Toxicity of the fungicide trifloxystrobin on tadpoles and its effect on fish-tadpole interaction.
Contamination of aquatic systems is a major environmental stress that can interfere with predator-prey interactions, altering prey or predator behavior differentially. We determined toxicity parameters of the fungicide trifloxystrobin (TFS) and examined its effects on predation rate, using a fish predator (Synbranchus marmoratus) and four anuran tadpole species as prey (Rhinella arenarum, Physalaemus santafecinus, Leptodactylus latrans, and Elachistocleis bicolor). TFS was not equally toxic to the four tadpole species, E. bicolor being the most sensitive species, followed by P. santafecinus, R. arenarum, and L. latrans. Predation rates were evaluated using different treatments that combined predator and prey exposed or not to this fungicide. TFS would alter the outcome of eel-tadpole interaction by reducing prey movements; thus, prey detection would decrease and therefore tadpole survival would increase. In addition, eels preyed selectively upon non-exposed tadpoles avoiding the exposed ones almost all throughout the period evaluated. Predation rate differed among prey species; such differences were not due to TFS exposure, but to interspecific differences in behavior. The mechanism that would explain TFS-induced reduction in predation rates remains unclear; however, what is clear is that sublethal TFS concentrations have the potential to alter prey behavior, thereby indirectly altering predator-prey interactions. In addition, we consider that predator-prey relationships are measurable responses of toxicant exposure and provide ecological insight into how contaminants modify predator-prey interactions.


Development of a Dual Fluorescent Microsphere Immunological Assay for Detection of Pseudorabies Virus gE and gB IgG Antibodies.
Pseudorabies, also known as Aujezsky's disease, is an acute viral infection caused by pseudorabies virus (PRV). Swine are one of the natural hosts of pseudorabies and the disease causes huge economic losses in the pig industry. The establishment of a differential diagnosis technique that can distinguish between wild-type infection and vaccinated responses and monitor vaccine-induced immunoglobulin G(IgG) is crucial for the eventual eradication of pseudorabies. The aim of this study was to develop a rapid dual detection method for PRV gE and gB protein IgG antibodies with high specificity and sensitivity. PRV gE codons at amino acid residues (aa) 52-238 and gB codons at aa 539-741 were expressed to obtain recombinant PRV gE and gB proteins via a pMAL-c5x vector. After purification with Qiagen Ni-nitrilotriacetic acid (NTA) agarose affinity chromatography, the two proteins were analyzed via SDS-PAGE and immunoblotting assays. Two single fluorescent-microsphere immunoassays (FMIAs) were established by coupling two recombinant proteins (gE and gB) to magnetic microbeads, and an effective dual FMIA was developed by integrating the two single assays. Optimal serum dilution for each assay, correlation with other common swine virus-positive sera, and comparison with ELISA for two PRV antigens were tested for validation. Compared with ELISA, the specificity and sensitivity were 99.26% and 92.3% for gE IgG antibody detection, and 95.74% and 96.3% for the gB IgG antibody detection via dual FMIA. We provide a new method for monitoring PRV protective antibodies in vaccinated pigs and differentiating wild-type PRV infection from vaccinated responses simultaneously.


o-Aminoacetophenone, a pheromone that repels honeybees (Apis mellifera L.).
o-Aminoacetophenone is a pheromone produced by virgin honeybee queens and released with feces. In small social groups, the pheromone repels and is used to terminate agonistic interactions between queens and workers.


3-[(E)-2-Phenyl-ethen-yl]-1H-indole-6-carbonitrile.
In the title compound, C(17)H(12)N(2), the inter-planar angle between the indole mean plane [max.deviation 0.030 (1) Å] and the phenyl ring is 24.32 (7)°. In the crystal, inter-molecular N-H⋯N C hydrogen bonds form zigzag chains in the a-axis direction augmented by weak C-H⋯N C contacts.


Cystatin C is a strong predictor of survival in patients with cirrhosis: is a cystatin C-based MELD better?
The model of end stage liver disease (MELD) includes serum creatinine, which is a poor surrogate marker of renal function in patients with cirrhosis. Especially in women and patients with advanced disease creatinine underestimates true renal function. Our objective was to assess whether or not the substitution of creatinine by cystatin C improves the prognostic performance of the model. The association between MELD parameters and cystatin C with survival was investigated using a Cox proportional hazards model. A cystatin C-based MELD score was calculated from the results and compared with creatinine-based MELD in terms of discrimination and calibration. Four hundred and twenty-nine patients were included in the study; 19% died and 12% underwent liver transplantation during a median follow-up of 602 days. In multivariate Cox regression, cystatin C was an independent predictor of 90-day mortality with a hazard ratio of 8.0 (95% CI: 2.2-29.6). The median cystatin C-based MELD was 15, the median creatinine-based MELD was 12. Calibration and discrimination for 3 month and 1 year mortality was similar between the scores (AUC > 0.85 for both scores). Gender differences in cystatin C-based MELD were less pronounced than those in the creatinine-based model, because creatinine but not cystatin C was affected by gender. Substitution of creatinine by cystatin C does not improve the predictive power of MELD.


Breathlessness and presentation to the emergency department: a survey and clinical record review.
Breathlessness is a frequently occurring symptom of cardiorespiratory conditions and is a common cause of emergency department presentation. The aim of this study was to estimate the prevalence of acute-on-chronic breathlessness as a cause for presentation to the major emergencies area of the emergency department. A prospective patient self-report survey and clinical record review of consecutive attendees to the major emergencies area of the emergency department in a single tertiary hospital between 12/5/14 and 29/5/14 was conducted. Eligible patients were clinically stable and had mental capacity to provide data. There were 2,041 presentations during the study period, of whom 1,345 (66%) were eligible. There was a 90% survey response rate (1,212/1,345); 424/1,212 (35%) self-reported breathlessness most days over the past month of whom 245 gave breathlessness as a reason for this presentation. Therefore, the prevalence of acute-on-chronic breathlessness as a reason to present to the major emergencies area was 20.2% (245/1,212, 95% CI 17.9% to 22.5%). During this period there were 4,692 major and minor presentations; breathlessness was therefore a cause of at least 5.2% (245/4,692, 95% CI 4.6 to 5.9%) of all emergency department presentations. This study found that one in five ambulance presentations to the ED were due to acute-on-chronic breathlessness. Most patients had non-malignant underlying conditions, had experienced considerable breathlessness for an extended period, had discussed breathlessness with their GP and presented out of daytime hours. Others were often involved in their decision to present. This represents clinically significant burden for patients, their family carers and the emergency health services.


[Results in the surgical treatment of giant acoustic neuromas].
To compare the results obtained in the resection of 21 giant vestibular schwannomas via retrosigmoid (RS) and combined retrosigmoid/translabyrinthine (RS/TL) approaches with respect to intra- and postoperative complications, facial nerve preservation and postsurgical sequelae. This was a retrospective study of 21 patients who underwent a resection of a giant vestibular neuroma according to the Tos & Thomsen Scale (greater than or equal to 4 centimetres) in a tertiary care centre in the period between 2000 and 2008. We present the most significant characteristics of the series studied and the analysis of the advantages and inconveniences of each approach. We also analyse the results regarding facial nerve function preservation. We highlight the absence of mortality in the 21-patient group. There were no important intraoperative complications. Total resection of the lesion was achieved in the 87% of the cases, with facial nerve preservation of 73% using the combined RS/TL approach, in comparison to 40% using the RS. Facial nerve function after two years was acceptable or good in 67% (including those with heteronerve anastomosis). A global percentage of 14.3% of cerebrospinal liquid fistula was observed, as well as 9.5% of meningitis. The results of the study demonstrate that the combined retrosigmoid translabyrinthine approach for giant schwannoma treatment offers increased facial nerve preservation and lower morbidity, constituting an important option in the treatment of this kind of tumours thanks to a multidisciplinary approach.


Scientization or parametrization? Which system is more advantageous to environmental conservation in the reform of China's state-owned forest farms?
Government leadership and grassroots participation are the most typical institutional arrangements in natural resource management, a topic which has been the subject of vigorous debate for a long time. Individually, these systems are referred to as scientization and parametrization. This paper takes the reform of China's state-owned forest farms (SSFs) as a pointcut, comparing the effects of the 2011 policy (representing scientization) and the 2015 policy (representing parametrization) on environmental conservation. For the period from 2006 to 2018, China's provinces are analyzed via difference-in-differences (DID) and principal components difference-in-differences (PCDID) empirical strategies. The results show that the 2015 policy increased new afforestation by an average of 0.903 units, but the 2011 policy had no significant impact. The influence path of the 2015 policy was to curb corruption, relieve fiscal stress, and stimulate innovation, playing mechanism effects of 20.49%, 14.17%, and 33.55%, respectively. However, the 2015 policy was not ideal in terms of its goal of incentivizing multi-agent participation in investments in conservation. Investors prefer to attempt afforestation projects with shorter payback periods, especially projects related to open forest land. Overall, this study supports the belief that parametric management is a better approach to natural resource management than scientific management, but the latter approach still has limitations. Therefore, we propose to prioritize the promotion of parametric management on the closed forest lands of SSFs, but there is no need to hastily mobilize grassroots participation in open forest land management projects.


The lymphocyte transformation response of fetal hemolymphatic tissue to mitogens and antigens.
Lymphocyte transformation responses to three different mitogens (phytohemagglutinin (PHA), pokeweed mitogen (PWM), and concanavalin A (Con A)) as well as four antigens (streptolysin O (SLO), keyhole limpet hemocyanin (KLH), streptokinase-streptodornase (SKSD) and tuberculin purified protein derivative (PPD)) were studied ontogenetically in 30 human fetuses ranging in gestational age from 6-19 weeks. In most organs lymphocyte responsiveness to Con A in human fetuses seemingly develops in concert with responsiveness to PHA and PWM. One 19 week fetus had an apparent antigen specific response to SLO with stimulation of cord blood and bone marrow lymphocytes. The same fetus also had mitogen responsiveness in bone marrow.


