Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome-wide associations.
Genome-wide association studies (GWAS) using high-density genotyping platforms offer an unbiased strategy to identify new candidate genes for osteoporosis. It is imperative to be able to clearly distinguish signal from noise by focusing on the best phenotype in a genetic study. We performed GWAS of multiple phenotypes associated with fractures [bone mineral density (BMD), bone quantitative ultrasound (QUS), bone geometry, and muscle mass] with approximately 433,000 single-nucleotide polymorphisms (SNPs) and created a database of resulting associations. We performed analysis of GWAS data from 23 phenotypes by a novel modification of a block clustering algorithm followed by gene-set enrichment analysis. A data matrix of standardized regression coefficients was partitioned along both axes--SNPs and phenotypes. Each partition represents a distinct cluster of SNPs that have similar effects over a particular set of phenotypes. Application of this method to our data shows several SNP-phenotype connections. We found a strong cluster of association coefficients of high magnitude for 10 traits (BMD at several skeletal sites, ultrasound measures, cross-sectional bone area, and section modulus of femoral neck and shaft). These clustered traits were highly genetically correlated. Gene-set enrichment analyses indicated the augmentation of genes that cluster with the 10 osteoporosis-related traits in pathways such as aldosterone signaling in epithelial cells, role of osteoblasts, osteoclasts, and chondrocytes in rheumatoid arthritis, and Parkinson signaling. In addition to several known candidate genes, we also identified PRKCH and SCNN1B as potential candidate genes for multiple bone traits. In conclusion, our mining of GWAS results revealed the similarity of association results between bone strength phenotypes that may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in identifying novel genes and pathways that underlie several correlated phenotypes, as well as in deciphering genetic and phenotypic modularity underlying osteoporosis risk.


The role of zinc in the treatment of tinnitus.
This study was designed to investigate the role of zinc administration in treatment of tinnitus. Randomized, prospective, placebo-controlled study. Patients with tinnitus were admitted to the ear, nose, and throat clinic of the authors' hospital. Patients with tinnitus with no know pathologic conditions of the ear, nose, and throat; the mean age of 28 patients receiving zinc was 51.2 years, and that of 13 patients given placebo was 55 years. Blood zinc levels were measured. Frequency was detected by audiometry, and loudness of tinnitus was screened by tinnitus match test. A questionnaire that scored tinnitus subjectively between 0 and 7 was given to patients before zinc treatment. After 2 months of treatment (zinc 50 mg daily to zinc group, placebo pill containing starch to placebo group), all of the tests were performed again. There was no difference in age, sex, duration of tinnitus, and affected ears between the patients treated with zinc and those treated with placebo. Blood zinc levels were lower than normal in 31% of patients before treatment. A decrease in tinnitus loudness by at least 10 dB was accepted as clinically favorable progress. A decrease of more than 1 point in subjective tinnitus scoring was accepted as valid. Clinically favorable progress was detected in 46.4% of patients given zinc. Although this decrease was not statistically significant, the severity of subjective tinnitus decreased in 82% of the patients receiving zinc. The mean of subjective tinnitus decreased from 5.25 +/- 1.08 to 2.82 +/- 1.81 ( < 0.001). However, the decrease in severity of the tinnitus was not significant in patients receiving placebo. It can be concluded that patients with tinnitus may have low blood zinc levels (31%) and clinical and subjective improvement can be achieved by oral zinc medication. However, it remains to be seen whether the longer duration of treatment has more significant results.


In vitro expansion of adipose-derived adult stromal cells in hypoxia enhances early chondrogenesis.
Cartilage is an avascular tissue, and chondrocytes in vivo experience a severely hypoxic environment. Using a defined in vitro model of early chondrogenesis, we attempted to enrich for cells with an enhanced ability for chondrogenic differentiation by pre-exposure of mouse adipose-derived adult stromal cells (ADASs) to a hypoxic (2% oxygen) environment. ADASs were subsequently expanded in 2% or 21% oxygen environments, resulting in 2 groups of cells, and then early chondrogenic differentiation was induced at 21% oxygen tension using a 3-dimensional micromass culture system. ADAS chondrogenesis was assessed using Alcian Blue staining for proteoglycans and quantification of sulfated glycosaminoglycans. Osteogenesis of the 2 cell groups was also studied. Two percent oxygen tension profoundly increased the proliferation of ADASs. ADASs expanded in 2% oxygen tension exhibited enhanced early chondrogenic differentiation and diminished osteogenesis, suggesting that the reduced oxygen environment may favor chondroprogenitors. Gene expression analysis suggested that matrix metalloproteinase synthesis was inhibited in cells expanded in 2% oxygen. Furthermore, re-oxygenation of the 2% oxygen-expanded ADASs before differentiation did not significantly affect early chondrogenesis. Thus, priming ADASs with 2% oxygen may have selected for chondrogenic progenitors with an enhanced ability to survive and differentiate. This study is relevant for the future application of cell-based therapies involving cartilage tissue regeneration.


Nursing homes and end-of-life care in Japan.
To describe end-of-life care in Japanese nursing homes by comparing facility and characteristics of residents dying in nursing homes with those who had been transferred and had died in hospitals, and by comparing the quality of end-of-life care with hospitals and with their respective counterparts in the United States. National sample of 653 nursing homes with responses from 371 (57%) on their facility characteristics, 241 (37%) on their resident characteristics, and 92 (14%) on the residents' quality of life. All 5 hospitals in a city 80 miles from Tokyo cooperated. Nursing home staff answered questionnaires on facility and resident characteristics. Resident level data were obtained from 1158. The questionnaire on the quality of care was responded to by 256 (63%) of the decedents' families in nursing homes and 205 (48%) in hospitals. Facility characteristics included items on physicians, nurse staffing, and the facility's end-of-life care policy. Resident characteristics included basic demographics, level of dementia, and resident's and family's preference for the site of death. The Toolkit was used to measure the quality of end-of-life care. The proportion of those dying within the nursing home was related to the facility's policy on end-of-life care and the family's preference. The quality of end-of-life care in nursing homes was generally better than in hospitals, and than in their respective counterparts in the United States. Financial incentives by the Japanese government to promote end-of-life care in nursing homes may have contributed to increasing the proportion of deaths within the facility. The quality of care in nursing homes was evaluated as being better than hospitals.


A Method for the Immortalization of Newborn Mouse Skin Keratinocytes.
Isolation and culture of mouse primary epidermal keratinocytes is a common technique that allows for easy genetic and environmental manipulation. However, due to their limited lifespan in culture, experiments utilizing primary keratinocytes require large numbers of animals, and are time consuming and expensive. To avoid these issues, we developed a method for the immortalization of primary mouse epidermal keratinocytes. Upon isolation of newborn epidermal keratinocytes according to established methods, the cells were cultured long-term in keratinocyte growth factor-containing medium. The cells senesced within a few weeks and eventually, small, slowly growing colonies emerged. After they regained confluency, the cells were passaged and slowly refilled the dish. With several rounds of subculture, the cells adapted to culture conditions, were easily subcultured, maintained normal morphology, and were apparently immortal. The immortalized cells retained the ability to differentiate with increased calcium concentrations, and were maintained to high passage numbers while maintaining a relatively stable karyotype. Analysis of multiple immortalized cell lines as well as primary keratinocyte cultures revealed increased numbers of chromosomes, especially in the primary keratinocytes, and chromosomal aberrations in most of the immortalized cultures and in the primary keratinocytes. Orthotopic grafting of immortalized keratinocytes together with fibroblasts onto nude mouse hosts produced skin while v-ras(Ha) infection of the immortalized keratinocytes prior to grafting produced squamous cell carcinoma. In summary, this method of cell line generation allows for decreased use of animals, reduces the expense and time involved in research, and provides a useful model for cutaneous keratinocyte experimentation.


Planning Risk-Based Statistical Quality Control Strategies: Graphical Tools to Support the New Clinical and Laboratory Standards Institute C24-Ed4 Guidance.
Clinical and Laboratory Standards Institute (CLSI)'s new guideline for statistical quality control (SQC; C24-Ed4) (CLSI C24-Ed4, 2016; Parvin CA, 2017) recommends the implementation of risk-based SQC strategies. Important changes from earlier editions include alignment of principles and concepts with the general patient risk model in CLSI EP23A (CLSI EP23A, 2011) and a recommendation for optimizing the frequency of SQC (number of patients included in a run, or run size) on the basis of the expected number of unreliable final patient results. The guideline outlines a planning process for risk-based SQC strategies and describes 2 applications for examination procedures that provide 9-σ and 4-σ quality. A serious limitation is that there are no practical tools to help laboratories verify the results of these examples or perform their own applications. Power curves that characterize the rejection characteristics of SQC procedures were used to predict the risk of erroneous patient results based on Parvin's MaxE(Nuf) parameter (Clin Chem 2008;54:2049-54). Run size was calculated from MaxE(Nuf) and related to the probability of error detection for the critical systematic error (Pedc). A plot of run size vs Pedc was prepared to provide a simple nomogram for estimating run size for common single-rule and multirule SQC procedures with Ns of 2 and 4. The "traditional" SQC selection process that uses power function graphs to select control rules and the number of control measurements can be extended to determine SQC frequency by use of a run size nomogram. Such practical tools are needed for planning risk-based SQC strategies.


