Mass spectrometry sampling under ambient conditions with desorption electrospray ionization.
A new method of desorption ionization is described and applied to the ionization of various compounds, including peptides and proteins present on metal, polymer, and mineral surfaces. Desorption electrospray ionization (DESI) is carried out by directing electrosprayed charged droplets and ions of solvent onto the surface to be analyzed. The impact of the charged particles on the surface produces gaseous ions of material originally present on the surface. The resulting mass spectra are similar to normal ESI mass spectra in that they show mainly singly or multiply charged molecular ions of the analytes. The DESI phenomenon was observed both in the case of conductive and insulator surfaces and for compounds ranging from nonpolar small molecules such as lycopene, the alkaloid coniceine, and small drugs, through polar compounds such as peptides and proteins. Changes in the solution that is sprayed can be used to selectively ionize particular compounds, including those in biological matrices. In vivo analysis is demonstrated.


The relationship between oral health-related quality of life, the need for orthodontic treatment and bullying, among Brazilian teenagers.
Orthodontic treatment aims at oral health and restoration of function as main objectives, however, psychological and social effects end up being the main reason for the demand for treatment. To determine the association between the oral health-related quality of life (OHRQoL), the need for orthodontic treatment and bullying among Brazilian teenagers. This was a cross-sectional epidemiological study. To assess the malocclusion, the Dental Aesthetic Index was used. And the Oral Health Impact Profile-14 was used to analyze the OHRQoL. The Kidscape questionnaire was used to investigate cases of bullying. The following variables were also included: previous orthodontic treatment and a desire to fix the teeth to improve one's appearance. Multivariate analysis was performed using logistic regression considering the poor OHRQoL as a response variable. 815 teenagers participated in the study. There was a statistically significant association between oral health-related quality of life and the variables: previous orthodontic treatment (p= 0.0270), desire to fix the teeth (p< 0.0001), sex (p= 0.0309), history of being a victim of bullying (p< 0.0001), frequency of bullying episodes (p= 0.0170), and consequences of bullying (p< 0.0001). The following were considered as risk factors for poor OHRQoL: lack of previous orthodontic treatment (OR = 2.191) and negative consequences of bullying (OR = 3.042). The need for orthodontic treatment was not associated with the OHRQoL; however, bullying and previous orthodontic treatment had a statistically significant association with this variable.


Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydranize metabolites.
Approximately 10% to 20% of isoniazid recipients manifest biochemical evidence of liver injury. A smaller number of patients develop clinically overt hepatitis. Isoniazid is metabolized in man at extremely variable rates, and the rate is under genetic control. Two separate clinical studies have noted a possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug. For this reason, 21 patients who had recovered from probable isoniazid hepatitis and 5 patients who previously had manifested biochemical evidence of mild isoniazid liver injury were genetically phenotyped as rapid or slow isoniazid acetylators by the sulfamethazine method. The rapid phenotype was found in 86% of patients with probable hepatitis and in 60% of the possible ones, whereas the expected frequency was 45%. Eximination of isoniazid metabolites revealed that rapid acetylators hydrolze much more isoniazid to isonic otinic hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazed is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. We suggest that release of the hepatotoxic hydrazino moiety of isoniazid in man is responsible for isoniazid liver injury.


Multimodality correlations of patellar height measurement on X-ray, CT, and MRI.
To investigate whether the universally accepted range of normal patellar height ratios derived from radiography for the Insall-Salvati (IS) and Blackburne-Peel (BP) methods could be similarly applied to both CT and MRI. Institutional review board approval was obtained with waiver of informed consent for this HIPPA-compliant study. A total of 45 knees in 42 patients (15 men, 27 women; age range 11 to 75 years, mean age 39 ± 20 years) who underwent tri-modality (radiograph, CT, and MRI) examinations were selected. All patients had knee imaging obtained for a variety of reasons and measurements were performed by two independent readers who were blinded to each other's measurements or the respective measurements derived from each of the methods. Paired t test was used to compare the mean values among the modalities. Inter-observer and inter-method agreements were assessed using intra-class correlation coefficients. Statistically significant, but small quantitative differences are noted between tri-modality patellar height ratios. For comparable results, the small addition of 0.13 and 0.10 are needed for the Insall-Salvati measurements on MRI and CT respectively, compared with radiographs. For the Blackburne-Peel ratio, an additional adjustment of 0.09 is needed between radiographs and MRI, but not between radiographs and CT. These adjustments are independent of gender. The interobserver reproducibility was excellent (ICC ≥ 0.94) for both the Insall-Salvati and Blackburne-Peel methods for all modalities. The results indicate that cut-off values for patella alta and baja derived from radiographs should not be directly transposed to CT and MRI; however, the adjustments are relatively minor. These measurements show excellent reproducibility for all modalities currently used for patellar height measurements.


Transfusion-free management of gastrointestinal bleeding: the experience of a bloodless institute.
The Institute for Patient Blood Management and Bloodless Medicine at the Englewood Hospital has considerable experience in managing patients with gastrointestinal bleeding who do not accept blood-derived products. We present our data and experience over the last 8 years in managing such patients. There is paucity of data on management and outcomes of gastrointestinal bleeding in patients who do not accept blood-derived products. We performed a retrospective study of patients from 2003 to 2011 presenting with gastrointestinal bleeding who do not accept blood-derived products. Inclusion criteria were either overt bleeding with a presenting hemoglobin (Hb) of <12 g/dL or a decrease in Hb of >1.5 g/dL. Ninety-six patients who met the inclusion criteria were included. Forty-one upper and 48 lower gastrointestinal bleeding sources were identified. Mean Hb was 8.8 g/dL and mean nadir was 6.9 g/dL. Among 37 patients (80.5%) with Hb ≤6.0 g/dL, 30 (81%) survived. Four of 7 patients (57%) with a Hb <3 g/dL survived. The overall mortality rate was 10.4%. In unadjusted logistic regression models, age [1.06 (1.01-1.12 y)], admission to ICU [6.37(1.27-31.9)], and anticoagulation use [6.95 (1.57-30.6)] were associated with increased mortality. Initial Hb [0.68 (0.51-0.92)] and nadir Hb [0.48 (0.29-0.78)] inversely predicted mortality. These results suggest that transfusion-free management of gastrointestinal hemorrhage can be effective with mortality comparable with the general population accepting medically indicated transfusion. Management of these patients is challenging and requires a dedicated multidisciplinary team approach knowledgeable in techniques of blood conservation.


[Assessment of androgenic decline in the elderly].
The gold standard to assess androgenic status is the measurement of free testosterone by equilibrium dialysis. However, the estimation of free testosterone using formulas based on the law of mass action can be an adequate standard. To assess androgenic decline in the elderly by different methods. Free testosterone by radioimmunoassay, total testosterone and steroid binding globulin (SHBG) by automated chemiluminiscence system and estradiol by automated electrochemiluminiscence system were measured in 30 male aged 64+/-5 years (range 60-70), and 25 males aged between 20 and 30 years, as control group; devoid of diseases or drugs that could cause hypogonadism. Free androgen index, free testosterone, biavailable testosterone, and free estradiol were calculated using a formula based on the law of mass action. Fifty seven percent of elderly subjects had hypogonadism, according to calculated free testosterone values. Their total testosterone was on average, 152 nd/dl lower than in young adults, figure that represents a 3.8 ng/dl decline per year. According to total testosterone values, 27% of elderly males had gonadal incompetence. The correlations between calculated free testosterone and total testosterone was 0,95 and between calculated free testosterone and measured free testosterone was 0,67. The methods employed overestimated (76.7% of hypogonadism when using the free androgen index) or underestimated (27 and 3% of hypogonadism, considering total or free testosterone, respectively) the ondrogen decline of the elderly. Among the elderly, 16 or 30% of subjects had an absolute hypoestrogenism, based on estradiol or calculated free estradiol values, respectively. On average there was a 20 and 30% reduction of estradiol and calculated free estradiol values in the elderly. Calculated free or bioavailable testosterone values should be used to assess androgen decline in elderly men.


Retinotopic Changes in the Gray Matter Volume and Cerebral Blood Flow in the Primary Visual Cortex of Patients With Primary Open-Angle Glaucoma.
To assess the cortical structure and cerebral blood flow changes in the brain of patients with primary open-angle glaucoma (POAG). High-resolution anatomical magnetic resonance imaging (MRI) and arterial spin labeling (ASL)-MRI were performed in 23 POAG patients and 29 controls. Patients were further divided into early-moderate and advanced groups based on mean deviation (MD) cutoff of 12 dB. A baseline scan was obtained and repeated during visual stimulation to the central preserved visual field in the more affected eye of POAG patients and a randomly selected eye of controls. Gray matter volume (GMV) and cerebral blood flow (CBF) throughout the whole brain were compared between patients and controls. Compared to controls, a region with significant reduction of GMV was detected in the anterior calcarine fissure of advanced POAG patients (P < 0.001, voxels = 503, 1698 mm3). Patients with early-moderate POAG had resting CBF similar to that of controls. However, a region with marked CBF decrease was detected in the anterior calcarine fissure of advanced POAG patients (P < 0.001, voxels = 1687, 13,496 mm3). The region with CBF reduction in advanced POAG showed good colocalization with the region with GMV decrease in this group. Following visual stimulation, patients with advanced POAG showed significantly lower increase in CBF in the occipital lobes (P < 0.001, voxels = 112, 896 mm3) as compared to controls (P < 0.001, voxels = 1880, 15,040 mm3) and early-moderate POAG (P < 0.001, voxels = 2233, 17,864 mm3). Primary open-angle glaucoma patients demonstrate a disease severity-dependent retinotopic pattern of cortical atrophy and CBF abnormalities in the visual cortex. Cerebral blood flow may be a potential biomarker for the brain involvement in glaucoma.


