Safe Kids Week: Analysis of gender bias in a national child safety campaign, 1997-2016.
Background and Purpose Child safety campaigns play an important role in disseminating injury prevention information to families. A critical discourse analysis of gender bias in child safety campaign marketing materials can offer important insights into how families are represented and the potential influence that gender bias may have on uptake of injury prevention information. Methods Our approach was informed by poststructural feminist theory, and we used critical discourse analysis to identify discourses within the poster materials. We examined the national Safe Kids Canada Safe Kids Week campaign poster material spanning twenty years (1997-2016). Specifically, we analyzed the posters' typeface, colour, images, and language to identify gender bias in relation to discourses surrounding parenting, safety, and societal perceptions of gender. Results The findings show that there is gender bias present in the Safe Kids Week poster material. The posters represent gender as binary, mothers as primary caregivers, and showcase stereotypically masculine sporting equipment among boys and stereotypically feminine equipment among girls. Interestingly, we found that the colour and typeface of the text both challenge and perpetuate the feminization of safety. Discussion It is recommended that future child safety campaigns represent changing family dynamics, include representations of children with non-traditionally gendered sporting equipment, and avoid the representation of gender as binary. This analysis contributes to the discussion of the feminization of safety in injury prevention research and challenges the ways in which gender is represented in child safety campaigns.


Discovery of DNA-Carbon Nanotube Sensors for Serotonin with Machine Learning and Near-infrared Fluorescence Spectroscopy.
DNA-wrapped single walled carbon nanotube (SWNT) conjugates have distinct optical properties leading to their use in biosensing and imaging applications. A critical limitation in the development of DNA-SWNT sensors is the current inability to predict unique DNA sequences that confer a strong analyte-specific optical response to these sensors. Here, near-infrared (nIR) fluorescence response data sets for ∼100 DNA-SWNT conjugates, narrowed down by a selective evolution protocol starting from a pool of ∼1010 unique DNA-SWNT candidates, are used to train machine learning (ML) models to predict DNA sequences with strong optical response to neurotransmitter serotonin. First, classifier models based on convolutional neural networks (CNN) are trained on sequence features to classify DNA ligands as either high response or low response to serotonin. Second, support vector machine (SVM) regression models are trained to predict relative optical response values for DNA sequences. Finally, we demonstrate with validation experiments that integrating the predictions of ensembles of the highest quality neural network classifiers (convolutional or artificial) and SVM regression models leads to the best predictions of both high and low response sequences. With our ML approaches, we discovered five DNA-SWNT sensors with higher fluorescence intensity response to serotonin than obtained previously. Overall, the explored ML approaches, shown to predict useful DNA sequences, can be used for discovery of DNA-based sensors and nanobiotechnologies.


Identification of proteins of the yeast protein map using genetically manipulated strains and peptide-mass fingerprinting.
In this study we used genetically manipulated strains in order to identify polypeptide spots of the protein map of Saccharomyces cerevisiae. Thirty-two novel polypeptide spots were identified using this strategy. They corresponded to the product of 23 different genes. We also explored the possibilities of using peptide-mass fingerprinting for the identification of proteins separated on our gels. According to this strategy, proteins contained in spots are digested with trypsin and the masses of generated peptides are determined by matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). The peptide masses are then used to search a yeast protein database for proteins that match the experimental data. Application of this strategy to previously identified polypeptide spots gave evidence of the feasibility of this approach. We also report predictions on the identities of nine unknown spots using MALDI-MS.


An interspecific analysis of relative jaw-joint height in primates.
Jaw-joint height (JJH) above the occlusal plane is thought to be influenced by cranial base angle (CBA) and facial angulation during growth. To better understand how JJH relates to midline craniofacial form, we test the hypothesis that relative increases in JJH are correlated with increasing CBA flexion and facial kyphosis (i.e., ventral bending) across primates. We compared JJH above the occlusal plane to CBA and the angle of facial kyphosis (AFK) across adults from 82 species. JJH scales with positive allometry relative to a skull geometric mean in anthropoids and most likely strepsirrhines. Anthropoid regressions for JJH are elevated above strepsirrhines, whereas catarrhines exhibit a higher slope than platyrrhines. Semipartial correlations between relative JJH and both CBA and AFK show no association across a small strepsirrhine sample, limited associations among catarrhines and anthropoids, but strong correlations in platyrrhines. Contrary to our hypothesis, however, increases in relative JJH are correlated with relatively less flexed basicrania and more airorhynch faces (i.e., reduced ventral bending) in platyrrhines. The mosaic pattern of relationships involving JJH across primate clades points to multiple influences on JJH across primates. In clades showing little association with basicranial and facial angles, such as strepsirrhines, the potential morphological independence of JJH may facilitate a relative freedom for evolutionary changes related to masticatory function. Finally, failure to associate relative JJH and basicranial flexion in most clades suggests that the relatively taller JJH and more flexed basicrania of anthropoids compared to strepsirrhines may have evolved as an isolated event during the origin of anthropoids.


Thromboembolic Events in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Study of Renal Impairment in Relation to Potential Thromboprophylaxis.
Recent studies on patients with muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC) have shown an association between NAC and thromboembolic events (TEE) prior to radical cystectomy (RC). Recent studies suggest that central venous access catheters (CVAs) may induce TEEs, and low-molecular-weight heparin (LMWH) has been mentioned as possible prophylaxis. However, other studies have shown a high incidence of decreased renal function in these patients. The purpose of this study was to determine the portion of MIBC patients with NAC-induced TEEs who had decreased preoperative renal function for whom LMWH potentially would not be beneficial as prophylaxis. We identified 459 cystectomized MIBC patients from two Swedish medical centers from 2009 to 2021. The inclusion criterion of cT2-T4aN0M0 resulted in 220 eligible patients, who were further divided into NAC-administered (n = 187) and NAC-eligible (n = 33), the tentative control group. Values of renal function before, during, and after each NAC cycle were retrospectively collected from individual medical records. Amongst the NAC-administered patients with TEE (n = 29), 41% (95% CI 23.5-61.1%) of patients had decreased renal function. Thus, a substantial portion of NAC-administered patients who developed TEEs had reduced renal function and would have been less likely to have benefited from renal clearance-dependent LMWH prophylaxis.


Association between Age of Menopause and Thickness of Crestal Cortical Bone at Dental Implant Site: A Cross-Sectional Observational Study.
Satisfactory host bone quality and quantity promote greater primary stability and better osseointegration, leading to a high success rate in the use of dental implants. However, the increase in life expectancy as a result of medical advancements has led to an aging population, suggesting that osteoporosis may become a problem in clinical dental implant surgery. Notably, relative to the general population, bone insufficiency is more common in women with post-menopausal osteoporosis. The objective of this study was to compare the thickness of the crestal cortical bone at prospective dental implant sites between menopausal and non-menopausal women. Prospective dental implant sites in the jawbone were evaluated in two groups of women: a younger group (<50 years old), with 149 sites in 48 women, and an older group (>50 years old) with 191 sites, in 37 women. The thickness of the crestal cortical bone at the dental implant site was measured based on each patient's dental cone-beam computed tomography images. For both groups, one-way analysis of variance and Tukey's post-test were used to assess the correlation between cortical bone thickness and the presence of implants in the four jawbone regions. Student's t-test was further used to compare differences between the older and younger groups. From the retrospective study results, for both groups, thickness of the crestal cortical bone was the highest in the posterior mandible, followed by anterior mandible, anterior maxilla, and posterior maxilla. Compared with the younger group, the older group had a lower mean thickness of the crestal cortical bone. Among the four regions, however, only in the posterior maxilla was the crestal cortical bone significantly thinner in the older group than in the younger group.


Long-range organization of plant satellite repeats investigated using strand-specific FISH.
The technique of chromosomal orientation and direction fluorescence in situ hybridization (COD-FISH) was adapted for plant chromosomes in order to study long-range organization of two families of satellite repeats, VicTR-B of Vicia sativa and PisTR-B of Pisum sativum. The technique allowed FISH to be performed on mitotic chromosomes in a strand-specific manner, resulting in visualization of the repeat orientation along the chromosomes and with respect to the direction of telomeric repeats. The VicTR-B probe applied to V. sativa chromosomes produced signals on a single chromatid at most regions containing corresponding sequences, thus confirming a presence of long arrays of head-to-tail arranged repeat monomers which is typical for satellite DNA. However, hybridization signals of different or equal intensities on both chromatids were also detected at some loci, suggesting a more complex arrangement of the repeats. Similar observations were made for PisTR-B repeats on P. sativum chromosomes, although the proportion of loci displaying signals on both chromatids was lower. In contrast to VicTR-B, orientation of the PisTR-B clusters with respect to telomeric sequences appeared to be conserved among subtelomeric regions of metacentric chromosomes and of the short arms of acrocentric chromosomes.


Distribution of Escherichia coli passaged through processing equipment during ground beef production using inoculated trimmings.
The contamination of raw ground beef by Escherichia coli O157:H7 is not only a public health issue but also an economic concern to meat processors. When E. coli O157:H7 is detected in a ground beef sample, the product lots made immediately before and after the lot represented by the positive sample are discarded or diverted to lethality treatment. However, there is little data to base decisions on how much product must be diverted. Therefore, five 2,000-lb (907-kg) combo bins of beef trimmings were processed into 10-lb (4.54-kg) chubs of raw ground beef, wherein the second combo of meat was contaminated with a green fluorescent protein (GFP)-expressing strain of E. coli. This was performed at two different commercial ground beef processing facilities, and at a third establishment where ground beef chubs from the second grinding establishment were mechanically split and repackaged into 3-lb (1.36-kg) loaves in trays. The GFP E. coli was tracked through the production of 10-lb (4.54-kg) chubs and the strain could not be detected after 26.5% more material (500 lb or 227 kg) and 87.8% more material (1,840 lb or 835 kg) followed the contaminated combo at each establishment, respectively. Three-pound (1.36-kg) loaves were no longer positive after just 8.6% more initially noncontaminated material (72 lb or 33 kg) was processed. The GFP strain could not be detected postprocessing in any residual meat or fat collected from the equipment used in the three trials. These results indicate that diversion to a safe end point (lethality or rendering) of the positive lot of ground beef, plus the lot before and lot after should remove contaminated ground beef, and as such provides support for the current industry practice. Further, the distribution and flow of E. coli on beef trimmings through various commercial equipment was different; thus, each establishment needs to consider this data when segregating lots of ground beef and establishing sampling protocols to monitor production.


