A Transcriptomic Comparison of Two Bambara Groundnut Landraces under Dehydration Stress.
The ability to grow crops under low-water conditions is a significant advantage in relation to global food security. Bambara groundnut is an underutilised crop grown by subsistence farmers in Africa and is known to survive in regions of water deficit. This study focuses on the analysis of the transcriptomic changes in two bambara groundnut landraces in response to dehydration stress. A cross-species hybridisation approach based on the Soybean Affymetrix GeneChip array has been employed. The differential gene expression analysis of a water-limited treatment, however, showed that the two landraces responded with almost completely different sets of genes. Hence, both landraces with very similar genotypes (as assessed by the hybridisation of genomic DNA onto the Soybean Affymetrix GeneChip) showed contrasting transcriptional behaviour in response to dehydration stress. In addition, both genotypes showed a high expression of dehydration-associated genes, even under water-sufficient conditions. Several gene regulators were identified as potentially important. Some are already known, such as WRKY40, but others may also be considered, namely PRR7, ATAUX2-11, CONSTANS-like 1, MYB60, AGL-83, and a Zinc-finger protein. These data provide a basis for drought trait research in the bambara groundnut, which will facilitate functional genomics studies. An analysis of this dataset has identified that both genotypes appear to be in a dehydration-ready state, even in the absence of dehydration stress, and may have adapted in different ways to achieve drought resistance. This will help in understanding the mechanisms underlying the ability of crops to produce viable yields under drought conditions. In addition, cross-species hybridisation to the soybean microarray has been shown to be informative for investigating the bambara groundnut transcriptome.


Prospective evaluation by computed tomography and pulmonary function tests of children with mediastinal masses.
Our ability to predict respiratory compromise during general anesthesia in a child with an anterior mediastinal mass is limited. Two prior reports have found a correlation between adequacy of ventilation during general anesthesia and the tracheal cross-sectional area obtained from computed tomograms (computed tomography [CT] scans). These and other reports have suggested that pulmonary function tests may provide additional information regarding anesthetic risks, but no studies have evaluated the extent of respiratory compromise in children with an anterior mediastinal mass. We prospectively evaluated 31 children with mediastinal masses before 34 surgical procedures. At each evaluation the tracheal area (as a percent of the predicted area on the basis of age and gender) was determined by CT. Pulmonary function tests were performed in the sitting and supine positions. The eleven children with either a tracheal area or peak expiratory flow rate (PEFR) of less than 50% of predicted received only a local anesthetic; the majority of children above these levels (17 of 22) received a general anesthetic. Eleven of 31 patients had significant pulmonary restriction as defined by total lung capacity of less than 75% of predicted. Eight patients had a PEFR in the supine position of less than 50% of predicted. PEFR was lower in the supine than the upright position in all patients (median value of decrease, 12%). In 28 of 34 evaluations the child had a tracheal area greater than 50% of predicted, a criterion proposed for safe utilization of general anesthesia. This latter guideline, however, did not identify all patients with significant impairment of pulmonary function; five patients had a PEFR of less than 50% of predicted but tracheal areas of greater than 50% of predicted. All children were administered anesthetics uneventfully with these guidelines. Although the tracheal area can be accurately measured with the CT scan, this does not identify all children with mediastinal masses and abnormal pulmonary function. A large mass may produce significant restrictive impairment and hence reduction in PEFR by the intrathoracic volume it occupies and yet not cause tracheal compression. It may also reduce the PEFR by narrowing the bronchi distal to the carina. Currently no CT standards exist for measuring bronchial areas in children. Our study did not evaluate whether impaired pulmonary function as measured by PEFR would be predictive of respiratory collapse during general anesthesia because all were excluded and operated on under local anesthesia. General anesthesia was well tolerated in children with tracheal area and PEFR greater than 50% of predicted. Pulmonary function tests in children with anterior mediastinal masses may add valuable information to the anatomic evaluation obtained by CT scan.


Flavopiridol and trastuzumab synergistically inhibit proliferation of breast cancer cells: association with selective cooperative inhibition of cyclin D1-dependent kinase and Akt signaling pathways.
Cyclin D1 is essential for Neu-induced cell growth and is induced by growth factors through Ras-dependent and Ras-independent signaling pathways (1). Because flavopiridol, a novel flavanoid cyclin-cyclin-dependent kinase inhibitor, may function through Ras-dependent and/or -independent pathways, we hypothesized that treatment of breast cancer cells with inhibitors of Neu signaling and flavopiridol might synergize to inhibit proliferation. Human breast cancer cell lines, which express high levels of endogenous Neu receptor, were treated with the anti-Neu antibody, trastuzumab, together with flavopiridol and subject to MTT assay. Cell lines were assayed for alterations in cell cycle by fluorescence-activated cell sorter and signaling proteins by Western blot. Flavopiridol and trastuzumab synergistically inhibited DNA synthesis, cellular proliferation, and contact-dependent growth. Cytotoxic synergy was observed independent of the sequence of addition of the two drugs to cultured cells. In SKBR3 cells, a combination of trastuzumab and flavopiridol inhibited the Ras-MAPK-Akt pathway, decreased cyclin D1 abundance, and kinase activity to a greater extent than either drug alone. Compared with single-agent treatment, combination treatment selectively inhibited Akt and pRB phosphorylation. Cytotoxic synergy was observed with flavopiridol plus LY294002 (selective phosphatidylinositol 3-kinase inhibitor) but not with PD98059 (selective mitogen-activated protein kinase kinase 1 inhibitor) suggesting that Akt inhibition may be important in synergy. Zinc-induced overexpression of cyclin D1 in T-47D deltaMTcycD1 cells were more resistant to drug-induced cell death when compared with vector-transfected T-47D deltaMT cells. Cyclin D1 overexpression reverses drug treatment induced cell cycle arrest in SKBR3 cells. Flavopiridol and trastuzumab yield cytotoxic synergy in human breast cancer cells overexpressing Neu. Cyclin D1 overexpression results in combination drug resistance. In addition, inhibition of Akt may prove to be a useful therapeutic strategy in combination with flavopiridol.


Screening of arsenic in tubewell water with field test kits: evaluation of the method from public health perspective.
There is an urgent need for Bangladesh to identify the arsenic (As) contaminated tubewells (TWs) in order to assess the health risks and initiate appropriate mitigation measures. This will involve testing water in millions of TWs and raising community awareness about the health problems related to chronic As exposure from drinking water. Field test kits offer the only practical tool within the time frame and financial resources available for screening and assessment of the As contaminated TWs as well as their monitoring than that of the laboratory measurement. A comparison of field test kit and laboratory measurements by AAS as "gold standard" for As in water of 12,532 TWs in Matlab Upazila in Bangladesh, indicates that the field kit correctly determined the status of 91% of the As levels compared to the Bangladesh Drinking Water Standard (BDWS) of 50 microg/L, and 87% of the WHO guideline value of 10 microg/L. Nevertheless, due to analytical and human errors during the determination of As by the field test kits, some misclassification of wells is inevitable. Cross-checking of the field test kit results, both by Field Supervisor and by the laboratory analyses reveal considerable discrepancies in the correct screening mainly at As concentration ranges of 10-24.9 microg/L and 50-99.9 microg/L, critical from a public health point of view. The uncertainties of misclassification of these two groups of TWs have severe public health implications due to As exposure from drinking water sources. This can be reduced through proper training of the field personnel, cross verification of the field test kit results with laboratory analyses and further development of the field test kits to determine As at low concentrations.


Concentrations of histamine in brain of guinea pig and rat during dietary protein malnutrition.
Protein malnutrition produced marked elevations in brain contents of histamine in guinea pigs (+142%) and rats (+257%) in comparison with findings in the control adequately fed animals. Associated with accumulation of this biogenic amine in each set of animals was an increase of similar magnitude in brain content of free histidine. It was concluded that the elevated brain content of histamine in protein malnutrition was due mainly to increased availability of the precursor amino acid, and that such alterations in amounts of neurotransmitter amines in the central nervous system might underlie some of the behavioural abnormalities seen in malnourished animals.


Neurological manifestations of HIV infection in Nigerians.
Nervous system complications commonly accompany HIV infection and are associated with significant morbidity and mortality. HIV incidence has been progressively increasing in Nigeria, yet the neurological manifestations of the disease have not been systematically studied in Nigerians. This study aimed to describe the nature and frequency of neurological manifestations associated with HIV infection in a sample of 202 Nigerians. This was a prospective study of patients with documented HIV infection who attended a referral centre clinic in Abuja in 2003. A personal history, general and neurological examinations, and other relevant medical investigations were carried out for all subjects. A mini mental-state exam was carried out with those willing to cooperate. In all, 89 patients (44%) were diagnosed with at least one neurological disorder. Herpes zoster and cognitive impairment were the most frequent, each present in 12.3% of the study group. Peripheral neuropathy and facial palsy were also present, in 10.4% and 3.9% of subjects, respectively. Brain mass lesions, seizure disorder, cryptococcal meningitis, cord compression syndrome, and trigeminal neuralgia were also documented. There was no significant difference demographically between subjects with or without neurological impairment. Future studies in this area should utilise nerve conduction studies and more detailed testing of cognitive function to further characterise the neurological manifestations of HIV infection.