Comparing polybrominated diphenyl ether and polychlorinated biphenyl bioaccumulation in a food web in Grand Traverse Bay, Lake Michigan.
Levels of polybrominated diphenyl ethers (BDEs) in Great Lakes salmonids and ambient air have been recently reported, but few studies worldwide have examined the accumulation of BDEs within aquatic food webs. Here we report some of the first measurements of six BDE congeners that are common components of the pentaBDE commercial mixture within an entire Lake Michigan food web. BDEs were detected in all samples and the dominant BDE congener was 2,2',4,4'-tetrabromodiphenyl ether (BDE 47). BDE 47 levels were consistently greater than those of the 2,2',4,4',5-pentabromodiphenyl ether (BDE 99), despite similar levels of these two compounds in commercial mixtures, suggesting differences in the bioavailability of the BDE congeners or differences in their ability to be metabolized. Additionally, congener composition was significantly different among deepwater sculpin, bloater chub, and lake trout, indicating differences in exposure or differences in biotransformation capacities. Total BDE concentrations in this food web were positively correlated (r = 0.94) with levels of PCBs previously measured in these samples (Stapleton et al. 2001a). Levels of BDE 47 and PCB 153, compounds with similar physicochemical properties, were compared to examine the relative exposure and bioaccumulation of these two classes of chemicals that have different environmental loading histories. Food web magnification factors calculated for these two congeners were 3.2 and 4.0 for BDE 47 and PCB 153, respectively, indicating a comparable potential for biomagnification in food webs.


The effect of diabetes on blood flow properties.
Blood flow is a complex process combining fluid shearing in both plasma and the interior of red blood cells with elastic deformation of blood's solid elements. The red cell membrane is the major solid in blood, but platelets and white cells contribute solid behavior as well. Changes in blood's flow properties are often hidden by blood's ability to change its pattern of response. Capillary viscometry can be used to examine serum, plasma, and hemoglobin solutions directly, but rotational viscometry, where regularity of fluid shearing can be controlled to a narrow shear rate range, is required to study blood flow effectively. The most striking diabetic blood flow abnormality is best seen in time-based rotational viscometer studies that demonstrate the pattern of development of shear stress as flow becomes established. In such studies blood demonstrates both viscoelastic and thixotropic behavior; in diabetes blood's thixotropy is substantially increased. The diabetic pattern appears to be produced by a combination of reduced erythrocyte deformability and increased erythrocyte aggregation due to plasma protein changes. The plasma protein changes observed in diabetes are linked to the development of glucose intolerance but they are not specific to diabetes. The combined increase in aggregation and resistance to deformation of red blood cells produces blood flow abnormalities that can be detected primarily at low shear rate. Plasma protein changes and alteration in blood viscosity are absent from children with diabetes, while such changes tend to be associated with diabetic microangiopathy in adults. In some in vivo conditions, the effects on blood flow that can be linked to erythrocyte deformability are magnified out of proportion to measurements made in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment Restrictions and the Risk of Death in Patients With Ischemic Stroke or Intracerebral Hemorrhage.
Do-not-resuscitate (DNR) orders in the first 24 hours after intracerebral hemorrhage have been associated with an increased risk of early death. This relationship is less certain for ischemic stroke. We assessed the relation between treatment restrictions and mortality in patients with ischemic stroke and in patients with intracerebral hemorrhage. We focused on the timing of treatment restrictions after admission and the type of treatment restriction (DNR order versus more restrictive care). We retrospectively assessed demographic and clinical data, timing and type of treatment restrictions, and vital status at 3 months for 622 consecutive stroke patients primarily admitted to a Dutch university hospital. We used a Cox regression model, with adjustment for age, sex, comorbidities, and stroke type and severity. Treatment restrictions were installed in 226 (36%) patients, more frequently after intracerebral hemorrhage (51%) than after ischemic stroke (32%). In 187 patients (83%), these were installed in the first 24 hours. Treatment restrictions installed within the first 24 hours after hospital admission and those installed later were independently associated with death at 90 days (adjusted hazard ratios, 5.41 [95% CI, 3.17-9.22] and 5.36 [95% CI, 2.20-13.05], respectively). Statistically significant associations were also found in patients with ischemic stroke and in patients with just an early DNR order. In those who died, the median time between a DNR order and death was 520 hours (interquartile range, 53-737). The strong relation between treatment restrictions (including DNR orders) and death and the long median time between a DNR order and death suggest that this relation may, in part, be causal, possibly due to an overall lack of aggressive care.


Reliability of self-reported breast screening information in a survey of lower income women.
Self-reported behavior is widely used to estimate the prevalence of breast cancer screening and to evaluate programs for promoting screening, but detailed studies of reliability have not previously been performed. Reliability was assessed by comparing responses to questions about screening behavior from repeat personal interviews of 382 women age 40 and older living in low-income census tracts of two Florida communities. Reliability was assessed using Pearson's correlation (r) and kappa (kappa) coefficients. Estimated reliabilities were kappa = 0.38 for "ever had clinical breast examination," kappa = 0.82 for "ever had mammogram," kappa = 0.65 for "mammogram in past year," r = 0.54 for "date of last mammogram," and r = 0.72 for "number of mammograms." The dates of last mammogram reported at the two interviews agreed within 1 month for 64% of the women, while the dates of last clinical breast examination agreed within 1 month for 50% of the women. Reliability of "ever had mammogram" was significantly related to demographic variables. Women reliably report ever having mammography, but information about timing and frequency has lower reliability. The results have implications for breast screening research because measurement error affects the precision of estimates and the sample sizes needed to detect program effects.


MutS deficiency and activity of the error-prone DNA polymerase IV are crucial for determining mucA as the main target for mucoid conversion in Pseudomonas aeruginosa.
Pseudomonas aeruginosa colonizes the respiratory tract of cystic fibrosis (CF) patients, where mutators along with mucoid variants emerge leading to chronic infection. Mucoid conversion generally involves mutations inactivating the mucA gene. This study correlates the frequency and nature of mucA mutations with the activity of factors determining the mutation rate, such as MutS and polymerase IV (Pol IV). Results show that: (i) the emergence frequency of mucoid variants was higher in isolates arising from mutS populations compared with the wild-type strain; (ii) in both strains mucoid conversion occurred mainly by mucA mutations; (iii) however, the mutator strain harboured mostly mucA22 (a common allele in CF isolates), while the wild type showed a wider spectrum of mucA mutations with low incidence of mucA22; (iv) disruption of dinB in the wild-type and mutS strains decreased drastically the emergence frequency of mucoid variants; (v) furthermore, the incidence of mucA mutations diminished in the mutS dinB double mutant strain which consisted only in mucA22; (vi) finally, the mucoid isolates obtained from the dinB strain showed an unexpected absence of mucA mutations. Taken together results demonstrate the implication of both MutS and Pol IV in determining mucA as the main target for conversion to mucoidy.


A novel approach to the 2-D blind deconvolution problem in medical ultrasound.
The finite frequency bandwidth of ultrasound transducers and the nonnegligible width of transmitted acoustic beams are the most significant factors that limit the resolution of medical ultrasound imaging. Consequently, in order to recover diagnostically important image details, obscured due to the resolution limitations, an image restoration procedure should be applied. The present study addresses the problem of ultrasound image restoration by means of the blind-deconvolution techniques. Given an acquired ultrasound image, algorithms of this kind perform either concurrent or successive estimation of the point-spread function (PSF) of the imaging system and the original image. In this paper, a blind-deconvolution algorithm is proposed, in which the PSF is recovered as a preliminary stage of the restoration problem. As the accuracy of this estimation affects all the following stages of the image restoration, it is considered as the most fundamental and important problem. The contribution of the present study is twofold. First, it introduces a novel approach to the problem of estimating the PSF, which is based on a generalization of several fundamental concepts of the homomorphic deconvolution. It is shown that a useful estimate of the spectrum of the PSF can be obtained by applying a proper smoothing operator to both log-magnitude and phase of the spectra of acquired radio-frequency (RF) images. It is demonstrated that the proposed approach performs considerably better than the existing homomorphic (cepstrum-based) deconvolution methods. Second, the study shows that given a reliable estimate of the PSF, it is possible to deconvolve it out of the RF-image and obtain an estimate of the true tissue reflectivity function, which is relatively independent of the properties of the imaging system. The deconvolution was performed using the maximum a-posteriori (MAP) estimation framework for a number of statistical priors assumed for the reflectivity function. It is shown in a series of in vivo experiments that reconstructions based on the priors, which tend to emphasize the "sparseness" of the tissue structure, result in solutions of higher resolution and contrast.


Plastic Bag Derived-Microplastics as a Vector for Metal Exposure in Terrestrial Invertebrates.
Microplastics are widespread contaminants in terrestrial environments but comparatively little is known about interactions between microplastics and common terrestrial contaminants such as zinc (Zn). In adsorption experiments fragmented HDPE bags c. one mm2 in size showed similar sorption characteristics to soil. However, when present in combination with soil, concentrations of adsorbed Zn on a per mass basis were over an order of magnitude lower on microplastics. Desorption of the Zn was minimal from both microplastics and soil in synthetic soil solution (0.01 M CaCl2), but in synthetic earthworm guts desorption was higher from microplastics (40-60%) than soil (2-15%), suggesting microplastics could increase Zn bioavailability. Individual Lumbricus terrestris earthworms exposed for 28 days in mesocosms of 260 g moist soil containing 0.35 wt % of Zn-bearing microplastic (236-4505 mg kg-1) ingested the microplastics, but there was no evidence of Zn accumulation, mortality, or weight change. Digestion of the earthworms showed that they did not retain microplastics in their gut. These findings indicate that microplastics could act as vectors to increase metal exposure in earthworms, but that the associated risk is unlikely to be significant for essential metals such as Zn that are well regulated by metabolic processes.