Effects of gender on nigral gene expression and parkinson disease.
To identify gene expression patterns in human dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of male and female control and Parkinson disease (PD) patients, we harvested DA neurons from frozen SNc from 16 subjects (4 male PDs, 4 female PDs, 4 male and 4 female controls) using Laser Capture microdissection and microarrays. We assessed for enrichment of functional categories with a hypergeometric distribution. The data were validated with QPCR. We observed that gender has a pervasive effect on gene expression in DA neurons. Genes upregulated in females relative to males are mainly involved in signal transduction and neuronal maturation, while in males some of the upregulated genes (alpha-synuclein and PINK1) were previously implicated in the pathogenesis of PD. In females with PD we found alterations in genes with protein kinase activity, genes involved in proteolysis and WNT signaling pathway, while in males with PD there were alterations in protein-binding proteins and copper-binding proteins. Our data reveal broad gender-based differences in gene expression in human dopaminergic neurons of SNc that may underlie the predisposition of males to PD. Moreover, we show that gender influences the response to PD, suggesting that the nature of the disease and the response to treatment may be gender-dependent.


Modulation of vascular response after injury in the rat Achilles tendon alters healing capacity.
Tendons are relatively hypovascular but become hypervascular during both injury and degeneration. This is due to the angiogenic response, or the formation of new blood vessels, to tissue injury. The objective of this study was to evaluate the effect of vascular modulation in the rat Achilles tendons during healing. Fischer rats received a bilateral Achilles incisional injury followed by local injections of vascular endothelial growth factor (VEGF), anti-VEGF antibody (B20.4-1-1), or saline either early or late during the healing process. Vascular modulation and healing were evaluated using multiple in vivo ultrasound imaging modalities, in vivo functional assessment, and ex vivo measures of tendon compositional and mechanical properties. The late delivery of anti-VEGF antibody, B20, caused a temporary reduction in healing capacity during a time point where vascularity was also decreased, and then an improvement during a later time point where vascularity was increased relative to control. However, VEGF delivery had a minimal impact on healing and vascular changes in both early and late delivery times. This study was the first to evaluate vascular changes using both in vivo imaging methods and ex vivo histological methods, as well as functional and mechanical outcomes associated with these vascular changes. Clinical significance: this study demonstrates that the alteration of vascular response through the delivery of angiogenic growth factors has the ability to alter tendon healing properties.


Candida albicans-epithelial interactions: dissecting the roles of active penetration, induced endocytosis and host factors on the infection process.
Candida albicans frequently causes superficial infections by invading and damaging epithelial cells, but may also cause systemic infections by penetrating through epithelial barriers. C. albicans is a remarkable pathogen because it can invade epithelial cells via two distinct mechanisms: induced endocytosis, analogous to facultative intracellular enteropathogenic bacteria, and active penetration, similar to plant pathogenic fungi. Here we investigated the contributions of the two invasion routes of C. albicans to epithelial invasion. Using selective cellular inhibition approaches and differential fluorescence microscopy, we demonstrate that induced endocytosis contributes considerably to the early time points of invasion, while active penetration represents the dominant epithelial invasion route. Although induced endocytosis depends mainly on Als3-E-cadherin interactions, we observed E-cadherin independent induced endocytosis. Finally, we provide evidence of a protective role for serum factors in oral infection: human serum strongly inhibited C. albicans adhesion to, invasion and damage of oral epithelial cells.


Fatigue and multidimensional disease severity in chronic obstructive pulmonary disease.
Fatigue is associated with longitudinal ratings of health in patients with chronic obstructive pulmonary disease (COPD). Although the degree of airflow obstruction is often used to grade disease severity in patients with COPD, multidimensional grading systems have recently been developed. The aim of this study was to investigate the relationship between perceived and actual fatigue level and multidimensional disease severity in patients with COPD. Twenty-two patients with COPD (aged 52-74 years) took part in the study. Multidimensional disease severity was measured using the SAFE and BODE indices. Perceived fatigue was assessed using the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS). Peripheral muscle endurance was evaluated using the number of sit-ups, squats, and modified push-ups that each patient could do. Thirteen patients (59%) had severe fatigue, and their St George's Respiratory Questionnaire scores were significantly higher (p < 0.05). The SAFE index score was significantly correlated with the number of sit-ups, number of squats, FSS score and FIS score (p < 0.05). The BODE index was significantly associated with the numbers of sit-ups, squats and modified push-ups, and with the FSS and FIS scores (p < 0.05). Peripheral muscle endurance and fatigue perception in patients with COPD was related to multidimensional disease severity measured with both the SAFE and BODE indices. Improvements in perceived and actual fatigue levels may positively affect multidimensional disease severity and health status in COPD patients. Further research is needed to investigate the effects of fatigue perception and exercise training on patients with different stages of multidimensional COPD severity.


The development of giant lipoma on the BCG vaccine caused scar.
Lipoma is the most common mesenchymal tumors that accounts for about 6% of all soft-tissue tumors in children. The lesion size is usually around 1-2 cm that rarely reaches the bigger diameter. A 14-month-old baby girl was brought to our clinic for a progressively growing lesion on the left shoulder. The lesion started 4 months ago, and then was rapidly growing that caused pain and movement restriction. On the same site, there was a scar of BCG vaccination. The clinical and histopathological findings of the lesion were consistent with lipoma. The lesion was totally resected with no recurrence within 12 months. There are several complications related to BCG vaccination. However, the occurrence of lipoma on BCG vaccine caused scar has not been reported in literature. We reported this case because of its rarity and to emphasize that lipoma can present as a giant lesion in child.


Review: interventions to increase influenza vaccination among healthcare workers in hospitals.
Annual influenza vaccination rates among hospital healthcare workers (HCW) are almost universally low despite recommendations from WHO and public health authorities in many countries. To assist in the development of successful vaccination programmes, we reviewed studies where interventions aimed to increase the uptake of influenza vaccination among hospital HCW. We searched PUBMED from 1990 up to December 2011 for publications with predetermined search strategies and of pre-defined criteria for inclusion or exclusion. We evaluated a large number of 'intervention programmes' each employing one or more 'intervention components' or strategies, such as easy access to vaccine or educational activities, with the goal to raise influenza vaccine uptake rates in hospital HCW during one influenza season. Included studies reported results of intervention programmes and compared the uptake with the season prior to the intervention (historical control) or to another intervention programme within the same season that started from the same set of baseline activities. Twenty-five studies performed in eight countries met our selection criteria and described 45 distinct intervention programmes. Most studies used their own facility as historical control and evaluated only one season. The following elements were used in intervention programmes that increased vaccine uptake: provision of free vaccine, easy access to the vaccine (e.g. through mobile carts or on-site vaccination), knowledge and behaviour modification through educational activities and/or reminders and/or incentives, management or organizational changes, such as the assignment of personnel dedicated to the intervention programme, long-term implementation of the strategy, requiring active declination and mandatory immunization policies. The number of these components applied appeared to be proportional to the increase in uptake. If influenza uptake in hospital HCW is to be increased on sustained basis, hospital managers need to be committed to conduct a well-designed long-term intervention programme that includes a variety of co-ordinated managerial and organizational elements.


Glucocorticoids manifest androgenic activity in a cell line derived from a metastatic prostate cancer.
The pathophysiological mechanism(s) by which androgen independence develops in prostate cancer remains to be determined. The identification in many prostate cancer specimens of a mutant androgen receptor, T877A, with altered ligand specificity has provided an explanation for some treatment failures. The T877A mutant androgen receptor recognizes a number of nonandrogenic compounds, including certain estrogens, progestins, and even antiandrogens as androgens. However, a comprehensive screen for hormonal agents which display agonist activity on this mutant has not been performed. In this study, we characterized this clinically important receptor mutant further and found that it can be activated by a wide range of compounds, including a number of endogenous glucocorticoids. Among the most clinically relevant compounds identified are DOC and corticosterone, both of which can effectively activate the mutant receptor at concentrations normally found in blood. Dexamethasone, a synthetic glucocorticoid frequently used in various contexts for prostate cancer therapy, is also recognized as an androgen by the mutant receptor. These unexpected findings suggest the need to: (a) reassess the role of adrenally derived glucocorticoids in prostate cancer disease progression; and (b) recognize the potential for iatrogenic stimulation of disease progression with certain glucocorticoid interventions.


Prenatal polycyclic aromatic hydrocarbon (PAH) exposure and child behavior at age 6-7 years.
Airborne polycyclic aromatic hydrocarbons (PAH) are widespread urban air pollutants from fossil fuel burning and other combustion sources. We previously reported that a broad spectrum of combustion-related DNA adducts in cord blood was associated with attention problems at 6-7 years of age in the Columbia Center for Children's Environmental Health (CCCEH) longitudinal cohort study. We evaluated the relationship between behavioral problems and two different measures of prenatal exposure--both specific to PAH--in the same cohort. Children of nonsmoking African-American and Dominican women in New York City (NYC) were followed from in utero to 6-7 years. Prenatal PAH exposure was estimated by personal air monitoring of the mothers during pregnancy as well as by the measurement of DNA adducts specific to benzo[a]pyrene (BaP), a representative PAH, in maternal and cord blood. At 6-7 years of age, child behavior was assessed using the Child Behavior Checklist (CBCL) (n = 253). Generalized linear models were used to test the association between prenatal PAH exposure and behavioral outcomes. In multivariate analyses, high prenatal PAH exposure, whether characterized by personal air monitoring (greater than the median of 2.27 ng/m³) or maternal and cord adducts (detectable or higher), was positively associated with symptoms of Anxious/Depressed and Attention Problems (p ≤ 0.05). These results provide additional evidence that environmental levels of PAH encountered in NYC air can adversely affect child behavior.