[Puppy feeding in Switzerland].
In this study breeders and owners of 8 different dog breeds (Beagle, Bernese Mountain Dog, Cavalier King Charles Spaniel, Great Dane, German Shepherd (GS), Labrador, Papillon, Sheltie) were interviewed to obtain information on puppy feeding in Switzerland. Besides answering a questionnaire (husbandry and feeding of the puppies), the participation in this study included weekly weighing of the animals as well as exact documentation of the amount fed to the animals. Totally 67 dog breeders and 131 new owners of puppies participated. The weight development of the puppies was mostly parallel to the growth curve in the GS, Labradors and Shelties. There were some substantial differences to the ideal growth curve within the other breeds. The daily mean energy requirement was estimated too high, when including the growth curves. 80 - 90 % of the recommendations would be sufficient for most animals. The calcium supply was in the range of tolerance in all breeds. Nearly all breeders used commercially available complete food while raising the puppies. No breed-specific differences could be shown.


Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas.
After n-heptanol removal of the total corneal epithelium and a limbal lamellar keratectomy, 23 rabbit eyes developed features of limbal stem cell deficiency including conjunctival epithelial ingrowth, vascularization and chronic inflammation. One month later, 10 control eyes received a total keratectomy, and 13 experimental eyes received additional transplantation of glycerin-preserved human amniotic membrane. In 3 months of follow-up, all control corneas were revascularized to the center with granuloma and retained a conjunctival epithelial phenotype. In contrast, five corneas in the experimental group became clear with either minimal or no vascularization; the rest had either mid peripheral (n = 5) or total (n = 3) vascularization and cloudier stroma. The success of corneal surface reconstruction correlated with the return of a cornea-like epithelial phenotype and the preservation of amniotic membrane, whereas the failure maintained a conjunctival epithelial phenotype and the amniotic membrane was either partially degraded or covered by host fibrovascular stroma. These results suggest that measures taken to facilitate epithelialization without allowing host fibrovascular ingrowth onto the amniotic membrane might prove this procedure clinically useful for ocular surface reconstruction.


Morbidity and mortality from road injuries: results from the Global Burden of Disease Study 2017.
The global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years. We used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury. Globally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change. While road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented.


Active-site remodelling in the bifunctional fructose-1,6-bisphosphate aldolase/phosphatase.
Fructose-1,6-bisphosphate (FBP) aldolase/phosphatase is a bifunctional, thermostable enzyme that catalyses two subsequent steps in gluconeogenesis in most archaea and in deeply branching bacterial lineages. It mediates the aldol condensation of heat-labile dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP) to FBP, as well as the subsequent, irreversible hydrolysis of the product to yield the stable fructose-6-phosphate (F6P) and inorganic phosphate; no reaction intermediates are released. Here we present a series of structural snapshots of the reaction that reveal a substantial remodelling of the active site through the movement of loop regions that create different catalytic functionalities at the same location. We have solved the three-dimensional structures of FBP aldolase/phosphatase from thermophilic Thermoproteus neutrophilus in a ligand-free state as well as in complex with the substrates DHAP and FBP and the product F6P to resolutions up to 1.3 Å. In conjunction with mutagenesis data, this pinpoints the residues required for the two reaction steps and shows that the sequential binding of additional Mg(2+) cations reversibly facilitates the reaction. FBP aldolase/phosphatase is an ancestral gluconeogenic enzyme optimized for high ambient temperatures, and our work resolves how consecutive structural rearrangements reorganize the catalytic centre of the protein to carry out two canonical reactions in a very non-canonical type of bifunctionality.


Modulation of Cathepsin L Expression in the Coronary Arteries of Atherosclerotic Swine.
Neointimal hyperplasia (NIH) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting remain a problem on a long-term basis by causing endothelial denudation and damage to the intima and media. Vascular sterile inflammation has been attributed to the formation of NIH. Cathepsin L (CTSL), a lysosome protease, is associated with diet-induced atherogenesis. Vitamin D regulates the actions and regulatory effects of proteases and protease inhibitors in different cell types. Objectives of this study are to evaluate the modulatory effect of vitamin D on CTSL activity in post-PTCA coronary arteries of atherosclerotic swine. Yucatan microswine were fed with high-cholesterol atherosclerotic diets. The swine were stratified to receive three diets: (1) vitamin D-deficient diet, (2) vitamin D-sufficient diet, and (3) vitamin D-supplement diet. After 6 mo, PTCA was performed in the left circumflex coronary artery (LCx). After 1 y, angiography and optical coherence tomography imaging were performed, and swine was euthanized. Coronary arteries were embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Expression of Ki67 and CTSL were evaluated by immunofluorescence. Increased number of Ki67 + cells were observed in the postangioplasty LCx in vitamin D-deficient compared with vitamin D-sufficient or vitamin D-supplemented swine. Notably, the expression of CTSL was significantly increased in postangioplasty LCx of vitamin D-deficient swine compared with the vitamin D-sufficient or vitamin D-supplemented animal groups. Increased expression of CTSL correlates with the formation of NIH in the PTCA-injured coronary arteries. However, in the presence of sufficient or supplemented levels of vitamin D in the blood, CTSL expression was significantly reduced.


Diet and metabolic state are the main factors determining concentrations of perfluoroalkyl substances in female polar bears from Svalbard.
Perfluoroalkyl substances (PFASs) have been detected in organisms worldwide, including Polar Regions. The polar bear (Ursus maritimus), the top predator of Arctic marine ecosystems, accumulates high concentrations of PFASs, which may be harmful to their health. The aim of this study was to investigate which factors (habitat quality, season, year, diet, metabolic state [i.e. feeding/fasting], breeding status and age) predict PFAS concentrations in female polar bears captured on Svalbard (Norway). We analysed two perfluoroalkyl sulfonates (PFSAs: PFHxS and PFOS) and C8-C13 perfluoroalkyl carboxylates (PFCAs) in 112 plasma samples obtained in April and September 2012-2013. Nitrogen and carbon stable isotope ratios (δ15N, δ13C) in red blood cells and plasma, and fatty acid profiles in adipose tissue were used as proxies for diet. We determined habitat quality based on movement patterns, capture position and resource selection functions, which are models that predict the probability of use of a resource unit. Plasma urea to creatinine ratios were used as proxies for metabolic state (i.e. feeding or fasting state). Results were obtained from a conditional model averaging of 42 general linear mixed models. Diet was the most important predictor of PFAS concentrations. PFAS concentrations were positively related to trophic level and marine diet input. High PFAS concentrations in females feeding on the eastern part of Svalbard, where the habitat quality was higher than on the western coast, were likely related to diet and possibly to abiotic factors. Concentrations of PFSAs and C8-C10 PFCAs were higher in fasting than in feeding polar bears and PFOS was higher in females with cubs of the year than in solitary females. Our findings suggest that female polar bears that are exposed to the highest levels of PFAS are those 1) feeding on high trophic level sea ice-associated prey, 2) fasting and 3) with small cubs.


Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder.
Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified. The protein p53 has been suggested to play a pivotal role in enabling cells to engage in pro-apoptotic processes, and thus figures prominently as a hub molecule in the intracellular cascade of responses elicited by alcohol exposure. In the present study we examined the effect of ethanol-induced cellular and molecular responses in primary somatosensory cortex (SI) and hippocampus of 7-day-old wild-type (WT) and p53-knockout (KO) mice. We quantified apoptosis by active caspase-3 immunohistochemistry and ApopTag™ labeling, then determined total RNA expression levels in laminae of SI and hippocampal subregions. Immunohistochemical results confirmed increased incidence of apoptotic cells in both regions in WT and KO mice following ethanol exposure. The lack of p53 was not protective in these brain regions. Molecular analyses revealed a heterogeneous response to ethanol exposure that varied depending on the subregion, and which may go undetected using a global approach. Gene network analyses suggest that the presence or absence of p53 alters neuronal function and synaptic modifications following ethanol exposure, in addition to playing a classic role in cell cycle signaling. Thus, p53 may function in a way that underlies the intellectual and behavioral deficits observed in FASD.


Surgical-experimental principles of anterior cruciate ligament (ACL) reconstruction with open growth plates.
To review surgical and animal experimental studies performed with open growth plates in relation with pediatric anterior cruciate ligament (ACL) reconstruction. When it comes to the treatment of ACL injured children, there is a lack of current international guidelines, leaving the treating physicians with a therapeutic dilemma. A variety of surgical and animal experimental studies have been undertaken over the last decades in relation with open growth plates and ACL-reconstruction. Based on our own previous animal experimental data, we highlighted 15 specific points concerning pediatric ACL-reconstruction and reviewed additional literature concerning these individual items. Pediatric ACL-reconstruction could be proven to be safe in animal models. Growth abnormalities, risk factors and factors, which were specifically related to biological healing processes in children, were identified. From them surgical principles for safe pediatric ACL replacements can be deducted. Applying these principles through a correct technical execution of surgery may prevent clinically significant growth changes. Over the last 2 decades it has been shown that a technically correct pediatric ACL reconstruction has little risk in creating clinically significant growth abnormalities. Animal experiments support this hypothesis despite the fact that the gained knowledge cannot be fully generalized to humans. More long time follow-up is needed to fully understand the complete risk factors related to ACL surgery with open growth plates.


