Comparison of childhood asthma incidence in 3 neighbouring cities in southwestern Ontario: a 25-year longitudinal cohort study.
Air pollution is a known trigger for exacerbations among individuals with asthma, but its role in the development of new-onset asthma is unclear. We compared the rate of new asthma cases in Sarnia, a city with high pollution levels, with the rates in 2 neighbouring regions in southwestern Ontario, Canada. Using a population-based birth cohort design and linked health administrative data, we compared the hazard of incident asthma among children 0 to 10 years of age between those born in Lambton (Sarnia) and those born in Windsor and London-Middlesex, for the period Apr. 1, 1993, to Mar. 31, 2009. We used Cox proportional hazards models to adjust for year of birth and exposure to air pollutants (nitrogen dioxide, sulphur dioxide [SO2], ozone and small particulate matter [PM2.5]), as well as maternal, geographic and socioeconomic factors. Among 114 427 children, the highest incidence of asthma was in Lambton, followed by Windsor and London-Middlesex (30.3, 24.4 and 19.8 per 1000 person-years, respectively; p < 0.001). Relative to Lambton, the hazard of asthma, adjusted for socioeconomic and perinatal factors, was lower in Windsor (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.67-0.77) and London-Middlesex (HR 0.65, 95% CI 0.61-0.69). Inclusion of air pollutants attenuated this relative difference in both Windsor (HR 0.79, 95% CI 0.62-1.01) and London-Middlesex (HR 0.89, 95% CI 0.64-1.24). We identified a higher incidence of asthma among children born in Lambton (Sarnia) relative to 2 other regions in southwestern Ontario. Higher levels of air pollution (particularly SO2 and PM2.5) in this region, as experienced by children in their first year of life, may be contributory.


Treatment options for chronic myeloid leukemia: imatinib versus interferon versus allogeneic transplant.
This review considers recent developments in the treatment of chronic myeloid leukemia with attention to current data evaluating the relative roles of imatinib mesylate, interferon-alpha, and allogeneic blood or marrow transplantation. Additionally, the review discusses advances in the basic understanding of the mechanisms by which these three different therapies function against chronic myeloid leukemia. Long-term follow-up has found that interferon-alpha was able to produce complete cytogenetic remission in15 to 25% of patients, with some of these patients achieving a molecular remission. Some patients who achieve a complete cytogenetic remission also achieve long-term disease-free survival and possibly cure. Imatinib has produced remarkable hematologic and cytogenetic responses in newly treated and in interferon-alpha-refractory patients, yet there are no long-term survival data at this point. Some laboratory findings imply that imatinib may primarily affect mature chronic myeloid leukemia progenitors and not chronic myeloid leukemia stem cells, leaving doubt that the improved rate of complete cytogenetic remissions will result in increased overall survival. Other clonal cytogenetic abnormalities have also been reported in the Philadelphia chromosome-negative cells present in complete cytogenetic remissions to imatinib. The use of donor lymphocytes infusion (DLI) continues to treat relapsed chronic myeloid leukemia effectively after allogeneic blood or marrow transplantation whereas the use of nonmyeloablative therapy has effectively reduced transplant-related mortality. Patients with chronic myeloid leukemia now have several potential treatment options from which to choose. Imatinib mesylate currently provides excellent hematologic and cytogenetic response rates with minimal toxicity. However, long-term data of efficacy is lacking. Emerging evidence that imatinib rarely leads to molecular complete remission and that many patients are still at risk of relapse and other clonal disorders is concerning and suggest the possibility that imatinib's early high response rates may not translate into survival advantage. Interferon-alpha continues to be effective therapy for many patients and, along with blood or marrow transplantation, is proved to prolong survival. The impacts of both are in part limited because of their toxicity profiles. Ongoing laboratory investigations and clinical trials remain paramount to providing the best treatment approach for our patients with chronic myeloid leukemia.


Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department.
For patients who present to the emergency departments (ED) with undifferentiated chest pain, the risk of major adverse cardiac events (MACE) may be underestimated in low-HEART score patients. We aimed to identify characteristics of patients who were classified as low risk by HEART score but subsequently developed MACE at 6 weeks. We studied a multiethnic cohort of patients who presented with chest pain arousing suspicion of acute coronary syndrome to EDs in the Netherlands and Singapore. Patients were risk-stratified using HEART score and followed up for MACE at 6 weeks. Risk factors of developing MACE despite low HEART scores (scores 0-3) were identified using logistic and Cox regression models. Among 1376 (39.8%) patients with low HEART scores, 63 (4.6%) developed MACE at 6 weeks. More males (53/806, 6.6%) than females (10/570, 2.8%) with low HEART score developed MACE. There was no difference in outcomes between ethnic groups. Among low-HEART score patients with 2 points for history, 21% developed MACE. Among low-HEART score patients with 1 point for troponin, 50% developed MACE, while 100% of those with 2 points for troponin developed MACE. After adjusting for HEART score and potential confounders, male sex was independently associated with increased odds (OR 4.12, 95%CI 2.14-8.78) and hazards (HR 3.93, 95%CI 1.98-7.79) of developing MACE despite low HEART score. Male sex, highly suspicious history and elevated troponin were disproportionately associated with MACE. These characteristics should prompt clinicians to consider further investigation before discharge.


Influence of vacuum-ageing duration of whole beef on retail shelf life of steaks packaged with oregano (Origanum vulgare L.) active film under high O2.
Beef Longissimus lumborum (LL) was no aged (LL0), aged for 7 days (LL7) and 14 days (LL14) under vacuum at 1 ± 1 °C. The obtained beefsteaks were packaged in high oxygen (Hi-O2) with active packaging (AP) during 13-21 days at 1 ± 1 °C. Redness (CIE a* values), metmyoglobin percentage (MetMb%), total flora (PCA), thiobarbituric acid-reactive substances (TBA-RS), instrumental tenderness (Warner-Bratzler shear force: WBSF), and sensory analyses were performed. The various variables differed amongst the ageing times and packaging systems (AP vs. control). Three and ten additional days of retail shelf life were observed for steaks from LL7 and LL14, respectively. AP increased efficiently the retail shelf life of beefsteaks, but did not affect meat tenderness. The extended ageing from 7 to 14 days also induced higher tenderness in beefsteaks and did not show any affect negative effect on other quality parameters. Innovative technology referring to ageing under vacuum combined with Hi-O2 MA/AP would be desirable for beefsteaks during display and constituted a good alternative for meat supermarkets.


Consensus summary of aerosolized antimicrobial agents: application of guideline criteria. Insights from the Society of Infectious Diseases Pharmacists.
Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital-acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence-based pharmacotherapy. Further research with well-designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.


Endocytosis as a mechanism for tyrosine kinase-dependent suppression of a voltage-gated potassium channel.
The voltage-gated potassium channel Kv1.2 undergoes tyrosine phosphorylation-dependent suppression of its ionic current. However, little is known about the physical mechanism behind that process. We have found that the Kv1.2 alpha-subunit protein undergoes endocytosis in response to the same stimuli that evoke suppression of Kv1.2 ionic current. The process is tyrosine phosphorylation-dependent because the same tyrosine to phenylalanine mutation in the N-terminus of Kv1.2 that confers resistance to channel suppression (Y132F) also confers resistance to channel endocytosis. Overexpression of a dominant negative form of dynamin blocked stimulus-induced Kv1.2 endocytosis and also blocked suppression of Kv1.2 ionic current. These data indicate that endocytosis of Kv1.2 from the cell surface is a key mechanism for channel suppression by tyrosine kinases.


Differential proteomics argues against a general role for CD9, CD81 or CD63 in the sorting of proteins into extracellular vesicles.
The tetraspanins CD9, CD81 and CD63 are major components of extracellular vesicles (EVs). Yet, their impact on EV composition remains under-investigated. In the MCF7 breast cancer cell line CD63 was as expected predominantly intracellular. In contrast CD9 and CD81 strongly colocalized at the plasma membrane, albeit with different ratios at different sites, which may explain a higher enrichment of CD81 in EVs. Absence of these tetraspanins had little impact on the EV protein composition as analysed by quantitative mass spectrometry. We also analysed the effect of concomitant knock-out of CD9 and CD81 because these two tetraspanins play similar roles in several cellular processes and associate directly with two Ig domain proteins, CD9P-1/EWI-F/PTGFRN and EWI-2/IGSF8. These were the sole proteins significantly decreased in the EVs of double CD9- and CD81-deficient cells. In the case of EWI-2, this is primarily a consequence of a decreased cell expression level. In conclusion, this study shows that CD9, CD81 and CD63, commonly used as EV protein markers, play a marginal role in determining the protein composition of EVs released by MCF7 cells and highlights a regulation of the expression level and/or trafficking of CD9P-1 and EWI-2 by CD9 and CD81.


Evidence-based clinical recommendations for the use of pit-and-fissure sealants: a report of the American Dental Association Council on Scientific Affairs.
This article presents evidence-based clinical recommendations for use of pit-and-fissure sealants developed by an expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs. The panel addressed the following clinical questions. Under what circumstances should sealants be placed to prevent caries? Does placing sealants over early (noncavitated) lesions prevent progression of the lesion? Are there conditions that favor the placement of resin-based versus glass ionomer cement sealants in terms of retention or caries prevention? Are there any techniques that could improve sealants' retention and effectiveness in caries prevention? Staff of the ADA Division of Science conducted a MEDLINE search to identify systematic reviews and clinical studies published after the identified systematic reviews.