Fluorescence lifetime tomography of live cells expressing enhanced green fluorescent protein embedded in a scattering medium exhibiting background autofluorescence.
We present a novel fluorescence lifetime tomography system applied to a highly scattering autofluorescent phantom containing live cells expressing the fluorophore enhanced green fluorescent protein (EGFP). The fluorescence signal was excited using a fiber-laser-pumped supercontinuum source and detected using wide-field time gating imaging. To facilitate rapid 3D reconstruction of the fluorescence lifetime distribution, the time-resolved data were Fourier-transformed in time to give complex functions that formed a data set for the Fourier domain reconstruction. Initially the presence of an unspecified background autofluorescence signal impeded reconstruction of the lifetime distribution, but we show that this problem can be addressed using a simple iterative technique.


Using a convex ostomy appliance to manage peristomal skin complications: introducing Aura Plus Soft Convex.
This article explores convex stoma appliances, introduces Aura Plus Soft Convex (CliniMed) and presents three case studies of its use. Convexity applies pressure to flatten uneven peristomal skin and form an effective adhesive seal, as well as increase protrusion of a poorly spouted stoma. This reduces the risk of leaks and peristomal skin damage, as well as minimising accessory use. Excess pressure can damage the skin, so convexity should be used with caution at the appropriate depth and firmness for the ostomate's body profile and stomal complications. Aura Plus Soft Convex has a soft and flexible baseplate for easy application and adherence, as well as a unique shape, comfort curves and a large adhesive area to reduce creases and leaks. The hydrocolloid contains Manuka honey to promote skin health, and integral belt loops offer additional security. The case studies show how this appliance can restore peristomal skin integrity and relieve stoma-related anxiety; provide gentle support for a flush stoma and a rounded abdomen; and prevent leaks and improve quality of life after years of stoma-related complications.


[Effect of ATP on the contractile activity of different sections of the digestive tract].
In chronic tests on fistulized dogs ATP only with its intravenous administration, starting from a dose of 0.33 mg/kg inhibited motility of the stomach, small and large intestines. The intensity and duration of the inhibitory effect depended on the dose of ATP administered, but beginning from the dose of 0.09 mg/kg the effect of saturation started developing. The adrenoblocking agents phentolamine and inderal, the sympatholytics isobarin and ornidum did not eliminate the inhibitory action of ATP. The latter effectively suppressed the periodic and food motility of the gastrointestinal tract, as well as the motility induced by the insulin-produced hypoglycemia, by carbacholine and methoclopramide.


A comprehensive urinary metabolomic approach for identifying kidney cancerr.
The diagnosis of cancer by examination of the urine has the potential to improve patient outcomes by means of earlier detection. Due to the fact that the urine contains metabolic signatures of many biochemical pathways, this biofluid is ideally suited for metabolomic analysis, especially involving diseases of the kidney and urinary system. In this pilot study, we test three independent analytical techniques for suitability for detection of renal cell carcinoma (RCC) in urine of affected patients. Hydrophilic interaction chromatography (HILIC-LC-MS), reversed-phase ultra performance liquid chromatography (RP-UPLC-MS), and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) all were used as complementary separation techniques. The combination of these techniques is best suited to cover a very large part of the urine metabolome by enabling the detection of both lipophilic and hydrophilic metabolites present therein. In this study, it is demonstrated that sample pretreatment with urease dramatically alters the metabolome composition apart from removal of urea. Two new freely available peak alignment methods, MZmine and XCMS, are used for peak detection and retention time alignment. The results are analyzed by a feature selection algorithm with subsequent univariate analysis of variance (ANOVA) and a multivariate partial least squares (PLS) approach. From more than 2000 mass spectral features detected in the urine, we identify several significant components that lead to discrimination between RCC patients and controls despite the relatively small sample size. A feature selection process condensed the significant features to less than 30 components in each of the data sets. In future work, these potential biomarkers will be further validated with a larger patient cohort. Such investigation will likely lead to clinically applicable assays for earlier diagnosis of RCC, as well as other malignancies, and thereby improved patient prognosis.


Artificial Intelligence in Diagnostic Radiology: Where Do We Stand, Challenges, and Opportunities.
Artificial intelligence (AI) is the most revolutionizing development in the health care industry in the current decade, with diagnostic imaging having the greatest share in such development. Machine learning and deep learning (DL) are subclasses of AI that show breakthrough performance in image analysis. They have become the state of the art in the field of image classification and recognition. Machine learning deals with the extraction of the important characteristic features from images, whereas DL uses neural networks to solve such problems with better performance. In this review, we discuss the current applications of machine learning and DL in the field of diagnostic radiology.Deep learning applications can be divided into medical imaging analysis and applications beyond analysis. In the field of medical imaging analysis, deep convolutional neural networks are used for image classification, lesion detection, and segmentation. Also used are recurrent neural networks when extracting information from electronic medical records and to augment the use of convolutional neural networks in the field of image classification. Generative adversarial networks have been explicitly used in generating high-resolution computed tomography and magnetic resonance images and to map computed tomography images from the corresponding magnetic resonance imaging. Beyond image analysis, DL can be used for quality control, workflow organization, and reporting.In this article, we review the most current AI models used in medical imaging research, providing a brief explanation of the various models described in the literature within the past 5 years. Emphasis is placed on the various DL models, as they are the most state-of-art in imaging analysis.


Technical comment on Adler et al. (2006): experimental design compromises conclusions.
The conclusion that herbivory induces 'alkaloids' in nectar but not in leaves, is likely an artefact of using pot-bound plants and analytical procedures that only measure anabasine, a minor alkaloid representing 0.3% of the total alkaloids produced by Nicotiana tabacum.


Overexpression of thioredoxin-1 reduces oxidative stress in the placenta of transgenic mice and promotes fetal growth via glucose metabolism.
Oxidative stress occurs where there is an imbalance between the production and scavenging of free radicals. Pregnancy per se is a state of oxidative stress due to the increased metabolic activity of placental mitochondria and reduced scavenging ability of antioxidant systems. Overproduction of reactive oxygen species may be associated with impaired fetal growth. However, the physiological influence of antioxidant systems on fetal growth is not well understood. In this study we assessed the effects of antioxidant systems on fetal growth using human thioredoxin (hTRX)-1 overexpressing transgenic (Tg) mice. Tg or C57BL/6 [wild-type (WT)] male mice were mated with WT female mice, and dams were killed to obtain the fetuses and placentas on gestational d 15. Tg fetuses were significantly heavier than WT fetuses, whereas placental weight did not differ significantly between the two groups. Immunohistochemically, hTRX-1 was localized to the nuclei of labyrinthine trophoblasts in Tg mice. In addition, placental expression of 8-hydroxy-2'-deoxyguanosine, which reflects DNA damage caused by oxidative stress, was reduced in Tg mice compared with WT mice. Placental expression of glucose transporter-1 mRNA and protein was significantly higher in Tg mice than WT mice, whereas no significant differences were observed for glucose transporter-3, IGF, and IGF-binding protein mRNA expression. These results suggest that placental and/or systemic antioxidant systems can influence fetal growth. In particular, increased hTRX-1 activity and the resulting modified placental redox state may play an important role in fetal growth by increasing the availability of glucose.


Carbon dioxide laser ablation combined with doxorubicin hydrochloride treatment for vaginal fibrosarcoma in a dog.
The combined use of CO2 laser ablation and doxorubicin hydrochloride (30 mg/m2) administered twice, 4 weeks apart, resulted in complete remission of vaginal fibrosarcoma in a 10-year-old Miniature Poodle. The tumor had redeveloped when only CO2 ablation was used for treatment and doxorubicin hydrochloride alone has had marginal influence on fibrosarcomas; however, use of both treatments in this dog resulted in a 20-month, disease-free period. This treatment combination was minimally traumatic to the dog, easily accomplished, and effective, and it allowed retention of the normal anatomy and function of the urogenital tract.


Mixed land use and obesity: an empirical comparison of alternative land use measures and geographic scales.
Obesity is a growing epidemic in the United States. Walkable neighborhoods, characterized as having the 3Ds of walkability (population Density, land use Diversity, and pedestrian-friendly Design), have been identified as a potentially promising factor to prevent obesity for their residents. Past studies examining the relationship between obesity and walkability vary in geographic scales of neighborhood definitions and methods of measuring the 3Ds. To better understand potential influences of these sometimes arbitrary choices, we test how four types of alternative measures of land use diversity measured at three geographic scales relate to body mass index for 4960 Salt Lake County adults. Generalized estimation equation models demonstrate that optimal diversity measures differed by gender and geographic scale and that integrating walkability measures at different scales improved the overall performance of models.