Cloning, expression analysis, and chromosomal localization of HIP1R, an isolog of huntingtin interacting protein (HIP1).
Huntington disease (HD) is an inherited neurodegenerative disorder which is associated with CAG expansion in the coding region of the gene for huntingtin protein. Recently, a huntingtin interacting protein, HIP1, was isolated by the yeast two-hybrid system. Here we report the isolation of a cDNA clone for HIP1R (huntingtin interacting protein-1 related), which encodes a predicted protein product sharing a striking homology with HIP1. RT-PCR analysis showed that the messenger RNA was ubiquitously expressed in various human tissues. Based on PCR-assisted analysis of a radiation hybrid panel and fluorescence in situ hybridization, HIP1R was localized to the q24 region of chromosome 12.


KITD816V mutation in blood for the diagnostic screening of systemic mastocytosis and mast cell activation syndromes.
Current diagnostic algorithms for systemic mastocytosis (SM) rely on the detection of KITD816V in blood to trigger subsequent bone marrow (BM) investigations. Here, we correlated the KITD816V mutational status of paired blood and BM samples from 368 adults diagnosed with mast cell activation syndrome (MCAS) and mastocytosis and determined the potential utility of investigating KITD816V in genomic DNA from blood-purified myeloid cell populations to increase diagnostic sensitivity. In a subset of 69 patients, we further evaluated the kinetics of the KITD816V cell burden during follow-up and its association with disease outcome. Our results showed a high correlation (P < .0001) between the KITD816V mutation burden in blood and BM (74% concordant samples), but with a lower mean of KITD816V-mutated cells in blood (P = .0004) and a high rate of discordant BM+ /blood- samples particularly among clonal MCAS (73%) and BM mastocytosis (51%), but also in cutaneous mastocytosis (9%), indolent SM (15%), and well-differentiated variants of indolent SM (7%). Purification of different compartments of blood-derived myeloid cells was done in 28 patients who were BM mast cell (MC)+ /blood- for KITD816V, revealing KITD816V-mutated eosinophils (56%), basophils (25%), neutrophils (29%), and/or monocytes (31%) in most (61%) patients. Prognostically, the presence of ≥3.5% KITD816V-mutated cells (P < .0001) and an unstable KITD816V mutation cell burden (P < .0001) in blood and/or BM were both associated with a significantly shortened progression-free survival (PFS). These results confirm the high specificity but limited sensitivity of KITD816V analysis in whole blood for the diagnostic screening of SM and other primary MCAS, which might be overcome by assessing the mutation in blood-purified myeloid cell populations.


Identification and functional analysis of miRNAs in skeletal muscle of juvenile and adult largemouth bass, Micropterus salmoides.
MicroRNAs (miRNAs) are considered key regulators to post-transcriptionally regulate gene expression affecting multiple biological activities. However, the developmental process of fish skeletal muscles is regulated by complicated molecular mechanism that has not been completely well-described. In this study, two small RNAs libraries from skeletal muscle of juvenile as well as adult largemouth bass (LMB) were obtained and sequenced using deep sequencing to investigate the development-related miRNAs. We identified an overall number of 486 already recognized miRNAs in addition to 43 novel miRNAs. Comparison of two different skeletal muscle development stages led to the identification of 220 differently expressed miRNAs between juvenile and adult LMB containing 116 up-regulated as well as 104 down-regulated miRNAs. Of them, confirmation of some differently expressed miRNAs was performed via a stem-loop qRT-PCR, which exhibited differently expressed level in juvenile and adult LMB. Furthermore, GO and KEGG enrichment analyses of targets of differently-expressed miRNAs were carried out. Additionally, the analysis of miRNAs-targets interaction network showed that miR-181b-5p_R-1, miR-725 and miR-103 as the nodal miRNAs has over 20 target genes. Moreover, miR-103 could bind the 3'-UTR of actr8, which was validated via dual-luciferase reporter assay. It has been reasonably hypothesized that miR-103 may play a crucial role, which regulate skeletal muscle development of LMB. The present study provides the first identification of miRNA expression profiles at two different skeletal muscle development stages in LMB. Results may be valuable in interpreting the regulatory role miRNAs plays in the growth and developmental process of skeletal muscle and its possible use in LMB breeding.


Tissue and sex differences in the activation of aromatic hydrocarbon hydroxylases in rats.
Betamethasone and alpha-naphthoflavone produced similar activation of biphenyl 2-hydroxylase and benzo[a]pyrene 3-hydroxylase in control male rat liver microsomes. In small intestinal epithelial microsomes, betamethasone had no effect whereas alpha-naphthoflavone caused a pronounced activation of benzo[a]pyrene hydroxylation and a lesser activation of biphenyl 2-hydroxylation. In lung microsomes, betamethasone had no effect on either enzyme activity whereas alpha-naphthoflavone had no effect on biphenyl 2-hydroxylase but inhibited benzo[a]pyrene hydroxylase. In kidney cortex microsomes from male rats both compounds caused inhibition or had no effect whereas in kidney cortex microsomes female rats betamethasone activated whereas alpha-naphthoflavone had no effect. Activation also occurred in isolated viable hepatocytes from male rats. The response of biphenyl 2-hydroxylase was very similar to that found in male rat liver microsomes but benzo[a]pyrene hydroxylase was more sensitive to activation and less sensitive to inhibition than in microsomes. The findings are interpreted as demonstrating the presence of more than one 'latent' aromatic hydrocarbon hydroxylase in rodents.


Planar Hall magnetoresistive aptasensor for thrombin detection.
The use of aptamer-based assays is an emerging and attractive approach in disease research and clinical diagnostics. A sensitive aptamer-based sandwich-type sensor is presented to detect human thrombin using a planar Hall magnetoresistive (PHR) sensor in cooperation with superparamagnetic labels. A PHR sensor has the great advantages of a high signal-to-noise ratio, a small offset voltage and linear response in the low-field region, allowing it to act as a high-resolution biosensor. In the system presented here, the sensor has an active area of 50 µm × 50 µm with a 10-nm gold layer deposited onto the sensor surface prior to the binding of thiolated DNA primary aptamer. A polydimethylsiloxane well of 600-µm radius and 1-mm height was prepared around the sensor surface to maintain the same specific area and volume for each sensor. The sensor response was traced in real time upon the addition of streptavidin-functionalized magnetic labels on the sensor. A linear response to the thrombin concentration in the range of 86 pM-8.6 µM and a lower detection limit down to 86 pM was achieved by the proposed present method with a sample volume consumption of 2 µl. The proposed aptasensor has a strong potential for application in clinical diagnosis.


Modified Corneosurfametry as a new accelerated high-throughput ex vivo methodology for predicting cleanser effects towards human skin.
Corneosurfametry (CSM) was originally developed as a tool to predict irritation potential of cleansers. In this method, surface skin stripped using cyanoacrylate is contacted with surfactants/products, rinsed and stained with toluidine blue and basic fuschin dyes. The intensity of staining increases with increases in irritation potential of surfactant. Our objective was to modify the CSM technique to achieve better control of the tape stripping process. Another objective was to correlate the modified CSM (MCSM) with a traditional in-vivo forearm controlled application test (FCAT) for mildness and to explore its utility to assess the state of corneum after a clinical test. Surface skin cells were tape stripped from forearms of volunteers with D-Squame Adhesive Discs. Discs were treated with a 10% solution of the product in a 96-plate well for 10 min, rinsed, dried and treated with basic fuschin-toluidine blue dye solution, rinsed and dried again. Forearm Controlled Application Test (FCAT) was based on a published protocol. Tape strips obtained after product treatment were also analyzed by the MCSM procedure without additional product treatment. Mildness/barrier damage assessed from in-vivo FCAT showed a similar ranking to the MCSM results. MCSM, TEWL and Erythema analysis of between-treatment differences showed a good correlation indicating that barrier damage seen in in-vivo studies can be predicted from ex-vivo MCSM studies. MCSM analysis of tape strips after the FCAT study showed that the damage decreased with increase in tape strip number. A moisturizing body wash (MBW) with mild surfactants showed the least damage in all layers. In contrast, harsh dish washing liquid showed significantly higher damage down to several layers. Another MBW with petrolatum in a harsher base showed damage almost similar to that of the harsh dish washing liquid in the surface layers. Thus, the MCSM was able to show underlying damage which would have been normally masked by the deposited petrolatum. The MCSM assay was shown to be a valuable tool for accelerated high throughput evaluation of mildness of surfactants and fully formulated products. MCSM can also be used to assess the state of the corneum after a product treatment.


Nutritional composition of the meat of Hereford and Braford steers finished on pastures or in a feedlot in southern Brazil.
Chemical and mineral composition and the intramuscular fatty acid (IMF) profile of the Longissimus dorsi muscle (LM) of 60 purebred Hereford, 1/4 Braford and 3/8 Braford steers finished either in a feedlot or on improved pastures of the Pampa biome were evaluated. Pastures were improved with the introduction of Lolium multiflorum, Trifolium repens, and Lotus corniculatus. On average, beef from pasture-fed steers presented higher concentrations of the fatty acids C18:3n-3 (P<0.001), C20:3n-3 (P=0.035), total n-3 (P<0.001) and lower n-6/n-3 ratio (P<0.001) in the IMF, and higher Mg and lower K content in muscle relative to those finished in the feedlot. C12:0 concentration in IMF was higher (P=0.027) for 3/8 Braford than the purebred Hereford steers, whereas purebred Herefords presented lower C14:1 (P=0.003) and higher C18:0 (P=0.022) concentrations than the two Braford groups. The meat composition of purebred Hereford and Braford steers was not substantially different; however, beef produced exclusively on improved pastures presented higher concentration of components that are considered beneficial to human health, such as n-3 fatty acids, and a lower n-6/n-3 ratio.


