[Spatio-temporal variation of subtidal meiofauna in a sandy beach from Northeastern Venezuela].
Meiofauna organisms that play an important role in the trophic ecology of soft bottom benthos, have short life cycles and they respond quickly to disturbance and pollution. The present study shows the spatio-temporal variation ofsubtidal meiofauna (metazoans passing a 500im sieve but retained on meshes of 40-63micro m) in four shallow subtidal stations. Samples were taken in the sandy beach of San Luis, in the Northeastern coast of Venezuela, from October 2005 until September 2006. For this, three replicate sediment core samples (4.91cm2), were collected monthly to a depth of 10cm into the sediment, and preserved in 6% formalin stained with rose Bengal. Specimens of 14 meiofaunal groups (Foraminifera excluded) were collected, being the nematodes, ostracods and harpacticoid copepods the most abundant. Monthly density was comprised between 64 and 503ind./10cm2, and mean density of stations between 173 and 449ind./10cm2. There is a trend of low densities from October to February (end of the rainy season until the middle of the dry season). The San Luis beach control of the meiofaunal community is shared by climatic conditions and by the biology of the species found. The meiofauna mean density in San Luis beach (263ind./10cm2) was low when compared to other studies in tropical areas.


A Telemedicine Intervention to Ensure the Correct Usage of Inhaler Devices.
Background: Chronic obstructive pulmonary disease and asthma patients' use of inhalers is error prone. Introduction: This study evaluated telemedicine to improve the use of inhalers. Materials and Methods: Prospective, single-center pilot study in 50 patients with long-term prescription of inhaled medicine and ongoing home health care visits. In an initial telemedicine intervention, tablet devices were used by the patient to record inhaler use at home in the real-time remote presence of a physician. Errors were identified, explained to the patient, and corrected remotely. When necessary, further telemedicine interventions were scheduled at 24-48 h intervals. Follow-up interventions were performed during routine outpatient visits. Patient satisfaction was evaluated on a scale of 0 (completely unsatisfied) to 10 (completely satisfied). Results: An initial telemedicine intervention was conducted for 42 of the 50 patients included. In these patients, 96 initial inhaler medicine administration telemedicine interventions were performed, of which 94 were usable. In the initial interventions, 71 errors were identified, of which 22 (31%) were considered critical. In 81 follow-up interventions in 39 patients (median delay 256 days), 32 errors were identified (p < 0.001 vs. initial 71 errors), of which 7 were critical (p = 0.0017 vs. initial 22 errors). Discussion: This paves the way for future studies testing putative benefits of telemedicine regarding inhaled drug delivery, treatment adherence, disease control, quality of life, and health care burden and costs. Conclusions: A telemedicine intervention aimed at improving the administration of inhaled medication by adult patients at home is feasible, highly appreciated by patients, and effective at correcting medicine administration errors.


Extreme rainfall, vulnerability and risk: a continental-scale assessment for South America.
Extreme weather continues to preoccupy society as a formidable public safety concern bearing huge economic costs. While attention has focused on global climate change and how it could intensify key elements of the water cycle such as precipitation and river discharge, it is the conjunction of geophysical and socioeconomic forces that shapes human sensitivity and risks to weather extremes. We demonstrate here the use of high-resolution geophysical and population datasets together with documentary reports of rainfall-induced damage across South America over a multi-decadal, retrospective time domain (1960-2000). We define and map extreme precipitation hazard, exposure, affectedpopulations, vulnerability and risk, and use these variables to analyse the impact of floods as a water security issue. Geospatial experiments uncover major sources of risk from natural climate variability and population growth, with change in climate extremes bearing a minor role. While rural populations display greatest relative sensitivity to extreme rainfall, urban settings show the highest rates of increasing risk. In the coming decades, rapid urbanization will make South American cities the focal point of future climate threats but also an opportunity for reducing vulnerability, protecting lives and sustaining economic development through both traditional and ecosystem-based disaster risk management systems.


Working time reduction, mental health, and early retirement among part-time teachers at German upper secondary schools - a cross-sectional study.
Many secondary school teachers work part-time in order to cope with the high workload and to remain as healthy as possible until regular retirement. However, due to the acute shortage of teachers, the increase in the teaching obligation for part-time teachers (PTT) has become a topic of discussion in Germany. Whether a reduction in teaching hours is associated with benefits for mental health has not yet become evident. Therefore, this study investigated the relationship between the real working hours of PTT and their mental health as well as individual pension prognosis. The cross-sectional study included 5,905 PTT at German upper secondary schools (female proportion: 81%, average age: 44 ± 9 years) who logged their working hours over four weeks. Four part-time groups (PTG) were formed based on the proportion of a full-time position worked: maximum (<100-90% = PTGmax - reference group - 17%), high (<90-75% = PTGhigh - 34%), medium (<75-50% = PTGmed - 40%) and low (<50% = PTGlow - 9%) teaching commitment. These groups were compared in terms of their average weekly working hours, mental health (inability to recover, risk of burnout) and predicted retirement age. The contractually agreed working time is exceeded to a relevant extent for PTT. The extent of unpaid overtime increases significantly the lower the teaching obligation is and lies on average between -0.4 (PTGmax) and 7.3 (PTGlow) hours/week. A reduction in teaching hours is neither related to the mental health of teachers nor to their decision to retire early (42%) or regularly (58%). However, predicted retirement is mainly explained by mental health status, gender and age (variance explanation: 24%, OR of predictors: maximum 2.1). One third of PTT reported inability to recover, 47% burnout symptoms and 3% a burnout syndrome. Mental health is also a risk for PTT; reducing teaching hours alone does not improve it. However, good mental health increases the chance of regular retirement. Therefore, instead of a legal obligation, PTT should be encouraged to increase the number of teaching hours voluntarily in order to counteract the general shortage of teachers.


Performance of the pediatric index of mortality 2 (PIM-2) in cardiac and mixed intensive care units in a tertiary children's referral hospital in Italy.
Mortality rate of patients admitted to Intensive Care Units is a widely adopted outcome indicator. Because of large case-mix variability, comparisons of mortality rates must be adjusted for the severity of patient illness at admission. The Pediatric Index of Mortality 2 (PIM-2) has been widely adopted as a tool for adjusting mortality rate by patients' case mix. The objective of this study was to assess the performance of PIM-2 in children admitted to intensive care units after cardiac surgery, other surgery, or for other reasons. This was a prospective cohort study, conducted in a 607 inpatient-bed tertiary-care pediatric hospital in Italy, with three pediatric intensive care Units (PICUs) and one cardiac Unit (CICU). In 2009-11, all consecutive admissions to PICUs/CICU of children aged 0-16 years were included in the study. Discrimination and calibration measures were computed to assess PIM-2 performance. Multivariable logistic regression analysis was used to assess the association of patients' main reason for intensive care admission (cardiac-surgical, other-surgical, medical), age, Unit and year with observed mortality, adjusting for PIM-2 score. PIM-2 data collection was completed for 91.2% of total PICUs/CICU patient admissions (2912), and for 94.8% of patients who died in PICUs/CICU (129). Overall observed mortality was 4.4% (95% CI, 3.7-5.2), compared to 6.4% (95% CI, 5.5-7.3) expected mortality. Standardised mortality ratio was 0.7 (95% CI: 0.6-0.8). PIM-2 discrimination was fair (area under the curve, 0.79; 95% CI: 0.75-0.83). Calibration was less satisfactory, mainly because of the over two-fold overprediction of deaths in the highest risk group (114.7 vs 53; p < 0.001), and particularly in cardiac-surgical patients. Multivariable logistic analysis showed that risk of death was significantly reduced in cardiac-surgical patients and in those aged 1 month to 12 years, independently from PIM-2. The children age distribution and the proportion of cardiac-surgical patients should be taken into account when interpreting SMRs estimated using the PIM-2 prediction model in different Units. A new calibration study of PIM-2 score might be needed, and more appropriate cardiac-focused risk-adjustment models should be developed. The role of age on risk of death needs to be further explored.


Species richness and ecological characterization of myxomycetes and myxomycete-like organisms in the canopy of a temperate deciduous forest.
The ecological community of myxomycetes and myxomycete-like organisms (MMLO) in the canopy of living deciduous trees was studied in a riparian deciduous forest at Leipzig, Germany. A systematic survey carried out with a total of 146 moist chamber cultures resulted in 386 records of 37 taxa, with 32 myxomycetes, two myxobacteria, two protostelids and the fruit body forming ciliate Sorogena stoianovitchae, the latter recorded for the first time for Europe. With 94% of all cultures positive for MMLO, these organisms are present consistently in the investigated sections of white-rotten twigs attached to living trees at 10-30 m above the ground. Our sampling recovered a majority of the likely species, with 37 out of the 42-45 predicted according to a species-accumulation curve and two other estimators of species richness. Nonmetric multidimensional scaling revealed pH, water-holding capacity and stage of decay to explain most of the variation in species distribution. Arcyria cinerea and Perichaena depressa as the most common species occurred in 32% and 29% of all samples, respectively. Viewing the sampled twigs as habitat islands and a single spore as sufficient to establish a population, a simulation program assuming a random spore rain estimated an average of 0.4 and 0.35 spore hits per twig as necessary to explain the observed frequencies. This is matched by the potential productivity of the substrate. All fruit bodies from the cultured twigs would be able to create a spore rain of 86 (A. cinerea) or 40 (P. depressa) spore hits per twig when dispersed evenly over the plot. The terminal fall velocity of spores was measured, revealing that it took about 5 h for a spore to land (30 m) in still air and indicating high dispersal ability for canopy-inhabiting MMLO.


