of-function T-DNA insertion mutants and generated gain-of-function overexpressing WRKY8 transgenic plants in Arabidopsis. Plants expressing the mutated WRKY8 gene showed increased resistance to P. syringae but slightly decreased resistance to B. cinerea. In contrast, transgenic plants overexpressing WRKY8 were more susceptible to P. syringae infection but more resistant to B. cinerea infection. The contrasting responses to the two pathogens were correlated with opposite effects on pathogen-induced expression of two genes; salicylic acid-regulated PATHOGENESIS-RELATED1 (PR1) and jasmonic acid-regulated PDF1.2. Therefore, our results suggest that WRKY8 is a negative regulator of basal resistance to P. syringae and positive regulator to B. cinerea.


Temperature fluctuations during development reduce male fitness and may limit adaptive potential in tropical rainforest Drosophila.
Understanding the potential for organisms to tolerate thermal stress through physiological or evolutionary responses is crucial given rapid climate change. Although climate models predict increases in both temperature mean and variance, such tolerances are typically assessed under constant conditions. We tested the effects of temperature variability during development on male fitness in the rainforest fly Drosophila birchii, by simulating thermal variation typical of the warm and cool margins of its elevational distribution, and estimated heritabilities and genetic correlations of fitness traits. Reproductive success was reduced for males reared in warm (mean 24 °C) fluctuating (±3 °C) vs. constant conditions but not in cool fluctuating conditions (mean 17 °C), although fluctuations reduced body size at both temperatures. Male reproductive success under warm fluctuating conditions was similar to that at constant 27 °C, indicating that briefly exceeding critical thermal limits has similar fitness costs to continuously stressful conditions. There was substantial heritable variation in all traits. However, reproductive success traits showed no genetic correlation between treatments reflecting temperature variation at elevational extremes, which may constrain evolutionary responses at these ecological margins. Our data suggest that even small increases in temperature variability will threaten tropical ectotherms living close to their upper thermal limits, both through direct effects on fitness and by limiting their adaptive potential.


The use of ayurvedic medicine in the context of health promotion--a mixed methods case study of an ayurvedic centre in Sweden.
Ayurveda has its historical roots in India, but has also been internationalised, partly via migration and partly through an increased interest in alternative medicine in the West, where studies point toward increased use. However, there is to date scarce knowledge about the use and experiences of ayurveda in Sweden. We have conducted a case study of a center for ayurvedic healthcare in Sweden. We have collected information on client background data from the center's documentation, and compiled data from all clients who visited the centre for ayurvedic consultation during spring 2014. In total, 55 individuals were included in the study, and 18 of them were chosen for individual semi-structured interviews, to gain a deeper understanding of their motives for seeking, and experiences of ayurvedic health care. The material was analysed and compiled through a mix of qualitative and quantitative methods. Among the 55 clients, 91% were female the mean age was 47 years, and 64% gave a specific illness as a reason for seeking ayurveda. The most common illnesses were respiratory, musculoskeletal, circulatory, tumor, and cutaneous illnesses. The qualitative results showed that ayurveda was being used in combination with other methods, including various diets, other alternative medicine methods and conventional medicine. Some participants recounted having sought ayurveda as a complement to conventional medicine, or in cases when conventional medicine had been experienced as insufficient in terms of diagnosis or treatment. However, some participants experienced it as difficult to follow the ayurvedic life-style advice in the midst of their everyday life. Many participants reported positive experiences of pulse diagnostics, which was the main diagnostic method used in ayurvedic consultation. Some reported concrete, physical improvement of their symptoms. This study points towards important aspects of participant experience of ayurveda, that may be subject to further research. The positive effects experienced by some clients should be studied more systematically in order to discern whether they are specific or non-specific. In addition, interesting knowledge may be gained through further study of the reported positive experiences of pulse diagnosis.