The possible role of nitric oxide signaling and NMDA receptors in allopurinol effect on maximal electroshock- and pentylenetetrazol-induced seizures in mice.
Allopurinol, a uric-acid-lowering medication, has shown its efficacy in several studies suggesting that allopurinol can be prescribed as adjunctive cure meant for intractable epilepsy. The exact mechanism of allopurinol is still unknown. This study evaluates allopurinol's effect on seizure threshold, seizure incidence, and mortality rate in mice models. Moreover, the possible involvement of nitric oxide (NO) pathway and N-methyl-D-aspartate (NMDA) receptors are investigated. To evaluate the effect of allopurinol on seizure, we used the pentylenetetrazole (PTZ)-induced seizure along with maximal electroshock (MES)-induced seizure. To assess the underlying mechanism behind the allopurinol activity, we used nitric oxide synthase (NOS) substrate (L-arginine), NOS inhibitors (L-NAME, aminoguanidine, 7-nitroindazole), and NMDA receptor antagonist (MK-801). Intraperitoneal allopurinol administration at a dose of 50 mg/kg in mice showed a significant (p < 0.001) anti-convulsant activity in the PTZ-induced seizure. Even though pre-treatment with L-Arginine (60 mg/kg) potentiates allopurinol's anti-convulsant effect in the PTZ-induced seizure, pre-treatment with L-NAME (10 mg/kg), aminoguanidine (100 mg/kg), and 7-nitroindazole (30 mg/kg) reversed the anti-convulsant effect of allopurinol in the PTZ-induced seizure. In addition, pre-treatment with MK-801 also decreased the anti-convulsant effect of allopurinol in the PTZ-induced seizure. While allopurinol at a dose of 50 mg/kg and 100 mg/kg did not induce protection against seizure incidence in the MES-induced seizure, it revealed a remarkable effect in reducing the mortality rate in the MES-induced seizure. Allopurinol increases the seizure threshold in PTZ-induced seizure and enhances the survival rate in MES-induced seizure. Allopurinol exerts its anti-convulsant effect, possibly through targeting NO pathway and NMDA receptors.


Pediatric obesity: preventive measures in early childhood.
This article reviews the factors contributing to early childhood obesity and the options for recognition and early intervention. The role for developing preschool wellness programs that incorporate nutrition education and physical activity is presented with a model under development in the state of Maryland.


Coronary reactivity in the porcine heart after short lasting myocardial ischaemia: effects of duration of ischaemia and myocardial stunning.
The aim was to characterise reactive hyperaemia and endothelium dependent (ADP) and independent (adenosine) vasodilatation after ischaemic periods of increasing duration, and in the stunned myocardium. The left anterior descending coronary artery was occluded 5-7 cm distal from its origin for consecutive periods of 2, 2, 5, 10, and 2 min separated by 30 min of reperfusion. Coronary flow was continuously measured by Doppler flowmetry proximal to the occlusion site. ADP and adenosine were infused into the left coronary artery proximal to the flowprobe. 11 domestic pigs, weight 25-36 kg, were used. In the stunned myocardium maximal reactive hyperaemia after 2 min of ischaemia was preserved, whereas all other variables describing reactive hyperaemia were diminished: time to maximal hyperaemia by 40% (p less than 0.01), duration of hyperaemia by 44% (p less than 0.001), volume of hyperaemia by 53% (p less than 0.001), and repayment of flow debt by 43% (p less than 0.001). The vasodilating effects of ADP and adenosine (dose-response curves) were not altered after development of stunning. Preserved maximal hyperaemia and vasodilation during ADP and adenosine infusion, but reduced volume of hyperaemia, indicate normal coronary reactivity but diminished release in the stunned myocardium of the vasodilator(s) responsible for the prolonged postischaemic flow increase.


Natural milk fatty acids affect survival and invasiveness of Listeria monocytogenes.
The effects of 12 fatty acids, naturally occurring in milk from several mammalian species, on the survival and invasion ability of Listeria monocytogenes, a food-borne pathogen, were determined. The survival was tested in the presence of 200 micrograms ml-1 fatty acids suspended in brain hearth infusion broth or in storage conditioning solution (NaCl 1%) of Mozzarella cheese, an Italian soft unripened cheese, at pH 7.0 or 5.0. Lauric (C12:0), linoleic (C18:2) and linolenic (C18:3) acids exerted the strongest bactericidal activity. The invasive efficiency of L. monocytogenes, determined in the Caco-2 enterocyte-like cell line, was strongly decreased in the presence of the fatty acids tested (from about 20 to 500-fold). This research suggests that naturally occurring fatty acids of milk, supplemented in milk derivatives, could affect both bacterial growth and invasiveness and consequently, could serve as barriers towards L. monocytogenes infection.


Chromosomal microarray analysis in fetuses with central nervous system anomalies: An 8-year long observational study from a tertiary care university hospital.
To evaluate the prevalence of DNA copy number variants (CNVs) detected with array comparative genomic hybridization (CGH) in fetuses with central nervous system (CNS) anomalies. Secondary objectives were to describe the prevalence of CNV in specific CNS abnormalities, in isolated defects or associated with other malformations or fetal growth restriction (FGR). Observational cohort study in 238 fetuses with CNS anomalies in which an array-CGH had been performed between January 2009 and December 2017. Pathogenic CNV and variants of unknown significance (VUS) were reported. Pathogenic CNVs were found in 16/238 cases (6.7%), VUS in 18/238 (7.6%), and normal result in 204/238 (85.7%) cases. Pathogenic CNVs were more frequent in posterior fossa anomalies (cerebellar hypoplasia 33%, megacisterna magna 20%), moderate ventriculomegaly (11%) and spina bifida (3.7%). Pathogenic CNVs and VUS were found in 7/182 (3.8%) and 14/182 (7.7%) cases of isolated anomalies, in 9/49 (18.4%) and 4/49 (8.2%) presenting another malformation, and in 0/7 and 0/7 cases with associated FGR (P = .001, P = .741, respectively). These results provide strong evidence toward performing array in fetuses with CNS anomalies, particular in cases of posterior fossa anomalies. The prevalence of pathogenic CNVs is higher in association with other malformations.


Optimization of imidazole 5-lipoxygenase inhibitors and selection and synthesis of a development candidate.
Structural modification of imidazole 5-lipoxygenase (5-LO) inhibitors for optimizing inhibitory potency, pharmacokinetic behavior and toxicity (ocular) profile led to 4-{3-[4-(2-methyl-1H-imidazol-1-yl)phenylthio]}phenyl-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide (6) with no observable ocular toxicity. The orally active and safe imidazole 5-LO inhibitor 6 was selected as a clinical candidate and advanced to clinical studies. An improved synthesis of 6 is also discussed.


Peritoneovenous shunt for pancreatic ascites.
A chronically ill patient with pancreatic ascites was successfully treated with a temporary LeVeen peritoneovenous shunt. This observation supports the use of a peritoneovenous shunt in the treatment of pancreatic ascites which is refractory to medical therapy and not amenable to major pancreatic surgery.


EMG levels in the occipitofrontalis muscles under an experimental stress condition.
In view of the importance attached to the frontalis muscles by researchers into the etiology of head pain and its treatment by biofeedback techniques, it is surprising that no data have yet been reported on the functioning of the occipitalis muscles, which have a close physiological relationship to the frontales. This study explores the response of the frontalis and occipitalis muscles under a condition of experimental stress. Migraine and tension-headache sufferers were separately compared with a headache-free control group under four conditions: baseline, while listening to instructions, while carrying out an auditory vigilance task, and for a further resting period equivalent to baseline. Results showed that tension levels in the frontalis muscles were not elevated at rest in any of the experimental groups, nor were they significantly responsive to the experimental task. The occipitales however proved to have significantly higher levels in both the tension-headache and migraine groups during the task and recovery periods. The results for the tension group reached significance because of a drop in control group values. These results may have significance in determining the best site for electrode placement in biofeedback.


Phenolic compounds in Hungarian acacia, linden, milkweed and goldenrod honeys.
Honey is a valuable source of nutrients, minerals and phenolic compounds. Phenolic acids and flavonoids are associated with health benefits of honey and can serve as markers for distinguishing honey types. This study aimed at determining the phenolic profile of four Hungarian unifloral honeys that were not analyzed previously. After verifying their botanical origin with melissopalynological analysis, total reducing capacity was determined with Folin-Ciocalteau method, and phenolic composition was analyzed with HPLC-DAD-MS. From the 25 phenolic substances examined, pinobanksin was the most abundant, followed by chrysin, p-hydroxybenzoic acid and galangin. Quercetin and p-syringaldehyde were detected only in acacia honey, which contained higher levels of chrysin and hesperetin compared to the other three honeys. Milkweed and linden honeys displayed higher levels of caffeic, chlorogenic, ferulic and p-coumaric acids compared to acacia and goldenrod honeys. Taxifolin may serve as a unique marker compound of milkweed honey. Goldenrod honey contained the highest level of syringic acid. Principal component analysis supported the indicator role of polyphenols in honey identification, discriminating clearly the four unifloral honeys. Our results suggest that phenolic profiles may be useful to find markers of honey's floral origin, but geographical origin can strongly influence the composition of characteristic compounds.


The development of a novel model of direct fracture healing in the rat.
Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing. A rat tibial osteotomy was created and fixed with compression plating similar to that used in patients. The procedure was evaluated in 15 cadaver rats and then in vivo in ten Sprague-Dawley rats. Controls had osteotomies stabilised with a uniaxial external fixator that used the same surgical approach and relied on the same number and diameter of screw holes in bone. Fracture healing occurred without evidence of external callus on plain radiographs. At six weeks after fracture fixation, the mean stress at failure in a four-point bending test was 24.65 N/mm(2) (sd 6.15). Histology revealed 'cutting-cones' traversing the fracture site. In controls where a uniaxial external fixator was used, bone healing occurred via external callus formation. A simple, reproducible model of direct fracture healing in rat tibia that mimics clinical practice has been developed for use in future studies of direct fracture healing.


