Aligning biodiversity conservation and ecosystem services in spatial planning: Focus on ecosystem processes.
Although the consideration of socio-economic demands with biodiversity conservation is now high on the environmental policy agenda, it is not yet standard practice in spatial planning. This is argued to be related, among others, to a lack of awareness among stakeholders and practitioners of the underpinning role of ecosystem functioning and biodiversity to support human well-being. Meanwhile, there is mounting critique on the absolute focus of biodiversity conservation on static properties such as species and habitats. The establishment of more ecologically sensible objectives that include ecosystem processes besides species and habitats is put forward as a more effective way of environmental conservation. Methodological approaches increasingly consider ecosystem processes. However, the processes that are included mostly relate to aspects of biodiversity such as dispersal and productivity, and rarely do they include abiotic mechanisms that underlie biodiversity. We here report on the development of a method that integrates two principles which we identify as key to advance the integration of ecosystem services with biodiversity conservation in planning practice: (1) consider the variety of ecosystem processes, biotic as well as abiotic, that support biodiversity and ecosystem services, and (2) link the ecosystem processes to biodiversity and to socio-economic benefits to identify the common ground between seemingly conflicting objectives. The methodology uses a stepwise approach and is based on an extensive review of available knowledge on ecosystem functioning, expert consultation and stakeholder involvement. We illustrate how the methodology supports the setting of strategic goals to accomplish a healthy coastal ecosystem in Belgium, and exemplify how this may affect spatial plans. The aim of this paper is to demonstrate how including processes opens opportunities to align biodiversity and ecosystem services and how this increases chances to provide long-term benefits for biodiversity and human well-being. The paper may provide inspiration to advance current spatial planning approaches.


Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model.
Previous work in this laboratory has indicated that the transplantation of adrenal medullary tissue into the subarachnoid space of the rat spinal cord can reduce pain sensitivity to acute noxious stimuli, particularly following stimulation by nicotine. This most likely results from the stimulated release of opioid peptides and catecholamines from the transplanted chromaffin cells. However, chronic pain models may more closely resemble human clinical pain, and the arthritic rat model has been used for screening potential therapeutic strategies. The purpose of the present study was to assess the potential for adrenal medullary tissue implanted into the spinal subarachnoid space to alleviate chronic pain. Adrenal medullary tissue was implanted into adjuvant-induced arthritic rats, and changes in body weight and vocalization responses were monitored over the 10 week course of the disease. Results indicate that the severe weight reduction normally associated with this inflammatory arthritis was attenuated by adrenal medullary, but not control, implants. In addition, vocalizations were reduced in animals implanted with adrenal medullary, but not control tissue following nicotine stimulation. This reduction was blocked by the opiate antagonist, naloxone, and partially attenuated by the alpha-adrenergic antagonist, phentolamine. Together, these results suggest that the transplantation of adrenal medullary tissue into the subarachnoid space of the spinal cord may provide a local source of opioid peptides and catecholamines for the reduction of chronic pain.


Adult burn patients with more than 60% TBSA involved-Meek and other techniques to overcome restricted skin harvest availability--the Viennese Concept.
Despite the fact that early excision and grafting has significantly improved outcome over the last decades, the management of severely burned adult patients with >/=60% total body surface area (% TBSA) burned still represents a challenging task for burn care specialists all over the world. In this article, we present our current treatment concept for this entity of severely burned patients and analyze its effect in a comparative cohort study. Surgical strategy comprised the use of split-thickness skin grafts (Meek, mesh) for permanent coverage, fluidized microsphere bead-beds for wound conditioning, temporary coverage (polyurethane sheets, Epigard; nanocrystalline silver dressings, Acticoat; synthetic copolymer sheets based on lactic acid, Suprathel; acellular bovine derived collagen matrices, Matriderm; allogeneic cultured keratinocyte sheets; and allogeneic split-thickness skin grafts), and negative-pressure wound therapy (vacuum-assisted closure). The autologous split-thickness skin graft expansion using the Meek technique for full-thickness burns and the delayed approach for treating dorsal burn wounds is discussed in detail. To demonstrate differences before and after the introduction of the Meek technique, we have compared patients of 2007 with >/=60% TBSA (n = 10) to those in a matched observation period (n = 7). In the first part of the comparative analysis, all patients of the two samples were analyzed with regard to age, abbreviated burn severity index, Baux, different entities of % TBSA, and survival. In the second step, only the survivors of both years were separated in two groups as follows: patients receiving skin grafts, using the Meek technique (n = 6), were compared with those without Meek grafting (n = 4). When comparing the severely burned patients of 2007 with a cohort of 2006, there were no differences for age (2007: 46.4 +/- 13.4 vs. 2006: 39.1 +/- 14.8 years), abbreviated burn severity index score (2007: 12.2 +/- 1.0 vs. 2006: 12.1 +/- 1.2) or % TBSA (2007: 72.1 +/- 11.7 vs. 2006: 69.3 +/- 8.7% TBSA). In these two rather small groups of severely burned patients with >/=60% TBSA, the overall survival rate of patients was 70.0% (7/10) in 2007 and 42.9% (3/7) in 2006, respectively. Almost all nonsurvivors in both years died within the first 5 days after admission. If assessing the different treatment modalities of the survivors, we found that although the Meek group patients were older (Meek 48.8 +/- 13.3 vs. non-Meek 26.8 +/- 11.5 years, P = .0381) and had consequently higher Baux scores (Meek 124.0 +/- 2.9 vs. non-Meek 93.8 +/- 8.5, P = .0095) than the non-Meek patients, this seemed to have no effect on length-of-stay (80.5 +/- 9.7 vs. non-Meek 79.8 +/- 33.0 days), hospital length-of-stay (85.7 +/- 14.8 vs. non-meek 84.3 +/- 26.1 days) or number of operations (6.5 +/- 1.0 vs. non-Meek 7.0 +/- 4.1 operations). The achieved results represent a combination of various treatment changes and, therefore, cannot be attributed to a single modality. The Meek technique is one of the technical options to choose from, to achieve permanent skin replacement; we think that it has its place if integrated in a whole treatment concept for management of severely burned patients.


Adaptive Plasticity in the Hippocampus of Young Mice Intermittently Exposed to MDMA Could Be the Origin of Memory Deficits.
(±)3,4-Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic neurotoxin in mice. This study was designed to evaluate whether MDMA exposure affects their recognition memory and hippocampal expression of plasticity markers. Mice were administered with increasing doses of MDMA once per week for 8 weeks (three times in 1 day, every 3 h) and killed 2 weeks (2w) or 3 months (3m) later. The treatment did not modify hippocampal tryptophan hydroxylase 2, a serotonergic indicator, but induced an initial reduction in dopaminergic markers in substantia nigra, which remained stable for at least 3 months. In parallel, MDMA produced a decrease in dopamine (DA) levels in the striatum at 2w, which were restored 3 months later, suggesting dopaminergic terminal regeneration (sprouting phenomenon). Moreover, recognition memory was assessed using the object recognition test. Young (2w) and mature (3m) adult mice exhibited impaired memory after 24-h but not after just 1-h retention interval. Two weeks after the treatment, animals showed constant levels of CREB but an increase in its phosphorylated form and in c-Fos expression. Brain-derived neurotrophic factor (BDNF) and especially Arc overexpression was sustained and long-lasting. We cannot rule out the absence of MDMA injury in the hippocampus being due to the generation of BDNF. The levels of NMDAR2B, PSD-95, and synaptophysin were unaffected. In conclusion, the young mice exposed to MDMA showed increased expression of early key markers of plasticity, which sometimes remained for 3 months, and suggests hippocampal maladaptive plasticity that could explain memory deficits evidenced here.


Punishment and Welfare: Paternal Incarceration and Families' Receipt of Public Assistance.
The United States criminal justice and welfare systems are two important government institutions in the lives of the poor. Despite many theoretical discussions about their relationship, their operation at the level of offenders and families remains poorly understood. This paper utilizes Fragile Families and Child Wellbeing data to examine how recent paternal incarceration is associated with families' receipt of TANF, food stamps, and Medicaid/SCHIP. Results robust to multiple tests find that incarceration is not related to subsequent TANF receipt but is significantly associated with increased receipt of food stamps and Medicaid/SCHIP. The findings suggest that greater government involvement among poor families is an unexpected consequence of mass imprisonment; however, increased participation does not include TANF-the cash assistance program of most concern to theorists.


A comparative study to evaluate the effect of honey dressing and silver sulfadiazene dressing on wound healing in burn patients.
To compare the effect of honey dressing and silver-sulfadiazene (SSD) dressing on wound healing in burn patients. Patients (n=78) of both sexes, with age group between 10 and 50 years and with first and second degree of burn of less than 50% of TBSA (Total body surface area) were included in the study, over a period of 2 years (2006-08). After stabilization, patients were randomly attributed into two groups: 'honey group' and 'SSD group'. Time elapsed since burn was recorded. After washing with normal saline, undiluted pure honey was applied over the wounds of patients in the honey group (n=37) and SSD cream over the wounds of patients in SSD group (n=41), everyday. Wound was dressed with sterile gauze, cotton pads and bandaged. Status of the wound was assessed every third and seventh day and on the day of completion of study. Patients were followed up every fortnight till epithelialization. The bacteriological examination of the wound was done every seventh day. The mean age for case (honey group) and control (SSD group) was 34.5 years and 28.5 years, respectively. Wound swab culture was positive in 29 out of 36 patients who came within 8 hours of burn and in all patients who came after 24 hours. The average duration of healing in patients treated with honey and SSD dressing at any time of admission was 18.16 and 32.68 days, respectively. Wound of all those patients (100%) who reported within 1 hour became sterile with honey dressing in less than 7 days while none with SSD. All of the wounds became sterile in less than 21 days with honey, while tthis was so in only 36.5% with SSD treated wounds. The honey group included 33 patients reported within 24 hour of injury, and 26 out of them had complete outcome at 2 months of follow-up, while numbers for the SSD group were 32 and 12. Complete outcome for any admission point of time after 2 months was noted in 81% and 37% of patients in the honey group and the SSD group. Honey dressing improves wound healing, makes the wound sterile in lesser time, has a better outcome in terms of prevention of hypertrophic scarring and post-burn contractures, and decreases the need of debridement irrespective of time of admission, when compared to SSD dressing.