Molecular and social regulation of worker division of labour in fire ants.
Reproductive and worker division of labour (DOL) is a hallmark of social insect societies. Despite a long-standing interest in worker DOL, the molecular mechanisms regulating this process have only been investigated in detail in honey bees, and little is known about the regulatory mechanisms operating in other social insects. In the fire ant Solenopsis invicta, one of the most studied ant species, workers are permanently sterile and the tasks performed are modulated by the worker's internal state (age and size) and the outside environment (social environment), which potentially includes the effect of the queen presence through chemical communication via pheromones. However, the molecular mechanisms underpinning these processes are unknown. Using a whole-genome microarray platform, we characterized the molecular basis for worker DOL and we explored how a drastic change in the social environment (i.e. the sudden loss of the queen) affects global gene expression patterns of worker ants. We identified numerous genes differentially expressed between foraging and nonforaging workers in queenright colonies. With a few exceptions, these genes appear to be distinct from those involved in DOL in bees and wasps. Interestingly, after the queen was removed, foraging workers were no longer distinct from nonforaging workers at the transcriptomic level. Furthermore, few expression differences were detected between queenright and queenless workers when we did not consider the task performed. Thus, the social condition of the colony (queenless vs. queenright) appears to impact the molecular pathways underlying worker task performance, providing strong evidence for social regulation of DOL in S. invicta.


COVID-19 Lung Injury and High Altitude Pulmonary Edema: A False Equation with Dangerous Implications.
Amid efforts to care for the large number of patients with COVID-19, there has been considerable speculation about whether the lung injury seen in these patients is different than ARDS from other causes. One idea that has garnered considerable attention, particularly on social media and in free open access medicine is the notion that lung injury due to COVID-19 is more similar to high altitude pulmonary edema (HAPE). Drawing on this concept, it has also been proposed that treatments typically employed in the management of HAPE and other forms of acute altitude illness, pulmonary vasodilators and acetazolamide, should be considered for COVID-19. Despite some similarities in clinical features between the two entities, such as hypoxemia, radiographic opacities and altered lung compliance, the pathophysiological mechanisms of HAPE and lung injury due to COVID-19 are fundamentally different and the entities cannot be viewed as equivalent. While of high utility in the management of HAPE and acute mountain sickness, systemically delivered pulmonary vasodilators and acetazolamide should not be used in the treatment of COVID-19, as they carry the risk of multiple adverse consequences including worsened ventilation-perfusion matching, impaired carbon dioxide transport, systemic hypotension and increased work of breathing.


The timing of action-monitoring processes in the anterior cingulate cortex.
The anterior cingulate cortex (ACC) has been shown to respond to conflict between simultaneously active, incompatible response tendencies. This area is active during high-conflict correct trials and also when participants make errors. Here, we use the temporal resolution of high-density event-related potentials (ERPs) in combination with source localization to investigate the timing of ACC activity during conflict and error detection. We predicted that the same area of the ACC is active prior to high-conflict correct responses and following erroneous responses. Dipole modeling supported this prediction: The frontocentral N2, occurring prior to the response on correct conflict trials, and the ERN, occurring immediately following error responses, could both be modeled as having a generator in the caudal ACC, suggesting the same process to underlie both peaks. Modeling further suggested that the rostral area of the ACC was also active following errors, but later in time, contributing to the error positivity (P(E)), and peaking at 200-250 msec following the ERN peak. Despite the inherent limitations of source localization, these data may begin to shed light on the timing of action-monitoring processes. First, the time course of caudal ACC activity follows the time course as predicted by the conflict theory of this region. Second, caudal ACC activity might be temporally dissociated from rostral ACC activity during error trials, which possibly reflects a separate, affective component of the evaluative functions of the ACC.


Psoriasiform Pemphigus Foliaceus in an African American Female: An Important Clinical Manifestation.
A 50-year-old African-American woman presented to the dermatology clinic with a pruritic eruption of 3 years' duration. On clinical examination, the patient had well-demarcated, pink, atrophic plaques and superficial erosions over the inframammary folds and mid-chest. She also had well-demarcated, hyperpigmented, hyperkeratotic scaly plaques over the abdomen, suprapubic region, elbows, knees, and back with sporadic small superficial blisters. A punch biopsy of the right abdomen was performed and revealed psoriasiform epidermal hyperplasia, focal parakeratosis, and acantholysis throughout the superficial spinous and granular layers. Only a sparse inflammatory infiltrate was present in the underlying dermis. Clinical and histological findings supported the diagnosis of pemphigus foliaceus (PF), but psoriasis was included in the differential diagnosis due to the presence of discrete plaques with an erythematous border. We hypothesize that patients with psoriasiform presentations of PF may be misdiagnosed with plaque psoriasis. It is important to distinguish between PF and psoriasis as there is evidence that ultraviolet light, a common treatment for psoriasis, may exacerbate PF. We document and highlight this atypical psoriasiform presentation of PF in a patient with skin of color to raise awareness and improve diagnosis and outcomes.
J Drugs Dermatol. 2018;17(4):471-473.
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Viral etiology of influenza-like illnesses in Antananarivo, Madagascar, July 2008 to June 2009.
In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs). From July 2008 to June 2009, we collected respiratory specimens from patients who presented ILIs symptoms in public and private clinics in Antananarivo (the capital city of Madagascar). ILIs were defined as body temperature ≥38°C and cough and at least two of the following symptoms: sore throat, rhinorrhea, headache and muscular pain, for a maximum duration of 3 days. We screened these specimens using five multiplex real time Reverse Transcription and/or Polymerase Chain Reaction assays for detection of 14 respiratory viruses. We detected respiratory viruses in 235/313 (75.1%) samples. Overall influenza virus A (27.3%) was the most common virus followed by rhinovirus (24.8%), RSV (21.2%), adenovirus (6.1%), coronavirus OC43 (6.1%), influenza virus B (3.9%), parainfluenza virus-3 (2.9%), and parainfluenza virus-1 (2.3%). Co-infections occurred in 29.4% (69/235) of infected patients and rhinovirus was the most detected virus (27.5%). Children under 5 years were more likely to have one or more detectable virus associated with their ILI. In this age group, compared to those ≥5 years, the risk of detecting more than one virus was higher (OR = 1.9), as was the risk of detecting of RSV (OR = 10.1) and adenovirus (OR = 4.7). While rhinovirus and adenovirus infections occurred year round, RSV, influenza virus A and coronavirus OC43 had defined period of circulation. In our study, we found that respiratory viruses play an important role in ILIs in the Malagasy community, particularly in children under 5 years old. These data provide a better understanding of the viral etiology of outpatients with ILI and describe for the first time importance of these viruses in different age group and their period of circulation.


Neuronal nitric oxide synthase within paraventricular nucleus: blood pressure and baroreflex in two-kidney, one-clip hypertensive rats.
The renin-angiotensin system is activated in the early phase of two-kidney, one-clip (2K-1C) hypertension. The paraventricular nucleus (PVN) integrates inputs regulating sympathetic outflow. The PVN receives inputs from plasma angiotensin II via projections from circumventricular organs and from renal afferent nerves transmitted via the nucleus tractus solitarii. Nitric oxide within the PVN may exert a sympathoinhibitory effect. These studies tested whether decreasing endogenous nitric oxide by introducing dominant negative (DN) constructs for neuronal nitric oxide synthase (nNOS) into PVN chronically augments hypertension and/or modulates baroreflex function. Male 6-week-old Sprague-Dawley rats underwent sham surgery or right renal artery clipping and placement of radiotelemetry transmitters. One week later, the PVN was injected bilaterally with 250 nl artificial cerebrospinal fluid containing 250 ng microl(-1) of RSV beta-galactosidase (beta-Gal), cytomegalovirus (CMV) wild-type (WT nNOS), or respiratory syncytial virus (RSV) haeme domain or RSV haemeRedF (DN nNOS). Haemodynamics were monitored for 5 weeks. Then left renal nerve electrodes were placed, and 2 days later the rats underwent baroreflex testing in the conscious state. The rise in mean arterial pressure (MAP) was significantly potentiated in the DN nNOS 2K-1C group beyond 15 days after PVN injection. By day 35, MAP in the 2K-1C groups was 152 +/- 6.3 (beta-Gal), 155.1 +/- 6.6 (WT nNOS) and 179 +/- 5.4 mmHg (DN nNOS; P < 0.01 versus all other groups). Sham-clipped rats remained normotensive. All groups displayed progressive bradycardia over time that was attenuated in the DN nNOS 2K-1C group. Baroreflex curves shifted to higher pressures, and baroreflex sensitivity of heart rate was diminished to a similar extent in all groups of 2K-1C rats. The baroreflex response of renal sympathetic nerve activity was preserved. The PVN tissue from DN nNOS rats had decreased dimerization of nNOS and generation of total nitric oxide. These findings indicate that chronic interference of nNOS dimerization required for generation of nitric oxide within the PVN potentiates the increase of blood pressure by modulating the sympathoexcitation that accompanies renovascular hypertension.


Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men.
The presence of the less-active form of alcohol dehydrogenase-1B encoded by ADH1B*1/*1 (vs. *2 allele) and active form of aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/*1 (vs. *2 allele) increases the risk of alcoholism in East Asians. The subjects in this cross-sectional survey were 1,902 Japanese alcoholic men (≥40 years) who underwent ADH1B/ALDH2 genotyping. Age-adjusted daily alcohol consumption did not differ according to the ADH1B/ALDH2 genotypes. The age-adjusted odds ratios (AORs; 95% confidence interval) for liver cirrhosis (LC; n = 359, 1.58 [1.19 to 2.09]), chronic calcific pancreatitis (CP; n = 80, 2.24 [1.20 to 4.20]), and diabetes mellitus (DM; n = 383, 1.51 [1.15 to 1.99]) were higher in the ADH1B*2 allele carriers than in the ADH1B*1/*1 carriers. The AORs for LC (1.43 [1.01 to 2.02]), CP (1.68 [0.80 to 3.53]), DM (1.63 [1.15 to 2.30]), and hypertension (HT; n = 495, 1.52 [1.11 to 2.07]) were higher in the ALDH2*1/*1 carriers than in the ALDH2*1/*2 carriers. The ADH1B*2-associated AOR for LC was 2.08 (1.46 to 2.94) among those aged 40 to 59 years, but 0.89 (0.56 to 1.43) among those aged 60 years or over, and the interaction between ADH1B genotype and age on the LC risk was significant (p = 0.009). When the group with non-LC and no/mild fibrosis was used as controls, the ADH1B*2-associated AORs increased according to the severity of their liver disease: 1.67 (1.32 to 2.11) for the group with non-LC and serum type IV collagen values ≥200 ng/ml, 1.81 (1.24 to 2.63) for the group of Child-Pugh class A LC, and 3.17 (1.98 to 5.07) for the group with Child-Pugh class B/C LC. Anti-hepatitis C virus (HCV) antibody was positive in 103 patients, and the groups with a high anti-HCV antibody titer and either the ADH1B*2/*2 genotype or the ALDH2*1/*1 genotype had the highest AORs (8.83 and 4.90, respectively). The population attributable fraction (PAF) due to the ADH1B*2 allele was 29% for LC, 47% for CP, and 27% for DM, and the PAF due to the ALDH2*1/*1 genotype was 26% for LC, 34% for DM, and 30% for HT. The ADH1B*2 allele increased the AORs for LC, CP, and DM of the alcoholics, and the ALDH2*1/*1 genotype increased their AORs for LC, DM, and HT. HCV infection and genetic susceptibility had a synergistic effect on the AOR for LC.