Rutin Promotes Pancreatic Cancer Cell Apoptosis by Upregulating miRNA-877-3p Expression.
(1) Background: pancreatic cancer is one of the most serious cancers due to its rapid and inevitable fatality, which has been proved very difficult to treat, compared with many other common cancers. Thus, developing an effective therapeutic strategy, especially searching for potential drugs, is the focus of current research. The exact mechanism of rutin in pancreatic cancer remains unknown. (2) Method: three pancreatic cancer cell lines were used to study the anti-pancreatic cancer effect of rutin. The potent anti-proliferative, anti-migration and pro-apoptotic properties of rutin were uncovered by cell viability, a wound-healing migration assay, and a cell apoptosis assay. High-throughput sequencing technology was used to detect the change of miRNAs expression. Immunoblotting analysis was used to detect the expression of apoptotic proteins. (3) Results: CCK-8 and EDU assays revealed that rutin significantly inhibited pancreatic cancer cells' proliferation (p < 0.05). A wound-healing assay showed that rutin significantly suppressed pancreatic cancer cells' migration (p < 0.05). A flow cytometric assay showed that rutin could promote pancreatic cancer cells' apoptosis. Intriguingly, rutin significantly upregulated miR-877-3p expression to repress the transcription of Bcl-2 and to induce pancreatic cancer cell apoptosis. Accordingly, rutin and miR-877-3p mimics could promote apoptotic protein expression. (4) Conclusions: our findings indicate that rutin plays an important role in anti-pancreatic cancer effects through a rutin-miR-877-3p-Bcl-2 axis and suggests a potential therapeutic strategy for pancreatic cancer.


Ventricular haemodynamics in Python molurus: separation of pulmonary and systemic pressures.
Vascular pressure separation by virtue of a two-chambered ventricle evolved independently in mammals and birds from a reptilian ancestor with a single ventricle, and allowed for high systemic perfusion pressure while protecting the lungs from oedema. Within non-crocodilian reptiles, ventricular pressure separation has only been observed in varanid lizards and has been regarded as a unique adaptation to an active predatory life style and high metabolic rate. The systemic and pulmonary sides of the ventricle in Python molurus are well separated by the muscular ridge, and a previous study using in situ perfusion of the heart revealed a remarkable flow separation and showed that the systemic side can sustain higher output pressures than the pulmonary side. Here we extend these observations by showing that systemic blood pressure P(sys) exceeded pulmonary pressure P(pul) almost seven times (75.7+/-4.2 versus 11.6+/-1.1 cm H(2)O). The large pressure difference between the systemic and pulmonary circulation persisted when P(sys) was altered by infusion of sodium nitroprusside or phenylephrine. Intraventricular pressures, measured in anaesthetised snakes, showed an overlap in the pressure profile between the pulmonary side of the ventricle (cavum pulmonale) and the pulmonary artery, while the higher pressure in the systemic side of the ventricle (cavum arteriosum) overlapped with the pressure in the right aortic arch. This verifies that the pressure differences originate within the ventricle, indicating that the large muscular ridge separates the ventricle during cardiac contraction.


Moderators of Treatment for Pediatric Bipolar Spectrum Disorders.
Objective: We review the current limited research on pediatric bipolar spectrum disorder (BPSD) treatment moderators..Method: Four pharmacotherapy and nine psychotherapy moderator studies in youth with pediatric BPSD is summarized.Results: Two pharmacotherapy studies suggest that younger children and those with more aggression fare worse. Regarding preferential outcomes, one study found that older youth respond better to lithium than younger youth; all youth, regardless of age, respond similarly to valproate. One study found non-obese youth and those with comorbid attention deficit hyper-activity disorder respond better to risperidone than lithium. Results are mixed for psychosis and disruptive behavior disorders on risperidone compared to divalproex. Tentatively, youth with generalized anxiety are more likely to respond to valproate while youth with panic preferentially respond to lithium. Psychotherapy findings from two studies suggest that sex, age, race, baseline mania, and past-month suicidal ideation/non-suicidal self-injury do not moderate outcomes. Although not replicated, higher baseline inflammatory markers are associated with greater decreases in depressive symptoms; baseline higher self-esteem and comorbid attention deficit hyperactivity disorder are associated with steeper decreases in (hypo)manic symptoms.Conclusions: Findings are mixed on the role of baseline mood severity, other comorbid disorders, parental depression, family income, and expressed emotion in moderating treatment outcomes. Replication of these possible moderators is needed for both pharmacotherapy and psychotherapy interventions before conclusive results can be determined. Examination of larger samples of youth with BPSD and longer duration follow-up are needed to clarify meaningful treatment moderators.


Phylogenomics insights into order and families of Lysobacterales.
Order Lysobacterales (earlier known Xanthomonadales ) is a taxonomically complex group of a large number of gamma-proteobacteria classified in two different families, namely Lysobacteraceae and Rhodanobacteraceae . Current taxonomy is largely based on classical approaches and is devoid of whole-genome information-based analysis. In the present study, we have taken all classified and poorly described species belonging to the order Lysobacterales to perform a phylogenetic analysis based on the 16 S rRNA sequence. Moreover, to obtain robust phylogeny, we have generated whole-genome sequencing data of six type species namely Metallibacterium scheffleri , Panacagrimonas perspica , Thermomonas haemolytica , Fulvimonas soli , Pseudofulvimonas gallinarii and Rhodanobacter lindaniclasticus of the families Lysobacteraceae and Rhodanobacteraceae . Interestingly, whole-genome-based phylogenetic analysis revealed unusual positioning of the type species Pseudofulvimonas , Panacagrimonas , Metallibacterium and Aquimonas at family level. Whole-genome-based phylogeny involving 92 type strains resolved the taxonomic positioning by reshuffling the genus across families Lysobacteraceae and Rhodanobacteraceae . The present study reveals the need and scope for genome-based phylogenetic and comparative studies in order to address relationships of genera and species of order Lysobacterales .


Semi-supervised semantic segmentation of prostate and organs-at-risk on 3D pelvic CT images.
The recent development of deep learning approaches has revoluted medical data processing, including semantic segmentation, by dramatically improving performance. Automated segmentation can assist radiotherapy treatment planning by saving manual contouring efforts and reducing intra-observer and inter-observer variations. However, training effective deep learning models usually Requires a large amount of high-quality labeled data, often costly to collect. We developed a novel semi-supervised adversarial deep learning approach for 3D pelvic CT image semantic segmentation. Unlike supervised deep learning methods, the new approach can utilize both annotated and un-annotated data for training. It generates un-annotated synthetic data by a data augmentation scheme using generative adversarial networks (GANs). We applied the new approach to segmenting multiple organs in male pelvic CT images. CT images without annotations and GAN-synthesized un-annotated images were used in semi-supervised learning. Experimental results, evaluated by three metrics (Dice similarity coefficient, average Hausdorff distance, and average surface Hausdorff distance), showed that the new method achieved comparable performance with substantially fewer annotated images or better performance with the same amount of annotated data, outperforming the existing state-of-the-art methods.


Chemical composition, antibacterial activity and cytotoxicity of essential oils of Tanacetum parthenium in different developmental stages.
Tanacetum parthenium Schultz Bip. (Asteraceae) is an aromatic perennial plant, widely distributed in the northern hemisphere. This species traditionally has been used in insecticides, cosmetics, balsams, dyes, medicines and preservatives. The essential oil of T. parthenium was obtained by hydrodistillation in three developmental stages and analyzed by gas chromatography-mass spectrometry. The antibacterial activity of the oils was investigated against four Gram-positive and four Gram-negative bacteria. The oil was tested for cytotoxicity against THP-1 cells using the Trypan blue assay. Twenty-nine components were identified in the essential oil; the highest amount was extracted at the flowering stage. The main component, in the flowering stage, was camphor (18.94%) and other major components were bornyl acetate (18.35%), camphene (13.74%), bornyl isovalerate (3.15%), borneol (10.93%), juniper camphor (6.23%) and β-eudesmol (2.65%). Minimum inhibitory concentration of essential oil was evaluated from 4 µL mL(-1) against Staphylococcus subtilis to 38 µL mL(-1) against Entrobacter aerogenes. Toxicity assay showed that the oil has no significant toxicity at 5-15% v/v concentrations on THP-1 cells. This study demonstrates the occurrence of camphor/bornyl acetate chemotype of T. parthenium in western regions of Iran. The finding showed also the studied oils have relatively good antibacterial activity without significant toxicity, thus have great potentiality to be used as natural health product.


Trends in Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Over Past 10 years: A Bibliometric Analysis.
As a common hemorrhagic cerebrovascular disease, subarachnoid hemorrhage (SAH) has high mortality and disability. Delayed cerebral ischemia (DCI) is among the major complications after SAH, severely affecting the patient prognosis. Through bibliometric analysis, this study investigated the global research status, trends, and hotspots of DCI after SAH from 2013 to 2022, providing a scientific reference for researchers in this field. We searched the Web of Science Core Collection for articles and associated records from 2013 to 2022. The data were analyzed and presented using VOSviewer software. This study covered 3436 articles, and the number of publications issued by DCI after SAH study increased annually. The United States published the most papers and had the highest number of citations. Harvard University and World Neurosurgery were the institutions and journals with the most published papers. Keyword analysis indicated that the recent research on DCI after SAH has focused on its pathophysiological mechanisms. DCI after SAH has drawn increasing interest in academic circles during the past decade. This study presented an objective, systematic, and comprehensive analysis of the literature on DCI after SAH. Currently, the hotspots in this field focus on pathophysiological mechanisms.