LS-VISM: A software package for analysis of biomolecular solvation.
We introduce a software package for the analysis of biomolecular solvation. The package collects computer codes that implement numerical methods for a variational implicit-solvent model (VISM). The input of the package includes the atomic data of biomolecules under consideration and the macroscopic parameters such as solute-solvent surface tension, bulk solvent density and ionic concentrations, and the dielectric coefficients. The output includes estimated solvation free energies and optimal macroscopic solute-solvent interfaces that are obtained by minimizing the VISM solvation free-energy functional among all possible solute-solvent interfaces enclosing the solute atoms. We review the VISM with various descriptions of electrostatics. We also review our numerical methods that consist mainly of the level-set method for relaxing the VISM free-energy functional and a compact coupling interface method for the dielectric Poisson-Boltzmann equation. Such numerical methods and algorithms constitute the central modules of the software package. We detail the structure of the package, format of input and output files, workflow of the codes, and the postprocessing of output data. Our demo application to a host-guest system illustrates how to use the package to perform solvation analysis for biomolecules, including ligand-receptor binding systems. The package is simple and flexible with respect to minimum adjustable parameters and a wide range of applications. Future extensions of the package use can include the efficient identification of ligand binding pockets on protein surfaces.


Outcomes of 807 Thompson hip hemiarthroplasty procedures and the effect of surgical approach on dislocation rates.
The majority of displaced intracapsular fractures in our unit are managed with a Thompson hip hemiarthroplasty. Recent UK guidance from the National Institute for Health and Care Excellence has, however, advised against the continued used of the Thompson implant in patients with hip fracture. The aim of this study was to review the outcomes and complications after Thompson hip hemiarthroplasty, including the impact of modern surgical approaches and cementing, whilst controlling for confounding factors. We reviewed the outcomes following Thompson hip hemiarthroplasty from a series of 807 cases performed between April 2008 and November 2013. Of these, 721 (89.3%) were cemented and 86 (10.7%) uncemented. A total of 575 (71.3%) procedures were performed in female patients. The anterolateral approach was performed in 753 (93.3%) and the posterior approach with enhanced soft tissue repair in 54 (6.7%). Overall, there were 23 dislocations (2.9%). Dislocation following the posterior approach occurred in 13.0% (seven of 54) in comparison to 2.1% (16 of 753) with the anterolateral approach (odds ratio (OR) 8.5 (95% confidence interval (CI) 2.8-26.3), p < 0.001). Patients were discharged home in 459 cases (56.9%), to a care home or other hospital in 273 cases (33.8%). Of the total number of patients, 75 died during their admission (9.3%), and 51.8% (338 of 653) returned home within 30 days. The 30-day mortality was 7.1% (57 cases) and the 1-year mortality was 16.6% (116 of 699). We recommend against the continued use of the posterior approach in hip hemiarthroplasty, as enhanced soft tissue repair did not reduce the dislocation rates to an acceptable level in this series utilising the Thompson implant. Our findings, however, demonstrate satisfactory results for patients treated with the Thompson hip hemiarthroplasty performed through an anterolateral approach. We suggest that the continued use of this implant in a carefully selected patient cohort is justifiable.


BactQuant: an enhanced broad-coverage bacterial quantitative real-time PCR assay.
Bacterial load quantification is a critical component of bacterial community analysis, but a culture-independent method capable of detecting and quantifying diverse bacteria is needed. Based on our analysis of a diverse collection of 16 S rRNA gene sequences, we designed a broad-coverage quantitative real-time PCR (qPCR) assay--BactQuant--for quantifying 16 S rRNA gene copy number and estimating bacterial load. We further utilized in silico evaluation to complement laboratory-based qPCR characterization to validate BactQuant. The aligned core set of 4,938 16 S rRNA gene sequences in the Greengenes database were analyzed for assay design. Cloned plasmid standards were generated and quantified using a qPCR-based approach. Coverage analysis was performed computationally using >670,000 sequences and further evaluated following the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. A bacterial TaqMan® qPCR assay targeting a 466 bp region in V3-V4 was designed. Coverage analysis showed that 91% of the phyla, 96% of the genera, and >80% of the 89,537 species analyzed contained at least one perfect sequence match to the BactQuant assay. Of the 106 bacterial species evaluated, amplification efficiencies ranged from 81 to 120%, with r2-value of >0.99, including species with sequence mismatches. Inter- and intra-run coefficient of variance was <3% and <16% for Ct and copy number, respectively. The BactQuant assay offers significantly broader coverage than a previously reported universal bacterial quantification assay BactQuant in vitro performance was better than the in silico predictions.


