Prevalence and Identification of Nasal Airway Obstruction in Patients Presenting to Otolaryngology Clinics: Results From a Large Descriptive Practice Survey.
Objective: Determine the prevalence of nasal airway obstruction (NAO) in patients presenting to general otolaryngology clinics using the Nasal Obstruction Symptom Evaluation Scale (NOSE) score as a screening tool. Study Design: The clinic staff at 149 otolaryngology specialty clinics geographically distributed in the United States administered the NOSE Scale assessment to 3533 patients presenting to the clinics over a period of 1 week, regardless of the reason for the visit. All patients completed the NOSE Scale score, and additional data were collected, including the primary reason for the visit. Demographic and patient characteristics were summarized using frequencies and percentages for categorical variables. Results: The overall mean NOSE Scale score for the 3533 patients surveyed was 37.6 (SD 31.5). A total of 37.4% (1320/3533) of surveyed patients, regardless of visit reason, had severe/extreme NAO symptoms. Overall, the most common visit reason category was "Other" (61.2%, 2162/3533), followed by "NAO" (22.6%, 798/3533) and "Sinus" (16.2%, 573/3533). The mean NOSE scores for patients in each of the visit categories were 23.4 (SD 25.9), 64.7 (SD 23.3), and 53.3 (SD 28.1); for "Other," "NAO," and "Sinus," respectively. Among the patients coming in with "NAO" or "Sinus" as a primary complaint, 76.2% (608/798) and 57.2.% (328/573) had severe or extreme NOSE scores. A total of 17.8% (384/2162) of patients coming in for "Other" reasons had NOSE scores indicating severe/extreme NAO symptoms. Conclusions: The findings of this large, descriptive otolaryngology practice survey found a high prevalence of moderate to severe/extreme NAO among patients presenting to otolaryngology practices. Incorporating assessments, such as the NOSE Scale score and other diagnostic practices into the patient intake workflow and assessments, could help identify symptomatic NAO patients that might otherwise be overlooked.


Multiple Resonances Induced by Plasmonic Coupling between Gold Nanoparticle Trimers and Hexagonal Assembly of Gold-Coated Polystyrene Microspheres.
Optical properties of a gold nanoparticle trimer assembly coupled with gold-coated hexagonally close-packed polystyrene microspheres were investigated by linear and nonlinear spectroscopy. The observed reflection spectrum shows multiple peaks from the visible to near-infrared spectral regions. The spectroscopic properties were also examined by a finite-difference time-domain simulation. We found that the optical response of plasmons excited in the gold nanoparticle trimers was significantly modulated by strong coupling of the plasmons and the photonic mode induced in the gold-coated polystyrene assembly. Two-photon induced photoluminescence and Raman scattering from the sample were investigated, and both signals were significantly enhanced at the gold nanoparticle assembly. The simulations reveal that the electric fields can be enhanced site-selectively, not only at the interstitial sites in the nanoparticle assembly but also at the gaps between the particle and the gold film due to plasmonic interactions, by tuning the wavelength and are responsible for the strong optical responses.


Stereotactic Body Radiation Therapy (SBRT) for a Patient with a Myocardial Metastasis: A Case Report.
Metastatic lesions of the heart are rare but have the potential to cause significant morbidity. We describe the case of a patient with renal cell carcinoma who presented with shortness of breath and palpitations and was found to have a metastatic myocardial lesion causing arrythmia. He received stereotactic body radiation therapy (SBRT) to alleviate symptoms and provide local control. SBRT planning was executed using a four-dimensional computed tomography (4DCT) scan to account for respiratory and cardiac motion. Images from a planning magnetic resonance imaging (MRI) scan and a gated diagnostic MRI scan of the heart were fused with the 4DCT to assist with delineating the tumour. A dose of 30 Gy in five fractions was delivered without incident. The patient's cardiac MRI at two months post-treatment showed stability of his cardiac lesion. He subsequently died of distant disease progression, without any recurrence of his cardiac symptoms. SBRT may be considered for patients who present with a symptomatic metastatic cardiac lesion.


A quantum crystallographic approach to short hydrogen bonds.
In this work we use high-resolution synchrotron X-ray diffraction for electron density mapping, in conjunction with ab initio modelling, to study short O-H⋯O and O+-H⋯O- hydrogen bonds whose behaviour is known to be tuneable by temperature. The short hydrogen bonds have donor-acceptor distances in the region of 2.45 Å and are formed in substituted urea and organic acid molecular complexes of N,N'-dimethylurea oxalic acid 2 : 1 (1), N,N-dimethylurea 2,4-dinitrobenzoate 1 : 1 (2) and N,N-dimethylurea 3,5-dinitrobenzoic acid 2 : 2 (3). From the combined analyses, these complexes are found to fall within the salt-cocrystal continuum and exhibit short hydrogen bonds that can be characterised as both strong and electrostatic (1, 3) or very strong with a significant covalent contribution (2). An additional charge assisted component is found to be important in distinguishing the relatively uncommon O-H⋯O pseudo-covalent interaction from a typical strong hydrogen bond. The electron density is found to be sensitive to the extent of static proton transfer, presenting it as a useful parameter in the study of the salt-cocrystal continuum. From complementary calculated hydrogen atom potentials, we attribute changes in proton position to the molecular environment. Calculated potentials also show zero barrier to proton migration, forming an 'energy slide' between the donor and acceptor atoms. The better fundamental understanding of the short hydrogen bond in the 'zone of fluctuation' presented in a salt-cocrystal continuum, enabled by studies like this, provide greater insight into their related properties and can have implications in the regulation of pharmaceutical materials.