A chemiluminescence immunoassay for the detection of NT-proBNP.
The aim of the study was to assess the analytical performance of the HISCL NT-proBNP assay, a newly developed chemiluminescence immunoassay, for the detection of NT-proBNP. The within-run and total imprecision of the NT-proBNP assay were determined with HISCL cardiac marker controls. The linear ranges of the NT-proBNP assays were evaluated based on the CLSI EP6-A document using selected serum samples. Two hundred serum samples were evaluated to compare the HISCL NT-proBNP and Elecsys NT-proBNP assays. Five additional high NT-proBNP concentrations serum samples were evaluated to assess if there was high-dose hook effect in the HISCL NT-proBNP assay. The total and within-run imprecision values of the HISCL NT-proBNP assay were 5.85%, 0.81%, 2.56% and 0.54% and 6.07%, 0.73%, 2.61% and 0.59% at 6.1, 129.83, 3732.84and39737.33 pg/ml, respectively. The assay was verified to be linear for NT-proBNP levels ranging between 6.1 and 39737.33 pg/ml. The assay comparison showed that HISCL NT-proBNP = 0.9803 × Elecsys NT-proBNP -4.383. The sensitivity of HISCL NT-proBNP was 87.23%, and the specificity was 85.61%. The AUC of HISCL NT-proBNP (0.90 (95% CI, 0.86-0.93)) did not differ from that of Elecsys NT-proBNP(0.89 (95% CI, 0.85-0.93)) (P = 0.638). The results of five high NT-proBNP concentrations samples (44448, 54206, 55634, 55728 and 109406 pg/ml, measured with the Elecsys NT-proBNP assay) tested with HISCL NT-proBNP assay were all displayed with ">40000 pg/ml". The HISCL NT-proBNP chemiluminescence immunoassay showed good analytical and diagnostic performance for the detection of NT-proBNP and could be used in routine clinical practice.


The role of the emergency physician in the prevention of domestic violence.
In the United States, every 7.4 seconds a woman is battered by her husband. Of women who present to emergency departments with traumatic injuries, 16% to 30% report that their injuries were secondary to domestic violence. Not infrequently, battered women's medical and surgical problems are treated by ED staff and the women are released without any intervention directed toward the prevention of future battering and/or injury. Protocols are presented that require only minimal reorganization of staffing in EDs to provide essential services directed toward battered women's most serious health problem, chronic victimization.


Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression.
Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.


Neuronal stretch reception - Making sense of the mechanosense.
The sensation of mechanical force underlies many of our daily activities. As the sense of touch determines the quality of life, the subconscious sense of proprioception and visceral mechanosensation is indispensible for survival. Many internal organs change shape, either as an active part of their physiology or passively due to body movements. Importantly, these shape changes need to be sensed and balanced properly to prevent organ failure and dysfunction. Consequently, a failure to properly sense volume changes of internal organs has a huge clinical relevance, manifested by a plethora of congenital and age-related diseases. Here we review novel data on mammalian stretch reception as well as classical studies from insect and nematode proprioceptors with the aim to highlight the missing link between organ-level deformation and mechanosensing on the molecular level.


[Neurological defects and developmental disorders following neonatal extracorporeal membrane oxygenation: results of a follow-up study after 5 years].
Descriptive study of the development of children 5 years after neonatal extracorporeal membrane oxygenation (ECMO). Descriptive. 98 treated children were subjected to a paediatric, neurological, psychological, physiotherapeutic and logopaedic examination. The children came from 2 Dutch ECMO-centres (the Erasmus MC-Sophia Children's Hospital in Rotterdam and the University Medical Centre St Radboud in Nijmegen, The Netherlands). Neurological disorders were found in 17 of the 98 investigated children, and in 6 cases these were serious. Among the remaining 92 children, 24 had motor disorders and 11 had delayed cognitive development. The average IQ (100.5) was within the normal range. A significant proportion ofthe children that had been treated with ECMO had long-term morbidity in the form of neurological defects and developmental disorders.


Chronic hypobaric hypoxia induced apoptosis in CA1 region of hippocampus: a possible role of NMDAR mediated p75NTR upregulation.
Hypobaric hypoxia has been implicated with neural degeneration and memory loss. Though there has been considerable knowledge on the role of the p75(NTR) in triggering apoptosis, the occurrence of a similar mechanism in hypoxic stress still remains to be explored. We, in the present study, have tried to explore the role of p75(NTR) in mediating apoptosis in hypobaric hypoxia. Male Sprague Dawley rats were exposed to an altitude of 7,620 m for different durations. To study the contribution of apoptosis to hypobaric hypoxia induced cell death in the hippocampus, rat brains were examined for the occurrence of apoptosis by determining the number of cells showing DNA breaks using terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) assay and chromatin condensation using Hoechst staining along with estimation of caspase activity and expression of active Caspase 3. Expression of p75(NTR) was studied to determine its possible role in triggering apoptosis in hypobaric hypoxia. Exposure to hypobaric hypoxia was found to progressively increase the number of TUNEL positive and Hoechst positive cells along with increase in caspase activity, thus suggesting apoptotic mode of cell death. p75(NTR) was found to be upregulated on prolonged exposure to hypobaric hypoxia corresponding to the increase in the number of apoptotic cells. Further, reduced expression of p75(NTR) expression by antisense nucleotide administration significantly decreased apoptosis in the CA1 region of hippocampus. Blocking of NMDA receptors by MK801 interestingly decreased p75(NTR) expression and the number of TUNEL positive cells as compared to hypoxic animals. These findings suggest the regulation of p75(NTR) by NMDA receptors and its role in inducing apoptosis in hypoxia.


Application of a Physiologically Based Pharmacokinetic Model to Study Theophylline Metabolism and Its Interactions With Ciprofloxacin and Caffeine.
Theophylline is a commonly used bronchodilator. However, due to its narrow therapeutic range, moderate elevation of serum concentration can result in adverse drug reactions (ADRs). ADRs occur because of interhuman pharmacokinetic variability and interactions with coprescribed medicines. We developed a physiologically based pharmacokinetic (PBPK) model of theophylline, caffeine, and ciprofloxacin metabolisms to: examine theophylline pharmacokinetic variability, and predict population-level outcomes of drug-drug interactions (DDIs). A simulation-based equation for personalized dosing of theophylline was derived. Simulations of DDI show that calculated personalized doses are safe even after cotreatment with large doses of strong inhibitors. Simulations of adult populations indicate that the elderly are most susceptible to ADRs stemming from theophylline-ciprofloxacin and theophylline-caffeine interactions. Females, especially Asians, due to their smaller average size, are more susceptible to DDI-induced ADRs following typical dosing practices. Our simulations also show that the higher adipose and lower muscle fractions in females significantly alter the pharmacokinetics of theophylline or ciprofloxacin.


How to be good at being bad: centrosome amplification and mitotic propensity drive intratumoral heterogeneity.
Cancer is truly an iconic disease--a tour de force whose multiple formidable strengths can be attributed to the bewildering heterogeneity that a tumor can manifest both spatially and temporally. A Darwinian evolutionary process is believed to undergird, at least in part, the generation of this heterogeneity that contributes to poor clinical outcomes. Risk assessment in clinical oncology is currently based on a small number of clinicopathologic factors (like stage, histological grade, receptor status, and serum tumor markers) and offers limited accuracy in predicting disease course as evidenced by the prognostic heterogeneity that persists in risk segments produced by present-day models. We posit that this insufficiency stems from the exclusion of key risk contributors from such models, especially the omission of certain factors implicated in generating intratumoral heterogeneity. The extent of centrosome amplification and the mitotic propensity inherent in a tumor are two such vital factors whose contributions to poor prognosis are presently overlooked in risk prognostication. Supernumerary centrosomes occur widely in tumors and are potent drivers of chromosomal instability that fosters intratumoral heterogeneity. The mitotic propensity of a proliferating population of tumor cells reflects the cell cycling kinetics of that population. Since frequent passage through improperly regulated mitotic divisions accelerates production of diverse genotypes, the mitotic propensity inherent in a tumor serves as a powerful beacon of risk. In this review, we highlight how centrosome amplification and error-prone mitoses contribute to poor clinical outcomes and urge the need to develop these cancer-specific traits as much-needed clinically-facile prognostic biomarkers with immense potential value for individualized cancer treatment in the clinic.


Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium.
The characterization and localization of endothelin A (ETA) and endothelin B (ETB) receptors have been determined in tissue sections of the human atrioventricular conducting system, surrounding regions of atrial and ventricular myocardium, and the left ventricular free wall by use of radioligand binding, polymerase chain reaction, and in situ hybridization. Selective ETA (BQ123) and ETB (BQ3020) compounds in conjunction with [125I]endothelin-1 revealed the presence of ETA and ETB receptors in the left ventricular free wall (BQ123: 57 +/- 5% ETA, 43 +/- 2% ETB, n = 3; BQ3020: 67 +/- 3% ETA, 33 +/- 3% ETB, n = 3). Autoradiography using [125I]endothelin-1 in the absence or presence of BQ3020, BQ123, or endothelin-1 showed ETA and ETB receptors localized to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. There was a higher proportion of ETB receptors in the atrioventricular node and the penetrating and branching bundles of His than in the surrounding interventricular and interatrial septa (p < 0.0001). There was a lower density of ETB receptors in the interventricular septum compared with the interatrial septum and the atrioventricular conducting system (p = 0.009) and a lower density of ETA receptors in the atrioventricular conducting system compared with interatrial and interventricular septa (p = 0.008). Isolated right atrial myocytes showed a higher proportion of ETA receptors (91 +/- 12%, n = 3). Amplification of left ventricular free wall cDNA by polymerase chain reaction revealed the presence of ETA and ETB receptor mRNA. mRNA for both subtypes was detected in isolated atrial myocytes. In situ hybridization showed ETA and ETB receptor mRNA localization to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. These studies demonstrate the presence of ETA and ETB receptors in human myocardium and the atrioventricular conducting system.


[Evaluation of the results of various technics of non-surgical therapy of varicocele].
A new method of non-surgical treatment of varicocele syndrome is described: it consists in sclerotherapy of spermatic vein by trans-femoral percutaneous catheterization with balloon-catheters. In 8 cases venous thrombosis has been induced by direct electric clotting. The techniques and a 6 months follow-up are discussed. It is pointed out that this procedure should be considered as the method of choice for tubular lesions and sub-fertility prophylaxis in young people and in childhood.


Maternal serum and amniotic fluid hydroxyproline levels in neural tube defects.
The present study was aimed to evaluate the alterations of maternal serum and amniotic fluid OH- proline levels in neural tube defects (NTD). 38 patients and 23 control subjects were selected from the patients followed up by the Departments of Genetics and Antenatal Care, Zekai Tahir Burak Women's Health, Education and Research Hospital. Amnion fluid and blood samples were synchronously obtained from NTD and control subjects. OH-proline levels were detected spectrophotometrically. Amniotic fluid OH-proline levels were found to be increased in NTD patients compared to control subjects (p < 0.05). There was no statistically significant difference in serum OH-proline levels between the groups. The results showed an increase in amniotic fluid OH-proline levels in NTD compared to the control group. It may be suggested that the increased OH-proline levels reflect increased collagen turnover in NTD patients. Indeed, amniotic fluid OH-proline levels may be a candidate as an additional diagnostic parameter in NTD.


