Mechanisms of mucosal and parenteral tuberculosis vaccinations: adenoviral-based mucosal immunization preferentially elicits sustained accumulation of immune protective CD4 and CD8 T cells within the airway lumen.
The mechanisms underlying better immune protection by mucosal vaccination have remained poorly understood. In our current study we have investigated the mechanisms by which respiratory virus-mediated mucosal vaccination provides remarkably better immune protection against pulmonary tuberculosis than parenteral vaccination. A recombinant adenovirus-based tuberculosis (TB) vaccine expressing Mycobacterium tuberculosis Ag85A (AdAg85A) was administered either intranasally (i.n.) or i.m. to mice, and Ag-specific CD4 and CD8 T cell responses, including frequency, IFN-gamma production, and CTL, were examined in the spleen, lung interstitium, and airway lumen. Although i.m. immunization with AdAg85A led to activation of T cells, particularly CD8 T cells, in the spleen and, to a lesser extent, in the lung interstitium, it failed to elicit any T cell response in the airway lumen. In contrast, although i.n. immunization failed to effectively activate T cells in the spleen, it uniquely elicited higher numbers of Ag-specific CD4 and CD8 T cells in the airway lumen that were capable of IFN-gamma production and cytolytic activities, as assessed by an intratracheal in vivo CTL assay. These airway luminal T cells of i.n. immunized mice or splenic T cells of i.m. immunized mice, upon transfer locally to the lungs of naive SCID mice, conferred immune protection against M. tuberculosis challenge. Our study has demonstrated that the airway luminal T cell population plays an important role in immune protection against pulmonary TB, thus providing mechanistic insights into the superior immune protection conferred by respiratory mucosal TB vaccination.


[Cross-cultural adaptation and analysis of the psychometric properties in the Brazilian version of the Human Activity Profile].
The aim of the present study was to evaluate the psychometric properties in the Brazilian version of the Human Activity Profile (HAP), an instrument for the assessment of daily functions and level of physical activity. The HAP was translated into Portuguese following the recommended methodology and applied to 230 community-dwelling elderly (66.32 +/- 8.5 years) from the city of Belo Horizonte, Minas Gerais State, Brazil. The data were submitted to Rasch analysis, which detected very easy and difficult items, making it possible to employ the instrument with both frail and highly functional individuals. The separation index of 3.1 indicated that the items divided the individuals into three levels of functional ability. Of the 94 HAP items, six (6.38%) did not fit the statistical model, which jeopardized its construct validity, since the items did not fit into a continuum. Therefore, caution should be taken when employing the HAP to individuals having similar characteristics. If HAP is applied to different samples and the proportion of erratic items is still more than 5%, modification, substitution, or exclusion of those items is suggested to guarantee that HAP measures a unidimensional construct.


Carotid artery and heart disease in subtypes of cerebral infarction.
The aim of the study was to determine the prevalences of carotid artery disease and major and minor potential cardioembolic sources (1) in patients with cerebral infarction and age-matched control subjects and (2) in different clinical subtypes of cerebral infarction. A series of 166 consecutive patients with cerebral infarction and 59 control subjects was examined. The study protocol included clinical subtyping of the cerebral infarctions, ultrasonography of the carotid arteries, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), ECG, and examination of the brain with computed tomography, magnetic resonance imaging, or autopsy. Carotid artery stenosis > or = 80% or occlusion was present in 35 (21%) patients but in no control subjects (P < .001; chi 2 test). A major potential cardioembolic source was detected in 65 (39%) patients and 3 (5%) control subjects. Atrial fibrillation was present in 35 (21%) patients and 3 (5%) control subjects at initial ECG (P < .01) and in 47 (28%) patients at repeat examination; 17 patients had paroxysmal atrial fibrillation. Sinus rhythm and a major potential cardioembolic source were detected in 18 (11%) patients but in no control subjects (P < .01) at TTE (all patients and control subjects examined) or TEE (118 patients and 52 control subjects examined). The frequency of a minor potential cardioembolic source detectable at TTE or TEE was similar in the patient and control groups (51% and 53%, respectively [NS]) and increased significantly with age. A finding of carotid artery stenosis > or = 80% or occlusion, atrial fibrillation, or a major cardioembolic source detected at TTE or TEE was more frequent among patients with cortical symptoms from anterior or middle cerebral artery territories than among those with lacunar syndromes (66% versus 22%, respectively). The probable source of cerebral infarction was identified in most of the 166 patients: cardiac embolism in 28% of cases (n = 46), carotid artery disease in 8% (n = 14), both cardiac embolism and carotid artery disease in 7% (n = 11), and lacunar infarction in 23% (n = 38). In 57 (34%) of the patients no unequivocal cause of the cerebral infarction was found. The prevalences of carotid artery and heart disease differ significantly between clinical subtypes of cerebral infarction. The cause of cerebral infarction remains uncertain in one third of patients. Because a minor potential cardioembolic source occurs in about 50% of both patients and control subjects, this finding is of questionable value as a risk factor for stroke in the elderly.


Recent trends in home and work smoking bans.
Home and work smoking bans at the national and state level in the USA, and their relation to smoking prevalence and to tobacco control policies, are examined. The Current Population Survey's 1992/93 and 1998/99 tobacco use supplement surveys are the primary data source, supplemented with information on state level tobacco control policies. The national and state rate of bans are estimated, and changes over the course of the 1990s and their relation to smoking rates and tobacco control policies are examined. The prevalence of work and home bans has increased considerably between 1992/93 and 1998/99. By 1999, over 65% of the population age 15 and above work in places with smoking bans, and over 60% live in homes with bans. We found that states with lower than average ban rates in 1993 tended to have had larger increases in ban rates between 1993 and 1999. We also found that home and work bans became more prevalent in states with initially low smoking rates, and that the growth in home bans coincided with a declining prevalence of smoking. States with higher levels of bans by 1999 also tended to have higher cigarette taxes, stricter clean air laws, and media/comprehensive campaigns in place. The results indicate that lower smoking rates are associated with higher rates of work and home bans, although substantial progress has also been made by those states with initially low rates of bans. While further work is needed to establish the direction of causality, it would appear that reductions in smoking rates, either through stronger tobacco control policies or otherwise, may reduce exposure to tobacco smoke not only by reducing the number of smokers, but also through increasing the number of firms and homes with smoking restrictions.


Multiple sclerosis-associated retrovirus and optic neuritis.
One prognostic factor for early multiple sclerosis (MS) patients to develop a definite MS may be the presence of the MS-associated retrovirus (MSRV) in the cerebrospinal fluid (CSF). We designed a specific study on a cohort of optic neuritis (ON) patients to evaluate the MSRV-dependent conversion to MS relative to the prediction conferred by magnetic resonance imaging (MRI) and CSF abnormalities. At follow-up, 33.3% MSRV+ and 0% MSRV- ON patients developed MS (P = 0.03). The prediction value is lower than that given by CSF and MRI abnormalities (42.3%). This intriguing finding is discussed in the light of the abundant discrepancies observed in the MSRV literature. Multiple Sclerosis 2006; 12: 357-359. www.multiplesclerosisjournal.com


Cardiovascular disease mortality and its association with socioeconomic status: findings from a population-based cohort study in rural Vietnam, 1999-2003.
Cardiovascular disease is an emerging epidemic in Vietnam, but because cause of death and other routine data are not widely available, it is difficult to characterize community-based disease patterns. Using 5-year data from an ongoing cause-specific mortality study conducted within a demographic surveillance system in Vietnam's Bavi district, this article estimates the rates of adult cardiovascular disease mortality in relation to the mortality rates of other noncommunicable diseases in rural northern Vietnam and examines the association of cardiovascular disease with certain demographic and socioeconomic factors. All causes of death of adults aged 20 and older occurring from 1999 through 2003 (n = 1067) were determined by using an established demographic surveillance system and data collected by trained interviewers who asked caretakers or relatives of the deceased individuals about signs and symptoms of disease during quarterly household visits. Deaths were classified as cardiovascular disease, cancer, or other noncommunicable diseases. These records were linked to demographic and socioeconomic data. Of the 1067 adult deaths that were recorded, there was an overall noncommunicable disease mortality rate of 7.8 per 1000 person-years. Cardiovascular disease accounted for 33% of male and 31% of female deaths. Compared with cancer and other noncommunicable causes of death in a Cox proportional hazards model, higher cardiovascular disease mortality rates were observed among men, older age groups, and those without formal education. To date, cohort studies and population-based mortality data in Vietnam have been scarce; this study provides insights into the public health aspects of cardiovascular disease in transitional Vietnam. The rates of cardiovascular disease mortality in this rural Vietnamese community were high, suggesting the need for both primary prevention and secondary treatment initiatives. The demographic surveillance system is an important tool for characterizing such an epidemic.


Spinal metastases of two different grade oligodendrogliomas: a case report and review of literature.
Oligodendrogliomas (OGD) are glial tumors, together with mixed oligoastrocytoma constituting 5-20% of all gliomas, which occur predominantly in younger populations and are managed with surgery and chemotherapy with good long-term prognosis after treatment and additionally present with low rates of metastases. We present the case of a 46-year-old patient with intracranial right frontal subcortical OGD [World Health Organisation (WHO) grade II] managed at the Neurosurgery Department in Foscal Clinic, Floridablanca, Colombia. Two years after brain surgery the patient presents with neurological symptomatology suggestive of spinal cord compression and is found to have a neoplastic lesion with extra medullary compressive strength on the conus medullary and wrapping all of the roots with the final report of pathology and immunohistochemistry indicating: OGD (WHO grade III), this lesion was the only one found, the brain studies shows any residual tumor or recurrence in the primary tumor site.


