Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records.
Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8-9 and a 5-min Apgar score of 9-10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. Hubei Science and Technology Plan, Wuhan University Medical Development Plan.


Functional and Developmental Analysis of CD4(+)CD25(+) Regulatory T Cells under the Influence of Streptococcal M Protein in Rheumatic Heart Disease.
The purpose of this study was to determine the role of streptococcal M protein in naturally-occurring CD4(+)CD25(+) regulatory T cells (nTregs) function and development in rheumatic heart disease in Iraqi patients. Streptococcus pyogenes was isolated for subsequent M protein extraction. Also, peripheral blood nTregs and CD4(+) T cells were isolated by using Magnetic Cell Separation System. Tissue culture for isolated cells was performed in the presence and absence of M protein. Cell count was performed, and tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4) were determined in culture supernatant using ELISA system. There was a significant positive correlation (P<0.01) between the number of proliferated nTregs and CD4(+) T cells in the presence as well as the absence of streptococcal M protein. Moreover, there was a significant negative correlation between the mean number of nTregs and CD4(+) T cells in mixed culture system in the absence of M protein (r=-0.995). There was also a positive, but not significant (P>0.05), association (r=0.353) between the mean number of nTregs and CD4(+) T cells in the presence of M protein. The M protein stimulated CD4(+) T cells to produce IL-4 in very little amount (<4 pg/ml) in all samples. Compared to the production of IL4, TNF-α was produced in higher concentrations in the culture supernatants. The findings of the study indicate that streptococcal M protein has an important role in increasing the proliferation of D4(+)CD25(+)regulatory T cells and CD4(+) T cells. However, CD4(+)CD25(+) regulatory T cells have lower suppressive activity against CD4(+) T cells in the presence of M protein.


Epithelial morphogenesis of MDCK cells in three-dimensional collagen culture is modulated by interleukin-8.
Epithelial morphogenesis is dependent upon a variety of factors, many of which involve complex interactions between cells and their surrounding environments. We analyzed the patterns of differential gene expression associated with Madin-Darby canine kidney (MDCK) renal epithelial cells grown within a collagen gel in three-dimensional (3D) culture compared with those grown atop a collagen gel in two-dimensional (2D) culture. Under these conditions, MDCK cells spontaneously formed either hollow spherical cysts or flat monolayer sheets, respectively. Microarray analysis of gene expression revealed a twofold or greater expression difference in 732 gene sets from MDCK cysts compared with monolayers (false discovery rate or FDR-adjusted P values <0.05). Interleukin-8 (IL-8) was reproducibly found to be among the genes whose expression was most dramatically upregulated, and this behavior was verified through real-time PCR analysis. The level of IL-8 protein expression was significantly increased in 3D MDCK cultures compared with that detected in cells in 2D culture. Hepatocyte growth factor (HGF) induces MDCK cells in 3D culture to form linear tubule-like structures. We found that HGF stimulation caused MDCK cells in 3D culture to decrease the expression of IL-8 at both the mRNA and protein levels. Furthermore, the addition of recombinant IL-8 to HGF-stimulated 3D MDCK cultures was sufficient to partially reverse the tubulogenic effects of HGF, resulting in the formation of cystic structures. These data suggest that IL-8 participates in the formation of cystic structures by MDCK cells in 3D culture and that HGF may stimulate tubulogenesis through the suppression of IL-8.


High frequency loss of heterozygosity in von Hippel-Lindau (VHL)-associated and sporadic pancreatic islet cell tumors: evidence for a stepwise mechanism for malignant conversion in VHL tumorigenesis.
Germ-line mutation of the von Hippel-Lindau (VHL) gene predisposes to the development of multifocal, benign lesions, including retinal and central nervous system hemangioblastomas, pheochromocytomas, and renal and pancreatic cysts. Progression to malignancy in VHL disease is associated primarily with the development of renal cell carcinoma (RCC) and pancreatic islet cell tumors (PICT). Although many reports have documented the multiple functions of the VHL protein, few have investigated the intriguing question related to the tissue-specificity of malignant conversion in VHL disease, a problem not easily explained by strict genotype-phenotype correlations. We investigated a novel VHL kindred with a preponderance of PICTs to determine whether loss of additional genetic loci associated with the sporadic forms of RCC and PICTs might play a role in malignant conversion in this disease. We report the high frequency loss of heterozygosity (LOH) of genetic loci distinct from and mapping proximal to VHL within human chromosome 3p in the VHL kindred under study. Furthermore, chromosome 3p LOH occurs subsequent to VHL mutation and cyst formation, and correlates with malignant progression in VHL-associated PICTs. High frequency LOH was also observed in sporadic PICTs in regions of 3p associated with LOH in sporadic clear cell RCC as well as homozygous deletion in lung cancer. A stepwise model for malignant conversion in VHL disease is herein proposed.


Efficacy of mediodorsal thalamic nucleus stimulation in a rat model of cortical seizure.
The mediodorsal thalamic nucleus (MD) has strong connectivity to the limbic systems and frontal lobe. The aim of this study was to determine whether the mediodorsal thalamic nucleus influences seizure induction by electrical stimulation in the rat frontal cortex. Juvenile male rats (n=7) were used in the experiment. At postnatal day 28 (P28), stainless steel skull screws were inserted for stimulating cortices. Depth-stimulating electrodes were stereotaxically inserted into the MD of the bilateral thalamus. Electrical stimulation, which produces afterdischarges, was applied to the frontal cortices once/day for four consecutive days from postnatal day 38. Additional conditioning electrical stimulation to the bilateral MD was fixed at 0.1 mA, and the stimulus frequency was increased from 0 Hz, 1 Hz, and 5 Hz to 10 Hz. All seven rats were stimulated with those frequencies by rotation every other day. The data of animals with 0 Hz MD stimulation were defined as controls. Afterdischarge thresholds and durations were measured at each frequency. Seizures were accompanied by bilateral tonic-clonic convulsions and cortical spikes. Seizure behaviors were not different among the groups and there were no statistically significant differences in the cortical afterdischarge (AD) thresholds between animals with MD stimulations and controls in all frequencies. In the cortical AD durations, there were also no statistically significant differences between animals with MD stimulation and controls although the mean duration at 10-Hz stimulation was less than the control animals. These results indicated that thalamic MD stimulation might not suppress epileptic seizure induction. Further studies are needed to analyze other stimulus parameters, altered stimulus locations, and different test paradigms.


Effect and process evaluation of a preschool-based intervention to promote an early childhood education and care teacher-parent partnership about healthy behaviours in children: Study protocol for the cluster randomised controlled trial CO-HEALTHY.
Early Childhood Education and Care (ECEC) teachers at urban preschools are potential key figures to promote healthy behaviours in disadvantaged young children and to engage parents in lifestyle-related topics. An ECEC teacher-parent partnership regarding healthy behaviours may support parents and stimulate their children's development. However, it is not an easy task to establish such a collaboration and ECEC teachers need tools to communicate with parents about lifestyle-related topics. This paper describes the study protocol of a preschool-based intervention (CO-HEALTHY) to promote an ECEC teacher-parent partnership regarding healthy eating, physical (in)activity and sleeping behaviours in young children. A cluster randomised controlled trial will be performed at preschools in Amsterdam, the Netherlands. Preschools will be randomly allocated to an intervention or control group. The intervention consists of a toolkit with 10 parent-child activities and associated training for ECEC teachers. The activities were composed using the Intervention Mapping protocol. At intervention preschools, ECEC teachers will carry out the activities during standard contact moments. Parents will receive associated intervention materials and will be encouraged to perform similar parent-child activities at home. At control preschools, the toolkit and training will not be implemented. The primary outcome will be the teacher- and parent-reported partnership regarding healthy eating, physical (in)activity and sleeping behaviours in young children. The perceived partnership will be assessed by a questionnaire at baseline and at 6 months. In addition, short interviews with ECEC teachers will be held. Secondary outcomes include the knowledge, attitude, food- and activity-related practices of ECEC teachers and parents. Furthermore, children's eating, physical (in)activity and sleeping behaviours, and weight development will be assessed. A process evaluation of the intervention will be made. The intervention aims to provide a practical tool for ECEC teachers at urban preschools to promote an ECEC teacher-parent partnership regarding a healthy lifestyle in young children. Netherlands Trial Register (NTR): NL8883. Date registered: September 8, 2020.


A network-based integrative approach to prioritize reliable hits from multiple genome-wide RNAi screens in Drosophila.
The recently developed RNA interference (RNAi) technology has created an unprecedented opportunity which allows the function of individual genes in whole organisms or cell lines to be interrogated at genome-wide scale. However, multiple issues, such as off-target effects or low efficacies in knocking down certain genes, have produced RNAi screening results that are often noisy and that potentially yield both high rates of false positives and false negatives. Therefore, integrating RNAi screening results with other information, such as protein-protein interaction (PPI), may help to address these issues. By analyzing 24 genome-wide RNAi screens interrogating various biological processes in Drosophila, we found that RNAi positive hits were significantly more connected to each other when analyzed within a protein-protein interaction network, as opposed to random cases, for nearly all screens. Based on this finding, we developed a network-based approach to identify false positives (FPs) and false negatives (FNs) in these screening results. This approach relied on a scoring function, which we termed NePhe, to integrate information obtained from both PPI network and RNAi screening results. Using a novel rank-based test, we compared the performance of different NePhe scoring functions and found that diffusion kernel-based methods generally outperformed others, such as direct neighbor-based methods. Using two genome-wide RNAi screens as examples, we validated our approach extensively from multiple aspects. We prioritized hits in the original screens that were more likely to be reproduced by the validation screen and recovered potential FNs whose involvements in the biological process were suggested by previous knowledge and mutant phenotypes. Finally, we demonstrated that the NePhe scoring system helped to biologically interpret RNAi results at the module level. By comprehensively analyzing multiple genome-wide RNAi screens, we conclude that network information can be effectively integrated with RNAi results to produce suggestive FPs and FNs, and to bring biological insight to the screening results.