The experimental emergence of convention in a non-human primate.
Conventions form an essential part of human social and cultural behaviour and may also be important to other animal societies. Yet, despite the wealth of evidence that has accumulated for culture in non-human animals, we know surprisingly little about non-human conventions beyond a few rare examples. We follow the literature in behavioural ecology and evolution and define conventions as systematic behaviours that solve a coordination problem in which two or more individuals need to display complementary behaviour to obtain a mutually beneficial outcome. We start by discussing the literature on conventions in non-human primates from this perspective and conclude that all the ingredients for conventions to emerge are present and therefore that they ought to be more frequently observed. We then probe the emergence of conventions by using a unique novel experimental system in which pairs of Guinea baboons (Papio papio) can voluntarily participate together in touchscreen-based cognitive testing and we show that conventions readily emerge in our experimental set-up and that they share three fundamental properties of human conventions (arbitrariness, stability and efficiency). These results question the idea that observational learning, and imitation in particular, is necessary to establish conventions; they suggest that positive reinforcement is enough. This article is part of a discussion meeting issue 'The emergence of collective knowledge and cumulative culture in animals, humans and machines'.


Dropping out of Ethiopia's community-based health insurance scheme.
Low contract renewal rates have been identified as one of the challenges facing the development of community-based health insurance (CBHI) schemes. This article uses longitudinal household survey data gathered in 2012 and 2013 to examine dropout in the case of Ethiopia's pilot CBHI scheme. We treat dropout as a function of scheme affordability, health status, scheme understanding and quality of care. The scheme saw enrolment increase from 41% 1 year after inception to 48% a year later. An impressive 82% of those who enrolled in the first year renewed their subscriptions, while 25% who had not enrolled joined the scheme. The analysis shows that socioeconomic status, a greater understanding of health insurance and experience with and knowledge of the CBHI scheme are associated with lower dropout rates. While there are concerns about the quality of care and the treatment meted out to the insured by providers, the overall picture is that returns from the scheme are overwhelmingly positive. For the bulk of households, premiums do not seem to be onerous, basic understanding of health insurance is high and almost all those who are currently enrolled signalled their desire to renew contracts.


Epstein-Barr virus susceptibility of normal human B lymphocyte populations.
Human blood and tonsil B lymphocytes were fractionated on density gradients and tested for virus binding and penetration into the cells. Epstein-Barr Virus (EBV) transformation was detected by immunofluorescence staining for EBV-determined nuclear antigen (EBNA). EBV bound to and penetrated all B cell populations, but only the high density populations were transformed. Activated B lymphocytes were found in the low density fractions and these cells were resistant to EBV infection. Infected and noninfected B lymphocytes were density-analyzed during in vitro culture. A spontaneous, not virus-induced, density decrease was found to precede the production of EBNA. Cells remaining at high density never expressed EBNA. The results suggest that EBV can transform only small resting B lymphocytes and that a virus-independent activation of the infected cells induces the EBNA production and transformation.


Depression and sexual risk behavior among long-distance truck drivers at roadside wellness clinics in Kenya.
Truck drivers in sub-Saharan Africa are at high risk for both mental health disorders and sexually transmitted infections. We sought to determine the prevalence of depression among a sample of long-distance truck drivers seeking services at roadside wellness clinics in Kenya and explore the relationship between depression and sexual risk behavior. We used data from an interviewer-administered questionnaire from 284 truck drivers in Kenya who participated in a randomized controlled trial evaluating whether offering oral HIV self-testing could increase HIV test uptake. Depression was categorized based on the Patient Health Questionnaire-9 score, with a score ≥10 indicative of probable major depressive disorder (MDD). Sexual risk behavior was operationalized as the number of condomless sex partners in the past 6 months. The mean participant age was 36.9 years, 83.0% were married, and 37.0% had a secondary school education or higher. Overall, 24% of participants had probable MDD, and 58.2% reported having one condomless sex partner in the past 6 months, whereas 27.3% reported having had two or more. In a multivariable Poisson regression model adjusted for demographic and other relevant variables, including number of sex partners, MDD was significantly associated with a greater number of condomless sex partners (adjusted prevalence ratio 1.63, 95% confidence interval [1.25-2.12], p < 0.001). General self-efficacy significantly mediated the association between MDD and number of condomless sex partners. The high prevalence of depression highlights the need to test the feasibility and acceptability of mental healthcare interventions for this population, possibly integrated with HIV prevention services. Future research is needed to better understand the association between depression and sexual risk behavior, as well as the role of self-efficacy.


Heat shock protein 70 inhibits the activity of Influenza A virus ribonucleoprotein and blocks the replication of virus in vitro and in vivo.
Heat shock protein 70 (Hsp70) was identified as a cellular interaction partner of the influenza virus ribonucleoprotein (RNP) complex. The biological significance of the interaction between Hsp70 and RNP has not been fully investigated. Here we demonstrated that Hsp70 was involved in the regulation of influenza A viral transcription and replication. It was found that Hsp70 was associated with viral RNP by directly interacting with the PB1 and PB2 subunits, and the ATPase domain of Hsp70 was required for the association. Immunofluorescence analysis showed that Hsp70 was translocated from the cytoplasm into the nucleus in infected cells. Then we found that Hsp70 negatively regulated the expression of viral proteins in infected cells. Real-time PCR analysis revealed that the transcription and replication of all eight viral segments were significantly reduced in Hsp70 overexpressed cells and greatly increased as Hsp70 was knocked down by RNA interference. Luciferase assay showed that overexpression of Hsp70 could inhibit the viral RNP activity on both vRNA and cRNA promoters. Biochemical analysis demonstrated that Hsp70 interfered with the integrity of RNP. Furthermore, delivered Hsp70 could inhibit the replication of influenza A virus in mice. Our study indicated that Hsp70 interacted with PB1 and PB2 of RNP and could interfere with the integrity of RNP and block the virus replication in vitro and in vivo possibly through disrupting the binding of viral polymerase with viral RNA.


Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population.
Matrix metalloproteinases (MMPs) are enzymes that are integral in extracellular matrix (ECM) remodeling. In age or disease, ECM may become dysregulated and contribute to fibrosis, which impairs cardiac electrical conduction. Two alleles regulate matrix metalloproteinase-3 (MMP-3) activity: one with five adenosine bases (5A; associated with higher MMP-3 activity and decreased fibrosis) and another with six adenosine bases (6A; associated with lower MMP-3 activity and increased fibrosis). Here, we determined whether ECG-derived QTc and related parameters are associated with the MMP-3 5A/6A genotype in a cross-section of the Australian rural population. A retrospective cross-sectional population was obtained from the Charles Sturt University Diabetes Screening Research Initiative. Genotype and resting 12-lead ECG parameters of 295 participants were analyzed. Amongst these participants, 85 individuals carried the 5A/5A genotype, 141 individuals carried the 5A/6A genotype, and 65 individuals carried the 6A/6A genotype. Compared to 5A/5A genotype carriers, 5A/6A genotype carriers had a significantly longer QTc duration by 9.50 ms (95% CI: 3.48-15.52, p = 0.002), whilst 6A/6A genotype carriers had an even longer QTc duration by 12.19 ms (95% CI: 5.04-19.34, p = 0.001). We found an association between MMP-3 5A/6A polymorphisms and QTc, independent of adjustments for age, gender, alcohol consumption, smoking status, body mass index and blood pressure.


Late recurrences of gastrointestinal stromal tumours (GISTs) after 5 years of follow-up.
In practice, relapses of gastrointestinal stromal tumours after long time of surgical resection occur. However, few published data are available for duration, intensity and imaging sources of follow-up in radically excised patients with localized disease. Therefore, every single institution chooses the surveillance schedule according to its experience. The aim of this study was to describe the late recurrences of disease 5 years after the primary tumour's excision in a series of patients with recurrent GIST from our institution. We retrospectively reviewed 42 patients with "recurrent" GIST, collected since 2001. Ten patients were always followed at our institution, and 32 patients came to our attention at the time of recurrence. The analysed series were divided into two groups: patients who developed recurrence before 5 years and patients who developed recurrence 5 years after the primary tumour's excision. Among 42 patients, 36 patients developed the recurrence within 5 years of the primary tumour excision, whereas 6 patients developed the recurrence 5 years after primary tumour excision diagnosed during follow-up or casually for other reasons. All patients had distant recurrence, involving liver and peritoneum, whereas no local relapse was observed. These patients were heterogeneous in primary tumour site, risk classification and molecular analysis. Duration of the follow-up for radically excised patients with GIST remains still unsettled; however, the integration of every clinical, pathological and molecular parameter is essential to optimize the duration and intensity of the follow-up for each single patient.


Immobilization of an artificial imine reductase within silica nanoparticles improves its performance.
Silica nanoparticles equipped with an artificial imine reductase display remarkable activity towards cyclic imine- and NAD(+) reduction. The method, based on immobilization and protection of streptavidin on silica nanoparticles, shields the biotinylated metal cofactor against deactivation yielding over 46 000 turnovers in pure samples and 4000 turnovers in crude cellular extracts.


The carboxy termini of Sir4 and Rap1 affect Sir3 localization: evidence for a multicomponent complex required for yeast telomeric silencing.
The Silent Information Regulatory proteins, Sir3 and Sir4, and the telomeric repeat-binding protein RAP1 are required for the chromatin-mediated gene repression observed at yeast telomeric regions. All three proteins are localized by immunofluorescence staining to foci near the nuclear periphery suggesting a relationship between subnuclear localization and silencing. We present several lines of immunological and biochemical evidence that Sir3, Sir4, and RAP1 interact in intact yeast cells. First, immunolocalization of Sir3 to foci at the yeast nuclear periphery is lost in rap1 mutants carrying deletions for either the terminal 28 or 165 amino acids of RAP1. Second, the perinuclear localization of both Sir3 and RAP1 is disrupted by overproduction of the COOH terminus of Sir4. Third, overproduction of the Sir4 COOH terminus alters the solubility properties of both Sir3 and full-length Sir4. Finally, we demonstrate that RAP1 and Sir4 coprecipitate in immune complexes using either anti-RAP1 or anti-Sir4 antibodies. We propose that the integrity of a tertiary complex between Sir4, Sir3, and RAP1 is involved in both the maintenance of telomeric repression and the clustering of telomeres in foci near the nuclear periphery.


Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent.
Parathyroid carcinoma is one cause of primary hyperparathyroidism, a condition in which there is hypercalcemia and dysregulated hypersecretion of PTH. In normal, and in some neoplastic parathyroid cells, PTH secretion is mediated by the cell surface calcium-sensing receptor. We describe the first therapeutic use of a novel molecule, a calcimimetic, that has agonist action at the calcium-sensing receptor. A 78-yr-old man with parathyroid carcinoma was admitted with hypercalcemia, markedly elevated PTH, and a change in mental status. He was treated for 17 days with conventional therapy, which included saline hydration, furosemide, pamidronate, and calcitonin. This was ineffective, and on hospital day 18, calcimimetic at a dose of 50 mg, orally, every 6 h was added. On hospital day 25, the dose was increased to 100 mg, orally, every 6 h, and on hospital day 30, saline and furosemide were discontinued. He was discharged on hospital day 40. With several dose adjustments, he has been treated with monotherapy calcimimetic for over 600 days and has not required any other interventions for his parathyroid carcinoma. Mean daily precalcimimetic treatment values of serum ionized calcium and PTH were 1.83 mmol/L and 872 pg/mL, respectively. During hospitalization, at the lower dose of calcimimetic, calcium and PTH decreased to 1.67 mmol/L and 538 pg/mL; with the higher dose they further decreased to 1.51 mmol/L and 444 pg/mL. Since discharge, and despite increasing levels of PTH, serum calcium has remained high, but lower than the admission level and acutely responsive to changes in calcimimetic doses. This compound, a calcimimetic, the first of a new class of compounds with activity at the calcium-sensing receptor, has been used to treat a patient with parathyroid carcinoma. During 2 yr of treatment, no adverse clinical effects have been observed, and it appears to have been effective at controlling hypercalcemia.


Prenatal alcohol exposure and language delay in 2-year-old children: the importance of dose and timing on risk.
The aim of this study was to investigate the association of dose and timing of prenatal alcohol exposure with early language acquisition. We examined language delay in a randomly selected, population-based sample of Western Australian children born in 1995-1996 whose mothers had agreed to participate in a longitudinal study on health-related behaviors and who had completed the 2-year questionnaire (N = 1739). Information on alcohol consumption was collected at 3 months after birth for four periods; the three months pre-pregnancy and for each trimester separately. Prenatal alcohol exposure was grouped into none, low, moderate-heavy and binge (>5) based on the total quantity consumed per week, quantity consumed per occasion, and frequency of consumption. The communication scale from the Ages & Stages Questionnaire was used to evaluate language delay. Logistic regression analysis was used to generate odds ratios and 95% confidence intervals, adjusted for confounding factors. There was no association between low levels of alcohol consumption and language delay at any time period, although there was a nonsignificant 30% increase in risk when moderate-to-heavy levels of alcohol were consumed in the third trimester. Children exposed to a binge pattern of maternal alcohol consumption in the second trimester had nonsignificant, three-fold increased odds of language delay, with a similar estimate following third trimester alcohol exposure after controlling for covariates. This study did not detect an association between low levels of prenatal alcohol exposure and language delay when compared with women who abstained from alcohol during pregnancy. A nonsignificant threefold increase in the likelihood of language delay was seen in children whose mothers binged during late pregnancy. However, the small numbers of women with a binge-drinking pattern in late pregnancy limited the power of this study; studies analyzing larger numbers of children exposed to binge drinking in late pregnancy are needed.


Fragmentation of riverine systems: the genetic effects of dams on bull trout (Salvelinus confluentus) in the Clark Fork River system.
Migratory bull trout (Salvelinus confluentus) historically spawned in tributaries of the Clark Fork River, Montana and inhabited Lake Pend Oreille as subadult and adult fish. However, in 1952 Cabinet Gorge Dam was constructed without fish passage facilities disrupting the connectivity of this system. Since the construction of this dam, bull trout populations in upstream tributaries have been in decline. Each year adult bull trout return to the base of Cabinet Gorge Dam when most migratory bull trout begin their spawning migration. However, the origin of these fish is uncertain. We used eight microsatellite loci to compare bull trout collected at the base of Cabinet Gorge Dam to fish sampled from both above and further downstream from the dam. Our data indicate that Cabinet Gorge bull trout are most likely individuals that hatched in above-dam tributaries, reared in Lake Pend Oreille, and could not return to their natal tributaries to spawn. This suggests that the risk of outbreeding depression associated with passing adults over dams in the Clark Fork system is minimal compared to the potential genetic and demographic benefits to populations located above the dams.


Effects of whole body vibration on bone mineral density in postmenopausal women: a systematic review and meta-analysis.
This systematic review and meta-analysis of randomized controlled trials (RCTs) identified significant effects of whole body vibration (WBV) on bone mineral density (BMD) of the lumbar spine (in the sensitivity analysis and seven subgroup analyses), femoral neck (in one subgroup analysis), and trochanter (four subgroup analyses) in postmenopausal women, but not other measurements of BMD. Interventions using WBV training have been conducted in postmenopausal women, aimed at increasing BMD; however, the results are contradictory. Our objective is to conduct a systematic review and meta-analysis of RCTs examining WBV effect on BMD. RCTs were considered eligible, with follow-up ≥6 months, which verified the effects of WBV on the BMD of postmenopausal women. The calculations of the meta-analysis were performed through the weighted mean difference between the WBV and control groups, or the WBV and combined training, through the absolute change between pre- and post-intervention in the areal bone mineral density (aBMD) or trabecular volumetric bone mineral density (vBMDt). Fifteen RCTs were included in the meta-analysis. No differences were observed in the primary analysis. WBV was found to improve aBMD compared with the control group, after exclusion of studies with low quality methodological (lumbar spine), when excluding the studies which combined WBV with medication or combined training (lumbar spine), with the use of low frequency and high magnitude (lumbar spine and trochanter), high frequency and low magnitude (lumbar spine), high cumulative dose and low magnitude (lumbar spine), low cumulative dose and high magnitude (lumbar spine and trochanter), with semi-flexed knee (lumbar spine, femoral neck, and trochanter), and side-alternating type of vibration (lumbar spine and trochanter). Despite WBV presenting potential to act as a coadjuvant in the prevention or treatment of osteoporosis, especially for aBMD of the lumbar spine, the ideal intervention is not yet clear. Our subgroup analyses helped to demonstrate the various factors which appear to influence the effects of WBV on BMD, contributing to clinical practice and the definition of protocols for future interventions.


Choosing proper normalization is essential for discovery of sparse glycan biomarkers.
Rapid progress in high-throughput glycomics analysis enables the researchers to conduct large sample studies. Typically, the between-subject differences in total abundance of raw glycomics data are very large, and it is necessary to reduce the differences, making measurements comparable across samples. Essentially there are two ways to approach this issue: row-wise and column-wise normalization. In glycomics, the differences per subject are usually forced to be exactly zero, by scaling each sample having the sum of all glycan intensities equal to 100%. This total area (row-wise) normalization (TA) results in so-called compositional data, rendering many standard multivariate statistical methods inappropriate or inapplicable. Ignoring the compositional nature of the data, moreover, may lead to spurious results. Alternatively, a log-transformation to the raw data can be performed prior to column-wise normalization and implementing standard statistical tools. Until now, there is no clear consensus on the appropriate normalization method applied to glycomics data. Nor is systematic investigation of impact of TA on downstream analysis available to justify the choice of TA. Our motivation lies in efficient variable selection to identify glycan biomarkers with regard to accurate prediction as well as interpretability of the model chosen. Via extensive simulations we investigate how different normalization methods affect the performance of variable selection, and compare their performance. We also address the effect of various types of measurement error in glycans: additive, multiplicative and two-component error. We show that when sample-wise differences are not large row-wise normalization (like TA) can have deleterious effects on variable selection and prediction.


Use of longitudinal invaginating matrix sutures in microarterial sleeve anastomoses.
A different approach to end in end anastomosis was tested to minimise the undesirable traits of classic and sleeve (telescoping) methods. Our approach aimed to maintain full contact at the level of the anastomosis by using longitudinal matrix sutures as a new invaginating suture technique in microarterial sleeve anastomosis. Classic end-to-end anastomosis with seven to eight stitches, Lauritzen's end-in-end anastomosis with four stitches, and our modified end-in-end anastomosis with two horizontal matrix sutures were made in 10, 20, and 25 rat femoral arteries, respectively. Nine, 17, and 18, respectively were patent at early evaluation; and eight, 13, and 14 at the time of late evaluation. There was no significant difference in between the patency rates of the groups. Histopathological examination showed large strictures and the formation of intra-luminal organised thrombus with thin intramural fibrin precipitation in occluded specimens. The longitudinal matrix sutures in the sleeve anastomoses, which passed through all layers of the vascular wall, injured the intima (a vertical rupture) and constricted the lumen.