Chemical Composition and Antioxidant Properties of Juniper Berry (Juniperus communis L.) Essential Oil. Action of the Essential Oil on the Antioxidant Protection of Saccharomyces cerevisiae Model Organism.
The essential oil of juniper berries (Juniperus communis L., Cupressaceae) is traditionally used for medicinal and flavoring purposes. As elucidated by gas chromatography/flame ionization detector (GC/FID) and gas chromatography/mass spectrometry (GC/MS methods), the juniper berry oil from Bulgaria is largely comprised of monoterpene hydrocarbons such as α-pinene (51.4%), myrcene (8.3%), sabinene (5.8%), limonene (5.1%) and β-pinene (5.0%). The antioxidant capacity of the essential oil was evaluated in vitro by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging, 2,2-azino-bis-3-ethylbenzothiazoline-6 sulfonic acid (ABTS) radical cation scavenging, hydroxyl radical (ОН(•)) scavenging and chelating capacity, superoxide radical ((•)O₂(-)) scavenging and xanthine oxidase inhibitory effects, hydrogen peroxide scavenging. The antioxidant activity of the oil attributable to electron transfer made juniper berry essential oil a strong antioxidant, whereas the antioxidant activity attributable to hydrogen atom transfer was lower. Lipid peroxidation inhibition by the essential oil in both stages, i.e., hydroperoxide formation and malondialdehyde formation, was less efficient than the inhibition by butylated hydroxytoluene (BHT). In vivo studies confirmed these effects of the oil which created the possibility of blocking the oxidation processes in yeast cells by increasing activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).


Diminished bone resorption in rats after oral xylitol administration: a dose-response study.
The effects of 5, 10, and 20% dietary xylitol supplementations on the resorption of bone were studied. The resorption was measured by the urinary excretion of [3H] radioactivity from [3H]tetracycline-prelabeled rats. The 10 and 20% oral xylitol administrations caused a significant decrease in the excretion of [3H] as compared with the control group with no xylitol supplementation. The effect was detected as early as 2 days after the beginning of xylitol-feeding and was maintained throughout the experimental period of 31 days. The retarding effect on bone resorption was about 25% in the 10% xylitol group, about 40% in the 20% xylitol group, and undetectable in the 5% xylitol group. The amount of preserved [3H] radioactivity in the tibiae of the 10 and 20% xylitol groups after the experiment clearly exceeded the values of the control group. The mechanism of the retarded bone resorption caused by dietary xylitol still remains obscure, but an increased absorption of calcium may be involved. In conclusion, dietary xylitol supplementation in rats seems to retard the bone resorption in a dose-dependent way. The effect is achieved rapidly and is maintained at least over a period of 1 month xylitol feeding.


Direct health care insurer and out-of-pocket expenditures of inflammatory bowel disease: evidence from a US national survey.
Crohn's disease (CD) and ulcerative colitis (UC) are chronic, debilitating conditions that can have important economic and clinical implications. To quantify individual and national estimates of the health care and patient out-of-pocket (OOP) costs of CD and UC. In a retrospective study using 1996 to 2009 data from the Medical Expenditure Panel Survey, individuals' self-reported health conditions were mapped to International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. Individuals with a code of 555.x (CD) or 556.x (UC) were identified. Health care services and costs included prescriptions and inpatient, outpatient, emergency room, office, and home health services. OOP costs were the portion of individuals' total payments for health care services. There were 358 individuals with CD (mean age 49.0 years; 55 % female), 198 individuals with UC (mean age 47.1 years; 64 % female), and 206,993 individuals without inflammatory bowel disease (IBD) (mean age 48.2 years; 58 % female). Annual per capita health insurer and OOP costs for individuals with CD were greater than those without IBD ($9,526 versus $3,781, p < 0.001 and $1,603 versus $866, p < 0.001, respectively). Health insurer and OOP costs were greater for UC compared with those without IBD ($6,443 versus $3,781, p < 0.001 and $1,263 versus $866, p < 0.001, respectively). US national aggregate annual estimates of health insurer, OOP, and total direct costs secondary to CD are $2.04 billion, $0.26 billion, and $2.29 billion, respectively. Aggregate health insurer, OOP, and total direct costs attributable to UC are $0.53 billion, $0.07 billion, and $0.61 billion, respectively. The direct costs associated with CD and UC are substantial. The extent to which appropriate diagnosis and treatment reduces the total health care costs for individuals with CD or UC should be examined.


Association of two polymorphisms of the IL28B gene with viral factors and treatment response in 1,518 patients infected with hepatitis C virus.
Two nucleotide polymorphisms of the interleukin-28B (IL28B) gene, at rs8099917 and rs12979860, influence the response to interferon (IFN)-based therapies in patients infected with hepatitis C virus (HCV) of genotype 1. We aimed to investigate whether these polymorphisms showed complete linkage in Japanese patients. A total of 1,518 Japanese patients infected with HCV were genotyped for the two IL28B loci, and the two sets of genotypes were compared. TT at rs8099917 and CC at rs12979860 were detected in 77.7 and 76.8%, respectively, of the 1,518 patients and TG/GG and CT/TT were detected in 22.3 and 23.2%. These two sets of IL28B genotype stood in strong linkage disequilibrium (r (2) = 0.98). Discordance between the two IL28B polymorphisms occurred in 16 (1.1%) patients, and 13 (0.9%) of them possessed IFN-sensitive TT at rs8099917 and IFN-resistant CT at rs12979860. Three of these 13 patients had HCV of genotype 1b and had received pegylated-interferon and ribavirin, and none of them gained a sustained virological response. At rs8099917, IFN-resistant TG/GG were more frequent in patients infected with HCV of genotype 1 than in those infected with HCV of genotype 2 [258/1,046 (24.7%) vs. 75/441 (17.0%), p = 0.001]. The response to pegylated-interferon/ribavirin in 279 patients who were infected with HCV-1 and the response to IFN monotherapy in 361 patients who were infected with HCV-1 , was higher in those with TT than in those with TG/GG at rs8099917, as well as being higher in those with CC than in those with CT/TT at rs12979860 (p < 0.001). Linkage disequilibrium between two IL28B polymorphisms at rs8099917 and rs12979860 is strong in Japanese HCV patients, but there are some discrepancies between the two sets of genotypes.


Induction of Tolerance and Immunity by Dendritic Cells: Mechanisms and Clinical Applications.
Dendritic cells (DCs) are key regulators of immune responses that operate at the interface between innate and adaptive immunity, and defects in DC functions contribute to the pathogenesis of a variety of disorders. For instance, cancer evolves in the context of limited DC activity, and some autoimmune diseases are initiated by DC-dependent antigen presentation. Thus, correcting aberrant DC functions stands out as a promising therapeutic paradigm for a variety of diseases, as demonstrated by an abundant preclinical and clinical literature accumulating over the past two decades. However, the therapeutic potential of DC-targeting approaches remains to be fully exploited in the clinic. Here, we discuss the unique features of DCs that underlie the high therapeutic potential of DC-targeting strategies and critically analyze the obstacles that have prevented the full realization of this promising paradigm.


The Development of Hand-Centered Visual Representations in the Primate Brain: A Computer Modeling Study Using Natural Visual Scenes.
Neurons that respond to visual targets in a hand-centered frame of reference have been found within various areas of the primate brain. We investigate how hand-centered visual representations may develop in a neural network model of the primate visual system called VisNet, when the model is trained on images of the hand seen against natural visual scenes. The simulations show how such neurons may develop through a biologically plausible process of unsupervised competitive learning and self-organization. In an advance on our previous work, the visual scenes consisted of multiple targets presented simultaneously with respect to the hand. Three experiments are presented. First, VisNet was trained with computerized images consisting of a realistic image of a hand and a variety of natural objects, presented in different textured backgrounds during training. The network was then tested with just one textured object near the hand in order to verify if the output cells were capable of building hand-centered representations with a single localized receptive field. We explain the underlying principles of the statistical decoupling that allows the output cells of the network to develop single localized receptive fields even when the network is trained with multiple objects. In a second simulation we examined how some of the cells with hand-centered receptive fields decreased their shape selectivity and started responding to a localized region of hand-centered space as the number of objects presented in overlapping locations during training increases. Lastly, we explored the same learning principles training the network with natural visual scenes collected by volunteers. These results provide an important step in showing how single, localized, hand-centered receptive fields could emerge under more ecologically realistic visual training conditions.