How to perform and report a cardiopulmonary exercise test in patients with chronic heart failure.
In the present practice review, we will explain how to perform and interpret a cardiopulmonary exercise test (CPET) in heart failure patients. Specifically, we will explain why cycle ergometer should be preferred to treadmill, the type of protocol needed, and the ideal exercise duration. Thereafter, we will discuss how to interpret CPET findings and determine the parameters that should be included. We will focus specifically on: peak VO2 (absolute value and a percentage of its predicted value), exercise duration, respiratory exchange ratio, peak work rate, heart rate, O2 pulse, end-tidal carbon dioxide pressure (PetCO2), PetO2, and -if blood gas samples are obtained-dead space to tidal volume ratio. Moreover, we will discuss the physiological and clinical value of anaerobic threshold, respiratory compensation point, ventilation vs. VCO2 and VO2 vs. work relationships. Finally, attention will be dedicated to exercise-induced periodic breathing. We will also discuss when and why CPET should be integrated with other measurements in the so-called complex CPET. Specifically: a) when and how to use a complex non-invasive CPET, which integrates CPET measurements with non-invasive cardiac output determination, working muscle near-infrared spectroscopy, transthoracic echocardiography, thoracic ultrasound, and lung diffusion analysis; b) when and how to use a complex minimally invasive CPET, in which CPET is combined with esophageal balloon recordings or with serial arterial blood sampling for blood gas analysis; c) when and how to use a complex invasive CPET, which usually implies the presence of a Swan Ganz catheter in the pulmonary artery and an arterial line.


A marginal band-associated protein has properties of both microtubule- and microfilament-associated proteins.
The marginal band of nucleated erythrocytes is a microtubule organelle under rigorous quantitative and spatial control, with properties quite different from those of the microtubule organelles of cultured cells. Previous results suggest that proteins other than tubulin may participate in organizing the marginal band, and may interact with elements of the erythrocyte cytoskeleton in addition to microtubules. To identify such species, we raised mAbs against the proteins that assemble from chicken brain homogenates with tubulin. One such antibody binds to a single protein in chicken erythrocytes, and produces an immunofluorescence pattern colocalizing with marginal band microtubules. Several properties of this protein are identical to those of ezrin, a protein isolated from brush border and localized to motile elements of cultured cells. A significant proportion of the antigen is not soluble in erythrocytes, as determined by extraction with nonionic detergent. This cytoskeleton-associated fraction is unaffected by treatments that solubilize the marginal band microtubules. The protein has properties of both microtubule- and microfilament-associated proteins. In the accompanying manuscript (Goslin, K., E. Birgbauer, G. Banker, and F. Solomon. 1989. J. Cell Biol. 109:1621-1631), we show that the same antibody recognizes a component of growth cones with a similar dual nature. In early embryonic red blood cells, the antigen is dispersed throughout the cell and does not colocalize with assembled tubulin. Its confinement to the marginal band during development follows rather than precedes that of microtubules. These results, along with previous work, suggest models for the formation of the marginal band.


Contribution of depression to cognitive impairment and dementia in older adults.
The objective of this review is to provide information for clinicians regarding current research and opinions on the association of depression to conditions of cognitive impairment and dementia. We also intend to integrate this current research and thinking into strategies for the assessment and treatment of depression in the context of cognitive impairment. Depression is highly prevalent in mild cognitive impairment and most dementias. It may be a risk factor for the subsequent development of dementia and in some conditions may be a prodromal symptom. It is important to detect and effectively treat depression because the comorbidity of depression and cognitive impairment is associated with greater cognitive and functional decline and higher rates of institutionalization. Depression often can be differentiated from Alzheimer disease and other dementias based on characteristics of clinical history and presentation. Screening of depression and cognitive impairment will help characterize the presence and severity of these conditions, but limitations in screening approaches may necessitate comprehensive assessment in complex cases where differential diagnosis is important to treatment planning. Although depression and cognitive impairment are important issues in the treatment of older adults, there are particular risks when they occur together. Appropriate assessment and screening can help guide the clinician to appropriate and timely interventions. Pharmacologic and nonpharmacologic treatment approaches are both efficacious in reducing depression in cognitive impairment and dementia.


Real-time rendering method and performance evaluation of composable 3D lenses for interactive VR.
We present and evaluate a new approach for real-time rendering of composable 3D lenses for polygonal scenes. Such lenses, usually called "volumetric lenses," are an extension of 2D Magic Lenses to 3D volumes in which effects are applied to scene elements. Although the composition of 2D lenses is well known, 3D composition was long considered infeasible due to both geometric and semantic complexity. Nonetheless, for a scene with multiple interactive 3D lenses, the problem of intersecting lenses must be considered. Intersecting 3D lenses in meaningful ways supports new interfaces such as hierarchical 3D windows, 3D lenses for managing and composing visualization options, or interactive shader development by direct manipulation of lenses providing component effects. Our 3D volumetric lens approach differs from other approaches and is one of the first to address efficient composition of multiple lenses. It is well-suited to head-tracked VR environments because it requires no view-dependent generation of major data structures, allowing caching and reuse of full or partial results. A Composite Shader Factory module composes shader programs for rendering composite visual styles and geometry of intersection regions. Geometry is handled by Boolean combinations of region tests in fragment shaders, which allows both convex and nonconvex CSG volumes for lens shape. Efficiency is further addressed by a Region Analyzer module and by broad-phase culling. Finally, we consider the handling of order effects for composed 3D lenses.


Neurokinin receptors mediating substance P-induced contraction in adult rabbit airways.
Airway contractile responses to substance P (SP) were examined in isolated adult rabbit bronchial (BSM) and tracheal smooth muscle (TSM) segments. The tissues were placed in organ baths containing modified Krebs-Ringer solution, and isometric contractions to SP were monitored in the presence of phosphoramidon, an inhibitor of neutral endopeptidase (NEP). Under these conditions, BSM segments were significantly more reactive and more sensitive to SP than TSM segments. Removal of SPs cholinergic component with atropine (ATP) eliminated these regional differences in reactivity without affecting sensitivity. In considering the basis for these observations, it has been suggested that SP activates up to three different neurokinin (NK) subset receptors. Accordingly, we examined the regional airway contractile responses to Senktide, a selective NK-3 receptor agonist, and Septide, a selective NK-1 receptor agonist. In the presence of ATR, Senktide was inactive in both BSM and TSM, whereas Septide produced significantly greater contractions in BSM than in TSM. Subsequent desensitization of NK-1 receptors with Septide virtually eliminated the regional differences in airway sensitivity to SP. These findings indicate that 1) endogenous NEP activity can mask significant regional airway differences in SP-mediated contraction; and 2) these latter differences are the result of cholinergic, NK-1, and NK-2 receptor influences.


Distribution of 14C-2,3,7,8-tetrachlorodibenzo-p-dioxin to the brain and peripheral tissues of fetal rats and its comparison with adults.
Some forms of reproductive and developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) occur via initial damage to the pituitary synthesis of gonadotropins followed by the reduced expression of gonadal steroidogenic proteins. Defects in gonadotropin synthesis are highly specific to the periods from late fetal to early newborn stages. The reason for this specificity remains unknown. To address this issue, we compared the tissue distribution of 14C-TCDD between fetal and adult rats. In adult male rats, the major portion of TCDD given orally (approximately 33-42% dose) accumulated in the liver during day 1 and 5 after treatment. Very little TCDD (approximately 0.01% of the dose) distributed into the brain. A similar picture was also observed in TCDD-treated pregnant rats. The amount of TCDD transferred from a dam to the fetuses was extremely low (around 0.02% of the maternal dose/fetus) after 1 day of treatment. Male and female fetuses showed the same pattern in the brain distribution of TCDD. The rate of TCDD distribution to fetal brain, which was calculated on the basis of body burden to a fetus, was 100 times or more than that in adults. However, the brain content of TCDD (ng/g tissue) was comparable in fetuses and their dams, and adult males exposed to TCDD. These results suggest that although TCDD easily translocates to fetal brain, this is not a major mechanism for a fetal age-specific reduction in gonadotropin synthesis.


The use of minimally invasive techniques in multi-level surgery for children with cerebral palsy: preliminary results.
This study compares the initial outcomes of minimally invasive techniques for single-event multi-level surgery with conventional single-event multi-level surgery. The minimally invasive techniques included derotation osteotomies using closed corticotomy and fixation with titanium elastic nails and percutaneous lengthening of muscles where possible. A prospective cohort study of two matched groups was undertaken. Ten children with diplegic cerebral palsy with a mean age of ten years six months (7.11 to 13.9) had multi-level minimally invasive surgery and were matched for ambulatory level and compared with ten children with a mean age of 11 years four months (7.9 to 14.4) who had conventional single-event multi-level surgery. Gait kinematics, the Gillette Gait Index, isometric muscle strength and gross motor function were assessed before and 12 months after operation. The minimally invasive group had significantly reduced operation time and blood loss with a significantly improved time to mobilisation. There were no complications intra-operatively or during hospitalisation in either group. There was significant improvement in gait kinematics and the Gillette Gait Index in both groups with no difference between them. There was a trend to improved muscle strength in the multi-level group. There was no significant difference in gross motor function between the groups. We consider that minimally invasive single-event multi-level surgery can be achieved safely and effectively with significant advantages over conventional techniques in children with diplegic cerebral palsy.


A quantitative metric to identify critical elements within seafood supply networks.
A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical.