Calcium-induced assembly of adherens junctions in keratinocytes.
Extracellular calcium concentration has been shown to control the stratification of cultured keratinocytes, presumably by regulation of formation of desmosomes. Previous studies have shown that keratinocytes cultured in medium containing 0.1 mM Ca++ form loose colonies without desmosomes. If the Ca++ is raised to 1 mM, desmosomes are assembled and the distribution of keratin filaments is altered. We have examined the disposition of vinculin and actin in keratinocytes under similar conditions. Using immunofluorescence microscopy we show that raising [Ca++] in the medium dramatically alters the distribution of vinculin and actin and results in the formation of adherens-type junctions within 15 min after switching to high calcium medium. Borders of cells at the edge of colonies, which are not proximal to other cells, are not affected, while cells in the interior of the colony form junctions around their periphery. Attachment plaques in keratinocytes grown in low calcium medium are located at the ventral plane of the cell, but junctions formed after switching to high calcium are not, as demonstrated by interference reflection microscopy. In cells colabeled with antibodies against vinculin and desmoplakin, vinculin-containing adherens junctions were visible before desmosomal junctions when cells were switched to high calcium. Although newly formed vinculin-containing structures in high calcium cells, like desmosomes, colocalize with phase-dense structures, superimposition of video fluorescence images using digitized fluorescence microscopy indicates that adherens junctions and desmosomes are discrete structures. Adherens junctions, like desmosomes, may play an essential role in controlling stratification of keratinocytes.


Developmental dyscalculia: a dysconnection syndrome?
Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10 years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia.


Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials.
To improve the evaluation of the possible antiarrhythmic effect of statins, we performed a meta-analysis of randomized trials with statins on the end point of incidence or recurrence of atrial fibrillation (AF). The use of statins had been suggested to protect against AF in some clinical observational and experimental studies but has remained inadequately explored. A systematic review of controlled trials with statins was performed. Eligible studies had to have been randomized controlled parallel-design human trials with use of statins that collected data on incidence or recurrence of AF. Six studies with 3,557 patients in sinus rhythm were included in the analysis. Three studies investigated the use of statins in patients with a history of paroxysmal AF (n = 1) or persistent AF undergoing electrical cardioversion (n = 2), and 3 investigated the use of statins in primary prevention of AF in patients undergoing cardiac surgery or after acute coronary syndrome. Incidence or recurrence of AF occurred in 386 patients. Overall, the use of statins was significantly associated with a decreased risk of AF compared with control (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18 to 0.85, p = 0.02). Benefit of statin therapy seemed more marked in secondary prevention of AF (OR 0.33, 95% CI 0.10 to 1.03, p = 0.06) than for new-onset or postoperative AF (OR 0.60, 95% CI 0.27 to 1.37, p = 0.23). Use of statins was significantly associated with a decreased risk of incidence or recurrence of AF in patients in sinus rhythm with a history of previous AF or undergoing cardiac surgery or after acute coronary syndrome.


Parameter optimization of a computer-aided diagnosis scheme for the segmentation of microcalcification clusters in mammograms.
Our purpose in this study is to develop a parameter optimization technique for the segmentation of suspicious microcalcification clusters in digitized mammograms. In previous work, a computer-aided diagnosis (CAD) scheme was developed that used local histogram analysis of overlapping subimages and a fuzzy rule-based classifier to segment individual microcalcifications, and clustering analysis for reducing the number of false positive clusters. The performance of this previous CAD scheme depended on a large number of parameters such as the intervals used to calculate fuzzy membership values and on the combination of membership values used by each decision rule. These parameters were optimized empirically based on the performance of the algorithm on the training set. In order to overcome the limitations of manual training and rule generation, the segmentation algorithm was modified in order to incorporate automatic parameter optimization. For the segmentation of individual microcalcifications, the new algorithm used a neural network with fuzzy-scaled inputs. The fuzzy-scaled inputs were created by processing the histogram features with a family of membership functions, the parameters of which were automatically extracted from the distribution of the feature values. The neural network was trained to classify feature vectors as either positive or negative. Individual microcalcifications were segmented from positive subimages. After clustering, another neural network was trained to eliminate false positive clusters. A database of 98 images provided training and testing sets to optimize the parameters and evaluate the CAD scheme, respectively. The performance of the algorithm was evaluated with a FROC analysis. At a sensitivity rate of 93.2%, there was an average of 0.8 false positive clusters per image. The results are very comparable with those taken using our previously published rule-based method. However, the new algorithm is more suited to generalize its performance on a larger population, depends on two monotonic outputs making its evaluation much easier and can be trained in an automatic way making practical its application on a large database.


Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.
Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and β-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from H2S and NH3. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.


Interfacial nanostructuring on the performance of polymer/TiO2 nanorod bulk heterojunction solar cells.
This work presents polymer photovoltaic devices based on poly(3-hexylthiophene) (P3HT) and TiO2 nanorod hybrid bulk heterojunctions. Interface modification of a TiO2 nanorod surface is conducted to yield a very promising device performance of 2.20% with a short circuit current density (J(sc)) of 4.33 mA/cm2, an open circuit voltage (V(oc)) of 0.78 V, and a fill factor (FF) of 0.65 under simulated A.M. 1.5 illumination (100 mW/cm2). The suppression of recombination at P3HT/TiO2 nanorod interfaces by the attachment of effective ligand molecules substantially improves device performance. The correlation between surface photovoltage and hybrid morphology is revealed by scanning Kelvin probe microscopy. The proposed method provides a new route for fabricating low-cost, environmentally friendly polymer/inorganic hybrid bulk heterojunction photovoltaic devices.


Fungal specificity and selectivity for algae play a major role in determining lichen partnerships across diverse ecogeographic regions in the lichen-forming family Parmeliaceae (Ascomycota).
Microbial symbionts are instrumental to the ecological and long-term evolutionary success of their hosts, and the central role of symbiotic interactions is increasingly recognized across the vast majority of life. Lichens provide an iconic group for investigating patterns in species interactions; however, relationships among lichen symbionts are often masked by uncertain species boundaries or an inability to reliably identify symbionts. The species-rich lichen-forming fungal family Parmeliaceae provides a diverse group for assessing patterns of interactions of algal symbionts, and our study addresses patterns of lichen symbiont interactions at the largest geographic and taxonomic scales attempted to date. We analysed a total of 2356 algal internal transcribed spacer (ITS) region sequences collected from lichens representing ten mycobiont genera in Parmeliaceae, two genera in Lecanoraceae and 26 cultured Trebouxia strains. Algal ITS sequences were grouped into operational taxonomic units (OTUs); we attempted to validate the evolutionary independence of a subset of the inferred OTUs using chloroplast and mitochondrial loci. We explored the patterns of symbiont interactions in these lichens based on ecogeographic distributions and mycobiont taxonomy. We found high levels of undescribed diversity in Trebouxia, broad distributions across distinct ecoregions for many photobiont OTUs and varying levels of mycobiont selectivity and specificity towards the photobiont. Based on these results, we conclude that fungal specificity and selectivity for algal partners play a major role in determining lichen partnerships, potentially superseding ecology, at least at the ecogeographic scale investigated here. To facilitate effective communication and consistency across future studies, we propose a provisional naming system for Trebouxia photobionts and provide representative sequences for each OTU circumscribed in this study.


Dual-color proteomic profiling of complex samples with a microarray of 810 cancer-related antibodies.
Antibody microarrays have the potential to enable comprehensive proteomic analysis of small amounts of sample material. Here, protocols are presented for the production, quality assessment, and reproducible application of antibody microarrays in a two-color mode with an array of 1,800 features, representing 810 antibodies that were directed at 741 cancer-related proteins. In addition to measures of array quality, we implemented indicators for the accuracy and significance of dual-color detection. Dual-color measurements outperform a single-color approach concerning assay reproducibility and discriminative power. In the analysis of serum samples, depletion of high-abundance proteins did not improve technical assay quality. On the contrary, depletion introduced a strong bias in protein representation. In an initial study, we demonstrated the applicability of the protocols to proteins derived from urine samples. We identified differences between urine samples from pancreatic cancer patients and healthy subjects and between sexes. This study demonstrates that biomedically relevant data can be produced. As demonstrated by the thorough quality analysis, the dual-color antibody array approach proved to be competitive with other proteomic techniques and comparable in performance to transcriptional microarray analyses.


The sexuality experience of older widows in Korea.
Sexuality plays an important role in elders' lives. However, few studies exist concerning the essential meaning crucial for the overall understanding of sexuality in later life. In this study we explored the experience of what sexuality implied and meant to older widows using the descriptive phenomenological approach. Purposive sampling yielded 10 elderly women who were in sexual relationships. We collected data through in-depth interviews with participants and conducted a thematic analysis. The findings were classified into eight themes: trying to find another side of herself, starting a romantic relationship, invigorating life, displaying femininity, being concerned about the perceptions of others, enjoying sexual freedom, feeling the limit of sexual intimacy, and facing up to reality. The sexual lives of older widows entailed a process of recovering their femininity, self-achievement, and self-esteem, which helped them to live independent lives by developing more active and flexible attitudes.


[Profiles of reading comprehension and written composition of children with high functioning autism].
Research about the academic profile of students with Autism Spectrum Disorder (ASD) reports a variable performance, although it tends to be lower than what it is expected according to the cognitive level. In the school context, reading and writing are crucial abilities for learning in different curricular areas and they have important implications for academic, social and occupational success. A brief review is carried out about the main reading and writing disabilities that students with ASD show. Studies about reading coincide to point out an adequate knowledge of the decodification processes. However, a lower performance in reading comprehension and, particularly, inferential comprehension has been frequently described. In addition, deficits in the different components of writing have been reported, especially, handwriting and text coherence. Different factors may explain this profile of difficulties, like linguistic factors or aspects related to the psychological theories of autism, which may contribute to possible interventions.