[Expression of orphanin in adenomyosis and its relationship with dysmenorrhea].
To study the expression of nociceptin in adenomyosis tissue and understand its relationship with the severity of dysmenorrhea. The myometrial specimens were collected from 55 patients undergoing hysterectomy at our hospital during December 2007 and June 2008. Their mean age was 41 - 52 years old. There were 34 adenomyosis patients in case group and 21 other patients in control group. Immunohistochemical staining was employed to detect nociceptin in eutopic endometrium and ectopic endometrial tissues in case group and normal endometrium and myometrial tissues in control group. The expression of nociceptin was significantly higher in the eutopic endometrial tissue (7.1 ± 1.7) of case group than those in endometrial (2.7 ± 2.0) and myometrial tissues of control group (P < 0.05); The expression of nociceptin was higher in the eutopic endometrial tissue (7.4 ± 1.5) of dysmenorrhea group than that of non-dysmenorrhea group (5.0 ± 1.2) in case group (P < 0.05); The expression of nociceptin in eutopic endometrium and myometrium was the highest in severe dysmenorrhea group (8.4 ± 1.3). And the non-dysmenorrhea and mild dysmenorrheal groups had no significant differences [(5.0 ± 1.2) vs (6.8 ± 1.4)]. And it decreased gradually in moderate dysmenorrhea, mild dysmenorrhea and non-dysmenorrhea groups. A high expression of nociceptin in adenomyosis may be one of the casual factors of dysmenorrhea. The severity of dysmenorrhea is positively correlated with the expression of nociceptin in eutopic endometrial tissue in case group (r = 0.515, P = 0.034) and ectopic endometrium tissue. And the endometrial expression of nociceptin may be monitored dynamically to track the development of adenomyosis.


Computer-aided detection of breast cancer nuclei.
A computer-aided detection system for tissue cell nuclei in histological sections is introduced and validated as part of the Biopsy Analysis Support System (BASS). Cell nuclei are selectively stained with monoclonal antibodies, such as the anti-estrogen receptor antibodies, which are widely applied as part of assessing patient prognosis in breast cancer. The detection system uses a receptive field filter to enhance negatively and positively stained cell nuclei and a squashing function to label each pixel value as belonging to the background or a nucleus. In this study, the detection system assessed all biopsies in an automated fashion. Detection and classification of individual nuclei as well as biopsy grading performance was shown to be promising as compared to that of two experts. Sensitivity and positive predictive value were measured to be 83% and 67.4%, respectively. One major advantage of BASS stems from the fact that the system simulates the assessment procedures routinely employed by human experts; thus it can be used as an additional independent expert. Moreover, the system allows the efficient accumulation of data from large numbers of nuclei in a short time span. Therefore, the potential for accurate quantitative assessments is increased and a platform for more standardized evaluations is provided.


[Presence of free-living amoebae in urban and communal water-supply systems of the Brest area].
During a preliminary study, from October 1975 until June 1976, we tried to find free-living limax amoebae in the waters proceeding from 6 systems which partly cover the wants of Brest and its bay (Finistère). From the 32 analysed samples, 19 were positive, of which 10 were able to grown at the first at 37 degrees C. The free-living amoebae belong to 3 genus: Harmanella, Vahlkampfia and Acanthamoeba. We have not found Naegleria species.


Alcohol prevention on college campuses: the moderating effect of the alcohol environment on the effectiveness of social norms marketing campaigns.
Evaluations of social norms marketing campaigns to reduce college student drinking have produced conflicting results. This study examines whether the effectiveness of such campaigns may be moderated by on-premise alcohol outlet density in the surrounding community. Multilevel analyses were conducted of student survey responses (N= 19,838) from 32 U.S. colleges that took part in one of two 4-year randomized, controlled trials completed for the Social Norms Marketing Research Project (SNMRP). In the models, students by year were nested within treatment (n = 16) and control group (n = 16) campuses, which were characterized by the on-premise outlet density in their surrounding community. The moderating effect of outlet density was introduced into the models as an interaction between the treatment effect (i.e., the effect of the social norms marketing campaigns over time) and outlet density. The models were also stratified by campus alcohol outlet density (high vs. low) to examine the effect of the intervention in each type of setting. There was a significant interaction between the treatment effect and on-premise alcohol outlet density for one of the drinking outcomes targeted by the SNMRP intervention, the number of drinks when partying, and marginal evidence of interaction effects for two other outcomes, maximum recent consumption and a composite drinking scale. In stratified analyses, an intervention effect was observed for three of the four outcomes among students from campuses with lower on-premise alcohol outlet density, whereas no intervention effect was observed among students from campuses with higher on-premise alcohol outlet density. The findings suggest that the campus alcohol environment moderates the effect of social norms marketing interventions. Social norms marketing intervention may be less effective on campuses with higher densities of on-sale alcohol outlets.


Toxicity of cypermethrin to Daphnia magna HB.
The acute toxic effect of the pesticide cypermethrin to Daphnia magna HB was examined. D. magna HB was exposed to cypermethrin at concentrations of 0, 1, 3, 5, 7, and 9 mg/L for 24 h. Data showed that the 24 h-LC50 of cypermthrin on D. magna HB was 4.81 mg/L. In contrast, the 24 h-LC50 of K2Cr2O7 (the national standard toxicant) to Daphnia magna was 0.38 mg/L in the current study. Results indicated that the Daphnia magna was very sensitive to pesticides. In addition, the effects of the culture condition (such as hardness, temperature and DO etc.) on Daphnia magna HB was also studied.


Polariton Exchange Interactions in Multichannel Optical Networks.
We examine the dynamics of Rydberg polaritons with dipolar interactions that propagate in multiple spatial modes. The dipolar excitation exchange between different Rydberg states mediates an effective exchange between polaritons that enables photons to hop across different spatial channels. Remarkably, the efficiency of this photon exchange process can increase with the channel distance and becomes optimal at a finite rail separation. Based on this mechanism, we design a simple photonic network that realizes a two photon quantum gate with a robust π phase, protected by the symmetries of the underlying photon interaction and the geometry of the network. These capabilities expand the scope of Rydberg electromagnetically induced transparency towards multidimensional geometries for nonlinear optical networks and explorations of photonic many-body physics.


The legal precariousness of work relations in the health sector during the COVID-19 pandemic, as a factor of worker suffering.
The present article analyzed the process of precarious work relations in the health sector, demonstrating how this situation generated illness and suffering among workers. The text sought to register how the institutional adoption of neoliberal economic conceptions, of the reduction of State social policies, coupled with a history of cultural rejection of labor rights, provided the attraction of mechanisms of precarious work for the public sector, notably, the outsourcing of labor and the provision of services. In a second moment, the text points out the legal improprieties committed, presenting the consequences of the weakening of the legal bond in the working conditions of these workers, mainly regarding working hours and remuneration, also highlighting how much the dissemination of these links represented a factor of a general reduction in wages and labor and social security rights in the sector. Data from Fiocruz surveys on working conditions during the pandemic were also presented. The article concludes by showing the urgency of rescuing the legal labor institutes that were abandoned in the historical path studied in order to guide the public health policies in a new direction.


Evidence for dimeric BACE-mediated APP processing.
beta-Secretase (BACE) is an aspartyl protease, which proteolytically processes amyloid precursor protein, making BACE an interesting pharmacological target in Alzheimer's disease. To study the enzymatic function of BACE, we mutated either of the two aspartic acid residues in the active site of BACE. This rendered BACE functionally inactive without affecting the degree of glycosylation or endosomal localization. In contrast, substituting both active site aspartic acid residues produced a functionally inactive, endoplasmic reticulum-retained and partially glycosylated BACE. Interestingly, co-expression of the two single active site mutants partially restored beta-site cleavage of amyloid precursor protein, and the restored activity was inhibited with similar dose-dependency and potency as wildtype BACE by a small molecule inhibitor raised against BACE. In sum, our data suggest that two different active site mutants can complement each other in a partially functional BACE dimer and mediate APP processing.


Diversity and host preference of leaf endophytic fungi in the Iwokrama Forest Reserve, Guyana.
Endophytic fungi were isolated from living symptomless leaves of 12 tree species from two locations in the Iwokrama Forest Reserve, Guyana. Sixty-four fungal morphotaxa were characterized from 2492 cultures, which were derived from a total of 2520 sample units. Species of Colletotrichum, Nodulisporium, Pestalotiopsis and Phomopsis were most frequently isolated. Colonization was greater in samples from the midrib than in those from laminar tissue, and slightly greater at the tip of the lamina compared with the base of the leaf. In contrast to studies in temperate ecosystems, no distinct fungal communities were identified for individual plant species, suggesting that the degree of host preference is low. The implications for estimation of fungal diversity in tropical systems are explored.


Flow diversion treatment for acutely ruptured aneurysms.
Flow diverters are sometimes used in the setting of acutely ruptured aneurysms. However, thromboembolic and hemorrhagic complications are feared and evidence regarding safety is limited. Therefore, in this multicenter study we evaluated complications, clinical, and angiographic outcomes of patients treated with a flow diverter for acutely ruptured aneurysms. We conducted a retrospective observational study of 44 consecutive patients who underwent flow diverter treatment within 15 days after rupture of an intracranial aneurysm at six centers. The primary end point was good clinical outcome, defined as modified Rankin Scale score (mRS) 0-2. Secondary endpoints were procedure-related complications and complete aneurysm occlusion at follow-up. At follow-up (median 3.4 months) 20 patients (45%) had a good clinical outcome. In 20 patients (45%), 25 procedure-related complications occurred. These resulted in permanent neurologic deficits in 12 patients (27%). In 5 patients (11%) aneurysm re-rupture occurred. Eight patients died resulting in an all-cause mortality rate of 18%. Procedure-related complications were associated with a poor clinical outcome (mRS 3-6; OR 5.1(95% CI 1.0 to 24.9), p=0.04). Large aneurysms were prone to re-rupture with rebleed rates of 60% (3/5) vs 5% (2/39) (p=0.01) for aneurysms with a size ≥20 mm and <20 mm, respectively. Follow-up angiography in 29 patients (median 9.7 months) showed complete aneurysm occlusion in 27 (93%). Flow diverter treatment of ruptured intracranial aneurysms was associated with high rates of procedure-related complications including aneurysm re-ruptures. Complications were associated with poor clinical outcome. In patients with available angiographic follow-up, a high occlusion rate was observed.