The scaffold protein MEK Partner 1 is required for the survival of estrogen receptor positive breast cancer cells.
MEK Partner 1 (MP1 or MAPKSP1) is a scaffold protein that has been reported to function in multiple signaling pathways, including the ERK, PAK and mTORC pathways. Several of these pathways influence the biology of breast cancer, but MP1's functional significance in breast cancer cells has not been investigated. In this report, we demonstrate a requirement for MP1 expression in estrogen receptor (ER) positive breast cancer cells. MP1 is widely expressed in both ER-positive and negative breast cancer cell lines, and in non-tumorigenic mammary epithelial cell lines. However, inhibition of its expression using siRNA duplexes resulted in detachment and apoptosis of several ER-positive breast cancer cell lines, but not ER-negative breast cancer cells or non-tumorigenic mammary epithelial cells. Inhibition of MP1 expression in ER-positive MCF-7 cells did not affect ERK activity, but resulted in reduced Akt1 activity and reduced ER expression and activity. Inhibition of ER expression did not result in cell death, suggesting that decreased ER expression is not the cause of cell death. In contrast, pharmacological inhibition of PI3K signaling did induce cell death in MCF-7 cells, and expression of a constitutively active form of Akt1 partially rescued the cell death observed when the MP1 gene was silenced in these cells. Together, these results suggest that MP1 is required for pro-survival signaling from the PI3K/Akt pathway in ER-positive breast cancer cells.


[Hepatitis B; sometimes co-infection with hepatitis D].
The Hepatitis delta virus (HDV) is a defect RNA virus that requires the presence of the hepatitis B virus (HBV) for cellular infection. Worldwide, 350 million people are infected with HBV; 5% of these are superinfected with HDV. A chronic superinfection with HDV has a higher morbidity and mortality rate. It is clinically difficult to differentiate between an HBV and an HDV infection. Diagnosis is made via detection of HDV antibodies and HDV-RNA using PCR techniques. The only treatment option is peginterferon-alpha 180 μg subcutaneously once a week for 48 weeks. A 37-year-old man with a Syrian background and a chronic HBV infection presented with high levels of ALT indicating severe hepatitis. The level of detected HBV-DNA-particles was low, however, indicating that the HBV infection alone could not be responsible for the inflammation. Further investigations revealed a superinfection with HDV. The patient was successfully treated with peginterferon-alpha. Severe hepatitis (high ALT level) in combination with a low HBV-DNA-particle level can indicate a HDV superinfection.


Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper).
Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).


A Retrospective Analysis of Rituximab Treatment for B Cell Depletion in Different Pediatric Indications.
Background: Rituximab (RTX) is used in cancer therapy as well as in the treatment of autoimmune diseases and alloimmune responses after transplantation. It depletes the disease-causing B cells by binding to the CD (cluster of differentiation) 20 antigen. We evaluate different pediatric treatment protocols (via fixed treatment schedule, B cell- or symptom-controlled) and their therapeutic effects. Methods: Demographic information, clinical and laboratory characteristics, and special laboratory values such as immunoglobulin G (IgG), CD19 positive B cells and Epstein-Barr viral load were retrospectively analyzed in children treated with RTX between 2008 and 2016. Results: Seventy-six patients aged 1 to 19 (median 13) years were treated with 259 RTX infusions. The spectrum of diseases was very heterogeneous. RTX led to a complete depletion of the B cells. The reconstitution time varied between patients and was dependent on the application schedule (median 11.8 months). Fourteen out of 27 (52%) patients developed hypogammaglobulinaemia. The risk of IgG deficiency was 2.6 times higher in children under 4 years of age than in olderones. In the last group IgG deficiency developed in only 38% of the cases (n = 8). Recurrent and severe infections were observed each in 11/72 (15%) patients. Treatment-related reactions occurred in 24/76 (32%) cases; however, treatment had to be discontinued in only 1 case. In 16/25 (76%), the Epstein-Barr viral load dropped below the detection limit after the first RTX infusion. Conclusion: RTX is an effective and well-tolerated drug for the treatment of oncological diseases as well as autoimmune and alloimmune conditions in children. B cell depletion and reconstitution varies both intra- und interindividually, suggesting that symptom-oriented and B cell-controlled therapy may be favorable. Treatment-related reactions, IgG deficiency and infections must be taken into account.


Initial response of phenology and yield components of wheat (Triticum durum L., CIRNO C2008) under experimental warming field conditions in the Yaqui Valley.
This work evaluates the experimental warming effects on phenology and grain yield components of wheat in the Yaqui Valley, Sonora, México, using CIRNO C2008 variety from Triticum durum L., as a model during the cropping cycle of 2016-2017 (December to April). Infrared radiators were deployed to induce experimental warming by 2 °C above ambient crop canopy temperature, in a temperature free-air controlled enhancement system. Temperature was controlled by infrared temperature sensors placed in eight plots which covered a circle of r = 1.5 m starting five days after germination until harvest. The warming treatment caused a reduction of phenophases occurrence starting at the stem extension phenophase. Such phenological responses generated a significant biological cycle reduction of 14 days. Despite this delay, CIRNO C2008 completed its biological cycle adequately. However, plant height under the warming treatment was reduced significantly and differences were particularly observed at the final phenophases of the vegetative cycle. Plant height correlated negatively with spikes length, spikes mass, and number of filled grains. Warming also reduced grain yield in 33%. The warming treatment caused a stress intensity (SI = 1-yield warming/yield control) of 39.4% and 33.2% in biomass and grain yield, respectively. The differences in stress intensities between biomass and grain yield were based on plant height reduction. Grain mass was not affected, demonstrating the crop capability for remobilization and adequate distribution of elaborated substances for the spikes under warming conditions.


A qualitative study on the perceptions of preventing falls as a health priority among older people in Northern India.
In India, fall-related injury morbidity and mortality is an emerging public health problem in older people. Despite awareness of a growing burden, there is a scarcity of literature on effective and acceptable interventions. This study was undertaken to explore the perceptions of older people regarding the risk of falls and understanding of fall prevention programmes. We conducted six focus group discussions (FGDs), comprising single gender for three socio-demographic groups in a north Indian city, Chandigarh, in 2011. FGDs were conducted in local language (Punjabi), recorded, transcribed and translated in English. Two researchers independently conducted thematic analysis. Focus group participants were aware of the devastating consequences of fall-related injuries. The predominant reasons for explaining an increased risk of falling was age, uneven surfaces, physical weakness and mental health. There were several other competing health priorities in this population. Preventive measures ranging from individual to government level initiatives were suggested. The experience, knowledge, perceptions and health priorities were diverse among the three socio-demographic groups. However, the feasibility, acceptability and effectiveness for improving balance and strength using yoga in this population needs to be evaluated. Careful consideration of health priorities is required for development of falls prevention, particularly among the urban poor. Further, initiatives that foster community engagement, such as participatory action may increase acceptability of initiatives to prevent fall-related injury among older people in India.


Tephrosia purpurea alleviates phorbol ester-induced tumor promotion response in murine skin.
In recent years, considerable emphasis has been placed on identifying new cancer chemopreventive agents, which could be useful for the human population. Tephrosia purpurea has been shown to possess significant activity against hepatotoxicity, pharmacological and physiological disorders. Earlier we showed that Tephrosia purpurea inhibits benzoyl peroxide-mediated cutaneous oxidative stress and toxicity. In the present study, we therefore assessed the effect of Tephrosia purpurea on 12-O-tetradecanoyl phorbal-13-acetate (TPA; a well-known phorbol ester) induced cutaneous oxidative stress and toxicity in murine skin. The pre-treatment of Swiss albino mice with Tephrosia purpurea prior to application of croton oil (phorbol ester) resulted in a dose-dependent inhibition of cutaneous carcinogenesis. Skin tumor initiation was achieved by a single topical application of 7,12-dimethyl benz(a)anthracene (DMBA) (25 microg per animal per 0.2 ml acetone) to mice. Ten days later tumor promotion was started by twice weekly topical application of croton oil (0.5% per animal per 0.2 ml acetone, v /v). Topical application of Tephrosia purpurea 1 h prior to each application of croton oil (phorbol ester) resulted in a significant protection against cutaneous carcinogenesis in a dose-dependent manner. The animals pre-treated with Tephrosia purpurea showed a decrease in both tumor incidence and tumor yield as compared to the croton oil (phorbol ester)-treated control group. In addition, a significant reduction in TPA-mediated induction in cutaneous ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation was also observed in animals pre-treated with a topical application of Tephrosia purpurea. The effect of topical application of Tephrosia purpurea on TPA-mediated depletion in the level of enzymatic and non-enzymatic molecules in skin was also evaluated and it was observed that topical application of Tephrosia purpurea prior to TPA resulted in the significant recovery of TPA-mediated depletion in the level of these molecules, namely glutathione, glutathione S-transferase, glutathione reductase and catalase. From these data we suggest that Tephrosia purpurea can abrogate the tumor-promoting effect of croton oil (phorbol ester) in murine skin.


Positive effect of the yellow morph on female reproductive success in the flower colour polymorphic Iris lutescens (Iridaceae), a deceptive species.
The deceptive Iris lutescens (Iridaceae) shows a heritable and striking flower colour polymorphism, with both yellow- and purple-flowered individuals growing sympatrically. Deceptive species with flower colour polymorphism are mainly described in the family Orchidaceae and rarely found in other families. To explain the maintenance of flower colour polymorphism in I. lutescens, we investigated female reproductive success in natural populations of southern France, at both population and local scales (within populations). Female reproductive success was positively correlated with yellow morph frequency, at both the population scale and the local scale. Therefore, we failed to observe negative frequency-dependent selection (NFDS), a mechanism commonly invoked to explain flower colour polymorphism in deceptive plant species. Flower size and local flower density could also affect female reproductive success in natural populations. Pollinator behaviour could explain the positive effect of the yellow morph, and our results suggest that flower colour polymorphism might not persist in I. lutescens, but alternative explanations not linked to pollinator behaviour are discussed. In particular, NFDS, although an appealingly simple explanation previously demonstrated in orchids, may not always contribute to maintaining flower colour polymorphism, even in deceptive species.