Synaptic activity mediates death of hypoxic neurons.
Cultured hippocampal neurons, when exposed to cyanide or an anoxic atmosphere in the early stages of differentiation, were not visibly affected. However, neurons in the mature cultures died when exposed to cyanide or anoxia. Cell death could be prevented by treatment with magnesium, which eliminates synaptic activity. These observations suggest that damage in hypoxic neurons is mediated by synaptic activity.


SLUG Bug: Quality Improvement With Orchestrated Testing Leads to NICU CLABSI Reduction.
Reduce central line-associated bloodstream infection (CLABSI) rates 15% over 12 months in children's hospital NICUs. Use orchestrated testing as an approach to identify important CLABSI prevention practices. Literature review, expert opinion, and benchmarking were used to develop clinical practice recommendations for central line care. Four existing CLABSI prevention strategies (tubing change technique, hub care monitoring, central venous catheter access limitation, and central venous catheter removal monitoring) were identified for study. We compared the change in CLABSI rates from baseline throughout the study period in 17 participating centers. Using orchestrated testing, centers were then placed into 1 of 8 test groups to identify which prevention practices had the greatest impact on CLABSI reduction. CLABSI rates decreased by 19.28% from 1.333 to 1.076 per 1000 line-days. Six of the 8 test groups and 14 of the 17 centers had decreased infection rates; 16 of the 17 centers achieved >75% compliance with process measures. Hub scrub compliance monitoring, when used in combination with sterile tubing change, decreased CLABSI rates by 1.25 per 1000 line-days. This multicenter improvement collaborative achieved a decrease in CLABSI rates. Orchestrated testing identified infection prevention practices that contribute to reductions in infection rates. Sterile tubing change in combination with hub scrub compliance monitoring should be considered in CLABSI reduction efforts.


Oxygen/glucose deprivation in hippocampal slices: altered intraneuronal elemental composition predicts structural and functional damage.
Effects of oxygen/glucose deprivation (OGD) on subcellular elemental composition and water content were determined in nerve cell bodies from CA1 areas of rat hippocampal slices. Electron probe x-ray microanalysis was used to measure percentage water and concentrations of Na, P, K, Cl, Mg, and Ca in cytoplasm, nucleus, and mitochondria of cells exposed to normal and oxygen/glucose deficient medium. As an early (2 min) consequence of OGD, evoked synaptic potentials were lost, and K, Cl, P, and Mg concentrations decreased significantly in all morphological compartments. As exposure to in vitro OGD continued, a negative DC shift in interstitial voltage occurred ( approximately 5 min), whereas general elemental disruption worsened in cytoplasm and nucleus (5-42 min). Similar elemental changes were noted in mitochondria, except that Ca levels increased during the first 5 min of OGD and then decreased over the remaining experimental period (12-42 min). Compartmental water content decreased early (2 min), returned to control after 12 min of OGD, and then exceeded control levels at 42 min. After OGD (12 min), perfusion of hippocampal slices with control oxygenated solutions (reoxygenation) for 30 min did not restore synaptic function or improve disrupted elemental composition. Notably, reoxygenated CA1 cell compartments exhibited significantly elevated Ca levels relative to those associated with 42 min of OGD. When slices were incubated at 31 degreesC (hypothermia) during OGD/reoxygenation, neuronal dysfunction and elemental deregulation were minimal. Results show that in vitro OGD causes loss of transmembrane Na, K, and Ca gradients in CA1 neurons of hippocampal slices and that hypothermia can obtund this damaging process and preserve neuronal function.


Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes.
Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T(4)) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T(4) during development. This supports the hypothesis that decreased T(4) may be a relevant predictor for long-lasting developmental neurotoxicity.


QSoas: A Versatile Software for Data Analysis.
Undoubtedly, the most natural way to confirm a model is to quantitatively verify its predictions. However, this is not done systematically, and one of the reasons for that is the lack of appropriate tools for analyzing data, because the existing tools do not implement the required models or they lack the flexibility required to perform data analysis in a reasonable time. We present QSoas, an open-source, cross-platform data analysis program written to overcome these problems. In addition to standard data analysis procedures and full automation using scripts, QSoas features a very powerful data fitting interface with support for arbitrary functions, differential equation and kinetic system integration, and flexible global fits. QSoas is available from http://www.qsoas.org .


The authenticity and quality of Rhodiola rosea products.
Rhodiola rosea L. Crassulaceae, root (Golden Root, Arctic Root) is a high-value herbal medicinal product, registered in the UK for the treatment of stress-induced fatigue, exhaustion and anxiety based on traditional use and used throughout Europe as a herbal medicinal product for similar indications. Numerous unregistered supplements are also available. There are several Chinese species used in traditional Chinese medicine (TCM), including Rhodiola crenulata (Hook.f. & Thomoson) that is believed to be a common adulterant in the R. rosea value chain. The project is embedded in a larger study aiming to investigate the diverse value chains that lead to the production of R. rosea as an herbal medicinal product or supplement. Here we focus on a comparison of the quality of the finished products and assess any phytochemical variation between products registered under the Traditional Herbal Medicine Products Directive (THMPD) and products obtained from the market without any registration (i.e. generally unlicensed supplements). Our key aim is to establish the extent of the problem in terms of adulteration of consumer products claiming to contain R. rosea (or R. crenulata). Approximately 40 commercial products (granulated powders and extracts) were sourced from different suppliers. We analysed these samples using high performance thin layer chromatography (HPTLC), mass spectrometry (MS) and (1)H NMR spectroscopy coupled with multi-variate analysis software following a method previously developed by our group for the analysis of turmeric products. We investigate the phytochemistry of the different species and assess the potential of R. crenulata as an adulterant at the end of the R. rosea value chains. The consistency of the products varies significantly. Approximately one fifth of commercial products that claimed to be R. rosea did not contain rosavin (the key reference markers used to distinguish R. rosea from related species). Moreover some products appeared not to contain salidroside, another marker compound found in other Rhodiola species. Approximately 80% of the remaining commercial products were lower in rosavin content than the registered products and appeared to be adulterated with other Rhodiola species. The variation in phytochemical constituents present in Rhodiola products available to European buyers via the internet and other sources is a major cause for concern. Adulteration with different species, and other sometimes unknown adulterants, appears to be commonplace. Good quality systems and manufacturing practices, including those required under the THMPD, enable consumers to have confidence that products are authentic and meet a high specification for quality and safety.


Cryogenic Etching of Silicon: An Alternative Method For Fabrication of Vertical Microcantilever Master Molds.
This paper examines the use of deep reactive ion etching (DRIE) of silicon with fluorine high-density plasmas at cryogenic temperatures to produce silicon master molds for vertical microcantilever arrays used for controlling substrate stiffness for culturing living cells. The resultant profiles achieved depend on the rate of deposition and etching of a SiO x F y polymer, which serves as a passivation layer on the sidewalls of the etched structures in relation to areas that have not been passivated with the polymer. We look at how optimal tuning of two parameters, the O2 flow rate and the capacitively coupled plasma (CCP) power, determine the etch profile. All other pertinent parameters are kept constant. We examine the etch profiles produced using e-beam resist as the main etch mask, with holes having diameters of 750 nm, 1 µm, and 2 µm.


Influence of operator experience and reporting time on the accuracy of esophageal capsule endoscopy screening for varices.
Conflicting data exist concerning the accuracy of esophageal capsule endoscopy (ECE) for the screening of varices. No study has examined the influence of operator factors on the accuracy of ECE reporting. The primary aims of this study were, therefore, to examine how operator experience with esophagogastroduodenoscopy (EGD) and operator reporting times of capsule videos influenced test accuracy. Twelve cirrhotic patients presenting for EGD had same-day ECE performed. The gold standard for variceal grade was determined using a panel of experienced endoscopists. Six novice capsule endoscopists, blinded to results of EGD, subsequently reported capsule videos for each of the 12 patients.Novice capsule endoscopists accurately identified high-risk varices. The mean area under the receiver operating characteristic curve for identifying high-risk varices for the six operators was 0.88 ±/-0.14. The mean sensitivity, specificity, positive, and negative predictive values for identifying high-risk varices for the six operators were 83%, 93%, 82%, and 97%, respectively. Years of prior EGD experience were not associated with accuracy of capsule reporting (OR = 0.9, 95% CI [0.74, 1.08]; p = .26). Time spent reporting capsule videos was associated with accuracy of capsule reporting for high-risk varices using British Society of Gastroenterology criteria (OR = 1.33, 95% CI [1.05, 1.08]; p = .018). Novice capsule endoscopists are able to accurately identify high-risk esophageal varices. Time taken to report capsule videos, but not amount of prior EGD experience, influenced capsule report accuracy. These findings may have implications for the design of further trials and the cost-effectiveness of ECE screening of varices.


Resistance to fluoroquinolones and treatment failure/short-term relapse of community-acquired urinary tract infections caused by Escherichia coli.
This study aims to evaluate the impact of resistance to fluoroquinolones on the short-term outcome of community-acquired urinary tract infections (UTIs) caused by Escherichia coli. Patients were identified and followed, during 2006, using the health care databases of the Emilia-Romagna Region. The outcome of interest was the treatment failure/short-term relapse (the re-isolation of E. coli from urine between 4 and 30 days after the first isolation). Resistance to fluoroquinolones increases the risk of treatment failure/short-term relapse in women with uncomplicated community-acquired UTIs caused by E. coli (Rate Ratio=1.85, 95% CI 1.32-2.60). The efficacy of fluoroquinolones for community-acquired UTIs of men was significantly modified by the resistance status of E. coli. Prescription of these agents was associated with a reduced occurrence of the outcome only in men with a ciprofloxacin sensitive first isolate (Rate Ratio=0.50, 95% CI 0.25-0.99). Resistance to fluoroquinolones of E. coli is a growing problem with a negative impact on the outcome of community-acquired UTIs; therefore, the prescription of these agents should be limited to infections for which they are recommended, avoiding their use in uncomplicated UTIs.