Growth-related quantitative trait loci in domestic and wild rainbow trout (Oncorhynchus mykiss).
Somatic growth is a complex process that involves the action and interaction of genes and environment. A number of quantitative trait loci (QTL) previously identified for body weight and condition factor in rainbow trout (Oncorhynchus mykiss), and two other salmonid species, were used to further investigate the genetic architecture of growth-influencing genes in this species. Relationships among previously mapped candidate genes for growth and their co-localization to identified QTL regions are reported. Furthermore, using a comparative genomic analysis of syntenic rainbow trout linkage group clusters to their homologous regions within model teleost species such as zebrafish, stickleback and medaka, inferences were made regarding additional possible candidate genes underlying identified QTL regions. Body weight (BW) QTL were detected on the majority of rainbow trout linkage groups across 10 parents from 3 strains. However, only 10 linkage groups (i.e., RT-3, -6, -8, -9, -10, -12, -13, -22, -24, -27) possessed QTL regions with chromosome-wide or genome-wide effects across multiple parents. Fewer QTL for condition factor (K) were identified and only six instances of co-localization across families were detected (i.e. RT-9, -15, -16, -23, -27, -31 and RT-2/9 homeologs). Of note, both BW and K QTL co-localize on RT-9 and RT-27. The incidence of epistatic interaction across genomic regions within different female backgrounds was also examined, and although evidence for interaction effects within certain QTL regions were evident, these interactions were few in number and statistically weak. Of interest, however, was the fact that these predominantly occurred within K QTL regions. Currently mapped growth candidate genes are largely congruent with the identified QTL regions. More QTL were detected in male, compared to female parents, with the greatest number evident in an F1 male parent derived from an intercross between domesticated and wild strain of rainbow trout which differed strongly in growth rate. Strain background influences the degree to which QTL effects are evident for growth-related genes. The process of domestication (which primarily selects faster growing fish) may largely reduce the genetic influences on growth-specific phenotypic variation. Although heritabilities have been reported to be relatively high for both BW and K growth traits, the genetic architecture of K phenotypic variation appears less defined (i.e., fewer major contributing QTL regions were identified compared with BW QTL regions).


Measuring the accuracy of particle position and force in optical tweezers using high-speed video microscopy.
We assess the performance of a CMOS camera for the measurement of particle position within optical tweezers and the associated autocorrelation function and power spectrum. Measurement of the displacement of the particle from the trap center can also be related to the applied force. By considering the Allan variance of these measurements, we show that such cameras are capable of reaching the thermal limits of nanometer and femtonewton accuracies, and hence are suitable for many of the applications that traditionally use quadrant photodiodes. As an example of a multi-particle measurement we show the hydrodynamic coupling between two particles.


The effect of diet on microfaunal population and function in the caecum of a subterranean naked mole-rat, Heterocephalus glaber.
The effect of dietary fibre and starch content on digestibility, microfaunal population and caecal function was investigated in a subterranean mole-rat, Heterocephalus glaber (Rodentia). Mole-rats were fed on a diet of either sweet potato (neutral-detergent fibre (NDF) 65 g/kg dry matter (DM), starch 638 g/kg DM) or carrot (NDF 157 g/kg DM, starch 258.7 g/kg DM) for 4 weeks. Daily intake and faecal output were monitored. Thereafter caecal microfaunal population, density and function were assessed using light and scanning electron microscopy and by measuring both gas and short chain fatty acid (SCFA) production. A 2.4-fold increase in fibre and 2.5-fold decrease in starch content resulted in a decrease in caecal DM content (390 g/kg). A concomitant dramatic decline (by 93%) in ciliate protozoa with a corresponding 2-fold increase in bacteria also accompanied this change in diet. Fermentative efficiency as indicated by gas production was 2.6 times greater on a carrot diet than on sweet potato. Microbial fermentation resulted in higher SCFA concentrations on the carrot diet, with a 42% reduction in SCFA concentration on the sweet potato diet. Here, SCFA contributed 5.1% of daily energy expenditure and this increased 5.0-fold on the carrot diet. Caecal micro-organism function, therefore, played an important role in the nutritional physiology of these naked mole-rats, and enabled maximum utilization of the food substrate.


Levels of cyclic nucleotides in autotransplanted 7, 12-dimethylbenz[a]anthracene-induced rat mammary tumors during their growth and regression.
Previous studies indicated that autotransplanted 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors were hormone-dependent and, if derived from a single primary tumor, many of their metabolic parameters varied little. Therefore, these tumors transplanted in multiple sites provided an opportunity for serial sampling of individual tumors for repeated biochemical evaluations. In the present study, primary mammary tumors induced by DMBA in female noninbred Sprague-Dawley rats were autotransplanted at six sites. When these grafts grew to an average size of 6 cm, the hosts were ovariectomized. Eighteen days later when all tumors were apparently regressing, a silastic tubing 2 cm long containing crystalline estradiol was implanted sc into each host for 14 days. Individual tumors were serially removed from each host before ovariectomy, after ovariectomy, and after estrogen replacement. Levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) in these tumors were measured by radioimmunoassay. Results indicated that tumor regression was associated with an elevation of cAMP levels and that tumor growth was accompanied by a decline in cAMP. The level of cGMP did not correlate with either tumor growth or regression. Therefore, the concept that cAMP is a biologic regulator for tissue proliferation and regression may be applied to the present model of autotransplanted, DMBA-induced rat mammary tumors.


Modeling Site Heterogeneity with Posterior Mean Site Frequency Profiles Accelerates Accurate Phylogenomic Estimation.
Proteins have distinct structural and functional constraints at different sites that lead to site-specific preferences for particular amino acid residues as the sequences evolve. Heterogeneity in the amino acid substitution process between sites is not modeled by commonly used empirical amino acid exchange matrices. Such model misspecification can lead to artefacts in phylogenetic estimation such as long-branch attraction. Although sophisticated site-heterogeneous mixture models have been developed to address this problem in both Bayesian and maximum likelihood (ML) frameworks, their formidable computational time and memory usage severely limits their use in large phylogenomic analyses. Here we propose a posterior mean site frequency (PMSF) method as a rapid and efficient approximation to full empirical profile mixture models for ML analysis. The PMSF approach assigns a conditional mean amino acid frequency profile to each site calculated based on a mixture model fitted to the data using a preliminary guide tree. These PMSF profiles can then be used for in-depth tree-searching in place of the full mixture model. Compared with widely used empirical mixture models with $k$ classes, our implementation of PMSF in IQ-TREE (http://www.iqtree.org) speeds up the computation by approximately $k$/1.5-fold and requires a small fraction of the RAM. Furthermore, this speedup allows, for the first time, full nonparametric bootstrap analyses to be conducted under complex site-heterogeneous models on large concatenated data matrices. Our simulations and empirical data analyses demonstrate that PMSF can effectively ameliorate long-branch attraction artefacts. In some empirical and simulation settings PMSF provided more accurate estimates of phylogenies than the mixture models from which they derive.


Long-term follow-up of a randomized controlled trial on additional core stability exercises training for improving dynamic sitting balance and trunk control in stroke patients.
Analyse the effect of core stability exercises in addition to conventional physiotherapy training three months after the intervention ended. A randomized controlled trial. Outpatient services. Seventy-nine stroke survivors. In the intervention period, both groups underwent conventional physiotherapy performed five days/week for five weeks, and in addition the experimental group performed core stability exercises for 15 minutes/day. Afterwards, during a three-month follow-up period, both groups underwent usual care that could eventually include conventional physiotherapy or physical exercise but not in a controlled condition. Primary outcome was trunk control and dynamic sitting balance assessed by the Spanish-Version of Trunk Impairment Scale 2.0 and Function in Sitting Test. Secondary outcomes were standing balance and gait evaluated by the Berg Balance Scale, Tinetti Test, Brunel Balance Assessment, Spanish-Version of Postural Assessment Scale for Stroke and activities of daily living using the Barthel Index. A total of 68 subjects out of 79 completed the three-month follow-up period. The mean difference (SD) between groups was 0.78 (1.51) points ( p = 0.003) for total score on the Spanish-Version of Trunk Impairment Scale 2.0, 2.52 (6.46) points ( p = 0.009) for Function in Sitting Test, dynamic standing balance was 3.30 (9.21) points ( p= 0.009) on the Berg Balance Scale, gait was 0.82 (1.88) points ( p = 0.002) by Brunel Balance Assessment (stepping), and 1.11 (2.94) points ( p = 0.044) by Tinetti Test (gait), all in favour of core stability exercises. Core stability exercises plus conventional physiotherapy have a positive long-term effect on improving dynamic sitting and standing balance and gait in post-stroke patients.


Biopterin derivatives in human body fluids and tissues.
Levels of biopterin derivatives in urine, serum, milk, cerebrospinal fluid, brain, and liver have been measured with the Crithidia fasciculata assay. Normal levels in serum and urine have been given and compared with those in a number of benign and malignant proliferative disorders, phenylketonuria, kidney disease, Parkinson's disease, schizophrenia, controlled epilepsy, rheumatoid arthritis, and pernicious anaemia. The active component of Crithidia factor in serum was 7,8-dihydrobiopterin. Tissue, urine, and some serum samples contained two active materials, the principal one being 7,8-dihydrobiopterin; a minor constituent was probably tetrahydrobiopterin. Serum biopterin levels following methotrexate administration were raised and subsequent administration of folic acid and 5-formyltetrahydrofolic acid further increased serum levels of biopterin derivatives; this was in contrast to the total absence of response to oral folates without prior methotrexate and to 5-methyltetrahydrofolic acid either with or without methotrexate being given.


Altered neural cholinergic receptor systems in cocaine-addicted subjects.
Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1- to 6-week abstinent, cocaine- (and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p<0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.


Molecular engineering: An approach to the development of general capabilities for molecular manipulation.
Development of the ability to design protein molecules will open a path to the fabrication of devices to complex atomic specifications, thus sidestepping obstacles facing conventional microtechnology. This path will involve construction of molecular machinery able to position reactive groups to atomic precision. It could lead to great advances in computational devices and in the ability to manipulate biological materials. The existence of this path has implications for the present.