Evidence for a central origin of the low-frequency oscillation in RR-interval variability.
Short-term variability of RR interval and blood pressure occurs predominantly at low frequency (LF; approximately 0.1 Hz) and high frequency (approximately 0.25 Hz). The arterial baroreflex is thought to be the predominant determinant of the LF component of RR variability. Patients with severe congestive heart failure (CHF) have an attenuated or absent LF oscillation in RR variability. The left ventricular assist device (LVAD) offers a unique possibility for analysis of spectral oscillations in RR interval independent of any effects of blood pressure that influence these oscillations via the baroreflex. We performed spectral analysis of RR, blood pressure, and respiration in 2 patients with CHF before and after LVAD implantation. LF components of the RR-interval and blood pressure variability were absent in both CHF patients before LVAD implantation. After LVAD implantation, spectral analysis of the RR interval showed restoration of a clear and predominant LF oscillation in the native hearts of both patients, with no such oscillation evident in the blood pressure profile. During total circulatory support with the LVAD, the LF oscillation in RR interval of the native heart, absent in CHF, is restored. This LF oscillation in RR interval occurs in the absence of LF oscillations in blood pressure and thus is unlikely to be explained by baroreflex mechanisms. Hence, the absence of LF oscillation in the RR interval in CHF is functional and is reversible by LVAD circulation. The presence of a predominant LF oscillation in RR interval independent of any oscillation in blood pressure suggests that the LF oscillation is a fundamental property of central autonomic outflow.


Transcriptional regulation of rat Na(+)/H(+) exchanger isoform-2 (NHE-2) gene by Sp1 transcription factor.
The rat Na(+)/H(+) exchanger isoform-2 (NHE-2) gene promoter lacks a TATA box and is very GC rich. A minimal promoter extending from bp -36 to +116 directs high-level expression of NHE-2 in mouse inner medullary collecting duct (mIMCD-3) cells. Four Sp1 consensus elements were found in this region. The introduction of mutations within these Sp1 consensus elements and DNA footprinting revealed that only two of them were utilized and are critical for basal transcriptional activation in mIMCD-3 cells. The use of Sp1, Sp3, and Sp4 antisera in electrophoretic mobility shift assays demonstrated that Sp1, Sp3, and Sp4 bound to this minimal promoter. We further analyzed the transcriptional regulation of NHE-2 by members of the Sp1 multigene family. In Drosophila SL2 cells, which lack endogenous Sp1, the minimal promoter cannot drive transcription. Introduction of Sp1 activated transcription over 100-fold, suggesting that Sp1 is critical for transcriptional regulation. However, neither Sp3 nor Sp4 was able to activate transcription in these cells. Furthermore, in mIMCD-3 cells, Sp1-mediated transcriptional activation was repressed by expression of Sp3 and Sp4. These data suggest that Sp1 is critical for the basal promoter function of rat NHE-2 and that Sp3 and Sp4 may repress transcriptional activation by competing with Sp1 for binding to core cis-elements.


Clinical data mining and research in the allergy office.
More data are anticipated from the expected increase in use of electronic health records (EHRs). Upcoming initiatives require reporting of quality measures, meaningful use of clinical decision support, alert systems, and pharmacovigilance - knowledge resulting through use of EHRs. Data mining is a new tool that will help us manage information and derive knowledge from these data, and is a part of evolving new disciplines of informatics and knowledge management. Studies are reported from smaller clinic data marts to larger repositories and warehouses in various health systems, biomedical registries, and the medical literature on the Internet. Data mining technologies show promise and challenges. Outcome measures as structured data and narrative text can be mined with human assistance and newer automated natural language processing software. Despite advances, the growing diversity of clinic EHRs lack integration and interoperability with Internet-based biomedical databases. Allergists have the capability to mine clinic EHRs to discover new information, which may be hidden in charts. A central allergy computer can serve not just as a registry but also allows functionalities to enable EHRs' meaningful use. Harmonization of technological and organizational standards will allow seamless use of new natural language processing (NLP) tools and ontologies through a semantic web.


A pseudomonas syringae pv. tomato DC3000 Hrp (Type III secretion) deletion mutant expressing the Hrp system of bean pathogen P. syringae pv. syringae 61 retains normal host specificity for tomato.
The plant pathogenic species Pseudomonas syringae is divided into numerous pathovars based on host specificity. For example, P. syringae pv. tomato DC3000 is pathogenic on tomato and Arabidopsis, whereas P. syringae pv. syringae 61 is pathogenic on bean. The ability of P. syringae strains to elicit the hypersensitive response (HR) in non-hosts or be pathogenic (or parasitic) in hosts is dependent on the Hrp (type III secretion) system and effector proteins this system is thought to inject into plant cells. To test the role of the Hrp system in determining host range, the hrp/hrc gene cluster (hrpK through hrpR) was deleted from DC3000 and complemented in trans with the orthologous cluster from strain 61. Mutant CUCPB5114 expressing the bean pathogen Hrp system on plasmid pCPP2071 retained the ability of wild-type DC3000 to elicit the HR in bean, to grow and cause bacterial speck in tomato, and to elicit a cultivar-specific (gene-for-gene) HR in tomato plants carrying the Pto resistance gene. However, the symptoms produced in compatible tomato plants involved markedly reduced chlorosis, and CUCPB5114(pCPP2071) did not grow or produce symptoms in Arabidopsis Col-0 although it was weakly virulent in NahG Arabidopsis. A hypersensitive-like collapse was produced by CUCPB5114(pCPP2071) in Arabidopsis Col-0 at 1 x 10(7) CFU/ml, but only if the bacteria also expressed AvrB, which is recognized by the RPM1 resistance gene in Col-0 and confers incompatibility. These observations support the concept that the P. syringae effector proteins, rather than secretion system components, are the primary determinants of host range at both the species and cultivar levels of host specificity.


A multifunctional Ni(ii) coordination polymer: synthesis, crystal structure and applications as a luminescent sensor, electrochemical probe, and photocatalyst.
Herein, a nickel coordination polymer (CP 1), {Ni(1,4-bib)1.5(TPA-Cl2)·H2O}n (1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene, H2TPA-Cl2 = 2,5-dichloro-terephthalic acid), has been synthesized under solvothermal conditions. The structure of CP 1 is a 3D 3-fold interpenetrating framework with the sqc12 topology. The thermal stability and luminescence properties of CP 1 were investigated. Scanning electron microscopy (SEM) images of this material display that it possesses an irregular block 3D structure. Interestingly, CP 1 can serve as a multifunctional material via its luminescence sensing, electrochemical sensing, and photocatalytic properties. The experimental results indicate that CP 1 is an efficient luminescent sensor for the detection of Fe3+ ions in an aqueous solution. In addition, CP 1 exhibits a sensitive and rapid electrochemical response to nitrite ions in water solution. The photocatalytic activities of CP 1 were evaluated in the degradation of different dye contaminants (MB, RhB, and MO), and the results demonstrate that its photocatalytic efficiency for the degradation of MB is highest (92.1% for MB, 85.7% for RhB, and 86.2% for MO). The effects of different dyes, different powers of UV light, and different amounts of catalyst CP 1 on the photocatalytic efficiency were also explored. Finally, the mechanism of the luminescence quenching effect toward Fe3+ ions, electroreduction of nitrite ions, and photocatalytic degradation of different dyes have been investigated in detail.


Cutaneous tactile allodynia associated with microvascular dysfunction in muscle.
Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia. Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist. Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia.


Effect of an on-hip load-carrying belt on physiological and perceptual responses during bimanual anterior load carriage.
Manual load carriage continues to be a major contributor of musculoskeletal injury. This study investigates the physiological and subjective effects of an on-hip load-carrying belt (HLCB) during bimanual anterior load carriage. Fifteen healthy male participants walked on a level ground treadmill at 4.5 km/h for 5 min carrying 5, 10 and 15 kg loads with hands and arms in front of the body, with and without using the HLCB (WD and ND). Heart rate, normalized oxygen uptake, minute ventilation and, central and peripheral ratings of perceived exertion were the dependent variables. The mean heart rate, normalized oxygen uptake, minute ventilation and peripheral rating of perceived exertion increased significantly with load under both WD and ND conditions. At a load of 15 kg, the mean heart rate, normalized oxygen uptake, minute ventilation and peripheral rating of perceived exertion were significantly lower by 6.6%, 8.0%, 11.8% and 13.9% respectively in WD condition when compared to the ND condition. There was no significant difference between WD and ND conditions with 5 or 10 kg load. It can be concluded that the HLCB could reduce a person's physiological and peripheral perceptual responses when walking on a level ground treadmill at 4.5 km/h with a load of 15 kg. Using a HLCB or similar device is therefore recommended for bimanual anterior load carriage for loads of 15 kg or probably larger.


Establishing a deanery teaching programme for trainees sitting the MRCPCH clinical examination.
Objectives MRCPCH is an essential qualification that all paediatric trainees in the UK must obtain to progress with their specialty training. In August 2009 a structured clinical teaching programme was initiated in the West of Scotland deanery to provide teaching in the clinical examination curriculum, the structure and examination standards. Design The training programme runs three times a year, commencing two months prior to each exam. Trainees are sent questionnaires to enable improvement of the programme. Results A total of 127 trainees have participated in the programme over five years (August 2009-2014). Trainees report strengths of the programme include communication teaching (n = 14) and general teaching (n = 11). Challenges encountered include difficulties attending teaching sessions due to clinical commitments (n = 5). Conclusions Future development will focus on creating a robust system enabling this programme to continue and establishment of a key group of paediatric consultants, who can provide consistent teaching reflecting the realities of the examination.