Transient pupil response is modulated by contrast-based saliency.
The sudden appearance of a novel stimulus in the environment initiates a series of orienting responses that include coordinated shifts of gaze and attention, and also transient changes in pupil size. Although numerous studies have identified a significant effect of stimulus saliency on shifts of gaze and attention, saliency effects on pupil size are less understood. To examine salience-evoked pupil responses, we presented visual, auditory, or audiovisual stimuli while monkeys fixated a central visual spot. Transient pupil dilation was elicited after visual stimulus presentation regardless of target luminance relative to background, and auditory stimuli also evoked similar pupil responses. Importantly, the evoked pupil response was modulated by contrast-based saliency, with faster and larger pupil responses following the presentation of more salient stimuli. The initial transient component of pupil dilation was qualitatively similar to that evoked by weak microstimulation of the midbrain superior colliculus. The pupil responses elicited by audiovisual stimuli were well predicted by a linear summation of each modality response. Together, the results suggest that the transient pupil response, as one component of orienting, is modulated by contrast-based saliency, and the superior colliculus is likely involved in its coordination.


Visualization of gene activity in living cells.
Chromatin structure is thought to play a critical role in gene expression. Using the lac operator/repressor system and two colour variants of green fluorescent protein (GFP), we developed a system to visualize a gene and its protein product directly in living cells, allowing us to examine the spatial organization and timing of gene expression in vivo. Dynamic morphological changes in chromatin structure, from a condensed to an open structure, were observed upon gene activation, and targeting of the gene product, cyan fluorescent protein (CFP) reporter to peroxisomes was visualized directly in living cells. We found that the integrated gene locus was surrounded by a promyelocytic leukaemia (PML) nuclear body. The association was transcription independent but was dependent upon the direct in vivo binding of specific proteins (EYFP/lac repressor, tetracycline receptor/VP16 transactivator) to the locus. The ability to visualize gene expression directly in living cells provides a powerful system with which to study the dynamics of nuclear events such as transcription, RNA processing and DNA repair.


Phylogenetic congruence of lichenised fungi and algae is affected by spatial scale and taxonomic diversity.
The role of species' interactions in structuring biological communities remains unclear. Mutualistic symbioses, involving close positive interactions between two distinct organismal lineages, provide an excellent means to explore the roles of both evolutionary and ecological processes in determining how positive interactions affect community structure. In this study, we investigate patterns of co-diversification between fungi and algae for a range of New Zealand lichens at the community, genus, and species levels and explore explanations for possible patterns related to spatial scale and pattern, taxonomic diversity of the lichens considered, and the level sampling replication. We assembled six independent datasets to compare patterns in phylogenetic congruence with varied spatial extent of sampling, taxonomic diversity and level of specimen replication. For each dataset, we used the DNA sequences from the ITS regions of both the fungal and algal genomes from lichen specimens to produce genetic distance matrices. Phylogenetic congruence between fungi and algae was quantified using distance-based redundancy analysis and we used geographic distance matrices in Moran's eigenvector mapping and variance partitioning to evaluate the effects of spatial variation on the quantification of phylogenetic congruence. Phylogenetic congruence was highly significant for all datasets and a large proportion of variance in both algal and fungal genetic distances was explained by partner genetic variation. Spatial variables, primarily at large and intermediate scales, were also important for explaining genetic diversity patterns in all datasets. Interestingly, spatial structuring was stronger for fungal than algal genetic variation. As the spatial extent of the samples increased, so too did the proportion of explained variation that was shared between the spatial variables and the partners' genetic variation. Different lichen taxa showed some variation in their phylogenetic congruence and spatial genetic patterns and where greater sample replication was used, the amount of variation explained by partner genetic variation increased. Our results suggest that the phylogenetic congruence pattern, at least at small spatial scales, is likely due to reciprocal co-adaptation or co-dispersal. However, the detection of these patterns varies among different lichen taxa, across spatial scales and with different levels of sample replication. This work provides insight into the complexities faced in determining how evolutionary and ecological processes may interact to generate diversity in symbiotic association patterns at the population and community levels. Further, it highlights the critical importance of considering sample replication, taxonomic diversity and spatial scale in designing studies of co-diversification.


[Hydrocortisone treatment and prevent post-dural puncture headache: case reports].
Post-dural puncture headache is the most frequent complication after spinal anesthesia or accidental dural perforation during attempted epidural block. This report aimed at describing the use of hydrocortisone to treat and prevent post-dural puncture headache (PDPH). Three cases in which hydrocortisone was used to treat and prevent post-dural puncture headache are reported. The first is an obstetric patient submitted to Cesarean section with postoperative headache not responding to conventional medication and epidural blood patch (EBP), however with total remission after intravenous hydrocortisone. The other two patients, who suffered accidental dural perforation during attempted epidural space location, were preventively treated with intravenous hydrocortisone and have not developed headache. In our cases, hydrocortisone was effective to treat PDPH after failed conservative measures and EBP. Hydrocortisone for accidental dural perforation patients may be useful since it is a noninvasive technique and the incidence of PDPH in this group of patients is high. Controlled studies are needed to determine the actual role of hydrocortisone in preventing and treating PDPH.


Mutagenesis in Caenorhabditis elegans. II. A spectrum of mutational events induced with 1500 r of gamma-radiation.
We previously established a gamma-ray dose-response curve for recessive lethal events (lethals) captured over the eT1 balancer. In this paper we analyze the nature of lethal events produced, with a frequency of 0.04 per eT1 region, at a dose of 1500 r. To do so, we developed a protocol that, in the absence of cytogenetics, allows balanced lethals to be analyzed for associated chromosomal rearrangements. A set of 35 lethal strains was chosen for the analysis. Although the dosage was relatively low, a large number of multiple-break events were observed. The fraction of lethals associated with rearrangements was found to be 0.76. Currently most X- and gamma-ray dosages used for mutagenesis in C. elegans are 6000-8000 r. From our data we conservatively estimated that 43% of rearrangements induced with 8000 r would be accompanied by additional chromosome breaks in the genome. With 1500 r the value was 5%. The 35 lethals studied were derived from 875 screened F1's. Among these lethals there were (1) at least two unc-36 duplications, (2) at least four translocations, (3) at least six deficiencies of chromosome V (these delete about 90% of the unc-60 to unc-42 region) and (4) several unanalyzed rearrangements. Thus, it is possible to recover desired rearrangements at reasonable rates with a dose of only 1500 r. We suggest that the levels of ionizing radiation employed in most published C. elegans studies are excessive and efforts should be made to use reduced levels in the future.


Japanese encephalitis in Hong Kong.
To review past and present patterns of occurrence of Japanese encephalitis in Hong Kong and across Asia. A better understanding of the disease should facilitate the formulation of an effective strategic plan to prevent a future epidemic. Report of local cases, and literature search of MEDLINE up to November 2004. Literature and data related to Japanese encephalitis. Relevant information and data were reviewed by the authors. Since 16 July 2004, under the ordinance of Hong Kong, Japanese encephalitis has been a notifiable disease. In the past, Japanese encephalitis has reached epidemic proportions in Japan, South Korea, and some areas in China. It has spread globally and has a worldwide incidence of 35 000 to 50 000 cases per year with 10 000 deaths. Mortality is about 30% and survivors often suffer serious long-term morbidity. In 2004, there were five local cases of Japanese encephalitis in Hong Kong. Subsequent serological surveillance of serum samples from 1547 local inhabitants revealed that 37 were positive, ie 2.4% of local inhabitants had been exposed to the Japanese encephalitis virus in the past. Most local inhabitants are immunologically naive to Japanese encephalitis virus. Most infections in endemic areas are asymptomatic. Patients with symptomatic Japanese encephalitis usually present with fever, headache, and confusion. Other signs include neurosis, poliomyelitis, and convulsion. Investigations including magnetic resonance imaging, electroencephalography, and single photon emission computed tomography are not specific. A definitive diagnosis depends on serological studies. Treatment is mainly supportive. The control of Japanese encephalitis in Hong Kong relies on an accurate surveillance system, vector control, vector avoidance, and vaccination of the at-risk population. At present, vaccination should be limited to travellers to endemic areas who would stay for longer than 1 month.


HPV-Positive Oropharyngeal Cancer: The Nurse's Role in Patient Management of Treatment-Related Sequelae.
Patients diagnosed with oropharyngeal cancer (OPC) make up about 3% of all new cancer cases in the United States, with increasing numbers of these patients being diagnosed aged younger than 45 years and with human papillomavirus (HPV)-positive disease. Treatment effects may alter patients' physical and mental states during and after treatment. This article provides an overview of possible OPC treatment long-term effects to equip oncology nurses with information needed to empower patients with OPC to perform self-care. The OPC literature was reviewed to identify incidence, survival, risk factors, symptoms, treatment options, and treatment effects. This article provides a foundation for the plan of care for patients with OPC and strategies for patients to contribute to their self-care.


Marine biofilms on different fouling control coating types reveal differences in microbial community composition and abundance.
Marine biofouling imposes serious environmental and economic impacts on marine applications, especially in the shipping industry. To combat biofouling, protective coatings are applied on vessel hulls which are divided into two major groups: biocidal and non-toxic fouling release. The current study aimed to explore the effect of coating type on microbial biofilm community profiles to better understand the differences between the communities developed on fouling control biocidal antifouling and biocidal-free coatings. Biocidal (Intersmooth® 7460HS SPC), fouling release (Intersleek® 900), and inert surfaces were deployed in the marine environment for 4 months, and the biofilms that developed on these surfaces were investigated using Illumina NGS sequencing, targeting the prokaryotic 16S rRNA gene. The results confirmed differences in the community profiles between coating types. The biocidal coating supported communities dominated by Alphaproteobacteria (Loktanella, Sphingorhabdus, Erythrobacter) and Bacteroidetes (Gilvibacter), while other taxa, such as Portibacter and Sva0996 marine group, proliferated on the fouling-release surface. Knowledge of these marine biofilm components on fouling control coatings will serve as a guide for future investigations of marine microfouling as well as informing the coatings industry of potential microbial targets for robust coating formulations.