Cytokinin controls polarity of PIN1-dependent auxin transport during lateral root organogenesis.
The plant hormones auxin and cytokinin mutually coordinate their activities to control various aspects of development [1-9], and their crosstalk occurs at multiple levels [10, 11]. Cytokinin-mediated modulation of auxin transport provides an efficient means to regulate auxin distribution in plant organs. Here, we demonstrate that cytokinin does not merely control the overall auxin flow capacity, but might also act as a polarizing cue and control the auxin stream directionality during plant organogenesis. Cytokinin enhances the PIN-FORMED1 (PIN1) auxin transporter depletion at specific polar domains, thus rearranging the cellular PIN polarities and directly regulating the auxin flow direction. This selective cytokinin sensitivity correlates with the PIN protein phosphorylation degree. PIN1 phosphomimicking mutations, as well as enhanced phosphorylation in plants with modulated activities of PIN-specific kinases and phosphatases, desensitize PIN1 to cytokinin. Our results reveal conceptually novel, cytokinin-driven polarization mechanism that operates in developmental processes involving rapid auxin stream redirection, such as lateral root organogenesis, in which a gradual PIN polarity switch defines the growth axis of the newly formed organ.


Evaluation of covalent antisickling compounds by PO2 scan ektacytometry.
The ektacytometer, a device to measure erythrocyte flexibility, has been used to evaluate antisickling agents that covalently modify hemoglobin S (HbS). The instrument has been adapted to produce a continuous gradient of oxygen pressure in the measuring cuvette, which permitted the rapid determination of sickle cell rigidity over the complete oxygenation range. Inspection of curves allows classification of the compounds according to their mode of action: altering oxygen affinity or increasing deoxy-HbS solubility. Reagents that modify amino groups, thiols, and histidine, as well as a crosslinking agent, were examined. The method directly evaluates deoxygenated cell deformability rather than cell shape. Many of the compounds that are effective in preventing the morphological sickling of deoxygenated sickle cells do not necessarily restore cell deformability. The method also readily detects membrane damage brought about by covalent agents that nonspecifically derivatize membrane proteins. Cystamine and pyridoxal appear to improve deformability in deoxygenated SS cells at concentrations that do not damage the membrane. This method, which examines the intact cell, fills a gap in the available experimental techniques for drug evaluation, between studies of isolated hemoglobin and in vivo studies.


A double recombinant adenovirus expressing the costimulatory molecule B7-1 (murine) and human IL-2 induces complete tumor regression in a murine breast adenocarcinoma model.
Tumors that express tumor-specific antigens can maintain growth in an immunocompetent organism. Current hypotheses tend toward T cell anergy as a key component for the inhibition of immunoreactivity against such tumors. Anergy is thought to occur from hyperactive stimulation of the TCR in the absence of costimulation (costimulation leads to proliferation via IL-2 production). Subcutaneous injection of transgenic polyoma middle T transformed breast adenocarcinoma tumor cells (PyMT) in the hind flank of FVB/n mice results in the formation of tumor nodules at this site. We determined the MHC class I and class II, B7-1, and B7-2 expression in the tumor cells by flow cytometry and showed positive staining for only MHC class I. We show that a single E1-deleted adenovirus constructed to express both the costimulatory molecule B7-1 (murine) and human IL-2 genes (Ad5E1 mB7-1/human IL-2) elicits a very potent antitumor response when administered intratumorally. Ad5E1 mB7-1/human IL-2 induced rapid and complete regression (100%) of all tumors compared with Ad5 E1 mB7-1 (38%), Ad CAIL-2 (42%), and Ad5E1 dl70-3 (control vector) (0%). All mice that exhibited complete tumor regression were fully protected in tumor cell challenge experiments. The systemic immunity generated by intratumoral administration of the Ad vectors was associated with a strong anti-PyMT CTL response. These observations indicate that augmenting the immunogenicity of the tumor with coincident expression of B7-1 in combination with IL-2 may prove beneficial in direct tumor immunotherapy.


Respirometric characterization of aerobic sulfide, thiosulfate and elemental sulfur oxidation by S-oxidizing biomass.
Respirometry was used to reveal the mechanisms involved in aerobic biological sulfide oxidation and to characterize the kinetics and stoichiometry of a microbial culture obtained from a desulfurizing biotrickling filter. Physical-chemical processes such as stripping and chemical oxidation of hydrogen sulfide were characterized since they contributed significantly to the conversions observed in respirometric tests. Mass transfer coefficient for hydrogen sulfide and the kinetic parameters for chemical oxidation of sulfide with oxygen were estimated. The stoichiometry of the process was determined and the different steps in the sulfide oxidation process were identified. The conversion scheme proposed includes intermediate production of elemental sulfur and thiosulfate and the subsequent oxidation of both compounds to sulfate. A kinetic model describing each of the reactions observed during sulfide oxidation was calibrated and validated. The product selectivity was found to be independent of the dissolved oxygen to hydrogen sulfide concentration ratio in the medium at sulfide concentrations ranging from 3 to 30 mg S L(-1). Sulfide was preferentially consumed (SOURmax = 49.2 mg DO g(-1) VSS min(-1)) and oxidized to elemental sulfur at dissolved oxygen concentrations above 0.8 mg DO L(-1). Substrate inhibition of sulfide oxidation was observed (K(i,S(2-))= 42.4 mg S L(-1)). Intracellular sulfur accumulation also affected negatively the sulfide oxidation rate. The maximum fraction of elemental sulfur accumulated inside cells was estimated (25.6% w/w) and a shrinking particle equation was included in the kinetic model to describe elemental sulfur oxidation. The microbial diversity obtained through pyrosequencing analysis revealed that Thiothrix sp. was the main species present in the culture (>95%).


Broad Spectrum Anti-Bacterial Activity and Non-Selective Toxicity of Gum Arabic Silver Nanoparticles.
Silver nanoparticles (AgNPs) are the most commercialized nanomaterials and presumed to be biocompatible based on the biological effects of the bulk material. However, their physico-chemical properties differ significantly to the bulk materials and are associated with unique biological properties. The study investigated the antimicrobial and cytotoxicity effects of AgNPs synthesized using gum arabic (GA), sodium borohydride (NaBH4), and their combination as reducing agents. The AgNPs were characterized using ultraviolet-visible spectrophotometry (UV-Vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FT-IR). The anti-bacterial activity was assessed using agar well diffusion and microdilution assays, and the cytotoxicity effects on Caco-2, HT-29 and KMST-6 cells using MTT assay. The GA-synthesized AgNPs (GA-AgNPs) demonstrated higher bactericidal activity against all bacteria, and non-selective cytotoxicity towards normal and cancer cells. AgNPs reduced by NaBH4 (C-AgNPs) and the combination of GA and NaBH4 (GAC-AgNPs) had insignificant anti-bacterial activity and cytotoxicity at ≥50 µg/mL. The study showed that despite the notion that AgNPs are safe and biocompatible, their toxicity cannot be overruled and that their toxicity can be channeled by using biocompatible polymers, thereby providing a therapeutic window at concentrations that are least harmful to mammalian cells but toxic to bacteria.


Expression of Histophilus somni IbpA DR2 protective antigen in the diatom Thalassiosira pseudonana.
Increasing demand for the low-cost production of valuable proteins has stimulated development of novel expression systems. Many challenges faced by existing technology may be overcome by using unicellular microalgae as an expression platform due to their ability to be cultivated rapidly, inexpensively, and in large scale. Diatoms are a particularly productive type of unicellular algae showing promise as production organisms. Here, we report the development of an expression system in the diatom Thalassiosira pseudonana by expressing the protective IbpA DR2 antigen from Histophilus somni for the production of a vaccine against bovine respiratory disease. The utilization of diatoms with their typically silicified cell walls permitted development of silicon-responsive transcription elements to induce protein expression. Specifically, we demonstrate that transcription elements from the silicon transporter gene SIT1 are sufficient to drive high levels of IbpA DR2 expression during silicon limitation and growth arrest. These culture conditions eliminate the flux of cellular resources into cell division processes, yet do not limit protein expression. In addition to improving protein expression levels by molecular manipulations, yield was dramatically increased through cultivation enhancement including elevated light and CO2 supplementation. We substantially increased recombinant protein production over starting levels to 1.2% of the total sodium dodecyl sulfate-extractable protein in T. pseudonana, which was sufficient to conduct preliminary immunization trials in mice. Mice exposed to 5 μg of diatom-expressed DR2 in whole or sonicated cells (without protein purification) exhibited a modest immune response without the addition of adjuvant.


[Cajal and neuroscience in the eve of the third millenium].
This is a brief history of the birth of Neuroscience as an independent branch of knowledge. The importance of Cajal's contribution to the structuralization of modern Neuroscience is described. Outstanding contributions to Neuroscience of the last century, particularly the Decade of the Brain, are summarized. The reason for the huge increase and interest in neuroscientific studies are given. Finally, I emphasize the challenge that multidisciplinary study and interinstitutional collaboration pose to advancing our knowledge of the human brain. The second part of the talk demonstrated the validity of Cajal's work in modern Neuroscience insisting on three aspects: 1) the microscopic study of the Mammalian central nervous system, 2) the neurogenesis and development of the nervous system and 3) the degeneration, regeneration and plasticity of the central nervous system. I conclude that Cajal's timeliness is reflected by the fact that there are few problems in modern Neuroscience which Cajal did not address at one time or other.