Phytoremediation of industrial mines wastewater using water hyacinth.
The wastewater at Sukinda chromite mines (SCM) area of Orissa (India) showed high levels of toxic hexavalent chromium (Cr VI). Wastewater from chromium-contaminated mines exhibit potential threats for biotic community in the vicinity. The aim of the present investigation is to develop a suitable phytoremediation technology for the effective removal of toxic hexavalent chromium from mines wastewater. A water hyacinth species Eichhornia crassipes was chosen to remediate the problem of Cr (VI) pollution from wastewater. It has been observed that this plant was able to remove 99.5% Cr (VI) of the processed water of SCM in 15 days. This aquatic plant not only removed hexavalent Cr, but is also capable of reducing total dissolved solids (TDS), biological oxygen demand (BOD), chemical oxygen demand (COD), and other elements of water also. Large-scale experiment was also performed using 100 L of water from SCM and the same removal efficiency was achieved.


The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China.
The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.


Cortical thinning in verbal, visual, and both memory-predominant mild cognitive impairment.
The amnestic form of mild cognitive impairment (aMCI) is likely a precursor of Alzheimer disease (AD). Both verbal and visual memory tests are used in the diagnosis of aMCI; however, it is unknown which type of test is superior at predicting the underlying pathologic changes associated with AD. In this study, we compared the topography of cortical thinning among 3 subtypes of patients with aMCI: 33 patients with predominant verbal memory impairment (verbal-aMCI), 35 with predominant visual memory impairment (visual-aMCI), and 56 with both verbal and visual memory-predominant impairment (both-aMCI), and 143 patients with normal cognition. As a result, patients with verbal-aMCI showed cortical thinning in the left anterior and medial temporal regions compared with individuals with normal cognition, while those with visual-aMCI did not show significant cortical thinning. The cortical thinning areas of both-aMCI group overlapped those of verbal-aMCI but were more widespread involving the bilateral temporal regions. These findings suggest that the verbal-aMCI and both-aMCI are more likely to be a precursor of AD than visual-aMCI, and that both-aMCI may be more advanced subtype than verbal-aMCI on the spectrum from MCI to AD.


Computation of breast ptosis from 3D surface scans of the female torso.
Stereophotography is now finding a niche in clinical breast surgery, and several methods for quantitatively measuring breast morphology from 3D surface images have been developed. Breast ptosis (sagging of the breast), which refers to the extent by which the nipple is lower than the inframammary fold (the contour along which the inferior part of the breast attaches to the chest wall), is an important morphological parameter that is frequently used for assessing the outcome of breast surgery. This study presents a novel algorithm that utilizes three-dimensional (3D) features such as surface curvature and orientation for the assessment of breast ptosis from 3D scans of the female torso. The performance of the computational approach proposed was compared against the consensus of manual ptosis ratings by nine plastic surgeons, and that of current 2D photogrammetric methods. Compared to the 2D methods, the average accuracy for 3D features was ~13% higher, with an increase in precision, recall, and F-score of 37%, 29%, and 33%, respectively. The computational approach proposed provides an improved and unbiased objective method for rating ptosis when compared to qualitative visualization by observers, and distance based 2D photogrammetry approaches.


Oral administration of heat-killed Lactobacillus brevis SBC8803 ameliorates the development of dermatitis and inhibits immunoglobulin E production in atopic dermatitis model NC/Nga mice.
We have previously shown that the oral administration of heat-killed Lactobacillus brevis (L. brevis) SBC8803 strain inhibits IgE production in ovalbumin (OVA)-sensitized BALB/c mice through improvement of the type-1 helper T (Th1)/Th2 balance toward Th1 dominance. Atopic dermatitis is one of the most common skin diseases and is frequently associated with elevated immunoglobulin E (IgE) antibodies against many kinds of allergens. In this study, we investigated the inhibitory effect of oral administration of L. brevis SBC8803 on the development of dermatitis and IgE elevation using the NC/Nga atopic dermatitis model mice. Male 8-week-old NC/Nga mice were sensitized by the topical application of picryl chloride to foot pads and shaved abdomen. These mice were boosted with picryl chloride by topical application onto the ears once a week for 9 weeks. The mice (n=10 per group) were fed a diet containing 0%, 0.05% or 0.5% of heat-killed L. brevis SBC8803 from 2 weeks before the first sensitization to the end of the study. Total IgE concentration in serum, clinical score, and ear thickness were periodically examined throughout the study. Finally, cytokine (interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12, IFN-gamma and transforming growth factor (TGF)-beta) productions from splenocytes and Peyer's patch (PP) cells of mice were measured. Oral administration of L. brevis SBC8803 significantly inhibited IgE production and ear swelling, and suppressed the development of dermatitis in a dose-dependent manner. Immunosuppressive cytokines such as IL-10 and TGF-beta production from PP cells significantly increased in the 0.5% group compared to the control group although Th1-type and Th2-type cytokines production was not affected.


Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation.
This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.


Mortality attributable to tobacco use in Canada and its regions, 1994 and 1996.
Using data from the National Population Health Survey and the Canadian Mortality Database, we applied the Smoking-Attributable Mortality, Morbidity and Economic Cost method to estimate national and regional smoking-attributable mortality for 1994 and 1996. The results indicate that 29,229 men and 15,986 women died in 1996 as a result of smoking, including 105 children under the age of 1. This total of approximately 45,200 deaths represents an increase of 3,807 deaths since 1991, of which 2,445 occurred in women. The increase in female mortality is almost entirely due to adult diseases, divided between cancers (1,026), cardiovascular diseases (743) and respiratory diseases (870).


Clinically Relevant Concentrations of Anticancer Drugs: A Guide for Nonclinical Studies.
Approved and marketed drugs are frequently studied in nonclinical models to evaluate the potential application to additional disease indications or to gain insight about molecular mechanisms of action. A survey of the literature reveals that nonclinical experimental designs (in vitro or in vivo) often include evaluation of drug concentrations or doses that are much higher than what can be achieved in patients (i.e., above the maximally tolerated dose or much higher than the clinically relevant exposures). The results obtained with these high concentrations may be particularly helpful in elucidating off-target effects and toxicities, but it is critical to have a dose-response curve that includes the minimally effective or clinically effective concentration for comparison. We have reviewed the clinical literature and drug product labels for all small molecules and biological agents approved by the FDA for use in oncology to identify and compile the available pharmacokinetic parameters. The data summarized here can serve as a guide for selection of in vitro concentrations and in vivo plasma exposures for evaluation of drug effects in nonclinical studies. Inclusion of drug concentrations or exposures that are relevant to those observed in clinical practice can improve translation of nonclinical mechanism of action findings into potentially relevant clinical effects. Clin Cancer Res; 23(14); 3489-98. ©2017 AACR.


Laboratory studies of homing orientation in the eastern red-spotted newt, Notophthalmus viridescens.
The orientation behaviour of adult male eastern red-spotted newts (Notophthalmus viridescens) was studied in laboratory tests. Newts were collected from ponds located 10-30 km from the laboratory, and housed in water-filled, all-glass aquaria located in a greenhouse or outdoors adjacent to the laboratory building. The aquaria were aligned on the magnetic north-south axis. Newts were tested in a dry, enclosed arena in four magnetic fields: the ambient magnetic field (magnetic north at North) and three altered fields (magnetic north rotated to East, West or South). Newts tested during January-March exhibited weak bimodal magnetic orientation along the axis of the holding tank. However, during the spring migratory period (April until early May), the bimodal response shifted to coincide with the direction of the pond from which the newts had been collected. Much stronger unimodal orientation was elicited by elevating the water temperature to 33-34 degrees C immediately prior to testing. If newts were held in a training tank with an artificial shoreline at one end and exposed to elevation of water temperature after several days of stable water temperatures, they exhibited unimodal shoreward orientation and did not show the seasonal switch to homing behaviour observed in the earlier tests. If, however, the elevation of water temperature followed a period of fluctuating water temperature (over a 20 degrees C range), the newts exhibited strong unimodal orientation in the direction of the pond from which they had been collected. These results suggest that newts possess a navigational system that enables them to home from distances in excess of 20 km. Moreover, these experiments provide the first opportunity to examine the sensory basis of navigational ability in any animal under controlled laboratory conditions.


A comparison of epidural and non-epidural anesthesia and analgesia in total hip or knee arthroplasty patients.
This retrospective study explores a number of variables encountered with the use of either epidural or non-epidural anesthesia and analgesia. Postoperative mobility, amount of narcotic used, incidence of blood transfusion, length of stay, and presence of urinary retention, pruritus, nausea and vomiting, or respiratory depression were compared in a group of 101 consecutive patients scheduled for total hip or knee arthroplasty. Fifty-two patients received epidural anesthesia and analgesia; the remaining 49 received non-epidural anesthesia, followed by standard IM/IV postoperative analgesia. Epidural patients required significantly less narcotic than the non-epidural group. There were significantly fewer blood transfusions in the epidural group; however, epidural patients had significantly increased incidence of urinary retention and pruritus. The use of epidural anesthesia and analgesia for total hip and knee arthroplasty patients has definite merit, but is most safely administered in a monitored, skilled nursing unit.