Bilberry-Derived Anthocyanins Modulate Cytokine Expression in the Intestine of Patients with Ulcerative Colitis.
We previously demonstrated that anthocyanin-rich bilberry extract (ARBE) inhibits IFN-γ-induced signalling and downstream effects in human monocytic cells and ameliorates disease activity in ulcerative colitis (UC) patients. Here, we studied the molecular mechanisms of ARBE-mediated effects in vitro and by analysing colonic tissue and serum samples of UC patients treated with an oral anthocyanin-rich bilberry preparation during an open label clinical trial. Colon specimens obtained during an open pilot study using ARBE for the treatment of mild-to-moderate UC were analyzed by immunohistochemistry. Cytokine levels in patients' serum were quantified by ELISA. Cell culture experiments were performed using THP-1 monocytic cells. ARBE treatment inhibited the expression of IFN-γ-receptor 2 in human THP-1 monocytic cells. Colon biopsies of UC patients who responded to the 6-week long ARBE treatment revealed reduced amounts of the pro-inflammatory cytokines IFN-γ and TNF-α. Levels of phosphorylated (activated) p65-NF-κB were reduced in these patients. Further, patients with successful ARBE treatment featured enhanced levels of Th17-cell specific cytokine IL-22 and immunoregulatory cytokine IL-10 as well as reduced serum levels of TNF-α and MCP-1, but enhanced levels of IL-17A, in contrast to patients that did not reach remission after ARBE treatment. Our data suggest a molecular mechanism underlying the anti-inflammatory effects of ARBE treatment in UC patients by modulating T-cell cytokine signalling and inhibiting IFN-γ signal transduction. These data are of particular interest, since ARBE is a promising therapeutic approach for the treatment of IBD.


Curcumin: An effective adjunct in patients with statin-associated muscle symptoms?
In spite of the unequivocal efficacy of statins in reducing primary and secondary cardiovascular events, the use of these drugs in a considerable number of patients is limited because of statin intolerance, mainly statin-associated muscle symptoms (SAMS). SAMS encompass a broad spectrum of clinical presentations, including mild muscular aching and other types of myalgias, myopathy with the significant elevation of creatine kinase, and the rare but life-threatening rhabdomyolysis. Among several pathophysiologic mechanisms of SAMS, mitochondrial dysfunction is thought to be one of the main one. Curcumin is the polyphenolic ingredient of Curcuma longa L., which has various pharmacological properties against a vast range of diseases. Curcumin has several mechanisms of actions relevant to the treatment of SAMS. These effects include the capacity to prevent and reduce delayed onset muscle soreness by blocking the nuclear factor inflammatory pathway, attenuation of muscular atrophy, enhancement of muscle fibre regeneration following injury, and analgesic and antioxidant effects. Curcumin can also increase the levels of cyclic adenosine monophosphate, which leads to an increase in the number of mitochondrial DNA duplicates in skeletal muscle cells. Finally, owing to its essential lipid-modifying properties, curcumin might serve as an adjunct to statin therapy in patients with SAMS, allowing for effective lowering of low-density lipoprotein cholesterol and possibly for statin dose reduction. Owing to the paucity of effective treatments, and the safety of curcumin in clinical practice, proof-of-concept trials are recommended to assess the potential benefit of this phytochemical in the treatment of SAMS.


Genetic variation of blast (Pyricularia oryzae Cavara) resistance in rice (Oryza sativa L.) accessions widely used in Kenya.
A total of 47 rice accessions collected from Kenya were investigated the genetic variations and classified into two cluster groups, A and B, by polymorphism data of 65 simple sequence repeat (SSR) markers. Clusters A and B corresponded to Japonica and Indica Groups, respectively. The number of Japonica Group accessions was limited in comparison with those of the Indica Group. Based on their patterns of reaction to standard differential blast isolates (SDBIs), these accessions and 57 control cultivars including differential varieties and several accessions harboring partial resistance genes were classified again into three cluster groups: Ia (high resistance), Ib (intermediate resistance) and II (susceptible). The rice accessions from Kenya were classified only into groups Ia and Ib. The accessions from Kenya were finally classified into three categories, A-Ia, B-Ia and B-Ib, based on the two classifications of polymorphism of SSR markers and resistance. The Indica Group accessions had wider genetic variation for blast resistance than did the Japonica Group accessions. The three leading cultivars (Basmati 217, Basmati 370 and ITA 310) categorized into Cluster group Ia were susceptible to some SDBIs from Kenya. The genetic variation for blast resistance in Kenya was demonstrated as the first report using SDBIs.


Iliac Crest Herniation Secondary to Autogenous Bone Grafting Found on Osteopathic Examination.
Surgical repair of difficult or nonunion fractures is frequently performed with autogenous bone grafts, most commonly from the iliac crest. Complications from this procedure may include vessel injury, nerve injury, pelvic instability, bowel herniation, and ileus. The authors report a case of iliac crest herniation in a patient presenting with a small-bowel obstruction 2 years after anterior iliac crest graft harvest for an open reduction and internal fixation repair of a right humeral shaft fracture. An emergency operation revealed that the right colon had herniated through an opening in the right iliac crest. The appendix had adhered to new osseous bone formed postoperatively, requiring an appendectomy. The hernia defect was successfully repaired with polypropylene mesh. A high index of suspicion for graft site herniation is needed for patients with a history of iliac crest bone grafting who present with symptoms of abdominal pain, flank or hip pain, ileus, or small-bowel obstruction.


AIDS testing and informed consent.
This article examines whether hospitals should obtain specific informed consent for HIV testing in addition to the general consent for routine procedures that is obtained upon admission. The article argues that specific consent should be obtained in all instances in which the HIV test is ordered. When the test is ordered to protect health care workers rather than to benefit the patient, the patient must be informed of the true purpose of the test: special care must be taken to avoid claims of fraud or duress that might invalidate the patient's consent. Furthermore, testing patients for the sole purpose of protecting health care workers should be discouraged, since the protection of health care workers can already be accomplished through universal blood and bodily fluid precautions. In balancing the inconvenience caused by universal blood and bodily fluid precautions against the privacy rights of patients, the patients' rights should prevail.


Practical guide to the management of acute pancreatitis.
Acute pancreatitis (AP) is characterised by inflammation of the exocrine pancreas and is associated with acinar cell injury and both a local and systemic inflammatory response. AP may range in severity from self-limiting, characterised by mild pancreatic oedema, to severe systemic inflammation with pancreatic necrosis, organ failure and death. Several international guidelines have been developed including those from the joint International Association of Pancreatology and American Pancreatic Association, American College of Gastroenterology and British Society of Gastroenterology. Here we discuss current diagnostic and management challenges and address the common dilemmas in AP.


Two rare schwannomas of head and neck.
Twenty-five to 45 percent of all schwannomas occur in the head and neck. Most of them arise along the vestibular portion of the eighth cranial nerve (acoustic neurinoma). They rarely originate from the peripheral facial nerve or other nerves within the parotid gland. Less than 4% of schwannomas involve the nasal cavity and paranasal sinuses. They arise from the branches of the trigeminal nerve and autonomic nervous system.We report two cases of schwannomas arisng from intraparotid facial nerve and nasal cavity. The first case diagnosed in a 62-year-old-man presented with 2-year-history of painless mass of the parotid gland. The lesion was found to be cystic through the pre operative examinations and investigations. The histology of the specimen retained an intraparotid cystic schwannoma. The second case concerned a 75-year-old-man presented with episodes of nasal obstruction, rhinorrhea, anosmia and headache. Histological study of the specimen showed fusiform cells with strongly and diffusely immunostaining for S100 protein suggesting a schwannoma. http://www.diagnosticpathology.diagnomx.eu/vs/1098335216112242.


Pitolisant: A Review in Narcolepsy with or without Cataplexy.
Pitolisant (Wakix®), an orally available, first-in-class antagonist/inverse agonist of the histamine 3 receptor, is approved in the EU (as of March 2016) for the treatment of narcolepsy with or without cataplexy in adults and in the USA (as of August 2019) for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy. Pitolisant was demonstrated to have minimal risk of abuse in preclinical and clinical studies, and is the only anti-narcoleptic drug not scheduled as a controlled substance in the USA. The totality of evidence from pivotal and supportive phase III trials suggests that pitolisant administered at up to the recommended maximum dose of 36 mg once daily reduces EDS and cataplexy in adults with narcolepsy relative to placebo. Noninferiority of pitolisant to modafinil in the management of EDS was not demonstrated. Pitolisant was generally well tolerated in clinical trials. Consistent with its mechanism of action, the most common treatment-emergent adverse events included headache, insomnia and anxiety. With minimal abuse potential and offering the convenience of oral, once-daily administration, pitolisant extends the range of approved treatment options available to adult patients with narcolepsy with or without cataplexy.