Tuned with a Tune: Talker Normalization via General Auditory Processes.
Voices have unique acoustic signatures, contributing to the acoustic variability listeners must contend with in perceiving speech, and it has long been proposed that listeners normalize speech perception to information extracted from a talker's speech. Initial attempts to explain talker normalization relied on extraction of articulatory referents, but recent studies of context-dependent auditory perception suggest that general auditory referents such as the long-term average spectrum (LTAS) of a talker's speech similarly affect speech perception. The present study aimed to differentiate the contributions of articulatory/linguistic versus auditory referents for context-driven talker normalization effects and, more specifically, to identify the specific constraints under which such contexts impact speech perception. Synthesized sentences manipulated to sound like different talkers influenced categorization of a subsequent speech target only when differences in the sentences' LTAS were in the frequency range of the acoustic cues relevant for the target phonemic contrast. This effect was true both for speech targets preceded by spoken sentence contexts and for targets preceded by non-speech tone sequences that were LTAS-matched to the spoken sentence contexts. Specific LTAS characteristics, rather than perceived talker, predicted the results suggesting that general auditory mechanisms play an important role in effects considered to be instances of perceptual talker normalization.


Body-Space Interactions: Same Spatial Encoding but Different Influence of Valence for Reaching and Defensive Purposes.
The space around our body, the so-called peripersonal space, is where interactions with nearby objects may occur. "Defensive space" and "Reaching space", respectively, refer to two opposite poles of interaction between our body and the external environment: protecting the body and performing a goal-directed action. Here, we hypothesized that mechanisms underlying these two action spaces are differentially modulated by the valence of visual stimuli, as stimuli with negative valence are more likely to activate protective actions whereas stimuli with positive valence may activate approaching actions. To test whether such distinction in cognitive/evaluative processing exists between Reaching and Defensive spaces, we measured behavioral responses as well as neural activations over sensorimotor cortex using EEG while participants performed several tasks designed to tap into mechanisms underlying either Defensive (e.g., respond to touch) or Reaching space (e.g., estimate whether object is within reaching distance). During each task, pictures of objects with either positive or negative valence were presented at different distances from the participants' body. We found that Defensive space was smaller for positively compared with negatively valenced visual stimuli. Furthermore, sensorimotor cortex activation (reflected in modulation of beta power) during tactile processing was enhanced when coupled with negatively rather than positively valenced visual stimuli regarding Defensive space. On the contrary, both the EEG and behavioral measures capturing the mechanisms underlying Reaching space did not reveal any modulation by valence. Thus, although valence encoding had differential effects on Reaching and Defensive spaces, the distance of the visual stimulus modulated behavioral measures as well as activity over sensorimotor cortex (reflected in modulations of mu power) in a similar way for both types of spaces. Our results are compatible with the idea that Reaching and Defensive spaces involve the same distance-dependent neural representations of sensory input, whereas task goals and stimulus valence (i.e., contextual information) are implemented at a later processing stage and exert an influence on motor output rather than sensory/space encoding.


Quinones as Reversible Electron Relays in Artificial Photosynthesis.
We explore the potential of various hydroquinone/quinone redox couples as electron relays in a homogenous water reduction system between a Re-based photosensitizer and a sacrificial electron donor [tris-(2-carboxyethyl)-phosphine, TCEP]. By using transient IR spectroscopy, flash photolysis as well as stopped-flow techniques covering timescales from picoseconds to 100 ms, we determine quenching rates and cage escape yields, the kinetics of the follow-up chemistry of the semiquinone, the recombination rates, as well as the re-reduction rates by TCEP. The overall quantum yield of hydrogen production is low, and we show that the limiting factors are the small cage escape yields and, more importantly, the slow regeneration rate by TCEP in comparison to the undesired charge recombination with the reduced water reduction catalyst.


A high-throughput screening system for barley/powdery mildew interactions based on automated analysis of light micrographs.
To find candidate genes that potentially influence the susceptibility or resistance of crop plants to powdery mildew fungi, an assay system based on transient-induced gene silencing (TIGS) as well as transient over-expression in single epidermal cells of barley has been developed. However, this system relies on quantitative microscopic analysis of the barley/powdery mildew interaction and will only become a high-throughput tool of phenomics upon automation of the most time-consuming steps. We have developed a high-throughput screening system based on a motorized microscope which evaluates the specimens fully automatically. A large-scale double-blind verification of the system showed an excellent agreement of manual and automated analysis and proved the system to work dependably. Furthermore, in a series of bombardment experiments an RNAi construct targeting the Mlo gene was included, which is expected to phenocopy resistance mediated by recessive loss-of-function alleles such as mlo5. In most cases, the automated analysis system recorded a shift towards resistance upon RNAi of Mlo, thus providing proof of concept for its usefulness in detecting gene-target effects. Besides saving labor and enabling a screening of thousands of candidate genes, this system offers continuous operation of expensive laboratory equipment and provides a less subjective analysis as well as a complete and enduring documentation of the experimental raw data in terms of digital images. In general, it proves the concept of enabling available microscope hardware to handle challenging screening tasks fully automatically.


Influence of Plasma Treatment on the Polyphenols of Food Products-A Review.
The consumption of bioactive compounds, especially phenolic compounds, has been associated with health benefits such as improving the health status and reducing the risk of developing certain diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders. However, the preservation of natural bioactive compounds in food products is a major challenge for the food industry. Due to the major impact of conventional thermal processing, nonthermal technologies such as cold plasma have been proposed as one of the most promising solutions for the food industry. This review will cover the current knowledge about the effects of cold plasma in polyphenols found in food products. The increasing number of studies in the last years supports the continuous search for specific treatment conditions for each type of food and the central role of plasma treatments as a food-processing technology.


Drinking in different social contexts among white, black, and Hispanic men.
This paper describes alcohol use by White, Black, and Hispanic men in eight different social settings. Data were obtained from a multi-stage probability sample of the household population of White, Black, and Hispanic adults aged 18 years and over, residing in the 48 contiguous United States. The response rate was 73 percent for Whites, 76 percent for Blacks, and 72 percent for Hispanics. Results show that Whites go more frequently and drink more frequently than Blacks and Hispanics at restaurants, in clubs or organizational meetings, and in bars. Blacks go more frequently than Whites and Hispanics to public settings such as parks, streets, and parking lots; however, the mean number of drinks consumed in these public places and the proportion of men drinking five or more drinks is higher for Hispanics than for Whites and Blacks. Other places where heavier drinking is common in all three ethnic groups are bars, taverns and cocktail lounges, and parties. In all three ethnic groups, men who are younger and those who are single go more frequently than other men to bars or public places such as streets, parks, and parking lots. Men who are younger and those who are single also have a higher rate of heavy drinking and of drunkenness than other men.


Interplay between shape and roughness in early-stage microcapillary imbibition.
Flows in microcapillaries and associated imbibition phenomena play a major role across a wide spectrum of practical applications, from oil recovery to inkjet printing and from absorption in porous materials and water transport in trees to biofluidic phenomena in biomedical devices. Early investigations of spontaneous imbibition in capillaries led to the observation of a universal scaling behavior, known as the Lucas-Washburn (LW) law. The LW allows abstraction of many real-life effects, such as the inertia of the fluid, irregularities in the wall geometry, and the finite density of the vacuum phase (gas or vapor) within the channel. Such simplifying assumptions set a constraint on the design of modern microfluidic devices, operating at ever-decreasing space and time scales, where the aforementioned simplifications go under serious question. Here, through a combined use of leading-edge experimental and simulation techniques, we unravel a novel interplay between global shape and nanoscopic roughness. This interplay significantly affects the early-stage energy budget, controlling front propagation in corrugated microchannels. We find that such a budget is governed by a two-scale phenomenon: The global geometry sets the conditions for small-scale structures to develop and propagate ahead of the main front. These small-scale structures probe the fine-scale details of the wall geometry (nanocorrugations), and the additional friction they experience slows the entire front. We speculate that such a two-scale mechanism may provide a fairly general scenario to account for extra dissipative phenomena occurring in capillary flows with nanocorrugated walls.


Clinical development of pharmacologic agents for acute heart failure syndromes: a proposal for a mechanistic translational phase.
Hospitalization for acute heart failure syndromes (AHFS) predicts a poor prognosis, with postdischarge mortality and rehospitalization rates reaching 45% within 60 to 90 days. Despite the use of evidence-based therapies and adherence to national process measures, these event rates have largely remained the same over the past decade. Given the current and growing burden of AHFS, there exists a substantial unmet need for novel therapies that improve outcomes. However, attempts to improve symptoms and/or reduce postdischarge events have failed to produce positive results, either because of safety and/or efficacy. These negative results may be related to the drug itself, the protocol in terms of patient selection and/or end points, and/or the trial execution. Although experts may not agree on the exact reasons to explain the lack of success to date of phase III trials in AHFS, there is agreement that clinical benefits observed in phase II trials were not reproduced in phase III trials. A different approach may be needed. In November of 2009, a meeting was held at the Food and Drug Administration with the primary purpose of identifying the reasons why benefits observed during phase II did not translate into benefits in phase III to improve future trial design. Although multiple domains of trial design were discussed, the participants identified a lack of in-depth understanding of novel molecules before pivotal trials in AHFS as a possible contributor to the disappointing results of recent large trials. In this brief report, we outline the T1 or translational phase of research for AHFS clinical development as an important first step toward greater success in AHFS clinical trials.


GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition.
Aberrant sympathetic nerve activity exacerbates cardiovascular risk in hypertension and diabetes, which are common comorbidities, yet clinically sympathetic nerve activity remains poorly controlled. The hypertensive diabetic state is associated with increased reflex sensitivity and tonic drive from the peripheral chemoreceptors, the cause of which is unknown. We have previously shown hypertension to be critically dependent on the carotid body (CB) input in spontaneously hypertensive rat, a model that also exhibits a number of diabetic traits. CB overstimulation by insulin and leptin has been similarly implicated in the development of increased sympathetic nerve activity in metabolic syndrome and obesity. Thus, we hypothesized that in hypertensive diabetic state (spontaneously hypertensive rat), the CB is sensitized by altered metabolic signaling causing excessive sympathetic activity levels and dysfunctional reflex regulation. Using a hypothesis-free RNA-seq approach, we investigated potential molecular targets implicated in energy metabolism mediating CB sensitization and its regulation of sympathetic outflow in experimental hypertension. Identified targets were characterized using molecular and functional techniques assessing peripheral chemoreflex sensitivity in situ and in vivo. We discovered GLP1R (glucagon-like peptide-1 receptor) expression in the CBs of rat and human and showed that its decreased expression is linked to sympathetic hyperactivity in rats with cardiometabolic disease. We demonstrate GLP1R to be localized to CB chemosensory cells, while targeted administration of GLP1R agonist to the CB lowered its basal discharge and attenuated chemoreflex-evoked blood pressure and sympathetic responses. Importantly, hyperglycemia-induced peripheral chemoreflex sensitization and associated basal sympathetic overactivity were abolished by GLP1R activation in the CB suggesting a role in a homeostatic response to high blood glucose. We show that GLP1 (glucagon-like peptide-1) modulates the peripheral chemoreflex acting on the CB, supporting this organ as a multimodal receptor. Our findings pinpoint CBs as potential targets for ameliorating excessive sympathetic activity using GLP1R agonists in the hypertensive-diabetic condition.


Individual-based modelling of bacterial cultures to study the microscopic causes of the lag phase.
The lag phase has been widely studied for years in an effort to contribute to the improvement of food safety. Many analytical models have been built and tested by several authors. The use of Individual-based Modelling (IbM) allows us to probe deeper into the behaviour of individual cells; it is a bridge between theories and experiments when needed. INDividual DIScrete SIMulation (INDISIM) has been developed and coded by our group as an IbM simulator and used to study bacterial growth, including the microscopic causes of the lag phase. First of all, the evolution of cellular masses, specifically the mean mass and biomass distribution, is shown to be a determining factor in the beginning of the exponential phase. Secondly, whenever there is a need for an enzyme synthesis, its rate has a direct effect on the lag duration. The variability of the lag phase with different factors is also studied. The known decrease of the lag phase with an increase in the temperature is also observed in the simulations. An initial study of the relationship between individual and collective lag phases is presented, as a complement to the studies already published. One important result is the variability of the individual lag times and generation times. It has also been found that the mean of the individual lags is greater than the population lag. This is the first in a series of studies of the lag phase that we are carrying out. Therefore, the present work addresses a generic system by making a simple set of assumptions.


Folate, vitamin B12, and homocysteine in major depressive disorder.
The authors examined the relationships between levels of three metabolites (folate, vitamin B12, and homocysteine) and both depressive subtype and response to fluoxetine treatment in depressed patients. Fluoxetine, 20 mg/day for 8 weeks, was given to 213 outpatients with major depressive disorder. At baseline, depressive subtypes were assessed, and a blood sample was collected from each patient. Serum metabolite levels were assayed. Response to treatment was determined by percentage change in score on the 17-item Hamilton Depression Rating Scale. Subjects with low folate levels were more likely to have melancholic depression and were significantly less likely to respond to fluoxetine. Homocysteine and B12 levels were not associated with depressive subtype or treatment response. Overall, the results are consistent with findings linking low folate levels to poorer response to antidepressant treatment. Folate levels might be considered in the evaluation of depressed patients who do not respond to antidepressant treatment.


Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer?
Numerous molecular markers have been investigated as potential predictors of tumor responses to preoperative chemoradiotherapy (preCRT) for rectal cancer. To develop a system in which biomarkers are used to predict the likelihood of a pathologic complete response (pCR) to preCRT. This is a retrospective analysis of tumor specimens collected prior to preCRT from 81 patients who underwent curative resection for primary rectal adenocarcinoma between June 2008 and February 2012. Using tissue microarrays and immunohistochemistry, expression levels of twelve candidate biomarkers (p53, p21, Bcl2, Bax, EGFR, Cox-2, MLH-1, MSH-2, Ku70, VEGF, TS, Ki-67) were evaluated in paraffin-embedded tumor samples collected before preCRT. The correlation between biomarker expression levels and the pathologic response to preCRT was assessed based on histopathological staging (pTNM) and tumor regression grade (TRG). Expression levels of 4 biomarkers (p53, VEGF, p21, Ki67) correlated with pCR. Patients showing low expression of p53 and/or high expression of VEGF, p21, and Ki67 exhibited a significantly greater pCR rate. A scoring system devised so that one point was given for each biomarker whose expression level correlated with pCR (score range: 0-4) showed that 1 of 26 patients with scores of 0 to 1 achieved pCR, whereas 26 of 55 patients with scores of 2 to 4 achieved pCR (3.8% vs. 47.3%, p < 0.001). For prediction of pCR, the scoring system showed 96.3% sensitivity, 46.3% specificity, a 47.3% positive predictive value, and a 96.2% negative predictive value. Immunohistochemistry has limitations related to reproducibility and the ability to provide quantitative information. In addition, this study lacks test and validation sets. Expression levels of 4 biomarkers correlated with pCR after preCRT for rectal cancer. A scoring system based on levels of biomarker expression showed good sensitivity and negative predictive value for pCR.


Apolipoprotein E isotype-dependent modulation of microRNA-146a in plasma and brain.
The Apolipoprotein E (ApoE) isotype ApoE4 is a prevalent genetic risk factor for Alzheimer's disease (AD) that can modulate systemic and central inflammation, independent of amyloid accumulation. Although disruption of innate immune toll receptor signaling is modulated by ApoE and observed in AD, ApoE isotype-specific effects remain poorly understood. Therefore, we examined the effect of the ApoE isotype on the brain levels of major regulators of TLR signaling including miR146a, a microRNA enriched in the brain. We used 6-month-old ApoE3 or ApoE4 targeted replacement mice with and without mutant familial AD transgenes. ApoE4 reduced the levels of miR146a compared with ApoE3, both in the brain (29%; P<0.0001) and in plasma (47%; P<0.05), which correlated with each other (r=0.74; P<0.05). The presence of 5xFAD transgenes increased brain miR146a in both ApoE3 (E3FAD) and ApoE4 (E4FAD) mice; however, miR146a levels in E4FAD mice remained lower than those in E3FAD mice (62%; P<0.05), despite increased amyloid and inflammation. Supporting these observations, ApoE4 brains showed increased expression of interleukin receptor-associated kinase-1 (160%; P<0.05) (normally downregulated by miR146) that correlated inversely with miR146a levels (r=0.637; P<0.0001). Reduced negative feedback of toll-like receptor signaling (by miRNA146a) can explain early-life hypersensitivity to innate immune stimuli (including Aβ) in ApoE4 carriers. Thus, ApoE4 causes early dysregulation of a central controller of the innate immune system both centrally and systemically. This defect persists with familial AD pathology and may be relevant to ApoE4 AD risk.


Comparison of self-adhering flowable composite microleakage with several types of bonding agent in class V cavity restoration.
The aim of the present study was to compare the marginal seal of self-adhering flowable composite resin with three universal bonding systems using the self-etch technique in Cl V cavities at enamel and dentin margins. In this in vitro study, Cl V cavities were prepared on the buccal surfaces of forty premolars, with the occlusal margin of each cavity on enamel and gingival margin on dentin. The teeth were divided into four groups (n = 10) in terms of the adhesive used; Group 1: Vertise Flow (VF) self-adhering composite resin, Group 2: Clearfil S3 Bond Universal (CS3BU), Group 3: G-Premio Bond (GPB), Group 4: Single Bond Universal (SBU). In Groups 2, 3, and 4, Z350 flowable composite resin was used to restore the cavities. After thermocycling, the samples were immersed in 10% methylene blue for 24 h and evaluated under a stereomicroscope after buccolingual sectioning; microleakage at enamel and dentin margins was recorded. Kruskal-Wallis and Mann-Whitney tests were used for statistical analyses. Statistical significance was set at P < 0.5. Vertis Flow self-adhering composite resin exhibited significantly higher microleakage at enamel and dentin margins compared to SBU and CS3BU; however, it had significantly less microleakage at enamel margin compared to GPB (P < 0.05). At the enamel and dentin margins, the minimum microleakage values were recorded at SBU and CS3BU margins, respectively. GPB exhibited the highest microleakage values among the groups evaluated and in all the groups, microleakage at dentin and enamel margins was significantly different (P < 0.05) except for SBU group. The marginal sealing ability of self-adhering flowable composite resin at enamel and dentin margins was poor compared to the majority of bonding agents evaluated.


Synthons and design in metal phosphates and oxalates with open architectures.
We briefly describe the structures of open-framework metal phosphates with different dimensionalities, such as the one-dimensional linear-chain and ladder structures, two-dimensional layer structures and three-dimensional structures with channels. We demonstrate the role of the zero-dimensional four-membered ring monomer and of the one-dimensional ladder structure as the starting building units or synthons involved in the formation of the complex architectures. Thus, we show how the one-dimensional ladder structure transforms to two- and three-dimensional structures under mild conditions. The two-dimensional layer structures also transform to three-dimensional structures, while the zero-dimensional monomer transforms to layered and three-dimensional structures under ordinary reaction conditions. These transformations provide an insight into the possible pathways involved in the building up of the complex structures of metal phosphates. The isolation of amine phosphates during the hydrothermal synthesis of metal phosphates and also the facile reactions between amine phosphates and metal ions to yield a variety of open-framework materials have thrown light on the mechanism of formation and design of these structures. The existence of a hierarchy of open-framework metal oxalates and their ready formation by employing amine oxalates as intermediates provides additional support to the observations made earlier with regard to the phosphates.