Seroprevalence evolution of selected pathogens in Iberian wild boar.
A total of 1279 Eurasian wild boar (Sus scrofa) sera were collected from 2000 to 2011 in the Iberian Peninsula to reveal time changes in serum antibody prevalences against selected infectious agents (porcine circovirus type 2, PCV2; porcine reproductive and respiratory syndrome virus, PRRSV; hepatitis E virus, HEV; and Erysipelothrix rhusiopathiae) and to identify putative individual or population factors driving such changes. Overall seroprevalences were 48%, 26%, 2% and 15% for PCV2, HEV, PRRSV and E. rhusiopathiae, respectively. The global observed prevalence of antibodies against PCV2 and HEV remained stable during the study period, while the global mean antibody seroprevalence against E. rhusiopathiae declined. The mean increment in prevalence was always lower for open than for fenced sites. This study evidenced for the first time that wild boar from the Iberian Peninsula have widespread contact with E. rhusiopathiae, and confirmed high prevalences of antibodies against PCV2 and HEV. Maintained high prevalences of transmissible agents in wild boar suggest that epidemiological drivers such as aggregation and high density are still acting. This will most probably also affect the transmission rates of other disease agents and should be taken into account regarding disease control at the wildlife-livestock interface.


Proactive screening approach for detecting groundwater contaminants along urban streams at the reach-scale.
Here we outline and demonstrate a screening approach for the detection of groundwater contaminants along urban streams within unconsolidated beds. It involves the rapid acquisition of groundwater samples along urban stream reaches at a spacing of about 10 m and from depths of about 25-75 cm below the streambed, with analyses for a suite of potential contaminants. This screening approach may serve two functions: a) providing information for assessing and mitigating the toxicity and eutrophication risks to aquatic ecosystems posed by groundwater contaminants and b) detecting and identifying groundwater contamination in urban settings more rapidly and inexpensively compared to land-based well installations. The screening approach was tested at three urban streams, each affected by a known chlorinated-solvent plume. All three known groundwater plumes were detected and roughly delineated. Multiple, previously unknown, areas or types of groundwater contamination were also identified at each stream. The newly identified contaminants and plumes included petroleum hydrocarbons (BTEX, naphthalene, MTBE), 1,4-dioxane, nitrate and phosphate, road salt, and various metals (including arsenic, cadmium, chromium, copper, lead) at elevated concentrations compared to background values and relevant Canadian water quality guidelines. These findings suggest that this screening approach may be a useful tool for both ecologists performing ecological assessments and stream restorations and for hydrogeologists undertaking groundwater protection activities. Given the numerous contaminants detected, it may be appropriate to apply this technique proactively to better determine the pervasiveness of urban groundwater contaminants, especially along urban streams.


Surface Functionalization of Black Phosphorus via Amine Compounds and Its Impacts on the Flame Retardancy and Thermal Decomposition Behaviors of Epoxy Resin.
Recently, lots of effort has been placed into stabilizing black phosphorus (BP) in the air to improve its compatibility with polymers. Herein, BP was chemically functionalized by aliphatic amine (DETA), aromatic amine (PPDA) and cyclamine (Pid) via a nucleophilic substitution reaction, aiming to develop an intensively reactive BP flame retardant for epoxy resin (EP). The -NH2 group on BP-DETA, BP-PPDA and BP-Pid reacted with the epoxide group at different temperatures. The lowest temperature was about 150 °C for BP-DETA. The impacts of three BP-NH2 were compared on the flame retardancy and thermal decomposition of EP. At 5 wt% loading, EP/BP-NH2 all passed UL 94 V 0 rating. The limiting oxygen index (LOI) of EP/BP-PPDA was as high as 32.3%. The heat release rate (HRR) of EP/BP-DETA greatly decreased by 46% and char residue increased by 73.8%, whereas HRR of EP/BP-Pid decreased by 11.5% and char residue increased by 50.8%, compared with EP. Average effective heat of combustion (av-EHC) of EP/BP-Pid was lower than that of EP/BP-DETA and EP/BP-PPDA. In view of the flame-retardant mechanism, BP nanosheets functionalized with aliphatic amine and aromatic amine played a dominant role in the condensed phase, while BP functionalized with cyclamine was more effective in the gas phase.


Global phylogeography of a cryptic copepod species complex and reproductive isolation between genetically proximate "populations".
The copepod Eurytemora affinis has a broad geographic range within the Northern Hemisphere, inhabiting coastal regions of North America, Asia, and Europe. A phylogenetic approach was used to determine levels of genetic differentiation among populations of this species, and interpopulation crosses were performed to determine reproductive compatibility. DNA sequences from two mitochondrial genes, large subunit (16S) rRNA (450 bp) and cytochrome oxidase I (COI, 652 bp), were obtained from 38 populations spanning most of the species range and from two congeneric species, E. americana and E. herdmani. Phylogenetic analysis revealed a polytomy of highly divergent clades with maximum sequence divergences of 10% in 16S rRNA and 19% in COI. A power test (difference of a proportion) revealed that amount of sequence data collected was sufficient for resolving speciation events occurring at intervals greater than 300,000 years, but insufficient for determining whether speciation events were approximately simultaneous. Geographic and genetic distances were not correlated (Mantel's test; r = 0.023, P = 0.25), suggesting that populations had not differentiated through gradual isolation by distance. At finer spatial scales, there was almost no sharing of mtDNA haplotypes among proximate populations, indicating little genetic exchange even between nearby sites. Interpopulation crosses demonstrated reproductive incompatibility among genetically distinct populations, including those that were sympatric. Most notably, two geographically distant (4000 km) but genetically proximate (0.96% 16S, 0.15% COI) populations exhibited asymmetric reproductive isolation at the F2 generation. Large genetic divergences and reproductive isolation indicate that the morphologically conservative E. affinis constitutes a sibling species complex. Reproductive isolation between genetically proximate populations underscores the importance of using multiple measures to examine patterns of speciation.


Costs and clinical outcomes in individuals without known coronary artery disease undergoing coronary computed tomographic angiography from an analysis of Medicare category III transaction codes.
Multidetector coronary computed tomographic angiography (CCTA) demonstrates high accuracy for the detection and exclusion of coronary artery disease (CAD) and predicts adverse prognosis. To date, opportunity costs relating the clinical and economic outcomes of CCTA compared with other methods of diagnosing CAD, such as myocardial perfusion single-photon emission computed tomography (SPECT), remain unknown. An observational, multicenter, patient-level analysis of patients without known CAD who underwent CCTA or SPECT was performed. Patients who underwent CCTA (n = 1,938) were matched to those who underwent SPECT (n = 7,752) on 8 demographic and clinical characteristics and 2 summary measures of cardiac medications and co-morbidities and were evaluated for 9-month expenditures and clinical outcomes. Adjusted total health care and CAD expenditures were 27% (p <0.001) and 33% (p <0.001) lower, respectively, for patients who underwent CCTA compared with those who underwent SPECT, by an average of $467 (95% confidence interval $99 to $984) for CAD expenditures per patient. Despite lower total health care expenditures for CCTA, no differences were observed for rates of adverse cardiovascular events, including CAD hospitalizations (4.2% vs 4.1%, p = NS), CAD outpatient visits (17.4% vs 13.3%, p = NS), myocardial infarction (0.4% vs 0.6%, p = NS), and new-onset angina (3.0% vs 3.5%, p = NS). Patients without known CAD who underwent CCTA, compared with matched patients who underwent SPECT, incurred lower overall health care and CAD expenditures while experiencing similarly low rates of CAD hospitalization, outpatient visits, myocardial infarction, and angina. In conclusion, these data suggest that CCTA may be a cost-efficient alternative to SPECT for the initial coronary evaluation of patients without known CAD.


[Clinical and economic analysis of the feasibility of using Dicarbamine for the prevention of the toxic effects of antineoplastic chemotherapy].
The aim of the study was to conduct clinical and economic analysis of the feasibility of using Dicarbamine for the prevention of toxic effects of chemotherapy. There were compared the direct medical costs on prevention and treatment of febrile neutropenia in 2 groups of breast cancer patients: chemotherapy alone in TAC mode or chemotherapy in the same way against oral Dicarbamine. Total costs due to hematologic toxicity were 1003945 rubles in the control group (22817 rubles on average by 1 patient) and 658980 rubles in the group treated with Dicarbamine (14 644 rubles on average by 1 patient). Also, the study found that in the group treated by Dicarbamine there were lower rates of dose reduction and delay of the next course of chemotherapy, which might have an impact on other costs arising from cancer. The results of this study demonstrate the clinical and economic feasibility of using Dicarbamine for the prevention of hematotoxic complications of chemotherapy.


Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats.
2-Hydroxyestrone (2-OHE1) has much lower uterotropic potency than might be predicted from its uterine estrogen receptor affinity. 2-OHE1 displaces saturably bound [3H]estradiol from rat uterine cytosol with a competitive inhibition constant of 8.6 nM, while the dissociation constant for 17 beta-estradiol (E2) is 0.42 nM. From this ratio of binding affinities, one would expect some agonist or antagonist activity of 2-OHE1 to be apparent at doses roughly 20-50 times the minimum effective dose of E2. Instead, at doses of 2-OHE1 1000 times an effective dose of E2, no uterotropic effect was observed. When 2-OHE1 was injected together with E2 at dose ratios of 500:1, there was no antagonism of the effect of E2. To examine this discrepancy, the plasma MCRs (MCRpS) of E2 and 2-OHE1 were determined by continuous infusion techniques. Plasma concentrations of 2-OHE1 and E2 during control and infusion periods were measured by RIAs. The MCRp of 2-OHE1 averaged 50,000 ml/h, more than 100 times that of E2 (approximately 400 ml/h). The extraordinarily high MCRp of 2-OHE1 may explain the failure to observe any biological effects of this catechol estrogen, even at high doses. This rapid metabolism, presumably occurring in the blood compartment, should be considered in handling blood samples for RIA and in devising studies of the actions of catechol estrogens.