Metal-Organic Framework Membrane Constructor: A Tool for High-Throughput Construction of Metal-Organic Framework Membrane Models.
With the rapid development of metal-organic framework (MOF) membranes for separation applications, computational screening of their separation performance has attracted increasing interest in the design and fabrication of such materials. Although bulk crystal models in MOF databases are often used to represent MOF membrane structures, membrane models in slab geometries are still essential for researchers to simulate the separation performance, particularly to understand the effects of the surface/interface structure, pore sieving, and exposed lattice plane on guest permeability. However, to date, no database or method has been established to provide researchers with numerous membrane models, restricting the further development of related theoretical studies. Herein, we propose an algorithm and develop a tool called the "MOF-membrane constructor" to realize the high-throughput construction of membrane models based on the MOF crystal structures. Using this tool, membrane models can be generated with desired sizes, reasonable surface terminations, and assigned exposed crystal planes. The tool can also deduce the most prominent surface in the Bravais-Friedel-Donnay-Harker morphology or identify the pores in MOF crystals and automatically determine an exposed plane for each membrane model. Thus, an MOF-membrane database can be established rapidly according to user simulation requirements. This study can considerably improve the efficiency of building MOF membrane models and may be beneficial for the future development of simulation studies on MOF membranes.


[Screening for retinopathy of prematurity: results of one centre between 1991 and 2002].
The aim of this study was to analyse the results of retinopathy of prematurity (ROP) screening, stage of disease and time of treatment from one tertiary care centre. Between 1991 and 2001, 666 infants with a gestational age (GA) < 33 weeks or birth weight (BW) less than < 1501 g were examined. Coagulation treatment was performed in accordance with the Cryo-ROP study, after reaching the threshold. All infants were followed-up until a stable retinal situation was reached. Mean GA of the 666 infants was 28.5 +/- 2.3 weeks. Mean BW was 1180 +/- 372 g. During the years of screening, the GA and BW significantly decreased, but no significant change in the yearly incidence of ROP was detected. 460 (69.1 %) of the infants did not develop any stage of ROP. Maximum stage of ROP in the worse eye was stage one in 51 (7.6 %) infants, stage two in 59 (8.9 %) infants and stage three below threshold in 62 (9.3 %) infants. 34 (5.1 %) infants were treated with coagulation treatment. Mean time of treatment was 36.5 weeks postmenstrual age, or 10.7 weeks postnatal age. Postnatal age showed a better correlation to treatment time than postmenstrual age. No infant was treated before seven weeks of life and not before 32 weeks postmenstrual age. In spite of the increasing survival of children with lower GA and BW the incidence of ROP has not increased, and the incidence of ROP in our centre appears to be comparable to other international studies. In contrast to the Cryo-ROP study, treatment time correlates better to postnatal age than to postmenstrual age. All infants who underwent treatment were detected at an appropriate time using German screening guidelines.


Detection of pesticide by polymeric enzyme electrodes.
Screen-printed electrodes (SPEs) containing immobilized acetylcholine esterase (AChE) enzyme were used for the electrochemical determination of organophosphorous (OP) and carbamate pesticides. The extent of AChE deactivation by the pesticide was determined in the presence of acetylcholine (AChCl) substrate. The unique nature of this approach lies in the enzyme immobilization procedure in which AChE was attached to the SPE by in situ bulk polymerization of acrylamide to ensure efficient adherence within the membrane with minimal losses in enzyme activity. Responses were observed for the pesticides Monocrotophos, Malathion, Metasystox and Lannate over the concentration range 0-10 ppb (microg L(-1)).


Perspective: Serious play: teaching medical skills with improvisational theater techniques.
The physician-patient encounter may be structured, but it is never scripted; every physician-patient interaction is to some degree improvised. Both physicians and improvisers must prepare for unpredictability, and the surprising and unrecognized overlap between improvisational theater and medical training and medical practice led the author to develop a seminar that tailors improvisational skills to physician needs, teaching communication, professionalism, and other medical skills through an approach she calls "medical improv." The author observes that there is no example of this teaching strategy as a recurring part of a medical school curriculum reported in the literature, and she describes the contributions medical improv can make to physician skills. The author reports on medical students' positive response to the medical improv seminar she has taught at Northwestern University Feinberg School of Medicine since 2002: 95% of students anonymously evaluating the seminar from 2002 to 2010 agreed with the statement, "Studying improv could make me a better doctor," and 100% agreed with the statement, "I would recommend this class to other medical students." The author proposes a medical improv teaching model that other medical schools and hospitals could adapt and adopt.


Tunable narrow band THz wave generation from laser induced gas plasma.
Tunable narrowband THz waveforms were generated from laser induced gas plasma using shaped optical pulses. Square wave phase patterns were fed to a spatial light modulator. The frequency and amplitude of the square wave phase were used as parameters to tailor the terahertz waveforms. The dependence of THz waveforms on these parameters has been studied in detail. The presence of the ionization thresholds for pulse shaping is also discussed. We have demonstrated the wide and continuous tunability of the central frequency of the narrowband THz waveform from 2.5 to 7.5THz.


[Chronic necrotizing pulmonary aspergillosis as a complication of silicosis].
Chronic necrotizing pulmonary aspergillosis is un uncommon disease which is found in people with underlying lung disease or in mildly immunocompromised patients. It is an exceptional complication in silicosis and its diagnosis is difficult because it simulates other diseases like tuberculosis and cancer which are more common in such patients. We report on three cases with a long history of silica dust exposure with pulmonary aspergillosis complicating progressive massive fibrosis (PMF). We review their clinical, radiological and treatment features.


Daily vocal exercise is necessary for peak performance singing in a songbird.
Vocal signals, including human speech and birdsong, are produced by complicated, precisely coordinated body movements, whose execution is fitness-determining in resource competition and mate choice. While the acquisition and maintenance of motor skills generally requires practice to develop and maintain both motor circuitry and muscle performance, it is unknown whether vocal muscles, like limb muscles, exhibit exercise-induced plasticity. Here, we show that juvenile and adult zebra finches (Taeniopygia castanotis) require daily vocal exercise to first gain and subsequently maintain peak vocal muscle performance. Experimentally preventing male birds from singing alters both vocal muscle physiology and vocal performance within days. Furthermore, we find females prefer song of vocally exercised males in choice experiments. Vocal output thus contains information on recent exercise status, and acts as an honest indicator of past exercise investment in songbirds, and possibly in all vocalising vertebrates.


Prevalence of diabetes among Hispanics/Latinos from diverse backgrounds: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
We examine differences in prevalence of diabetes and rates of awareness and control among adults from diverse Hispanic/Latino backgrounds in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The HCHS/SOL, a prospective, multicenter, population-based study, enrolled from four U.S. metropolitan areas from 2008 to 2011 16,415 18-74-year-old people of Hispanic/Latino descent. Diabetes was defined by either fasting plasma glucose, impaired glucose tolerance 2 h after a glucose load, glycosylated hemoglobin (A1C), or documented use of hypoglycemic agents (scanned medications). Diabetes prevalence varied from 10.2% in South Americans and 13.4% in Cubans to 17.7% in Central Americans, 18.0% in Dominicans and Puerto Ricans, and 18.3% in Mexicans (P < 0.0001). Prevalence related positively to age (P < 0.0001), BMI (P < 0.0001), and years living in the U.S. (P = 0.0010) but was negatively related to education (P = 0.0005) and household income (P = 0.0043). Rate of diabetes awareness was 58.7%, adequate glycemic control (A1C <7%, 53 mmol/mol) was 48.0%, and having health insurance among those with diabetes was 52.4%. Present findings indicate a high prevalence of diabetes but considerable diversity as a function of Hispanic background. The low rates of diabetes awareness, diabetes control, and health insurance in conjunction with the negative associations between diabetes prevalence and both household income and education among Hispanics/Latinos in the U.S. have important implications for public health policies.


Calibration of an in-water multi-excitation fluorometer for the measurement of phytoplankton chlorophyll-a fluorescence quantum yield.
A multi-excitation fluorometer (MFL, JFE Advantech Co., Ltd.), originally designed to discriminate between phytoplankton species present within a population, has been redirected for use in fluorescence quantum yield (FQY) determination. While this calibration for apparent FQY requires no modification of the MFL, it is necessary to have an independent measurement of the spectral absorption coefficient of the subject fluid. Two different approaches to calibration were implemented. The primary method made use of reference fluorescent dye solutions of known quantum yield. The second method made use of acrylic fluorescent plaques and films. The two methods yielded consistent results, except in the 570 and 590 nm LED channels of the MFL. Application of the MFL in FQY determination is illustrated with an in situ Southern Ocean sample.


Profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets using gastrointestinal simulation technology.
The aim of the present study was to correlate in vitro properties of drug formulation to its in vivo performance, and to elucidate the deciding properties of oral absorption. Gastrointestinal simulation technology (GST) was used to simulate the in vivo plasma concentration-time curve and was implemented by GastroPlus™ software. Lansoprazole, a typical BCS class II drug, was chosen as a model drug. Firstly, physicochemical and pharmacokinetic parameters of lansoprazole were determined or collected from literature to construct the model. Validation of the developed model was performed by comparison of the predicted and the experimental plasma concentration data. We found that the predicted curve was in a good agreement with the experimental data. Then, parameter sensitivity analysis (PSA) was performed to find the key parameters of oral absorption. The absorption was particularly sensitive to dose, solubility and particle size for lansoprazole enteric-coated tablets. With a single dose of 30 mg and the solubility of 0.04 mg/ml, the absorption was complete. A good absorption could be achieved with lansoprazole particle radius down to about 25 μm. In summary, GST is a useful tool for profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets and guiding the formulation optimization.