Evaluation of Protein Elastic Network Models Based on an Analysis of Collective Motions.
Elastic network models (ENMs) are valuable tools for investigating collective motions of proteins, and a rich variety of simple models have been proposed over the past decade. A good representation of the collective motions requires a good approximation of the covariances between the fluctuations of the individual atoms. Nevertheless, most studies have validated such models only by the magnitudes of the single-atom fluctuations they predict. In the present study, we have quantified the agreement between the covariance structure predicted by molecular dynamics (MD) simulations and those predicted by a representative selection of proposed coarse-grained ENMs. We then contrast this approach with the comparison to MD-predicted atomic fluctuations and comparison to crystallographic B-factors. While all the ENMs yield approximations to the MD-predicted covariance structure, we report large and consistent differences between proposed models. We also find that the ability of the ENMs to predict atomic fluctuations is correlated with their ability to capture the covariance structure. In contrast, we find that the models that agree best with B-factors model collective motions less reliably and recommend against using B-factors as a benchmark.


The presentation of metabolic dysfunction and the relationship with energy output in breast cancer survivors: a cross-sectional study.
Breast cancer prognosis can be adversely influenced by obesity, physical inactivity and metabolic dysfunction. Interventions aimed at improving surrogate markers of breast cancer risk such as insulin resistance may result in improved breast cancer outcomes. The design of such interventions may be improved through increased understanding of metabolic presentation in this cohort. This cross-sectional study aimed to characterise the metabolic profile of breast cancer survivors relative to abdominal obesity and insulin resistance. A secondary aim was to compare measures of energy output across these groups. Sixty-nine women (mean (SD) age 53.43 (9.39) years) who had completed adjuvant chemotherapy and radiotherapy for breast cancer were recruited. All measures were completed during one assessment conducted 3.1 (1.0) years post diagnosis. Body composition was measured by bioimpedance analysis and waist circumference (WC). Fasting (12 hour) blood samples were drawn to measure lipid profile, glucose, insulin, glycosylated haemoglobin A1c (HBA1c) and C-reactive protein (CRP). Insulin resistance was estimated by the homeostatic model assessment index (HOMA-IR)). Energy output was evaluated by resting metabolic rate (RMR) measured by indirect calorimetry and physical activity measured by accelerometry. Characteristics were compared across four groups (1. WC <80 cm, not insulin resistant; 2. WC 80-87.9 cm, not insulin resistant; 3. WC >88 cm, not insulin resistant; 4. WC >80 cm, insulin resistant) using ANOVA (p < 0.05). Group 4 was characterised by significant disturbances in measures of glucose metabolism (glucose, insulin, HOMA-IR and HBA1c) and raised CRP compared to other groups. Group 4 also displayed evidence of dyslipidemia and higher body composition values compared to Groups 1 and 2. Both absolute and adjusted RMR were significantly higher in the Group 4 versus all other groups. Physical activity levels were similar for all groups. The results from this study suggest that participants who were both centrally obese and insulin resistant showed evidence of dyslipidemia, low-grade inflammation and glucose dysregulation. Metabolic profiles of participants who were centrally obese only were not significantly different from lean participants. Consideration of baseline metabolic presentation may be useful when considering the therapeutic targets for future interventions in this cohort.


Effectiveness of massage therapy for subacute low-back pain: a randomized controlled trial.
The effectiveness of massage therapy for low-back pain has not been documented. This randomized controlled trial compared comprehensive massage therapy (soft-tissue manipulation, remedial exercise and posture education), 2 components of massage therapy and placebo in the treatment of subacute (between 1 week and 8 months) low-back pain. Subjects with subacute low-back pain were randomly assigned to 1 of 4 groups: comprehensive massage therapy (n = 25), soft-tissue manipulation only (n = 25), remedial exercise with posture education only (n = 22) or a placebo of sham laser therapy (n = 26). Each subject received 6 treatments within approximately 1 month. Outcome measures obtained at baseline, after treatment and at 1-month follow-up consisted of the Roland Disability Questionnaire (RDQ), the McGill Pain Questionnaire (PPI and PRI), the State Anxiety Index and the Modified Schober test (lumbar range of motion). Of the 107 subjects who passed screening, 98 (92%) completed post-treatment tests and 91 (85%) completed follow-up tests. Statistically significant differences were noted after treatment and at follow-up. The comprehensive massage therapy group had improved function (mean RDQ score 1.54 v. 2.86-6.5, p < 0.001), less intense pain (mean PPI score 0.42 v. 1.18-1.75, p < 0.001) and a decrease in the quality of pain (mean PRI score 2.29 v. 4.55-7.71, p = 0.006) compared with the other 3 groups. Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function. At 1-month follow-up 63% of subjects in the comprehensive massage therapy group reported no pain as compared with 27% of the soft-tissue manipulation group, 14% of the remedial exercise group and 0% of the sham laser therapy group. Patients with subacute low-back pain were shown to benefit from massage therapy, as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists.


Fibroblasts from phenotypically normal palmar fascia exhibit molecular profiles highly similar to fibroblasts from active disease in Dupuytren's Contracture.
Dupuytren's contracture (DC) is a fibroproliferative disorder characterized by the progressive development of a scar-like collagen-rich cord that affects the palmar fascia of the hand and leads to digital flexion contractures. DC is most commonly treated by surgical resection of the diseased tissue, but has a high reported recurrence rate ranging from 27% to 80%. We sought to determine if the transcriptomic profiles of fibroblasts derived from DC-affected palmar fascia, adjacent phenotypically normal palmar fascia, and non-DC palmar fascial tissues might provide mechanistic clues to understanding the puzzle of disease predisposition and recurrence in DC. To achieve this, total RNA was obtained from fibroblasts derived from primary DC-affected palmar fascia, patient-matched unaffected palmar fascia, and palmar fascia from non-DC patients undergoing carpal tunnel release (6 patients in each group). These cells were grown on a type-1 collagen substrate (to better mimic their in vivo environments). Microarray analyses were subsequently performed using Illumina BeadChip arrays to compare the transcriptomic profiles of these three cell populations. Data were analyzed using Significance Analysis of Microarrays (SAM v3.02), hierarchical clustering, concordance mapping and Venn diagram. We found that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected fascia of DC patients exhibited a much greater overlap than fibroblasts derived from the palmar fascia of patients undergoing carpal tunnel release. Quantitative real time RT-PCR confirmed the differential expression of select genes validating the microarray data analyses. These data are consistent with the hypothesis that predisposition and recurrence in DC may stem, at least in part, from intrinsic similarities in the basal gene expression of diseased and phenotypically unaffected palmar fascia fibroblasts. These data also demonstrate that a collagen-rich environment differentially alters gene expression in these cells. In addition, Ingenuity pathway analysis of the specific biological pathways that differentiate DC-derived cells from carpal tunnel-derived cells has identified the potential involvement of microRNAs in this fibroproliferative disorder. These data show that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected palmar fascia in DC patients are highly similar, and differ significantly from the transcriptomic profiles of fibroblasts from the palmar fascia of patients undergoing carpal tunnel release.


Functional characterisation of missense variations in the Kir4.1 potassium channel (KCNJ10) associated with seizure susceptibility.
Recent genetic linkage studies have identified an association between missense variations in the gene encoding the Kir4.1 potassium channel (KCNJ10) and seizure susceptibility phenotypes in both humans and mice. The results of this study demonstrate that these variations (T262S and R271C) do not produce any observable changes in channel function or in predicted channel structure. It is therefore unlikely that the seizure susceptibility phenotypes associated with these missense variations are caused by changes in the intrinsic functional properties of Kir4.1.


Differential effects of lercanidipine/enalapril versus amlodipine/enalapril and hydrochlorothiazide/enalapril on target organ damage and sympathetic activation in non-obese essential hypertensive subjects.
The aim of the present study was to compare the effects of the combination of lercanidipine/enalapril versus amlodipine/enalapril and hydrochlorothiazide/enalapril on blood pressure, target organ damage and sympathetic activation in patients with grade 2 essential hypertension. This was a 3 month, randomized, blinded-endpoint study in essential hypertensive patients. Office and ambulatory blood pressure, arterial stiffness, urinary albumin to creatinine ratio, renal arterial resistive index, and muscle sympathetic nerve activity were evaluated at baseline, after a 2 week run-in placebo period, at 1 month and at 3 months. In total, 56 patients were assigned to lercanidipine/enalapril (n = 19), enalapril/amlodipine (n = 18) and hydrochlorothiazide/enalapril (n = 19). Each pharmacological combination tested was effective in reducing office blood pressure at 1 month and 3 months, and 24 h ambulatory blood pressure at 3 months. Renal arterial resistive index (RI) significantly improved at 1 month and 3 months compared with baseline in all groups. However in the lercanidipine/enalapril and hydrochlorothiazide/enalapril groups, RI was favorably reduced (0.53 ± 0.03 and 0.54 ± 0.04 respectively, p < 0.05) in comparison with the enalapril/amlodipine RI value (0.57 ± 0.03) at 3 months. Moreover, after 3 months of treatment, a significant decrease (by -5.47 bursts/min) (p < 0.05) in muscle sympathetic nerve activity was observed in the lercanidipine/enalapril group (50.79 ± 6.49) compared with baseline (56.26 ± 6.05), while no differences were detected in the amlodipine/enalapril and hydrochlorothiazide/enalapril groups. Our study provides evidence of the efficacy of the lercanidipine/enalapril combination in ameliorating hypertension-related target organ damage and in reducing sympathetic overdrive.