Plasma Aβ but not tau is related to brain PiB retention in early Alzheimer's disease.
Recent advances in biomarkers provide the possibility of early or preclinical diagnosis of Alzheimer's pathology. Currently, decreased levels of Aβ-42 and increased levels of tau proteins in cerebral spinal fluid are considered reliable biomarkers of Alzheimer's disease (AD); however, little evidence exists for the use of amyloid and tau protein levels in the plasma as useful biomarkers. We investigated the potential use of plasma biomarkers to diagnose AD and explored their relationships with brain Aβ deposition in amyloid imaging. We used an immunomagnetic reduction assay to measure the plasma levels of Aβ40, Aβ42, and tau proteins in 20 older control participants and 25 participants who had either mild cognitive impairment due to AD or early AD dementia. All participants received (11)C-labeled Pittsburgh compound B PET scans. The sensitivity of the plasma tau level at the cutoff value of 28.27 pg/mL was 92%, and the specificity was 100%; the sensitivity of the Aβ42/40 ratio at the cutoff value of 0.3693 was 84%, and the specificity was 100%. Regression analyses of the effects of plasma protein levels on brain amyloid retention, as determined by standard uptake value ratios in either side of the frontal, parietal, and temporal lobes and the precuneus, are predicted only by ratios of plasma Aβ42/40 (R(2) 0.326-0.449, all p < 0.001) but not by plasma tau levels. Plasma Aβ in terms of Aβ42/40 might provide an indirect estimation of Aβ deposition in the brain.


Sodium and epithelial sodium channels participate in the regulation of the capacitation-associated hyperpolarization in mouse sperm.
In a process called capacitation, mammalian sperm gain the ability to fertilize after residing in the female tract. During capacitation the mouse sperm plasma membrane potential (E(m)) hyperpolarizes. However, the mechanisms that regulate sperm E(m) are not well understood. Here we show that sperm hyperpolarize when external Na(+) is replaced by N-methyl-glucamine. Readdition of external Na(+) restores a more depolarized E(m) by a process that is inhibited by amiloride or by its more potent derivative 5-(N-ethyl-N-isopropyl)-amiloride hydrochloride. These findings indicate that under resting conditions an electrogenic Na(+) transporter, possibly involving an amiloride sensitive Na(+) channel, may contribute to the sperm resting E(m). Consistent with this proposal, patch clamp recordings from spermatogenic cells reveal an amiloride-sensitive inward Na(+) current whose characteristics match those of the epithelial Na(+) channel (ENaC) family of epithelial Na(+) channels. Indeed, ENaC-alpha and -delta mRNAs were detected by reverse transcription-PCR in extracts of isolated elongated spermatids, and ENaC-alpha and -delta proteins were found on immunoblots of sperm membrane preparations. Immunostaining indicated localization of ENaC-alpha to the flagellar midpiece and of ENaC-delta to the acrosome. Incubations known to produce capacitation in vitro or induction of capacitation by cell-permeant cAMP analogs decreased the depolarizing response to the addition of external Na(+). These results suggest that increases in cAMP content occurring during capacitation may inhibit ENaCs to produce a required hyperpolarization of the sperm membrane.


Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books.
The goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern. A retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors. Seven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3-8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called "the magic potion". Although over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).


Tracking the Implementation of Electronic Medical Records in Dubai, United Arab Emirates, Using an Adoption Benchmarking Tool.
In the United Arab Emirates (UAE), health services have developed greatly in the past 40 years. To ensure they continue to meet the needs of the population, innovation and change are required including investment in a strong e-Health infrastructure with a single transferrable electronic patient record. In this paper, using the Emirate of Dubai as a case study, we report on the Middle East Electronic Medical Record Adoption Model (EMRAM). Between 2011-2016, the number of participating hospitals has increased from 23 to 33. Currently, while 20/33 of hospitals are at Stage 2 or less, 10/33 have reached Stage 5. Also Dubai's median EMRAM score in 2016 (2.5) was higher than the scores reported from Australia (2.2), New Zealand (2.3), Malaysia (0.06), the Philippines (0.06) and Thailand (0.5). EMRAM has allowed the tracking of the progress being made by healthcare facilities in Dubai towards upgrading their information technology infrastructure and the introduction of electronic medical records.


Socio-cultural determinants of timely and delayed treatment of Buruli ulcer: Implications for disease control.
Public health programmes recommend timely medical treatment for Buruli ulcer (BU) infection to prevent pre-ulcer conditions from progressing to ulcers, to minimise surgery, disabilities and the socio-economic impact of BU. Clarifying the role of socio-cultural determinants of timely medical treatment may assist in guiding public health programmes to improve treatment outcomes. This study clarified the role of socio-cultural determinants and health system factors affecting timely medical treatment for BU in an endemic area in Ghana. A semi-structured explanatory model interview based on the explanatory model interview catalogue (EMIC) was administered to 178 BU-affected persons. Based on research evidence, respondents were classified as timely treatment (use of medical treatment 3 months from awareness of disease) and delayed treatment (medical treatment 3 months after onset of disease and failure to use medical treatment). The outcome variable, timely treatment was analysed with cultural epidemiological variables for categories of distress, perceived causes of BU, outside-help and reasons for medical treatment in logistic regression models. The median time for the onset of symptoms to treatment was computed in days. Qualitative phenomenological analysis of respondents' narratives clarified the meaning, context and dynamic features of the relationship of explanatory variables with timely medical treatment. The median time for initiating treatment was 25 days for pre-ulcers, and 204 days for ulcers. Income loss and use of herbalists showed significantly negative associations with timely treatment. Respondents' use of herbalists was often motivated by the desire for quick recovery in order to continue with work and because herbalists were relatives and easily accessible. However, drinking unclean water was significantly associated with timely treatment and access to health services encouraged timely treatment (OR 8.5, p = 0.012). Findings show that health system factors of access are responsible for non-compliance to treatment regimes. Findings highlight the importance of an integrated approach to BU control and management considering the social and economic features that influence delayed treatment and factors that encourage timely medical treatment. This approach should consider periodic screening for early case-detection, collaboration with private practitioners and traditional healers, use of mobile services to improve access, adherence and treatment outcomes.


Palliative care for AIDS: challenges and opportunities in the era of highly active anti-retroviral therapy.
In contrast to the first decade of the AIDS epidemic, the past decade has seen an increasing separation between AIDS care and palliative care services. While this may be due in part to the perception that AIDS is no longer a uniformly fatal illness, AIDS in fact remains an important cause of morbidity and mortality for young adult populations in the United States, particularly among certain racial-ethnic minorities. Death rates have remained steady since the dramatic decreases noted in the mid-1990s, and causes of death now increasingly include co-morbidities such as hepatitis B, C, end-organ failure, and various malignancies. Moreover, as AIDS has been transformed into a more manageable, chronic disease in the era of 'highly active antiretroviral therapy' (HAART), the opportunities for palliative care interventions have only increased. Patients with AIDS continue to experience a high burden of pain and other chronic symptoms, over a longer period of time, with a disease course marked by more cumulative exacerbations and remissions than when AIDS was a stereotypic, rapidly fatal illness. Advance care planning and discussions of goals of care are more complex and involve more uncertainty than was the case when prognosis was clear-cut and treatment options were more limited. For all of these reasons, it is important for the distance which has developed between HIV and palliative care providers to be bridged. Contrary to popular perceptions, palliative medicine continues to have much to offer in the HAART era for the care of patients and families with HIV/AIDS, for whom treatment outcomes will only benefit from greater integration of disease-specific and palliative interventions. The challenge for care providers is now to implement successful strategies for integrating AIDS and palliative care services in all relevant clinical environments.


Operando and three-dimensional visualization of anion depletion and lithium growth by stimulated Raman scattering microscopy.
Visualization of ion transport in electrolytes provides fundamental understandings of electrolyte dynamics and electrolyte-electrode interactions. However, this is challenging because existing techniques are hard to capture low ionic concentrations and fast electrolyte dynamics. Here we show that stimulated Raman scattering microscopy offers required resolutions to address a long-lasting question: how does the lithium-ion concentration correlate to uneven lithium deposition? In this study, anions are used to represent lithium ions since their concentrations should not deviate for more than 0.1 mM, even near nanoelectrodes. A three-stage lithium deposition process is uncovered, corresponding to no depletion, partial depletion, and full depletion of lithium ions. Further analysis reveals a feedback mechanism between the lithium dendrite growth and heterogeneity of local ionic concentration, which can be suppressed by artificial solid electrolyte interphase. This study shows that stimulated Raman scattering microscopy is a powerful tool for the materials and energy field.


Virgin olive oil as a fundamental nutritional component and skin protector.
Fats are indispensable to life not only as an energy source but also for their structural role in the skin, retina, nervous system, lipoproteins, and biologic membranes. They are also precursors of important hormones and constitute the vehicle for the absorption of liposoluble vitamins. Nutritionists recommend a balanced lipid intake corresponding to a total amount of fats equal to 25% to 30% of total calories with a ratio in monounsaturated and polyunsaturated fatty acids. Thus, olive oil, with its balanced fatty acid composition, is of high nutritional value. Moreover, extra virgin olive oil, extracted from a fruit, has an important value related to the antioxidant power of minor components. Extra virgin olive oil contains 98% to 99% triglycerides and 1% to 2% minor components. In the triglycerides, the main fatty acids are represented by monounsaturates (oleic), with a slight amount of saturates and an adequate amount of polyunsaturates. The minor components are alpha-tocopherol, phenol compounds, carotenoids, squalene, phytosterols, and chlorophyll. Factors that can influence olive oil's composition, especially in regard to its minor components, are the cultivar, area of production, time of harvesting, and degree of technology used in its production. Therefore, an evaluation of the biologic value of extra virgin olive oil and its use as a topical raw material in cosmetic dermatology is reported.