Space use of bumblebees (Bombus spp.) revealed by radio-tracking.
Accurate estimates of movement behavior and distances travelled by animals are difficult to obtain, especially for small-bodied insects where transmitter weights have prevented the use of radio-tracking. Here, we report the first successful use of micro radio telemetry to track flight distances and space use of bumblebees. Using ground surveys and Cessna overflights in a Central European rural landscape mosaic we obtained maximum flight distances of 2.5 km, 1.9 km and 1.3 km for Bombus terrestris (workers), Bombus ruderatus (worker), and Bombus hortorum (young queens), respectively. Bumblebee individuals used large areas (0.25-43.53 ha) within one or a few days. Habitat analyses of one B. hortorum queen at the landscape scale indicated that gardens within villages were used more often than expected from habitat availability. Detailed movement trajectories of this individual revealed that prominent landscape structures (e.g. trees) and flower patches were repeatedly visited. However, we also observed long (i.e. >45 min) resting periods between flights (B. hortorum) and differences in flower-handling between bumblebees with and without transmitters (B. terrestris) suggesting that the current weight of transmitters (200 mg) may still impose significant energetic costs on the insects. Spatio-temporal movements of bumblebees can now be tracked with telemetry methods. Our measured flight distances exceed many previous estimates of bumblebee foraging ranges and suggest that travelling long distances to food resources may be common. However, even the smallest currently available transmitters still appear to compromise flower handling performance and cause an increase in resting behavior of bees. Future reductions of transmitter mass and size could open up new avenues for quantifying landscape-scale space use of insect pollinators and could provide novel insights into the behavior and requirements of bumblebees during critical life stages, e.g. when searching for mates, nest locations or hibernation sites.


lines and bowl affect the specification of cyst stem cells and niche cells in the Drosophila testis.
To function properly, tissue-specific stem cells must reside in a niche. The Drosophila testis niche is one of few niches studied in vivo. Here, a single niche, comprising ten hub cells, maintains both germline stem cells (GSC) and somatic stem cells (CySC). Here, we show that lines is an essential CySC factor. Surprisingly, lines-depleted CySCs adopted several characteristics of hub cells, including the recruitment of new CySCs. This led us to examine the developmental relationship between CySCs and hub cells. In contrast to a previous report, we did not observe significant conversion of steady-state CySC progeny to hub fate. However, we found that these two cell types derive from a common precursor pool during gonadogenesis. Furthermore, lines mutant embryos exhibited gonads containing excess hub cells, indicating that lines represses hub cell fate during gonadogenesis. In many tissues, lines acts antagonistically to bowl, and we found that this is true for hub specification, establishing bowl as a positively acting factor in the development of the testis niche.


Peppermint Oil: Evaluating Efficacy on Nausea in Patients Receiving Chemotherapy in the Ambulatory Setting.
Nausea is one of the most commonly reported side effects in patients receiving chemotherapy. Patients who experience nausea during chemotherapy may also experience depression, metabolic imbalances, dehydration, decreased ability to function, and treatment delays, which can ultimately affect outcomes. This study aimed to determine the efficacy of a cool damp washcloth with peppermint essential oil versus a cool damp washcloth alone on the self-reported intensity of nausea in patients receiving chemotherapy in the outpatient ambulatory setting. 79 adult patients receiving chemotherapy were recruited from an outpatient ambulatory infusion center in the southeastern United States. Patients were separated into two groups (no scent and peppermint) and asked to rate the intensity of their chemotherapy-induced nausea at pre- and postintervention using the Baxter Retching Faces pictorial scale. The results demonstrated that the use of peppermint oil was effective in decreasing the intensity of nausea experienced by patients compared to a cool washcloth alone.


Tracking scientific interest in the dissociative disorders: a study of scientific publication output 1984-2003.
We attempted to track scientific interest in dissociative amnesia and dissociative identity disorder by estimating the annual output of publications regarding these entities over the last 20 years. Using a standard medical index, PsycINFO, we counted the number of indexed publications involving dissociative amnesia and dissociative identity disorder listed for each year. We then compared these rates with those of well-established diagnoses such as anorexia nervosa, alcohol abuse, and schizophrenia. We also systematically reviewed all publications involving dissociative amnesia that appeared in 2003. Annual publications involving dissociative amnesia and dissociative identity disorder rose from low levels in the 1980's to a sharp peak in the mid 1990's, followed by an equally sharp decline to only about one quarter of their peak levels by 2002 and 2003. In contrast, all of the 25 comparison diagnoses in our survey showed constant or steadily rising publication rates; none showed the 'bubble' pattern of the dissociative disorders. Of the 34 papers involving dissociative amnesia identified by PsycINFO for 2003, 10 (32%) appeared skeptical of the validity of dissociative amnesia and/or recovered-memory therapy. Despite a detailed search using multiple medical indices and search terms, we could find only 13 explicit cases of individuals with dissociative amnesia worldwide in the 2003 literature. Dissociative amnesia and dissociative identity disorder have not generated consistent scientific interest over the years, but instead apparently enjoyed a brief period of fashion that now has waned. Overall, our observations suggest that these diagnostic entities presently do not command widespread scientific acceptance.


VEMPs and dynamic posturography after intratympanic gentamycin in Menière's disease.
In this study, we investigated whether vestibular evoked myogenic potentials (VEMPs) and dynamic posturography (DP) are useful in the evaluation of the vestibular function in patients affected by active monoaural Menière's disease (MD) treated with intratympanic gentamycin. Twelve subjects affected by monoaural MD were treated with weekly intratympanic injections of 0.5 ml of gentamycin at a concentration of 20 mg/ml. VEMPs were used to test saccular function, while postural control was analyzed by DP. The results obtained with these two techniques were compared with those obtained by using bithermal caloric test. The mean follow-up was 15.3 months (6--28 months). Therapy resulted in complete absence of the caloric response in six subjects (50) and in caloric test-induced asymmetry in the remaining individuals, ranging from 83 to 27. At follow-up, eleven patients (91.6%) were free of vertigo, while one patient had two vertigo spells 9 months after treatment. Before treatment, VEMPs were present in the affected ear of eleven patients. After treatment VEMPs were absent in all the patients. At the end of follow-up, reappearance of VEMPs was observed in two patients, with no changes in latency values and amplitude ratio. DP demonstrated a reduction of the Composite Score (CS) one week after therapy, with a prevalent reduction of the vestibular component. After 6 months, there was an improvement of the CS and, in particular, of the vestibular component. The present study demonstrates that bithermal caloric test and VEMPs allow for the functional evaluation of both the horizontal semicircular canal and the sacculus, suggesting that these techniques might be used together to monitor the efficacy of intratympanic gentamycin therapy. In addition, our data indicate that DP might provide important information on compensation phenomena and show that intratympanic gentamycin can improve postural control in MD patients.


Kava: an overview.
Since the first significant contact with Europeans in the 18th century, the Oceanic plant, Piper methysticum Forst. (Piperaceae) and the beverage prepared from it, both of which are called kava, have become familiar to much of the outside world through both the written and visual media. The ceremonial preparation and consumption of the beverage are probably its most conspicuous and spectacular features. Kava continues to occupy a central place in everyday life in the islands concerned, although its role has been somewhat diminished by time and outside influences. Despite the large body of literature on kava--about 800 entries are listed in a recent bibliography by Singh (1986)--there has been no comprehensive review on the subject. Earlier contributions by Keller and Klohs (1963) and Shulgin (1973) were selective in treatment and dealt primarily with chemical and pharmacological aspects. The monograph by Steinmetz (1960) remains a standard reference but understandably some of the information in it has become dated. The attention of the reader is also drawn to two excellent additions to the recent kava literature, by Lebot and Cabalion (1988) and Brunton (1989), which are, although somewhat restricted in focus, are very significant contributions to the subject. The present review paper provides an updated and a multidisciplinary overview of the subject. It was prepared on the basis of the author's personal experience--he is a native of Fiji and lived in that country for about 30 years--as well as the relevant literature listed in the Singh (1986) bibliography and some more recent publications.


Human keratinocytes migrate to the negative pole in direct current electric fields comparable to those measured in mammalian wounds.
Previous measurements of the lateral electric fields near skin wounds in guinea pigs have detected DC fields between 100-200 mV/mm near the edge of the wound. We have studied the translocation response of motile primary human keratinocytes migrating on a collagen substrate while exposed to similar physiological DC electric fields. We find that keratinocytes migrate randomly on collagen in fields of 5 mV/mm or less, but in larger fields they migrate towards the negative pole of the field, exhibiting galvanotaxis. Since these cells have an average cell length of 50 microns, this implies that they are able to detect a voltage gradient as low as 0.5 mV along their length. This cath-odally-directed movement exhibits increased directedness with increasing field strengths between 10 and 100 mV/mm. We observe a maximally directed response at 100 mV/mm with half of the cells responding to the field within 14 minutes. The average speed of migration tended to be greater in fields above 50 mV/mm than in smaller fields. We conclude that human keratinocytes migrate towards the negative pole in DC electric fields that are of the same magnitude as measured in vivo near wounds in mammalian skin.


Transfection with thymidine kinase permits bromodeoxyuridine labelling of DNA replication in the human malaria parasite Plasmodium falciparum.
Plasmodium falciparum, the causative agent of severe human malaria, is an early-diverging protozoan whose lifecycle has many unusual features, including its modes of replication. Research on the Plasmodium cell cycle, which occurs primarily via schizogony instead of canonical binary fission, has been hampered by a lack of tools and markers that can be transferred from cell cycle studies in model organisms. A common tool used to study DNA replication and the cell cycle in human cells is the labelling of newly-replicated DNA with the modified nucleotide bromodeoxyuridine (BrdU), followed by immunofluorescent detection. Plasmodium parasites, however, do not incorporate BrdU because they rely only on de novo synthesis of pyrimidines and do not salvage thymidine analogues like BrdU for conversion into nucleotides. Analysis of biochemical pathways in Plasmodium indicated that the absence of the enzyme thymidine kinase (TK) may be the only impediment to BrdU incorporation in this organism. A TK gene from Herpes simplex was, therefore, introduced into the Plasmodium falciparum 3D7 strain and the effect on BrdU labelling was assessed by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Introduction of a TK gene produces parasites that can indeed incorporate BrdU. This forms a sensitive indicator of DNA replication, which can be detected by both quantitative and qualitative assays on either a population level or a single-cell level. Plasmodium falciparum, when expressing TK, becomes unusually sensitive to BrdU toxicity. BrdU labelling represents a significant new tool for investigating DNA replication and the cell cycle in Plasmodium.


[The student diagnostic vignette. Electrocardiographical criteria for the diagnosis of ventricular tachycardia].
Recording of a regular wide QRS tachycardia is often source of panic and anxiety for the young clinician who has to make the differential diagnosis between ventricular tachycardia and supraventricular tachycardia with aberration associated with fundamentally different vital prognosis. Most of the time, a rigorous approach and a systematic analysis of the electrocardiogram associated with clinical examination allow to obtain the correct diagnosis.