[Shock in children; no child's play].
Shock comprises of circulatory insufficiency accompanied by a discrepancy between oxygen demand and supply at tissue level. This results in tissue hypoxia, which when persisting, can lead to (severe) organ failure. In this article we will discuss pathophysiologic backgrounds of shock following the mechanisms that cause hemodynamic deterioration and tissue hypoxia. Subsequently the role of various cytokines in the pathogenesis of septic shock, which occurs relatively frequent in childhood, are discussed. As far as fluid substitution and vasoactive medication is concerned, therapeutic strategies can be chosen more rationally these days. This is mainly due to the availability of smaller i.v. cannula, central venous catheters and advances in (non) invasive hemodynamic measurements in childhood e.g. central venous pressure, cardiac output, peripheral vascular resistance and left ventricular shortening fraction. Despite these developments, shock (in particular septic shock) remains to have a high mortality, also in childhood.


Durability of antibody response against hepatitis B virus in healthcare workers vaccinated as adults.
Follow-up studies of recipients of hepatitis B vaccine from endemic areas have reported loss of antibody to hepatitis B surface antigen (anti-HBs) in a high proportion of persons vaccinated at birth. In contrast, the long-term durability of antibody in persons vaccinated as adults in nonendemic areas is not well defined. We aimed to assess the durability of anti-HBs among healthcare workers (HCWs) vaccinated as adults and response to a booster among those without protective levels of antibody. Adult HCWs aged 18-60 at the time of initial vaccination were recruited. All were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and anti-HBs level. HCWs with anti-HBs <12 mIU/mL were offered a booster and levels were measured 1, 7, and 21 days afterward. Anti-HBs levels were <12 mIU/mL in 9 of 50 (18%), 13 of 50 (26%), and 14 of 59 (24%) HCWs 10-15, 16-20, and >20 years postvaccination, respectively, (P = ns). Four HCWs were anti-HBc positive; none had HBsAg. By logistic regression, older age at vaccination was the only predictor of inadequate anti-HBs level (P = .0005). Thirty-four of 36 subjects with inadequate anti-HBs levels received a booster and 32 (94%) developed levels >12 mIU/mL within 3 weeks. Anti-HBs levels decrease after 10-31 years and fall below a level considered protective in approximately 25% of cases. The rapid and robust response to a booster vaccine suggests a long-lasting amnestic response. Hepatitis B vaccination provides long-term protection against hepatitis B and booster vaccination does not appear to be necessary in HCWs. Clinical Trials Registration. NCT01182311.


Costs and Effects of an Ambulatory Geriatric Unit (the AGe-FIT Study): A Randomized Controlled Trial.
To examine costs and effects of care based on comprehensive geriatric assessment (CGA) provided by an ambulatory geriatric care unit (AGU) in addition to usual care. Assessor-blinded, single-center randomized controlled trial. AGU in an acute hospital in southeastern Sweden. Community-dwelling individuals aged 75 years or older who had received inpatient hospital care 3 or more times in the past 12 months and had 3 or more concomitant medical diagnoses were eligible for study inclusion and randomized to the intervention group (IG; n = 208) or control group (CG; n = 174). Mean age (SD) was 82.5 (4.9) years. Participants in the IG received CGA-based care at the AGU in addition to usual care. The primary outcome was number of hospitalizations. Secondary outcomes were days in hospital and nursing home, mortality, cost of public health and social care, participant' sense of security in care, and health-related quality of life (HRQoL). Baseline characteristics did not differ between groups. The number of hospitalizations did not differ between the IG (2.1) and CG (2.4), but the number of inpatient days was lower in the IG (11.1 vs 15.2; P = .035). The IG showed trends of reduced mortality (hazard ratio 1.51; 95% confidence interval [CI] 0.988-2.310; P = .057) and an increased sense of security in care interaction. No difference in HRQoL was observed. Costs for the IG and CG were 33,371 £ (39,947 £) and 30,490 £ (31,568 £; P = .432). This study of CGA-based care was performed in an ambulatory care setting, in contrast to the greater part of studies of the effects of CGA, which have been conducted in hospital settings. This study confirms the superiority of this type of care to elderly people in terms of days in hospital and sense of security in care interaction and that a shift to more accessible care for older people with multimorbidity is possible without increasing costs. This study can aid the planning of future interventions for older people. clinicaltrials.gov identifier: NCT01446757.


Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage.
The profibrogenic role of transforming growth factor (TGF)-beta in liver has mostly been attributed to hepatic stellate cell activation and excess matrix synthesis. Hepatocytes are believed to contribute to increased rates of apoptosis. Primary hepatocyte outgrowths and AML12 cells were used as an in vitro model to detect TGF-beta effects on the cellular phenotype and expression profile. Furthermore, a transgenic mouse model was used to determine the outcome of hepatocyte-specific Smad7 expression on fibrogenesis following CCl(4)-dependent damage. Samples from patients with chronic liver diseases were assessed for (partial) epithelial-to-mesenchymal transition (EMT) in hepatocytes. In primary cell cultures and in vivo, the majority of hepatocytes survive despite activated TGF-beta signaling. These cells display phenotypic changes and express proteins characteristic for (partial) EMT and fibrogenesis. Experimental expression of Smad7 in hepatocytes of mice attenuated TGF-beta signaling and EMT, resulted in less accumulation of interstitial collagens, and improved CCl(4)-provoked liver damage and fibrosis scores compared with controls. The data indicate that hepatocytes undergo TGF-beta-dependent EMT-like phenotypic changes and actively participate in fibrogenesis. Furthermore, ablation of TGF-beta signaling specifically in this cell type is sufficient to blunt the fibrogenic response.


[Influence of nifedipine on the neuromuscular block produced by atracurium and cistracurium: study in rat phrenic-diaphragmatic nerve preparation.].
Calcium channel blockers may interact with neuromuscular blockers, increasing its effects. Research studies about this interaction display controversial results. In some studies these drugs produced neuromuscular blockage, or contracture, or no effect at all was proved over skeletal neuromuscular response. This study assessed the nifedipine effects over muscular responses and its possible interaction with neuromuscular blockers in rat diaphragm. A number of 25 rats were used, weighing between 250 and 300 g and sacrificed under anesthesia with intraperitoneal pentobarbital (40 mg.kg-1). Preparation was mounted according to the technique described by Bulbring. Diaphragm was kept under tension, connected to an isometric transducer and subjected to an indirect stimulation of 0.1 Hz frequency. Diaphragm contractions were registered on a physiograph. In order to evaluate the effect of these drugs on neuromuscular transmission, they were added separately or associated to the preparation, on the following concentrations: nifedipine (4 microg.mL-1); atracurium (20 microg.mL-1); cistracurium (3 microg.mL-1). On phrenic-nerve preparation, the assessed items were: 1) the extent of diaphragm muscle response to indirect stimulation, before and 45 minutes after adding nifedipine and neuromuscular blockers separately and after the association of both drugs; 2) nifedipine effects on membrane potentials (MP) and miniature end-plate potentials (MEPP). Employed separately, nifedipine did not alter the extent of muscular responses, but it did significantly increase the neuromuscular blocking activity of atracurium and cistracurium. Nifedipine did not alter the membrane potential and caused an initial increase on MEPP frequencies, followed by a blockage. Nifedipine, on the employed concentration, increased the neuromuscular blockage produced by atracurium and cistracurium. Electrophysiological studies demonstrate the existence of presynaptic action and absence of depolarizing action over the muscle fiber.