Newborn Screening for Lysosomal Storage Disorders in Illinois: The Initial 15-Month Experience.
To assess the outcomes of newborn screening for 5 lysosomal storage disorders (LSDs) in the first cohort of infants tested in the state of Illinois. Tandem mass spectrometry was used to assay for the 5 LSD-associated enzymes in dried blood spot specimens obtained from 219 973 newborn samples sent to the Newborn Screening Laboratory of the Illinois Department of Public Health in Chicago. The total number of cases with a positive diagnosis and the incidence for each disorder were as follows: Fabry disease, n = 26 (1 in 8454, including the p.A143T variant); Pompe disease, n = 10 (1 in 21 979); Gaucher disease, n = 5 (1 in 43 959); mucopolysaccharidosis (MPS) type 1, n = 1 (1 in 219 793); and Niemann-Pick disease type A/B, n = 2 (1 in 109 897). Twenty-two infants had a positive screen for 1 of the 5 disorders but could not be classified as either affected or unaffected after follow-up testing, including genotyping. Pseudodeficiencies for alpha-L-iduronidase and alpha-glucosidase were detected more often than true deficiencies. The incidences of Fabry disease and Pompe disease were significantly higher than published estimates, although most cases detected were predicted to be late onset. The incidences of Gaucher disease, MPS I, and Niemann-Pick disease were comparable with previously published estimates. A total of 16 infants could not be positively identified as either affected or unaffected. To validate the true risks and benefits of newborn screening for LSD, long term follow-up in these infants and those detected with later-onset disorders will be essential.


How much will it cost to eradicate lymphatic filariasis? An analysis of the financial and economic costs of intensified efforts against lymphatic filariasis.
Lymphatic filariasis (LF), a neglected tropical disease (NTD) preventable through mass drug administration (MDA), is one of six diseases deemed possibly eradicable. Previously we developed one LF elimination scenario, which assumes MDA scale-up to continue in all countries that have previously undertaken MDA. In contrast, our three previously developed eradication scenarios assume all LF endemic countries will undertake MDA at an average (eradication I), fast (eradication II), or instantaneous (eradication III) rate of scale-up. In this analysis we use a micro-costing model to project the financial and economic costs of each of these scenarios in order to provide evidence to decision makers about the investment required to eliminate and eradicate LF. Costing was undertaken from a health system perspective, with all results expressed in 2012 US dollars (USD). A discount rate of 3% was applied to calculate the net present value of future costs. Prospective NTD budgets from LF endemic countries were reviewed to preliminarily determine activities and resources necessary to undertake a program to eliminate LF at a country level. In consultation with LF program experts, activities and resources were further reviewed and a refined list of activities and necessary resources, along with their associated quantities and costs, were determined and grouped into the following activities: advocacy and communication, capacity strengthening, coordination and strengthening partnerships, data management, ongoing surveillance, monitoring and supervision, drug delivery, and administration. The costs of mapping and undertaking transmission assessment surveys and the value of donated drugs and volunteer time were also accounted for. Using previously developed scenarios and deterministic estimates of MDA duration, the financial and economic costs of interrupting LF transmission under varying rates of MDA scale-up were then modelled using a micro-costing approach. The elimination scenario, which includes countries that previously undertook MDA, is estimated to cost 929 million USD (95% Credible Interval: 884m-972m). Proceeding to eradication is anticipated to require a higher financial investment, estimated at 1.24 billion USD (1.17bn-1.30bn) in the eradication III scenario (immediate scale-up), with eradication II (intensified scale-up) projected at 1.27 billion USD (1.21bn-1.33bn), and eradication I (slow scale-up) estimated at 1.29 billion USD (1.23bn-1.34bn). The economic costs of the eradication III scenario are estimated at approximately 7.57 billion USD (7.12bn-7.94bn), while the elimination scenario is projected to have an economic cost of 5.21 billion USD (4.91bn-5.45bn). Countries in the AFRO region will require the greatest investment to reach elimination or eradication, but also stand to gain the most in cost savings. Across all scenarios, capacity strengthening and advocacy and communication represent the greatest financial costs, whereas mapping, post-MDA surveillance, and administration comprise the least. Though challenging to implement, our results indicate that financial and economic savings are greatest under the eradication III scenario. Thus, if eradication for LF is the objective, accelerated scale-up is projected to be the best investment.


Gold-Nanoclustered Hyaluronan Nano-Assemblies for Photothermally Maneuvered Photodynamic Tumor Ablation.
Optically active nanomaterials have shown great promise as a nanomedicine platform for photothermal or photodynamic cancer therapies. Herein, we report a gold-nanoclustered hyaluronan nanoassembly (GNc-HyNA) for photothermally boosted photodynamic tumor ablation. Unlike other supramolecular gold constructs based on gold nanoparticle building blocks, this system utilizes the nanoassembly of amphiphilic hyaluronan conjugates as a drug carrier for a hydrophobic photodynamic therapy agent verteporfin, a polymeric reducing agent, and an organic nanoscaffold upon which gold can grow. Gold nanoclusters were selectively installed on the outer shell of the hyaluronan nanoassembly, forming a gold shell. Given the dual protection effect by the hyaluronan self-assembly as well as by the inorganic gold shell, verteporfin-encapsulated GNc-HyNA (Vp-GNc-HyNA) exhibited outstanding stability in the bloodstream. Interestingly, the fluorescence and photodynamic properties of Vp-GNc-HyNA were considerably quenched due to the gold nanoclusters covering the surface of the nanoassemblies; however, photothermal activation by 808 nm laser irradiation induced a significant increase in temperature, which empowered the PDT effect of Vp-GNc-HyNA. Furthermore, fluorescence and photodynamic effects were recovered far more rapidly in cancer cells due to certain intracellular enzymes, particularly hyaluronidases and glutathione. Vp-GNc-HyNA exerted a great potential to treat tumors both in vitro and in vivo. Tumors were completely ablated with a 100% survival rate and complete skin regeneration over the 50 days following Vp-GNc-HyNA treatment in an orthotopic breast tumor model. Our results suggest that photothermally boosted photodynamic therapy using Vp-GNc-HyNA can offer a potent therapeutic means to eradicate tumors.


A pyrosequencing-based assay for the rapid detection of the 22q11.2 deletion in DNA from buccal and dried blood spot samples.
The 22q11.2 deletion syndrome is one of the most common deletion syndromes in newborns. Some affected newborns may be diagnosed shortly after birth because of the presence of heart defects, palatal defects, or severe immune deficiencies. However, diagnosis is often delayed in patients presenting with other associated conditions that would benefit from early recognition and treatment, such as speech delays, learning difficulties, and schizophrenia. Fluorescence in situ hybridization (FISH) is the gold standard for deletion detection, but it is costly and time consuming and requires a whole blood specimen. Our goal was to develop a suitable assay for population-based screening of easily collectible specimens, such as buccal swabs and dried blood spots (DBS). We designed a pyrosequencing assay and validated it using DNA from FISH-confirmed 22q11 deletion syndrome patients and normal controls. We tested DBS from nine patients and paired buccal cell and venous blood specimens from 20 patients. Results were 100% concordant with FISH assay results. DNA samples from normal controls (n = 180 cell lines, n = 15 DBS, and n = 88 buccal specimens) were negative for the deletion. Limiting dilution experiments demonstrated that accurate results could be obtained from as little as 1 ng of DNA. This method represents a reliable and low-cost alternative for detection of the common 22q11.2 microdeletions and can be adapted to high-throughput population screening.


GDF15 Is a Novel Biomarker for Impaired Fasting Glucose.
Growth differentiation factor-15 (GDF15) is a protein that belongs to the transforming growth factor β superfamily. An elevated serum level of GDF15 was found to be associated with type 2 diabetes mellitus (T2DM). T2DM is an inflammatory disease that progresses from normal glucose tolerance (NGT) to impaired fasting glucose (IFG). Hence, we aimed to validate the relationship between GDF15 and IFG. The participants were divided into the following three groups: NGT (n=137), IFG (n=29), and T2DM (n=75). The controls and T2DM outpatients visited the hospital for routine health check-ups. We used fasting blood glucose to detect IFG in nondiabetic patients. We checked the body mass index (BMI), C-reactive protein level, metabolic parameters, and fasting serum GDF15 level. Age, BMI, triglyceride, insulin, glucose, homeostatic model assessment-insulin resistance (HOMA-IR), and GDF15 levels were elevated in the IFG and T2DM groups compared to the NGT group. In the correlation analysis between metabolic parameters and GDF15, age and HOMA-IR had a significant positive correlation with GDF15 levels. GDF15 significantly discriminated between IFG and NGT, independent of age, BMI, and HOMA-IR. The serum levels of GDF15 were more elevated in men than in women. As a biomarker for IFG based on the receiver operating characteristic curve analysis, the cutoff value of GDF15 was 510 pg/mL in males and 400 pg/mL in females. GDF15 had a positive correlation with IR independent of age and BMI, and the serum level of GDF15 was increased in the IFG and T2DM groups. GDF15 may be a novel biomarker for detecting IFG in nondiabetic patients.


hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial.
Eleven patients with moderate to severe erectile dysfunction (ED) were given a single-dose corpus cavernosum injection of hMaxi-K, a "naked" DNA plasmid carrying the human cDNA encoding hSlo (for human slow-poke), the gene for the alpha, or pore-forming, subunit of the human smooth muscle Maxi-K channel. Three patients each were given 500, 1000, and 5000 microg, and two patients were given 7500 microg, of hMaxi-K and monitored for 24 weeks. The primary objectives of this phase I study were safety and tolerability of escalating hMaxi-K doses as assessed by clinical evaluations and laboratory tests. Secondary efficacy objectives were measured primarily by use of the International Index of Erectile Function (IIEF) scale. Patient responses were validated by partner responses. There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry, and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of hMaxi-K had apparent sustained improvements in erectile function (EF) as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 microg and one given 7500 microg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study. Efficacy conclusions cannot be drawn from results of a phase I trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that hMaxi-K gene transfer is a viable approach to the treatment of ED and that further studies investigating the efficacy of hMaxi-K in patients with ED should be performed.