Effect of the S-to-S bridge on the redox properties and H2 activation performance of diiron complexes related to the [FeFe]-hydrogenase active site.
Three biomimetic models of the [FeFe]-hydrogenase active site, namely diiron dithiolates of [(μ-edt){Fe(CO)3}{Fe(CO)(κ2-PNP)}] (1, edt = ethane-1,2-dithiolate, PNP = Ph2PCH2N(nPr)CH2PPh2), [(μ-bdtMe){Fe(CO)3}{Fe(CO)(κ2-PNP)}] (2, bdtMe = 4-methylbenzene-1,2-dithiolate), and [(μ-adtBn){Fe(CO)3}{Fe(CO)(κ2-PNP)}] (3, adtBn = N-benzyl-2-azapropane-1,3-dithiolate), were prepared and structurally characterized. These complexes feature the same PNP ligand but different S-to-S bridges. Influence of the S-to-S bridge on the electrochemical properties and chemical oxidation reactivity of 1-3 was studied by cyclic voltammetry and by in situ IR spectroscopy. The results reveal that the S-to-S bridge has a considerable effect on the oxidation reactivity of 1-3 and on the stability of in situ generated single-electron oxidized complexes, [1]+, [2]+, and [3]+. The performances of [1]+ and [2]+ for H2 activation were explored in the presence of a mild chemical oxidant, while rapid decomposition of [3]+ thwarted the further study of this complex. Gratifyingly, 1 was found to be catalytically active, although in a low turnover number, for H2 oxidation in the presence of excess mild oxidant and a proton trapper under 1 atm H2 at room temperature.


Keratin modifications and solubility properties in epithelial cells and in vitro.
The gains that have been made in characterizing some of the keratin posttranslational modifications have helped answer some questions regarding these modifications and have generated an information base for asking additional refined questions in future studies. Highlights of where we believe we currently stand with regard to keratin posttranslational modifications are as follows: 1. Keratin glycosylation, via O-GlcNAc, is a dynamic modification that has been conclusively identified in K13, K8, and K18. Three serine glycosylation sites in the head domain of K18 have been identified, and it is possible that all keratins are glycosylated. The function of this modification remains to be defined, but is likely to be different from phosphorylation, since the two modifications are generally segregated on different molecules and several examples exist whereby both modifications increase simultaneously. 2. Keratin phosphorylation occurs within the tail and/or head domains of all keratins that have been examined. Several serine phosphorylation sites and some of the relevant kinases have been characterized in K8, K6, and K18, and serine/threonine sites have been identified in K1. Functions of keratin phosphorylation that have significant experimental support include a role in filament solubility and reorganization and a role in regulating keratin binding with other cytoplasmic proteins. The significance of filament reorganization and increased solubility under a variety of physiologic conditions such as mitosis and cell stress are important areas of future and ongoing investigation. Other associations with keratin phosphorylation include protection against cell stress, cell signaling, apoptosis, and cell compartment-specific roles. At this stage, however, it is not known if these associations play direct or indirect roles. 3. Keratin transglutamination occurs in epidermal and simple epithelial keratins under physiologic and pathologic states, respectively. In the physiological context, the role of this modification is clear in terms of providing a compact protective structure, while in the pathologic context of liver disease the role remains ambiguous. 4. Proteolysis of K18 and K19 by caspases occurs during apoptosis, and generates stable keratin fragments that are highly enriched within the cytoskeletal compartment. Proteolysis of the type II keratins appears to be spared for reasons that remain to be defined. It is likely that this apoptosis-associated degradation involves all type I keratins. Keratin fragments are also noted in sera of patients in association with a variety of epithelial tumors. If a signal does exist for the apoptosis-associated fragmentation, aside from caspase activation, then it appears that the overall increase in keratin phosphorylation during apoptosis does not account for this signal. 5. Keratins undergo several other posttranslational modifications including disulfide bond formation (not found in K8/18 due to lack of cystienes) and acetylation of their N-terminal serines. Modification by lipids is also possible, but this modification requires further confirmation. 6. Keratin solublility is highly dynamic and varies profoundly depending on the keratin pair and the physiologic state of the cell. Within the keratin family, simple epithelial keratins are among the most soluble (approximately 5% of K8/18 is soluble at basal conditions). Phosphorylation plays an important role in modulating keratin solubility, and distinct differences occur in site-specific phosphorylation depending on the soluble versus cytoskeletal partitioning of the keratin. Keratin solubility (at least for K8/18) also appears to be regulated by 14-3-3 proteins via K18 Ser33 phosphorylation.


A pH-responsive self-healing hydrogel based on multivalent coordination of Ni2+ with polyhistidine-terminated PEG and IDA-modified oligochitosan.
Metal coordination hydrogels have drawn intensive attention in controlled drug release due to their facile incorporation of stimuli and dynamic self-healing properties. However, many metal coordination hydrogels which are responsive to mild physiologically relevant stimuli are restricted by their poor stability in non-triggering environments. Here, we reported a new strategy for enhancing the neutral stability of a pH-responsive self-healing hydrogel based on multivalent metal coordination without loss of its responsiveness. The hydrogel was formed by multivalent coordination of Ni2+ with polyhistidine (PHis) and multiple iminodiacetic acid (IDA) ligands which were modified on the terminal groups of polyethylene glycol (PEG) and the side groups of oligochitosan (OChi), respectively. By incorporating multivalent coordination, the hydrogel maintains its self-healing character and weak acid responsiveness; it can also be used as an injectable hydrogel by injecting it into a neutral environment. Through varying the PHis : IDA ratio, the mechanical strength and dynamic relaxation of the hydrogel can be regulated conveniently. More importantly, the hydrogels with multivalent coordination can remain stable and integral in neutral buffer (pH 7.4); meanwhile, they dissolve quickly in a weak acid environment (pH 5.5), which is similar to some tissue disease conditions. In contrast, the control hydrogel without multivalent coordination disintegrated within 4 hours in the neutral non-triggering buffer. Because the hydrogel consists of large amounts of coordinative Ni2+ ions, it naturally possesses relatively high affinity to molecules containing polyhistidine motifs. Thus, pH-tuned controlled release of a model molecule, rhodamine-modified polyhistidine, was accomplished, with limited neutral leakage and quick release in weak acid. These results indicate potential applications for this multivalent coordination hydrogel in the controlled release field.


Planar lipid bilayers containing gramicidin A as a molecular sensing system based on an integrated current.
The channel activity of gramicidin A in free-standing planar lipid bilayers with different charges of polar head groups and various lengths of hydrocarbon tails were analyzed in terms of the channel conductance, the lifetime of channel events and the magnitude of integrated currents. The channel activity of gramicidin A in lipid bilayers is tunable by adjusting the membrane composition. The in situ coupling of the anti-BSA antibody as a model protein to the amine moiety of phosphatidylethanolamine (PE) in a lipid bilayer by the amine coupling method allowed us to design an antigen (BSA)-sensitive interface, in which the integrated current, rather than the frequency of channel event, can be used as an analytical signal. The potential of the present system for highly sensitive and selective detection of BSA at 10(-9) g/mL level is demonstrated.


Comparing genomic variant identification protocols for Candida auris.
Genomic analyses are widely applied to epidemiological, population genetic and experimental studies of pathogenic fungi. A wide range of methods are employed to carry out these analyses, typically without including controls that gauge the accuracy of variant prediction. The importance of tracking outbreaks at a global scale has raised the urgency of establishing high-accuracy pipelines that generate consistent results between research groups. To evaluate currently employed methods for whole-genome variant detection and elaborate best practices for fungal pathogens, we compared how 14 independent variant calling pipelines performed across 35 Candida auris isolates from 4 distinct clades and evaluated the performance of variant calling, single-nucleotide polymorphism (SNP) counts and phylogenetic inference results. Although these pipelines used different variant callers and filtering criteria, we found high overall agreement of SNPs from each pipeline. This concordance correlated with site quality, as SNPs discovered by a few pipelines tended to show lower mapping quality scores and depth of coverage than those recovered by all pipelines. We observed that the major differences between pipelines were due to variation in read trimming strategies, SNP calling methods and parameters, and downstream filtration criteria. We calculated specificity and sensitivity for each pipeline by aligning three isolates with chromosomal level assemblies and found that the GATK-based pipelines were well balanced between these metrics. Selection of trimming methods had a greater impact on SAMtools-based pipelines than those using GATK. Phylogenetic trees inferred by each pipeline showed high consistency at the clade level, but there was more variability between isolates from a single outbreak, with pipelines that used more stringent cutoffs having lower resolution. This project generated two truth datasets useful for routine benchmarking of C. auris variant calling, a consensus VCF of genotypes discovered by 10 or more pipelines across these 35 diverse isolates and variants for 2 samples identified from whole-genome alignments. This study provides a foundation for evaluating SNP calling pipelines and developing best practices for future fungal genomic studies.


Adding ofloxacin to standard triple-drug regimens increased the Helicobacter pylori eradication rate: Data from randomized clinical trial.
The rate of Helicobacter pylori (H.pylori) eradication in dyspeptic patients using bismuth- based triple therapy is low due to bacterial that are resistant to antibiotics. The results of recent studies regarding levofloxacin have been encouraging, but the high cost of treatment prevents its routine administration. We, therefore, performed the present double-blind clinical trial to compare the efficiency of quadruple-drug regimen containing ofloxacin, clarithromycin, amoxicillin, and omeprazole and the same standard triple-therapy regimen minus ofloxacin in H. pylori positive dyspepsia. The study patients were recruited among dyspeptic patients requiring gastroscopy. Patients with the history of H.pylori treatment, renal failure and pregnancy were excluded. Diagnosis of H.pylori infection was confirmed by rapid urease test and response to treatment was confirmed via negative urease breath test (UBT) 20 days after completion of treatment. Patients were allocated intermittently to standard triple therapy containing amoxicillin, clarithromycin, omeprazole alone or plus ofloxacin for ten days. Response to treatment was compared between the two groups. A total of 140 patients entered the study (70 patients in each group). At endpoint 30 (42.9%) patients of group 1 and 39 (55.7%) patients of group 2 became asymptomatic. Furthermore, 55 (78.6%) patients of group 1 and 66 (94.3%) patients of group 2 revealed negative urea breath test (P= 0.01). This study indicates adding ofloxacin to standard triple-therapy for H.pylorri infection significantly increases the rate of eradication. These findings highlight ofloxacin as empiric treatment of H. pylori infection.