Anti-plasmodial activity of Dicoma tomentosa (Asteraceae) and identification of urospermal A-15-O-acetate as the main active compound.
Natural products could play an important role in the challenge to discover new anti-malarial drugs. In a previous study, Dicoma tomentosa (Asteraceae) was selected for its promising anti-plasmodial activity after a preliminary screening of several plants traditionally used in Burkina Faso to treat malaria. The aim of the present study was to further investigate the anti-plasmodial properties of this plant and to isolate the active anti-plasmodial compounds. Eight crude extracts obtained from D. tomentosa whole plant were tested in vitro against two Plasmodium falciparum strains (3D7 and W2) using the p-LDH assay (colorimetric method). The Peters' four-days suppressive test model (Plasmodium berghei-infected mice) was used to evaluate the in vivo anti-plasmodial activity. An in vitro bioguided fractionation was undertaken on a dichloromethane extract, using preparative HPLC and TLC techniques. The identity of the pure compound was assessed using UV, MS and NMR spectroscopic analysis. In vitro cytotoxicity against WI38 human fibroblasts (WST-1 assay) and haemolytic activity were also evaluated for extracts and pure compounds in order to check selectivity. The best in vitro anti-plasmodial results were obtained with the dichloromethane, diethylether, ethylacetate and methanol extracts, which exhibited a high activity (IC50 ≤ 5 μg/ml). Hot water and hydroethanolic extracts also showed a good activity (IC50 ≤ 15 μg/ml), which confirmed the traditional use and the promising anti-malarial potential of the plant. The activity was also confirmed in vivo for all tested extracts. However, most of the active extracts also exhibited cytotoxic activity, but no extract was found to display any haemolytic activity. The bioguided fractionation process allowed to isolate and identify a sesquiterpene lactone (urospermal A-15-O-acetate) as the major anti-plasmodial compound of the plant (IC50 < 1 μg/ml against both 3D7 and W2 strains). This was also found to be the main cytotoxic compound (SI = 3.3). While this melampolide has already been described in the plant, this paper is the first report on the biological properties of this compound. The present study highlighted the very promising anti-plasmodial activity of D. tomentosa and enabled to identify its main active compound, urospermal A-15-O-acetate. The high anti-plasmodial activity of this compound merits further study about its anti-plasmodial mechanism of action. The active extracts of D. tomentosa, as well as urospermal A 15-O-acetate, displayed only a moderate selectivity, and further studies are needed to assess the safety of the use of the plant by the local population.


Need for and use of family leave among parents of children with special health care needs.
Parents of children with special health care needs are especially vulnerable to work-family conflicts that family leave benefits might help resolve. We examined leave-taking among full-time-employed parents of children with special health care needs. We identified all children with special health care needs in 2 large inpatient/outpatient systems in Chicago, Illinois, and Los Angeles, California, and randomly selected 800 per site. From November 2003 to January 2004, we conducted telephone interviews with 1105 (87% of eligible and successfully contacted) parents. Among the sample's 574 full-time-employed parents, we examined whether leave benefits predicted missing any work for child illness, missing >4 weeks for child illness, and ability to miss work whenever their child needed them. Forty-eight percent of full-time-employed parents qualified for federal Family and Medical Leave Act benefits; 30% reported employer-provided leave benefits (not including sick leave/vacation). In the previous year, their children averaged 20 missed school/child care days, 12 doctor/emergency department visits, and 1.7 hospitalizations. Although 81% of parents missed work for child illness, 41% reported not always missing work when their child needed them, and 40% of leave-takers reported returning to work too soon. In multivariate regressions, parents who were eligible for Family and Medical Leave Act benefits and aware of their eligibility had 3.0 times greater odds of missing work for child illness than ineligible parents. Parents with >4 weeks of employer-provided leave benefits had 4.7 times greater odds of missing >4 weeks than parents without benefits. Parents with paid leave benefits had 2.8 times greater odds than other parents of missing work whenever their child needed them. Full-time-employed parents of children with special health care needs experience severe work-family conflicts. Although most have leave benefits, many report unmet need for leave. Access to Family and Medical Leave Act benefits and employer-provided leave may greatly affect leave-taking.