Vestibular function and vertigo control after intratympanic gentamicin for Ménière's disease.
The aim of this study was to correlate long-term vertigo control with reduction in vestibular function after intratympanic (IT) gentamicin therapy for unilateral Ménière's disease. IT gentamicin injections were given as needed to control vertigo attacks. Vertigo frequency and changes in angular vestibulo-ocular reflex (AVOR) gain (measured using magnetic search coils and manual head thrusts) and caloric weakness were assessed before and after treatment. Better vertigo control after treatment was found with >or=60% reduction in quantitative ipsilateral horizontal semicircular canal AVOR gain from pre-treatment values and/or with caloric unilateral weakness (UW) >50%. However, no correlations were found between the continuous variables of vertigo control and either gain or gain recovery, nor between gain and UW because of the large variability in vertigo control in subjects with lesser reductions in these measures.


New actinosporean description prompts union of the raabeia and echinactinomyxon collective groups (Cnidaria, Myxozoa).
We describe, morphologically and molecularly, a new actinosporean from the intestinal epithelium of the freshwater oligochaete Ilyodrilus templetoni in the upper estuary of the River Minho, Northern Portugal. Mature actinospores resembled both echinactinomyxon and raabeia types, emphasizing the previously known lack of a clear boundary between these 2 collective groups. Historically, raabeia and echinactinomyxon types have been differentiated solely based on the shape of the valvular processes being curved or straight, respectively. Our observations, however, show that this morphological character is too variable for distinguishing between these 2 collective groups, since the actinospores of the raabeia described here displayed valvular processes that could either be straight, downward or upward curved. Several similar cases can be found in the available literature. Considering this overlap in actinospore morphology, we propose that echinactinomyxon be deemed invalid and its types be included in raabeia, as the latter constitutes the older of the 2 groups. Known echinactinomyxon types, however, should not be renamed as raabeia, as this would create unnecessary confusion. Accordingly, a more comprehensive definition of the raabeia collective group is provided. Phylogenetic analyses revealed polyphyletic clustering of raabeia/echinactinomyxon types among members of the myxosporean suborders Variisporina and Platysporina, reiterating the lack of agreement between actinosporean morphotypes and myxosporean genera. The new type described here specifically clusters within the Paramyxidium clade, alongside other SSU rDNA sequences of raabeia, echinactinomyxon, aurantiactinomyxon and synactinomyxon. Considering that most Paramyxidium spp. parasitize Anguilla anguilla (Linnaeus, 1758), future myxozoan surveys in the River Minho should include this species.


Vmax regulation through domain and subunit changes. The active form of phosphoglycerate dehydrogenase.
An active conformation of phosphoglycerate dehydrogenase (PGDH) from Escherichia coli has been obtained using X-ray crystallography. The X-ray crystal structure is used to examine the potential intermediates for V(max) regulation, for the redox reaction, and for cooperative effects of serine binding. The crystal structure at 2.2 A resolution contains bound NAD(+) cofactor, either sulfate or phosphate anions, and alpha-ketoglutarate, a nonphysiological substrate. A PGDH subunit is formed from three distinct domains: regulatory (RBD), substrate (SBD), and nucleotide binding (NBD). The crystal conformation of the homotetramer points to the fact that, in the absence of serine, coordinated movement of the RBD-SBD domains occurs relative to the NBD. The result is a conformational change involving the steric relationships of both the domains and the subunits. Within the active site of each subunit is a bound molecule of alpha-ketoglutarate and the coenzyme, NAD. The catalytic or active site cleft is changed slightly although it is still solvent exposed; therefore, the catalytic reaction probably involves additional conformational changes. By comparing the inhibited with the uninhibited complex, it is possible to describe changes in conformation that are involved in the inhibitory signal transduction of serine.


Characterization of Newcastle disease viruses isolated from cormorant and gull species in the United States in 2010.
Newcastle disease virus (NDV), a member of the genus Avulavirus of the family Paramyxoviridae, is the causative agent of Newcastle disease (ND), a highly contagious disease that affects many species of birds and which frequently causes significant economic losses to the poultry industry worldwide. Virulent NDV (vNDV) is exotic in poultry in the United States; however, the virus has been frequently associated with outbreaks of ND in cormorants, which poses a significant threat to poultry species. Here, we present the characterization of 13 NDV isolates obtained from outbreaks of ND affecting cormorants and gulls in the states of Minnesota, Massachusetts, Maine, New Hampshire, and Maryland in 2010. All 2010 isolates are closely related to the viruses that caused the ND outbreaks in Minnesota in 2008, following the new evolutionary trend observed in cormorant NDV isolates since 2005. Similar to the results obtained with the 2008 isolates, the standard United States Department of Agriculture F-gene real-time reverse-transcription PCR (RRT-PCR) assay failed to detect the 2010 cormorant viruses, whereas all viruses were detected by a cormorant-specific F-gene RRT-PCR assay. Notably, NDV-positive gulls were captured on the eastern shore of Maryland, which represents a significant geographic expansion of the virus since its emergence in North America. This is the first report of vNDV originating from cormorants isolated from wild birds in Maryland and, notably, the first time that genotype V vNDV has been isolated from multiple wild bird species in the United States. These findings highlight the need for constant epidemiologic surveillance for NDV in wild bird populations and for consistent biosecurity measures to prevent the introduction of the agent into domestic poultry flocks.


Membrane currents of retinal bipolar cells in culture.
1. Retinal bipolar cells were isolated from white bass retinas and maintained in a cell culture preparation. Two morphological types of bipolar cells were observed in cell culture. These were labeled large- and small-bipolar cells based mainly on the size of their somata and primary dendrites. Two types of small-bipolar cells were observed. Isolated bass bipolar cells are very similar to those described in the intact retina. 2. Under current clamp, to depolarizing current injection, small-bipolar cells produced a spike followed by a plateau. Large-bipolar cells showed a slow depolarization to a plateau level. 3. Voltage-gated membrane currents were studied using whole-cell patch-clamp techniques. Channel blocking agents were used to define the ion channels found in the membranes of these cells. 4. The large-bipolar cells were found to possess an A-current, a calcium current, and a calcium-dependent potassium current. 5. Large bipolar cells also possessed an inward rectifier that did not correspond to any previously described. 6. The two types of small-bipolar cells were found to have very similar membrane properties to one another. They lacked a large A-current but possessed a slowly activating, outward rectifying potassium current. Similar to the large-bipolar cells, they showed a calcium current and a calcium-activated potassium current. 7. The inward rectifier of small-bipolar cells was characterized as an H-current. 8. The results suggest that the membrane currents of bipolar cells set a narrow operating range about which the cells function in the intact retina. In addition these currents help shape the responses of bipolar cells to light stimuli but do not confer ON or OFF properties.


Association of family and health care provider opinion on infant feeding with mother's breastfeeding decision.
In the United States, about 25% of women choose not to initiate breastfeeding, yet little is known about how opinions of individuals in a woman's support network influence her decision to breastfeed. In the 2005-2007 Infant Feeding Practices Study II, women completed questionnaires from the last trimester of pregnancy until 12 months postpartum. Mothers indicated prenatally their family members' and health care providers' opinion on how newborns should be fed: breastfed only, formula fed only, breast and formula fed, or no opinion/don't know. Breastfeeding initiation was determined by asking mothers around 4 weeks postpartum (n=2,041) whether they ever breastfed. Logistic regression was used to examine the association between mothers' perception of family members' and health care providers' opinion on how to feed the infant and the initiation of breastfeeding, adjusting for sociodemographic characteristics. Nearly 14% of mothers surveyed did not initiate breastfeeding. Mothers who believed their family members or health care providers preferred breastfeeding only were least likely not to initiate breastfeeding. Never breastfeeding was significantly associated with the following perceptions: the infant's father (odds ratio [OR]=110.4; 95% CI 52.0 to 234.4) or maternal grandmother (OR=15.9; 95% CI 7.0 to 36.0) preferred only formula feeding; the infant's father (OR=3.2; 95% CI 1.7 to 5.9) or doctor (OR=2.7; 95% CI 1.2 to 6.2) preferred both breast and formula feeding; and the infant's father (OR=7.6; 95% CI 4.5 to 12.7), maternal grandmother (OR=5.4; 95% CI 2.6 to 11.0), or doctor (OR=1.9; 95% CI 1.0 to 3.7) had no opinion/didn't know their feeding preference. The prenatal opinions of family members and health care providers play an important role in a woman's breastfeeding decisions after the infant's birth.


BIOCHAM: an environment for modeling biological systems and formalizing experimental knowledge.
BIOCHAM (the BIOCHemical Abstract Machine) is a software environment for modeling biochemical systems. It is based on two aspects: (1) the analysis and simulation of boolean, kinetic and stochastic models and (2) the formalization of biological properties in temporal logic. BIOCHAM provides tools and languages for describing protein networks with a simple and straightforward syntax, and for integrating biological properties into the model. It then becomes possible to analyze, query, verify and maintain the model with respect to those properties. For kinetic models, BIOCHAM can search for appropriate parameter values in order to reproduce a specific behavior observed in experiments and formalized in temporal logic. Coupled with other methods such as bifurcation diagrams, this search assists the modeler/biologist in the modeling process. BIOCHAM (v. 2.5) is a free software available for download, with example models, at http://contraintes.inria.fr/BIOCHAM/.


The genetic basis of laboratory adaptation in Caulobacter crescentus.
The dimorphic bacterium Caulobacter crescentus has evolved marked phenotypic changes during its 50-year history of culture in the laboratory environment, providing an excellent system for the study of natural selection and phenotypic microevolution in prokaryotes. Combining whole-genome sequencing with classical molecular genetic tools, we have comprehensively mapped a set of polymorphisms underlying multiple derived phenotypes, several of which arose independently in separate strain lineages. The genetic basis of phenotypic differences in growth rate, mucoidy, adhesion, sedimentation, phage susceptibility, and stationary-phase survival between C. crescentus strain CB15 and its derivative NA1000 is determined by coding, regulatory, and insertion/deletion polymorphisms at five chromosomal loci. This study evidences multiple genetic mechanisms of bacterial evolution as driven by selection for growth and survival in a new selective environment and identifies a common polymorphic locus, zwf, between lab-adapted C. crescentus and clinical isolates of Pseudomonas aeruginosa that have adapted to a human host during chronic infection.