Cardiac vagal control in the severity and course of depression: the importance of symptomatic heterogeneity.
Impaired cardiac vagal control (CVC), as indexed by respiratory sinus arrhythmia, has been investigated as a risk factor for major depressive disorder (MDD), but prior findings are mixed with respect to whether impaired CVC predicts greater global depression severity and/or a more severe course of disorder. One possible explanation for mixed findings is that CVC abnormalities in MDD are related more closely to specific depression symptoms than to the syndrome as a whole. Depression severity (both global and symptom-specific indices) and electrocardiogram measures of resting CVC were obtained from 151 diagnosed MDD participants at intake, before randomization to a novel treatment for depression (acupuncture), and again after 8 and 16 weeks. Resting CVC did not predict global indices of depression in cross-sectional or longitudinal analyses. In symptom-specific analyses, resting CVC was positively related to sad mood and crying and inversely related to middle and late insomnia. Improvement in late insomnia was related to increases in CVC over time. Relationships between CVC and MDD were studied only within the clinical range of severity. Symptom analyses were exploratory and hence did not correct for Type I error. Resting CVC did not exhibit concurrent or prospective relations with overall depression severity but a few specific symptoms did. Symptomatic heterogeneity across samples may account for mixed findings within the CVC-depression literature.


Nondigestible oligosaccharides enhance bacterial colonization resistance against Clostridium difficile in vitro.
Clostridium difficile is the principal etiologic agent of pseudomembranous colitis and is a major cause of nosocomial antibiotic-associated diarrhea. A limited degree of success in controlling C. difficile infection has been achieved by using probiotics; however, prebiotics can also be used to change bacterial community structure and metabolism in the large gut, although the effects of these carbohydrates on suppression of clostridial pathogens have not been well characterized. The aims of this study were to investigate the bifidogenicity of three nondigestible oligosaccharide (NDO) preparations in normal and antibiotic-treated fecal microbiotas in vitro and their abilities to increase barrier resistance against colonization by C. difficile by using cultural and molecular techniques. Fecal cultures from three healthy volunteers were challenged with a toxigenic strain of C. difficile, and molecular probes were used to monitor growth of the pathogen, together with growth of bifidobacterial and bacteroides populations, over a time course. Evidence of colonization resistance was assessed by determining viable bacterial counts, short-chain fatty acid formation, and cytotoxic activity. Chemostat studies were then performed to determine whether there was a direct correlation between bifidobacteria and C. difficile suppression. NDO were shown to stimulate bifidobacterial growth, and there were concomitant reductions in C. difficile populations. However, in the presence of clindamycin, activity against bifidobacteria was augmented in the presence of NDO, resulting in a further loss of colonization resistance. In the absence of clindamycin, NDO enhanced colonization resistance against C. difficile, although this could not be attributed to bifidobacterium-induced inhibitory phenomena.


The Impact of Early Robotics Education on Students' Understanding of Coding, Robotics Design, and Interest in Computing Careers.
Early robotics education has been sparsely researched, especially for children in elementary education. This research pertains to an early education study that introduced robotics design and programming to children in early education with the purpose of increasing their robotics design knowledge, improving their coding skills, and inspiring their aspirations for future careers. It represents a seven-year study of students ages seven through ten years in a large urban school district. The study engaged a pre-post program comparison of the robotics and coding intervention that focused on children's improved understanding of robotics in addition to their career aspirations. The study resulted in increases in the participating students' understanding of robotics design as well as improved coding skills in robotics contexts. Furthermore, the study also led to increases in the students' career aspirations toward computing fields.


Perceptual space in the dark affected by the intrinsic bias of the visual system.
Correct judgment of egocentric/absolute distance in the intermediate distance range requires both the angular declination below the horizon and ground-surface information being represented accurately. This requirement can be met in the light environment but not in the dark, where the ground surface is invisible and hence cannot be represented accurately. We previously showed that a target in the dark is judged at the intersection of the projection line from the eye to the target that defines the angular declination below the horizon and an implicit surface. The implicit surface can be approximated as a slant surface with its far end slanted toward the frontoparallel plane. We hypothesize that the implicit slant surface reflects the intrinsic bias of the visual system and helps to define the perceptual space. Accordingly, we conducted two experiments in the dark to further elucidate the characteristics of the implicit slant surface. In the first experiment we measured the egocentric location of a dimly lit target on, or above, the ground, using the blind-walking-gesturing paradigm. Our results reveal that the judged target locations could be fitted by a line (surface), which indicates an intrinsic bias with a geographical slant of about 12.4 degrees. In the second experiment, with an exocentric/relative-distance task, we measured the judged ratio of aspect ratio of a fluorescent L-shaped target. Using trigonometric analysis, we found that the judged ratio of aspect ratio can be accounted for by assuming that the L-shaped target was perceived on an implicit slant surface with an average geographical slant of 14.4 degrees. That the data from the two experiments with different tasks can be fitted by implicit slant surfaces suggests that the intrinsic bias has a role in determining perceived space in the dark. The possible contribution of the intrinsic bias to representing the ground surface and its impact on space perception in the light environment are also discussed.


Nonactive antenna compensation for fixed-array microwave imaging: Part II--Imaging results.
Model-based imaging techniques utilizing microwave signal illumination rely heavily on the ability to accurately represent the wave propagation with a suitable numerical model. To date, the highest quality images from our prototype system have been achieved utilizing a single transmitter/single receiver measurement system where both antennas are manually repositioned to facilitate multiple illuminations of the imaging region, thus requiring long data acquisition times. In an effort to develop a system that can acquire data in a real time manner, a 32-channel network has been fabricated with all ports capable of being electronically selected for either transmit or receive mode. The presence of a complete array of antenna elements at data collection time perturbs the field distributions being measured, which can subsequently degrade the image reconstruction due to increased data-model mismatch. Incorporating the nonactive antenna-compensation model from Part I of this paper into our hybrid element near field image reconstruction algorithm is shown to restore image quality when fixed antenna-array data acquisition is used. Improvements are most dramatic for inclusions located in near proximity to the antenna array itself, although cases of improvement in the recovery of centered heterogeneities are also illustrated. Increases in the frequency of illumination are found to warrant an increased need for nonactive antenna compensation. Quantitative measures of recovered inclusion shape and position reveal a systematic improvement in image reconstruction quality when the nonactive antenna-compensation model is employed. Improvements in electrical property value recovery of localized heterogeneities are also observed. Image reconstructions in freshly excised breast tissue illustrate the applicability of the approach when used with our two-dimensional microwave imaging system.


Helping Alliance and Unmet Needs in Routine Care of People With Severe Mental Illness Across Europe: A Prospective Longitudinal Multicenter Study.
The helping alliance (HA) refers to the collaborative bond between patient and therapist, including shared goals and tasks. People with severe mental illness have a complex mixture of clinical and social needs. Using mixed-effects regression, this study examined in 588 people with severe mental illness whether an increase in the HA is associated with fewer unmet needs over time, and whether change in the HA precedes change in unmet needs. It was found that a reduction in unmet needs was slower in patients with higher HA (B = 0.04, p < 0.0001) only for patient-rated measures. Improvement in both patient-rated and staff-rated HA over time was associated with fewer subsequent patient-rated (B = -0.10, p < 0.0001) and staff-rated (B = -0.08, p = 0.0175) unmet needs. With positive changes in the HA preceding fewer unmet needs, findings provide further evidence for a causal relationship between alliance and outcome in the treatment of people with severe mental illness.


Use of Gen-Probe AccuProbe Group B streptococcus test to detect group B streptococci in broth cultures of vaginal-anorectal specimens from pregnant women: comparison with traditional culture method.
Detection of vaginal-anorectal colonization with group B streptococci (GBS) is critical to the prevention of neonatal GBS disease. The recommended method for the detection of GBS is culture of the distal vagina and anorectum in a selective broth medium followed by subculture to solid media and identification of GBS on the solid media. The purpose of this study was to compare this standard culture method with the detection of GBS directly from an enrichment broth by utilizing the Gen-Probe AccuProbe Group B Streptococcus Culture Identification Test (GPGB). A total of 502 specimens were tested in this study. Both culture and the GPGB detected 90 of 95 positive specimens (sensitivity, 94.7%). There were two false-positive GPGB results (specificity, 99.5%). An analysis of 100 consecutive specimens was performed to compare the costs associated with the use of a primary tryptic soy agar plate with 5% sheep blood (BAP) and a 3-ml tube of Todd-Hewitt broth supplemented with 10 micrograms of nalidixic acid per ml and 15 micrograms of colistin per ml (LIM broth) with subculture to another BAP and the costs associated with the GPGB. Our estimated costs were $3.68 for a negative culture including 7.0 min of labor, $5.41 for a positive culture including 8.9 min of labor, and $5.16 for the GPGB including 3.6 min of labor (based upon a test run of 10 specimens and two controls and a cost of $70.00 for a 20-test GPGB kit). Accessioning and reporting of results are not included in these costs. In conclusion, we found that the GPGB was equivalent in sensitivity to our standard culture method. While overall costs were somewhat higher for the GPGB, the GPGB has lower labor costs and offers the potential for incremental savings with higher test volumes and computer interface capability.