Shortening during stimulation vs. during relaxation. How do the costs compare?
White muscle fibres from dogfish were used to investigate the energetic cost of shortening by fully active muscle and by relaxing muscle. The muscle preparation was tetanized for 0.6 s and shortened by 1 mm (about 15% L0) at 7 mm/s (about 30% V0) either during stimulation or during relaxation. Isometric tetani at L0 were also investigated. Mechanical work was calculated from force and length change. Work + heat was taken as a measure of energetic cost. Both work and energetic cost were higher for shortening during stimulation than during relaxation. We also evaluated separately the work and heat associated with the contractile component and with the series elastic component. Work stored in the series elasticity could be completely recovered as external work when the shortening occurred during relaxation.


Minimax-optimal decoding of movement goals from local field potentials using complex spectral features.
We consider the problem of predicting eye movement goals from local field potentials (LFP) recorded through a multielectrode array in the macaque prefrontal cortex. The monkey is tasked with performing memory-guided saccades to one of eight targets during which LFP activity is recorded and used to train a decoder. Previous reports have mainly relied on the spectral amplitude of the LFPs as decoding feature, while neglecting the phase without proper theoretical justification. This paper formulates the problem of decoding eye movement intentions in a statistically optimal framework and uses Gaussian sequence modeling and Pinsker's theorem to generate minimax-optimal estimates of the LFP signals which are used as decoding features. The approach is shown to act as a low-pass filter and each LFP in the feature space is represented via its complex Fourier coefficients after appropriate shrinking such that higher frequency components are attenuated; this way, the phase information inherently present in the LFP signal is naturally embedded into the feature space. We show that the proposed complex spectrum-based decoder achieves prediction accuracy of up to [Formula: see text] at superficial cortical depths near the surface of the prefrontal cortex; this marks a significant performance improvement over conventional power spectrum-based decoders. The presented analyses showcase the promising potential of low-pass filtered LFP signals for highly reliable neural decoding of intended motor actions.


Smartphone applications for triaging adults with skin lesions that are suspicious for melanoma.
Melanoma accounts for a small proportion of all skin cancer cases but is responsible for most skin cancer-related deaths. Early detection and treatment can improve survival. Smartphone applications are readily accessible and potentially offer an instant risk assessment of the likelihood of malignancy so that the right people seek further medical attention from a clinician for more detailed assessment of the lesion. There is, however, a risk that melanomas will be missed and treatment delayed if the application reassures the user that their lesion is low risk. To assess the diagnostic accuracy of smartphone applications to rule out cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with concerns about suspicious skin lesions. We undertook a comprehensive search of the following databases from inception to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Studies of any design evaluating smartphone applications intended for use by individuals in a community setting who have lesions that might be suspicious for melanoma or atypical intraepidermal melanocytic variants versus a reference standard of histological confirmation or clinical follow-up and expert opinion. Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and poor quality of studies, we did not perform a meta-analysis for this review. For illustrative purposes, we plotted estimates of sensitivity and specificity on coupled forest plots for each application under consideration. This review reports on two cohorts of lesions published in two studies. Both studies were at high risk of bias from selective participant recruitment and high rates of non-evaluable images. Concerns about applicability of findings were high due to inclusion only of lesions already selected for excision in a dermatology clinic setting, and image acquisition by clinicians rather than by smartphone app users.We report data for five mobile phone applications and 332 suspicious skin lesions with 86 melanomas across the two studies. Across the four artificial intelligence-based applications that classified lesion images (photographs) as melanomas (one application) or as high risk or 'problematic' lesions (three applications) using a pre-programmed algorithm, sensitivities ranged from 7% (95% CI 2% to 16%) to 73% (95% CI 52% to 88%) and specificities from 37% (95% CI 29% to 46%) to 94% (95% CI 87% to 97%). The single application using store-and-forward review of lesion images by a dermatologist had a sensitivity of 98% (95% CI 90% to 100%) and specificity of 30% (95% CI 22% to 40%).The number of test failures (lesion images analysed by the applications but classed as 'unevaluable' and excluded by the study authors) ranged from 3 to 31 (or 2% to 18% of lesions analysed). The store-and-forward application had one of the highest rates of test failure (15%). At least one melanoma was classed as unevaluable in three of the four application evaluations. Smartphone applications using artificial intelligence-based analysis have not yet demonstrated sufficient promise in terms of accuracy, and they are associated with a high likelihood of missing melanomas. Applications based on store-and-forward images could have a potential role in the timely presentation of people with potentially malignant lesions by facilitating active self-management health practices and early engagement of those with suspicious skin lesions; however, they may incur a significant increase in resource and workload. Given the paucity of evidence and low methodological quality of existing studies, it is not possible to draw any implications for practice. Nevertheless, this is a rapidly advancing field, and new and better applications with robust reporting of studies could change these conclusions substantially.


Suprapapillary needle puncture for common bile duct access: laboratory profile.
[corrected] Biliary cannulation to perform endoscopic retrograde cholangiopancreatography may be difficult due to technical reasons and often is necessary to perform papillotomy, where complications as pancreatitis and perforation may occur To show minimal complications by a new model of biliary access by means of the suprapapillary needle puncture and its laboratory profile. After the approval of the protocol by the Scientific Ethics Committee of the institution a free and informed consent was signed by all patients participating in the study. From July 2003 to August 2004, fulfilling the inclusion and exclusion criteria, 30 patients were selected for endoscopic retrograde cholangiopancreatography, using the suprapapillary puncture technique. All patients remained hospitalized, fasting and with basal hydroelectrolytic replacement, were clinically followed up and samples for the determination of serum amylase, lipase and C-RP (C-reactive protein) were collected before and 4 h, 12 h and 24 h after the procedure and reevaluated 60 days after the procedure. Laboratory parameters were submitted to statistical study using analysis of variance for repeated measurements. Multiple comparisons were made based on Wald's statistics The technique was successful in 93.4% (28/30) of the patients. No statistically significant difference regarding to the laboratory profile were observed. Complications related to the technique of papillary puncture occurred in 1/28 patients by not using the guide wire and in 1/28 where mild hemorrhage after dilation of the papillary fistula occurred. Regarding complications related to therapeutic procedures, there were 2/28 retroduodenal perforations, with one (1/30) following unsuccessful puncture and another due to the passage of Dormia's basket through the dilated fistula path. All patients submitted to diagnostic puncture and evaluated 60 days after the procedure presented with the major duodenal papilla of normal aspect. The patients with dilation of the suprapapillary fistula showed the fistula continuing to drain clear bile Suprapapillary puncture allows investigative and therapeutic procedures without significant increases in amylase, lipase and C-RP. Patients submitted to diagnostic puncture present complete recovery of the papilla, while dilation of the fistula maintains it pervious later on, but without complications.


Pteropus lylei primarily forages in residential areas in Kandal, Cambodia.
Bats are the second most species-rich Mammalian order and provide a wide range of ecologically important and economically significant ecosystem services. Nipah virus is a zoonotic emerging infectious disease for which pteropodid bats have been identified as a natural reservoir. In Cambodia, Nipah virus circulation has been reported in Pteropus lylei, but little is known about the spatial distribution of the species and the associated implications for conservation and public health.We deployed Global Positioning System (GPS) collars on 14 P. lylei to study their movements and foraging behavior in Cambodia in 2016. All of the flying foxes were captured from the same roost, and GPS locations were collected for 1 month. The habitats used by each bat were characterized through ground-truthing, and a spatial distribution model was developed of foraging sites.A total of 13,643 valid locations were collected during the study. Our study bats flew approximately 20 km from the roost each night to forage. The maximum distance traveled per night ranged from 6.88-105 km and averaged 28.3 km. Six of the 14 bats visited another roost for at least one night during the study, including one roost located 105 km away.Most foraging locations were in residential areas (53.7%) followed by plantations (26.6%). Our spatial distribution model confirmed that residential areas were the preferred foraging habitat for P. lylei, although our results should be interpreted with caution due to the limited number of individuals studied. Synthesis and applications: Our findings suggest that the use of residential and agricultural habitats by P. lylei may create opportunities for bats to interact with humans and livestock. They also suggest the importance of anthropogenic habitats for conservation of this vulnerable and ecologically important group in Cambodia. Our mapping of the probability of occurrence of foraging sites will help identification of areas where public awareness should be promoted regarding the ecosystem services provided by flying foxes and potential for disease transmission through indirect contact.


Dental erosion protection by fermented shrimp paste in acidic food.
The aim of this study was to determine the extent to which fermented shrimp paste (which has a high calcium concentration) reduces dental erosion in vitro. In experiment 1, enamel specimens were exposed to various concentrations of shrimp paste in tamarind juice for 15 min, once a day, for a total of 29 days. In experiment 2, pre-softened enamel specimens were exposed to different concentrations of shrimp paste in water, using an exposure method similar to experiment 1. Profilometry and a microhardness test were used to assess changes in enamel loss and softening. The results showed that shrimp paste can reduce the erosive potential of tamarind juice and re-harden softened enamel.


Comparing HD knockin pigs and mice reveals the pathological role of IL-17.
Our previous work has established a knockin (KI) pig model of Huntington's disease (HD) that can replicate the typical pathological features of HD, including selective striatal neuronal loss, reactive gliosis, and axonal degeneration. However, HD KI mice exhibit milder neuropathological phenotypes and lack overt neurodegeneration. By performing RNA sequencing to compare the gene expression profiles between HD KI pigs and mice, we find that genes related to interleukin-17 (IL-17) signaling are upregulated in the HD pig brains compared to the mouse brains. Delivery of IL-17 into the brain striatum of HD KI mice causes greater reactive gliosis and synaptic deficiency compared to HD KI mice that received PBS. These findings suggest that the upregulation of genes related to IL-17 signaling in HD pig brains contributes to severe glial pathology in HD and identify this as a potential therapeutic target for treating HD.