Experimental determination of magnetic field quality conversion factors for eleven ionization chambers in 1.5 T and 0.35 T MR-linac systems.
The static magnetic field present in magnetic resonance (MR)-guided radiotherapy systems can influence dose deposition and charged particle collection in air-filled ionization chambers. Thus, accurately quantifying the effect of the magnetic field on ionization chamber response is critical for output calibration. Formalisms for reference dosimetry in a magnetic field have been proposed, whereby a magnetic field quality conversion factor kB,Q is defined to account for the combined effects of the magnetic field on the radiation detector. Determination of kB,Q in the literature has focused on Monte Carlo simulation studies, with experimental validation limited to only a few ionization chamber models. The purpose of this study is to experimentally measure kB,Q for 11 ionization chamber models in two commercially available MR-guided radiotherapy systems: Elekta Unity and ViewRay MRIdian. Eleven ionization chamber models were characterized in this study: Exradin A12, A12S, A28, and A26, PTW T31010, T31021, and T31022, and IBA FC23-C, CC25, CC13, and CC08. The experimental method to measure kB,Q utilized cross-calibration against a reference Exradin A1SL chamber. Absorbed dose to water was measured for the reference A1SL chamber positioned parallel to the magnetic field with its centroid placed at the machine isocenter at a depth of 10 cm in water for a 10 × 10 cm2 field size at that depth. Output was subsequently measured with the test chamber at the same point of measurement. kB,Q for the test chamber was computed as the ratio of reference dose to test chamber output, with this procedure repeated for each chamber in each MR-guided radiotherapy system. For the high-field 1.5 T Elekta Unity system, the dependence of kB,Q on the chamber orientation relative to the magnetic field was quantified by rotating the chamber about the machine isocenter. Measured kB,Q values for our test dataset of ionization chamber models ranged from 0.991 to 1.002, and 0.995 to 1.004 for the Elekta Unity and ViewRay MRIdian, respectively, with kB,Q tending to increase as the chamber sensitive volume increased. Measured kB,Q values largely agreed within uncertainty to published Monte Carlo simulation data and available experimental data. kB,Q deviation from unity was minimized for ionization chamber orientation parallel or antiparallel to the magnetic field, with increased deviations observed at perpendicular orientations. Overall (k = 1) uncertainty in the experimental determination of the magnetic field quality conversion factor, kB,Q was 0.71% and 0.72% for the Elekta Unity and ViewRay MRIdian systems, respectively. For a high-field MR-linac, the characterization of ionization chamber performance as angular orientation varied relative to the magnetic field confirmed that the ideal orientation for output calibration is parallel. For most of these chamber models, this study represents the first experimental characterization of chamber performance in clinical MR-linac beams. This is a critical step toward accurate output calibration for MR-guided radiotherapy systems and the measured kB,Q values will be an important reference data source for forthcoming MR-linac reference dosimetry protocols.


Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies.
To analyze the pathogenesis of the neurotropic murine coronavirus JHMV, we used monoclonal antibodies to the E2 viral glycoprotein to select antigenic variant viruses. Monoclonal antibodies J.7.2 and J.2.2 were shown to bind to topographically distinct regions of the E2 molecule, and the variants selected with the two antibodies demonstrated very different disease pictures in mice. Variants selected with J.7.2 were, like the parental virus, highly virulent and caused an acute encephalitic illness. By contrast, J.2.2-selected variants predominantly caused a subacute paralytic disease clinically and extensive demyelination histologically. Antigenic differences among the variants and parental virus were readily demonstrable with anti-E2 monoclonal antibodies. However, no differences between the viruses could be shown in binding studies with monoclonal antibodies directed against either E1 or N, the other two JHMV structural proteins. Since only J.2.2 selected demyelinating variants with reduced neurovirulence, it is likely that this monoclonal antibody recognizes a subregion of the E2 molecule that is particularly important in JHMV pathogenesis.


Feasibility and effectiveness of psychosocial resilience training: a pilot study of the READY program.
Despite many studies on the characteristics associated with resilience, there is little research on interventions to promote resilience in adults. The aims of this study were to gather preliminary information regarding the feasibility of implementing a group psychosocial resilience training program (REsilience and Activity for every DaY, READY) in a workplace setting, and to assess if program would potentially promote well-being. The program targets five protective factors identified from empirical evidence: Positive emotions, cognitive flexibility, social support, life meaning, and active coping. Resilience enhancement strategies reflect core acceptance and commitment therapy (ACT) processes and cognitive behavior therapy strategies. Sessions involve psychoeducation, discussions, experiential exercises, and home assignments. Sixteen participants completed 11 x two h group sessions over 13 weeks. Baseline and post-intervention assessment included self-administered questionnaires, pedometer step counts, and physical and hematological measures. Data were analyzed using standardized mean differences and paired t-tests. There was a significant improvement between baseline and post intervention scores on measures of mastery (p = 0.001), positive emotions (p = 0.002), personal growth (p = 0.004), mindfulness (p = 0.004), acceptance (p = 0.012), stress (p = 0.013), self acceptance (p = 0.016), valued living (p = 0.022), autonomy (p = 0.032) and total cholesterol (p = 0.025). Participants rated the program and materials very highly. These results indicate that the READY program is feasible to implement as a group training program in a workplace setting to promote psychosocial well-being.


Is transoral sphenopalatine ganglion blockade more effective on postoperative pain than endoscopic sphenopalatine ganglion blockade?
In this study, we aimed to examine and compare the effects of endoscopic SPGB and transoral SPGB on postoperative pain control and patient satisfaction in patients undergoing septoplasty. Participants were randomly divided into three groups, no blockade (n:20), endoscopic SPGB (n:20), and transoral SPGB (n:20). Those who had no blockage were included in the control group. Demographic data of patients, such as age and sex, VAS (visual analogue scale) and postoperative pain scores (PPS) [determined at arrival in the post-anesthesia care unit (PACU) and after 2, 6, 12, and 24 h], general analgesic use (24 and 168 h after surgery) and postoperative Quality of Recovery (QoR-15) values were recorded and compare them. The PPS PACU of 2 h, 6 h, 12 h, and 24-h values of the transoral group were lower than the endoscopic and control groups (p < 0.001).The values of 24 h and 168 h of analgesic use in the transoral group were lower than in the control and endoscopic groups (p < 0.001).The average recovery QoR-15 scores at 12 h and 24 h differed according to the groups (p < 0.001) and the highest values were in the transoral group (p < 0.001). Transoral SPGB is more effective in postoperative pain control than endoscopic SPGB, it decreases the use of postoperative analgesics and improves postoperative recovery scores.


Physical conditions and challenging behaviour in people with intellectual disability: a systematic review.
Challenging behaviour is a major problem among people with intellectual disabilities. Physical factors may be an important cause. The aim of the present systematic review was to determine the physical conditions associated with challenging behaviour. A literature search was conducted in PubMed and the Cochrane systematic review database for empirical studies published between 1990 and 2008. The quality of all the studies that met the inclusion criteria was assessed using the SIGN-50 methodology checklists. The search identified 45 studies, which looked at general medical conditions, motor impairment, epilepsy, sensory impairment, gastrointestinal disease, sleep disorders, dementia and others. There were four high-quality observational studies, seven well-conducted observational studies, 21 observational studies of low methodological quality and 13 non-analytical studies. There were significant and independent associations between challenging behaviours and urinary incontinence, pain related to cerebral palsy and chronic sleep problems, and between self-injurious behaviour and visual impairment. No association was found with hearing impairment, bowel incontinence, mobility impairment or epilepsy. Many other physical conditions were not addressed at all. Medical conditions can play a role in challenging behaviour, and this should be evaluated in the clinical setting. So far, the level of evidence is generally low, and longitudinal studies are completely lacking. We recommend a systematic approach to research examining the role of physical conditions in challenging behaviour, the ultimate aim being to establish a basis for the development of clinical guidelines.


Continuity and adherence to long-term drug treatment by geriatric patients after hospital discharge: a prospective cohort study.
Increased life expectancy is associated with an increased prevalence of chronic diseases and drug consumption. Changes often occur in the medication regimen after hospitalization. The extent and nature of these changes and the adherence of elderly patients have not yet been fully investigated. To investigate the extent and reasons for modifications to the medication regimens of elderly patients and their adherence to treatment during the first month following hospital discharge. This was a prospective cohort study of 198 patients aged>or=65 years in the Acute Geriatric Ward, Beilinson Hospital, Rabin Medical Center, Israel. Clinical, demographic and medication regimen data were recorded for all patients at an interview conducted prior to discharge. After 1 month, the patient, caregiver or general practitioner (GP) were interviewed regarding the extent and reasons for modifications to the medication regimen and adherence to treatment. At 1-month post-discharge, on average, 36.7% of patient medications had been modified compared with the discharge prescription. No modification was found in 16% of patients. During the observation month, 62% of prescribed long-term medications were taken without modification as recommended at discharge and during follow-up, 50% of all changes were characterized by the addition of a drug or an increase in dosage, and 26%, 16% and 8% consisted of cancelling, omission or switching within the same medication type, respectively. Seventy percent of medication regimen changes were based on specialists' recommendations or secondary to a change in the patients' medical state, and 13%, 8%, 3% and 6% were as a result of poor adherence, adverse effects, administrative restrictions and other reasons, respectively. There was no correlation between medication regimen change and age, gender, physical function, cognitive function and length of hospital stay. Patients discharged home experienced less regimen modification than those discharged elsewhere (p=0.02). Patients who visited their GP only once experienced less regimen modification (p=0.03). Regression analysis showed that the only factors affecting medication regimen changes were GP visits and chronic diseases (p<0.01, R2=0.09). The overall mean adherence among 145 home-dwelling patients was 96.7%. Twenty-seven percent and 6% were under- and over-adherent, respectively, to at least one drug; under-adherence was more widespread than over-adherence. No correlation was found between the overall mean adherence and other clinical parameters or regimen change. However, non-adherence to at least one drug was associated with more medication regimen changes (p=0.001), was more common in patients discharged with prescriptions for seven or more drug types per day (p=0.01) and was associated with failing to visit the patient's GP 1 month after discharge (p=0.02). The majority of elderly patients experienced modifications in their medication regimen during the first month following hospital discharge. Thirty percent of patients were non-adherent to at least one drug. To improve adherence to a hospital medication regimen, patients should be encouraged to visit their GP and the number of long-term drugs should be reduced.