Real time patient safety audits: improving safety every day.
Timely error detection including feedback to clinical staff is a prerequisite for focused improvement in patient safety. Real time auditing, the efficacy of which has been repeatedly demonstrated in industry, has not been used previously to evaluate patient safety. Methods successful at improving quality and safety in industry may provide avenues for improvement in patient safety. Pilot study to determine the feasibility and utility of real time safety auditing during routine clinical work in an intensive care unit (ICU). A 36 item patient safety checklist was developed via a modified Delphi technique. The checklist focused on errors associated with delays in care, equipment failure, diagnostic studies, information transfer and non-compliance with hospital policy. Safety audits were performed using the checklist during and after morning work rounds thrice weekly during the 5 week study period from January to March 2003. A total of 338 errors were detected; 27 (75%) of the 36 items on the checklist detected >or=1 error. Diverse error types were found including unlabeled medication at the bedside (n = 31), ID band missing or in an inappropriate location (n = 70), inappropriate pulse oximeter alarm setting (n = 22), and delay in communication/information transfer that led to a delay in appropriate care (n = 4). Real time safety audits performed during routine work can detect a broad range of errors. Significant safety problems were detected promptly, leading to rapid changes in policy and practice. Staff acceptance was facilitated by fostering a blame free "culture of patient safety" involving clinical personnel in detection of remediable gaps in performance, and limiting the burden of data collection.


Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series.
Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (≥1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modern legacy of past equestrian civilizations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modern breeding impacted genetic diversity more dramatically than the previous millennia of human management.


Identification of protease and rpoN-associated genes of uropathogenic Proteus mirabilis by negative selection in a mouse model of ascending urinary tract infection.
Proteus mirabilis, a motile gram-negative bacterium, is a principal cause of urinary tract infections in patients with functional or anatomical abnormalities of the urinary tract or those with urinary catheters in place. Thus far, virulence factors including urease, flagella, haemolysin, various fimbriae, IgA protease and a deaminase have been characterized based on the phenotypic traits conferred by these proteins. In this study, an attempt was made to identify new virulence genes of P. mirabilis that may not have identifiable phenotypes using the recently described technique of signature-tagged mutagenesis. A pool of chromosomal transposon mutants was made through conjugation and kanamycin/tetracycline selection; random insertion was confirmed by Southern blotting of chromosomal DNA isolated from 16 mutants using the aphA gene as a probe. From the total pool, 2.3% (9/397) auxotrophic mutants and 3.5% (14/397) swarming mutants were identified by screening on minimal salts agar and Luria agar plates, respectively. Thirty per cent of the mutants, found to have either no tag or an unamplifiable tag, were removed from the input pool. Then 10(7) c.f.u. from a 96-mutant pool (approximately 10(5) c.f.u. of each mutant) were used as an input pool to transurethrally inoculate seven CBA mice. After 2 d infection, bacteria were recovered from the bladders and kidneys and yielded about 10(5) c.f.u. as an output pool. Dot blot analysis showed that two of the 96 mutants, designated B2 and B5, could not be hybridized by signature tags amplified from the bladder output pool. Interrupted genes from these two mutants were cloned and sequenced. The interrupted gene in B2 predicts a polypeptide of 37.3 kDa that shares amino acid similarity with a putative protease or collagenase precursor. The gene in B5 predicts a polypeptide of 32.6 kDa that is very similar to that encoded by ORF284 of the rpoN operon controlling expression of nitrogen-regulated genes from several bacterial species. The virulence of the two mutants was tested further by co-challenging CBA mice with each mutant and the parental strain. After 1 week of infection, the B2 and B5 mutants were recovered in numbers 100-fold and 1000-fold less than the parental strain, respectively. Using an in vitro assay, it was shown that the B2 mutant had significantly less (P = 0.0001) extracellular protease activity than the wild-type strain. These findings demonstrate that signature-tagged mutagenesis is a viable approach to identify bacterial genes associated with the ability to infect the urinary tract.


Multivariate evaluation of factors influencing the performance of a formic acid biosensor for use in air monitoring.
A formic acid biosensor for air monitoring has been evaluated using chemometric methods. Using experimental design eleven factors that could influence the performance of the biosensor were examined. The response matrices consisted of six parameters (steady state currents at three different formic acid concentrations and response rates during changes in formic acid concentrations) describing the performance of the biosensor. The data were evaluated using a combination of principal component analysis (PCA) and multiple linear regression (MLR). To confirm the conclusions from the PCA-MLR partial least squares (PLS) was also used. The most important factor for the biosensor performance was found to be the enzyme concentration. Using the information from the chemometric analyses the optimum operation conditions for the biosensor were determined. The steady state currents were increased by 18-30% and the initial two response rates increased by 47-89% compared with a biosensor that had not been optimised.


Prevalence of childhood trauma in a community sample of substance-abusing women.
The purpose of this study was to estimate the prevalence of positive trauma histories in a community sample of intravenous drug using (IVDU) women for five subsets of childhood trauma (emotional abuse or neglect, physical abuse or neglect, and sexual abuse) and to compare demographic variables between the abused versus nonabused groups. Of the 181 women who completed the Childhood Trauma Questionnaire (CTQ), 109 (60.2%) were sexually abused, 100 (55.2%) were physically abused, 83 (45.9%) were emotionally abused, 151 (83.4%) were emotionally neglected, and 108 (59.7%) were physically neglected. There were no statistically significant findings for age, ethnicity, and educational level. Those subjects that were physically neglected were more likely not to be in a current relationship compared to those subjects that were not abused (p = .036). The findings suggest that the prevalence of all five childhood traumas was higher than what has been reported in the general population, and that physical neglect of individuals may predict lack of current significant relationships.


Mastopexy preferences: a survey of board-certified plastic surgeons.
The purpose of this survey was to assess the current trends in mastopexy techniques and to compare satisfaction rates and complications associated with different techniques. In September of 2002, a mastopexy survey was sent to 1500 members of the American Society for Aesthetic Plastic Surgery; 487 complete responses were received, for a response rate of 32.5 percent. Questions elicited categorical answers, and the data were evaluated using the chi-square test and the comparison of two proportions. The inverted-T incision technique is the most popular. Satisfaction was reported to be highest with the short scar periareolar inferior pedicle reduction (or SPAIR) and Hall-Findlay techniques. Physician satisfaction was lowest with the periareolar technique. The three most common complications for all techniques were suture spitting, excess scarring, and bottoming out. The periareolar group had a greater frequency of revision (p = 0.002). The inverted-T group had a greater frequency of bottoming out (p = 0.043). The short scar group had a greater frequency of asymmetry (p = 0.008). The traditional inverted-T technique is the most popular, but the newer short scar techniques have become more popular in the last 5 years. The inverted-T incision continues to be associated with bottoming out and excess scarring. The periareolar technique has the greatest need for revision and the lowest physician satisfaction, despite its application to a greater volume of mastopexies per year.


A convenient guideline to determine if two Y-STR profiles are from the same lineage.
Y chromosome STR loci are used in forensics primarily for identification purposes by determining the male lineages. The Henan province in China has established a large Y-STR (>200 000 profiles) database for criminal investigations. A large proportion of the Y-STR profiles in the database were generated using either the Applied Biosystems Yfiler(ۛ) or Yfiler(ۛ) Plus PCR Amplification kits. The additional loci in the Yfiler Plus kit as compared to the Yfiler kit results in a concomitant cumulative mutation rate increase across the loci. Therefore, in those cases when two profiles have one to a few mismatched loci, it is difficult to determine if they are from the same lineage. In this study, 7405 unrelated male profiles were manually selected from the database. Analysis showed higher power of discrimination than the corresponding Yfiler haplotypes. Further, the distributions of the number of mismatched loci and the mismatched steps were generated for father-son, grandfather-grandson, uncle-nephew, and cousins (i.e. one, two, three, and four meioses, respectively) by exhaustive pairwise comparison of the unrelated profiles using a dynamic programming approach. The same distributions were generated for unrelated pairs with mutation rates of the loci. With the distributions, the false negative and false positive rates were determined. Two Yfiler profiles with ≤2 mismatched loci or ≤2 steps are more likely from the same lineage than unrelated lineages, and two Yfiler Plus profiles with ≤4 mismatched loci or ≤5 mismatched steps are more likely from the same lineage.


Physical Collaboration of Human-Human and Human-Robot Teams.
Human partners working on a target acquisition task perform faster than do individuals on the same task, even though the partners consider each other to be an impediment. We recorded the force profile of each partner during the task, revealing an emergent specialization of roles that could only have been negotiated through a haptic channel. With this understanding of human haptic communication we attempted a "haptic Turing test," replicating human behaviors in a robot partner. Human participants consciously and incorrectly believed their partner was human. However, force profiles did not show specialization of roles in the human partner, nor enhanced dyadic performance, suggesting that haptic interaction holds a greater subconscious subtlety. We further report observations of a non-zero dyadic steady state force perhaps analogous to co-contraction within the limb of an individual, where it contributes to limb stiffness and disturbance rejection. We present results on disturbance rejection in a dyad, showing lack of an effective dyadic strategy for brief events.