Bayesian analysis of retinotopic maps.
Human visual cortex is organized into multiple retinotopic maps. Characterizing the arrangement of these maps on the cortical surface is essential to many visual neuroscience studies. Typically, maps are obtained by voxel-wise analysis of fMRI data. This method, while useful, maps only a portion of the visual field and is limited by measurement noise and subjective assessment of boundaries. We developed a novel Bayesian mapping approach which combines observation-a subject's retinotopic measurements from small amounts of fMRI time-with a prior-a learned retinotopic atlas. This process automatically draws areal boundaries, corrects discontinuities in the measured maps, and predicts validation data more accurately than an atlas alone or independent datasets alone. This new method can be used to improve the accuracy of retinotopic mapping, to analyze large fMRI datasets automatically, and to quantify differences in map properties as a function of health, development and natural variation between individuals.


Complex care needs of patients with late-stage HIV disease: a retrospective study.
This retrospective chart review provides a profile of an emerging population of vulnerable HIV patients with complex comorbidities. Data were abstracted from all 83 patients admitted in 2008 to Casey House, a community-based hospital dedicated to supportive and palliative care for persons with HIV in Toronto, Canada. We describe patient characteristics, including medical and psychiatric conditions, and use a Venn diagram and case study to illustrate the frequency and reality of co-occurring conditions that contribute to the complexity of patients' health and health care needs. The mean age at admission was 49.2 years (SD10.5). Sixty-seven patients (80.7%) were male. Patients experienced a mean of 5.9 medical comorbidities (SD2.3) and 1.9 psychiatric disorders (lifetime Axis I diagnoses). Forty patients (48.2%) experienced cognitive impairment including HIV-associated dementia. Patients were on a mean of 11.5 (SD5.3) medications at admission; 74.7% were on antiretroviral medications with 55.0% reporting full adherence. Current alcohol and drug use was common with 50.6% reporting active use at admission. Our Venn diagram illustrates the breadth of complexity in the clients with 8.4% of clients living in unstable housing with three or more medical comorbidities and two or more psychiatric diagnoses. Comprehensive HIV program planning should include interventions that can flexibly adapt to meet the multidimensional and complex needs of this segment of patients. Researchers, policy-makers, and clinicians need to have greater awareness of overlapping medical, psychiatric and psychosocial comorbidities. Inclusion of the needs of these most vulnerable patients in the development of evidence-based guidelines is an important step for effectively treating, preventing, and planning for the future of HIV/AIDS care.


Regulation of K3 keratin gene transcription by Sp1 and AP-2 in differentiating rabbit corneal epithelial cells.
Rabbit corneal epithelial cells cultured in the presence of 3T3 feeder cells undergo biochemical differentiation, as evidenced by their initial expression of K5 and K14 keratins characteristic of basal keratinocytes, followed by the subsequent expression of K3 and K12 keratin markers of corneal epithelial differentiation. Previous data established that mutations of an Sp1 site in a DNA element, E, that contains overlapping Sp1 and AP-2 motifs reduce K3 gene promoter activity by 70% in transfection assays. We show here that Sp1 activates while AP-2 represses the K3 promoter. Although undifferentiated corneal epithelial basal cells express equal amounts of Sp1 and AP-2 DNA-binding activities, the differentiated cells down-regulate their Sp1 activity slightly but their AP-2 activity drastically, thus resulting in a six- to sevenfold increase in the Sp1/AP-2 ratio. This change coincides with the activation and suppression of the differentiation-related K3 gene and the basal cell-related K14 keratin gene, respectively. In addition, we show that polyamines, which are present in a high concentration in proliferating basal keratinocytes, can inhibit the binding of Sp1 to its cognate binding motif but not that of AP-2. These results suggest that the relatively low Sp1/AP-2 ratio as well as the polyamine-mediated inhibition of Sp1 binding to the E motif may account, in part, for the suppression of the K3 gene in corneal epithelial basal cells, while the elevated Sp1/AP-2 ratio may be involved in activating the K3 gene in differentiated corneal epithelial cells. Coupled with the previous demonstration that AP-2 activates the K14 gene in basal cells, the switch of the Sp1/AP-2 ratio during corneal epithelial differentiation may play a role in the reciprocal expression of the K3 and K14 genes in the basal and suprabasal cell layers.


Mate Choice Copying in Humans.
There is substantial evidence that in human mate choice, females directly select males based on male display of both physical and behavioral traits. In non-humans, there is additionally a growing literature on indirect mate choice, such as choice through observing and subsequently copying the mating preferences of conspecifics (mate choice copying). Given that humans are a social species with a high degree of sharing information, long-term pair bonds, and high parental care, it is likely that human females could avoid substantial costs associated with directly searching for information about potential males by mate choice copying. The present study was a test of whether women perceived men to be more attractive when men were presented with a female date or consort than when they were presented alone, and whether the physical attractiveness of the female consort affected women's copying decisions. The results suggested that women's mate choice decision rule is to copy only if a man's female consort is physically attractive. Further analyses implied that copying may be a conditional female mating tactic aimed at solving the problem of informational constraints on assessing male suitability for long-term sexual relationships, and that lack of mate choice experience, measured as reported lifetime number of sex partners, is also an important determinant of copying.


Ethaverine, a derivative of papaverine, inhibits cardiac L-type calcium channels.
Ethaverine is a derivative of papaverine used in the treatment of peripheral vascular disease and is thought to cause vasodilation by reducing intracellular Ca2+ concentrations in vascular smooth muscle cells. We tested its effects on single, dihydropyridine-sensitive, L-type calcium channels from porcine cardiac muscle, incorporated into planar lipid bilayers. L-type calcium channels were activated by step depolarizations from a holding potential of -60 mV to a test potential of 0 mV, and unitary currents carried by 100 mM BaCl2 were recorded. Channel activity was enhanced by the presence of the dihydropyridine agonist (+)-202-791 (0.5 microM) and the activated alpha subunit of the stimulatory GTP-binding protein, Gs. We found that 0.3-30 microM ethaverine on either side of the channel caused a reduction in the channel open probability (EC50 approximately 1 microM), with the higher concentrations inhibiting channel activity almost completely. In addition, the ethaverine caused a small reduction in the unitary current amplitude of single open channels (approximately 20%). To test whether the effect of ethaverine on open probability was due to a displacement of the dihydropyridine agonist, we studied the effect of ethaverine on the binding of [3H]nitrendipine to cardiac sarcolemma and found that ethaverine inhibited [3H]nitrendipine binding with a Ki of approximately 8.5 microM. Ethaverine also inhibited the binding of [3H]diltiazem and [3H]verapamil, with Ki values of 1-2 microM. Because ethaverine is structurally related to verapamil, it is likely that ethaverine acts by binding to the verapamil binding sites on the L-type calcium channels to inhibit channel activation and dihydropyridine binding.


A 24-week, parallel-group, open-label, randomized clinical trial comparing the early antiviral efficacy of telbivudine and entecavir in the treatment of hepatitis B e antigen-positive chronic hepatitis B virus infection in adult Chinese patients.
Because drug-resistant strains of hepatitis B virus (HBV) have developed, and because serum HBV-DNA levels may rebound in patients who receive treatment with nucleoside/nucleotide analogues for up to 2 years, there remains a largely unmet clinical need for agents to induce potent virologic suppression in the initial stage of the disease course of HBV infection. The aim of this work was to compare the early antiviral effectiveness of telbivudine and entecavir in the treatment of patients with hepatitis B e antigen (HBeAg)-positive HBV. In this parallel-group, open-label trial, adult Chinese patients with previously untreated HBeAg-positive HBV (HBV-DNA concentration: >or=6 log(10) copies/mL; alanine aminotransferase [ALT] level: >or=2 times the upper limit of normal) were randomized to receive telbivudine 600 mg or entecavir 0.5 mg daily for 24 weeks. Blood samples were collected at the baseline and at 12 and 24 weeks after the treatment. The primary end point was the mean reduction from baseline in serum HBV-DNA concentration at week 24. Secondary end points included mean reduction from baseline in serum HBV-DNA concentration at week 12, the absence of serum HBV-DNA, absence of serum HBeAg, HBeAg seroconversion at week 24, the normalization of serum ALT at week 24, and occurrence of adverse events through week 24. A total of 131 patients were enrolled in the study: 91 men and 40 women, with a mean (SD) age of 32.5 (8.9) years. All patients were ethnic Han Chinese. The baseline demographic characteristics and serum HBV-DNA concentrations in the 2 treatment groups were well matched. Sixty-five patients were randomized to receive telbivudine and 66 to receive entecavir. The mean reductions from baseline in serum HBV-DNA were 4.99 and 4.69 log(10) copies/mL at week 12, respectively, and 6.00 and 5.80 log(10) copies/mL at week 24 (both time points, P = NS between groups). At week 12, HBV-DNA was undetectable in 43.1% (28/65) of the telbivudine group and 34.8% (23/66) of the entecavir group (P = NS); at week 24, it was undetectable in 67.7% (44/65) of the telbivudine group and 57.6% (38/66) of the entecavir group (P = NS). At week 12, HBeAg absence and seroconversion rates were significantly greater in the telbivudine group than the entecavir group (absence: 20.0% [13/65] vs 3.0% [2/66], respectively [P = 0.002]; seroconversion: 13.8% [9/65] vs 3.0% [2/66] [P = 0.030]). However, at week 24, HBeAg absence and seroconversion rates were comparable between the telbivudine and entecavir groups (absence: 36.9% [24/65] vs 28.8% [19/66] [P = NS]; seroconversion: 24.6% [16/65] vs 13.6% [9/66] [P = NS]). In addition, the normalization of ALT levels was observed in 78.5% (51/65) and 74.2% (49/66) of patients treated with telbivudine and entecavir, respectively, at week 24 (P = NS). The adverse events were upper respiratory tract infection (12.3% of telbivudine patients vs 9.1% of entecavir patients), fatigue (6.2% vs 7.6%), diarrhea (1.5% vs 3.0%), and coughing (0% vs 1.5%), most of which were mild to moderate. Elevated creatinine phosphokinase was noted in 8 telbivudine-treated patients (12.3%). There were no statistically significant differences in rates of adverse events between groups except for creatinine phosphokinase. In this study of ethnic Han Chinese adults with previously untreated HBeAg-positive HBV infection, there were no statistically significant differences in effectiveness or tolerability between telbivudine 600 mg and entecavir 0.5 mg at the end of 24 weeks of treatment. ChiCTR.org identifier: ChiCTR-TRC-00000341.