Indications and rationale for use of vascularized fibula bone flaps in cervical spine arthrodeses.
Anterior cervical spine arthrodesis for large defects using autograft or allograft fibula for anterior structural support is a widely accepted procedure. In unique demand situations, a vascularized fibular flap is regarded as an "improvement" to the standard procedure. While a vascularized flap does deliver living tissue to the region, it does so with added potential morbidity and increased technical demand. The indications in the literature for this procedure have not been clearly defined. In this article, the authors review specific high-demand situations where they believe a vascularized flap is indicated. They also review patient outcomes after this procedure. Fibular free flaps were used in six patients with failed previous cervical spine arthrodeses. Three of the six patients had preoperative radiation therapy, and one received postoperative radiation treatment. All six patients had tumor and/or osteomyelitis present. One patient died of intraoperative hypotension 3 days after a successful free flap transfer during an elective posterior spine instrumentation procedure. One flap was lost from a venous thrombosis, and the patient was then treated successfully with a second fibular free flap. Clinical and radio-graphic evidence of fusion was obtained at 3 months in the five surviving patients, and neurologic function remained stable or improved. Analyzing their results and the literature, the authors propose that fibular free flaps are indeed a useful adjunct in difficult cervical spine stabilization procedures. Indications for this flap include combinations of the following situations: failed prior attempts at fusion, anterior cervical arthrodeses of three or more vertebral levels, osteomyelitis of the spine, and tumor cases when the spine has been or will be radiated.


Two-Year Outcomes After Transcatheter Aortic Valve Replacement With Mechanical vs Self-expanding Valves: The REPRISE III Randomized Clinical Trial.
To our knowledge, REPRISE III is the first large randomized comparison of 2 different transcatheter aortic valve replacement platforms: the mechanically expanded Lotus valve (Boston Scientific) and self-expanding CoreValve (Medtronic). To evaluate outcomes of Lotus vs CoreValve after 2 years. A total of 912 patients with high/extreme risk and severe, symptomatic aortic stenosis enrolled between September 22, 2014, and December 24, 2015, were randomized 2:1 to receive Lotus (607 [66.6%]) or CoreValve (305 [33.4%] at 55 centers in North America, Europe, and Australia. The first 2-year visit occurred on October 17, 2016, and the last was conducted on April 12, 2018. Clinical and echocardiographic assessments are complete through 2 years and will continue annually through 5 years. All-cause mortality and all-cause mortality or disabling stroke at 2 years. Other clinical factors included overall stroke, disabling stroke, repeated procedures, rehospitalization, valve thrombosis, and pacemaker implantation. Echocardiographic analyses included effective orifice area, mean gradient, and paravalvular leaks (PVLs). Of 912 participants, the mean (SD) age was 82.8 (7.3) years, 465 (51%) were women, and the mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 6.8% (4.0%). At 2 years, all-cause death was 21.3% with Lotus vs 22.5% with CoreValve (hazard ratio [HR], 0.94; 95% CI, 0.69-1.26; P = .67) and all-cause mortality or disabling stroke was 22.8% with Lotus and 27.0% with CoreValve (HR, 0.81; 95% CI, 0.61-1.07; P = .14). Overall stroke was 8.4% vs 11.4% (HR, 0.75; 95% CI, 0.48-1.17; P = .21); disabling stroke was more frequent with CoreValve vs Lotus (4.7% Lotus vs 8.6% CoreValve; HR, 0.53; 95% CI, 0.31-0.93; P = .02). More Lotus patients received a new permanent pacemaker (41.7% vs 26.1%; HR, 1.87; 95% CI, 1.41-2.49; P < .01) or had a valve thrombosis (3.0% vs 0.0%; P < .01) compared with CoreValve. More patients who received CoreValve experienced a repeated procedure (0.6% Lotus vs 2.9% CoreValve; HR, 0.19; 95% CI, 0.05-0.70; P < .01), valve migration (0.0% vs 0.7%; P = .05), or embolization (0.0% vs 2.0%; P < .01) than Lotus. Valve areas remained significantly larger and the mean gradient was lower with CoreValve than Lotus (valve area, mean [SD]: Lotus, 1.53 [0.49] cm2 vs CoreValve, 1.76 [0.51] cm2; P < .01; valve gradient, mean [SD]: Lotus, 13.0 [6.7] mm Hg vs 8.1 [3.7] mm Hg; P < .01). Moderate or greater PVL was more frequent with CoreValve (0.3% Lotus vs 3.8% CoreValve; P < .01) at 2 years. Larger improvements in New York Heart Association (NYHA) functional class were observed with Lotus compared with CoreValve (improved by ≥1 NYHA class: Lotus, 338 of 402 [84.1%] vs CoreValve, 143 of 189 [75.7%]; P = .01; improved by ≥2 NYHA classes: 122 of 402 [37.3%] vs 65 of 305 [21.3%]). After 2 years, all-cause mortality rates, mortality or disabling stroke were similar between Lotus and CoreValve. Disabling stroke, functional class, valve migration, and PVL favored the Lotus arm whereas valve hemodynamics, thrombosis, and new pacemaker implantation favored the CoreValve arm. clinicaltrials.gov Identifier: NCT02202434.