Radiological evidence of spontaneous spinal arthrodesis in patients with lower lumbar spondylolisthesis.
Retrospective review of a consecutive series of patients with radiological evidence of spondylolisthesis. To establish the incidence and characteristics of spontaneous spinal arthrodesis in the setting of lower lumbar spondylolisthesis. Spontaneous spinal arthrodesis of lumbar spondylolisthesis is a finding that is not discussed in the literature outside of isolated case reports. Identifying spontaneous spinal arthrodesis may impact the surgical plan, as patients with existing fusion may not require instrumentation and might require more work to reduce their spondylolisthesis. We reviewed a consecutive series of 1490 lumbar spine computed tomography scans from the year 2010 for radiological evidence of spondylolisthesis at either L4-L5 or L5-S1. Patients were excluded if they had undergone previous lumbar surgery. Scans were assessed for the presence of spontaneous fusion based on the following criteria: (1) a solid bridging anterior or posterior vertebral body osteophyte, (2) contiguous bone formation from one vertebral body to another, or (3) contiguous bone across the facet joints bilaterally. Patients were characterized by demographic variables, radiological characteristics including type of spondylolisthesis, and presenting symptomology. Differences between patients in the fused and nonfused cohorts were compared with univariate analysis. A total of 86 separate instances of spondylolisthesis were identified, of which 18 (20.9%) had radiological evidence of spontaneous fusion. The most common site of fusion was in the bilateral facets, followed by directly in the intervertebral disc space, and bridging osteophytes adjoining the vertebral bodies. There were significant differences between patients in the fused and nonfused cohorts in terms of average age (fused: 74.3 ± 10.7 yr vs. nonfused: 63.3 ± 18.6 yr, P = 0.019), sex (fused: 88.9% female vs. nonfused: 57.4% female, P = 0.013), and rate of pars defects (fused: 11.1% vs. nonfused: 35.3%, P = 0.047). In this study, 20.9% of patients with lumbar spondylolisthesis have radiological signs of spontaneous fusion. Further work is needed to better characterize the natural history and clinical-radiological correlation of spontaneous fusion in spondylolisthesis. 4.


Characterization of lipid composition and diffusivity in OLA generated vesicles.
Giant Unilamellar Vesicles (GUVs) are a versatile tool in many branches of science, including biophysics and synthetic biology. Octanol-Assisted Liposome Assembly (OLA), a recently developed microfluidic technique enables the production and testing of GUVs within a single device under highly controlled experimental conditions. It is therefore gaining significant interest as a platform for use in drug discovery, the production of artificial cells and more generally for controlled studies of the properties of lipid membranes. In this work, we expand the capabilities of the OLA technique by forming GUVs of tunable binary lipid mixtures of DOPC, DOPG and DOPE. Using fluorescence recovery after photobleaching we investigated the lateral diffusion coefficients of lipids in OLA liposomes and found the expected values in the range of 1 μm2/s for the lipid systems tested. We studied the OLA derived GUVs under a range of conditions and compared the results with electroformed vesicles. Overall, we found the lateral diffusion coefficients of lipids in vesicles obtained with OLA to be quantitatively similar to those in vesicles obtained via traditional electroformation. Our results provide a quantitative biophysical validation of the quality of OLA derived GUVs, which will facilitate the wider use of this versatile platform.


[FeFe]-Hydrogenases: recent developments and future perspectives.
[FeFe]-Hydrogenases are the most efficient enzymes for catalytic hydrogen turnover. Their H2 production efficiency is hitherto unrivalled. However, functional details of the catalytic machinery and possible modes of application are discussed controversially. The incorporation of synthetically modified cofactors and utilization of semi-artificial enzymes only recently allowed us to shed light on key steps of the catalytic cycle. Herein, we summarize the essential findings regarding the redox chemistry of [FeFe]-hydrogenases and discuss their catalytic hydrogen turnover. We furthermore will give an outlook on potential research activities and exploit the utilization of synthetic cofactor mimics.


Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells.
Etoposide (Vepesid, VP-16), an inhibitor of topoisomerase II, is a chemotherapeutic drug commonly used for treatment of different types of malignant diseases. By inhibiting the topoisomerase II enzyme activity in cancer cells, this drug leads to DNA damage and subsequently to cell death. In this study, we investigated the effect of this anticancer drug alone and in combination with a histone deacetylase (HDAC) inhibitor, valproic acid (VPA), on a human UKF-NB-4 neuroblastoma cell line. The effects of etoposide and VPA on UKF-NB-4 cells were tested under the normoxic and also the hypoxic (1% O2) cultivation conditions. The cytotoxicity of etoposide and VPA to a UKF-NB-4 neuroblastoma cell line was evaluated with MTT assay. Apoptosis of the cells was analyzed by flow cytometry using an Annexin V and propidium iodide binding method. The effect of etoposide and VPA on the cell cycle distribution was determined by flow cytometric analysis using propidium iodide staining. The results of the study demonstrate that UKF-NB-4 neuroblastoma cells are sensitive both to etoposide and to VPA. They also indicate that the impact of VPA on cytotoxicity of etoposide in these tumor cells varies depending on the sequence of cultivation of the cells with the drugs. As a suitable sequence of cultivation, with a high rate of suppression of neuroblastoma cell growth was found the preincubation of the cells with etoposide, which was followed by their cultivation with VPA. In contrast, the reversed combination (preincubation of the cells with VPA before their treating with etoposide) did not give any increase in etoposide cytotoxicity. The effect of such combined treatment can be explained by measuring the cell cycle distribution, which shows that both etoposide and VPA change the cell cycle phase distribution. Etoposide and VPA were found as cycle phase specific drugs that are cytotoxic to human UKF-NB-4 neuroblastoma cells used either as single drugs or both together. However, whereas VPA might sensitize the cells to etoposide, inappropriate sequence of cultivation of the cells with VPA can decrease the etoposide cytotoxic efficacy. The results found here warrant further studies of combined treatment of neuroblastoma cells with etoposide with HDAC inhibitors and may help in the design of new protocols geared to the treatment of high risk neuroblastomas.


APC inhibits ERK pathway activation and cellular proliferation induced by RAS.
Inactivating mutations in the adenomatous polyposis coli gene (APC), and activating mutations in RAS, occur in a majority of colorectal carcinomas. However, the relationship between these changes and tumorigenesis is poorly understood. RAS-induced activation of the ERK pathway was reduced by overexpressing APC in DLD-1 colorectal cancer cells. ERK activity was increased by Cre-virus-induced Apc knockout in primary Apc(flox/flox) mouse embryonic fibroblasts, indicating that APC inhibits ERK activity. ERK activity was increased by overexpression and decreased by knock down of beta-catenin. The activation of Raf1, MEK and ERK kinases by beta-catenin was reduced by co-expression of APC. These results indicate that APC inhibits the ERK pathway by an action on beta-catenin. RAS-induced activation of the ERK pathway was reduced by the dominant negative form of TCF4, indicating that the ERK pathway regulation by APC/beta-catenin signaling is, at least, partly caused by effects on beta-catenin/TCF4-mediated gene expression. The GTP loading and the protein level of mutated RAS were decreased in cells with reduced ERK activity as a result of APC overexpression, indicating that APC regulates RAS-induced ERK activation at least partly by reduction of the RAS protein level. APC regulates cellular proliferation and transformation induced by activation of both RAS and beta-catenin signaling.


Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention.
Nickel is a ubiquitous metal added to jewelry and metallic substances for its hardening properties and because it is inexpensive. Estimates suggest that at least 1.1 million children in the United States are sensitized to nickel. Nickel allergic contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type hypersensitivity reaction worldwide. The incidence among children tested has almost quadrupled over the past 3 decades. The associated morbidities include itch, discomfort, school absence, and reduced quality of life. In adulthood, individuals with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD in children has been postulated to result from early and frequent exposure to metals with high amounts of nickel release (eg, as occurs with ear piercing or with products used daily in childhood such as toys, belt buckles, and electronics).To reduce exposure to metal sources with high nickel release by prolonged and direct contact with human skin, Denmark and the European Union legislated a directive several decades ago with the goal of reducing high nickel release and the incidence of Ni-ACD. Since then, there has been a global reduction in incidence of Ni-ACD in population-based studies of adults and studies of children and young adults being tested for allergic contact dermatitis. These data point to nickel exposure as a trigger for elicitation of Ni-ACD and, further, provide evidence that legislation can have a favorable effect on the economic and medical health of a population.This policy statement reviews the epidemiology, history, and appearances of Ni-ACD. Examples of sources of high nickel release are discussed to highlight how difficult it is to avoid this metal in modern daily lives. Treatments are outlined, and avoidance strategies are presented. Long-term epidemiological interventions are addressed. Advocacy for smarter nickel use is reviewed. The American Academy of Pediatrics supports US legislation that advances safety standards (as modeled by the European Union) that protect children from early and prolonged skin exposure to high-nickel-releasing items. Our final aim for this article is to aid the pediatric community in developing nickel-avoidance strategies on both individual and global levels.


Synthesis of NaYF4:Yb3+, Er3+ upconversion nanoparticles in normal microemulsions.
An interface-controlled reaction in normal microemulsions (water/ethanol/sodium oleate/oleic acid/n-hexane) was designed to prepare NaYF4:Yb3+, Er3+ upconversion nanoparticles. The phase diagram of the system was first studied to obtain the appropriate oil-in-water microemulsions. Transmission electron microscopy and X-ray powder diffractometer measurements revealed that the as-prepared nanoparticles were spherical, monodisperse with a uniform size of 20 nm, and of cubic phase with good crystallinity. Furthermore, these nanoparticles have good dispersibility in nonpolar organic solvents and exhibit visible upconversion luminescence of orange color under continuous excitation at 980 nm. Then, a thermal treatment for the products was found to enhance the luminescence intensity. In addition, because of its inherent merit in high yielding and being economical, this synthetic method could be utilized for preparation of the UCNPs on a large scale.


Doppler Assessment of Uterine Blood Flow in Pre-eclampsia: A Review.
Doppler ultrasonography plays an ever-increasing role in obstetric imaging. Although commonly purported to assess blood flow, most studies in this area report purely on velocimetric parameters, rather than true volumetric flow. This review article highlights the physiological importance of this distinction, and reports on a literature review of uterine artery Doppler interrogation in the context of pre-eclampsia, which identified only four original research papers that attempted to assess blood flow. Attention is needed for true volumetric flow assessment in pre-eclampsia research, which may permit a more complete conceptualisation of the pathogenesis and haemodynamic consequences of this condition.