Coracoid Process Morphology using 3D-CT Imaging in a Malaysian Population.
Introduction: The aims of this study are to define the coracoid process anatomy in a Malaysian population, carried out on patients in Hospital Serdang with specific emphasis on the dimension of the base of coracoid process which is important in coraco-acromial (CC) ligament reconstruction, to define the average amount of bone available for use in coracoid transfer, and to compare the size of coracoid process based on gender and race, and with findings in previous studies. Materials and Methods: Fifteen pairs of computed tomography (CT) based 3-dimensional models of shoulders of patients aged between 20 to 60 years old were examined. The mean dimensions of coracoid were measured and compared with regards to gender and race. The data were also compared to previously published studies. Results: The mean length of the coracoid process was 37.94 ± 4.30 mm. Male subjects were found to have larger-sized coracoids in all dimensions as compared to female subjects. The mean tip of coracoid dimension overall was 19.99 + 1.93mm length × 10.03 + 1.48mm height × 11.63 + 2.12mm width. The mean base of coracoid dimension was 18.96 + 3.71mm length × 13.84 + 1.76mm width. No significant differences were observed with regards to racial denomination. The overall coracoid size measurements were found to be smaller compared to previous studies done on the Western population. Conclusion: This study may suggest that Malaysians have smaller coracoid dimension compared to Caucasians. The findings further suggest that the incidence of coracoid fracture and implants pull out in Malaysian subjects may be higher.


Identification and localisation of the NB-LRR gene family within the potato genome.
The potato genome sequence derived from the Solanum tuberosum Group Phureja clone DM1-3 516 R44 provides unparalleled insight into the genome composition and organisation of this important crop. A key class of genes that comprises the vast majority of plant resistance (R) genes contains a nucleotide-binding and leucine-rich repeat domain, and is collectively known as NB-LRRs. As part of an effort to accelerate the process of functional R gene isolation, we performed an amino acid motif based search of the annotated potato genome and identified 438 NB-LRR type genes among the ~39,000 potato gene models. Of the predicted genes, 77 contain an N-terminal toll/interleukin 1 receptor (TIR)-like domain, and 107 of the remaining 361 non-TIR genes contain an N-terminal coiled-coil (CC) domain. Physical map positions were established for 370 predicted NB-LRR genes across all 12 potato chromosomes. The majority of NB-LRRs are physically organised within 63 identified clusters, of which 50 are homogeneous in that they contain NB-LRRs derived from a recent common ancestor. By establishing the phylogenetic and positional relationship of potato NB-LRRs, our analysis offers significant insight into the evolution of potato R genes. Furthermore, the data provide a blueprint for future efforts to identify and more rapidly clone functional NB-LRR genes from Solanum species.


Thrombospondin-1 at the crossroads of corpus luteum fate decisions.
The multimodular matricellular protein thrombospondin-1 (THBS1) was among the first identified endogenous antiangiogenic molecules. Recent studies have shown THBS1-mediated suppression of angiogenesis and other critical activities for corpus luteum (CL) regression. THBS1 is specifically induced by prostaglandin F2alpha in mature CL undergoing regression, whereas luteinizing signals such as luteinizing hormone and insulin reduced its expression. THBS1 interacts both synergistically and antagonistically with other essential luteal factors, such as fibroblast growth factor 2, transforming growth factor beta1 and serpin family E member 1, to promote vascular instability, apoptosis and matrix remodeling during luteal regression. Expression of THBS1 is also downregulated by pregnancy recognition signals to maintain the CL during early pregnancy. This dynamic pattern of luteal expression, the extensive interactivity with other luteal factors and strong antiangiogenic and proapoptotic activities indicate that THBS1 is a major determinant of CL fate.


Deranged Pulmonary Function Tests in Allergic Rhinitis in North Indian Patients.
Significant associations between allergic rhinitis and bronchial asthma have been established and as a result of bronchial hyper-responsiveness, patients can have deranged pulmonary function tests. We aim to compare previous such studies with the result of our study done in India wherein we identify among allergic rhinitis patients who despite not having overt asthmatic symptoms, have pulmonary function derangements, quite possibly at a subclinical disease level. We studied 74 patients of allergic rhinitis and after meticulous clinical work up, they underwent blood tests including hemogram, absolute eosinophil count, and total serum IgE followed by pulmonary function tests. Out of 74 patients 60 (81%) had intermittent allergic rhinitis whereas only 14 (19%) had persistent allergic rhinitis. Pulmonary function tests showed reversible obstruction, ie, >10% improvement in FEV1 with inhaled bronchodilators (as seen in asthma) in 18 (24.3%), mild obstruction in 14, and moderate obstruction in 4 cases. The study emphasizes the importance of pulmonary symptoms and the performance of pulmonary function tests in cases of allergic rhinitis patients to rule out latent asthma.


Experimental detection of iron overload in liver through neutron stimulated emission spectroscopy.
Iron overload disorders have been the focus of several quantification studies involving non-invasive imaging modalities. Neutron spectroscopic techniques have demonstrated great potential in detecting iron concentrations within biological tissue. We are developing a neutron spectroscopic technique called neutron stimulated emission computed tomography (NSECT), which has the potential to diagnose iron overload in the liver at clinically acceptable patient dose levels through a non-invasive scan. The technique uses inelastic scatter interactions between atomic nuclei in the sample and incoming fast neutrons to non-invasively determine the concentration of elements in the sample. This paper discusses a non-tomographic application of NSECT investigating the feasibility of detecting elevated iron concentrations in the liver. A model of iron overload in the human body was created using bovine liver tissue housed inside a human torso phantom and was scanned with a 5 MeV pulsed beam using single-position spectroscopy. Spectra were reconstructed and analyzed with algorithms designed specifically for NSECT. Results from spectroscopic quantification indicate that NSECT can currently detect liver iron concentrations of 6 mg g(-1) or higher and has the potential to detect lower concentrations by optimizing the acquisition geometry to scan a larger volume of tissue. The experiment described in this paper has two important outcomes: (i) it demonstrates that NSECT has the potential to detect clinically relevant concentrations of iron in the human body through a non-invasive scan and (ii) it provides a comparative standard to guide the design of iron overload phantoms for future NSECT liver iron quantification studies.


Integrated self-management program effects on hemodialysis patients: A quasi-experimental study.
To evaluate the effects of an integrated self-management program using a mobile application, a short message service using a smartphone, and face-to-face counseling and education among hemodialysis patients. A quasi-experimental study design was used. The participants of this study were 84 hemodialysis patients (42 in the experimental group and 42 in the control group). The experimental group received the integrated self-management program for 8 weeks. The data were analyzed by using the independent t-test and Mann-Whitney U test to identify differences in self-efficacy, treatment compliance, the ratio of interdialytic weight gain to dry weight, and serum potassium and phosphorus levels between the experimental group and the control group at the end of the program. The scores for self-efficacy and treatment compliance were significantly higher in the experimental group than in the control group. The ratio of interdialytic weight gain to dry weight significantly decreased in the experimental group, compared to the control group. The serum potassium and phosphorus levels in the experimental group were not significantly lower than those of the control group. The findings suggest that the integrated self-management program that was implemented in this study could be a potentially effective intervention to improve the self-management of hemodialysis patients. Further research on various nursing intervention programs is warranted, including a mobile application program to improve hemodialysis patients' self-management.


The effect of cost on adherence to prescription medications in Canada.
Many patients do not adhere to treatment because they cannot afford their prescription medications, putting them at increased risk of adverse health outcomes. We determined the prevalence of cost-related nonadherence and investigated its associated characteristics, including whether a person has drug insurance. Using data from the 2007 Canada Community Health Survey, we analyzed the responses of 5732 people who answered questions about cost-related nonadherence to treatment. We determined the national prevalence of cost-related nonadherence and used logistic regression to evaluate the association between cost-related nonadherence and a series of demographic and socioeconomic variables, including province of residence, age, sex, household income, health status and having drug insurance. Cost-related nonadherence was reported by 9.6% (95% confidence interval [CI] 8.5%-10.6%) of Canadians who had received a prescription in the past year. In our adjusted model, we found that people in poor health (odds ratio [OR] 2.64, 95% CI 1.77-3.94), those with lower income (OR 3.29, 95% CI 2.03-5.33), those without drug insurance (OR 4.52, 95% CI 3.29-6.20) and those who live in British Columbia (OR 2.56, 95% CI 1.49-4.42) were more likely to report cost-related nonadherence. Predicted rates of cost-related nonadherence ranged from 3.6% (95% CI 2.4-4.5) among people with insurance and high household incomes to 35.6% (95% CI 26.1%-44.9%) among people with no insurance and low household incomes. About 1 in 10 Canadians who receive a prescription report cost-related nonadherence. The variability in insurance coverage for prescription medications appears to be a key reason behind this phenomenon.


Protecting young women from HIV/AIDS: the case against child and adolescent marriage.
In most developing countries, the majority of sexually active female adolescents are married. Although married adolescents are often assumed to be at low risk for HIV infection, little is known about the actual HIV risks these adolescents face or about ways to minimize these risks. Demographic and Health Survey data from 29 countries in Africa and Latin America were used to examine the frequency of factors that may increase HIV risk in married women aged 15-19. Several behavioral and social factors may increase the vulnerability of married female adolescents to HIV infection. First, these young women engage in frequent unprotected sex: In most countries, more than 80% of adolescents who had had unprotected sex during the previous week were married. Second, women who marry young tend to have much older husbands (mean age difference, 5-14 years) and, in polygamous societies, are frequently junior wives, factors that may increase the probability that their husbands are infected and weaken their bargaining power within the marriage. Third, married adolescents have relatively little access to educational and media sources of information about HIV. Finally, the most common AIDS prevention strategies (abstinence, condom use) are not realistic options for many married adolescents. New policies and interventions, tailored to the sexual and behavioral profiles of women in each country, are needed to address the vulnerabilities of adolescent wives. In some countries, delaying age at marriage may be an important strategy; in others, making intercourse within marriage safer may be more valuable.