The role of sulphate reduction on the reductive S decolorization of the azo dye reactive orange 14.
The aim of this study was to investigate the impact of a broad range of sulphate concentrations (0-10g SO4(-2) L(-1)) on the reduction of an azo dye (reactive orange 14 (RO14)) by an anaerobic sludge. An increase in the sulphate concentration generally stimulated the reduction of RO14 by sludge incubations supplemented with glucose, acetate or propionate as electron donor. Sulphate and azo dye reductions took place simultaneously in all incubations. However, there was a decrease on the rate of decolorization when sulphate was supplied at 10g SO4(-2) L(-1). Abiotic incubations at different sulphide concentrations (0-2.5 g sulphide L(-1)) promoted very poor reduction of RO14. However, addition of riboflavin (20 microM), as a redox mediator, accelerated the reduction of RO14 up to 44-fold compared to a control lacking the catalyst. Our results indicate that sulphate-reduction may significantly contribute to the reduction of azo dyes both by biological mechanisms and by abiotic reductions implicating sulphide as an electron donor. The contribution of abiotic decolorization by sulphide, however, was only significant when a proper redox mediator was included. Our results also revealed that sulphate-reduction can out-compete with azo reduction at high sulphate concentrations leading to a poor decolorising performance when no sufficient reducing capacity is available.


Simultaneous Inhibition of MEK and Hh Signaling Reduces Pancreatic Cancer Metastasis.
Pancreatic cancer, mostly pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal cancer types, with an estimated 44,330 death in 2018 in the US alone. While targeted therapies and immune checkpoint inhibitors have significantly improved treatment options for patients with lung cancer and renal cell carcinomas, little progress has been made in pancreatic cancer, with a dismal 5-year survival rate currently at ~8%. Upon diagnosis, the majority of pancreatic cancer cases (~80%) are already metastatic. Thus, identifying ways to reduce pancreatic cancer metastasis is an unmet medical need. Furthermore, pancreatic cancer is notorious resistant to chemotherapy. While Kirsten RAt Sarcoma virus oncogene (K-RAS) mutation is the major driver for pancreatic cancer, specific inhibition of RAS signaling has been very challenging, and combination therapy is thought to be promising. In this study, we report that combination of hedgehog (Hh) and Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase (MEK) signaling inhibitors reduces pancreatic cancer metastasis in mouse models. In mouse models of pancreatic cancer metastasis using human pancreatic cancer cells, we found that Hh target gene Gli1 is up-regulated during pancreatic cancer metastasis. Specific inhibition of smoothened signaling significantly altered the gene expression profile of the tumor microenvironment but had no significant effects on cancer metastasis. By combining Hh signaling inhibitor BMS833923 with RAS downstream MEK signaling inhibitor AZD6244, we observed reduced number of metastatic nodules in several mouse models for pancreatic cancer metastasis. These two inhibitors also decreased cell proliferation significantly and reduced CD45⁺ cells (particularly Ly6G⁺CD11b⁺ cells). We demonstrated that depleting Ly6G⁺ CD11b⁺ cells is sufficient to reduce cancer cell proliferation and the number of metastatic nodules. In vitro, Ly6G⁺ CD11b⁺ cells can stimulate cancer cell proliferation, and this effect is sensitive to MEK and Hh inhibition. Our studies may help design novel therapeutic strategies to mitigate pancreatic cancer metastasis.


Estrogen receptor alpha mediates acute potassium channel stimulation in human coronary artery smooth muscle cells.
The pleiotropic effects of estrogen are mediated via stimulation of two estrogen receptor (ER) subtypes, ERalpha and ERbeta. Although a number of studies have identified expression of one or both subtypes in estrogen target tissues, fewer studies have correlated ER expression with a functional role of these proteins in regulating cellular excitability. In the present study, we have combined cellular fluorescence, immunocytochemistry, and molecular expression techniques with single-channel patch-clamp studies to determine which ER mediates estrogen-stimulated potassium channel activity in human coronary artery smooth muscle cells (HCASMC). We had demonstrated previously that estrogen stimulates activity of the large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channel in HCASMC via a nongenomic mechanism. We now demonstrate expression of both ERalpha and ERbeta subtypes in HCASMC. Functionally, however, expression of ERalpha antisense plasmid abolished the acute effect of estrogen on these channels, whereas estrogen retained its ability to stimulate BK(Ca) channels in cells transfected with only green fluorescence protein. In contrast, overexpression of ERalpha enhanced the stimulatory action of estrogen in HCASMC. Transfection with ERalpha antisense/sense plasmid did not alter ERbeta expression. These findings indicate that the ERalpha isoform mediates estrogen-induced stimulation of BK(Ca) channels in HCASMC and thereby provide evidence for a receptor-dependent signaling mechanism that can mediate estrogen-induced inhibition of cellular excitability.


The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion.
Zopiclone is a poorly soluble psychotherapeutic agent. The aim of this study was to prepare and characterize an amorphous form of zopiclone as well as the characterization and performance of a stable amorphous solid dispersion. The amorphous form was prepared by the well-known method of quench-cooling of the melt. The solid dispersion was prepared by a solvent evaporation method of zopiclone, polyvinylpyrrolidone-25 (PVP-25), and methanol, followed by freeze-drying. The physico-chemical properties and stability of amorphous zopiclone and the solid dispersion was studied using differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), hot-stage microscopy (HSM), X-ray diffractometry (XRD), solubility, and dissolution studies. The zopiclone amorphous solid-state form was determined to be a fragile glass; it was concluded that the stability of the amorphous form is influenced by both temperature and water. Exposure of amorphous zopiclone to moisture results in rapid transformation of the amorphous form to the crystalline dihydrated form. In comparison, the amorphous solid dispersion proved to be more stable with increased aqueous solubility.


Differences in the robustness of clusters involving the Mycobacterium tuberculosis strains most frequently isolated from immigrant cases in Madrid.
Tuberculosis cases infected by the same Mycobacterium tuberculosis (MTB) strain are considered to be clustered and involved in a transmission chain. Large clusters are assumed to represent active transmission chains in a population. In the present study, we focused on the analysis of large clusters defined by IS6110-restriction fragment length polymorphism (RFLP) typing in the immigrant population in Madrid. We identified 12 large clusters (involving 43% of the isolates) comprising 4-23 representatives. We proposed a gradient of epidemiological certainty for these large clusters. For a cluster to be considered robust and a good indicator of recent transmission, the MTB strain involved should not have been identified in a geographically and epidemiologically unrelated population and the cluster had to be re-confirmed by another highly discriminative molecular marker (MIRU-VNTR). The clusters that we discovered were classified into three categories: high, intermediate and low expected epidemiological value. In the largest cluster in the study (cluster M6; 23 representatives), failures by both criteria were identified: the representative seven-band RFLP pattern was also the most prevalent in the unrelated population (25 cases) and the cluster was fully split by MIRU-15, suggesting a lack of epidemiological value. The RFLP pattern representative of this cluster was also identified in 64 isolates from five countries in the Latin American genotype database, and again proved to be heterogeneous according to the MIRU-15 analysis. Specific analysis of large clusters, combined with the application of criteria for evaluating their robustness, could help identify uninformative clusters and target epidemiological resources towards those clusters with higher expected epidemiological value.


Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells.
Metargidin (ADAM-15) is a type I transmembrane glycoprotein belonging to the ADAM (A Disintegrin and Metalloprotease Domain) family of proteins and is widely expressed in different tissues and cell types. Members of this family contain an amino-terminal metalloprotease domain followed by a disintegrin domain, a cysteine-rich region and a membrane proximal EGF-like domain. The disintegrin domain of metargidin contains an RGD tripeptide sequence, suggesting that it may potentially interact with the integrin family of proteins. Here we identify integrin ligands for metargidin on haemopoietic cells, by using a chimeric protein containing the extracellular domain of metargidin fused to the Fc portion of human IgG. Binding activity to a panel of human cell lines was analysed by solid-phase cell-adhesion assays. Metargidin bound to a monocytic cell line, U937, and a T cell line, MOLT-4, in a specific manner. Adhesion was divalent cation- and temperature- dependent and strongly enhanced by Mn2+, all features of integrin-mediated binding. Using a panel of anti-integrin antibodies we show that alphavbeta3 is a ligand for metargidin on U937 cells. In contrast, for MOLT-4 cells, the integrin alpha5beta1 contributes to cell binding. Adhesion was mediated by the disintegrin domain of metargidin as RGD-based peptides inhibited cell binding to both cell lines. The specificity of the interaction between both alphavbeta3 and alpha5beta1 and metargidin was further confirmed by solid-phase adhesion assays using purified recombinant integrins. These results together indicate that metargidin can function as a cell adhesion molecule via interactions with alphavbeta3 and alpha5beta1 integrins.


Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells.
Reticulo-endothelial macrophages together with duodenal enterocytes coordinate body iron homeostasis. The aim of this study was to investigate the regulatory actions of the hormone hepcidin on ferroportin expression in these two cell types. We investigated the in vitro effects of hepcidin in well-characterised human cell culture models of macrophages (differentiated THP-1 cells) and intestinal epithelial cells (Caco-2 cells). The in vivo effects of hepcidin were also investigated in mice injected with a synthetic hepcidin peptide. Exposure to hepcidin (presented either as conditioned medium from interleukin-6-stimulated HuH7 cells or as a synthetic peptide) resulted in a rapid (within 4 h) decrease in ferroportin expression in THP-1 macrophages but had no effect on ferroportin levels in Caco-2 cells. To determine whether these rapid effects of hepcidin were also evident in vivo we injected mice with a synthetic hepcidin peptide. Four hours post-injection, ferroportin levels in the macrophage-rich red pulp of the spleen were decreased significantly and the hepcidin-treated mice developed hypoferraemia. Interestingly, in the same mice there was no effect of hepcidin on duodenal ferroportin protein expression or duodenal iron transport. These data suggests that the rapid response to hepcidin is cell type and tissue specific. Upon its release, hepcidin initially targets macrophage iron recycling. The duodenum appears to be less sensitive to this initial rise in hepcidin levels. We believe the fact that macrophages respond more acutely to a hepcidin challenge is fully consistent with their central role in maintaining body iron homeostasis.


Absence of aflatoxin biosynthesis in koji mold (Aspergillus sojae).
Ten strains isolated from industrial soy sauce producing koji mold were identified as Aspergillus sojae and distinguished from Aspergillus parasiticus morphologically and physiologically. There was no detectable aflatoxin in any culture extracts of A. sojae strains. Strain 477 was chosen as a representative strain of industrial A. sojae for further molecular analysis. All enzymatic activities associated with the aflatoxin biosynthesis were not detected or negligible in strain 477 compared with that of the A. parasiticus strain. Southern analysis suggested that the genomic DNA of strain 477 contained aflatoxin biosynthetic pathway genes. In contrast, all industrial strains lacked detectable transcripts of aflR, the main regulatory gene for aflatoxin biosynthesis, under the aflatoxin-inducing condition. Our data suggest that defects in aflR expression cause the lack of expression of aflatoxin-related genes which results in the absence of aflatoxin biosynthesis in A. sojae strains.


A Mediterranean diet supplemented with dairy foods improves markers of cardiovascular risk: results from the MedDairy randomized controlled trial.
The Mediterranean diet (MedDiet) offers benefits to cardiovascular health but may not meet Western recommendations for calcium and dairy intake, which could impede long-term adoption. The current study aimed to determine the effect of a MedDiet supplemented with dairy foods on cardiovascular risk factors. A randomized, controlled, crossover design compared a MedDiet with 3-4 daily servings of dairy (MedDairy) and a low-fat (LF) control diet. Forty-one participants aged ≥45 y and at risk of cardiovascular disease (CVD) were randomly allocated to their first intervention, either the MedDairy or LF diet. Participants followed each intervention for 8 wk, and an 8-wk washout period separated interventions. The primary outcome was home-measured systolic blood pressure (SBP) assessed in the morning, afternoon, and evening. Secondary outcomes included clinic-measured blood pressure (morning), body composition, blood lipids, C-reactive protein (CRP), plasma glucose, serum insulin, and the Framingham Risk Score. Compared with the LF intervention, the MedDairy intervention resulted in a significantly lower morning SBP (mean difference: -1.6 mm Hg; 95% CI: -2.8, -0.4 mm Hg; P = 0.01), lower morning diastolic blood pressure (mean difference: -1.0; 95% CI: -1.7, -0.2 mm Hg; P = 0.01) and clinic SBP (mean difference: -3.5 mm Hg; 95% CI: -6.4, -0.7 mm Hg; P = 0.02), significantly higher HDL cholesterol (mean difference: 0.04 mmol/L; 95% CI: 0.01, 0.06 mmol/L; P < 0.01), lower triglycerides (mean difference: = -0.05 mmol/L; 95% CI: -0.08, -0.01 mmol/L; P < 0.01), and lower ratio of total to HDL cholesterol (mean difference: -0.4; 95% CI: -0.6, -0.2; P < 0.001). No effects were observed for other outcome measures. Following a MedDiet with additional dairy foods led to significant changes in markers of cardiovascular risk over 8 wk. The MedDiet supplemented with dairy may be appropriate for an improvement in cardiovascular risk factors in a population at risk of CVD. This trial was registered at anzctr.org.au as ACTRN12616000309482.


p53 immunoprofiling of potentially malignant oral disorders: a case series analysis.
p53 tumor suppressor gene which is a frequent target for mutations in a high percentage of oral cancer is regarded as an early event in carcinogenesis. The role of p53 was assessed in potentially malignant oral disorders (PMOD) to ascertain its prognostic significance. Retrospective case series analysis was carried out on 30 paraffin-embedded tissue blocks of confirmed oral leukoplakia with dysplasia. 10 cases of each of mild, moderate, and severe dysplasia were immunohistochemically analyzed for p53 expression. The intensity of staining, intracellular localization, and basal and/or suprabasal distribution were assessed. The intensity of p53 staining and its distribution were analyzed by the Chi-square test. The intracellular localization of p53 in different grades of dysplasia was subjected to one way ANOVA. P<0.05 was considered significant. 21/30 cases of epithelial dysplasia were positive for p53 immunopositivity. Intensity of p53 expression was strong in 12 cases and weak in 9 cases (P<0.05). p53 positivity was confined to basal cells in mild dysplasia, while severe dysplasia showed both basal and suprabasal staining (P<0.05). Nuclear and cytoplasmic staining between and within the groups were F=9.027 and F=6.465 respectively with high significance noted between mild dysplasia and severe dysplasia. Increased p53 expressivity and greater cellular localization with increase in the severity of dysplasia indicated a direct association between the degree of epithelial dysplasia and p53 accretion, which occurs as an early event in oral carcinogenesis.


Mupirocin resistance in nasal carriage of Staphylococcus aureus among healthcare workers of a tertiary care rural hospital.
Mupirocin (pseudomonic acid A) is a topical antimicrobial agent with excellent antistaphylococcal and antistreptococcal activity. A nasal formulation is approved by the United States Food and Drug Administration for eradicating nasal carriage in adult patients as well as in health care personnel. Resistance to mupirocin has already been reported worldwide. The increasing prevalence of mupirocin resistance among Staphylococcus aureus and coagulase-negative Staphylococcus (CoNS) species could be an important threat to the future use of mupirocin against methicillin-resistant S. aureus (MRSA). Thus, this study was carried out to find the prevalence of mupirocin resistance in S. aureus and CoNS by disc diffusion and to determine the rates of high-level and low-level mupirocin resistance in S. aureus and CoNS by disc diffusion. A total of 140 healthcare workers (HCWs) (doctor, nursing staff, housekeeping staff) were randomly selected. S. aureus and CoNS isolates were tested for mupirocin resistance by the disk diffusion method using 5 μg and 200 μg mupirocin discs. MRSA isolates were tested for antibiotics by Kirby-Bauer disc-diffusion method as per Clinical and Laboratory Standards Institute guidelines. Out of 140 nasal swabs collected from HCWs, S. aureus was isolated in 38 (27.14%), and CoNS was isolated in 73 (52.14%). MRSA was isolated in 20 (14.28%) and methicillin-resistant coagulase-negative Staphylococci (MRCoNS) in 34 (24.29%. Methicillin-sensitive S. aureus (MSSA) and MSCoNS isolates were 100% sensitive to mupirocin, but two isolates from MRSA (1.43%) and five from MRCoNS (3.57%) were mupirocin resistant. The presence of mupirocin resistance in MRSA and MRCoNS is a cause for concern. It could be limited by regular surveillance and effective infection control initiatives so to inform health care facilities to guide therapeutic and prophylactic use of mupirocin.


Controlling healthcare-associated infections: the role of infection control and antimicrobial use practices.
Healthcare-associated infections are a major cause of morbidity and mortality in pediatric patients in the United States and throughout the world. Overall rates of infection range widely depending on the pediatric population, with the highest rates being in patients in neonatal intensive care units, followed by those in pediatric intensive care units, immunocompromised patients, and those undergoing surgical procedures. Risk factors for healthcare-associated infection include intrinsic and extrinsic factors. The major intrinsic factors are age, birth weight, underlying diseases, and immune status. The major extrinsic factors are presence of invasive devices and procedures. The major risk factors for healthcare-associated infection caused by antimicrobial-resistant pathogens are either the transmission of pathogens from person to person (directly or indirectly, usually via the hands of healthcare workers) or the emergence of resistance after exposure to antimicrobials. Preventing healthcare-associated infections caused by antimicrobial-resistant pathogens requires a comprehensive approach that includes: 1) preventing infections through the use of vaccines and prophylaxis; 2) minimizing the use of invasive devices; 3) understanding and fully implementing (and complying with) current guideline recommendations for the prevention of infections; and 4) using antimicrobials judiciously. Implementing such a comprehensive program will reduce healthcare-associated infections, reduce the prevalence of antimicrobial-resistant pathogens, improve patient outcomes, and reduce health care costs.