A case of thoracoabdominal splenosis.
We describe a case of a 38-year-old male with a remote history of motor vehicle trauma who presented to the emergency department with 1-week history of progressively worsening abdominal pain localized to the epigastric region. Patient history included splenectomy. Computerized tomography demonstrated multiple masses in the left pleural space as well as masses continuous with the diaphragm and abdominal wall in the left upper quadrant. In addition, a lobulated mass was identified in the right upper quadrant along the anterior right hepatic lobe. A diaphragmatic defect was noted containing splenic tissue. A diagnosis of splenosis was made. Disseminated splenosis presenting in both the thorax and abdomen is rare and poorly documented. This case serves to further illuminate this condition.


Covert visual attention in patients with early-onset schizophrenia.
The aim of the present study is to examine attentional costs (inhibition) in covert visual attention in a group of acutely ill adolescents with schizophrenia without long histories of neuroleptic treatment. Variations in reaction time were analyzed for possible age and sex differences. Adolescents with schizophrenia (n = 19) were compared to a group of ADHD subjects (n = 20) and a group of normally functioning adolescents (n = 30) on a measure of covert visual attention. The results support a hypothesis of abnormally rapid disengagement (reduced costs) in male adolescents with schizophrenia. Such an abnormality has also been found in adults with chronic schizophrenia. Whether this holds true for both sexes of adolescents with schizophrenia or is restricted to male subjects cannot be answered with certainty due to the small number of females with schizophrenia in our sample. Our findings indicate, however, that there are some general sex differences and some specific sex differences related to covert visual attention in adolescents with schizophrenia.


Growth factor receptor regulation in the Minn-1 leprechaun: defects in both insulin receptor and epidermal growth factor receptor gene expression.
Leprechaunism is a disorder characterized by intrauterine growth retardation, distinctive dysmorphology, and extreme insulin resistance due to structural abnormalities of the insulin receptor (IR). In addition to the IR, it has been suggested that abnormalities of the other growth factor receptors may occur in this syndrome. Using fibroblasts from the Minn-1 leprechaun, we have now investigated the expression of three different growth factor receptor genes: the IR, the insulin-like growth factor-I receptor (IGF-IR), and the epidermal growth factor receptor (EGFR). In agreement with previous studies, we found decreased insulin binding to fibroblasts from the Minn-1 leprechaun. In these cells, the IR transcription rate was not decreased, and sequence analysis of the IR promoter region of the patient showed no abnormalities. Both single-stranded conformational polymorphism analysis (SSCP) and DNA sequencing confirmed a previously reported nonsense mutation in one of the patient's two IR alleles at exon 14. mRNA levels for the IR were markedly decreased, suggesting that IR mRNA turnover was enhanced. We then studied the expression of the closely related IGF-IR Ligand binding, mRNA content, and transcription rate were all normal. In contrast to the IGF-IR, when the EGFR was studied, ligand binding and mRNA content were markedly decreased. These studies therefore raise the possibility that the phenotypic expression of leprechaunism results from defects in the expression of both the IR and the EGFR.


Climate change in estuarine systems: Patterns and gaps using a meta-analysis approach.
Although regional studies and projections suggest the deterioration of estuaries as a consequence of climate change, it is still difficult to fully understand the importance of such changes in estuarine systems. This limitation is particularly important considering their high dynamism and the lack of temporally extended in situ databases with a good spatial coverage for these systems worldwide. Furthermore, contradictory patterns have been observed across the globe. Motivated by these issues, in this study we question the availability of in situ observational evidence of climate change in estuarine systems through a detailed meta-analysis of existing publications. A topic-related search considering the outputs of the Web of Science library was conducted in order to obtain a characterization of the existing studies on climate change in estuarine systems. Results confirmed that climate change has increasingly been studied since 2000 and that marine climate change constituted the focus of 9.69 % of those studies. From these, only 9.30 % encompassed estuarine studies and just 1.13 % used in situ observations from estuarine systems (i.e., 0.11 % of the total climate change publications). Reanalysis products were the most used tools to assess changes in estuarine systems and sea temperature was the most analyzed variable. These results highlight the need to further address such questions using in situ observational data and to implement long-term observatories to fully identify evidence of climate change in estuarine systems, supporting modelling approaches and promoting the development of effective mitigation plans.


TroCCAP recommendations for the diagnosis, prevention and treatment of parasitic infections in dogs and cats in the tropics.
The Tropical Council for Companion Animal Parasites Ltd. (TroCCAP) is a not-for-profit organisation whose mission is to independently inform, guide and make best-practice recommendations for the diagnosis, treatment and control of companion animal parasites in the tropics and sub-tropics, with the aim of protecting animal and human health. In line with this primary mission, TroCCAP recently developed guidelines for the diagnosis, treatment and control of feline and canine parasites in the tropics. The development of these guidelines required unique and complex considerations to be addressed, often inapplicable to developed nations. Much of the tropics encompass middle-to-low income countries in which poor standards of environmental hygiene and large populations of stray dogs and cats coexist. In these regions, a range of parasites pose a high risk to companion animals, which ultimately may place their owners at risk of acquiring parasitic zoonoses. These considerations led to the development of unique recommendations with regard, for example, to deworming and endoparasite testing intervals for the control of both global and 'region-specific' parasites in the tropics. Moreover, the 'off-' or 'extra'-label use of drugs for the treatment and control of parasitic infections is common practice in many tropical countries and many generic products lack manufacturers' information on efficacy, safety, and quality control. Recommendations and advice concerning the use of such drugs and protocols are also addressed in these guidelines. The formation of these guidelines is an important first step towards improving the education of veterinarians specifically regarding best-practice for the diagnosis, treatment and control of canine and feline parasites in the tropics.


Stimulation of motility and energy metabolism of spermatozoa from asthenozoospermic patients by 17 beta-estradiol.
Spermatozoa from nine asthenozoospermic patients were incubated for 3 h in Krebs Phosphate Ringer (KRP), supplemented or not with 17 beta-estradiol. 17 beta-estradiol increased the mean velocity and maintained the percentage of motility during the first 2 h of incubation. Oxydative metabolism and intracellular ATP concentrations were enhanced, too, whereas glycolysis remained unchanged.


Wernicke-Korsakoff syndrome in Sydney hospitals after 6 years of thiamin enrichment of bread.
To estimate the incidence of Wernicke's encephalopathy (WE) and Korsakoff's psychosis (KP) before and after the introduction of thiamin enrichment of bread in Australia. Inpatient records were examined in 17 major public general hospitals in greater Sydney for the 4 years 1993-96 (inclusive) with the International Classification of Diseases (ICD) 9 diagnoses 265.1 (WE), 291.1 and 294.0 (KP). Relevant clinical data were recorded on a specially designed form so that cases could be classified as confirmed or probable WE, confirmed or probable KP, confirmed or probable Wernicke-Korsakoff syndrome (WE + KP) or not WE or KP. The average number of cases of WE + KP was 38 acute (new) cases and 69 total (acute + chronic) cases per annum for all the hospitals combined. This study used the same methods as our earlier retrospective examination of Wernicke-Korsakoff cases in essentially the same hospitals for 1978-93. Records for 1993 were thus pulled twice and, while individual cases (using hospital index number) did not always coincide, the total numbers for 1993 were 69 and 70. For the 5 years after 1991 the number of acute cases of WE and KP in Sydney hospitals was 61% of the number for the 5 years before 1991 (P<0.01). There is, however, no continuing downward trend. These results are consistent with a 40% reduction of the incidence of acute WE and KP since bread has been enriched with thiamin. The disease complex has, however, not been eliminated. To achieve this, further public health action would be needed, such as addition of thiamin to beer.


Contribution of whole-body protein synthesis to basal metabolism in layer and broiler chickens.
The effect of starvation on whole-body protein synthesis and on the contribution of protein synthesis to basal metabolic rate was investigated in young chickens (Expt 1). Strain differences between layer and broiler chickens in whole-body protein synthesis and degradation rates were examined when the birds were starved (Expt 2). In Expt 1, 15-d-old White Leghorn male chickens were used, while in Expt 2 Hubbard (broiler) and White Leghorn (layer) male chickens at 14 d of age were used. They were starved for 4 d, and heat production was determined by carcass analysis after 2 and 4 d of starvation. Whole-body protein synthesis rates were measured on 0, 2 and 4 d of starvation (Expt 1), and on 0 and 4 d of starvation (Expt 2). The results showed that starving reduced whole-body protein synthesis in terms of fractional synthesis rate and the amount synthesized. Whole-body protein degradation was increased by starvation both in terms of fractional synthesis rate and the amount degraded on a per kg body-weight basis. Reduced fractional synthesis rate of protein in the whole body was accounted for by reductions in both protein synthesis per unit RNA and RNA:protein ratio. In the fed state, whole-body protein synthesis and degradation rates, whether expressed as fractional rates or amounts per unit body-weight, tended to be higher in layer than in broiler chickens. In the starved state, the difference in the rate of protein synthesis between the two strains virtually disappeared, while the degradation rates were higher in layer than in broiler birds.(ABSTRACT TRUNCATED AT 250 WORDS)


Urgent care study of the LumiraDx SARS-CoV-2 Ag Test for rapid diagnosis of COVID-19.
Testing individuals suspected of severe acute respiratory syndrome-like coronavirus 2 (SARS-CoV-2) infection is essential to reduce the spread of disease. The purpose of this retrospective study was to determine the false negativity rate of the LumiraDx SARS-CoV-2 Ag Test when utilized for testing individuals suspected of SARS-CoV-2 infection. Concurrent swab samples were collected from patients suspected of SARS-CoV-2 infection by their healthcare provider within two different urgent care centers located in Easton, MA, USA and East Bridgewater, MA, USA. One swab was tested using the LumiraDx SARS-CoV-2 Ag Test. Negative results in patients considered at moderate to high risk of SARS-CoV-2 infection were confirmed at a regional reference laboratory by polymerase chain reaction (PCR) using the additional swab sample. The data included in this study was collected retrospectively as an analysis of routine clinical practice. From October 19, 2020 to January 3, 2021, a total of 2241 tests were performed using the LumiraDx SARS-CoV-2 Ag Test, with 549 (24.5%) testing positive and 1692 (75.5%) testing negative. A subset (800) of the samples rendering a negative LumiraDx SARS-CoV-2 Ag Test was also tested using a PCR-based test for SARS-CoV-2. Of this subset, 770 (96.3%) tested negative, and 30 (3.8%) tested positive. Negative results obtained with the LumiraDx SARS-CoV-2 Ag test demonstrated 96.3% agreement with PCR-based tests (CI 95%, 94.7-97.4%). A cycle threshold (CT) was available for 17 of the 30 specimens that yielded discordant results, with an average CT value of 31.2, an SD of 3.0, and a range of 25.2-36.3. CT was > 30.0 in 11/17 specimens (64.7%). This study demonstrates that the LumiraDx SARS-CoV-2 Ag Test had a low false-negative rate of 3.8% when used in a community-based setting.