Building chronic disease management capacity in General Practice: The South Australian GP Plus Practice Nurse Initiative.
This paper draws on the implementation experience of the South Australian GP Plus Practice Nurse Initiative in order to establish what is needed to support the development of the chronic disease management role of practice nurses. The Initiative was delivered between 2007 and 2010 to recruit, train and place 157 nurses across 147 General Practices in Adelaide. The purpose was to improve chronic disease management in General Practice, by equipping nurses to work as practice nurses who would coordinate care and establish chronic disease management systems. Secondary analysis of qualitative data contained in the Initiative evaluation report, specifically drawing on quarterly project records and four focus groups conducted with practice nurses, practice nurse coordinators and practice nurse mentors. As evidenced by the need to increase the amount of support provided during the implementation of the Initiative, nurses new to General Practice faced challenges in their new role. Nurses described a big learning curve as they dealt with role transition to a new work environment and learning a range of new skills while developing chronic disease management systems. Informants valued the skills development and support offered by the Initiative, however the ongoing difficulties in implementing the role suggested that change is also needed at the level of the Practice. While just over a half of the placement positions were retained, practice nurses expressed concern with having to negotiate the conditions of their employment. In order to advance the role of practice nurses as managers of chronic disease support is needed at two levels. At one level support is needed to assist practice nurses to build their own skills. At the level of the Practice, and in the wider health workforce system, support is also needed to ensure that Practices are organisationally ready to include the practice nurse within the practice team.


Primary total knee arthroplasty in patients with fibromyalgia.
No data on the results of total knee arthroplasty (TKA) in patients with fibromyalgia have been published. The purposes of this study were to review a cohort of patients with fibromyalgia undergoing TKA to determine the level of postoperative pain and satisfaction with the surgery, the incidence of postoperative surgical complications, and revision rates and their relationship to TKA design. One hundred ten patients with fibromyalgia (141 knees) who underwent primary TKA between 1990 and 2001 were studied. The average age was 64 years (range, 39-86 years), and the average follow-up was 7 years (range, 2-16 years). Forty-five knees were cruciate retaining, and 96 had a posterior stabilized design. Clinical outcome was assessed using the Knee Society Knee Score and satisfaction regarding the results of the procedure. Postoperative surgical complications and reoperations were obtained from the registry. Sixty-two patients (44%) continued with some pain after TKA. Eighty-five patients (82%) were satisfied with the results. The most common complications were arthrofibrosis and symptomatic instability. The revision rate was 6% (8 knees). Survivorship free from revision at 7 years was 89% for cruciate retaining knees and 98% for posterior stabilized knees. Patients with fibromyalgia undergoing primary TKA have a high prevalence of complications and pain. Despite continued pain, the majority of patients were satisfied with the results and reported improvements after TKA. This data should be used to counsel patients with fibromyalgia preoperatively regarding limited goals with respect to pain relief and suggests that a multimodal individualized treatment program may be necessary to achieve optimal outcomes in patients with fibromyalgia.


Association of vascular endothelial growth factor single nucleotide polymorphisms on the prognosis of breast cancer patients.
Vascular endothelial growth factor (VEGF), a major mediator of vascular permeability and angiogenesis, may play a pivotal role in mediating the development and progression of breast cancer. In the present study, we examined the genetic variations of the VEGF gene to assess its possible relation to breast cancer. A total of 200 patients with histologically confirmed cases of breast cancer and 200 healthy women were genotyped for VEGF single nucleotide polymorphisms (405G > C and -1154G > A) by polymerase chain reaction-restriction fragment length polymorphism analysis. Pre-operative plasma VEGF levels were determined by enzyme-linked immunosorbent assay in 200 women with breast cancer and in 200 normal female controls. The genotype frequencies of the +405G > C, -1154G > A polymorphisms did not show a significant deviation from the Hardy-Weinberg expectation. The minor allele frequencies of the +405G > C and -1154G > A polymorphisms among cases and controls were 33.5% (C allele), 31.5% (A allele) and 35% (C allele), 34.5% (A allele) respectively. +405GG and -1154GG genotypes were associated with higher levels of VEGF among breast cancer cases and controls. Increased plasma VEGF levels were significantly associated with, clinical stage of the disease (P = 0.035). Although none of the polymorphisms were significantly associated with breast cancer, some of the VEGF genotypes may influence tumor growth through an altered expression of VEGF and tumor angiogenesis.


Sequential photo-bleaching to delineate single Schwann cells at the neuromuscular junction.
Sequential photo-bleaching provides a non-invasive way to label individual SCs at the NMJ. The NMJ is the largest synapse of the mammalian nervous system and has served as guiding model to study synaptic structure and function. In mouse NMJs motor axon terminals form pretzel-like contact sites with muscle fibers. The motor axon and its terminal are sheathed by SCs. Over the past decades, several transgenic mice have been generated to visualize motor neurons and SCs, for example Thy1-XFP and Plp-GFP mice, respectively. Along motor axons, myelinating axonal SCs are arranged in non-overlapping internodes, separated by nodes of Ranvier, to enable saltatory action potential propagation. In contrast, terminal SCs at the synapse are specialized glial cells, which monitor and promote neurotransmission, digest debris and guide regenerating axons. NMJs are tightly covered by up to half a dozen non-myelinating terminal SCs - these, however, cannot be individually resolved by light microscopy, as they are in direct membrane contact. Several approaches exist to individually visualize terminal SCs. None of these are flawless, though. For instance, dye filling, where single cells are impaled with a dye-filled microelectrode, requires destroying a labelled cell before filling a second one. This is not compatible with subsequent time-lapse recordings. Multi-spectral "Brainbow" labeling of SCs has been achieved by using combinatorial expression of fluorescent proteins. However, this technique requires combining several transgenes and is limited by the expression pattern of the promoters used. In the future, expression of "photo-switchable" proteins in SCs might be yet another alternative. Here we present sequential photo-bleaching, where single cells are bleached, and their image obtained by subtraction. We believe that this approach - due to its ease and versatility - represents a lasting addition to the neuroscientist's technology palette, especially as it can be used in vivo and transferred to others cell types, anatomical sites or species. In the following protocol, we detail the application of sequential bleaching and subsequent confocal time-lapse microscopy to terminal SCs in triangularis sterni muscle explants. This thin, superficial and easily dissected nerve-muscle preparation has proven useful for studies of NMJ development, physiology and pathology. Finally, we explain how the triangularis sterni muscle is prepared after fixation to perform correlated high-resolution confocal imaging, immunohistochemistry or ultrastructural examinations.


Pharmacokinetic analysis of factors determining elimination pathways for sulfate and glucuronide metabolites of drugs. I: studies by in vivo constant infusion.
1. The hepatic and renal handling of glucuronides and sulphates of three phenolic compounds, 4-methylumbelliferone (4-MU), p-nitrophenol (pNP) and acetaminophen (APAP), were evaluated pharmacokinetically by in vivo constant infusion experiments in rat. It was shown that the urinary excretion rate at steady-state was larger than the biliary excretion rate for both glucuronides and sulfates, and sulfates, in particular, were extensively excreted into the urine. 2. For each glucuronide, however, biliary excretion clearances (CL(b)) calculated based on the total concentration and unbound concentration in the liver were much larger than the corresponding renal excretion clearances (CL(r)). Even in the case of sulfates, there was not any large difference between CL(r) and CL(b) based on the total and unbound concentration in tissues, which could not explain their extensive urinary excretion. From these results, these excretion clearances were recognized not to reflect necessarily the actual excretion rate obtained. 3. On the other hand, the tissue-to-plasma concentration ratio (K(p)) of both glucuronides and sulfates for every phenolic compound was much higher in the kidney than that in the liver. The results suggested that one of the most important determinants for the preferential excretion of these conjugates into the bile or urine is the extent of disposition of each compound to the liver or kidney. 4. In addition, K(p) of both glucuronides and sulfates in the liver, where these conjugates are mainly formed, was small. The K(p) of sulfates was quite low, suggesting that sulfates generated in the liver were subject to extensive sinusoidal efflux.


Penile cancer.
Penile cancer, while relatively rare in the western world, remains a disease with severe morbidity and mortality, not to mention significant psychological ramifications. Furthermore, the disease is observed with dramatically increased incidence in other parts of the world. A review of the literature has shown that the overwhelming majority of penile cancers are in situ or invasive squamous cell carcinomas, including a well-differentiated variant, verrucous carcinoma. Important predisposing factors are lack of circumcision, human papillomavirus infections, and penile lichen sclerosus, although other factors have occasionally been reported as well. Prevention, careful monitoring of patients at risk, and early diagnosis are essential to reduce the incidence of penile carcinoma and to provide a definitive cure. Public health measures, such as prophylactic use of circumcision, have proved successful but are controversial. Also, no standard therapeutic guidelines as to the best treatment strategy according to different stages, including efficacy of conservative nonsurgical modalities and indications for lymph nodal dissection, are available so far. It is common opinion that penile cancer is an emerging problem that deserves further investigations, and physicians, especially dermatologists, should be aware of this issue. At the completion of this learning activity, participants should be familiar with penile carcinoma, its risk factors, its clinical and histologic presentation, and the treatments currently available for its management.


Involvement of the toxic AGEs (TAGE)-RAGE system in the pathogenesis of diabetic vascular complications: a novel therapeutic strategy.
Diabetic vascular complications are leading causes of acquired blindness, end-stage renal failure, a variety of neuropathies, and accelerated atherosclerosis, which may be involved in the disabilities and high mortality rates suffered by diabetic patients. Continuous hyperglycemia is involved in the pathogenesis of diabetic micro- and macrovascular complications via various metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including increased generation of various types of advanced glycation end-products (AGEs). Recently, we demonstrated that glyceraldehyde-derived AGEs (Glycer-AGEs), the predominant components of toxic AGEs (TAGE), play an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, a growing body of evidence suggests that the interaction of TAGE with the receptor for AGEs (RAGE) alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and elicits oxidative stress generation in numerous types of cells, all of which may contribute to the pathological changes observed in diabetic vascular complications. Therefore, the inhibition of TAGE formation, blockade of TAGE-RAGE interaction, and the suppression of RAGE expression or its downstream pathways are promising targets for therapeutic interventions against diabetic vascular complications. In this review, we discuss the pathophysiological role of the TAGE-RAGE-oxidative stress system and related therapeutic interventions for preventing the development and progression of diabetic vascular complications.