A framework for comparative analysis of health systems: experiences from the Asia Pacific Observatory on Health Systems and Policies.
Drawing on published work from the Asia Pacific Observatory on Health Systems and Policies, this paper presents a framework for undertaking comparative studies on the health systems of countries. Organized under seven types of research approaches, such as national case-studies using a common format, this framework is illustrated using studies of low- and middle-income countries published by the Asia Pacific Observatory. Such studies are important contributions, since much of the health systems research literature comes from high-income countries. No one research approach, however, can adequately analyse a health system, let alone produce a nuanced comparison of different countries. Multiple comparative studies offer a better understanding, as a health system is a complex entity to describe and analyse. Appreciation of context and culture is crucial: what works in one country may not do so in another. Further, a single research method, such as performance indicators, or a study of a particular health system function or component, produces only a partial picture. Applying a comparative framework of several study approaches helps to inform and explain progress against health system targets, to identify differences among countries, and to assess policies and programmes. Multi-method comparative research produces policy-relevant learning that can assist countries to achieve Sustainable Development Goal 3: ensure healthy lives and promoting well-being for all at all ages by 2030.


Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
Wnt/beta-catenin and NF-kappaB signaling mechanisms provide central controls in development and disease, but how these pathways intersect is unclear. Using hair follicle induction as a model system, we show that patterning of dermal Wnt/beta-catenin signaling requires epithelial beta-catenin activity. We find that Wnt/beta-catenin signaling is absolutely required for NF-kappaB activation, and that Edar is a direct Wnt target gene. Wnt/beta-catenin signaling is initially activated independently of EDA/EDAR/NF-kappaB activity in primary hair follicle primordia. However, Eda/Edar/NF-kappaB signaling is required to refine the pattern of Wnt/beta-catenin activity, and to maintain this activity at later stages of placode development. We show that maintenance of localized expression of Wnt10b and Wnt10a requires NF-kappaB signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-kappaB target. These data reveal a complex interplay and interdependence of Wnt/beta-catenin and EDA/EDAR/NF-kappaB signaling pathways in initiation and maintenance of primary hair follicle placodes.


Colloid-in-liquid crystal gels that respond to biomolecular interactions.
This paper advances the design of stimuli-responsive materials based on colloidal particles dispersed in liquid crystals (LCs). Specifically, thin films of colloid-in-liquid crystal (CLC) gels undergo easily visualized ordering transitions in response to reversible and irreversible (enzymatic) biomolecular interactions occurring at the aqueous interfaces of the gels. In particular, LC ordering transitions can propagate across the entire thickness of the gels. However, confinement of the LC to small domains with lateral sizes of ∼10 μm does change the nature of the anchoring transitions, as compared to films of pure LC, due to the effects of confinement on the elastic energy stored in the LC. The effects of confinement are also observed to cause the response of individual domains of the LC within the CLC gel to vary significantly from one to another, indicating that manipulation of LC domain size and shape can provide the basis of a general and facile method to tune the response of these LC-based physical gels to interfacial phenomena. Overall, the results presented in this paper establish that CLC gels offer a promising approach to the preparation of self-supporting, LC-based stimuli-responsive materials.


Predictive value of platelet reactivity unit (PRU) value for thrombotic and hemorrhagic events during flow diversion procedures: a meta-analysis.
Platelet function testing prior to flow diversion procedures, although initially heavily debated, has seen a substantial increase in its adoption to assess the risk of operative and perioperative thrombotic and hemorrhagic events. This meta-analysis was conducted to assess platelet function testing, particularly the VerifyNow Platelet Reactivity Unit (PRU) assay, for a relationship between the reported assay PRU value and thrombotic and hemorrhagic events. The currently available literature (2013-2018) was surveyed with PubMed and Google Scholar searches. Included studies were those for which there were at least 30 cases during the study period, for which VerifyNow platelet reactivity unit values were obtained prior to the procedures and for which intraoperative and perioperative adverse events were noted. PRU value cut-offs ranging from >200 to >240 comprised the hyporesponse group while values ranging from <60 to <70 comprised the hyper-response group. The data were subject to statistical analysis to assess the relationship between PRU values and thrombotic and hemorrhagic events. The collected data were subsequently statistically analyzed to assess for publication bias. The searches yielded 27 studies, of which 12 met the inclusion criteria for the meta-analysis. The meta-analysis included data from 1464 reported Pipeline cases. The study included 273 men and 1177 women with a mean age across the analyzed procedures of 58 years (range 25-85). After loading with antiplatelet medications, preprocedural platelet hyper-responsiveness was associated with a greater incidence of hemorrhagic events with an increased absolute risk of 12%, but showed no relationship with thrombotic events. Preprocedural platelet hyporesponsiveness was associated with a greater incidence of thrombotic events with an absolute risk of 15%, but showed no relationship with hemorrhagic events. VerifyNow PRU values that correspond to platelet hyporesponse or hyper-response to dual antiplatelet therapy are associated with a higher risk of thrombotic and hemorrhagic events, respectively. Thus, the PRU value may offer some predictive value for these events.


An early modern human from the Peştera cu Oase, Romania.
The 2002 discovery of a robust modern human mandible in the Peştera cu Oase, southwestern Romania, provides evidence of early modern humans in the lower Danubian Corridor. Directly accelerator mass spectrometry radiocarbon (14C)-dated to 34,000-36,000 14C years B.P., the Oase 1 mandible is the oldest definite early modern human specimen in Europe and provides perspectives on the emergence and evolution of early modern humans in the northwestern Old World. The moderately long Oase 1 mandible exhibits a prominent tuber symphyseos and overall proportions that place it close to earlier Upper Paleolithic European specimens. Its symmetrical mandibular incisure, medially placed condyle, small superior medial pterygoid tubercle, mesial mental foramen, and narrow corpus place it closer to early modern humans among Late Pleistocene humans. However, its cross-sectional symphyseal orientation is intermediate between late archaic and early modern humans, the ramus is exceptionally wide, and the molars become progressively larger distally with exceptionally large third molars. The molar crowns lack derived Neandertal features but are otherwise morphologically undiagnostic. However, it has unilateral mandibular foramen lingular bridging, an apparently derived Neandertal feature. It therefore presents a mosaic of archaic, early modern human and possibly Neandertal morphological features, emphasizing both the complex population dynamics of modern human dispersal into Europe and the subsequent morphological evolution of European early modern humans.


Lymphatic route of transport and pharmacokinetics of Micrurus fulvius (coral snake) venom in sheep.
The contribution of the lymphatic system to the absorption and systemic bioavailability of Micrurus fulvius venom after subcutaneous (SC) administration was assessed using a central lymph-cannulated sheep model. Micrurus fulvius venom was administered either by intravenous bolus (IV) or subcutaneous injection (SC) in 12 sheep with and without thoracic duct cannulation and drainage. Venom concentration in serum and lymph was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) in samples collected over a 6-hour period and in tissues harvested at the end of the experiment. Pharmacokinetic parameters were determined by a non-compartmental analysis. In the lymphatic cannulated group, over the 6 hours after the venom was administered, 69% of administered dose was accounted for in blood (45%) and lymph (25%). Negligible levels of venom were detected in organs and urine implying that the steady state observed after SC administration is maintained by a slow absorption process. Comparison of kinetics of the thoracic duct cannulated and non-cannulated groups showed that lymphatic absorption contributed in an important way to maintenance of this steady state. These results show that the limiting process in the pharmacokinetics of Micrurus fulvius venom following SC administration is absorption, and that the lymphatic system plays a key role in this process.


The brain Kv1.1 potassium channel: in vitro and in vivo studies on subunit assembly and posttranslational processing.
While combined cloning, mutagenesis, and electrophysiological techniques have provided great insight into K+ channel structure/function relationships, little is known about K+ channel biosynthesis. To examine K+ channel biosynthesis, immune purifications were conducted on Triton X-100 extracts of 35S-met-labeled channels from in vitro translations and transfected mouse L-cells. When Kv1.1 and Kv1.4 were cotranslated in vitro, isoform-specific antisera copurified both proteins even at early time points, suggesting rapid subunit assembly. The non-Shaker Kv2.1 channel did not assemble with Kv1.1 or Kv1.4. Mouse L-cells transfected with Kv1.1 cDNA yielded 1000-4000 functional surface channels, and immune purification from Kv1.1 cells with Kv1.1 antisera produced a 57-59 kDa doublet on SDS-PAGE but not in sham-transfected cells. Immune purification of surface channels isolated both the 57 and 59 kDa proteins, suggesting cell surface channels are represented by two species. Pulse-chase metabolic labeling studies were consistent with a precursor-product relationship with the 57 kDa species giving rise to the 59 kDa protein within several minutes of synthesis. At longer chase times, the 57 kDa species reappeared, indicating both an early precursor and a mature protein ran with identical electrophoretic mobility. Mutation of the extracellular glycosylation site (N207) yielded two proteins at steady state, a 55 kDa core peptide and a 57 kDa species. Lack of glycosylation at N207 had little effect on channel synthesis, turnover, or function. Together these results suggest (1) heteromeric assembly of Shaker-like channels is cotranslational, and (2) N207 glycosylation of Kv1.1 occurs but is not required for subunit assembly, transport, or function.


Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair.
Ubiquitin-conjugating enzyme variant (UEV) proteins resemble ubiquitin-conjugating enzymes (E2s) but lack the defining E2 active-site residue. The MMS2-encoded UEV protein has been genetically implicated in error-free postreplicative DNA repair in Saccharomyces cerevisiae. We show that Mms2p forms a specific heteromeric complex with the UBC13-encoded E2 and is required for the Ubc13p-dependent assembly of polyubiquitin chains linked through lysine 63. A ubc13 yeast strain is UV sensitive, and single, double, and triple mutants of the UBC13, MMS2, and ubiquitin (ubiK63R) genes display a comparable phenotype. These findings support a model in which an Mms2p/Ubc13p complex assembles novel polyubiquitin chains for signaling in DNA repair, and they suggest that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation.