Vaccine-Mediated Activation of Human TLR4 Is Affected by Modulation of Culture Conditions during Whole-Cell Pertussis Vaccine Preparation.
The potency of whole-cell pertussis (wP) vaccines is still determined by an intracerebral mouse protection test. To allow development of suitable in vitro alternatives to this test, insight into relevant parameters to monitor the consistency of vaccine quality is essential. To this end, a panel of experimental wP vaccines of varying quality was prepared by sulfate-mediated suppression of the BvgASR master virulence regulatory system of Bordetella pertussis during cultivation. This system regulates the transcription of a range of virulence proteins, many of which are considered important for the induction of effective host immunity. The protein compositions and in vivo potencies of the vaccines were BvgASR dependent, with the vaccine containing the highest amount of virulence proteins having the highest in vivo potency. Here, the capacities of these vaccines to stimulate human Toll-like receptors (hTLR) 2 and 4 and the role these receptors play in wP vaccine-mediated activation of antigen-presenting cells in vitro were studied. Prolonged BvgASR suppression was associated with a decreased capacity of vaccines to activate hTLR4. In contrast, no significant differences in hTLR2 activation were observed. Similarly, vaccine-induced activation of MonoMac-6 and monocyte-derived dendritic cells was strongest with the highest potency vaccine. Blocking of TLR2 and TLR4 showed that differences in antigen-presenting cell activation could be largely attributed to vaccine-dependent variation in hTLR4 signalling. Interestingly, this BvgASR-dependent decrease in hTLR4 activation coincided with a reduction in GlcN-modified lipopolysaccharides in these vaccines. Accordingly, expression of the lgmA-C genes, required for this glucosamine modification, was significantly reduced in bacteria exposed to sulfate. Together, these findings demonstrate that the BvgASR status of bacteria during wP vaccine preparation is critical for their hTLR4 activation capacity and suggest that including such parameters to assess consistency of newly produced vaccines could bring in vitro testing of vaccine quality a step closer.


Grasping and dissecting instrument for hand-assisted laparoscopic surgery: development and early clinical experience.
The operative potential of hand-assisted laparoscopic surgery (HALS) could be enhanced by the introduction of a new generation of assisting instruments. These tools will have to meet specific requirements of shape, function, and safety of use. Problems related to the working environment of HALS and deriving projectual restrictions of HALS instruments were analyzed in order to develop and manufacture a working prototype with grasping and dissecting properties to assist during HALS procedures. The resulting instrument was mechanically and clinically tested in 22 HALS procedures. The additional benefit of the new device was particularly appreciated during dissection and isolation of vascular pedicles (nephrectomies and splenectomies). It was shown to be safe and effective in providing the additional assistance it was designed for. The described grasping and dissecting instrument for HALS is of great value in assisting the surgeon during fine dissection, as required in selected procedures. New generation of HALS instruments should comply with the functional and safety issues analyzed in this report.


The role of Schlemm's canal in aqueous outflow from the human eye.
A mathematical model of Schlemm's canal is developed to simulate collapse of the canal and its effect on resistance to flow through the aqueous outflow network. Schlemm's canal is modeled as a porous, compliant channel that is held open by the trabecular meshwork. The trabecular meshwork is modeled as a series of linear springs that allow the inner wall of Schlemm's canal to deform in proportion to the local pressure drop across it. Based on comparisons between the model and results in the literature, the following tentative conclusions are reached: (1) Most of the resistance in the aqueous outflow network occurs in the inner wall of Schlemm's canal. (2) Glaucoma is not caused by a weakening of the trabecular meshwork and a resultant collapse of Schlemm's canal alone. Instead, glaucoma probably results from an increased flow resistance of the inner wall of the canal.


Metabolomics in epidemiology: from metabolite concentrations to integrative reaction networks.
Metabolomics is becoming feasible for population-scale studies of human disease. In this review, we survey epidemiological studies that leverage metabolomics and multi-omics to gain insight into disease mechanisms. We outline key practical, technological and analytical limitations while also highlighting recent successes in integrating these data. The use of multi-omics to infer reaction rates is discussed as a potential future direction for metabolomics research, as a means of identifying biomarkers as well as inferring causality. Furthermore, we highlight established analysis approaches as well as simulation-based methods currently used in single- and multi-cell levels in systems biology.


[Finite element analysis of an additional implant for intramedullary nailing].
In the surgical treatment of fractured femurs, the fracture is bridged by a medullary nail fixed in the bone with interlocking screws. Failure of bone substance in the region of the interlocking screws is the most common complication in the treatment of osteoporotic bone. With the aim of preventing this complication, an additional implant was developed. A finite element analysis of an ideal bone/implant system was carried out to investigate the role of the additional implant. Three defined finite element models were generated, and the associated stress situations compared. The first model is a standard fixation without the additional implant. In the second model, the additional implant is integrated within the bone/implant system. The third model uses a modified form of the additional implant. The results show that both additional implants reduce the stresses occurring, both in the bone substance and at the screws. The modified form of the additional implant proved to be the most favorable version. In the case of the original additional implant, the negative effect of the sharp edges of the thread was demonstrable.


Efficacy of neem seed extract shampoo on head lice of naturally infected humans in Egypt.
Sixty heavily lice-infested male and female children (4-15 years) were selected and subjected to the treatment with a neem seed extract shampoo. Twenty to thirty milliliter of the shampoo were thoroughly mixed with completely wet hair and rubbed in to reach the skin of the scalp. After 5, 10, 15 and 30 min, the shampoo was washed out and the hair basically combed. Head lice were collected and examined. The neem seed extract shampoo proved to be highly effective against all stages of head lice. No obvious differences regarding the efficacy of the shampoo were observed between an exposure time of 10, 15 or 30 min. No side effects, such as skin irritation, burning sensations, or red spots on the scalp, forehead or neck, respectively, were observed.


Multi-Fading Factor and Updated Monitoring Strategy Adaptive Kalman Filter-Based Variational Bayesian.
Aiming at the problem that the performance of adaptive Kalman filter estimation will be affected when the statistical characteristics of the process and measurement of the noise matrices are inaccurate and time-varying in the linear Gaussian state-space model, an algorithm of multi-fading factor and an updated monitoring strategy adaptive Kalman filter-based variational Bayesian is proposed. Inverse Wishart distribution is selected as the measurement noise model and the system state vector and measurement noise covariance matrix are estimated with the variational Bayesian method. The process noise covariance matrix is estimated by the maximum a posteriori principle, and the updated monitoring strategy with adjustment factors is used to maintain the positive semi-definite of the updated matrix. The above optimal estimation results are introduced as time-varying parameters into the multiple fading factors to improve the estimation accuracy of the one-step state predicted covariance matrix. The application of the proposed algorithm in target tracking is simulated. The results show that compared with the current filters, the proposed filtering algorithm has better accuracy and convergence performance, and realizes the simultaneous estimation of inaccurate time-varying process and measurement noise covariance matrices.


Parish nursing: advancing practice nursing. Model for healthier communities.
Advanced practice nurses (APNs) in the community are in a prime position to respond to the changing health care environment stimulated by health care reform. An emerging practice model for APNs is parish nursing, community-based nursing practice set in communities of faith. Parish nursing stimulates shared public-private partnerships and is a consumer-oriented delivery system. The article describes the models, context, and practice of parish nursing, emphasizing the problem of evaluating outcomes. It also discusses implications for research and education. Parish nursing is a significant practice model affording APNs the opportunity to contribute to healthier communities.


ECT is generally regarded as a safe and efficient treatment. In this case report, a 76-year-old female patient did not wake up as expected after ECT. The patient was transferred to the emergency department, and a CT-scan showed an intracerebral haemorrhage. She died within two days of the event, and an autopsy confirmed the diagnosis and did not reveal any underlying cerebral pathology.


A study of prospective surveillance for inhibitors among persons with haemophilia in the United States.
Inhibitors are a rare but serious complication of treatment of patients with haemophilia. Phase III clinical trials enrol too few patients to adequately assess new product inhibitor risk. This project explores the feasibility of using a public health surveillance system to conduct national surveillance for inhibitors. Staff at 17 U.S. haemophilia treatment centres (HTC) enrolled patients with haemophilia A and B into this prospective study. HTC staff provided detailed historic data on product use and inhibitors at baseline, and postenrolment patients provided monthly detailed infusion logs. A central laboratory performed inhibitor tests on blood specimens that were collected at baseline, annually, prior to any planned product switch or when clinically indicated. The central laboratory also performed genotyping of all enrolled patients. From January 2006 through June 2012, 1163 patients were enrolled and followed up for 3329 person-years. A total of 3048 inhibitor tests were performed and 23 new factor VIII inhibitors were identified, 61% of which were not clinically apparent. Infusion logs were submitted for 113,205 exposure days. Genotyping revealed 431 distinct mutations causing haemophilia, 151 of which had not previously been reported elsewhere in the world. This study provided critical information about the practical issues that must be addressed to successfully implement national inhibitor surveillance. Centralized testing with routine monitoring and confirmation of locally identified inhibitors will provide valid and representative data with which to evaluate inhibitor incidence and prevalence, monitor trends in occurrence rates and identify potential inhibitor outbreaks associated with products.


Amino acid transport systems in bovine mammary tissue.
Nutrient provision to the lactating mammary gland involves three factors: blood nutrient concentration, blood flow, and cellular uptake. This paper reviews uptake of amino acids by bovine mammary tissue relative to interorgan blood flows, red blood cell contribution, arteriovenous differences, specific mammary amino acid transport systems, and glutathione and gamma-glutamyl transpeptidase. Recent studies with ruminant amino acid blood fluxes and the role of the red blood cell in providing nitrogenous substrates to tissues have brought to light new considerations of nutrient availability to mammary tissue. Previous studies measured arteriovenous differences to quantitate net amino acid uptake. These studies are considered relative to seven specific and separate amino acid transport systems, some of which have been identified in bovine mammary tissue. Uptake of sulfur amino acids by mammary tissue has been of interest because it appeared that insufficient quantities were provided during lactation. Glutathione, a tripeptide, may be a principle source of cysteine to mammary tissue via mechanisms involving gamma-glutamyl transpeptidase, glutathione, and red blood cells. The paper considers these mechanisms in relationship to amino acid transport systems.


Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes.
A novel transferrin receptor (TfR)-targeted liposomal formulation was synthesized and evaluated for the delivery of a phosphorothioate antisense oligodeoxyribonucleotide (ODN) (G3139, oblimerson sodium, or Genasense) to Bcl-2 in K562 leukemia cells. Liposomes composed of DC-Chol/egg PC/PEG-DSPE (25:73.5:1.5, mol/mol/mol) were loaded with G3139 with high efficiency (70-80%). To prepare targeted liposomes, transferrin was first coupled to PEG-DSPE and then incorporated into the bilayer by post-insertion. The liposomes had a mean diameter of 100 to 150 nm and exhibited colloidal stability for up to 8 weeks. Uptake of Tf-conjugated G3139-containing liposomes in TfR positive K562 cells was found to be more efficient than that of the non-targeted control formulation and could be blocked by excess free Tf. Treatment with Tf-conjugated liposomes resulted in Bcl-2 protein downregulation in K562 cells that was approximately 2-fold greater than with non-targeted liposomes (p<0.05) and 10-fold greater than with free G3139. Treatment with 2 microM G3139 in Tf-conjugated liposomes resulted in >80% reduction in Bcl-2 transcript. In addition, Tf-conjugated liposomal G3139-sensitized K562 cells to daunorubicin, lowering IC50 from 1.8 microM to 0.18 microM. In conclusion, Tf-conjugated liposomes are effective delivery vehicles for G3139 antisense oligos in TfR positive K562 cells and warrant further investigation as an in vivo oligo delivery vehicle.


[Morphogenetic function of the nuclei in the early development of the common freshwater snail, Limnaea stagnalis].
The early embryos L. stagnalis were placed in the actinomycin solution at the successive developmental stages. The permeability to actinomycin was previously increased by the pricking through egg capsules. The inactivation of nuclei by actinomycin up to the stage of 12 blastomeres resulted in the arrest of development at the 22 cell stage. The inactivation of nuclei at the subsequent development stages resulted in the developmental arrest at later stages. These data suggest that the embryonic development up to the 22 cell stage is provided by the nuclear function during oogenesis. The morphogenetic nuclear function of the embryo begins at the stage of 12 blastomeres and provides the embryonic development beyond the 22 cell stage.


Human walking along a curved path. I. Body trajectory, segment orientation and the effect of vision.
Task-related characteristics of gait and segment orientation during natural locomotion along a curved path have been described in order to gain insight into the neural organization of walking. The locomotor task implied continuous deviation from straight-ahead, thereby requiring continuous adjustment of body movement to produce and assist turn-related torques. Performance was compared to straight-ahead locomotion. Subjects easily reproduced both trajectories with eyes open (EO). The actual-to-required trajectory difference increased blindfolded (BF), more so during turning. Stride length was unchanged for the outer but decreased for the inner leg. The feet anticipated subsequent body rotation by pivoting toward the inner side of the curve at heel strike. A shift of body centre of mass and trunk roll toward the inner side accompanied turning. The head turned more than dictated by the heading change, and the absolute range of yaw oscillation increased. Head yaw anticipated body yaw by approximately 200 ms. Despite the minor effect of vision on the behaviour of all other segments, a difference in head pitch occurred between EO and BF; with EO, the head was flexed (P < 0.01), as to look at the path, while pitch was negligible with BF. In general, the changes in the amplitude of head, trunk and feet movements proved to be well related to the kinematics of the steering body, and constituted a sort of basic library of motor synergies.


Familial cavernous hemangioma: An expanding ocular spectrum.
To describe the clinical and genetic findings in a family with multiple cases of cavernous hemangiomas. Investigational clinical and genetic study in which 3 generations of a family consisting of 12 members were screened with magnetic resonance brain imaging, dilated ophthalmoscopic examination, and cutaneous survey coupled with linkage analysis to determine affected individuals and to better define manifestations of this neuro-oculo-cutaneous syndrome. The proband had multiple cerebral cavernous hemangiomas and a choroidal hemangioma. Her son was found to harbor a retinal cavernous hemangioma. The proband's sister manifested a cerebral cavernous hemangioma, cutaneous hemangiomas, and a presumed choroidal hemangioma; her daughter demonstrated radiological findings suggestive of a cerebral cavernous hemangioma. The father of the proband demonstrated multiple, cutaneous hemangiomas. The remaining family members were free of lesions. The 7q locus could not be excluded as harboring the causative gene. This family may have a dominantly inherited neuro-oculo-cutaneous condition of cavernous hemangiomas with variable expressivity. The presence of choroidal hemangiomas in this phacomatosis has not been described previously to our knowledge. The presence of either retinal cavernous or choroidal hemangioma should alert the physician to search for features suggestive of systemic and familial involvement; either lesion may constitute the ocular component of the neuro-oculo-cutaneous phacomatosis, sometimes referred to as cavernoma multiplex. Arch Ophthalmol. 2000;118:969-973


Development of porcine embryos in vivo and in vitro; evidence for embryo 'cross talk' in vitro.
The in vitro development of zygotes of domestic species to the blastocyst stage is facilitated by culture in groups, suggesting a role for autocrine/paracrine factors. A novel method was used to investigate the potential role of such factors using in-vitro-produced and in-vivo-derived porcine embryos. The development of individual zygotes to the blastocyst stage was optimal when they were cultured 81-160 mum apart. As the distance between the embryos was increased, blastocyst rates declined significantly, reaching zero beyond 640 mum. Blastocyst volume and cell number (both inner cell mass and trophectoderm) were also increased when the distance apart was between 81 and 160 mum. Culturing embryos in groups at different stages of development suggested that group culture confers a greater advantage to development after the activation of the genome. Group culture of in-vivo-derived embryos showed a weak distance effect. The results suggest a role for as yet unknown diffusible paracrine/autocrine factors released by early porcine embryos in promoting the growth of neighbouring embryos in vitro. This advantage is observed to a lesser extent by in-vivo-derived zygotes which are likely to have been better conditioned for development in vitro by being conceived in the female reproductive tract.


The longitudinal study of chronic sarcoidosis.
Although spontaneous remissions are frequent in sarcoidosis, chronic persistent disabling disease is also observed. This feature seems more frequent and more severe in black patients, as has been previously reported (10). The more extensive and severe the initial disease manifestations, the more likely it is that the disease will continue. Corticosteroids are usually beneficial and complications are infrequent. Delayed or interrupted treatment seems to allow progression or irreversible disease or both. Patient compliance is an obvious important factor. Relapses are frequent as treatment is withdrawn but are usually at least partially reversible. Some deterioration is observed with repeated relapses. Low dose daily prednisone (5-15 mg) seems to prevent relapses. Patient compliance is facilitated with daily treatment rather than alternate day therapy. Prolonged treatment for 10 to 15 or more years is often required. Chloroquine is particularly helpful in skin and mucosal disease. The necessity for long-term thoughtful management is obvious.


Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression.
We used total lymphoid irradiation (TLI; total dose = 3400 rad) to treat the lupus-like renal disease of 6-mo-old female NZB/NZW mice. Similar to our past studies, this treatment resulted in a marked prolongation of survival, decrease in proteinuria, and decrease in serum anti-DNA antibodies compared with untreated littermate controls. Although there was no evidence of disease recurrence in TLI-treated mice until after 12 mo of age, the in vitro proliferative response to phytohemagglutinin by NZB/NZW spleen cells recovered within 6 wk such that responses were greater than control NZB/NZW animals. A similar recovery and overshoot after TLI were evident in the primary antibody response to the T cell-dependent antigen sheep red blood cells (SRBC). Both the total and IgG anti-SRBC antibody responses after TLI were greater than those of untreated NZB/NZW controls, and were comparable with those of untreated non-autoimmune mice. Despite this increased response to mitogens and antigens after TLI, we noted a decrease in spontaneous splenic IgG-secreting cells and a decrease in IgG but not IgM antinuclear antibody production. Nonspecific suppressor cells of the mixed leukocyte response were detectable in the spleens of NZB/NZW mice early after TLI. However, the disappearance of suppressor cells was not associated with recrudescence of disease activity. Furthermore, transfer of large numbers of spleen cells from TLI-treated NZB/NZW mice did not result in disease suppression in untreated age-matched recipients. In summary, treatment of NZB/NZW mice with TLI results in a prolonged remission in autoimmune disease, which is achieved in the absence of generalized immunosuppression.


Compartment syndrome surgical management techniques associated with tibial plateau fractures.
Compartment syndrome is an orthopaedic emergency that can be challenging to diagnose and manage when associated with a tibial plateau fracture. This technique article discusses one- and two-incision fasciotomy surgical techniques, and the surgical decision making and technique modifications when there is an associated tibial plateau fracture.


Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts.
The architecture and structural mechanics of the cell nucleus are defined by the nuclear lamina, which is formed by A- and B-type lamins. Recently, gene duplication and protein overexpression of lamin B1 (LB1) have been reported in pedigrees with autosomal dominant leukodystrophy (ADLD). However, how the overexpression of LB1 affects nuclear mechanics and function and how it may result in pathology remain unexplored. Here, we report that in primary human skin fibroblasts derived from ADLD patients, LB1, but not other lamins, is overexpressed at the nuclear lamina and specifically enhances nuclear stiffness. Transient transfection of LB1 in HEK293 and neuronal N2a cells mimics the mechanical phenotype of ADLD nuclei. Notably, in ADLD fibroblasts, reducing LB1 protein levels by shRNA knockdown restores elasticity values to those indistinguishable from control fibroblasts. Moreover, isolated nuclei from ADLD fibroblasts display a reduced nuclear ion channel open probability on voltage-step application, suggesting that biophysical changes induced by LB1 overexpression may alter nuclear signaling cascades in somatic cells. Overall, the overexpression of LB1 in ADLD cells alters nuclear mechanics and is linked to changes in nuclear signaling, which could help explain the pathogenesis of this disease.