Return to running and sports participation after limb salvage.
The ability to return to running and sports participation after lower extremity limb salvage has not been well documented previously. Although the ability to ambulate without pain or assistive devices is generally a criteria for a good limb salvage outcome, many patients at our institution have expressed a desire to return to a more athletic lifestyle to include running and sports participation. The purpose of this study was to investigate the types of athletic endeavors our high-energy lower extremity trauma patients were able to pursue after limb salvage. We retrospectively analyzed lower extremity limb salvage patients who were at least 12 weeks status after external fixation removal and participated in our limb salvage return-to-running clinical pathway. Patients were rehabilitated to their highest functional level through a sports medicine-based approach. A custom energy-storing ankle-foot orthosis was implemented to help augment plantarflexion strength in conjunction with running gait retraining. The first 10 patients to complete the clinical pathway were identified. All patients were treated at the same institution by the same orthopedic surgeon and physical therapist. Eight patients have returned to running, and 10 patients have returned to weight-lifting. Seven patients have returned to cycling, three have returned to golf, three to basketball, and two to softball. Two patients have completed a mini-triathlon. Aggressive rehabilitation, an energy-storing ankle-foot orthosis, and running gait retraining can restore an active recreational lifestyle to patients who have undergone lower extremity limb salvage.


Ambient air pollution and hypertensive disorder of pregnancy.
Ambient air pollution has been implicated in the development of hypertensive disorders of pregnancy (HDP). However, evidence of the association between air pollution and HDP is still limited, and the effects of gaseous air pollutants on HDP and their time windows of exposure have not been well studied. We used the Florida birth registry data to investigate the associations between air pollutants (NO2, SO2, PM(2.5), O3 and CO) and the risks of HDP in 22,041 pregnant women in Jacksonville, Florida, USA from 2004 to 2005. Further, we examined whether air pollution exposure during different time windows defined by trimesters and the entire pregnancy had different effects on HDP. The single-pollutant logistic regression model showed that exposure to four pollutants during the full pregnancy period was significantly associated with prevalence of HDP after adjusting for covariates: NO2 (OR=1.21, 95% CI 1.09 to 1.35), PM2.5 (OR=1.24, 95% CI 1.08 to 1.43), SO2 (OR=1.13, 95% CI 1.01 to 1.25) and CO (OR=1.12, 95% CI 1.03 to 1.22) per IQR increase. Similar effects were observed when first trimester exposure to NO2, SO2 and CO, and second trimester exposures to PM2.5 were examined. Consistent results were confirmed in multiple-pollutant models. This study suggests that exposure to high levels of air pollution during early pregnancy and the full gestational period was associated with increased prevalence of HDP in Florida, USA.


Comparative proteomic profiling of plasma very-low-density and low-density lipoproteins.
Low-density lipoprotein (LDL) is a natural metabolite of very-low-density lipoprotein (VLDL) in the circulation. Systematic investigation of total protein components and dynamics might provide insights into this normal metabolic process. VLDL and LDL were purified from normolipidemia pooled plasma by gradient ultracentrifugation with either ionic or non-ionic media. The protein contents were compared by liquid chromatography tandem mass analyses based on isobaric tag for relative and absolute quantitation and two-dimensional gel electrophoresis. Our comparative lipoproteomes revealed 21 associated proteins. Combined with Western blot analysis, and on the basis of the differential expression levels we classified them into 3 groups: (i) VLDL>LDL [apolipoprotein (apo) A-IV, apo(a), apoCs, apoE, apoJ and serum amyloid A-4]; (ii) VLDL<LDL [albumin, alpha-1-antitrypsin, apoD, apoF, apoM, and paraoxonase-1]; and (iii) VLDL=LDL [apoA-I, apoA-II, apoB-100, apoL-I and prenylcysteine oxidase-1]. The apoA-I level positively correlated with PCYOX1 but negatively with apoM in VLDL and LDL. Furthermore, the two-dimensional maps displayed 5 apoA-I isoforms in which phosphorylation at Ser55, Ser166, Thr185, Thr221 and Ser252 residues were identified. This study revealed the VLDL- and LDL lipoproteomes and the full-spectrum protein changes during physiological VLDL-to-LDL transition. It provides a valuable dataset VLDL and LDL proteomes potentially applied to the development of diagnostics.


Laser induced damage in optical materials: tenth ASTM symposium.
The tenth annual Symposium on Optical Materials for High Power Lasers (Boulder Damage Symposium) was held at the National Bureau of Standards in Boulder, Colorado, 12-14 September 1978. The symposium was held under the auspices of ASTM Committee F-1, Subcommittee on Laser Standards, with the joint sponsorship of NBS, the Defense Advanced Research Project Agency, the Department of Energy, and the Office of Naval Research. About 175 scientists attended, including representatives of the United Kingdom, France, Canada, Japan, West Germany, and the Soviet Union. The symposium was divided into sessions concerning the measurement of absorption characteristics, bulk material properties, mirrors and surfaces, thin film damage, coating materials and design, and breakdown phenomena. As in previous years, the emphasis of the papers presented was directed toward new frontiers and new developments. Particular emphasis was given to materials for use from 10.6 microm to the UV region. Highlights included surface characterization, thin film-substrate boundaries, and advances in fundamental laser-matter threshold interactions and mechanisms. The scaling of damage thresholds with pulse duration, focal area, and wavelength was also discussed. In commemoration of the tenth symposium in this series, a number of comprehensive review papers were presented to assess the state of the art in various facets of laser induced damage in optical materials. Alexander J. Glass of Lawrence Livermore Laboratory and Arthur H. Guenther of the Air Force Weapons Laboratory were co-chairpersons. The eleventh annual symposium is scheduled for 30-31 October 1979 at the National Bureau of Standards, Boulder, Colorado.


Vygotsky's, Leontiev's and Engeström's Cultural-Historical (Activity) Theories: Overview, Clarifications and Implications.
At the social turn in education, Vygotsky's cultural-historical/sociocultural theory (VST) has become particularly influential. There are other cultural-historical traditions associated with VST, including Leontiev's and Engeström's versions of cultural-historical activity theory (CHAT). These approaches are frequently conflated, resulting in confusion that can be consequential in interpreting educational research findings. Unravelling these frameworks is thus an important and urgent task. In addressing this gap, the paper first provides an overview of the origins and fundamental tenets of these cultural-historical perspectives, followed by a critical evaluation of and comparison among them. Implications for utilising these cultural-historical traditions are discussed.


DAX-1 represses the high-density lipoprotein receptor through interaction with positive regulators sterol regulatory element-binding protein-1a and steroidogenic factor-1.
The high-density lipoprotein receptor (HDL-R) mediates the selective uptake of high-density lipoprotein cholesterol in nonplacental steroidogenic tissues. We have previously demonstrated that sterol regulatory element-binding protein-1a (SREBP-1a) and steroidogenic factor-1 (SF-1) positively regulate HDL-R gene transcription. In the present study, we examined whether DAX-1 (dosage-sensitive sex adrenal hypoplasia congenital critical region on the X chromosome, gene-1) could influence the expression of the HDL-R gene. Cotransfection studies demonstrated that DAX-1 was able to repress SREBP-1a and SF-1-dependent activation of the HDL-R promoter. Mammalian two-hybrid assays demonstrated that DAX-1 could interact with SREBP-1a. In addition, electrophoretic mobility shift assays demonstrated that initial incubation of DAX-1 with SREBP-1a protein in the absence of DNA prevented subsequent binding of SREBP-1a to the HDL-R sterol regulatory elements in a dose-dependent manner, whereas, in the case of SF-1, DAX-1 formed a complex with SF-1 protein on the DNA. These data suggest that DAX-1 inhibits SREBP-1a- and SF-1-dependent activation of the HDL-R promoter through different mechanisms. This investigation confirms that DAX-1 has an important role in regulating steroidogenesis by interfering with SREBP-1a and SF-1 induction of a gene involved in the transport of cholesterol, thereby limiting the amount of substrate available for steroid hormone production.


An Overview of Phytoconstituents, Biotechnological Applications, and Nutritive Aspects of Coconut (Cocos nucifera).
Cocos nucifera is one of the highest nutritional and medicinal value plants with various fractions of proteins which play a major role in several biological applications such as anti-microbial, anti-inflammatory, anti-diabetic, anti-neoplastic, anti-parasitic, insecticidal, and leishmanicidal activities. This review is focused on several biotechnological, biomedical aspects of various solvent extracts collected from different parts of coconut and the phytochemical constituents which are present in it. The results obtained from this source will facilitate most of the researchers to focus their work toward the process of diagnosing diseases in future.