Red cell transfusion practices and the impact of phlebotomy in an adult intensive care unit in Trinidad--a prospective observational study.
To determine the pattern of current red cell transfusion practices in an adult intensive care unit (ICU) in Trinidad and the impact of phlebotomy on transfusions. A prospective observational study was conducted over a six-month period to include all patients who received transfusions in the ICU of Port-of-Spain General Hospital, Trinidad. Demographic data including age, gender and weight were recorded. Clinical data recorded were the admission APACHE II scores, daily phlebotomy volumes, haemoglobin levels, transfusions and outcome during the first thirty days following ICU admission. Patients were grouped according to diagnoses and transfusion patterns. Of 134 patients admitted, 40 (29.8%) were transfused packed red cells 18 (29%) of the requests were for single unit transfusion. The mean phlebotomy volume was 13.5 +/- 4.3 (SD) mL day. The adjusted phlebotomy volume to body weight did not correlate with the amount of transfusions. The mean haemoglobin level for triggering blood transfusion was 6.73 g dL. The mean transfusion rate was 2.9 +/- 1.8 (SD) units per patient. Ten per cent of the patients received more than 5 units. Twenty nine per cent of the units were transfused on the first day of ICU admission and 69% were transfused during the first week of LCU stay. Transfusion practices in the study ICU pointed towards a restrictive strategy, although there were some inappropriate transfusions. The phlebotomy volumes did not contribute towards transfusion requirements.


Surgical treatment of epulides in dogs: 25 cases (1974-1984).
Epulides were diagnosed and surgically removed in 25 dogs. Histologic examination of the epulides indicated that 40% (10/25) were acanthomatous, 32% (8/25) were ossifying, and 28% (7/25) were fibromatous. Recurrence of the tumor directly resulted in the death of 2 dogs. One of these dogs died of malnutrition 13 months after removal of an ossifying epulis, and regrowth of an acanthomatous epulis that was not resected completely resulted in malnutrition and death in another dog 6 months after surgery. Malignant transformation was observed in a third dog 6 months after removal of an ossifying epulis when an osteosarcoma developed where the epulis had been removed. The range of survival was 6 to 134 months, mean survival time was 43.1 months, median survival time was 49 months, and 1-year survival rate was 92%. Satisfactory long-term tumor control was achieved by aggressive surgical treatment of epulides.


Effect of molecular therapeutics on liver regeneration in a murine model.
Unresectable metastatic colorectal cancer (CRC) can be rendered resectable with systemic chemotherapy in approximately 20% of cases. Most patients with metastatic CRC receive chemotherapy with the addition of targeted therapy with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) antibodies. We sought to determine whether anti-VEGF receptor (VEGFR) or anti-EGFR therapy would impair liver regeneration after partial hepatectomy (PH) in mice. Mice underwent either 66% PH or sham laparotomy. In the first experiment, mice in the PH group were randomly assigned to receive daily intraperitoneal injections of monoclonal antibodies (MoABs) to murine VEGFR-2 or nonspecific MoABs (control). In the second experiment, mice in the PH group were randomly assigned to receive intraperitoneal injections of antimurine EGFR or nonspecific (control) MoABs. In both experiments, therapy was initiated the day before surgery and continued until the mice were killed on day 5. Livers were collected and processed. Anti-VEGFR-2 therapy slightly impaired liver regeneration and hepatic cell proliferation compared with control. Hematoxylin and eosin staining showed no differences in liver morphology. CD105 staining showed decreased levels of activated endothelium in livers in the VEGFR-2 MoAB group. VEGFR-2 MoAB therapy decreased the levels of the cell cycle regulators cyclin D1 and cyclin D3 and the regenerative cytokine interleukin-6. Anti-EGFR therapy had no effect on liver regeneration or cellular proliferation. Anti-VEGFR-2 therapy slightly impaired liver regeneration in this murine model, whereas anti-EGFR therapy had no effect on liver regeneration.


The impact of COVID-19 on Children's Social Care in England.
As a response to COVID-19 the population of England was asked to stay at home and work from there wherever possible. This included those working in children's social care (CSC) who have responsibility for child protection and other safeguarding duties. The study was designed to understand how CSC made the transition from being an office-based agency to one where the majority of social workers were based at home and to understand how CSC perceived the impact on children and their families. Participants and setting Senior members of CSC staff in 15 local authorities took part in the research in June 2020. Nine interviews were conducted by video call, three by telephone, and three consisted of initial written responses that were then followed by telephone calls. Service delivery had been maintained across all the authorities with most visits being made virtually after assessments of risk had been conducted on all cases. Multiagency working had improved, with greater involvement of general practitioners and paediatricians. Overall activity in CSC had been lower than normal but as lockdown eased this was changing. Concerns were expressed about how to manage the response that would be required to meet the expected level of harm that had occurred but been hidden. Responses to COVID-19 prompted widespread innovation and it will be an imperative to evaluate which initiatives have worked for children and families, as well as practitioners, and which should be discarded, sustained or reshaped.


Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer?
Prostate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. It emerges through the acquisition of genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications and microRNA deregulation. These generate heritable transformations in the expression of genes but do not change the DNA sequence. Alterations in DNA methylation (hypo and hypermethylation) are the most characterized in PCa. They lead to genomic instability and inadequate gene expression. Major and minor-specific modifications in chromatin recasting are involved in PCa, with signs suggesting a dysfunction of enzymes modified by histones. MicroRNA deregulation also contributes to the initiation of PCa, including involvement in androgen receptor signalization and apoptosis. The influence of inflammation on prostate tumor carcinogenesis is currently much better known. Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation, promoting prostate inflammatory atrophy and eventually leading to PCa. Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa. The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis, treatment decisions, evaluation of prognosis and posttreatment surveillance.


Orientation-selective inhibition and binocular rivalry.
It is hypothesized that a negative correlation exists between the readiness with which two visual stimuli display rivalry and the magnitude of the inhibition effects between the corresponding neural channels. With binocular rivalry being more readily observed than monocular rivalry, it is predicted that lateral inhibition between neural channels selectively sensitive to such fundamental parameters as orientation, is primarily confined to those monocularly driven channels deriving their sensory input from the same eye. In confirmation, it is shown that the visual tilt illusion, thought to reflect lateral inhibition between orientation-sensitive channels, is very much reduced under dichoptic viewing conditions. Moreover, it is shown that those subjects displaying the greatest interocular transfer of the illusion least readily experience binocular rivalry.


Ptolemaic political activities on the west coast of Hellenistic Asia Minor had a significant impact on the local spread of the Isiac cults: A spatial network analysis.
During the reign of the first Ptolemaic kings in Egypt, mainly in the 3rd and 2nd centuries BCE, the Egyptian cults related to the divine couple of Isis and Sarapis (i.e. the Isiac cults) spread successfully from Egypt to ports and coastal cities of the ancient Mediterranean. The discussion on the topic of the factors involved in the process of the early spread of these cults outside Egypt is still open and, so far, the research in this area has been conducted mainly by using established historiographical methods. However, these methods are limited when dealing with the interplay among different variables involved in complex historical processes. This article aims to overcome these limits by using a quantitative spatial network analysis. The results of our previous published research, which focused on a quantitative evaluation of the impact of individual factors on the early spread of the Isiac cults across the ancient Aegean Islands, suggest that the process was promoted by military and commercial activities of the Ptolemaic dynasty, and that the Ptolemaic military operations were the most influential factor. Following these results, this article focuses on the early spread of the Isiac cults on the west coast of Hellenistic Asia Minor, i.e. the region which the Ptolemies attempted to control in the 3rd and 2nd centuries BCE. The statistically significant results presented in this article support the hypothesis that the Ptolemaic political engagement in Asia Minor had a positive impact on the early spread of the Isiac cults. The results also suggest that the activities of the Seleucid dynasty, a political rival of the Ptolemies, in the area of interest could have constituted an immunological factor limiting the spread of the Isiac cults further to the eastern parts of Asia Minor.


Optical twists in phase and amplitude.
Light beams with helical phase profile correspond to photons having orbital angular momentum (OAM). A Laguerre-Gaussian (LG) beam is an example where its helical phase sets a phase-singularity at the optical axis and forms a ring-shaped transverse amplitude profile. Here, we describe a unique beam where both phase and amplitude express a helical profile as the beam propagates in free space. Such a beam can be accurately referred to as an optical twister. We characterize optical twisters and demonstrate their capacity to induce spiral motion on particles trapped along the twisters' path. Unlike LG beams, the far field projection of the twisted optical beam maintains a high photon concentration even at higher values of topological charge. Optical twisters have therefore profound applications to fundamental studies of light and atoms such as in quantum entanglement of the OAM, toroidal traps for cold atoms and for optical manipulation of microscopic particles.


Nonsurgical retrieval of embolized coronary stents.
Embolization of coronary stents before deployment is a rare but challenging complication of coronary stenting. Different methods for nonsurgical stent retrieval have been suggested. There were 20 cases (0.90%) of intracoronary stent embolization among 2,211 patients who underwent implantation of 4,066 stents. Twelve of 1,147 manually crimped stents (1.04%) and eight of 2,919 premounted stents were lost (0.27%, P < 0.01) during retraction of the delivery system, because the target lesion could not be either reached or crossed. Percutaneous retrieval was successfully carried out in 10 of 14 patients (71%) in whom retrieval was attempted. In 10 patients, stent retrieval was tried with 1.5-mm low-profile angioplasty balloon catheters (success in 7/10) and in seven cases with myocardial biopsy forceps or a gooseneck snare (success in 3/7). Three patients (15%) underwent urgent coronary artery bypass surgery after failed percutaneous retrieval, but their outcomes were fatal. In two patients, stents were compressed against the vessel wall by another stent, without compromising coronary blood flow. In two patients, a stent was lost to the periphery without clinical side effects; treatment was conservative in these cases. Embolization of stents before deployment is a rare but serious complication of coronary stenting, with hazardous potential for the patient. Manual mounting of stents is associated with a significantly higher risk of stent embolization. Stent retrieval from the coronary circulation with low-profile angioplasty balloon catheters is a readily available and technically familiar approach that has a relatively high success rate.