Care-seeking in the development of severe community acquired pneumonia in Ugandan children.
Improved case management of paediatric pneumonia is recognised as a key strategy for pneumonia control. Since symptoms of pneumonia and malaria often overlap, there are concerns that children with pneumonia are treated with antimalarial drugs. There is a need to describe how children with severe pneumonia have been managed prior to their arrival at hospital, including possible risks of developing more severe disease. A case-series study of 140 children, aged 2-59 months, with severe radiologically verified pneumonia at Mulago Hospital, Kampala was undertaken. Caretakers were interviewed about initial symptoms, treatment given and care sought. Using WHO definitions, children were clinically classified as having severe or very severe pneumonia. The children had been ill for a median of 7 days before arrival at hospital, 90/140 (64%) had received treatment at home, and 72/140 (51%) had seen another health-care provider prior to presentation at hospital. Altogether, 32/140 (23%) children had reportedly received antibiotics only prior to admission, 18/140 (13%) had received anti-malarials only and 35/140 (25%) had received both. Being classified as very severe pneumonia was more common among children who had received anti-malarials only (OR 5.5, 1.8-16.4). Although the majority of caretakers were able to recognise the key symptoms of pneumonia, they did not respond with any immediate care-giving action. Since progression from first recognition of pneumonia symptoms to severe disease is rapid, management guidelines regarding timing of care-seeking need to be clearly defined. The reason why children who sought health facility care failed to improve should be investigated. Meanwhile, there is a need to increase caretakers' and health workers' awareness of the urgency to act promptly when key pneumonia symptoms are observed.


A unified scaling model for flow through a lattice of microfabricated posts.
A scaling model is presented for low Reynolds number viscous flow within an array of microfabricated posts. Such posts are widely used in several lab-on-a-chip applications such as heat pipes, antibody arrays and biomolecule separation columns. Finite element simulations are used to develop a predictive model for pressure driven viscous flow through posts. The results indicate that the flow rate per unit width scales as approximately h1.17g1.33/d0.5 where h is the post height, d post diameter and g is the spacing between the posts. These results compare favorably to theoretical limits. The scaling is extended to capillary pressure driven viscous flows. This unified model is the first report of a scaling that incorporates both viscous and capillary forces in the microfabricated post geometry. The model is consistent with Washburn dynamics and was experimentally validated to within 8% using wetting on microfabricated silicon posts.


Imbalanced kynurenine pathway in schizophrenia.
Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls (P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.


Genetic and biological characterization of Newcastle disease viruses circulating in Bangladesh during 2010-2017: further genetic diversification of class II genotype XIII in Southcentral Asia.
Newcastle disease virus (NDV) is endemic in Bangladesh and is a major threat to commercial poultry operations. While complete fusion (F) genes are recommended for molecular characterization and classification of NDV isolates, heretofore, only partial F gene data have been available for Bangladeshi NDVs. To this end, we obtained the full-length F gene coding sequences of 11 representative NDVs isolated in Bangladesh between 2010 and 2017. In addition, one of the viruses (MK934289/chicken/Bangladesh/C161/2010) was used in an experimental infection of chickens to establish the viral pathotype and study gross and microscopic lesions. Phylogenetic analysis provided evidence that all studied Bangladeshi isolates belong to genotype XIII.2 of class II NDVs. Six of the viruses were isolated between 2010 and 2017 and grouped together with isolates from neighbouring India during 2013-2016. Another four Bangladeshi isolates (2010-2016) formed a separate monophyletic branch within XIII.2 and showed high nucleotide distance from the isolates from India and the other six Bangladeshi viruses within the sub-genotype; however, none of these groups fulfils all classification criteria to be named as a separate sub-genotype. The eleventh Bangladeshi virus studied here (C162) was genetically more distant from the remaining isolates. It out-grouped the viruses from sub-genotypes XIII.2.1 and XIII.2.2 and showed more than 9.5 % nucleotide distance from all genotype XIII sub-genotypes. This isolate may represent an NDV variant that is evolving independently from the other viruses in the region. The experimental infection in chickens revealed that the tested isolate (C161) is a velogenic viscerotropic virus. Massive haemorrhages, congestion and necrosis in different visceral organs, and lymphoid depletion in lymphoid tissues, typical for infection with velogenic NDV, were observed. Our findings demonstrate the endemic circulation of sub-genotype XIII.2 in Southcentral Asia and further genetic diversification of these viruses in Bangladesh and neighbouring India. This constant evolution of the viruses may lead to the establishment of new genetic groups in the region. Additional historical and prospective virus and surveillance data from the region and neighbouring countries will allow a more detailed epidemiological inference.


Pharmacokinetic/pharmacodynamic modelling of ciprofloxacin 250 mg/12 h versus 500 mg/24 h for urinary infections.
A simulation study was performed to evaluate and compare the standard dosage regimen of 250 mg/12 h versus 500 mg/24 h of ciprofloxacin for the treatment of urinary tract infections (UTIs). Pharmacokinetic parameters reported for healthy young and old individuals were used for the simulation of drug levels in urine, at different mean urine flow rates (1-2.5 L/day). Pharmacokinetic/pharmacodynamic analysis of the results revealed that 500 mg ciprofloxacin once a day produced a more favourable profile in urine than 250 mg/12 h, particularly in the elderly, due to the slower elimination of the drug in this group of patients. Circadian rhythms were also considered for the simulation of drug levels in urine. According to the results, 500 mg once a day administered in the morning would be a better choice than 250 mg/12 h at least for uncomplicated UTI; nevertheless, clinical assays are needed to prove this hypothesis.


Drug disposition in obesity and protein-energy malnutrition.
Clinical response to medication can differ between patients. Among the known sources of variability is an individual's nutrition status. This review defines some pharmacokinetic terms, provides relevant body size metrics and describes the physiologic influences of protein-energy malnutrition and obesity on drug disposition. Weight-based drug dosing, which presumes a healthy BMI, can be problematic in the protein-energy malnourished or obese patient. The use of total body weight, lean body weight, or an adjusted body weight depends on the drug and how it is differently handled in malnutrition or obesity. Most of the recognized influences are seen in drug distribution and drug elimination as a result of altered body composition and function. Distribution characteristics of each drug are determined by several drug-related factors (e.g. tissue affinity) in combination with body-related factors (e.g. composition). Drug elimination occurs through metabolic and excretory pathways that can also vary with body composition. The current data are limited to select drugs that have been reported in small studies or case reports. In the meantime, a rational approach to evaluate the potential influences of malnutrition and obesity can be used clinically based on available information. Antimicrobials are discussed as a useful example of this approach. Further advancement in this field would require collaboration between experts in body composition and those in drug disposition. Until more data are available, routine monitoring by the clinician of the protein-energy malnourished or obese patient receiving weight-based drug regimens is necessary.


[Comparative study of the energy metabolic enzymatic activity of pigmented and pigment-free strains of Serratia marcescens].
The activity of enzymes involved in energy metabolism was investigated in the pigmented strain of Serratia marcescens and in its pigmentless variant with an elevated activity of nuclease. The pigmentless strain was found to exhibit a higher specific activity of several enzymes participating in glycolysis, the pentose phosphate cycle, and the citric acid cycle. The pigmentless strain accumulated lesser amounts of lactic acid in the medium and was characterized by the negative Voges--Proskauer reaction.


Sexual dimorphism in base of skull.
Sex determination is an important task in forensic medicine and physical anthropology. The aims of this study were to assess the presence of sexual dimorphism in the base of the skull and to compare the accuracy of sex estimation by this method with that achieved in other metric studies of this region. The sample comprised 109 individuals (53 males and 56 females) of known sex, age, and cause of death from San José cemetery in Granada (Spain). Six dimensions were analyzed and discriminant function analysis was performed. The discriminant capacity of the selected variables was then evaluated by using a cross-validation procedure. All dimensions were significantly higher in males than in females. The percentage accuracy was 75.7% (77.8% for males and 73.7% for females). Highest dimorphic values were for occipital condyle length and foramen magnum width. Skull base measurements should only serve to corroborate findings.


A Complete Color Normalization Approach to Histopathology Images Using Color Cues Computed From Saturation-Weighted Statistics.
In digital histopathology, tasks of segmentation and disease diagnosis are achieved by quantitative analysis of image content. However, color variation in image samples makes it challenging to produce reliable results. This paper introduces a complete normalization scheme to address the problem of color variation in histopathology images jointly caused by inconsistent biopsy staining and nonstandard imaging condition. Method : Different from existing normalization methods that either address partial cause of color variation or lump them together, our method identifies causes of color variation based on a microscopic imaging model and addresses inconsistency in biopsy imaging and staining by an illuminant normalization module and a spectral normalization module, respectively. In evaluation, we use two public datasets that are representative of histopathology images commonly received in clinics to examine the proposed method from the aspects of robustness to system settings, performance consistency against achromatic pixels, and normalization effectiveness in terms of histological information preservation. As the saturation-weighted statistics proposed in this study generates stable and reliable color cues for stain normalization, our scheme is robust to system parameters and insensitive to image content and achromatic colors. Extensive experimentation suggests that our approach outperforms state-of-the-art normalization methods as the proposed method is the only approach that succeeds to preserve histological information after normalization. The proposed color normalization solution would be useful to mitigate effects of color variation in pathology images on subsequent quantitative analysis.