Recent paradigm shift in the assembly of bacterial tripartite efflux pumps and the type I secretion system.
Tripartite efflux pumps and the type I secretion system of Gram-negative bacteria are large protein complexes that span the entire cell envelope. These complexes expel antibiotics and other toxic substances or transport protein toxins from bacterial cells. Elucidating the binary and ternary complex structures at an atomic resolution are crucial to understanding the assembly and working mechanism. Recent advances in cryoelectron microscopy along with the construction of chimeric proteins drastically shifted the assembly models. In this review, we describe the current assembly models from a historical perspective and emphasize the common assembly mechanism for the assembly of diverse tripartite pumps and type I secretion systems.


Identification of sex pheromone components of blueberry spanworm Itame argillacearia (Lepidoptera: Geometridae).
Blueberry spanworm, Itame argillacearia (Packard), is an important defoliator of lowbush (syn. 'wild') blueberry, Vaccinium angustifolium Aiton, in north-eastern North America. The goal of the present study was to identify the female I. argillacearia sex pheromone, which could be used in traps for monitoring or mass-trapping this pest. Gas chromatography/mass spectrometry (GC/MS) and electroantennogram (EAG) recordings of sex pheromone gland extracts, in combination with chemical synthesis, a Y-tube olfactometer study and field experiments confirmed (2R,3S)-2-ethyl-3-((Z,Z)-tridecadi-2,5-enyl) oxirane (hereafter (Z,Z)-(3R,4S)-3,4-epoxy-6,9-heptadecadiene) and (Z,Z,Z)-3,6,9-heptadecatriene as female-produced sex pheromone components. (Z,Z)-(3R,4S)-3,4-Epoxy-6,9-heptadecadiene elicited a response from male I. argillacearia antennae during EAG recording, and in the Y-tube olfactometer tests males did not discriminate between a live female and (Z,Z)-(3R,4S)-3,4-epoxy-6,9-heptadecadiene. Field-trapping experiments showed that a blend of (Z,Z)-(3R,4S)-3,4-epoxy-6,9-heptadecadiene and (Z,Z,Z)-3,6,9-heptadecatriene was more attractive to male moths than (Z,Z)-(3R,4S)-3,4-epoxy-6,9-heptadecadiene alone.


Oxygen activation by P450(cin): Protein and substrate mutagenesis.
A conserved threonine found in the majority of cytochromes P450 (P450s) has been implicated in the activation of dioxygen during the catalytic cycle. P450(cin) (CYP176A) has been found to be an exception to this paradigm, where the conserved threonine has been replaced with an asparagine. Prior studies with a P450(cin) N242A mutant established that the Asn-242 was not a functional replacement for the conserved threonine but was essential for the regio- and stereocontrol of the oxidation of cineole. To explore further how P450(cin) controls the activation of the dioxygen in the absence of the conserved threonine, two concurrent lines of investigation were followed. Modification of P450(cin) indicated that the Thr-243 was not involved in controlling the protonation of the hydroperoxy species. In addition, the N242T mutant did not enhance the rate and/or efficiency of catalytic turnover of cineole by P450(cin). In parallel experiments, the substrate cineole was modified by removing the ethereal oxygen to produce camphane or 2,2-dimethylbicyclo[2.2.2]octane (cinane). An analogous experiment with P450(EryF) showed that a hydroxyl group on the substrate was vital, and in its absence catalytic turnover was effectively abolished. Catalytic turnover of P450(cin) with either of these alternative substrates (camphane or cinane) revealed that in the absence of the ethereal oxygen there was still a significant amount of coupling of the NADPH-reducing equivalents to the formation of oxidised product. Again the substrate itself was not found to be important in controlling oxygen activation, in contrast to P450(EryF), but was shown to be essential for regio- and stereoselective substrate oxidation. Thus, it still remains unclear how dioxygen activation in the catalytic turnover of cineole by P450(cin) is controlled.


Learning curve analysis of radiofrequency ablation for benign thyroid nodules.
Radiofrequency ablation (RFA) has been increasingly accepted as an alternative to surgery in the treatment of symptomatic benign thyroid nodules. However, the learning curve of thyroid RFA has yet to be defined. We hypothesized a temporal relationship between proficiency of the skill and midterm volume reduction. Consecutive patients who underwent RFA and had at least a six-month follow-up were identified from an institutional database. The cumulative sum (CUSUM) analysis was applied to visualize the learning curve on the adjusted volume reduction rate (VRR). A total of 102 nodules in 93 patients were included in the analysis. Linear regression revealed that nodule composition was the main predictor of the VRR. The composition-adjusted VRR increased with the chronological treatment order. The series was divided into three phases based on inflection points of the CUSUM analysis: the initial learning phase (case 1-20), consolidation phase (case 21-65), and proficiency phase (case 66-102). In the later phase, more solid nodules were treated, power output used by the operator was higher, and RFA treatment time was longer. The treatment efficiency of thyroid RFA was associated with technical proficiency, suggesting the presence of a learning curve effect.


Inverse effectiveness and multisensory interactions in visual event-related potentials with audiovisual speech.
In recent years, it has become evident that neural responses previously considered to be unisensory can be modulated by sensory input from other modalities. In this regard, visual neural activity elicited to viewing a face is strongly influenced by concurrent incoming auditory information, particularly speech. Here, we applied an additive-factors paradigm aimed at quantifying the impact that auditory speech has on visual event-related potentials (ERPs) elicited to visual speech. These multisensory interactions were measured across parametrically varied stimulus salience, quantified in terms of signal to noise, to provide novel insights into the neural mechanisms of audiovisual speech perception. First, we measured a monotonic increase of the amplitude of the visual P1-N1-P2 ERP complex during a spoken-word recognition task with increases in stimulus salience. ERP component amplitudes varied directly with stimulus salience for visual, audiovisual, and summed unisensory recordings. Second, we measured changes in multisensory gain across salience levels. During audiovisual speech, the P1 and P1-N1 components exhibited less multisensory gain relative to the summed unisensory components with reduced salience, while N1-P2 amplitude exhibited greater multisensory gain as salience was reduced, consistent with the principle of inverse effectiveness. The amplitude interactions were correlated with behavioral measures of multisensory gain across salience levels as measured by response times, suggesting that change in multisensory gain associated with unisensory salience modulations reflects an increased efficiency of visual speech processing.


Immunocytochemical evidence for the GABAergic innervation of the stretch receptor neurons in crayfish.
The GABAergic innervation of the stretch receptor neurons of the crayfish Orconectes limosus has been investigated by means of light- and electron microscope immunocytochemistry using an antibody to GABA. Both whole-mount preparations and post-embedding semithin sections revealed a massive GABAergic innervation of both the slowly and the fast adapting receptor neurons. The stretch receptor organ is supplied by one principle GABA-immunoreactive axon, which gives off several branches that innervate the receptor neurons. Cell body, initial axon segment and dendritic region of the sensory neurons are covered by numerous GABA-immunoreactive varicose fibers. Electron microscopy revealed that the GABA-immunoreactive varicosities establish specialized synaptic contacts with the sensory neurons. The functional significance of the occurrence of GABA-immunoreactive varicosities on the different parts of the sensory neurons is discussed. The results support the physiological and pharmacological evidence that GABA is a transmitter substance of the efferent inhibitory neurons which innervate the crayfish stretch receptor neurons.


Unusual interventional management in an adult with tetralogy of Fallot.
A 53-year-old man with tetralogy of Fallot had been palliated with two classic Blalock-Taussig shunts. Cardiac catheterization in our center revealed acquired atresia of the pulmonary valve. We perforated and dilated the valve as a palliative procedure with a new system using radiofrequency energy.


Occupational obstructive airway diseases in Germany: Frequency and causes in an international comparison.
Occupational inhalative exposures contribute to a significant proportion of obstructive airway diseases (OAD), namely chronic obstructive pulmonary disease (COPD) and asthma. The number of occupational OAD in the German industrial sector for the year 2003 are presented. Other analyses of surveillance data were retrieved from Medline. Most confirmed reports of OAD are cases of sensitizer induced occupational asthma (625 confirmed cases) followed by COPD in coal miners (414 cases), irritant induced occupational asthma (156 cases), and isocyanate asthma (54 cases). Main causes of occupational asthma in Germany comprise flour/flour constituents (35.9%), food/feed dust (9.0%), and isocyanates (6.5%). Flour and grain dust is a frequent cause of occupational asthma in most European countries and South Africa. Isocyanates are still a problem worldwide. Although wide differences in the estimated incidences between countries exist due to deficits in the coverage of occupational OAD, the high numbers necessitate improvement of preventive measures.


HuGE Watch: tracking trends and patterns of published studies of genetic association and human genome epidemiology in near-real time.
HuGE Watch is a web-based application for tracking the evolution of published studies on genetic association and human genome epidemiology in near-real time. The application allows users to display temporal trends and spatial distributions as line charts and google maps, providing a quick overview of progress in the field. http://www.hugenavigator.net/HuGENavigator/startPageWatch.do


[New antiplatelet drugs].
Platelet-aggregation inhibitors are the cornerstone of the treatment and prevention of atherothrombotic events. Long limited to aspirin alone, new drugs have appeared in the past two decades. But only very recently have new targets been developed. The synergy of their mechanisms of action now makes it possible to obtain ever stronger inhibition of platelet aggregation.