Prevalence of Continuous Pulse Oximetry Monitoring in Hospitalized Children With Bronchiolitis Not Requiring Supplemental Oxygen.
US national guidelines discourage the use of continuous pulse oximetry monitoring in hospitalized children with bronchiolitis who do not require supplemental oxygen. Measure continuous pulse oximetry use in children with bronchiolitis. A multicenter cross-sectional study was performed in pediatric wards in 56 US and Canadian hospitals in the Pediatric Research in Inpatient Settings Network from December 1, 2018, through March 31, 2019. Participants included a convenience sample of patients aged 8 weeks through 23 months with bronchiolitis who were not receiving active supplemental oxygen administration. Patients with extreme prematurity, cyanotic congenital heart disease, pulmonary hypertension, home respiratory support, neuromuscular disease, immunodeficiency, or cancer were excluded. Hospitalization with bronchiolitis without active supplemental oxygen administration. The primary outcome, receipt of continuous pulse oximetry, was measured using direct observation. Continuous pulse oximetry use percentages were risk standardized using the following variables: nighttime (11 pm to 7 am), age combined with preterm birth, time after weaning from supplemental oxygen or flow, apnea or cyanosis during the present illness, neurologic impairment, and presence of an enteral feeding tube. The sample included 3612 patient observations in 33 freestanding children's hospitals, 14 children's hospitals within hospitals, and 9 community hospitals. In the sample, 59% were male, 56% were white, and 15% were black; 48% were aged 8 weeks through 5 months, 28% were aged 6 through 11 months, 16% were aged 12 through 17 months, and 9% were aged 18 through 23 months. The overall continuous pulse oximetry monitoring use percentage in these patients, none of whom were receiving any supplemental oxygen or nasal cannula flow, was 46% (95% CI, 40%-53%). Hospital-level unadjusted continuous pulse oximetry use ranged from 2% to 92%. After risk standardization, use ranged from 6% to 82%. Intraclass correlation coefficient suggested that 27% (95% CI, 19%-36%) of observed variation was attributable to unmeasured hospital-level factors. In a convenience sample of children hospitalized with bronchiolitis who were not receiving active supplemental oxygen administration, monitoring with continuous pulse oximetry was frequent and varied widely among hospitals. Because of the apparent absence of a guideline- or evidence-based indication for continuous monitoring in this population, this practice may represent overuse.


Effects of sleep restriction on the human plasma metabolome.
This study examined the effects of recurrent sleep restriction on the plasma metabolome of adults with familial risk of type 2 diabetes. Eleven healthy adults (6M/5F; mean [SD] age: 26 [3]years; BMI 23.5 [2.3]kg/m(2)) with parental history of type 2 diabetes participated in a two-condition, two-period randomized crossover study at the Clinical Resource Center at an academic hospital. Each participant completed two 8-night inpatient sessions with restricted (5.5-h time-in-bed) vs. adequate (8.5-h time-in-bed) sleep opportunity while daily food intake and physical activity were carefully controlled. A combination of two UHPLC/MS/MS platforms and one GC/MS platform was used to measure 362 biochemicals in fasting plasma samples collected from study participants the morning after each 8-night sleep treatment. Relative concentrations of 12 amino acids and related metabolites were increased when sleep was curtailed. Sleep restriction also induced elevations in several fatty acid, bile acid, steroid hormone, and tricarboxylic acid cycle intermediates. In contrast, circulating levels of glucose, some monosaccharides, gluconate, and five-carbon sugar alcohols tended to decline when sleep was reduced. Recurrent sleep curtailment affected multiple pathways of intermediary metabolism in adults at risk for type 2 diabetes. An elevation in plasma amino acids and related biochemicals was the most pronounced metabolic signature seen in response to 8 nights of sleep restriction.


Medicare advantage plans at a crossroads--yet again.
Since risk-taking, private health insurance plans were introduced into Medicare twenty-five years ago, policymakers have disagreed on these plans' fundamental purposes. Articulated objectives, which include improving quality, reducing government spending, providing additional benefits (without expanding the entitlement), increasing choices for beneficiaries, and providing benchmark competition for traditional Medicare, are plausible but sometimes conflicting. The program's history demonstrates continuous shifts in emphasis on these objectives. We enumerate the differing advantages of public and private plans in Medicare and argue that policymakers should focus their efforts on leveling the public-private playing field, thereby dealing forthrightly with the reality of growing fiscal problems.


The erosive effects of some mouthrinses on enamel. A study in situ.
There are both anecdotal clinical and laboratory experimental data suggesting that low pH mouthrinses cause dental erosion. This evidence is particularly relevant to acidified sodium chlorite (ASC) formulations since they have plaque inhibitory properties comparable to chlorhexidine but without the well known local side effects. Studies in situ and in vitro were planned to measure enamel erosion by low pH mouthrinses. The study in situ measured enamel erosion by ASC, essential oil and hexetidine mouthrinses over 15-day study periods. The study was a 5 treatment, single blind cross over design involving 15 healthy subjects using orange juice, as a drink, and water, as a rinse, as positive and negative controls respectively. 2 enamel specimens from unerupted human third molar teeth were placed in the palatal area of upper removable acrylic appliances which were worn from 9 a.m. to 5 p.m., Monday to Friday for 3 weeks. Rinses were used 2x daily and 250 ml volumes of orange juice were imbibed 4x daily. Enamel loss was determined by profilometry on days 5, 10 and 15. The study in vitro involved immersing specimens in the 4 test solutions together with a reduced acid ASC formulation for a period of 4 h under constant stirring; Enamel loss was measured by profilometry every hour. Enamel loss was in situ progressive over time with the 3 rinses and orange juice but negligible with water. ASC produced similar erosion to orange juice and significantly more than the two proprietary rinses and water. The essential oil and hexetidine rinses produced similar erosion and significantly more than water. Enamel loss in vitro was progressive over time, and the order from low to high erosion was reduced acid ASC, ASC, Essential oil, and hexetidine mouthrinses and orange juice. Based on the study in situ, it is recommended that low pH mouthrinses should not be considered for long term or continuous use and never as pre-brushing rinses. In view of the plaque inhibitory efficacy of ASC, short- to medium-term applications similar to those of chlorhexidine would be envisaged.


Magnetic Properties of the Distorted Kagomé Lattice Mn3(1,2,4-(O2C)3C6H3)2.
Kagomé lattice types have been of intense interest as idealized examples of extended frustrated spin systems. Here we demonstrate how the use of neutron diffraction and inelastic neutron scattering coupled with spin wave theory calculations can be used to elucidate the complex magnetic interactions of extended spin networks. We show that the magnetic properties of the coordination polymer Mn3(1,2,4-(O2C)3C6H3)2, a highly distorted kagomé lattice, have been erroneously characterized as a canted antiferromagnet in previous works. Our results demonstrate that, although the magnetic structure is ferrimagnetic, with a net magnetic moment, frustration persists in the system. We conclude by showing that the conventions of the Goodenough-Kanamori rules, which are often applied to similar magnetic exchange interactions, are not relevant in this case.


Aspergilloma of the brain: an overview.
Fungal infections of the central nervous system (CNS) are almost always a clinical surprise. Their presentation is subtle, often without any diagnostic characteristics, and they are frequently mistaken for tuberculous meningitis, pyogenic abscess, or brain tumor. Granulocytopenia, cellular and humoral mediated immune dysfunction are predisposing factors to the development of CNS infections in immunosuppressed patients. Aspergillus fumigatus is the most common human pathogen in the genus Aspergillus. Maxillary sinusitis of dental origin or the lungs are the most common sites of primary Aspergillus infection. Infection reaches the brain directly from the nasal sinuses via vascular channels or is blood borne from the lungs and gastrointestinal tract. Single or multiple abscess formation with blood vessel invasion leading to thrombosis is a characteristic feature of Aspergillosis on neuropathologic examination. Aspergillosis should be considered in cases manifesting with acute onset of focal neurologic deficits resulting from a suspected vascular or space-occupying lesion especially in immunocompromised hosts. Aspergillosis is diagnosed on direct examinations and culture, however the diagnosis of aspergillosis of the CNS is difficult. Diagnosis of an intracranial mass lesion is best confirmed with a computed tomography or magnetic resonance imaging of the head with or without intravenous contrast. Aggressive neurosurgical intervention for surgical removal of Aspergillus abscesses, granulomas, and focally infracted brain; correction of underlying risk factors; Amphotericin B combined with flucytosine and treatment of the source of infection should form the mainstay of the management. Off late Liposomal Amphotericin B was found to be more effective and safe than conventional Amphotericin B in the management of Apergillus infections Only with a high index of suspicion, an aggressive approach to diagnosis, and rapid vigorous therapy may we hope to alter the clinical course in this group of patients.


Development of an orange juice surrogate for the study of dental erosion.
The aim of this study was to create a synthetic juice (SJ) to be used as a surrogate for natural orange juices in erosion studies, verifying its erosive potential. The SJ was formulated based on the chemical composition of orange juices from different locations. Forty enamel and 40 root dentin specimens were randomly assigned into 4 experimental groups (n = 10): SJ; 1% Citric Acid (CA); Minute Maid Original® (MM) and Florida Natural Original® (FN). The specimens were immersed in their respective solutions for 5 min, 6x/day for 5 days, in an erosion-remineralization cycling model. Enamel specimens were analyzed by surface Knoop microhardness and optical profilometry and dentin specimens only by optical profilometry. Outcomes were analyzed statistically by ANOVA followed by Tukey's test considering a significance level of 5%. For enamel, the surface loss and microhardness changes found for MM and SJ groups were similar (p>0.05) and significantly lower (p<0.01) than those found in the CA group. For dentin, CA promoted significantly greater (p<0.01) surface loss compared with all the other groups. No significant difference (p>0.05) was observed in dentin surface loss between MM and SJ. In conclusion, CA was the most erosive solution, and SJ had a similar erosive potential to that of MM natural orange juice.


CONSORT for reporting randomized controlled trials in journal and conference abstracts: explanation and elaboration.
Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract. We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item. CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help authors of abstracts of these trials provide the detail and clarity needed by readers wishing to assess a trial's validity and the applicability of its results.


Prevalence of female genital cutting in Upper Egypt: 6 years after enforcement of prohibition law.
The objective of this study was to evaluate the prevalence of female genital cutting (FGC) in Upper Egypt, after 6 years of putting prohibition law into action. A total number of 3730 girls between the ages of 10-14 years were recruited to participate in this study. They were mainly preparatory school students (three urban and three rural areas). Social workers interviewed them as to whether they had undergone circumcision within the last 6 years or not. Subsequently, a questionnaire was sent to parents of girls who were positive for circumcision as to the circumstances surrounding the procedure. The prohibition law of FGC seems not to have altered the prevalence of this procedure. The majority of girls (84.9%) had had circumcision within the last 6 years with high prevalence in rural areas (92.5%). Circumcision was done for a combination of reasons, according to parents, with high rates of non-medical personnel participation (64.15%). This study's results indicate that the practice of FGC in Upper Egypt remains high despite enforcement of law. Extensive efforts are needed both to revise public awareness and to change attitudes regarding FGC.