Comparative three-dimensional imaging of living neurons with confocal and atomic force microscopy.
Atomic force microscopy applications extend across a number of fields; however, limitations have reduced its effectiveness in live cell analysis. This report discusses the use of AFM to evaluate the three-dimensional (3-D) architecture of living chick dorsal root ganglia and sympathetic ganglia. These data sets were compared to similar images acquired with confocal laser scanning microscopy of identical cells. For this comparison we made use of visualization techniques which were applicable to both sets of data and identified several issues when coupling these technologies. These direct comparisons offer quantitative validation and confirmation of the character of novel images acquired by AFM. This paper is one in a series emphasizing various new applications of AFM in neurobiology.


Development of feed composition tables using a statistical screening procedure.
Millions of feed composition records generated annually by testing laboratories are valuable assets that can be used to benefit the animal nutrition community. However, it is challenging to manage, handle, and process feed composition data that originate from multiple sources, lack standardized feed names, and contain outliers. Efficient methods that consolidate and screen such data are needed to develop feed composition databases with accurate means and standard deviations (SD). Considering the interest of the animal science community in data management and the importance of feed composition tables for the animal industry, the objective was to develop a set of procedures to construct accurate feed composition tables from large data sets. A published statistical procedure, designed to screen feed composition data, was employed, modified, and programmed to operate using Python and SAS. The 2.76 million data received from 4 commercial feed testing laboratories were used to develop procedures and to construct tables summarizing feed composition. Briefly, feed names and nutrients across laboratories were standardized, and erroneous and duplicated records were removed. Histogram, univariate, and principal component analyses were used to identify and remove outliers having key nutrients outside of the mean ± 3.5 SD. Clustering procedures identified subgroups of feeds within a large data set. Aside from the clustering step that was programmed in Python to automatically execute in SAS, all steps were programmed and automatically conducted using Python followed by a manual evaluation of the resulting mean Pearson correlation matrices of clusters. The input data set contained 42, 94, 162, and 270 feeds from 4 laboratories and comprised 25 to 30 nutrients. The final database included 174 feeds and 1.48 million records. The developed procedures effectively classified by-products (e.g., distillers grains and solubles as low or high fat), forages (e.g., legume or grass-legume mixture by maturity), and oilseeds versus meal (e.g., soybeans as whole raw seeds vs. soybean meal expellers or solvent extracted) into distinct sub-populations. Results from these analyses suggest that the procedure can provide a robust tool to construct and update large feed data sets. This approach can also be used by commercial laboratories, feed manufacturers, animal producers, and other professionals to process feed composition data sets and update feed libraries.


Smoking status and antithrombin therapy in patients with non-ST-segment elevation acute coronary syndrome.
Smoking remains a major public health issue. We investigated the incidence of smoking and outcomes in high-risk patients with acute coronary syndromes. Differences in treatment effect of antithrombin therapies were also investigated. Using data from SYNERGY, patients were categorized by their self-reported smoking status. They were followed at 30 days and 6 months for death, nonfatal myocardial infarction (MI), revascularization procedures, stroke, and need for rehospitalization, and at 1 year for occurrences of death. Overall, 9,971 patients were evaluated, of whom 2,404 (24%) were current smokers, 3,491 (35%) were former smokers, and 4076 (41%) had never smoked. Current smokers were younger (median age 61 years, interquartile range [IQR] 52-67) than former smokers (median age 69 years, IQR 63-75) and never smokers (median age 70 years, IQR 64-77) and had fewer additional coronary artery disease risk factors (hypertension, diabetes, hypercholesterolemia). The 30-day death/MI rate was similar for former versus never smokers (15% vs 13.6%, P = .079) and for current versus never smokers (14% vs 13.6%, P = .585). Adjusted odds ratios for 30-day death/MI in patients receiving enoxaparin compared with those receiving unfractionated heparin were 1.065 (95% CI 0.883-1.283, P = .51) in never smokers, 1.034 (95% CI 0.853-1.254, P = .733) in former smokers, and 0.742 (95% CI 0.582-0.948, P = .017) in current smokers. A significant interaction for treatment and smoking status was found at 30 days (P = .0215), but not at 6 months (P = .1381) or 1 year (P = .1054). One-year unadjusted mortality rates were higher for former versus never smokers (9.1% vs 6.7%, P = .0002) but were similar for current versus never smokers (6.5% vs 6.7%, P = .7226). On follow-up at 30 days, 62.3% (n =1397) of current smokers reported not smoking. Smokers with non-ST-segment elevation acute coronary syndrome are generally younger and have fewer cardiac risk factors. A significant interaction of smoking and enoxaparin was seen at 30 days, but not sustained at 6 months and 1 year. More than 60% of smokers quit within 30 days of their cardiac event. There was little difference in outcomes from 30 days to 1 year for these smokers who quit versus those who did not.


Systematic analysis of head-to-head gene organization: evolutionary conservation and potential biological relevance.
Several "head-to-head" (or "bidirectional") gene pairs have been studied in individual experiments, but genome-wide analysis of this gene organization, especially in terms of transcriptional correlation and functional association, is still insufficient. We conducted a systematic investigation of head-to-head gene organization focusing on structural features, evolutionary conservation, expression correlation and functional association. Of the present 1,262, 1,071, and 491 head-to-head pairs identified in human, mouse, and rat genomes, respectively, pairs with 1- to 400-base pair distance between transcription start sites form the majority (62.36%, 64.15%, and 55.19% for human, mouse, and rat,respectively) of each dataset, and the largest group is always the one with a transcription start site distance of 101 to 200 base pairs. The phylogenetic analysis among Fugu, chicken, and human indicates a negative selection on the separation of head-to-head genes across vertebrate evolution, and thus the ancestral existence of this gene organization. The expression analysis shows that most of the human head-to-head genes are significantly correlated,and the correlation could be positive, negative, or alternative depending on the experimental conditions. Finally, head to-head genes statistically tend to perform similar functions, and gene pairs associated with the significant cofunctions seem to have stronger expression correlations. The findings indicate that the head-to-head gene organization is ancient and conserved, which subjects functionally related genes to correlated transcriptional regulation and thus provides an exquisite mechanism of transcriptional regulation based on gene organization. These results have significantly expanded the knowledge about head-to-head gene organization. Supplementary materials for this study are available at http://www.scbit.org/h2h.


Subcritical Thermal Convection of Liquid Metals in a Rapidly Rotating Sphere.
Planetary cores consist of liquid metals (low Prandtl number Pr) that convect as the core cools. Here, we study nonlinear convection in a rotating (low Ekman number Ek) planetary core using a fully 3D direct numerical simulation. Near the critical thermal forcing (Rayleigh number Ra), convection onsets as thermal Rossby waves, but as Ra increases, this state is superseded by one dominated by advection. At moderate rotation, these states (here called the weak branch and strong branch, respectively) are smoothly connected. As the planetary core rotates faster, the smooth transition is replaced by hysteresis cycles and subcriticality until the weak branch disappears entirely and the strong branch onsets in a turbulent state at Ek<10^{-6}. Here, the strong branch persists even as the thermal forcing drops well below the linear onset of convection (Ra=0.7Ra_{crit} in this study). We highlight the importance of the Reynolds stress, which is required for convection to subsist below the linear onset. In addition, the Péclet number is consistently above 10 in the strong branch. We further note the presence of a strong zonal flow that is nonetheless unimportant to the convective state. Our study suggests that, in the asymptotic regime of rapid rotation relevant for planetary interiors, thermal convection of liquid metals in a sphere onsets through a subcritical bifurcation.


Metabolic fate of polyphenols in the human superorganism.
Dietary polyphenols are components of many foods such as tea, fruit, and vegetables and are associated with several beneficial health effects although, so far, largely based on epidemiological studies. The intact forms of complex dietary polyphenols have limited bioavailability, with low circulating levels in plasma. A major part of the polyphenols persists in the colon, where the resident microbiota produce metabolites that can undergo further metabolism upon entering systemic circulation. Unraveling the complex metabolic fate of polyphenols in this human superorganism requires joint deployment of in vitro and humanized mouse models and human intervention trials. Within these systems, the variation in diversity and functionality of the colonic microbiota can increasingly be captured by rapidly developing microbiomics and metabolomics technologies. Furthermore, metabolomics is coming to grips with the large biological variation superimposed on relatively subtle effects of dietary interventions. In particular when metabolomics is deployed in conjunction with a longitudinal study design, quantitative nutrikinetic signatures can be obtained. These signatures can be used to define nutritional phenotypes with different kinetic characteristics for the bioconversion capacity for polyphenols. Bottom-up as well as top-down approaches need to be pursued to link gut microbial diversity to functionality in nutritional phenotypes and, ultimately, to bioactivity of polyphenols. This approach will pave the way for personalization of nutrition based on gut microbial functionality of individuals or populations.


Urinary biomarkers of smokers' exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach.
There are established guidelines for bioanalytical assay validation and qualification of biomarkers. In this review, they were applied to a panel of urinary biomarkers of tobacco smoke exposure as part of a "fit for purpose" approach to the assessment of smoke constituents exposure in groups of tobacco product smokers. Clinical studies have allowed the identification of a group of tobacco exposure biomarkers demonstrating a good doseresponse relationship whilst others such as dihydroxybutyl mercapturic acid and 2-carboxy-1-methylethylmercapturic acid - did not reproducibly discriminate smokers and non-smokers. Furthermore, there are currently no agreed common reference standards to measure absolute concentrations and few inter-laboratory trials have been performed to establish consensus values for interim standards. Thus, we also discuss in this review additional requirements for the generation of robust data on urinary biomarkers, including toxicant metabolism and disposition, method validation and qualification for use in tobacco products comparison studies.