Systemic structural gender discrimination and inequality in the health workforce: theoretical lenses for gender analysis, multi-country evidence and implications for implementation and HRH policy.
This commentary brings together theory, evidence and lessons from 15 years of gender and HRH analyses conducted in health systems in six WHO regions to address selected data-related aspects of WHO's 2016 Global HRH Strategy and 2022 Working for Health Action Plan. It considers useful theoretical lenses, multi-country evidence and implications for implementation and HRH policy. Systemic, structural gender discrimination and inequality encompass widespread but often masked or invisible patterns of gendered practices, interactions, relations and the social, economic or cultural background conditions that are entrenched in the processes and structures of health systems (such as health education and employment institutions) that can create or perpetuate disadvantage for some members of a marginalized group relative to other groups in society or organizations. Context-specific sex- and age-disaggregated and gender-descriptive data on HRH systems' dysfunctions are needed to enable HRH policy planners and managers to anticipate bottlenecks to health workforce entry, flows and exit or retention. Multi-method approaches using ethnographic techniques reveal rich contextual detail. Accountability requires that gender and HRH analyses measure SDGs 3, 4, 5 and 8 targets and indicators. To achieve gender equality in paid work, women also need to achieve equality in unpaid work, underscoring the importance of SDG target 5.4. HRH policies based on principles of substantive equality and nondiscrimination are effective in countering gender discrimination and inequality. HRH leaders and managers can make the use of gender and HRH evidence a priority in developing transformational policy that changes the actual conditions and terms of health workers' lives and work for the better. Knowledge translation and intersectoral coalition-building are also critical to effectiveness and accountability. These will contribute to social progress, equity and the realization of human rights, and expand the health care workforce. Global HRH strategy objectives and UHC and SDG goals will more likely be realized.


Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients.
To identify significant prognostic factors after irradiation of metastatic spinal cord compression (MSCC) in 335 breast cancer patients. The potential prognostic factors investigated included involved vertebra, other bone metastases, visceral metastases, performance status, pretreatment ambulatory status, time until motor deficits developed before RT, radiation schedule (shorter-course RT [one fraction of 8 Gy/five fractions of 4 Gy] vs. longer-course RT [10 fractions of 3 Gy/15 fractions of 2.5 Gy/20 fractions of 2 Gy), and the response to RT. On multivariate analysis, better functional outcome was associated with slower development of motor deficits (p <0.001) and being ambulatory before RT (p <0.001). The overall recurrence rate of MSCC was greater if other bone metastases were present (p <0.001) and if shorter-course RT was used (p <0.001). In-field recurrences alone were more frequent after shorter-course RT (p = 0.008). Survival was negatively affected by the presence of visceral metastases (p <0.001), deterioration of motor function after RT (p <0.001), reduced performance status (p <0.001), and the rapid development of motor deficits (p = 0.044). Outcomes and survival after RT for MSCC in breast cancer patients are associated with several prognostic factors. Patients with poor expected survival may be treated with shorter-course RT to keep the overall treatment time short. If survival is expected to be relatively favorable, longer-course RT appears preferable, because it is associated with fewer MSCC recurrences.


Neuroimaging in Epilepsy.
In recent years, the field of neuroimaging has undergone dramatic development. Specifically, of importance for clinicians and researchers managing patients with epilepsies, new methods of brain imaging in search of the seizure-producing abnormalities have been implemented, and older methods have undergone additional refinement. Methodology to predict seizure freedom and cognitive outcome has also rapidly progressed. In general, the image data processing methods are very different and more complicated than even a decade ago. In this review, we identify the recent developments in neuroimaging that are aimed at improved management of epilepsy patients. Advances in structural imaging, diffusion imaging, fMRI, structural and functional connectivity, hybrid imaging methods, quantitative neuroimaging, and machine-learning are discussed. We also briefly summarize the potential new developments that may shape the field of neuroimaging in the near future and may advance not only our understanding of epileptic networks as the source of treatment-resistant seizures but also better define the areas that need to be treated in order to provide the patients with better long-term outcomes.


Interaction between succinylcholine and cimetidine in rats.
The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (+/- 1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 10, 17.8, 23.7, 31.6, or 56.2 mg.kg-1 was then administered in groups of two to three rats. Cimetidine produced an immediate potentiation of twitch suppression followed by a transient reversal and then a continued potentiation. Peak potentiation occurred within 19.0 (+/- 2.7) sec and was maintained in 11 rats at steady-state. Reversal was evident 4.1 (+/- 0.4) min after cimetidine administration. There was a good relationship between peak potentiation and serum cimetidine concentration with 50% potentiation occurring at 46.5 (+/- 4.6) micrograms.ml-1. Potentiation at steady-state was not correlated to serum cimetidine concentration but there was a weak relationship between reversal and serum cimetidine concentration. These results support reports from patients of an interaction between cimetidine and succinylcholine.


Postoperative thrombotic effects of tranexamic acid in open heart surgery.
Following the administration of tranexamic acid, the occurrence of thromboembolic events is a controversial issue. In this retrospective cohort study, we aimed to determine the possible thromboembolic complications due to tranexamic acid as a prophylactic method in patients undergoing open heart surgery. The data of 172 adult patients undergoing open heart surgery were analyzed. All patients received tranexamic acid at a dose of 50 mg/kg. The patients were divided into 3 groups as multiple-valve surgery (group 1), coronary bypass alone (group 2), and coronary bypass with valve surgery (group 3). The amount of blood transfusion, bleeding in intra- and postoperative period, and the presence of thromboembolic events including myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis were investigated. Patient demographics and duration of surgery were not significantly different in groups (p > 0.05). Hb, Htc, INR, and platelet levels of all groups did not differ significantly (p > 0.05). In total, 7 patients underwent reexploration. Postoperative DVT, stroke, and seizure were not seen at all. There was no statistically significant difference between groups in terms of the amount of blood transfusion, drainage, or peritoneal hematoma. The length of hospital stay and the mortality rate did not differ (p > 0.05). In patients receiving tranexamic acid infusion at 50 mg/kg dose, reexploration rates remained at 4.1% even after major cardiac surgeries. No thrombosis, stroke, or seizure were reported. Our findings support that tranexamic acid is a safe drug which has positive effect on reducing perioperative bleeding.


Multidimensional analysis of the essential elements in pregnant women's whole blood and characterization of maternal status by elemental pattern.
During pregnancy, the fetus needs to obtain a lot of nutrients from the mother, but the micronutrient deficiencies in pregnancy are not clear at present, and there is no reliable basis for nutrient intake and supplement. The purpose of this study was to understand the levels of essential elements in whole blood of pregnant women during various pregnancy stages at different ages and in different regions, to evaluate the deficiency of essential elements in Chinese pregnant women, and to explore the feasibility of using the elemental pattern to characterize maternal status. Whole blood samples of 11222 healthy pregnant women enrolled in different areas of China from Jan-Dec 2019, were analyzed for concentrations of six essential elements including Mn, Cu, Zn, Ca, Mg, and Fe, using the inductively coupled plasma mass spectrometer. A retrospective comparative study during different pregnancy periods at different ages and in different regions in whole blood essential elements content from non-pregnant normal women and pregnant normal women was developed using multivariate statistical analysis. Principal component analysis evaluation elemental pattern was used to characterize pregnancy status of pregnant women. In general, the levels of six essential elements in whole blood of pregnant women can satisfy the needs of normal physiological activities. With the development of pregnancy, the contents of Cu and Mn increased, while the contents of Fe and Mg decreased, and the contents of Zn and Ca have no noteworthy change. At the same gestation stage, the Cu content in whole blood of elderly pregnant women was higher. There were some differences in whole blood essential elements content of pregnant women in different regions. Principal component analysis and heat map analysis showed the feasibility of using bioinformatics research strategies to identify different pregnancies. There are differences in the content of whole blood essential elements of women at different stages of pregnancy in different regions. It was found that there was no obvious deficiency in whole blood essential elements levels of pregnant women in recent years. The pattern of essential elements has a certain application potential in the evaluation of pregnancy and pregnant women's health status.


Synthetic lethal targeting of TET2-mutant hematopoietic stem and progenitor cells (HSPCs) with TOP1-targeted drugs and PARP1 inhibitors.
Inactivating mutations in TET2 serve as an initiating genetic lesion in the transformation of hematopoietic stem and progenitor cells (HSPCs). Thus, effective therapy for this subset of patients would ideally include drugs that are selectively lethal in TET2-mutant HSPCs, at dosages that spare normal HSPCs. In this study, we tested 129 FDA-approved anticancer drugs in a tet2-deficient zebrafish model and showed that topoisomerase 1 (TOP1)-targeted drugs and PARP1 inhibitors selectively kill tet2-mutant HSPCs. We found that Tet2-deficient murine bone marrow progenitors and CRISPR-Cas9-induced TET2-mutant human AML cells were more sensitive to both classes of drugs compared with matched control cells. The mechanism underlying the selective killing of TET2-mutant blood cells by these drugs was due to aberrantly low levels of tyrosyl-DNA phosphodiesterase 1 (TDP1), an enzyme that is important for removing TOP1 cleavage complexes (TOP1cc). Low TDP1 levels yield sensitivity to TOP1-targeted drugs or PARP1 inhibitors and an inability to remove TOP1 cleavage complexes, leading to DNA double-strand breaks and cell death. The finding that TET2 mutations render HSPCs uniquely vulnerable to disruption of TOP1 and PARP1 activity may therefore represent a unique opportunity to use relatively low dosages of these drugs for the "precision therapy" of TET2-mutant myeloid malignancies.


Recent trends in childhood blood lead levels.
Blood lead levels in children in the United States have declined through 1994, the date of the most recent National Health and Nutrition Examination Survey. In this investigation, the authors analyzed whether blood lead levels have changed since 1994 and quantified the magnitude of any change. The authors evaluated blood lead levels from 12 longitudinal data sets from 11 states and 1 city. Geometric mean blood lead levels declined between 4%/year and 14%/year in 8 of the data sets. No differences in decline rates were observed between data sets from states that had universal screening as a goal or that included repeat measures for an individual child and those data sets that did not. The authors' best estimate for these populations was a decline rate of 4-7%/year, which was comparable to the decline rate prior to 1994.