Domain motions and electron transfer dynamics in 2Fe-superoxide reductase.
Superoxide reductases are non-heme iron enzymes that represent valuable model systems for the reductive detoxification of reactive oxygen species. In the present study, we applied different theoretical methods to study the structural dynamics of a prototypical 2Fe-superoxide reductase and its influence on electron transfer towards the active site. Using normal mode and essential dynamics analyses, we could show that enzymes of this type are capable of well-defined, electrostatically triggered domain movements, which may allow conformational proofreading for cellular redox partners involved in intermolecular electron transfer. Moreover, these global modes of motion were found to enable access to molecular configurations with decreased tunnelling distances between the active site and the enzyme's second iron centre. Using all-atom classical molecular dynamics simulations and the tunnelling pathway model, however, we found that electron transfer between the two metal sites is not accelerated under these conditions. This unexpected finding suggests that the unperturbed enzymatic structure is optimized for intramolecular electron transfer, which provides an indirect indication of the biological relevance of such a mechanism. Consistently, efficient electron transfer was found to depend on a distinct route, which is accessible via the equilibrium geometry and characterized by a quasi conserved tyrosine that could enable multistep-tunnelling (hopping). Besides these explicit findings, the present study demonstrates the importance of considering both global and local protein dynamics, and a generalized approach for the functional analysis of these aspects is provided.


Screening Eucalyptus cloeziana and E. argophloia Populations for Resistance to Puccinia psidii.
Disease screening to determine the threat Puccinia psidii poses to plantation and native eucalypts in Australia was undertaken in half-sib families of two contrasting eucalypt species, Eucalyptus cloeziana and E. argophloia. Artificial inoculation with a single-lesion isolate of P. psidii was used to screen these species for resistance to the biotype of P. psidii established in Australia. The objective was to characterize resistance to P. psidii within these two distinct species: E. argophloia, a vulnerable species with a narrow distribution, and E. cloeziana, a species with a broad and extensive distribution in Queensland. Results for E. cloeziana indicate that inland provenances are more resistant to P. psidii infection than provenances from coastal regions. Heritability estimates for the two assessment systems used (resistance on a 1-to-5 ordinal scale verses resistance on a 0-to-1 binomial scale) were low to high (0.24 to 0.63) for E. argophloia and moderate to high (0.4 to 0.91) for E. cloeziana, indicating a significant level of additive genetic variance for rust resistance within the populations. This study demonstrates the potential to select resistant families within the tested populations and indicates that P. psidii could detrimentally affect these species in native forests, nurseries, and plantations.


Comparative Genomics and Mutational Analysis Reveals a Novel XoxF-Utilizing Methylotroph in the Roseobacter Group Isolated From the Marine Environment.
The Roseobacter group comprises a significant group of marine bacteria which are involved in global carbon and sulfur cycles. Some members are methylotrophs, using one-carbon compounds as a carbon and energy source. It has recently been shown that methylotrophs generally require a rare earth element when using the methanol dehydrogenase enzyme XoxF for growth on methanol. Addition of lanthanum to methanol enrichments of coastal seawater facilitated the isolation of a novel methylotroph in the Roseobacter group: Marinibacterium anthonyi strain La 6. Mutation of xoxF5 revealed the essential nature of this gene during growth on methanol and ethanol. Physiological characterization demonstrated the metabolic versatility of this strain. Genome sequencing revealed that strain La 6 has the largest genome of all Roseobacter group members sequenced to date, at 7.18 Mbp. Multilocus sequence analysis (MLSA) showed that whilst it displays the highest core gene sequence similarity with subgroup 1 of the Roseobacter group, it shares very little of its pangenome, suggesting unique genetic adaptations. This research revealed that the addition of lanthanides to isolation procedures was key to cultivating novel XoxF-utilizing methylotrophs from the marine environment, whilst genome sequencing and MLSA provided insights into their potential genetic adaptations and relationship to the wider community.


Immune function responds to selection for cuticular colour in Tenebrio molitor.
Cuticular colour in the mealworm beetle (Tenebrio molitor) is a quantitative trait, varying from tan to black. Population level variation in cuticular colour has been linked to pathogen resistance in this species and in several other insects: darker individuals are more resistant to pathogens. Given that cuticular colour has a heritable component, we have taken an experimental evolution approach: we selected 10 lines for black and 10 lines for tan adult cuticular phenotypes over at least six generations and measured the correlated responses to selection in a range of immune effector systems. Our results show that two immune parameters related to resistance (haemocyte density and pre-immune challenge activity of phenoloxidase (PO)) were significantly higher in selection lines of black beetles compared to tan lines. This may help to explain increased resistance to pathogens in darker individuals. Cuticular colour is dependent upon melanin production, which requires the enzyme PO that is present in its inactive form inside haemocytes. Thus, the observed correlated response to selection upon cuticular colour and immune variables probably results from these traits' shared dependence on melanin production.


Histone H3 lysine 9 methylation occurs rapidly at the onset of random X chromosome inactivation.
In female mammals, a single X chromosome is stably and heritably silenced early in embryogenesis. The inactive X is characterized by asynchronous DNA replication and epigenetic chromatin modifications, including DNA methylation, histone H3/H4 hypoacetylation, and incorporation of a variant histone macroH2A. X inactivation is initiated by a cis-acting RNA molecule, the X-inactive specific transcript (Xist), which coats the chromosome. However, the mechanism by which Xist induces chromosome silencing is poorly understood. An important approach towards answering this question has been to determine the temporal order of epigenetic chromatin modifications in an in vitro model system, differentiating XX embryonic stem (ES) cells, and thereby to identify candidate targets for Xist RNA. To date, these studies have demonstrated that, following accumulation of Xist RNA, the transition to late replication of the X chromosome is the earliest detectable event. H4 hypoacetylation, macroH2A1.2 incorporation, and DNA methylation all occur subsequently. Recently, it has been shown that chromatin of the inactive X is also characterized by methylation of histone H3 at lysine 9 (H3-K9). Here we show that H3-K9 methylation is a very early event in the process of X inactivation, which closely parallels the onset of Xist RNA accumulation.


Frontotemporal activation differs between perception of simulated cochlear implant speech and speech in background noise: An image-based fNIRS study.
In this study we used functional near-infrared spectroscopy (fNIRS) to investigate neural responses in normal-hearing adults as a function of speech recognition accuracy, intelligibility of the speech stimulus, and the manner in which speech is distorted. Participants listened to sentences and reported aloud what they heard. Speech quality was distorted artificially by vocoding (simulated cochlear implant speech) or naturally by adding background noise. Each type of distortion included high and low-intelligibility conditions. Sentences in quiet were used as baseline comparison. fNIRS data were analyzed using a newly developed image reconstruction approach. First, elevated cortical responses in the middle temporal gyrus (MTG) and middle frontal gyrus (MFG) were associated with speech recognition during the low-intelligibility conditions. Second, activation in the MTG was associated with recognition of vocoded speech with low intelligibility, whereas MFG activity was largely driven by recognition of speech in background noise, suggesting that the cortical response varies as a function of distortion type. Lastly, an accuracy effect in the MFG demonstrated significantly higher activation during correct perception relative to incorrect perception of speech. These results suggest that normal-hearing adults (i.e., untrained listeners of vocoded stimuli) do not exploit the same attentional mechanisms of the frontal cortex used to resolve naturally degraded speech and may instead rely on segmental and phonetic analyses in the temporal lobe to discriminate vocoded speech.


Open-source data reveal how collections-based fungal diversity is sensitive to global change.
Fungal diversity (richness) trends at large scales are in urgent need of investigation, especially through novel situations that combine long-term observational with environmental and remotely sensed open-source data. We modeled fungal richness, with collections-based records of saprotrophic (decaying) and ectomycorrhizal (plant mutualistic) fungi, using an array of environmental variables across geographical gradients from northern to central Europe. Temporal differences in covariables granted insight into the impacts of the shorter- versus longer-term environment on fungal richness. Fungal richness varied significantly across different land-use types, with highest richness in forests and lowest in urban areas. Latitudinal trends supported a unimodal pattern in diversity across Europe. Temperature, both annual mean and range, was positively correlated with richness, indicating the importance of seasonality in increasing richness amounts. Precipitation seasonality notably affected saprotrophic fungal diversity (a unimodal relationship), as did daily precipitation of the collection day (negatively correlated). Ectomycorrhizal fungal richness differed from that of saprotrophs by being positively associated with tree species richness. Our results demonstrate that fungal richness is strongly correlated with land use and climate conditions, especially concerning seasonality, and that ongoing global change processes will affect fungal richness patterns at large scales.


Methods for managing variation in clinical drug names.
To develop normalization methods for managing the variation in clinical drug names. Manual examination of drug names from RxNorm and local variants collected from formularies led to the identification of three types of drug-specific normalization rules: expansion of abbreviations (e.g., tab to tablet);reformatting of specific elements (e.g., space between number and unit); and removal of salt variants (e.g., succinate from metoprolol succinate). After drug-specific normalization, recall of 3397 previously non-matching names from formularies reaches 45% overall (70% of some subsets), compared to 10-20% after generic normalization. Ambiguity has not increased significantly in the RxNorm dataset. A limited number of drug-specific normalization operations provide significant improvement over general language normalization.