[Steroid responsive encephalopathy associated with auto-immune thyroiditis].
Since the first description of encephalopathy associated with Hashimoto's thyroiditis in 1966, more than 100 cases of this entity called Hashimoto's encephalopathy or SREAT [steroid-responsive encephalopathy associated with auto-immune thyroiditis] have been reported. The two cases reported here illustrate different diagnostic criteria and offer the opportunity to discuss the many pathophysiological hypotheses based on particularly pertinent biological data, especially the activity of anti-TPO and anti-TG antibodies present in serum and cerebrospinal fluid and the recent discovery of anti-alpha-enolase antibody. Different treatment options are also discussed, in particular corticosteroid therapy.


Preparation of 14C-labeled sterigmatocystin in liquid media.
14C-labeled sterigmatocystin was prepared from surface cultures of Aspergillus versicolor A-18074 maintained in liquid media by multiple additions of (1-14C)acetate to the cultures. The highest yield of 7.75 mg/10 ml was found with a sucrose-asparagine-ammonium medium in which more than 3% of the radioactivity of the added (1-14C)acetate was recovered ithe purified (ring-14C) sterigmatocystin. The method offers an easy way to prepare 14C-labeled sterigmatocystin for studies of this mycotoxin.


Reduced emotion regulatory selection flexibility in post-traumatic stress disorder: converging performance-based evidence from two PTSD populations.
Contemporary views of emotion dysregulation in post-traumatic stress disorder (PTSD) highlight reduced ability to flexibly select regulatory strategies according to differing situational demands. However, empirical evidence of reduced regulatory selection flexibility in PTSD is lacking. Multiple studies show that healthy individuals demonstrate regulatory selection flexibility manifested in selecting attentional disengagement regulatory strategies (e.g. distraction) in high-intensity emotional contexts and selecting engagement meaning change strategies (e.g. reappraisal) in low-intensity contexts. Accordingly, we hypothesized that PTSD populations will show reduced regulatory selection flexibility manifested in diminished increase in distraction (over reappraisal) preference as intensity increases from low to high intensity. Study 1 compared student participants with high (N = 22) post-traumatic symptoms (PTS, meeting the clinical cutoff for PTSD) and participants with low (N = 22) post-traumatic symptoms. Study 2 compared PTSD diagnosed women (N = 31) due to childhood sexual abuse and matched non-clinical women (N = 31). In both studies, participants completed a well-established regulatory selection flexibility performance-based paradigm that involves selecting between distraction and reappraisal to regulate negative emotional words of low and high intensity. Beyond demonstrating adequate psychometric properties, Study 1 confirmed that relative to the low PTS group, the high PTS group presented reduced regulatory selection flexibility (p = 0.01, ŋ²ₚ= 0.14). Study 2 critically extended findings of Study 1, in showing similar reduced regulatory selection flexibility in a diagnosed PTSD population, relative to a non-clinical population (p = 0.002, ŋ²ₚ= 0.114). Two studies provide converging evidence for reduced emotion regulatory selection flexibility in two PTSD populations.


Item response theory in affective instrument development: an illustration.
The benefits of item response theory (IRT) analysis in obtaining empirical support for construct validity make it an essential step in the instrument development process. IRT analysis can result in finer construct interpretations that lead to more thorough descriptions of low- and high-scoring respondents. A critical function of IRT is its ability to determine the adequacy with which the attitude continuum underlying each dimension is assessed by the respective items in an instrument. Many nurse researchers, however, are not reaping the benefits of IRT in the development of affective instruments. The purpose of this article is to familiarize nurse researchers with this valuable approach through a description of the Facets computer program. Facets uses a one parameter (i.e., item difficulty) Rasch measurement model. Data from a survey of 525 new mothers that assessed the psychometric properties of the Postpartum Depression Screening Scale are used to illustrate the Facets program. It is hoped that IRT will gain increased prominence in affective instrument development as more nurse researchers become aware of computer programs such as Facets to assist in analysis.