The effect of remote patient monitoring on the primary care clinic visit frequency among adults with type 2 diabetes.
Healthcare organizations are increasingly using technology to assist in diabetes management based on telemedicine's proven ability to improve glycemic regulation, decrease cost, and overcome barriers to effective healthcare. Nevertheless, it remains unclear how telemedicine intersects with primary care. We aim to measure the impact of a remote monitoring program for diabetes on primary care delivery through analysis of primary care office visit frequency. Patients eligible to participate in our institution's remote diabetes monitoring program were identified and classified as enrolled or not enrolled (i.e. "usual care"). The number of scheduled and completed primary care office visits in the 12 months prior to and after the index date were measured for both groups. The index date was the enrollment date or, for the patients who received usual care, the next available enrollment session after eligibility screen. Two-sample t-tests were used to examine the change in frequency of office visits prior to and after enrollment for participants, as well as the difference in visit frequency between enrolled patients versus patients receiving usual care. There was no statistical difference in the number of scheduled or completed primary care clinic visits before or after enrollment in telehealth. Furthermore, there was no difference in the number of scheduled or completed primary care visits between patients enrolled in telehealth versus those receiving usual care. Participation in telehealth has been shown to be associated with significant HbA1c reductions in prior work, yet our data suggest that remote monitoring is not associated with a change in primary care office visit frequency. This suggests that telehealth may improve diabetes management independently of primary care visits.


Three-hit hypothesis in astrocytoma: tracing the polymorphism D1853N in ATM gene through a pedigree of the proband affected with primary brain tumor.
Ataxia telangictasia mutated (ATM) is involved in DNA repair pathway and cell-cycle checkpoints. ATM alterations were found in medulloblastomas, gliomas, but not in astrocytoma. The polymorphism D1853N was reported in healthy individuals and medulloblastomas. We could observe this polymorphism, heterozygously, in a proband affected with astrocytoma and traced it through her pedigree. We propose the three-hit hypothesis as a triangle initiators includes D1853N as a first predisposing hit, IVS 38- 63T --> A as a second hit deriving from the first somatic evolution before differentiation and IVS 38- 30 A --> G as a third hit through the development of an astrocytoma. In addition, the D1853N polymorphism was occurred in different allele from IVS 38- 63T --> A and IVS 38- 30 A --> G.


Adverse outcomes following hospitalization in acutely ill older patients.
The longitudinal outcomes of patients admitted to acute care for elders units (ACE) are mixed. We studied the associations between socio-demographic and functional measures with hospital length of stay (LOS), and which variables predicted adverse events (non-independent living, readmission, death) 3 and 6 months later. Prospective cohort study of community-living, medical patients age 75 or over admitted to ACE at a teaching hospital. The population included 147 subjects, median LOS of 9 days (interquartile range 5-15 days). All returned home/community after hospitalization. Just prior to discharge, baseline timed up and go test (TUG, P < 0.001), bipedal stance balance (P = 0.001), and clinical frailty scale scores (P = 0.02) predicted LOS, with TUG as the only independent predictor (P < 0.001) in multiple regression analysis. By 3 months, 59.9% of subjects remained free of an adverse event, and by 6 months, 49.0% were event free. The 3 and 6-month mortality was 10.2% and 12.9% respectively. Almost one-third of subjects had developed an adverse event by 6 months, with the highest risk within the first 3 months post discharge. An abnormal TUG score was associated with increased adjusted hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03 to 1.59, P = 0.03. A higher FMMSE score (adjusted HR 0.89, 95% CI 0.82 to 0.96, P = 0.003) and independent living before hospitalization (adjusted HR 0.42, 95% CI 0.21 to 0.84, P = 0.01) were associated with reduced risk of adverse outcome. Some ACE patients demonstrate further functional decline following hospitalization, resulting in loss of independence, repeat hospitalization, or death. Abnormal TUG is associated with prolonged LOS and future adverse outcomes.


[CAMDEX-R in the clinical evaluation of dementias].
CAMDEX has been very useful both for clinical use as epidemiological enquiries about dementia. However, the knowledge evolution about means that nowadays this schedule shows several shortcoming. A new version, CAMDEX-R, has adapted and introduced enough items to satisfy the actual requirements. The present article describes the changes and new contributions accomplished on the schedule.


Osmotically induced motility of outer hair cells: implications for Menière's disease.
Osmolarity changes in inner ear fluids have long been considered to be contributing factors to Menière's disease. Our present study demonstrates that small changes in the osmolarity of a surrounding in vitro medium induce fast contractions (hypo-osmotic solution) or elongations (hyperosmotic solution) in isolated outer hair cells of the guinea pig. These changes were reversible upon returning cells to iso-osmotic conditions. Up to five cycles of shape change could be sustained by these cells without obvious detriment to their morphology. These findings suggest that fluctuant changes in osmolarity of inner ear fluids can result in similar fluctuant changes of hair cell shape. Since the outer hair cells may control cochlear micromechanics and function by their active motility, osmotically induced abnormalities of cell dimensions and motility may contribute to the audiological manifestations of fluctuant hearing loss.


Scale up cultivation of primary human umbilical vein endothelial cells on microcarriers from spinner vessels to bioreactor fermentation.
Five types of dextran-based microcarriers (Dormacell(™), Pfeifer and Langen) with different concentrations of dimeric DEAE anion-exchange groups (nitrogen contents from 1.2 up to 2.9%) were tested as growth substrates for the cultivation of human umbilical vein endothelial cells (HUVECs). All microcarriers were gelatinized before use to improve cell adhesion. The one with the highest DEAE-group density was found to be most suitable for HUVEC propagation reaching final cell densities of 8×10(5) viable cells ml(-1) (95% viability) using microcarrier concentrations of 3 g l(-1). Furthermore, metabolic data of glucose/lactate and amino acid metabolism are presented in this study. The concentrations of 18 amino acids were monitored throughout cultivation. A considerable decrease of glutamine and inverse increase of glutamate was observed. Cultivation with initial glucose concentration of 16.5 mmol l(-1) resulted in high glutamine consumption rates, whereas high glucose-supplemented starting culture medium (30 mmol l(-1)) gave considerably lowered rates, indicating altered glutamine metabolism due to different glucose feeding. The glucose consumption and lactate production rates increased 2.6 fold and 3.5 fold, respectively, due to switch over from low to high glucose supplemented cultures. The rate of glucose metabolism was found not to be directly related to cell growth, because almost identical growth rates and doubling times were obtained. Considering the remaining 16 amino acids measured, serine concentrations considerably declined and glycine as well as alanine concentrations raised strongly. Most amino acid values were found insignificantly altered during 14 days of cultivation. Spinner vessel cultures served as inoculum for up scale propagation of HUVECs in membrane stirred 2 liter bioreactors. About 5×10(9) HUVECs were produced, which were used for the isolation and structural characterization of glycosphingolipids, cell membrane compounds, which are suggested to be involved in e.g. selectin-carbohydrate interaction (cell-cell adhesion), carcinogenesis and atherogenesis.


Accessibility of nutritional services for children with autism spectrum disorder in the United Arab Emirates: Insights from special education teachers and parents.
Goal 2 of United Nation's Sustainable Development Goals exhorts countries to provide guidelines on better nutrition for all children. In response, the United Arab Emirates (UAE) government designed a national nutrition framework to encourage better eating habits. However, large body of literature has reported that children with ASD are at high risks of malnutrition and poor eating habits. Yet, in the UAE and other contexts, there is limited research on accessibility of nutritional services to adults in the lives of children with ASD. As parents and teachers spend the most time with children with ASD, this study sought to understand their perceptions of the availability of nutritional services for such children in the UAE. Penchansky and Thomas' (1981) health access theory served as the theoretical framework; its five tenets (geography, finance, accommodation, resources and acceptability) informed the design of a semi-structured interview guide. Data were collected from 21 participants, comprising 6 parents and 15 teachers of children with ASD. Thematic analysis revealed that participants perceived accommodation, acceptability, and human resource availability as barriers to accessibility. However, geographical and financial accessibility were not identified as challenges. The study calls for health policymakers to formalise nutritional services as an integrated part of the UAE health system, while also extending services to children with ASD. This study makes a substantial contribution to the literature. First, it addresses the needs for nutritional services for children with ASD. There is a limited body of knowledge on whether children with ASD have access to the requisite nutrition for development This study sheds light on an area that has received limited scholarly insight. Second, it adds to the usage of health access theory in studies on nutritional services for children with ASD.


Circulating Tissue Factor Levels and Risk of Stroke: Findings From the EPICOR Study.
Tissue factor (TF) expression is increased in inflammatory atherosclerotic plaques and has been related to their thrombogenicity. Blood-borne TF has been also demonstrated to contribute to thrombogenesis. However, few studies have evaluated the association of circulating levels of TF with stroke. We investigated the association of baseline circulating levels of TF with stroke events occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Using a nested case-cohort design, a center-stratified random sample of 839 subjects (66% women; age range, 35-71 years) was selected as subcohort and compared with 292 strokes in a mean follow-up of 9 years. Blood samples were collected at baseline in citrate, plasma was stored in liquid nitrogen and TF was measured by ELISA (IMUBIND, TF ELISA, Instrumentation Laboratory, Milan, Italy). The odd ratios and 95% confidence intervals, adjusted by relevant confounders (covariates of TF) and stratified by center, were estimated by a Cox regression model using Prentice method. Individuals in the highest compared with the lowest quartile of TF plasma levels had significantly increased risk of stroke (odds ratioIVvsI quartile, 2.01; 95% confidence interval, 1.25-3.23). The association was independent from several potential confounders (odds ratioIVvsI quartile, 1.91; 95% confidence interval, 1.15-3.19). No differences were observed between men and women. The increase in risk was restricted to ischemic strokes (odds ratioIVvsI quartile, 2.13; 95% confidence interval, 1.10-4.12; fully adjusted model), whereas high levels of TF were not associated with the risk of hemorrhagic stroke (odds ratioIVvsI quartile, 1.12; 95% confidence interval, 0.49-2.55; fully adjusted model). Our data provide evidence that elevated levels of circulating TF are potential risk factors for ischemic strokes.