Detection of Plasmodium falciparum histidine-rich protein II in saliva of malaria patients.
Detection of Plasmodium falciparum parasites in patients with malaria necessitates drawing blood, which increases the risk of accidental infections and is poorly accepted in communities with blood taboos. Thus, non-invasive, cost-effective malaria tests that minimize the need for blood collection are needed. Plasmodium falciparum histidine-rich protein II (PfHRP II) levels in plasma and saliva were compared in malaria-positive and -negative patients in Ghana. Plasma and saliva obtained from 30 thick-film positive and 10 negative children were evaluated for PfHRP II by ELISA. Among the 30 children with positive blood smear, 16 (53%) were PfHRP II positive in plasma and 13 (43%) had PfHRP II positive saliva. The sensitivity of PfHRP II detection was 53% for plasma and 43% for saliva. The specificity was 100% with no false positive for both plasma and saliva when compared with blood smear. Thus, rapid detection of PfHRP II antigen in saliva may be a useful non-invasive and cost-effective malaria diagnostic technique.


HIV/AIDS in Costa Rica: epidemiological and sociological features, 1993.
Acquired immunodeficiency syndrome (AIDS) was first detected in Costa Rica in 1983. For four years most known cases were in hemophiliac men. Thereafter, AIDS in homosexual and bisexual men predominated. By December 31 of 1993, 563 persons had been diagnosed with the syndrome, 71% of them homosexual and bisexual men, 10% heterosexual men and women, 6% hemophiliacs, 2% intravenous drug abusers (IVDA's), 2% women and men who had blood transfusions, 1.4% infants born to HIV-infected mothers and 7% unknown. The epidemics in homosexual/bisexual men and in heterosexual women and men are rising; cases in infants and in persons who received blood or coagulation factors, are stagnant. The steady increase in AIDS among women is linked to exposure to bisexual partners. The moderate nature of the national epidemic reflects, in part, the low incidence of IVDA, the universal screening of blood donors for antibodies to the human immunodeficiency virus (HIV) since 1985, and the prompt banning of unsafe coagulation factors. The projection of AIDS for the year 2000 is 2,304 cases (606 accumulated incidence per million inhabitants). A national educational campaign, radio and television programs and other preventive actions, apparently did not influence the rate of receptive anal intercourse without condom (about 80%) during 9 years of the epidemic. Persons with HIV/AIDS often are deprived of social and medical benefits or are subjected to harassment and exploitation by the health sector. More efficient prevention must target children, adolescents and adults in reproductive age, to promote safer lifestyles, through education and counseling effected through primary health care.


Integromics network meta-analysis on cardiac aging offers robust multi-layer modular signatures and reveals micronome synergism.
The avalanche of integromics and panomics approaches shifted the deciphering of aging mechanisms from single molecular entities to communities of them. In this orientation, we explore the cardiac aging mechanisms - risk factor for multiple cardiovascular diseases - by capturing the micronome synergism and detecting longevity signatures in the form of communities (modules). For this, we developed a meta-analysis scheme that integrates transcriptome expression data from multiple cardiac-specific independent studies in mouse and human along with proteome and micronome interaction data in the form of multiple independent weighted networks. Modularization of each weighted network produced modules, which in turn were further analyzed so as to define consensus modules across datasets that change substantially during lifespan. Also, we established a metric that determines - from the modular perspective - the synergism of microRNA-microRNA interactions as defined by significantly functionally associated targets. The meta-analysis provided 40 consensus integromics modules across mouse datasets and revealed microRNA relations with substantial collective action during aging. Three modules were reproducible, based on homology, when mapped against human-derived modules. The respective homologs mainly represent NADH dehydrogenases, ATP synthases, cytochrome oxidases, Ras GTPases and ribosomal proteins. Among various observations, we corroborate to the involvement of miR-34a (included in consensus modules) as proposed recently; yet we report that has no synergistic effect. Moving forward, we determined its age-related neighborhood in which HCN3, a known heart pacemaker channel, was included. Also, miR-125a-5p/-351, miR-200c/-429, miR-106b/-17, miR-363/-92b, miR-181b/-181d, miR-19a/-19b, let-7d/-7f, miR-18a/-18b, miR-128/-27b and miR-106a/-291a-3p pairs exhibited significant synergy and their association to aging and/or cardiovascular diseases is supported in many cases by a disease database and previous studies. On the contrary, we suggest that miR-22 has not substantial impact on heart longevity as proposed recently. We revised several proteins and microRNAs recently implicated in cardiac aging and proposed for the first time modules as signatures. The integromics meta-analysis approach can serve as an efficient subvening signature tool for more-oriented better-designed experiments. It can also promote the combinational multi-target microRNA therapy of age-related cardiovascular diseases along the continuum from prevention to detection, diagnosis, treatment and outcome.


The abrupt onset of the modern South Asian Monsoon winds.
The South Asian Monson (SAM) is one of the most intense climatic elements yet its initiation and variations are not well established. Dating the deposits of SAM wind-driven currents in IODP cores from the Maldives yields an age of 12. 9 Ma indicating an abrupt SAM onset, over a short period of 300 kyrs. This coincided with the Indian Ocean Oxygen Minimum Zone expansion as revealed by geochemical tracers and the onset of upwelling reflected by the sediment's content of particulate organic matter. A weaker 'proto-monsoon' existed between 12.9 and 25 Ma, as mirrored by the sedimentary signature of dust influx. Abrupt SAM initiation favors a strong influence of climate in addition to the tectonic control, and we propose that the post Miocene Climate Optimum cooling, together with increased continentalization and establishment of the bipolar ocean circulation, i.e. the beginning of the modern world, shifted the monsoon over a threshold towards the modern system.


Designing temperature-responsive biocompatible copolymers and hydrogels based on 2-hydroxyethyl(meth)acrylates.
Free-radical copolymerization of 2-hydroxyethyl methacrylate with 2-hydroxyethyl acrylate can be successively utilized for the synthesis of water-soluble polymers and hydrogels with excellent physicochemical properties, thus showing promise for pharmaceutical and biomedical applications. In the work presented it has been demonstrated that water-soluble copolymers based on 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate exhibit lower critical solution temperature in aqueous solutions, whereas the corresponding high molecular weight homopolymers do not have this unique property. The temperature-induced transitions observed upon heating the aqueous solutions of these copolymers proceed via liquid-liquid phase separation. The hydrogels were also synthesized by copolymerizing 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate in the absence of a bifunctional cross-linker. The cross-linking of these copolymers during copolymerization is believed to be due to the presence of bifunctional admixtures or transesterification reactions. Transparency, swelling behavior, mechanical properties, and porosity of the hydrogels are dependent upon the monomer ratio in the copolymers. Hydrogel samples containing more 2-hydroxyethyl methacrylate are less transparent, have lower swelling capacity, higher elastic moduli, and pores of smaller size. The assessment of the biocompatibility of the copolymers using the slug mucosal irritation test revealed that they are also less irritant than poly(acrylic acid).


Health Economic Analysis of Access Site Practice in England During Changes in Practice: Insights From the British Cardiovascular Interventional Society.
Transradial access (TRA) for percutaneous coronary intervention (PCI) is associated with a reduced risk of mortality compared with transfemoral access, access site-related bleeding complications, and shorter length of stay. The budget impact from a healthcare system that has largely transitioned to TRA for PCI has not been previously published. Data from 323 656 patients undergoing PCI between 2010 and 2014 were obtained from the British Cardiovascular Intervention Society database. Costs for TRA and transfemoral access PCI were estimated based on procedure cost, length of stay, and differences in the rates of complications (major bleeding and vascular complications). In the base case, a propensity-matched data set between transfemoral access and TRA was used to directly compare the cost per PCI, whereas in the real-world analysis, the full data set was used. Across all indications and all years, TRA offered an average cost saving of £250.59 per procedure (22% reduction) versus transfemoral access with the majority of cost saving derived from reduced length of stay (£190.43) rather than direct costs of complications (£3.71). In the real-world analysis, adoption of TRA was estimated to have provided cost savings of £13.31 million across England between 2010 and 2014; however, if operators in all regions had adopted TRA at the rate of the region with the highest utilization, cost savings of £33.40 million could have been achieved. The transition to TRA in England has been associated with significant cost savings across the national healthcare system, in addition to the well-established clinical benefits.


Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.
The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.


MCSF expression is induced in healing myocardial infarcts and may regulate monocyte and endothelial cell phenotype.
Myocardial infarction is associated with the rapid induction of mononuclear cell chemoattractants that promote monocyte infiltration into the injured area. Monocyte-to-macrophage differentiation and macrophage proliferation allow a long survival of monocytic cells, critical for effective healing of the infarct. In a canine infarction-reperfusion model, newly recruited myeloid leukocytes were markedly augmented during early reperfusion (5-72 h). By 7 days, the number of newly recruited myeloid cells was reduced, and the majority of the inflammatory cells remaining in the infarct were mature macrophages. Macrophage colony-stimulating factor (MCSF) is known to facilitate monocyte survival, monocyte-to-macrophage conversion, and macrophage proliferation. We demonstrated marked induction of MCSF mRNA in ischemic segments persisting for at least 5 days after reperfusion. MCSF expression was predominantly localized to mature macrophages infiltrating the infarcted myocardium; the expression of the MCSF receptor, c-Fms, a protein with tyrosine kinase activity, was found in these macrophages but was also observed in a subset of microvessels within the infarct. Many infarct macrophages expressed proliferating cell nuclear antigen, a marker of proliferative activity. In vitro MCSF induced monocyte chemoattractant protein-1 synthesis in canine venous endothelial cells. MCSF-induced endothelial monocyte chemoattractant protein-1 upregulation was inhibited by herbimycin A, a tyrosine kinase inhibitor, and by LY-294002, a phosphatidylinositol 3'-kinase inhibitor. We suggest that upregulation of MCSF in the infarcted myocardium may have an active role in healing not only through its effects on cells of monocyte/macrophage lineage, but also by regulating endothelial cell chemokine expression.