Survey of attitudes of physicians toward the current evaluation and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD).
We aimed in this study to determine the opinion of the medical directors of dialysis centers in the Kingdom of Saudi Arabia (KSA) about the updates of strategies for evaluation and treatment of chronic kidney disease-mineral and bone Disorder (CKD-MBD). A questionnaire was sent to medical directors of 174 dialysis centers in the KSA between July and November 2009. The questionnaire was opinion based and comprised the prevalence of the CKD-MBD, strategies of therapy and indications of cinacalcet, a new therapy in the CKD patients. A total of 154 medical directors of the 174 (88.5%), who are the therapeutic decision-makers for 10100 (89%) dialysis patients, answered the questionnaire. There were 84 respondents (54%) who believed that the parathormone (PTH) blood levels initially increase at a glomerular filtration rate (GFR) < 30%. There were 80 (53%) respondents who believed that changes of phosphorus (PO4) and calcium (Ca) blood levels are initially observed at GFR < 30 mL/min. The majority of respondents, 115 (77%), 116 (80%), 95 (66%), and 134 (90%) currently have observed increased prevalence of vascular calcifications, adynamic bone disease, PTH > 500 pmol/L, and elevated Ca blood levels, respectively, only in the minority of advanced CKD. However, 88 (58%) respondents observed increased prevalence of elevated PO4 blood levels in the majority of new dialysis and advanced CKD patients. There were 137 (89%) respondents who believed from the current published evi-dence that CKD-MBD may result in increased morbidity (e.g. fractures) and mortality (e.g. cardiovascular) in advanced CKD and new dialysis patients. However, only 41 (27%) respondents follow the PTH levels in their patients every 2-3 months, while 81(53%) follow it every 6 months. There were 127 (83%), 129 (84%), 114 (75%) respondents who would start vitamin D (vit D) in dialysis and CKD patients for hypocalcemia, high PTH, and vit D 1,25 deficiency, respectively. However, only 51 (34%) respondents would start vit D therapy for vit D 25 deficiency. There were 98 (75%), 73 (57%) 74 (59%), and 88 (68%) respondents who claimed that they could achieve control of calcium levels alone, control of PO4 levels alone PTH levels alone , and all parameters of CKD-MBD in > 50% of their patients, respectively. There were 126 (82%) and 126 (82%) respondents who agreed to the indications of the cinacalcet that include refractory secondary hyperparathyroidism of dialysis patients to vit D and diet and phosphate binders together, and when surgical parathyroidectomy is contraindicated or fail in this population, respectively. However, 127 (83%) and 139 (91%) respondents disagreed to the indications that include indiscriminate prescription to all CKD patients or off label to some early CKD patients, respectively. We conclude that the medical directors of the active dialysis centers in Saudi Arabia are well aware of the morbidity and mortality caused by the CKD-MBD in addition to the indications of vit D and phosphate binders and cinacalcet therapy. However, the study suggests inadequate assessment of the prevalence, patterns of CKD-MBD, and results of intervention in the CKD patients such as treatment of vit D 25 deficiency, and knowledge of the availability of cinacalcet for the treatment of CKD-MBD. More local studies and guidelines are required to disseminate information about the current patterns of CKD-MBD for better approach to the management of this disorder in the kidney centers in this country.


Pd-catalyzed asymmetric allylic amination using easily accessible metallocenyl P,N-ligands.
Compared to their C1-symmetric counterparts, planar chiral C2-symmetric metallocenyl P,N-ligands are efficient chiral ligands for Pd-catalyzed asymmetric allylic aminations, providing a number of amination products with high enantioselectivities. A non-C2-symmetric ferrocenyl P,N-ligand (a by-product obtained during the synthesis of the above C2-symmetric species) was also found to be an efficient ligand for asymmetric allylic aminations. A mixed ligand system consisting of both C2- and non-C2-symmetric ferrocene complexes was examined and showed high catalytic activity with the amination products being obtained with excellent enantioselectivities.


Passive cigarette smoke exposure of infants: importance of nonparental sources.
To learn whether cigarette smoking by persons other than parents significantly contributes to the passive environmental tobacco smoke (ETS) exposure of infants. A cohort of infants prospectively followed up from birth to age 2 years with monthly questionnaires concerning smoking by different categories of adults coming into contact with the infants. Health maintenance organization members residing in several suburban communities of Detroit, Mich, defined by contiguous ZIP codes. Ninety-seven (83%) of 117 healthy, full-term infants, thought to be at high risk of allergic disease based on cord blood IgE, who were born to eligible mothers and who completed 24 months of follow-up. Average of bimonthly urinary cotinine-creatinine ratios (CCRs) during the 2 years of the study. There were significant correlations (r</=0.28, P</=.005) between the frequency of smoking by all 7 categories of adults considered and the average CCRs of the infants. Multivariable analysis demonstrated that average urinary CCRs were significantly associated not only with smoking by the infant's parents, but also with smoking by workers at day care away from the home, persons visited away from the home, and persons other than parents residing in the home (overall R(2) = 0.72, P =.001). Smoking by multiple individuals, other than the parents, significantly contributes to the ETS exposure of infants. These findings suggest that, at least for infants, efforts to reduce the adverse health effects of ETS exposure should extend beyond curtailing parental smoking. Arch Pediatr Adolesc Med. 2000;154:1237-1241.


7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice.
Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.


Amniotic fluid-borne hepatocyte growth factor protects rat pups against experimental necrotizing enterocolitis.
Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a key role in gut mucosal development. Preterm birth interrupts this exposure to amniotic fluid-borne growth factors, possibly contributing to the increased risk of necrotizing enterocolitis (NEC) in premature infants. We hypothesized that supplementation of formula feeds with amniotic fluid can provide amniotic fluid-borne growth factors and prevent experimental NEC in rat pups. We compared NEC-like injury in rat pups fed with infant formula vs. formula supplemented either with 30% amniotic fluid or recombinant hepatocyte growth factor (HGF). Cytokines/growth factors in amniotic fluid were measured by immunoassays. Amniotic fluid and HGF effects on enterocyte migration, proliferation, and survival were measured in cultured IEC6 intestinal epithelial cells. Finally, we used an antibody array to investigate receptor tyrosine kinase (RTK) activation and immunoblots to measure phosphoinositide 3-kinase (PI3K) signaling. Amniotic fluid supplementation in oral feeds protected rat pups against NEC-like injury. HGF was the most abundant growth factor in rat amniotic fluid in our panel of analytes. Amniotic fluid increased cell migration, proliferation, and cell survival in vitro. These effects were reproduced by HGF and blocked by anti-HGF antibody or a PI3K inhibitor. HGF transactivated several RTKs in IEC6 cells, indicating that its effects extended to multiple signaling pathways. Finally, similar to amniotic fluid, recombinant HGF also reduced the frequency and severity of NEC-like injury in rat pups. Amniotic fluid supplementation protects rat pups against experimental NEC, which is mediated, at least in part, by HGF.


Governing complexity: Integrating science, governance, and law to manage accelerating change in the globalized commons.
The speed and uncertainty of environmental change in the Anthropocene challenge the capacity of coevolving social-ecological-technological systems (SETs) to adapt or transform to these changes. Formal government and legal structures further constrain the adaptive capacity of our SETs. However, new, self-organized forms of adaptive governance are emerging at multiple scales in natural resource-based SETs. Adaptive governance involves the private and public sectors as well as formal and informal institutions, self-organized to fill governance gaps in the traditional roles of states. While new governance forms are emerging, they are not yet doing so rapidly enough to match the pace of environmental change. Furthermore, they do not yet possess the legitimacy or capacity needed to address disparities between the winners and losers from change. These emergent forms of adaptive governance appear to be particularly effective in managing complexity. We explore governance and SETs as coevolving complex systems, focusing on legal systems to understand the potential pathways and obstacles to equitable adaptation. We explore how governments may facilitate the emergence of adaptive governance and promote legitimacy in both the process of governance despite the involvement of nonstate actors, and its adherence to democratic values of equity and justice. To manage the contextual nature of the results of change in complex systems, we propose the establishment of long-term study initiatives for the coproduction of knowledge, to accelerate learning and synergize interactions between science and governance and to foster public science and epistemic communities dedicated to navigating transitions to more just, sustainable, and resilient futures.


Roles for mating and environment in C. elegans sex determination.
In Caenorhabditis elegans the two sexes, hermaphrodites and males, are thought to be irreversibly determined at fertilization by the ratio of X chromosomes to sets of autosomes: XX embryos develop as hermaphrodites and XO embryos as males. We show instead that both sex and genotype of C. elegans can be altered postembryonically and that this flexibility requires sexual reproduction. When grown in specific bacterial metabolites, some XX larvae generated by mating males and hermaphrodites develop as males and lose one X chromosome. However, XX larvae produced by hermaphrodite self-fertilization show no such changes. We propose that sexual reproduction increases developmental flexibility of progeny, allowing for better adaptation to changing environments.