β-Adrenergic receptor blockade blunts postexercise skeletal muscle mitochondrial protein synthesis rates in humans.
β-Adrenergic receptor (AR) signaling is a regulator of skeletal muscle protein synthesis and mitochondrial biogenesis in mice. We hypothesized that β-AR blockade blunts postexercise skeletal muscle mitochondrial protein synthesis rates in adult humans. Six healthy men (mean ± SD: 26 ± 6 yr old, 39.9 ± 4.9 ml·kg(-1)·min(-1) peak O(2) uptake, 26.7 ± 2.0 kg/m(2) body mass index) performed 1 h of stationary cycle ergometer exercise (60% peak O(2) uptake) during 1) β-AR blockade (intravenous propranolol) and 2) administration of saline (control). Skeletal muscle mitochondrial, myofibrillar, and sarcoplasmic protein synthesis rates were assessed using [(2)H(5)]phenylalanine incorporation into skeletal muscle proteins after exercise. The mRNA content of signals for mitochondrial biogenesis was determined using real-time PCR. β-AR blockade decreased mitochondrial (from 0.217 ± 0.076 to 0.135 ± 0.031%/h, P < 0.05), but not myofibrillar or sarcoplasmic, protein synthesis rates. Peroxisome proliferator-activated receptor-γ coactivator-1α mRNA was increased ∼2.5-fold (P < 0.05) at 5 h compared with 1 h postexercise but was not influenced by β-AR blockade. We conclude that decreased β-AR signaling during cycling can blunt the postexercise increase in mitochondrial protein synthesis rates without affecting mRNA content.


Noise analysis of inward and outward Na+ currents across the apical border of ouabain-treated frog skin.
The passive Na+ transport across the apical membrane of frog skin (Rana catesbeiana) was studied under the following circumstances: (1) control conditions (sulfate Ringer's, K+ depolarised serosal membranes); (2) after blocking the active transport step with ouabain; (3) with an outward oriented Na+ current. The amiloride-induced Na+ current fluctuations were analysed to calculate the density of amiloride blockable channels and the current through one single channel. Despite the large reduction of the macroscopic current by ouabain, the single channel current remained unchanged, while the number of amiloride blockable Na+ channels was reduced by a factor of eight. It is concluded from these observations that the earlier described reduction of the permeability of the apical membrane is caused by a decrease of the number of electrically conductive Na+ channels. The outward oriented single channel currents were less than 50% of the currents in the opposite direction. After ouabain, the number of Na+ channels was independent from the current direction.


Cosmological classicalization: maintaining unitarity under relevant deformations of the Einstein-Hilbert action.
Generic relevant deformations of Einstein's gravity theory contain additional degrees of freedom that have a multifaceted stabilization dynamics on curved spacetimes. We show that these relevant degrees of freedom are self-protected against unitarity violations by the formation of classical field lumps that eventually merge to a new background geometry. The transition is heralded by the massive decay of the original vacuum and evolves through a strong coupling regime. This process fits in the recently proposed classicalization mechanism and extends it further to free field dynamics on curved backgrounds.