Determinants of Higher-Risk Sexual Behavior in Some Selected African Countries.
Although higher-risk sexual behavior (H-RSB) is a major contributor to the rapid rising rate of new HIV infections, there exists paucity of comprehensive evidence across the sub-Saharan African region. The purpose of this study was to determine the prevalence of H-RSB and its determinants across sub-Saharan Africa to inform policy. Data were obtained from the Demographic and Health Survey (DHS) of ten sub-Saharan African (SSA) countries with their three most current DHS surveys from 2000 to 2016. Only participants who ever had sexual encounters in their lifetime were included in the study. Weighted adjusted Cox regression with robust variance and constant time was used to investigate disparities of H-RSB among the ten SSA countries. Relationships between sociodemographic, socioeconomic, knowledge, mass media, and H-RSB were investigated. The trend and prevalence of higher-risk sexual behavior show that Lesotho experienced a decreasing trend of the prevalence of H-RSB from 8.92 in period one to 6.42 in period three. Ghana experienced a marginal increase from 6.22 in period one to 6.76 in period two and then to 6.43 in the third period. However, Malawi, Zambia, and Zimbabwe obtained a marginal increasing trend in the prevalence of H-RSB from period one to three: 2.75 to 3.74, 4.33 to 6.24, and 6.11 to 7.99, respectively. Meanwhile, the prevalence of H-RSB in Namibia and Uganda decreased in period two to 1.84 and 5.76 but increased in period three to 2.01 and 6.83, respectively. Generally, determinants of H-RSB among the countries include age, sex, religious affiliation, marital status, educational level, employment status, economic status, age at first sex, and status of circumcision. Trend of relatively high prevalence of H-RSB has been found across majority of the countries with key sociodemographic factors influencing H-RSB. Therefore, different targeted interventional approaches are needed in all the countries to help reduce H-RSB and the overall HIV incidence. If issues regarding sexual behavior and sexual health are not addressed adequately, H-RSB can negate all the appreciable efforts aimed at ending the HIV pandemic by 2030.


Effect of telmisartan, valsartan and candesartan on mycophenolate mofetil pharmacokinetics in Japanese renal transplant recipients.
The aim of this study was to elucidate the effect of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activating angiotensin receptor blocker (ARB) telmisartan and the non-PPAR-gamma activating ARB valsartan and candesartan on mycophenolic acid (MPA) pharmacokinetics in renal transplant recipients. Recipients (n = 10 each group) were randomly given either 40 mg of telmisartan, 80 mg of valsartan or 8 mg of candesartan cilexetil for at least 6 months, and no ARB. Blood was sampled a year after transplantation. Dose-adjusted maximum and trough plasma concentration of MPA co-administered with telmisartan were the lowest in all groups. The mean dose-adjusted area under the concentration curve from 0 to 12 h (AUC(0-12)) and AUC(0-6) of MPA co-administered with telmisartan were significantly lower than that without ARB (98 vs. 138 ng x h/mL/mg, P = 0.0353 and 63 vs. 96 ng x h/mL/mg, P = 0.0305). Coadministration of valsartan and candesartan did not alter MPA pharmacokinetics. The AUC ratio of MPA glucuronide (MPAG)/MPA co-administered with telmisartan was higher than that without ARBs, but not significantly (14.2 vs. 9.1). The mean maximum and minimum plasma concentrations of telmisartan (40 mg) after oral administration were 84 and 15 ng/mL, respectively, and that of valsartan (80 mg) 2220 and 441 ng/mL, respectively. Plasma concentrations of candesartan in most transplant patients were not observed 19 h after oral administration of candesartan cilexeil (8 mg). The degree of drug interaction between MPA and telmisartan was significantly greater than that between MPA and valsartan or candesartan. Uridine diphosphate-glucuronosyltransferase (UGT) 1A9 has been identified as a PPAR-gamma target gene. UGT induction by telmisartan might stimulate MPA glucuronidation. A combination of telmisartan and mycophenolate mofetil might require periodic monitoring of MPA.


Mock clinic. An approach to clinical education.
This paper presents a new clinical education experience initiated at the University of Wisconsin-La Crosse. A Mock Clinic was developed that simulates a real-life physical therapy department: students adopt roles of both physical therapist and patient. Each student is student-therapist and student-patient at least once each session. At the beginning of each session, the student-therapist selects a patient treatment card (containing instructions submitted by academic and clinical faculty members) and a faculty supervisor discusses the role of the patient with the student-patient to assist him in accurately displaying signs and symptoms. The student-therapist alos meets with the faculty supervisor to review the patient and the approach. The student-therapist then "evaluates" and "treats" the student-patient. A group discussion concludes each session. Mock Clinic is a role-playing experience that provides the opportunity for students to see themselves in clinical situations and enables them to learn without involving real clients. Strengths and weaknesses of Mock Clinic identified by all participants are discussed.


Diagnosing and managing androgen deficiency in men.
Androgens play a crucial role in bone, muscle and fat metabolism, erythropoiesis and cognitive health. In men aged 40-79 years the incidence of biochemical deficiency and symptomatic hypogonadism is 2.1-5.7%. Decreased libido or reduced frequency and quality of erections, fatigue, irritability, infertility or a diminished feeling of wellbeing may be presenting complaints. However, a significant proportion of men with androgen deficiency will be identified when they present for unrelated concerns. Important factors to elicit from the history in addition to the presenting complaint include: a medical history of obesity, type 2 diabetes, systemic diseases or metabolic syndrome which all impact on testosterone physiology. A comprehensive medical review will identify agents which can cause low testosterone levels such as statins, steroids, opioids, dopamine antagonists and 5-alpha reductase inhibitors. Alcohol, anabolic steroids and illicit substance use such as marihuana can impact on testosterone levels and non-prescribed drug use should be routinely discussed. The mainstay of treatment in persisting androgen deficiency is to restore normal physiological levels of testosterone by using exogenous testosterone. It may take at least three to six weeks to notice any clinical improvement in symptoms. Men receiving testosterone supplementation should be followed closely and have their testosterone, haematocrit and PSA levels checked at three, six and twelve months after initiation of testosterone replacement therapy. Men should then be reviewed at least annually thereafter.


Selective modification of the acid-base properties of ceria by supported Au.
Au supported on CeO(2) prepared by deposition-precipitation with urea leads to a basic catalyst. Au acts in two ways as surface modifier. First, Au selectively interacts with Ce(4+) cations by either blocking access to or reducing Ce(4+) to Ce(3+). Second, the resulting Au atoms (presumably as Au(+) ions) act as soft, weak Lewis acid sites stabilizing carbanion intermediates and enhancing hydride abstraction in the dehydrogenation of alcohols. In consequence, the thus-synthesized basic catalyst catalyzes the dehydrogenation of propan-2-ol to acetone with high efficiency and without notable deactivation. Additionally, the dehydration pathway of propan-2-ol is eliminated, as Au also quantitatively blocks access to strongly acidic Ce(4+) ions or reduces them to Ce(3+).


Measles seroprevalence in adolescents and young adults living with HIV and response to MMR booster in seronegative ones.
The study analyzed people with HIV (PWH) measles seroprevalence and response to MMR booster given to seronegative individuals. A prospective cohort study with four groups: vertically (v-HIV), horizontally infected (h-HIV) individuals, and two control groups. An MMR booster was offered to seronegative individuals. Measles seropositivity and IgG antibodies were significantly lower in v-HIV than in the other groups. All measles seronegative patients responded to booster. An MMR booster must be sought during adolescence in vertically PWH.


Influence of the Topographic Vascular Distribution of the Face on Dermal Filler Accidents.
Dermal fillers are an important tool in the field of aesthetic dermatology. Fillers are relatively noninvasive and easy to use but are not free of secondary complications. The main complications are vascular and are due to either the compression of an artery or the direct introduction of the product into the arterial lumen. The aim of this study is to provide an overview of the vascular territories of the face to avoid many possible complications when using facial fillings. Anatomical localization of the main arterial supply to the face has been described to assess the risk of vascular injury. The authors dissected 17 hemifaces of embalmed adult cadavers that had previously been injected, through the common carotid artery, with latex containing a red dye. A topographic distribution was generated by facial regions following a clinical approach from where the facial fillings were placed and related to the pathways of the arteries. Following these criteria, we established 8 topographic regions (I-VIII) that indicate the main vascular problems of each of these regions. Detailed anatomical localizations of the main arteries in these topographic regions of the face and their relationships are described. The highest index of vascular lesions and especially visual alterations occurred for fillings of the upper third of the face. To prevent and avoid this type of lesion, it is advisable to avoid, as much as possible, treatments with filling materials in the upper third of the face, mainly including the glabellar and nasal region (III) and supraorbital region (VIII).


Strategies for Longitudinal Research with Youth in Foster Care: A Demonstration of Methods, Barriers, and Innovations.
Longitudinal research on youth in foster care is important, but often challenging to accomplish. To assist the field, a thorough description of the development of the SPARK (Studying Pathways to Adjustment and Resilience in Kids) project, a longitudinal research project on the mechanisms of resilience for foster youth and their caregivers, is presented. Authors explain the difficult task for researchers in accessing youth in foster care and suggest strategies for success. Recruitment approaches for foster youth and their families are also provided along with examples of effective techniques. Data collection concerns are discussed, and the authors provide recommendations for researchers to consider when asking youth sensitive questions. Finally, data collection on academic information from teachers and how the SPARK project works with the academic community to gain information on school functioning for youth in the project is described. Suggestions for methodology utilized in future research along with examples of innovative adjustments to typical research procedures are provided as guidance for how research on maltreated youth can be conducted.


Both central command and exercise pressor reflex reset carotid sinus baroreflex.
In decerebrate unanesthetized cats, we determined whether either "central command," the exercise pressor reflex, or the muscle mechanoreceptor reflex reset the carotid baroreflex. Both carotid sinuses were vascularly isolated, and the carotid baroreceptors were stimulated with pulsatile pressure. Carotid baroreflex function curves were determined for aortic pressure, heart rate, and renal vascular conductance. Central command was evoked by electrical stimulation of the mesencephalic locomotor region (MLR) in cats that were paralyzed. The exercise pressor reflex was evoked by statically contracting the triceps surae muscles in cats that were not paralyzed. Likewise, the muscle mechanoreceptor reflex was evoked by stretching the calcaneal tendon in cats that were not paralyzed. We found that each of the three maneuvers shifted upward the linear relationship between carotid sinus pressure and aortic pressure and heart rate. Each of the maneuvers, however, had no effect on the slope of these baroreflex function curves. Our findings show that central command arising from the MLR as well as the exercise pressor reflex are capable of resetting the carotid baroreflex.