Increasing Cellular Uptake and Permeation of Curcumin Using a Novel Polymer-Surfactant Formulation.
Several therapeutically active molecules are poorly water-soluble, thereby creating a challenge for pharmaceutical scientists to develop an active solution for their oral drug delivery. This study aimed to investigate the potential for novel polymer-surfactant-based formulations (designated A and B) to improve the solubility and permeability of curcumin. A solubility study and characterization studies (FTIR, DSC and XRD) were conducted for the various formulations. The cytotoxicity of formulations and commercial comparators was tested via MTT and LDH assays, and their permeability by in vitro drug transport and cellular drug uptake was established using the Caco-2 cell model. The apparent permeability coefficients (Papp) are considered a good indicator of drug permeation. However, it can be argued that the magnitude of Papp, when used to reflect the permeability of the cells to the drug, can be influenced by the initial drug concentration (C0) in the donor chamber. Therefore, Papp (suspension) and Papp (solution) were calculated based on the different values of C0. It was clear that Papp (solution) can more accurately reflect drug permeation than Papp (suspension). Formulation A, containing Soluplus® and vitamin E TPGs, significantly increased the permeation and cellular uptake of curcumin compared to other samples, which is believed to be related to the increased aqueous solubility of the drug in this formulation.


Age at menarche: risk factor for gestational diabetes.
This study examines the relationship between the age at menarche and gestational diabetes mellitus (GDM). This retrospective study included subjects who were diagnosed with GDM at a pregnancy polyclinic in Kocaeli, Turkey between 2014 and 2018. The mean ages at menarche were 12.6 and 13.03 years in the GDM group and control group, respectively. The analysis results showed that pre-pregnancy cycle duration, age at menarche and pre-pregnancy BMI are statistically significant in terms of the development of gestational diabetes. (p < .05).In our study showed that the risk of GDM was found to be 2.3 times higher in pregnant women with a menarche age of <12 years. If the pre-pregnancy BMI value is more than 25 kg/cm2, the risk of GDM was found to be approximately 2 times higher. The study indicated that age at menarche, cycle duration, and BMI were risk factors for GDM. IMPACT STATEMENTWhat is already known on this subject? GDM has a lasting health impact on both the mother and the foetus. While several risk factors have previously been identified for GDM such as family history, obesity, advanced maternal age, significant gaps remain in our understanding of the risk factor and pathogenesis. Recent studies suggested that earlier menarche was significantly associated with an increased risk of GDM.What do the results of this study add? There might be ethnic differences on the relationship between the GDM and menarche age. There is no study examining the relationship between the age of menarche and GDM in Turkey. In presented study, we determined the risk factors of GDM including the age of menarche, cycle duration and BMI.What are the implications of these findings for clinical practice and / or further research? Therefore, a comprehensive evaluation of the menstrual history by healthcare professionals is important for future pregnancy risks. It is important to understand risk factors for GDM and to establish preventive strategies among high-risk populations. In addition, this study will shed light on future epidemiological and cohort studies.


Retrosplenial cortical activation in the fibromyalgia syndrome.
To study the CNS in chronic muscular pain typical of fibromyalgia we compared PET measures of regional cerebral blood flow (rCBF) in eight fibromyalgic patients and controls at rest. Higher rCBF for patients than controls was found bilaterally in the retrosplenial cortex. Lower rCBF for patients than controls were seen in the left frontal, temporal, parietal, and occipital cortices. The higher retroplenial rCBF in patients than controls may reflect increased attention towards sub-noxious somatosensory signaling, and agrees with the notion that fibromyalgic pain reflects secondary hyperalgesia. The brain regions with lower rCBF in fibromyalgic patients than controls participate in the normal cognitive processing of pain, which may be dysfunctional in fibromyalgia.


Hair analysis for biomonitoring of environmental and occupational exposure to organic pollutants: state of the art, critical review and future needs.
This paper presents the current state of the art in human hair analysis for the detection of organic pollutants associated with environmental and occupational exposure. The different chemical classes are reviewed with a special focus set on compounds that were only recently investigated. The importance of methods sensitivity and particularly the influence of this parameter on the results presented in previous publications is highlighted. This report also investigates the relevance of hair analysis as an indicator of subjects' level of exposure and underlines limitations that are still associated with this matrix. This study also presents a critical assessment of some specific aspects presented in the literature as well as future needs to strengthen the position of hair as a relevant biomarker of exposure to be used in epidemiological studies.


Interventional effect of compound sugar and salt on the thermal instability behavior of liquid egg yolk.
In this study, the influence of compound sugar (glucose, sucrose, trehalose, and arabinose) and compound sugar and salt (glucose, sucrose, trehalose, arabinose, and NaCl) on the thermal stability of heat-treated liquid egg yolk was explored. The results showed that the addition of 4% compound sugar or 4% compound sugar salt could significantly enhance the heat resistance of liquid egg yolk and increase the denaturation temperature of liquid egg yolk to above 77°C. Moreover, the addition of sugar and salt could improve the functional properties of liquid egg yolk to varying degrees, allowing it to maintain excellent emulsification and soluble protein content after heat treatment. Further analysis using Fourier transform infrared spectroscopy showed that the increase in α-helix content in liquid egg yolk treated with sugar salt also contributes to improving the thermal stability of egg yolk. The method of inhibiting egg yolk aggregation caused by heat treatment provided in this study provides a selective method and theoretical basis for the commercial production of heat-resistant liquid egg yolk.


Molecular nature of spontaneous mutations in mouse lactate dehydrogenase-A processed pseudogenes.
The presence of at least ten mouse LDH-A pseudogenes was demonstrated in the genomic blot analysis, and four different processed pseudogenes have thus far been isolated and characterized. In this report, the nucleotide sequences to two different mouse lactate dehydrogenase-A processed pseudogenes, M11 and M14, were determined and compared with the protein-coding sequences of the mouse and rat LDH-A functional genes. In the pseudogene M11, the sequence of 64 nucleotides from codon no. 257 to 278 was tandemly duplicated. In the pseudogene M14, the sequence of 22 nucleotides from codon no. 68 to 75 was replaced by an inserted repetitive sequence of 242 nucleotides homologous to a mouse truncated R element. The pattern of nucleotide substitutions accumulated in mouse LDH-A pseudogenes M11 and M14, as well as that of pseudogene M10 identified previously, was analyzed, and the substitution frequencies of the C or G at the CG dinucleotide were found to be high.


Injectable calcium phosphate cement as a graft material for maxillary sinus augmentation: an experimental pilot study.
The aim of the present study was to evaluate the efficiency of injectable CaP cement as a graft material around dental implants in the maxillary sinus augmentation procedure. Bilateral sinus augmentation process was carried out in three sheep and two implants were inserted during the same session. Out of a total of 12 installed implants, eight belonged to the so-called experimental group. In the experimental group, injectable CaP cement was used as augmentation material while autologous bone served as control. Histological examination revealed that newly formed bone surrounded the cement completely without an intervening fibrous tissue layer. Following a healing period of 12 weeks, mean bone-to-implant contact (BIC) values in the experimental and control groups were 36+/-5 and 37+/-3, respectively. The percentage of BIC was comparable with other experimental sinus augmentation studies. Further, it appeared that the thickness of the cortical bone that covered the outer surface of the maxillary sinus was < 2-3 mm, which affected the primary stability of the implants negatively. CaP cement is indeed effective to stimulate bone formation in the sinus elevation procedure. Nevertheless, additional improvements in the cement composition are required to allow final clinical utilization of the material.


Straightness measurements with a reflection confocal optical system-an experimental study.
Straightness measurement is an important technique in the field of mechanical engineering. We previously proposed a novel optical method for measuring straightness of motion using reflection confocal optics. The advantage of this method in comparison with the transmission optical systems of others [Opt. Laser Technol. 6, 166 (1974)] is that the lateral displacements in the two axes perpendicular to the optical axis and the rotation angles around all three axes can be measured simultaneously. We demonstrate straightness measurements using reflection confocal optics and show these measurements to be in good agreement with the theory.


Conservative management in congenital severe bilateral hydronephrosis related to uretero-pelvic junction obstruction.
We report our experience in conservative management of patients with prenatal and neonatal diagnosis of severe bilateral ureteropelvic junction obstruction (UPJO), focusing on the actual predictors of renal function impairment or spontaneous resolution. Between 1996 and 2006, 20 patients with bilateral severe hydronephrosis related to UPJO were included in the study. Indications for surgery were an increased hydronephrosis, decreased renal function, onset of symptoms. Conservatively treated patients were followed up for 3 months to 10 years with renal ultrasound, DTPA diuretic, urine culture. At first renal scan, 22 out of 40 renal units had a poor, 10 an intermediary and 8 a good drainage. Pyeloplasty was required in 10 of the 40 kidneys, while 30 out of 40 kidneys were followed conservatively. At the end of follow up, sieric normalized creatinine and estimated glomerular filtration rate were normal in all patients. Our data showed that bilateral severe hydronephrosis related to UPJO can be safely managed in a similar manner of a unilateral case. A poor drainage could be considered a negative predictive factor in the feasibility of a conservative management.


Accuracy of the Number Needed to Treat Compared With Diagnostic Testing: Brief Critical Review.
Number needed to treat (NNT) seems simple and is widely used. But its derivation from the absolute risk reduction is difficult to visualize. Like diagnostic sensitivity, absolute risk reduction is a measure of treatment accuracy. Thus, NNT is a measure of accuracy. NNT is inversely proportional to the relative risk reduction and the baseline risk that may be torturous when accuracy is poor. In order to better visualize the accuracy and weaknesses of NNT, NNT is compared with variables in diagnostic science that are often better understood, such as diagnostic sensitivity, specificity, and positive predictive value. To better understand the accuracy of NNT. Receiver operating characteristic curves are used to help visualize accuracy. It is shown that baseline risk and prevalence are highly correlated. Like positive predictive value, NNT is dependent on prevalence. Similar to diagnostic testing, symptoms and additional testing can increase prevalence and improve accuracy of the NNT. Examples are shown where changes in prevalence cause alterations in NNT. Moreover, data indicate that when accuracy of NNT is low, although the average NNT may be favorable, some subgroups may exhibit very poor response and even harm. It is shown that manipulations to increase prevalence can produce smaller, more selective groupings that can improve the accuracy and reduce the cost of expensive drugs. When the power of prediction is poor, the value of NNT must be carefully deliberated because it may be misleading. Indeed, the upper confidence interval may be a better reflection of NNT than the average.