[Leptospirosis seroprevalence and associated features in rice farmers of tropical region of Peru].
To estimate the seroprevalence of leptospirosis in rice farmers of the Alto Mayo Valley in the Peruvian region of San Martín and to identify factors associated with infection. A cross-sectional study was conducted between October and November of 2010 on a sample of 254 farmers from eleven irrigation committees in the Alto Mayo Valley. A blood sample was collected as well as sociodemographic, household and labor characteristics in the form of a questionnaire. The presence of antibodies against leptospira was determined using the microscopic agglutination test and the IgM ELISA. The seroprevalence by agglutination was 64.6% (95% CI: 58.6-70.6). The IgM ELISA test was reactive in 15,0% (95% CI: 10.5-19.5). The most frequent serovar were Icterohaemorrhagiae, Autumnalis, Australis, Panama and Grippotyphosa. Independently associated factors were handling rodents (adjusted OR (aOR): 7.9; 95% CI: 1.6-37.9), working barefoot (aOR: 2.9; 95% CI: 1.2-6.8) and male sex (aOR: 4.5; 95% CI: 1.3-15.3). The Alto Mayo Valley is a hyperendemic for leptospirosis. The most important factors were associated with working barefoot and handling rodents in crop fields. Consequently, it is recommended to implement interventions that affect these two factors in order to reduce the risk of infection in rice farmers.


Characterization of lactobacilli from Scotch malt whisky distilleries and description of Lactobacillus ferintoshensis sp. nov., a new species isolated from malt whisky fermentations.
Sixty-four strains of Lactobacillus were isolated from fermentation samples from 23 malt whisky distilleries located in the major whisky producing regions of Scotland. The strains were assigned to 26 ribotype patterns. Strains of some ribotype patterns were widely distributed and recovered from distilleries throughout Scotland, while strains representing other ribotypes were particular to a specific region or even a certain distillery. Repeated sampling of a single distillery over a 12 month period showed that the range of bacteria present, as indicated by ribotyping, was stable, but was influenced by changes in malt supply and the period of closure for annual maintenance. Partial 16S rDNA sequence analysis of ribotype representatives revealed Lactobacillus brevis, Lactobacillus fermentum, Lactobacillus paracasei and Lactobacillus pentosus as the major species present in the distilleries; however, four isolates could not be identified by this procedure. Determination of the full 16S rDNA gene sequence from one of these isolates (strain R7-84) revealed >98.5% similarity to Lactobacillus buchneri and its phylogenetic neighbours. DNA from two other strains showed greater than 70% hybridization to DNA from R7-84 under non-stringent renaturation conditions and DNA from strain R7-84 shared less than 65% hybridization with members of the L. buchneri group. It is proposed that these three strains should be placed in a new species for which the name Lactobacillus ferintoshensis represented by the type strain R7-84(T) is suggested.


Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support.
Randomized trials assessing the effect of systemic corticosteroids on chronic obstructive pulmonary disease (COPD) exacerbations excluded patients who were mechanically ventilated or admitted to the intensive care unit (ICU). Critically ill patients constitute a population of persons who are prone to develop complications that are potentially associated with the use of corticosteroids (eg, infections, hyperglycemia, ICU-acquired paresis) that could prolong the duration of mechanical ventilation and even increase mortality. A double-blind placebo-controlled trial was conducted to evaluate the efficacy and safety of systemic corticosteroid treatment in patients with an exacerbation of COPD who were receiving ventilatory support (invasive or noninvasive mechanical ventilation). A total of 354 adult patients who were admitted to the ICUs of 8 hospitals in 4 countries from July 2005 through July 2009 were screened, and 83 were randomized to receive intravenous methylprednisolone (0.5 mg/kg every 6 hours for 72 hours, 0.5 mg/kg every 12 hours on days 4 through 6, and 0.5 mg/kg/d on days 7 through 10) or placebo. The main outcome measures were duration of mechanical ventilation, length of ICU stay, and need for intubation in patients treated with noninvasive mechanical ventilation. There were no significant differences between the groups in demographics, severity of illness, reasons for COPD exacerbation, gas exchange variables, and corticosteroid rescue treatment. Corticosteroid treatment was associated with a significant reduction in the median duration of mechanical ventilation (3 days vs 4 days; P = .04), a trend toward a shorter median length of ICU stay (6 days vs 7 days; P = .09), and significant reduction in the rate of NIV failure (0% vs 37%; P = .04). Systemic corticosteroid therapy in patients with COPD exacerbations requiring mechanical ventilation is associated with a significant increase in the success of noninvasive mechanical ventilation and a reduction in the duration of mechanical ventilation. clinicaltrials.gov Identifier: NCT01281748.