Assessment of three variations of the 1,9-dimethylmethylene blue assay for measurement of sulfated glycosaminoglycan concentrations in equine synovial fluid.
To determine whether 3 variations of the 1,9-dimethylmethylene blue (DMMB) assay yield comparable results when measuring sulfated glycosaminoglycan (sGAG) concentrations in equine synovial fluid (SF). 25 samples of SF collected from affected joints of 13 horses and 13 samples of SF collected from nonaffected (control) joints of 4 horses. Sulfated glycosaminoglycan concentrations were measured by the direct spectrophotometric (ie, Farndale), microplate, and indirect DMMB assays in samples of SF collected from normal and affected joints and in samples digested with nucleases, papain, and hyaluronidase. All 3 assays reacted similarly to standard solutions of sGAGs and digestion of SF samples with nucleases, papain, and hyaluronidase. Nucleic acids were not important interfering substances, and papain and hyaluronidase could not be used interchangeably to digest SE All 3 assays proved to have satisfactory precision (SD < 10%), but each DMMB assay resulted in significantly different measures of sGAG in equine SF. Samples of SF should be digested with papain or hyaluronidase prior to measurement via DMMB assay. Researchers currently are unable to compare clinical information when variations of the DMMB assay are used, because each DMMB assay yields substantially different sGAG concentrations in SF. Of the 3 assays examined here, we recommend use of the direct spectrophotometric DMMB assay.


Liquidus Tracking: Large scale preservation of encapsulated 3-D cell cultures using a vitrification machine.
Currently, cryo-banking of multicellular structures such as organoids, especially in large volumes at clinical scale >1 L, remains elusive for reasons such as insufficient dehydration and cryoprotectant additive (CPA1) penetration, slow cooling and warming rates and devitrification processes. Here we introduce the concept of Liquidus Tracking (LT) using a semi-automated process for liquid volumes of up to 450 ml including 130 ml of alginate encapsulated liver cells (AELC) that archived controlled and reversible vitrification with minimized toxicity. First a CPA solution with optimal properties for LT was developed by employing different small scale test systems. Combining sugars such as glucose and raffinose with Me2SO improved post-exposure (at +0.5 °C) viabilities from 6% ±3.6 for Me2SO alone up to 58% ±6.1 and 65% ±14.2 respectively (p < 0.01). Other permeating CPAs (e.g. ethylene glycol, propylene glycol, methanol) were investigated as partial replacements for Me2SO. A mixture of Me2SO, ethylene glycol and glucose (ratio 4:2:1- termed LTdeg) supported glass-forming tendencies with appropriate low viscosities and toxicities required for LT. When running the full LT process, using Me2SO alone, no viable cells were recovered; using LTdeg, viable recoveries were improved to 40% ±8 (p<0.001%). Further refinements of improved mixing technique further improved recovery after LT. Recoveries of specific liver cell functions such as synthesis of albumin and alpha-fetoprotein (AFP) were retained in post thaw cultures. In summary: By developing a low-toxicity CPA solution of low viscosity (LTdeg) suitable for LT and by improving the stirring system, post-warming viability of AELC of up to 90% and a AFP secretion of 89% were reached. Results show that it may be possible to develop LT as a suitable cryogenic preservation process for different cell therapy products at large scale.


Structured clinical examinations in labor: rekindling the craft of obstetrics.
Exact knowledge of fetal station and position is of paramount importance for reliable surveillance of labor progress and a prerequisite for safe operative vaginal procedures. Detailed clinical assessments are thoroughly described in old textbooks, but almost forgotten in contemporary obstetrics. Ultrasound is suggested as an objective diagnostic tool in active labor. Several publications have demonstrated a low correlation between ultrasound and clinical assessment of fetal head station and position, but the methods of clinical assessment in these studies are poorly described. We wanted to explore if a quality clinical assessment could perform better than clinical assessment in previous publications, by analyzing the correlation between a structured method of clinical assessment and intrapartum ultrasound. In all, 100 laboring women with cervical dilatation ≥7 cm were included in a prospective cohort study at Oslo University Hospital-Ullevål from October to December 2016. The study design was cross-sectional. Clinical examinations were performed by one special educated consultant (JKI), and transabdominal and transperineal ultrasound clips were recorded and examined by a blinded expert in intrapartum ultrasound (TME). Fetal position was classified as a clock face with 12 units (hourly divisions) and thereafter categorized as occiput anterior (OA), left occiput transverse (LOT), occiput posterior (OP), and right occiput transverse (ROT) positions. Fetal station was categorized clinically from -5 to +5 and measured with ultrasound as angle of progression (AoP) and head-perineum distance (HPD). AoP is the angle between a longitudinal line through the symphysis and a tangent to the head contour. HPD is the shortest distance between the fetal skull and the perineum. Eight women were excluded due to strong contractions between clinical assessments and ultrasound measurements, fetal distress, or incomplete examinations. Fetal position assessed with ultrasound and clinical examination agreed exactly in 48/92 (52%) of cases, within one unit (hour) in 87/92 (95%) of cases and within two units in 90/92 (98%) of cases. It differed by three units in one case and by five units in one case. The agreement categorized into OA, LOT, OP, and ROT was good (Cohen's kappa 0.72; 95% CI 0.61-0.84). For station, the agreement was very good for both HPD (Pearson correlation coefficient r = 0.86; 95% CI 0.80-0.91) and AoP (r = 0.77; 95% CI to 0.67-0.84). The correlation between HPD and AoP was good (r = 0.76; 95% CI 0.65-0.84). We found very good correlations between structured clinical assessments and ultrasound examinations, suggesting that an objective quality in clinical examinations is possible to achieve. More focus on clinical skills training may improve accuracy for clinicians.


Interaction of Moringa oleifera seed protein with a mineral surface and the influence of surfactants.
The paper describes the adsorption of purified protein from seeds of Moringa oleifera to a sapphire interface and the effects of addition of the anionic surfactant sodium dodecylsulfate (SDS) and the cationic surfactant hexadecyltrimethylammonium bromide (CTAB). Neutron reflection was used to determine the structure and composition of interfacial layers adsorbed at the solid/solution interface. The maximum surface excess of protein was found to be about 5.3 mg m(-2). The protein does not desorb from the solid/liquid interface when rinsed with water. Addition of SDS increases the reflectivity indicating co-adsorption. It was observed that CTAB is able to remove the protein from the interface. The distinct differences to the behavior observed previously for the protein at the silica/water interface are identified. The adsorption of the protein to alumina in addition to other surfaces has shown why it is an effective flocculating agent for the range of impurities found in water supplies. The ability to tailor different surface layers in combination with various surfactants also offers the potential for adsorbed protein to be used in separation technologies.


APRIL/BLyS deficient rats prevent donor specific antibody (DSA) production and cell proliferation in rodent kidney transplant model.
APRIL (A proliferation inducing ligand) and BLyS (B Lymphocyte Stimulator) are two critical survival factors for B lymphocytes and plasma cells, the main source of alloantibody. We sought to characterize the specific effects of these cytokines in a kidney transplant model of antibody mediated rejection (AMR). We engineered APRIL-/- and BLyS-/- Lewis rats using CRISPR/Cas9. APRIL-/- and BLyS-/- rats were sensitized with Brown Norway (BN) blood (complete MHC mismatch). Twenty-one days following sensitization, animals were harvested and collected tissues were analyzed using flow cytometry, ELISPOT, and immunohistochemistry. Flow cross match and a 3 day mixed lymphocyte reaction (MLR) was performed to assess donor specific antibody (DSA) production and T-cell proliferation, respectively. Sensitized dual knock out Lewis rats (APRIL-/-/BLyS-/-) underwent kidney transplantation and were sacrificed on day 7 post-transplant. Sensitized BLyS-/- had significant decreases in DSA and cell proliferation compared to WT and APRIL-/- (p<0.02). Additionally, BLyS-/- rats had a significant reduction in IgG secreting cells in splenic marginal zone B lymphocytes, and in cell proliferation when challenged with alloantigen compared to WT and APRIL-/-. Transplanted APRIL-/-/BLyS-/- rodents had significantly less DSA and antibody secreting cells compared to WT (p<0.05); however, this did not translate into a significant difference in AMR seen between groups. In summary, our studies suggest that APRIL and BLyS play a greater role in DSA generation rather than AMR, highlighting the role of cellular pathways that regulate AMR.


A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation.
Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are effective in cancers with defective homologous recombination DNA repair (HRR), including BRCA1/2-related cancers. A test to identify additional HRR-deficient tumors will help to extend their use in new indications. We evaluated the activity of the PARPi olaparib in patient-derived tumor xenografts (PDXs) from breast cancer (BC) patients and investigated mechanisms of sensitivity through exome sequencing, BRCA1 promoter methylation analysis, and immunostaining of HRR proteins, including RAD51 nuclear foci. In an independent BC PDX panel, the predictive capacity of the RAD51 score and the homologous recombination deficiency (HRD) score were compared. To examine the clinical feasibility of the RAD51 assay, we scored archival breast tumor samples, including PALB2-related hereditary cancers. The RAD51 score was highly discriminative of PARPi sensitivity versus PARPi resistance in BC PDXs and outperformed the genomic test. In clinical samples, all PALB2-related tumors were classified as HRR-deficient by the RAD51 score. The functional biomarker RAD51 enables the identification of PARPi-sensitive BC and broadens the population who may benefit from this therapy beyond BRCA1/2-related cancers.