The renal nerves in chronic heart failure: efferent and afferent mechanisms.
The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF.


Longer term quality of life and outcome in stroke patients: is the Barthel index alone an adequate measure of outcome?
To consider whether the Barthel Index alone provides sufficient information about the long term outcome of stroke. Cross sectional follow up study with a structured interview questionnaire and measures of impairment, disability, handicap, and general health. The scales used were the hospital anxiety and depression scale, mini mental state examination, Barthel index, modified Rankin scale, London handicap scale, Frenchay activities index, SF36, Nottingham health profile, life satisfaction index, and the caregiver strain index. South east London. People, and their identified carers, resident in south east London in 1989-90 when they had their first in a life-time stroke aged under 75 years. Observational study. Comparison and correlation of the individual Barthel index scores with the scores on other outcome measures. One hundred and twenty three (42%) people were known to be alive, of whom 106 (86%) were interviewed. The median age was 71 years (range 34-79). The mean interval between the stroke and follow up was 4.9 years. The rank correlation coefficients between the Barthel and the different dimensions of the SF36 ranged from r = 0.217 (with the role emotional dimension) to r = 0.810 (with the physical functioning dimension); with the Nottingham health profile the range was r = -0.189 (with the sleep dimension, NS) to r = -0.840 (with the physical mobility dimension); with the hospital and anxiety scale depression component the coefficient was r = -0.563, with the life satisfaction index r = 0.361, with the London handicap scale r = 0.726 and with the Frenchay activities index r = 0.826. The place of the Barthel index as the standard outcome measure for populations of stroke patients is still justified for long term follow up, and may be a proxy for different outcome measures intended for the assessment of other domains.


Regulatory B cells are induced by gut microbiota-driven interleukin-1β and interleukin-6 production.
Regulatory B cells (Breg cells) differentiate in response to inflammation and subsequently restrain excessive immune responses via the release of interleukin-10 (IL-10). However, the precise inflammatory signals governing their differentiation remain to be elucidated. Here we show that the gut microbiota promotes the differentiation of Breg cells in the spleen as well as in the mesenteric lymph nodes. Perturbation of the gut microbiome imposed either by antibiotic treatment or by changes in the sterility of housing conditions reduces the number and function of Breg cells. Following the induction of arthritis, IL-1β and IL-6 are produced only in conventionally housed mice and both cytokines directly promote Breg cell differentiation and IL-10 production. Mice lacking IL-6 receptor (IL-6R) or IL-1 receptor 1 (IL-1R1) specifically on B cells have a reduced number of IL-10-producing B cells and develop exacerbated arthritis compared to control animals. Thus, in response to inflammatory signals induced by both the gut flora and arthritis, Breg cells increase in number and restrain excessive inflammation.


Overcoming perceptual features in logical reasoning: a parametric functional magnetic resonance imaging study.
Participants experience difficulty detecting that an item depicting an H-in-a-square confirms the logical rule, "If there is not a T then there is not a circle." Indeed, there is a perceptual conflict between the items mentioned in the rule (T and circle) and in the test item (H and square). Much evidence supports the claim that correct responding depends on detecting and resolving such conflicts. One aim of this study is to find more precise neurological evidence in support of this claim by using a parametric event-related functional magnetic resonance imaging (fMRI) paradigm. We scanned 20 participants while they were required to judge whether or not a conditional rule was verified (or falsified) by a corresponding target item. We found that the right middorsolateral prefrontal cortex (mid-DLPFC) was specifically engaged, together with the medial frontal (anterior cingulate and presupplementary motor area [pre-SMA]) and parietal cortices, when mismatching was present. Activity in these regions was also linearly correlated with the level of mismatch between the rule and the test item. Furthermore, a psychophysiological interaction analysis revealed that activation of the mid-DLPFC, which increases as mismatching does, was accompanied by a decrease in functional integration with the bilateral primary visual cortex and an increase in functional integration with the right parietal cortex. This indicates a need to break away from perceptual cues in order to select an appropriate logical response. These findings strongly indicate that the regions involved in inhibitory control (including the right mid-DLPFC and the medial frontal cortex) are engaged when participants have to overcome perceptual mismatches in order to provide a logical response. These findings are also consistent with neuroimaging studies investigating the belief bias, where prior beliefs similarly interfere with logical reasoning.


Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection.
In 2015, a twenty-fold increase in the prevalence of microcephaly in Brazil was reported, and the Ministry of Health associated this abnormal prevalence with the maternal-fetal Zika virus (ZIKV) transmission. We assessed the ophthalmological findings of ten mothers and their infants that had been clinically diagnosed with ZIKV-related microcephaly and presented ocular abnormalities, born from May to December 2015. Seven mothers (70.0%) referred symptoms during pregnancy (malaise, rash and arthralgia), of which six (85.7%) were in the first trimester. At the time of exam, no ophthalmological abnormalities were identified in the mothers and they did not report ocular symptoms during pregnancy. Serology was negative in all infants for Toxoplasmosis, Rubella, Cytomegalovirus, Syphilis and Human Immunodeficiency Viruses. Ocular findings included macular alterations (gross pigment mottling and/or chorioretinal atrophy) in fifteen eyes (75.0%), and optic nerve abnormalities (hypoplasia with double-ring sign, pallor, and/or increased cup-to-disk ratio) in nine eyes (45.0%). Patients presented normal anterior segment and important macular and optic nerve abnormalities. Further studies will assess the visual significance of these alterations.


Leishmania major: differential resistance to infection in C57BL/6 (high interferon-alpha/beta) and congenic B6.C-H-28c (low interferon-alpha/beta) mice.
In murine cutaneous leishmaniasis caused by Leishmania major (Lm), resistance often associates with the outgrowth of Lm-specific Th1 cells. Parasites are eliminated by Th1-mediated activation of infected macrophages (M phi) which destroy Lm by producing toxic nitrogen and oxygen radicals. The cytokine IFN-alpha activates microbicidal functions of M phis and facilitates outgrowth of Th1 cells. Therefore, we compared the course of infection with Lm in resistant C57BL/6 mice, bearing the If-1h high expression allele for IFN-alpha/beta, with the congenic B6.C-H-28c mouse, bearing the If-1I low expression allele from the Lm-susceptible BALB/c strain. We observed that B6.C-H-28c animals developed up to 70% larger footpad lesions and harbored up to 1000-fold more parasites than C57BL/6 mice. Furthermore, peak Lm-specific IFN-gamma production in the B6.C-H-28c animals was lower and delayed by approximately 2 weeks, whereas IL-4 production was higher and persisted approximately 2 weeks longer. Since these results suggested that IFN-alpha/beta plays a protective role in mice infected with Lm, we determined whether infusing B6.C-H-28c mice with IFN-alpha would influence the course of infection with Lm. Unfortunately, the mice developed severe peritoneal hemorrhaging in response to injection with IFN-alpha. Therefore, we examined the ability of IFN-alpha to activate M phis to destroy Lm in vitro. We observed that rIFN-alpha could synergize with subactivating doses of LPS to activate both C57BL/6 and BALB/c peritoneal M phis to produce NO and to kill intracellular Lm. Taken as a whole, these results suggest that type I interferons may play a protective role in cutaneous leishmaniasis.


Sound reduction management in the neonatal intensive care unit for preterm or very low birth weight infants.
Infants in the neonatal intensive care unit (NICU) are subjected to stress, including sound of high intensity. The sound environment in the NICU is louder than most home or office environments and contains disturbing noises of short duration and at irregular intervals. There are competing auditory signals that frequently challenge preterm infants, staff and parents. The sound levels in NICUs often exceed the maximum acceptable level of 45 decibels (dB), recommended by the American Academy of Pediatrics. Hearing impairment is diagnosed in 2% to 10% of preterm infants versus 0.1% of the general paediatric population. Noise may cause apnoea, hypoxaemia, alternation in oxygen saturation, and increased oxygen consumption secondary to elevated heart and respiratory rates and may, therefore, decrease the amount of calories available for growth. Elevated levels of speech are needed to overcome the noisy environment in the NICU, thereby increasing the negative impacts on staff, newborns, and their families. High noise levels are associated with an increased rate of errors and accidents, leading to decreased performance among staff. The aim of interventions included in this review is to reduce sound levels to 45 dB or less. This can be achieved by lowering the sound levels in an entire unit, treating the infant in a section of a NICU, in a 'private' room, or in incubators in which the sound levels are controlled, or reducing the sound levels that reaches the individual infant by using earmuffs or earplugs. By lowering the sound levels that reach the neonate, the resulting stress on the cardiovascular, respiratory, neurological, and endocrine systems can be diminished, thereby promoting growth and reducing adverse neonatal outcomes. Primary objective To determine the effects of sound reduction on growth and long-term neurodevelopmental outcomes of neonates. Secondary objectives 1. To evaluate the effects of sound reduction on short-term medical outcomes (bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity). 2. To evaluate the effects of sound reduction on sleep patterns at three months of age. 3. To evaluate the effects of sound reduction on staff performance. 4. To evaluate the effects of sound reduction in the neonatal intensive care unit (NICU) on parents' satisfaction with the care. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings, clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp), Pediatric Academic Societies Annual meetings 2000 to 2014 (Abstracts2ViewTM), reference lists of identified trials, and reviews to November 2014. Preterm infants (< 32 weeks' postmenstrual age (PMA) or < 1500 g birth weight) cared for in the resuscitation area, during transport, or once admitted to a NICU or a stepdown unit. We performed data collection and analyses according to the Cochrane Neonatal Review Group. One small, high quality study assessing the effects of silicone earplugs versus no earplugs qualified for inclusion. The original inclusion criteria in our protocol stipulated an age of < 48 hours at the time of initiating sound reduction. We made a deviation from our protocol and included this study in which some infants would have been > 48 hours old. There was no significant difference in weight at 34 weeks postmenstrual age (PMA): mean difference (MD) 111 g (95% confidence interval (CI) -151 to 374 g) (n = 23). There was no significant difference in weight at 18 to 22 months corrected age between the groups: MD 0.31 kg, 95% CI -1.53 to 2.16 kg (n = 14). There was a significant difference in Mental Developmental Index (Bayley II) favouring the silicone earplugs group at 18 to 22 months corrected age: MD 14.00, 95% CI 3.13 to 24.87 (n = 12), but not for Psychomotor Development Index (Bayley II) at 18 to 22 months corrected age: MD -2.16, 95% CI -18.44 to 14.12 (n =12). To date, only 34 infants have been enrolled in a randomised controlled trial (RCT) testing the effectiveness of reducing sound levels that reach the infants' ears in the NICU. Based on the small sample size of this single trial, we cannot make any recommendations for clinical practice. Larger, well designed, conducted and reported trials are needed.


Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies.
For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor biomarkers that can predict the disease progression would be an important advancement. Most muscle diseases involve accelerated muscle fiber degradation, inflammation, fatty tissue substitution and/or fibrosis. All these pathological traits have been shown to give rise to serological peptide biomarkers in other tissues, underlining the potential application of existing biomarkers of such traits in muscle disorders. A significant quantity of tissue is involved in these pathological mechanisms alongside with qualitative changes in protein turnover in myofibrillar, extra-cellular matrix and immunological cell protein fractions accompanied by alterations in body fluids. We propose that protein and peptides can leak out of the afflicted muscles and can be of use in diagnosis, prediction of pathology trajectory and treatment efficacy. Proteolytic cleavage systems are especially modulated during a range of muscle pathologies, thereby giving rise to peptides that are differentially released during disease manifestation. Therefore, we believe that pathology-specific post-translational modifications like cleavages can give rise to neoepitope peptides that may represent a promising class of peptides for discovery of biomarkers pertaining to neuromuscular diseases.


Identification and characterization of a novel RPGR isoform in human retina.
Retinitis pigmentosa (RP) constitutes a major cause of blindness and the Retinitis Pigmentosa GTPase Regulator (RPGR) gene accounts for up to 80% of all X-linked RP cases. A novel isoform of RPGR, expressed in the human retina, was identified and characterized. It truncates the Regulator of Chromosome Condensation 1 (RCC1) homologous protein domain (RCC1h) of RPGR and mediates the formation of isoform-specific complexes with the RPGR-interacting protein 1 (RPGRIP1). Immunohistochemistry localized the novel RPGR isoform predominantly to inner segments of cone photoreceptors, where it colocalizes with RPGRIP1 in the human retina. In a patient with a mild RP phenotype, we identified a nucleotide substitution in a splicing regulator, which leads to 3.5 times higher levels of the transcripts coding for the novel RPGR isoform. The nucleotide substitution affects regulated alternative splicing of the novel RPGR isoform and suggests a tight adjustment of splicing as a prerequisite for proper function of photoreceptors.


Engineering superficial zone features in tissue engineered cartilage.
A major challenge in cartilage tissue engineering is the need to recreate the native tissue's anisotropic extracellular matrix structure. This anisotropy has important mechanical and biological consequences and could be crucial for integrative repair. Here, we report that hydrodynamic conditions that mimic the motion-induced flow fields in between the articular surfaces in the synovial joint induce the formation of a distinct superficial layer in tissue engineered cartilage hydrogels, with enhanced production of cartilage matrix proteoglycan and Type II collagen. Moreover, the flow stimulation at the surface induces the production of the surface zone protein Proteoglycan 4 (aka PRG4 or lubricin). Analysis of second harmonic generation signature of collagen in this superficial layer reveals a highly aligned fibrillar matrix that resembles the alignment pattern in native tissue's surface zone, suggesting that mimicking synovial fluid flow at the cartilage surface in hydrodynamic bioreactors could be key to creating engineered cartilage with superficial zone features.


Camera-sampling field and its applications.
In this paper, we propose a novel vector field, called a camera-sampling field, to represent the sampling density distribution of a pinhole camera. We give the derivation and discuss some essential properties of the camera-sampling field, including flux, divergence, curl, gradient, level surface, and sampling patterns. This vector field reveals camera-sampling concisely and facilitates camera sampling analysis. The usage for this vector field in several computer graphics applications is introduced, such as determining the splat kernel for image-based rendering, texture filtering, mipmap level selection, level transition criteria for LOD, and LDI-construction.


The impact of hearing aids and age-related hearing loss on auditory plasticity across three months - An electrical neuroimaging study.
The present study investigates behavioral and electrophysiological auditory and cognitive-related plasticity in three groups of healthy older adults (60-77 years). Group 1 was moderately hearing-impaired, experienced hearing aid users, and fitted with new hearing aids using non-linear frequency compression (NLFC on); Group 2, also moderately hearing-impaired, used the same type of hearing aids but NLFC was switched off during the entire period of study duration (NLFC off); Group 3 represented individuals with age-appropriate hearing (NHO) as controls, who were not different in IQ, gender, or age from Group 1 and 2. At five measurement time points (M1-M5) across three months, a series of active oddball tasks were administered while EEG was recorded. The stimuli comprised syllables consisting of naturally high-pitched fricatives (/sh/, /s/, and /f/), which are hard to distinguish for individuals with presbycusis. By applying a data-driven microstate approach to obtain global field power (GFP) as a measure of processing effort, the modulations of perceptual (P50, N1, P2) and cognitive-related (N2b, P3b) auditory evoked potentials were calculated and subsequently related to behavioral changes (accuracy and reaction time) across time. All groups improved their performance across time, but NHO showed consistently higher accuracy and faster reaction times than the hearing-impaired groups, especially under difficult conditions. Electrophysiological results complemented this finding by demonstrating longer latencies in the P50 and the N1 peak in hearing aid users. Furthermore, the GFP of cognitive-related evoked potentials decreased from M1 to M2 in the NHO group, while a comparable decrease in the hearing-impaired group was only evident at M5. After twelve weeks of hearing aid use of eight hours each day, we found a significantly lower GFP in the P3b of the group with NLFC on as compared to the group with NLFC off. These findings suggest higher processing effort, as evidenced by higher GFP, in hearing-impaired individuals when compared to those with normal hearing, although the hearing-impaired show a decrease of processing effort after repeated stimulus exposure. In addition, our findings indicate that the acclimatization to a new hearing aid algorithm may take several weeks.


HIV and HLA class I: an evolving relationship.
Successful vaccine development for infectious diseases has largely been achieved in settings where natural immunity to the pathogen results in clearance in at least some individuals. HIV presents an additional challenge in that natural clearance of infection does not occur, and the correlates of immune protection are still uncertain. However, partial control of viremia and markedly different outcomes of disease are observed in HIV-infected persons. Here, we examine the antiviral mechanisms implicated by one variable that has been consistently associated with extremes of outcome, namely HLA class I alleles, and in particular HLA-B, and examine the mechanisms by which this modulation is likely to occur and the impact of these interactions on evolution of the virus and the host. Studies to date provide evidence for both HLA-dependent and epitope-dependent influences on viral control and viral evolution and have important implications for the continued quest for an effective HIV vaccine.


In vitro quenching of fish pathogen Edwardsiella tarda AHL production using marine bacterium Tenacibaculum sp. strain 20J cell extracts.
Quorum quenching (QQ) has become an interesting alternative for solving the problem of bacterial antibiotic resistance, especially in the aquaculture industry, since many species of fish-pathogenic bacteria control their virulence factors through quorum sensing (QS) systems mediated by N-acylhomoserine lactones (AHLs). In a screening for bacterial strains with QQ activity in different marine environments, Tenacibaculum sp. strain 20J was identified and selected for its high degradation activity against a wide range of AHLs. In this study, the QQ activity of live cells and crude cell extracts (CCEs) of strain 20J was characterized and the possibilities of the use of CCEs of this strain to quench the production of AHLs in cultures of the fish pathogen Edwardsiella tarda ACC35.1 was explored. E. tarda ACC35.1 produces N-hexanoyl-L-homoserine lactone (C6-HSL) and N-oxohexanoyl-L-homoserine lactone (OC6-HSL). This differs from profiles registered for other E. tarda strains and indicates an important intra-specific variability in AHL production in this species. The CCEs of strain 20J presented a wide-spectrum QQ activity and, unlike Bacillus thuringiensis serovar Berliner ATCC10792 CCEs, were effective in eliminating the AHLs produced in E. tarda ACC35.1 cultures. The fast and wide-spectrum AHL-degradation activity shown by this member of the Cytophaga-Flexibacter-Bacteroidetes group consolidates this strain as a promising candidate for the control of AHL-based QS pathogens, especially in the marine fish farming industry.


The effect of dietary protein supplementation on the pathophysiology of Haemonchus contortus infection in West African Dwarf goats.
The effect of dietary protein on the pathophysiology of Haemonchus contortus infection in reproducing first pregnancy West African Dwarf (WAD) goats was studied. Eighteen 10-12-month-old pubertal female WAD goats divided into two equal groups were used and confined separately. One group was maintained on high-protein diet (HPD) while the other was maintained on low-protein diet (LPD) from day 1 of pregnancy up to week 6 post-partum. Each animal was infected with 600 infective larvae of H. contortus weekly for 4 weeks and blood collected by jugular venipuncture for the determination of packed cell volume and serum proteins. The results of the study showed that improved protein nutrition significantly enhanced the level of serum albumin (p<0.05). It also significantly lowered the level of serum globulin (p<0.05) that otherwise would be high in haemonchosis. However, improvement in the dietary protein level appeared not to have any effect on the packed cell volume and total serum protein level.