Student selection to a rural veterinary school. 1: applicant demographics and predictors of success within the application process.
To determine demographic details of applicants to the veterinary degree program at and relate this information to student selection processes. Retrospective evaluation of applicant data. Database records of 4042 applicants to the veterinary program (2006-2016) were retrieved from university records. Summary statistics were used to determine basic demographic data, which were related to pre-entry academic achievement and results of selection processes using univariable and multivariable analyses. The number of applications, interviews and acceptance of offers fluctuated but did not vary substantively for the duration of the study. Gender, rurality (as assessed by residential and school postcodes), socioeconomic background, academic background and pre-entry academic achievement all significantly influenced written application and interview scores in the multivariate models. Rural background, written application score, number of applications, pre-entry academic history and achievement significantly affected the chances of receiving an interview. Chances of receiving an offer and subsequent program entry were significantly influenced by academic background, interview score and pre-entry academic achievement. Male applicants were more likely to receive an offer, but gender had no effect on program entry. Rural residential and school background was associated with significantly reduced ATAR in comparison with city-based applicants. Selection processes effectively identified applicants with demographic backgrounds and life experiences consistent with the School's commitment to the veterinary needs of rural and regional Australia. Findings support the provision of an academic loading for the ATAR results of rural students. Effects of these selection outcomes on student performance should be evaluated.


Childhood cancer incidence in a cohort of twin babies.
We studied childhood cancer incidence in a population-based twin cohort using record linkage to the National Registry of Childhood Tumours. After correcting for mortality, an incidence deficit was observed (Standardized Incidence Ratio (SIR) 79; 95% Confidence Interval (CI) 39-120). Pooled analysis with data from published cohort studies indicates a similar significant incidence reduction (SIR 81, 95% CI 67-96). Further studies are warranted.


Biomarker-based trials in neuro-oncology.
Treatment of brain tumors is increasingly informed by biomarkers. One use is to appropriately group tumors with similar genetic/genomic characteristics and to design trials separately for the individual groups. The biomarker's use is to predict patient response so that the most effective treatment can be selected for patients based on their tumor characteristics. Trial designs that recruit unselected patients are poorly suited for identifying treatments effective only in subsets of patients given the relatively small numbers of patients available for trials. Investigators are beginning to use different designs that better account for tumor heterogeneity. In this article, an overview of the role of biomarkers in brain tumor trials is presented in the context of existing clinical trials as well as trials that may be launched within the next several years.


Reactivity of sulfenic acid in human serum albumin.
Sulfenic acid is formed upon oxidation of thiols and is a central intermediate in the redox modulation of an increasing number of proteins. Methods for quantifying or even detecting sulfenic acid are scarce. Herein, the reagent 7-chloro-4-nitrobenz-2-oxa-1,3-diazole was determined not to be suitable as a chromophoric probe for sulfenic acid in human serum albumin (HSA-SOH) because of lack of specificity. Thionitrobenzoate (TNB) reacted with HSA exposed to hydrogen peroxide, but not control or thiol-blocked HSA. The reaction was biphasic. The first phase was approximately 20-fold faster than the second phase and first order in HSA-SOH and TNB (105 +/- 11 M-1 s-1, 25 degrees C, pH 7.4), allowing quantitative data on HSA-SOH formation and reactivity to be obtained. Exposure of reduced HSA (0.5 mM) to hydrogen peroxide (4 mM, 37 degrees C, 4 min) yielded 0.18 +/- 0.02 mol of HSA-SOH per mol of HSA. HSA-SH reacted with hydrogen peroxide at 2.7 +/- 0.7 M-1 s-1 (37 degrees C, pH 7.4), while HSA-SOH reacted at 0.4 +/- 0.2 M-1 s-1, yielding sulfinic acid (HSA-SO2H), as detected by mass spectrometry. The rate constants of HSA-SOH with targets of analytical interest such as dimedone and sodium arsenite were determined. HSA-SOH did not react appreciably with the plasma reductants ascorbate or urate, nor with free basic amino acids. In contrast, HSA-SOH reacted rapidly with the plasma thiols cysteine, glutathione, homocysteine, and cysteinylglycine at 21.6 +/- 0.2, 2.9 +/- 0.5, 9.3 +/- 0.9, and 55 +/- 3 M-1 s-1 (25 degrees C, pH 7.4), respectively, supporting a role for HSA-SOH in the formation of mixed disulfides.


Medial arterial calcification and diabetic neuropathy.
X-ray examinations of the feet, knees, and hands were performed on 20 diabetics with severe neuropathy and 20 diabetics with no evidence of neuropathy but with a similar mean age and duration of diabetes. All were under 53 years old with no clinical evidence of peripheral vascular disease. Medial arterial calcification was much more common and extensive in the patients with neuropathy, occurring in the feet in 15 and in the hands in eight compared with in four (p less than 0.001) and none (p less than 0.001) of the controls respectively. Although there was some correlation between calcification and both proteinuria (p less than 0.05) and proliferative retinopathy (p less than 0.02), the association between calcification and neuropathy (p less than 0.001) was much stronger. Neuropathy, with sympathetic denervation of the smooth muscle of the tunica media, may be important in the aetiology of medial arterial calcification.


Tryptophan-Requiring Mutants of the Plant Arabidopsis thaliana.
Although amino acid auxotrophs are among the most frequently isolated mutations in microorganisms, no mutants that require amino acids have been isolated at the whole plant level. Tryptophan-requiring mutants of the cruciferous plant Arabidopsis thaliana have now been isolated by selecting for resistance to 5-methylanthranilic acid. The tryptophan requirement of one mutant, trpl-1, results from a defect in the second step of the tryptophan pathway catalyzed by anthranilate phosphoribosyl transferase. Mutant trpl-1 plants are highly fluorescent and aromatic because they accumulate anthranilic acid and anthranilate beta-glucoside. Plants homozygous for the trpl-1 mutation exhibit a syndrome of morphological defects suggestive of a defect in the biosynthesis, metabolism, or localization of a tryptophan derivative such as auxin. All of these morphological phenotypes cosegregate with the tryptophan requirement as a simple Mendelian recessive trait.


Efficacy and toxicity of chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel for unresectable stage III non-small cell lung cancer.
In 2003, consolidation docetaxel was a promising concept for unresectable stage IIIA/B nonsmall cell lung cancer (NSCLC). To test the hypothesis that chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel would be feasible and clinically active, we conducted a phase II study. Thirty-two patients with unresectable stage IIIA/B NSCLC received irinotecan (30 mg/m) and carboplatin dosed to a target area under the concentration curve of 2, each administered weekly for 7 weeks. Concurrent radiotherapy was administered more than 7 weeks to a total dose of 63 Gy in 35 fractions. Consolidation docetaxel (75 mg/m) was administered every 3 weeks for 3 doses 4 weeks after chemoradiotherapy. The primary end point was objective response rate by RECIST. Complete responses occurred in 4 patients and partial responses occurred in 14, for an objective response rate of 56.3% (95% confidence interval [CI], 37.7-73.6%). Median progression-free survival was 6.5 months (95% CI, 4.6-13.5); median duration of survival was 14.8 months (95% CI, 6.9-27.3). The most common hematologic toxicity was leukopenia, which were grade 3 or 4 in 16 patients (50%). Radiation pneumonitis (grade >or=2) occurred in 13 of 31 treated patients (42%). These findings suggested that concurrent chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel is clinically active based on median survival in patients with unresectable stage III NSCLC; however, the 42% incidence of clinical radiation pneumonitis was unexpected and warrants further investigation to determine the mechanism and preventive strategies.


The molecular mechanism of programmed cell death in C. elegans.
Programmed cell death or apoptosis plays a fundamental role during animal development, metamorphosis, and tissue homeostasis. It is a genetically controlled physiological process that comprises two distinct and sequential processes: the death of cells, and their subsequent removal by engulfing cells. In the nematode C. elegans, genetic studies led to the discovery of 15 genes that function in programmed cell death (FIG. 1). These 15 genes have been divided into four groups based on the order of their activity during the process of programmed cell death: (1) those involved in the decision making (ces-1 and ces-2); (2) in the process of execution (ced-3, ced-4, ced-9 and egl-1); (3) in the engulfment of dying cells by engulfing cells (ced-1, ced-2, ced-5, ced-6, ced-7, ced-10, ced-12); and (4) those in the degradation of cell corpses within engulfing cells (nuc-1). In the last five years, several genes in the genetic pathway of programmed cell death have been shown to be conserved across a wide range of species; all genes involved in the step of execution in C. elegans have their corresponding mammalian homologs (FIG. 2). Furthermore, emerging evidence from molecular studies of engulfment genes in several species suggests that the signaling process from apoptotic cells to engulfing cells and the subsequent engulfment process might be also conserved across species (TABLE 1).


TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Adipokines affect mammary growth and function in farm animals.
The essential role of mammary fat pads in mammary growth and morphogenesis was the first indication that biologically active molecules, secreted from adipocytes or other stromal cells, could regulate endocrine cues for growth and function of the mammary gland. The presence of leptin and adiponectin receptors in mammary tissues suggested that locally produced or circulating adipokines could affect mammary growth and function. Herein, we present the current knowledge on the role of adipokines in mammary cell proliferation and differentiation and in lactogenesis and galactopoiesis in farm animals. We also address the role of milk adipokines in the neonate. Accumulating evidence suggests that adipokines could act as metabolic sensors, regulating mammary growth and function in periods of metabolic adaptations such as late pregnancy and early lactation. Indeed, different experiments reported that adiponectin and leptin expression varies according to physiological stages and nutritional status of the animal. The current review also demonstrates that adipokines, such as leptin and adiponectin, are important regulators of the action of lactogenic hormones in the mammary gland. Findings also suggest important roles for adipokines in growth and intestinal maturation of the neonate.