Playing it safe: an examination of risk-avoidance in an anxious treatment-seeking sample.
It has been argued that individuals who are anxious are less likely and willing to take perceived risks across multiple behavioral domains (e.g., social, recreational, financial etc.), and that this bias is likely implicated in the etiology of pathological anxiety. While evidence is accumulating, there has been minimal research investigating the characteristics of risk-avoidance across anxiety disorders and across the specific risk-taking domains. The current study investigated risk-avoidance across domains in an anxious treatment-seeking sample. We hypothesized that: (i) individuals with anxiety would be more risk averse across domains relative to healthy controls; and, (ii) risk-avoidance would predict unique variance in anxiety symptoms, above and beyond other vulnerability factors (e.g., neuroticism). Individuals diagnosed with one or more anxiety disorders (n=67) completed measures of risk-taking, anxiety and depression symptoms, personality, and psychological distress. Healthy controls (n=58) completed measures of risk-taking and psychological distress. Results partially confirmed our hypotheses, demonstrating that anxious individuals were significantly more risk averse relative to controls across most domains, even after controlling for age and psychological distress. Furthermore, specific domains were found to account for unique variance in specific anxiety symptoms, as well as symptoms of depression. The results of this study provide novel evidence to suggest that risk-aversion is a possible transdiagnostic factor contributing to anxiety pathology.


Pseudodominant inheritance in a family with nonautoimmune hypothyroidism due to biallelic DUOX2 mutations.
Mutations in the dual oxidase 2 gene (DUOX2) is the most common genetic cause of congenital hypothyroidism (CH) in Japan. All previously described DUOX2 mutation-carrying families have followed autosomal recessive inheritance. We report a nonconsanguineous Japanese family harbouring biallelic DUOX2 mutations, which presented an apparently dominant inheritance of nonautoimmune hypothyroidism. The proband and her two sisters had been diagnosed as having CH on newborn screening and were treated with levothyroxine. Their mother had subclinical hypothyroidism. We sequenced DUOX2 in the proband and her family members. Pathogenicity of the identified novel mutation (p.Y1347C) was verified in vitro. We found that the proband and her sisters were compound heterozygous for a novel DUOX2 mutation p.Y1347C and a previously reported functional variant p.H678R. Unexpectedly, we found that the mother was homozygous for p.H678R. Expression experiments showed that the p.Y1347C mutant had reduced H2 O2 -producing activity, although there was no significant difference in the level of protein expression or localization, between wild type and p.Y1347C. We report a DUOX2 mutation-carrying pedigree presenting pseudodominant inheritance of nonautoimmune hypothyroidism. We speculate that the relatively high frequency of DUOX2 mutations could lead to pseudodominant inheritance in Japan.


Is vaccinating monkeys against yellow fever the ultimate solution for the Brazilian recurrent epizootics?
Vaccinating monkeys against yellow fever (YF) has been a common practice in the beginning of the 17D vaccine development. Although it may seem strange at first sight, vaccinating monkeys as a public health strategy is, we think, feasible and theoretically could eliminate the infection among non-human primates, interrupting the virus circulation (or significantly reducing it) and therefore reducing the risk of spilling over to the human population. We propose a series of studies that could demonstrate (or not) the efficacy and feasibility of vaccinating non-human primates YF reservoirs living in green areas of urban centres to cut off or curb the virus circulation that recurrently spill over to the human population. Therefore, vaccinating monkeys in relatively small green areas of the urban centres is perhaps the ultimate solution for the Brazilian recurrent YF epizootics.


Lack of association between human papillomavirus type 16 and 18 infections and female lung cancer.
A carcinogenic role of human papillomavirus (HPV) in lung cancer development has been suggested through both clinical and laboratory research during the last two decades. We did a population-based case-control study nested within the Finnish Maternity Cohort to assess the role of HPV16/18 infections in female lung carcinogenesis. The Finnish Maternity Cohort containing samples from more than 600,000 subjects were linked with nationwide cancer registries (1973-2006). Serum samples were retrieved from 311 women who developed lung cancer and 930 matched controls. The samples were analyzed for antibodies to HPV types 16 and 18 and cotinine (a biomarker of tobacco exposure). Conditional logistic regression-based estimates of odds ratios and 95% confidence intervals adjusted for cotinine levels were calculated. Overall, there was no evidence of increased risk of lung cancer associated with HPV 16 and 18 type-specific infections among nonsmokers and smokers, assessed via cotinine levels. The question of HPV etiologic effect on lung carcinoma deserves further longitudinal studies using different HPV detection methods. Our results bring new insights into female HPV lung cancer research.


[Subtotal leiomyomatosis of the esophagus and proximal part of the stomach].
Generalized leiomyomatosis of the esophagus and stomach is a rare disease. According to literature data, age of the patients ranges from 9 to 84 years, in men this disease is diagnosed 2 times more often than in women. It is necessary to differentiate this disease with cancer, esophageal diverticulum, achalasia of the cardia, hiatal hernia. In our case a woman of 32 years was ill from 5 years of age. Correct diagnosis was not made before surgery. Endoscopic examination suspected leiomyoma. Only repeated urgent histological tests during surgery resulted in accurate diagnosis (subtotal leiomyomatosis of the esophagus and proximal stomach) and in adequate surgical policy--subtotal resection of the esophagus and proximal resection of the stomach with Toprover gastrostoma creation. Then, retrosternal esophagocoloplasty was performed. 2 years after the first surgery the state of the patients is satisfactory, there are no symptoms of recurrence of the disease.


Molecular mechanisms in uterine epithelium during trophoblast binding: the role of small GTPase RhoA in human uterine Ishikawa cells.
BACKGROUND: Embryo implantation requires that uterine epithelium develops competence to bind trophoblast to its apical (free) poles. This essential element of uterine receptivity seems to depend on a destabilisation of the apico-basal polarity of endometrial epithelium. Accordingly, a reorganisation of the actin cytoskeleton regulated by the small GTPase RhoA plays an important role in human uterine epithelial RL95-2 cells for binding of human trophoblastoid JAR cells. We now obtained new insight into trophoblast binding using human uterine epithelial Ishikawa cells. METHODS: Polarity of Ishikawa cells was investigated by electron microscopy, apical adhesiveness was tested by adhesion assay. Analyses of subcellular distribution of filamentous actin (F-actin) and RhoA in apical and basal cell poles were performed by confocal laser scanning microscopy (CLSM) with and without binding of JAR spheroids as well as with and without inhibition of small Rho GTPases by Clostridium difficile toxin A (toxin A). In the latter case, subcellular distribution of RhoA was additionally investigated by Western blotting. RESULTS: Ishikawa cells express apical adhesiveness for JAR spheroids and moderate apico-basal polarity. Without contact to JAR spheroids, significantly higher signalling intensities of F-actin and RhoA were found at the basal as compared to the apical poles in Ishikawa cells. RhoA was equally distributed between the membrane fraction and the cytosol fraction. Levels of F-actin and RhoA signals became equalised in the apical and basal regions upon contact to JAR spheroids. After inhibition of Rho GTPases, Ishikawa cells remained adhesive for JAR spheroids, the gradient of fluorescence signals of F-actin and RhoA was maintained while the amount of RhoA was reduced in the cytosolic fraction with a comparable increase in the membrane fraction. CONCLUSION: Ishikawa cells respond to JAR contact as well as to treatment with toxin A with rearrangement of F-actin and small GTPase RhoA but seem to be able to modify signalling pathways in a way not elucidated so far in endometrial cells. This ability may be linked to the degree of polar organisation observed in Ishikawa cells indicating an essential role of cell phenotype modification in apical adhesiveness of uterine epithelium for trophoblast in vivo.


Genetic and environmental relations of executive functions to antisocial personality disorder symptoms and psychopathy.
Meta-analytic findings suggest that antisocial behavior, broadly defined, may relate to a Common Executive Function (EF) factor that captures covariance across response inhibition, working memory updating, and mental set shifting tasks. However, it is unclear whether this common factor, which is isomorphic with individual differences in response inhibition, accounts for all of the EF variance in antisocial behavior and psychopathy, or if they also relate to updating- and shifting-specific abilities. Moreover, findings that antisocial behavior and lower cognitive ability are particularly associated with the psychopathy dimension reflecting impulsivity and irresponsibility, compared to the dimension reflecting affective-interpersonal functioning, raise the possibility that EF relates to the variance shared between the impulsive-irresponsible psychopathy dimension and antisocial personality disorder. We examined these questions in a young adult twin sample (N = 765) with measures of multiple EF latent variables, Levenson Self-Report Psychopathy (LSRP) Primary (affective-interpersonal) and Secondary (impulsive-irresponsible) scales, and antisocial personality disorder symptoms (ASPDsx). Phenotypically, higher ASPDsx and LSRP Secondary psychopathy, but not LSRP Primary psychopathy, were associated with lower Common EF. Moreover, both psychopathy dimensions were negatively correlated with Updating-Specific ability, which was unrelated to ASPDsx. Results from twin models indicated that the association between LSRP Secondary psychopathy and ASPDsx was due to both genetic and nonshared environmental influences; however, Common EF's association with ASPDsx was primarily genetic, whereas its association with LSRP Secondary psychopathy had a significant environmental component. Thus, the interrelations among these constructs may reflect heterogeneous etiological pathways.