Plasmon-mediated magneto-optical transparency.
Magnetic field control of light is among the most intriguing methods for modulation of light intensity and polarization on sub-nanosecond timescales. The implementation in nanostructured hybrid materials provides a remarkable increase of magneto-optical effects. However, so far only the enhancement of already known effects has been demonstrated in such materials. Here we postulate a novel magneto-optical phenomenon that originates solely from suitably designed nanostructured metal-dielectric material, the so-called magneto-plasmonic crystal. In this material, an incident light excites coupled plasmonic oscillations and a waveguide mode. An in-plane magnetic field allows excitation of an orthogonally polarized waveguide mode that modifies optical spectrum of the magneto-plasmonic crystal and increases its transparency. The experimentally achieved light intensity modulation reaches 24%. As the effect can potentially exceed 100%, it may have great importance for applied nanophotonics. Further, the effect allows manipulating and exciting waveguide modes by a magnetic field and light of proper polarization.


Optimization of water quality monitoring network in a large river by combining measurements, a numerical model and matter-element analyses.
A monitoring network that resolves the spatial and temporal variations of the water quality is essential in the sustainable management of water resources and pollution control. Due to cost concerns, it is important to optimize the monitoring locations so to use the least number of stations required to obtain the most comprehensive monitoring. The optimal design of monitoring networks is commonly based on the limited data available from existing measuring stations. The main contribution of this paper is the use of a numerical water quality model, calibrated with the available data. This model yields information on the water quality in any cross-section along the river, including the river reaches that are not monitored. Another contribution of the paper is the use of a matter-element analysis that allows for an objective division of the river in reaches that are homogeneous with respect to the water quality as assessed from multiple water quality parameters. The optimal monitoring network consists of one measuring station in each of these homogeneous reaches. The method has been applied to optimize the water quality monitoring network on the 1890 km long upper and middle reaches of the Heilongjiang River in Northeast China. The results suggest that the monitoring network improves considerably by relocating three stations, and not by adding extra stations.


Maternal Report of Advice Received for Infant Care.
Advice has been associated with increased adherence to recommended infant care practices, and may represent a modifiable factor to promote infant health. A stratified, 2-stage, clustered design, with oversampling of black and Hispanic mothers, was used to survey a nationally representative sample of 1031 mothers of infants aged 2 to 6 months. Survey questions assessed advice received from doctors, birth hospital nurses, family, and media regarding immunization, breastfeeding, sleep position, sleep location, and pacifier use. Weighted frequencies of no advice and advice consistent with recommendations were calculated to obtain prevalence estimates. Multivariable logistic regression analyses were performed to assess factors associated with receipt of recommendation consistent advice. Although doctors were the most prevalent source of reported advice, ∼20% of mothers reported no doctor advice for breastfeeding or sleep position, and more than 50% reported no advice regarding sleep location or pacifier use. Reported advice from nurses was generally similar to doctors. The prevalence of any advice from family or media was 20% to 56% for nearly all care practices, and advice given was often inconsistent with recommendations. The only factors that were consistently associated with receipt of recommendation consistent advice were race/ethnicity and parity; black and Hispanic mothers and first-time mothers were more likely to report recommendation consistent advice. Mothers commonly report receiving either no advice or recommendation inconsistent advice from each of the 4 sources we studied. By identifying care practices with low prevalence of recommendation consistent advice from potentially important advisors, our findings highlight opportunities for future intervention.


Regulation by adrenal corticosteroids of sodium and potassium transport in loop of Henle and distal tubule of rat kidney.
Studies were conducted to examine the effects of adrenalectomy (ADX) and selective, physiological adrenal corticosteroid replacement on sodium and potassium transport by the superficial loop of Henle and distal tubule of rat kidney in vivo. In the loop of Henle, ADX inhibited sodium reabsorption by 33%. Whereas dexamethasone had no effect on reabsorption, aldosterone increased sodium transport to control levels. Thus, physiological levels of mineralocorticoids, but not glucocorticoids, control a fraction of sodium reabsorption in the loop of Henle. ADX also inhibited potassium reabsorption in the loop of Henle. Both dexamethasone and aldosterone reversed the inhibition, although only aldosterone increased reabsorption to control levels. In the distal tubule, ADX reduced sodium reabsorption by 44%. Both aldosterone and dexamethasone stimulated reabsorption: however, only aldosterone increased transport to control. Potassium secretion by the distal tubule was also reduced 34% by ADX. Aldosterone, but not dexamethasone, stimulated secretion. Thus, physiological levels of aldosterone regulate a fraction of sodium reabsorption and potassium secretion in the distal tubule.


A portable laser photostimulation and imaging microscope.
We describe a compact microscope that uses a spatial light modulator (SLM) to control the excitation laser light. The flexibility of SLMs, which can mimic virtually any optical transfer function, enables the experimenter to create, in software, arbitrary spatio-temporal light patterns, including focusing and beam scanning, simply by calculating the appropriate phase mask. Our prototype, a scan-less device with no moving parts, can be used for laser imaging or photostimulation, supplanting the need for an elaborate optical setup. As a proof of principle, we generate complex excitation patterns on fluorescent samples and also perform functional imaging of neuronal activity in living brain slices.


Physiological optics at the national bureau of standards.
Published work in physiological optics at the National Bureau of Standards is summarized under the headings: evaluation of light-dark patterns, light measurements, color measurement, color differences, and color perception. The bearing of this work on standard methods of the American Society of Testing and Materials, of the Illuminating Engineering Society, and of the American Standards Association, and on recommendations of the International Commission on Illumination is indicated. The purposes and methods of current work are briefly described.


Regulation of Schizosaccharomyces pombe Atf1 protein levels by Sty1-mediated phosphorylation and heterodimerization with Pcr1.
The Atf1 transcription factor plays a vital role in the ability of Schizosaccharomyces pombe cells to respond to various stress conditions. It regulates the expression of many genes in a stress-dependent manner, and its function is dependent upon the stress-activated MAPK, Sty1/Spc1. Moreover, Atf1 is directly phosphorylated by Sty1. Here we have investigated the role of such phosphorylation. Atf1 protein accumulates following stress, and this accumulation is lost in a strain defective in the Sty1 signaling pathway. In addition, accumulation of a mutant Atf1 protein that can no longer be phosphorylated is lost. Measurement of the half-life of Atf1 demonstrates that changes in Atf1 stability are responsible for this accumulation. Atf1 stability is also regulated by its heterodimeric partner, Pcr1. Similarly, Pcr1 levels are regulated by Atf1. Thus multiple pathways exist that ensure that Atf1 levels are appropriately regulated. Phosphorylation of Atf1 is important for cells to mount a robust response to H(2)O(2) stress, because the Atf1 phospho-mutant displays sensitivity to this stress, and induction of gene expression is lower than that observed in wild-type cells. Surprisingly, however, loss of Atf1 phosphorylation does not lead to the complete loss of stress-activated expression of Atf1 target genes. Accordingly, the Atf1 phospho-mutant does not display the same overall stress sensitivities as the atf1 deletion mutant. Taken together, these data suggest that Sty1 phosphorylation of Atf1 is not required for activation of Atf1 per se but rather for modulating its stability.


Estimating determinants of dentist productivity: new evidence.
Productivity (output per unit of input) is a major driver of dental service capacity. This study uses 2006-2007 data to update available knowledge on dentist productivity. In 2006-2007, the authors surveyed 1,604 Oregon general dentists regarding-hours worked, practice size, payment and patient mix, prices, dentist visits, and dentist characteristics. Effects of practice inputs and other independent variables on productivity were estimated by multiple regression and path analysis. The survey response rate was 55.2 percent. Dentists responding to the productivity-related questions were similar to dentists in the overall sampling frame and nationwide. Visits per week are significantly positively related to dentist hours worked, number of assistants, hygienists, and number of operatories. Dentist ownership status, years of experience, and percentage of Medicaid patients are significantly positively related to practice output. The contributions of dentist chairside time and assistants to additional output are smaller for owners, but the number of additional dentist visits enabled by more hygienists is larger for owners. As in earlier studies of dental productivity, the key determinant of dentist output is the dentist's own chairside time. The incremental contributions of dentist time, auxiliaries, and operatories to production of dentist visits have not changed substantially over the past three decades. Future studies should focus on ultimate measures of output--oral health--and should develop more precise measures of the practice's actual utilization of auxiliaries and their skill and use of technology.


Comparative study of obstructive urolithiasis and its sequelae in buffalo calves.
The present work was designed to study the incidence of obstructive urolithiasis and to apply comparative diagnosis to urine retention cases. A total of 78 non-castrated buffalo calves aging 3-11 months were included in this study, 68 calves were admitted to the Veterinary Teaching Hospital, Zagazig University, Egypt, during the study period with a history of anuria, and they were classified into three groups; intact bladder group (19 calves), uroperitoneum group (45 calves), and ruptured urethra group (4 calves). 10 apparently healthy calves were used for comparison. On the basis of history, clinical, laboratory, and ultrasonographic findings diagnosis was achieved. There was a marked increase in the incidence of obstructive urolithiasis in winter season, especially in winter months of 2016. Calves within the age of 3-4 months and 6-8 months were mostly affected. Inappetence to anorexia, restlessness or depression, and abdominal distension were the most observed signs in the diseased calves. Laboratory findings revealed hemoconcentration and a significant increase in blood urea nitrogen and serum creatinine levels in all diseased groups. Hyperproteinemia, hypocalcemia, and hyperphosphatemia with electrolytes imbalance were recorded in the uroperitoneum group. Ultrasonographically, distended urinary bladder with distal acoustic enhancement revealed obstructive urolithiasis with intact bladder while anechoic fluid in abdominal cavity indicates uroperitoneum. On the basis of all findings, calves with intact bladder were in superior condition than those with a ruptured urethra and both were better than those with uroperitoneum.