In silico analysis of the effects of disease-associated mutations of β-hexosaminidase A in Tay-Sachs disease.
Tay-Sachs disease (TSD), a deficiency of b-hexosaminidase A (Hex A), is a rare but debilitating hereditary metabolic disorder. Symptoms include extensive neurodegeneration and often result in death in infancy. We report an in silico study of 42 Hex A variants associated with the disease. Variants were separated into three groups according to the age of onset: infantile (n=28), juvenile (n=9) and adult (n=5). Protein stability, aggregation potential and the degree of conservation of residues were predicted using a range of in silico tools. We explored the relationship between these properties and the age of onset of TSD. There was no significant relationship between proteinstability and disease severity or between protein aggregation and disease severity. Infantile TSD had a significantly higher mean conservation score than nondisease associated variants. This was not seen in either juvenile or adult TSD. This study has established that the degree of residue conservation may be predictive of infantile TSD. It is possible that these more highly conserved residues are involved in trafficking of the protein to the lysosome. In addition, we developed and validated software tools to automate the process of in silico analysis of proteins involved in inherited metabolic diseases. Further work is required to identify the function of well-conserved residues to establish an in silico predictive model of TSD severity.


Germline Genetic Variants and Lung Cancer Survival in African Americans.
Background: African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases.Methods: Incident non-small cell lung cancer cases (N = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies (N = 316 and 298) were used for replication.Results: One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54-0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71-0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33-0.66).Conclusions: We identified an association between rs1878022 in CMKLR1 and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene-environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival.Impact: We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. Cancer Epidemiol Biomarkers Prev; 26(8); 1288-95. ©2017 AACR.


Comprehending care in a medical home: a usual source of care and patient perceptions about healthcare communication.
To examine whether having a usual source of care (USC) is associated with positive patient perceptions of health care communication and to identify demographic factors among patients with a USC that are independently associated with differing reports of how patients perceive their involvement in health care decision making. Cross-sectional analyses of nationally representative data from the 2002 Medical Expenditure Panel Survey. Among adults with a health care visit in the past year (n = approximately 16,700), we measured independent associations between having a USC and patient perceptions of health care communication. Second, among respondents with a USC (n = approximately 18,000), we assessed the independent association between various demographic factors and indicators of patients' perceptions of their autonomy in making health care decisions. Approximately 78% of adults in the United States reported having a USC. Those with a USC were more likely to report that providers always listened to them, always explained things clearly, always showed respect, and always spent enough time with them. Patients who perceived higher levels of decision-making autonomy were non-Hispanic, had health insurance coverage, lived in rural areas, and had higher incomes. Patients with a USC were more likely to perceive positive health care interactions. Certain demographic factors among the subgroups of Medical Expenditure Panel Survey respondents with a USC were associated with patient perceptions of greater decision-making autonomy. Efforts to ensure universal access to a USC must be partnered with broader awareness and training of USC providers to engage patients from various demographic backgrounds equally when making health care decisions at the point of care.


Nutritional effect of including egg yolk in the weaning diet of breast-fed and formula-fed infants: a randomized controlled trial.
Egg yolks can be a source of docosahexaenoic acid (DHA) and iron but are often associated with adverse consequences on plasma cholesterol. Our goal was to investigate the effect of consumption of 4 egg yolks/wk on infant DHA status and hemoglobin, ferritin, and plasma cholesterol concentrations. Secondary outcomes included plasma iron, transferrin, and transferrin saturation. This was a randomized controlled trial comparing no dietary intervention, consumption of 4 regular egg yolks/wk, and consumption of 4 n-3 fatty acid-enriched egg yolks/wk in breast-fed and formula-fed infants from 6 to 12 mo of age. Erythrocyte DHA concentrations, cholesterol, and iron status were assessed at 6 and 12 mo of age. Of the 82 breast-fed infants recruited, 23 of 28 (no intervention), 23 of 27 (regular eggs), and 24 of 27 (n-3 eggs) completed the trial. Of the 79 formula-fed infants enrolled, 23 of 27 (no intervention), 24 of 26 (regular eggs), and 20 of 26 (n-3 eggs) completed the trial. Erythrocyte DHA concentrations were 30-40% higher after the n-3 egg intervention than after treatment with regular eggs or no eggs in both breast-fed and formula-fed infants. Egg treatment had no significant effect on plasma cholesterol, hemoglobin, ferritin, and transferrin but did result in improvements in plasma iron and transferrin saturation compared with no egg treatment. n-3 Fatty acid-enriched eggs may provide a means of increasing dietary DHA during the second 6 mo of life. Egg yolks may also be a useful source of iron during the weaning period and can be safely included in the weaning diet with no perturbations in plasma cholesterol.


Reliability of questionnaires to assess the healthy eating and activity environment of a child's home and school.
Childhood overweight and obesity are a growing concern globally, and environments, including the home and school, can contribute to this epidemic. This paper assesses the reliability of two questionnaires (parent and teacher) used in the evaluation of a community-based childhood obesity prevention intervention, the eat well be active (ewba) Community Programs. Parents and teachers were recruited from two primary schools and they completed the same questionnaire twice in 2008 and 2009. Data from both questionnaires were classified into outcomes relevant to healthy eating and activity, and target outcomes, based on the goals of the ewba Community Programs, were identified. Fourteen and 12 outcomes were developed from the parent and teacher questionnaires, respectively. Sixty parents and 28 teachers participated in the reliability study. Intraclass correlation coefficients for outcomes ranged from 0.37 to 0.92 (parent) (P < 0.05) and from 0.42 to 0.86 (teacher) (P < 0.05). Internal consistency, measured by Cronbach's alpha, of teacher scores ranged from 0.11 to 0.91 and 0.13 to 0.78 for scores from the parent questionnaire. The parent and teacher questionnaires are moderately reliable tools for simultaneously assessing child intakes, environments, attitudes, and knowledge associated with healthy eating and physical activity in the home and school and may be useful for evaluation of similar programs.


Chronic skeletal unloading of the rat femur: mechanisms and functional consequences of vascular remodeling.
Chronic skeletal unloading diminishes hindlimb bone blood flow. The purpose of the present investigation was to determine 1) whether 7 and 14days of skeletal unloading alter femoral bone and marrow blood flow and vascular resistance during reloading, and 2) whether putative changes in bone perfusion are associated with a gross structural remodeling of the principal nutrient artery (PNA) of the femur. Six-month old male Sprague-Dawley rats were assigned to 7-d or 14-d hindlimb unloading (HU) or weight-bearing control groups. Bone perfusion was measured following 10min of standing (reloading) following the unloading treatment. Histomorphometry was used to determine PNA media wall thickness and maximal diameter. Bone blood flow, arterial pressure and PNA structural characteristics were used to calculate arterial shear stress and circumferential wall stress. During reloading, femoral perfusion was lower in the distal metaphyseal region of 7-d HU rats, and in the proximal and distal metaphyses, diaphysis and diaphyseal marrow of 14-d HU animals relative to that in control rats. Vascular resistance was also higher in all regions of the femur in 14-d HU rats during reloading relative to control animals. Intraluminal diameter of PNAs from 14-d HU rats (138±5μm) was smaller than that of control PNAs (162±6μm), and medial wall thickness was thinner in PNAs from 14-d HU (14.3±0.6μm) versus that of control (18.0±0.8μm) rats. Decreases in both shear stress and circumferential stress occurred in the PNA with HU that later returned to control levels with the reductions in PNA maximal diameter and wall thickness, respectively. The results demonstrate that chronic skeletal unloading attenuates the ability to increase blood flow and nutrient delivery to bone and marrow with immediate acute reloading due, in part, to a remodeling of the bone resistance vasculature.


Oxygen uptake kinetics and maximal aerobic power are unaffected by inspiratory muscle training in healthy subjects where time to exhaustion is extended.
The aim of this study was to determine whether 4 weeks of inspiratory muscle training (IMT) would be accompanied by alteration in cardiopulmonary fitness as assessed through moderate intensity oxygen uptake (V(.)O(2)) kinetics and maximal aerobic power (V(.)O(2max)). Eighteen healthy males agreed to participate in the study [training group (Tra) n=10, control group (Con) n=8]. Measurements of spirometry and maximal static inspiratory mouth pressure ( PI(max)) were taken pre- and post-training in addition to: (1) an incremental test to volitional exhaustion, (2) three square-wave transitions from walking to running at a moderate intensity (80% ventilatory threshold) and (3) a maximal aerobic constant-load running test to volitional fatigue for the determination of time to exhaustion ( T(lim)). Training was performed using an inspiratory muscle trainer (Powerbreathe). There were no significant differences in spirometry either between the two groups or when comparing the post- to pre-training results within each group. Mean PI(max) increased significantly in Tra ( P<0.01) and showed a trend for improvement ( P<0.08) in Con. Post-training T(lim) was significantly extended in both Tra [232.4 (22.8) s and 242.8 (20.1) s] ( P<0.01) and Con [224.5 (19.6) and 233.5 (12.7) s] ( P<0.05). Post-training T(lim) was significantly extended in Tra compared to Con ( P<0.05). In conclusion, the most plausible explanation for the stability in V(.)O(2) kinetics and V(.)O(2max) following IMT is that it is due to insufficient whole-body stress to elicit either central or peripheral cardiopulmonary adaptation. The extension of post-training T(lim) suggests that IMT might be useful as a stratagem for producing greater volumes of endurance work at high ventilatory loads, which in turn could improve cardiopulmonary fitness.


Model-informed COVID-19 vaccine prioritization strategies by age and serostatus.
Limited initial supply of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine raises the question of how to prioritize available doses. We used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20 to 49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults greater than 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact. Although maximum impact prioritization strategies were broadly consistent across countries, transmission rates, vaccination rollout speeds, and estimates of naturally acquired immunity, this framework can be used to compare impacts of prioritization strategies across contexts.