Revision surgery of metal-on-metal hip arthroplasties for adverse reactions to metal debris.
Background and purpose - The initial outcomes following metal-on-metal hip arthroplasty (MoMHA) revision surgery performed for adverse reactions to metal debris (ARMD) were poor. Furthermore, robust thresholds for performing ARMD revision are lacking. This article is the second of 2. The first article considered the various investigative modalities used during MoMHA patient surveillance (Matharu et al. 2018a ). The present article aims to provide a clinical update regarding ARMD revision surgery in MoMHA patients (hip resurfacing and large-diameter MoM total hip arthroplasty), with specific focus on the threshold for performing ARMD revision, the surgical strategy, and the outcomes following revision. Results and interpretation - The outcomes following ARMD revision surgery appear to have improved with time for several reasons, among them the introduction of regular patient surveillance and lowering of the threshold for performing revision. Furthermore, registry data suggest that outcomes following ARMD revision are influenced by modifiable factors (type of revision procedure and bearing surface implanted), meaning surgeons could potentially reduce failure rates. However, additional large multi-center studies are needed to develop robust thresholds for performing ARMD revision surgery, which will guide surgeons' treatment of MoMHA patients. The long-term systemic effects of metal ion exposure in patients with these implants must also be investigated, which will help establish whether there are any systemic reasons to recommend revision of MoMHAs.


Toward designed singlet fission: solution photophysics of two indirectly coupled covalent dimers of 1,3-diphenylisobenzofuran.
In order to identify optimal conditions for singlet fission, we are examining the photophysics of 1,3-diphenylisobenzofuran (1) dimers covalently coupled in various ways. In the two dimers studied presently, the coupling is weak. The subunits are linked via the para position of one of the phenyl substituents, in one case (2) through a CH2 linker and in the other (3) directly, but with methyl substituents in ortho positions forcing a nearly perpendicular twist between the two joint phenyl rings. The measurements are accompanied with density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. Although in neat solid state, 1 undergoes singlet fission with a rate constant higher than 10(11) s(-1); in nonpolar solutions of 2 and 3, the triplet formation rate constant is less than 10(6) s(-1) and fluorescence is the only significant event following electronic excitation. In polar solvents, fluorescence is weaker because the initial excited singlet state S1 equilibrates by sub-nanosecond charge transfer with a nonemissive dipolar species in which a radical cation of 1 is attached to a radical anion of 1. Most of this charge transfer species decays to S0, and some is converted into triplet T1 with a rate constant near 10(8) s(-1). Experimental uncertainties prevent an accurate determination of the number of T1 excitations that result when a single S1 excitation changes into triplet excitation. It would be one if the charge-transfer species undergoes ordinary intersystem crossing and two if it undergoes the second step of two-step singlet fission. The triplet yield maximizes below room temperature to a value of roughly 9% for 3 and 4% for 2. Above ∼360 K, some of the S1 molecules of 3 are converted into an isomeric charge-transfer species with a shorter lifetime, possibly with a twisted intramolecular charge transfer (TICT) structure. This is not observed in 2.


Isothiazolinone derivatives and allergic contact dermatitis: a review and update.
Allergic contact dermatitis (ACD) from isothiazolinones has frequently been described in the literature. Following an epidemic of sensitization to methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) in the 1980s, and more recently to MI, the Scientific Committee on Consumer Safety of the European Commission banned their use in leave-on products, while restricting that in rinse-off cosmetics. Despite a decreasing prevalence of ACD from MCI/MI and MI, cases caused by occupational exposure and non-cosmetic isothiazolinone sources are on the rise. Moreover, sensitization to newer and lesser known isothiazolinones has been reported. This paper reviews the epidemiology of contact allergy to different isothiazolinones, clinical presentation of isothiazolinone-induced ACD, most relevant sensitization sources and potential cross-reactions between isothiazolinone derivatives. It also provides an update on recent legislative measures.


Effect of Troponin I Elevation on Duration of Mechanical Ventilation and Length of Intensive Care Unit Stay in Patients With Sepsis.
Sepsis is a leading cause of mortality and morbidity. Recent studies suggest that troponin elevation is associated with increased mortality in sepsis patients. The purpose of this study is to determine the effect of troponin elevation on mechanical ventilation duration and intensive care unit (ICU) length of stay in patients with sepsis. Additionally, we investigated the association between troponin elevation and septic shock. The study is a retrospective observational cohort study, conducted in a community teaching hospital between October 2015 and April 2018. All adult ICU patients with sepsis who required invasive mechanical ventilation were included. Primary outcomes were mechanical ventilation duration and ICU length of stay. Secondary outcomes were hospital length of stay, in-hospital mortality and association with septic shock. A total of 125 patients were included. Troponin was elevated in 36% (45/125) of the patients. Duration of mechanical ventilation in hours was longer for troponin-positive group (troponin positive: 55.6 h vs. troponin negative: 49.6 h, 95% CI 0.001 - 0.063, P = 0.032). ICU length of stay was similar (troponin positive: 4.6 days vs. troponin negative: 4.3 days, 95% CI 0.130 - 0.270). Septic shock had higher occurrence in elevated troponin group (troponin positive: 62.2% (28/45) vs. troponin negative: 43.8% (35/80), risk ratio (RR) 1.4, P = 0.04, 95% CI 1.015 - 1.99). Troponin elevation was associated with longer duration of mechanical ventilation in patients admitted to ICU with sepsis. Troponin elevation was associated with higher risk for development of septic shock. No significant effect was observed in ICU length of stay and hospital length of stay.


Rural-urban differences in acute stroke management practices: a modifiable disparity.
Acute stroke management practices in rural areas of the United States are suboptimal, which creates an unacceptable health disparity between urban patients with stroke and their rural counterparts. The existing gap between urban and rural stroke care may widen in the future as more urban-tested interventions are incorporated into the treatment of acute stroke. We conducted a PubMed search to identify all the articles published from 1997 to 2007 that addressed acute stroke, paramedics, ambulances, emergency services, and interhospital transportation pertaining to the US rural, urban, or nonurban environment. We review herein the problems and potential solutions that exist in 3 aspects of the current rural stroke care system: prehospital care, rural local hospital emergency department care, and interhospital transfer of patients and subsequent reception at a larger tertiary care institution, which often involve long distances and considerable time. We conclude that the current gap in rural-urban stroke management practices could be overcome with a comprehensive strategy that addresses the existing issues, including further education of rural caregivers, remote support from tertiary care institutions, and implementation of future acute clinical trials that test the rural strategies to stroke care.


Genetic diversity and population structure of Rhipicephalus sanguineus sensu lato across different regions of Colombia.
There has been a long-standing debate over the taxonomic status of Rhipicephalus sanguineus sensu lato. Different studies worldwide have reported the occurrence of different well-defined lineages, in addition to Rhipicephalus sanguineus sensu stricto. To date, there are very few studies examining the diverse aspects of this tick in Colombia. We assessed the population structure and genetic diversity of R. sanguineus s.l. in eight departmental regions across Colombia. A total of 170 ticks were collected from dogs in different departments of Colombia. All specimens were morphologically compatible with R. sanguineus s.l. and subjected to genetic analysis. DNA sequences were obtained for the 12S rDNA, cytochrome oxidase I (COI) and internal transcribed spacer 2 (ITS2) markers. A concatenated set of all mitochondrial markers was also constructed. Next, maximum likelihood phylogenetic trees were constructed using the sequences generated herein and sequences available in GenBank. Finally, we assessed different summary statistics and analysed population structure and divergence with Fst and Dxy and demographic changes with Tajima's D and Fu and Li's statistical tests. Analysis of the 12S rDNA and COI revealed that all R. sanguineus s.l. specimens collected across different regions of Colombia clustered within the tropical lineage. Micro-geographical analyses showed that the tick population from Amazonas formed a distinct cluster separated from the other sequences, with moderate Fst and Dxy values. However, no signs of a robust population structure were found within the country. The results of Fu's FS tests, together with the haplotype networks and diversity values, signal a possible population expansion of this tick species in Colombia. Evidence provided herein supports the tropical lineage as the main circulating lineage in Colombia, exhibiting a general lack of genetic structure except for the Amazonas region.


Recognition and verification of unconstrained handwritten words.
This paper presents a novel approach for the verification of the word hypotheses generated by a large vocabulary, offline handwritten word recognition system. Given a word image, the recognition system produces a ranked list of the N-best recognition hypotheses consisting of text transcripts, segmentation boundaries of the word hypotheses into characters, and recognition scores. The verification consists of an estimation of the probability of each segment representing a known class of character. Then, character probabilities are combined to produce word confidence scores which are further integrated with the recognition scores produced by the recognition system. The N-best recognition hypothesis list is reranked based on such composite scores. In the end, rejection rules are invoked to either accept the best recognition hypothesis of such a list or to reject the input word image. The use of the verification approach has improved the word recognition rate as well as the reliability of the recognition system, while not causing significant delays in the recognition process. Our approach is described in detail and the experimental results on a large database of unconstrained handwritten words extracted from postal envelopes are presented.