Chemoprevention of intestinal polyps in ApcMin/+ mice fed with western or balanced diets by drinking annurca apple polyphenol extract.
The Western diet (WD) is associated with a higher incidence of colorectal cancer (CRC) than the Mediterranean diet. Polyphenols extracted from Annurca apple showed chemopreventive properties in CRC cells. A multifactorial, four-arm study by using wild-type (wt) and Apc(Min/+) mice was carried out to evaluate the effect on polyp number and growth of APE treatment (60 μmol/L) ad libitum in drinking water combined with a WD or a balanced diet (BD) for 12 weeks. Compared with APE treatment, we found a significant drop in body weight (P < 0.0001), severe rectal bleeding (P = 0.0076), presence of extraintestinal tumors, and poorer activity status (P = 0.0034) in water-drinking Apc(Min/+) mice, more remarkably in the WD arm. In the BD and WD groups, APE reduced polyp number (35% and 42%, respectively, P < 0.001) and growth (60% and 52%, respectively, P < 0.0001) in both colon and small intestine. Increased antioxidant activity was found in wt animals fed both diets and in Apc(Min/+) mice fed WD and drinking APE. Reduced lipid peroxidation was found in Apc(Min/+) mice drinking APE fed both diets and in wt mice fed WD. In normal mucosa, mice drinking water had lower global levels of DNA methylation than mice drinking APE. APE treatment is highly effective in reducing polyps in Apc(Min/+) mice and supports the concept that a mixture of phytochemicals, as they are naturally present in foods, represent a plausible chemopreventive agent for CRC, particularly in populations at high risk for colorectal neoplasia.


Non-inferiority of pulsed xenon UV light versus bleach for reducing environmental Clostridium difficile contamination on high-touch surfaces in Clostridium difficile infection isolation rooms.
The standard for Clostridium difficile surface decontamination is bleach solution at a concentration of 10 % of sodium hypochlorite. Pulsed xenon UV light (PX-UV) is a means of quickly producing germicidal UV that has been shown to be effective in reducing environmental contamination by C. difficile spores. The purpose of this study was to investigate whether PX-UV was equivalent to bleach for decontamination of surfaces in C. difficile infection isolation rooms. High-touch surfaces in rooms previously occupied by C. difficile infected patients were sampled after discharge but before and after cleaning using either bleach or non-bleach cleaning followed by 15 min of PX-UV treatment. A total of 298 samples were collected by using a moistened wipe specifically designed for the removal of spores. Prior to disinfection, the mean contamination level was 2.39 c.f.u. for bleach rooms and 22.97 for UV rooms. After disinfection, the mean level of contamination for bleach was 0.71 c.f.u. (P = 0.1380), and 1.19 c.f.u. (P = 0.0017) for PX-UV disinfected rooms. The difference in final contamination levels between the two cleaning protocols was not significantly different (P = 0.9838). PX-UV disinfection appears to be at least equivalent to bleach in the ability to decrease environmental contamination with C. difficile spores. Larger studies are needed to validate this conclusion.


Midrapidity antiproton-to-proton ratio from Au+Au collisions at sqrt [s(NN)]=130 GeV.
We report results on the ratio of midrapidity antiproton-to-proton yields in Au+Au collisions at sqrt[s(NN)] = 130 GeV per nucleon pair as measured by the STAR experiment at RHIC. Within the rapidity and transverse momentum range of /y/<0.5 and 0.4<p(t)<1.0 GeV/c, the ratio is essentially independent of either transverse momentum or rapidity, with an average of 0.65+/-0.01((stat))+/-0.07((syst)) for minimum bias collisions. Within errors, no strong centrality dependence is observed. The results indicate that at this RHIC energy, although the p-p pair production becomes important at midrapidity, a significant excess of baryons over antibaryons is still present.


Organochlorine pesticides in elementary school yards along the Texas-Mexico border.
A reconnaissance study was undertaken to determine potential contaminant exposures to children through soil from elementary school playgrounds. Soil samples were collected from areas along the Texas-Mexico border, inland areas (soils from elementary school yards in cities/towns within the state of Texas), and three National Parks (one on the border, one in Tennessee, and one in Washington). The present study focused on organochlorine (OC) pesticides as the potential contaminants of concern because of their historical (and possibly current) use, and their importance as persistent organic pollutants (POPs). DDE and heptachlor were the most frequently detected OCs (69 and 63%, respectively), although heptachlor concentrations in soil never exceeded 5 ppb. Relatively higher concentrations of DDE were observed in agricultural areas along the border (50-60 ppb in soils from McAllen, Palmview, and San Benito) than in other soils. However, a school yard in Lubbock, TX had the highest OC concentration observed (70 ppb dieldrin). These results may be due to historical agriculture activity prior to the banning of OC pesticides such as DDT in the early 1970s, as well as the more recent use of DDT in Central and South America for malaria control.


Acute systemic inflammatory response to lipopolysaccharide stimulation in pigs divergently selected for residual feed intake.
It is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs' immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells. LPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p = 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count or levels of several plasma cytokines were detected between the two lines. Profiling blood transcriptomes at 0, 2, 6, and 24 hpi by RNA-sequencing revealed that LPS induced dramatic transcriptional changes, with 6296 genes differentially expressed at at least one time point post injection relative to baseline in at least one line (n = 4 per line) (|log2(fold change)| ≥ log2(1.2); q < 0.05). Furthermore, applying the same cutoffs, we detected 334 genes differentially expressed between the two lines at at least one time point, including 33 genes differentially expressed between the two lines at baseline. But no significant line-by-time interaction effects were detected. Genes involved in protein translation, defense response, immune response, and signaling were enriched in different co-expression clusters of genes responsive to LPS stimulation. The two lines were largely similar in their peripheral blood transcriptomic responses to LPS stimulation at the pathway level, although the low-RFI line had a slightly lower level of inflammatory response than the high-RFI line from 2 to 6 hpi and a slightly higher level of inflammatory response than the high-RFI line at 24 hpi. The pig lines divergently selected for RFI had a largely similar response to LPS stimulation. However, the low-RFI line had a relatively lower-level, but longer-lasting, inflammatory response compared to the high-RFI line. Our results suggest selection for feed efficient pigs does not significantly compromise a pig's acute systemic inflammatory response to LPS, although slight differences in intensity and duration may occur.


Saccadic underaction in concomitant strabismus and Hering's law: a new neurophysiologic model for binocular motor correspondence.
Hering's law of equal innervation has remained so far as an universal truth with no scientific basis. However, recent reports of Saccadic underactions in concomitant strabismus indicating asymmetric ocular motor innervation is in contradiction to the law. In an effort to understand the inequalities of binocular movements, we propose a neurophysiologic model for both normal and abnormal eye movements. The model hypothesizes that any binocular movement results from the yoking of two monocular reflex loops corresponding to the two eyes, during the plastic stage of development of ocular motor reflexes. The retinal target discrepancy triggers the reflex loop resulting in a monocular corrective movement. As there is a common binocular field, the stimuli to the two eyes are similar causing a similar binocular corrective movement. In abnormal cases coupling of asymmetric motor loops may occur resulting in alternate or unilateral saccadic underactions.


How Can Adult Children Influence Parents' Long-Term Care Insurance Purchase Decisions?
Long-term care (LTC) poses a significant strain on public health insurance financing. In response, there is policy interest in bolstering the private long-term care insurance (LTCI) market. Although families are central to LTC provision, their role in LTCI demand remains unclear. The purpose of this study was to obtain in-depth information concerning: (a) How do older parents evaluate the need for LTCI, (b) what role do adult children play? and (c) How do families communicate about parents' LTC preferences and plans, including LTCI purchase? We conducted focus groups with older parents and adult children in diverse markets. Two groups were conducted with older parents who had purchased LTCI and two with parents who had not purchased LTCI. Four groups were conducted with adult children, mixed as to whether their parents had purchased LTCI. Probes were informed by published reasons for purchasing or not purchasing LTCI. We analyzed transcriptions using directed content analysis and constant comparative method. Older parents valued autonomy for themselves and their children. Older parent purchasers regarded LTCI as supporting this value while nonpurchasers perceived limitations. Adult children described unstated expectations that they would care for their parents. Though discussions between parents and children about LTCI were rare, successful influence occurred when children appealed to shared values, specifically avoiding burden and remaining home. Messages that emphasize autonomy over LTC decisions and interventions that start the LTC conversation among families, with attention to shared values, could increase private LTCI uptake.


Protecting patients, protecting healthcare workers: a review of the role of influenza vaccination.
Many health authorities recommend routine influenza vaccination for healthcare workers (HCWs), and during the 2009 A (H1N1) pandemic, the World Health Organization (WHO) recommended immunization of all HCWs worldwide. As this remains an important area of policy debate, this paper examines the case for vaccination, the role of local guidelines, barriers to immunization and initiatives to increase uptake. Seasonal influenza is a major threat to public health, causing up to 1 million deaths annually. Extensive evidence supports the vaccination of priority groups, including HCWs. Immunization protects HCWs themselves, and their vulnerable patients from nosocomial influenza infections. In addition, influenza can disrupt health services and impact healthcare organizations financially. Immunization can reduce staff absences, offer cost savings and provide economic benefits. This paper reviews official immunization recommendations and HCW vaccination studies, including a recent International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) survey of 26 countries from each region of the world. HCW immunization is widely recommended and supported by the WHO. In the IFPMA study, 88% of countries recommended HCW vaccination, and 61% supported this financially (with no correlation to country development status). Overall, coverage can be improved, and research shows that uptake may be impacted by lack of conveniently available vaccines and misconceptions regarding vaccine safety/efficacy and influenza risk. Many countries recommend HCW vaccination against influenza. In recent years, there has been an increased uptake rate among HCWs in some countries, but not in others. Several initiatives can increase coverage, including education, easy access to free vaccines and the use of formal declination forms. The case for HCW vaccination is clear, and in an effort to further accelerate uptake as a patient safety measure, an increasing number of healthcare organizations, particularly in the USA, are implementing mandatory immunization policies, similar to other obligatory hygiene measures. However, it would be desirable if similar high vaccination uptake rates could be achieved through voluntary procedures.