D121 Located within the DRY Motif of P2Y12 Is Essential for P2Y12-Mediated Platelet Function.
Platelets are anucleate cells that mediate hemostasis. This occurs via a primary signal that is reinforced by secreted products such as ADP that bind purinergic receptors (P2Y1 and P2Y12) on the platelet surface. We recently identified a human subject, whom we termed platelet defect subject 25 (PDS25) with a platelet functional disorder associated with the P2Y12 receptor. PDS25 has normal blood cell counts and no history of bleeding diathesis. However, platelets from PDS25 have virtually no response to 2-MeSADP (a stable analogue of ADP). Genetic analysis of P2Y12 from PDS25 revealed a heterozygous mutation of D121N within the DRY motif. Rap1b activity was reduced in platelets from PDS25, while VASP phosphorylation was enhanced, suggesting that signaling from the P2Y12 receptor was interrupted by the heterozygous mutation. To explore this further, we produced knock-in mice that mimic our subject. Bleeding failed to cease in homozygous KI mice during tail bleeding assays, while tail bleeding times did not differ between WT and heterozygous KI mice. Furthermore, occlusions failed to form in most homozygous KI mice following carotid artery injury via FeCl3. These data indicate that the aspartic acid residue found in the DRY motif of P2Y12 is essential for P2Y12 function.


Oral health attitudes and behaviours of final-year dental students.
The objectives of this study of final-year dental students in 10 classes (1997, 2001-2009) were to examine their self-reported oral health attitudes and behaviours and describe any trends in these attributes. Students were surveyed in final semester via an anonymous questionnaire (34 behaviour questions; eight attitude statements). Distributions, trends over time and attitude-behaviour associations were examined. Of 583 students, 459 responded (79%). All tooth-brushed with fluoride toothpaste; 80% brushed ≥2/day. Overall, 85% flossed; over time flossing behaviour increased significantly (P < 0.05), and those flossing 1-2/day increased (P < 0.005). Over time, significant decreases occurred in those taught toothbrushing (P < 0.001) and flossing (P < 0.05), and in use of mouth rinses (P < 0.05) and tooth cleansing sticks/picks (P < 0.001). Almost all (96%) had received a dental examination; 77% attended a dentist 1-3/year. Between-meal snacking was common (84%); 71% chewed gum. Although 18% had ever smoked, 5% currently smoked. Most strongly agreed they expected to keep most of their teeth for all their life (76%); their future needs for fillings would be minimal (61%); smoking could adversely affect their teeth or gums (85%); and regular dental attendance was important for their dental health (51%). Congruent attitudes and behaviours favouring oral health were widely held concerning dental attendance, flossing and smoking. Final-year dental students showed well established, favourable oral hygiene attitudes and behaviours, with evidence to suggest this knowledge was developed whilst in dental school. Despite many ceasing smoking, 5% still smoked. All dental students should receive training in motivational counselling and tobacco cessation to ensure this is included in patient care.


Dracunculiasis (guinea worm disease): eradication without a drug or a vaccine.
Dracunculiasis, commonly known as guinea worm disease, is a nematode infection transmitted to humans exclusively via contaminated drinking water. The disease prevails in the most deprived areas of the world. No vaccine or medicine is available against the disease: eradication is being achieved by implementing preventive measures. These include behavioural change in patients and communities--such as self-reporting suspected cases to health workers or volunteers, filtering drinking water and accessing water from improved sources and preventing infected individuals from wading or swimming in drinking-water sources--supplemented by active surveillance and case containment, vector control and provision of improved water sources. Efforts to eradicate dracunculiasis began in the early 1980s. By the end of 2012, the disease had reached its lowest levels ever. This paper reviews the progress made in eradicating dracunculiasis since the eradication campaign began, the factors influencing progress and the difficulties in controlling the pathogen that requires behavioural change, especially when the threat becomes rare. The challenges of intensifying surveillance are discussed, particularly in insecure areas containing the last foci of the disease. It also summarizes the broader benefits uniquely linked to interventions against dracunculiasis.


Use of wild and semi-wild edible plants in nutrition and survival of people in 1430 days of siege of Sarajevo during the war in Bosnia and Herzegovina (1992-1995).
This study is a systematic overview of data on use of wild and semi-wild edible plants in nutrition of people in 1430 days of the siege of Sarajevo during aggression on Bosnia and Herzegovina (1992-1995). The author of this study spent all that time in Sarajevo. In 1993, the author prepared a survival program for people that included usage of edible wild plants. In addition, he conducted a detailed survey, including special interviews, on 630 people of average age 37.4 years (55% residential inhabitants, the rest were refuges), 310 males and the rest were females. According to survey, 91 species of mostly wild plants and three species of fungus were used: Küchneromyces mutabilis, Armillariella mellea and Coprinus comatus. Wild vegetables included 49 species, spices 24, wild fruits 16, and 2 species of bread-plants. They belong to 26 plants communities, and grew on 24 different habitats (urban surfaces, river coasts, low forest and scrubs, meadows and rocky grasslands). The 156 plant parts (leaves, young branches, fruit, flower, seed, root and rhizome) from 91 plant species were used. Vegetables were dominant category of use (soups, pottages, sauces) with 80 ways of preparation (30.53%), then salads 41 (15.65%), spices 39 (14.89%), different beverages 38 (14.50%), sweets 21 (8.02%), nutritive teas 15 (5.73%), and other preparations. In order to improve conventional food (war pasta, rice, lentils, old beans) people used spices made from different wild plants.


The mother-cell-membrane adenosine triphosphatase of sporulating Clostridium pasteurianum.
1. Sporulation of Clostridium pasteurianum effects several changes in its proton-translocating cell-membrane H(+)-ATPase. Notable among these are the acquisition of susceptibility to activation by trypsin and a changed protein subunit composition. 2. A protein was isolated from the mother-cell membrane that inhibited the ATP phosphohydrolase activity of purified vegetative-cell-membrane H(+)-ATPase [BF(0)F(1) complex, which consists of soluble ATPase (BF(1)) and the proton-channel component (BF(0))] and rendered it susceptible to trypsin activation. 3. This trypsin-sensitive inhibitor protein had a molecular weight of 10000 and on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis was indistinguishable from the novel protein subunit e of the mother-cell-membrane ATPase 4. In bacteriorhodopsin-containing everted membrane vesicles, the specific ATP synthetase activity of the mother-cell-membrane ATPase was significantly greater than that of the vegetative-cell-membrane ATPase. 5. Treatment with trypsin-sensitive inhibitor protein of artificial proteoliposomes containing bacteriorhodopsin and vegetative-cell-membrane H(+)-ATPase (BF(0)F(1)) significantly increased the specific ATP synthetase activity of this enzyme. 6. The ATP synthetase activity of crude cell-membrane preparations from cultures of Clostridium pasteurianum increased during that period in the course of sporulation when the membrane ATP phosphohydrolase was both most rapidly decreasing in specific activity and acquiring its susceptibility to activation by trypsin.


When is the use of pacifiers justifiable in the baby-friendly hospital initiative context? A clinician's guide.
The use of pacifiers is an ancient practice, but often becomes a point of debate when parents and professionals aim to protect and promote breastfeeding as most appropriately for nurturing infants. We discuss the current literature available on pacifier use to enable critical decision-making regarding justifiable use of pacifiers, especially in the Baby-Friendly Hospital Initiative context, and we provide practical guidelines for clinicians. Suck-swallow-breathe coordination is an important skill that every newborn must acquire for feeding success. In most cases the development and maintenance of the sucking reflex is not a problem, but sometimes the skill may be compromised due to factors such as mother-infant separation or medical conditions. In such situations the use of pacifiers can be considered therapeutic and even provide medical benefits to infants, including reducing the risk of sudden infant death syndrome. The argument opposing pacifier use, however, is based on potential risks such as nipple confusion and early cessation of breastfeeding. The Ten Steps to Successful Breastfeeding as embedded in the Baby-Friendly Hospital Initiative initially prohibited the use of pacifiers in a breastfeeding friendly environment to prevent potential associated risks. This article provides a summary of the evidence on the benefits of non-nutritive sucking, risks associated with pacifier use, an identification of the implications regarded as 'justifiable' in the clinical use of pacifiers and a comprehensive discussion to support the recommendations for safe pacifier use in healthy, full-term, and ill and preterm infants. The use of pacifiers is justifiable in certain situations and will support breastfeeding rather than interfere with it. Justifiable conditions have been identified as: low-birth weight and premature infants; infants at risk for hypoglyceamia; infants in need of oral stimulation to develop, maintain and mature the sucking reflex in preterm infants; and the achievement of neurobehavioural organisation. Medical benefits associated with the use of pacifiers include providing comfort, contributing towards neurobehavioural organisation, and reducing the risk of sudden infant death syndrome. Guidelines are presented for assessing and guiding safe pacifier use, for specific design to ensure safety, and for cessation of use to ensure normal childhood development.


Quantitative Analysis of TDLUs using Adaptive Morphological Shape Techniques.
Within the complex branching system of the breast, terminal duct lobular units (TDLUs) are the anatomical location where most cancer originates. With aging, TDLUs undergo physiological involution, reflected in a loss of structural components (acini) and a reduction in total number. Data suggest that women undergoing benign breast biopsies that do not show age appropriate involution are at increased risk of developing breast cancer. To date, TDLU assessments have generally been made by qualitative visual assessment, rather than by objective quantitative analysis. This paper introduces a technique to automatically estimate a set of quantitative measurements and use those variables to more objectively describe and classify TDLUs. To validate the accuracy of our system, we compared the computer-based morphological properties of 51 TDLUs in breast tissues donated for research by volunteers in the Susan G. Komen Tissue Bank and compared results to those of a pathologist, demonstrating 70% agreement. Secondly, in order to show that our method is applicable to a wider range of datasets, we analyzed 52 TDLUs from biopsies performed for clinical indications in the National Cancer Institute's Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project and obtained 82% correlation with visual assessment. Lastly, we demonstrate the ability to uncover novel measures when researching the structural properties of the acini by applying machine learning and clustering techniques. Through our study we found that while the number of acini per TDLU increases exponentially with the TDLU diameter, the average elongation and roundness remain constant.