Molecular dynamics calculations of collision-induced absorption in a gas mixture of neon and krypton.
We continue the development of the in-house molecular dynamics software package SpaCIAL and test it for the computation of the collision-induced absorption coefficients for a neon (Ne) and krypton (Kr) gas mixture. An apodization procedure for the dipole autocorrelation function is implemented and tested. We also carry out a statistical study of the convergence rate with respect to ensemble size. The resulting absorption coefficients show a good accordance with quantum mechanical results. Comparison with laboratory measurements shows agreement within 10%-20% at T = 295 K. At T = 480 K, a larger difference of 40%-80% is observed, which can presumably be explained by experimental uncertainties. For the study, an empirical (Barker, Fisher, and Watts) interaction-potential [Mol. Phys. 21, 657 (1971)] for Ne-Kr has been developed. Ab initio {coupled cluster with singles and doubles (triples) [CCSD(T)]} potentials for Ne-Ne, Kr-Kr, and Ne-Kr have been computed, as well as the CCSD(T) interaction-induced Ne-Kr dipole moment curve.


Influence of malnutrition on the body temperature of children.
The mean auricular temperature of 10 malnourished Jamaican infants was 0.84 degrees C lower on admission to hospital than it was after recovery. Body temperature was influenced by ambient temperature in the malnourished state. During the rapid growth that accompanies recovery the mean auricular temperature was raised. Five malnourished children with hypothermia were given a standard high-calorie feed, and this caused the body temperature to return to normal levels within two hours in every case. These results suggest that reduced mean temperature in malnourished children may be an adaptation to conserve calories, and that severe hypothermia in malnutrition results from an acute shortage of energy reserves. Frequent feeding of malnourished children is most important in their management.


[Factors for expulsion of intrauterine device Tcu380A applied immediately postpartum and after a delayed period].
To determine the frequency of expulsion of the intrauterine device TCu380A (IUD) inserted either immediately postpartum or after a delayed period. We aimed to identify the factors associated with expulsion. A longitudinal and comparative study was carried out in three Family Medicine Units of the Instituto Mexicano del Seguro Social (IMSS) of Leon, Guanajuato. One hundred twenty-five women who had a vaginal delivery and who elected to have IUD inserted immediately after delivery participated in the study along with 125 women who elected to have the IUD inserted after a delayed period after delivery. Studied factors were parity, technique, and insertion by the doctors assigned to the service and medical personnel in training (pre or postdegree). A medical review was performed one month and three months after insertion of the IUD. Results were analyzed by chi-square and Student t test. The expulsion rates of IUDs during immediate puerperium and also after a delayed period were 16 and 2.7%, respectively (p<0.0004). There was no statistically significant association between expulsion of the IUD and the following factors that were taken into account: age, primipara, personnel who inserted the device, and the application technique. In immediate puerperium, 25.9% of women who had multiple deliveries expelled the IUD, and in those who delayed IUD insertion, it was 4% (p=0.03). There is a greater risk of expulsion if the IUD is inserted immediately after delivery and it is associated with multiparity. The percentage of expulsion in immediate puerperium is similar to that reported in the literature.


Activation of mitochondrial oxidative phosphorylation during (+/-)-isoproterenol-induced cell injury of myocardium.
Hydrolytic and synthetic activities of mitochondrial ATPase were studied during (+/-)-isoproterenol-induced cell injury of the myocardium (67 mg/kg body weight). This research was a long-term study (72 h) in which rat heart homogenates, and a potentiometric method were used. Hydrolytic activities in homogenates from (+/-)-isoproterenol-treated rats were not statistically different, during the whole long-term study, from the hydrolytic activity in normal homogenates. The synthetic activity (mitochondrial oxidative phosphorylation) of mitochondrial ATPase increased at 3, 6, and 18 h (35, 48 and 23% respectively) after (+/-)-isoproterenol administration with regard to the control group. At 12 h and 21-72 h after drug administration, the data revealed no differences between synthetic activity of mitochondrial ATPase in control vs (+/-)-isoproterenol treated homogenates. The facts that synthetic and hydrolytic activities in homogenates from (+/-)-isoproterenol treated rats were never lower than the synthetic and hydrolytic activities in normal homogenates, and that activation of mitochondrial oxidative phosphorylation occurred at some times after (+/-)-isoproterenol treatment, suggest that no considerable and "negative" modifications occur in the active configuration of mitochondrial ATPase during (+/-)-isoproterenol-induced injury of the myocardium (67 mg/kg body weight).


[Recent and future innovations in the treatment of heart failure].
Heart failure is still an important public health problem despite important advances regarding its treatment. Several new treatment strategies are being investigated in order to contend with this disease. Strategies proved to be safe and effective in clinical trials are being adapted to clinical practice. In this review, we will first focus on most recent treatment strategies that are recommended to be used in clinical practice and then try to mention novel strategies which are still being explored in preclinical studies.


Synergistic Chemopreventive and Therapeutic Effects of Co-drug UA-Met: Implication in Tumor Metastasis.
The anticancer properties of ursolic acid (UA) and metformin (Met) have been well demonstrated. However, whether these compounds can act synergistically to prevent and treat cancer is not known. We present in this study, the synergism between UA and Met, and that of a new codrug made of UA and Met (UA-Met) against several cancer cell lines. The combination of high concentration of UA (25, 50, 75, 100 μM) and Met (5, 10, 20, 40 mM) resulted in synergetic cytotoxicity on MDA-MB-231 and MCF-7 cells (CI < 0.8). Molecular and cellular studies showed that codrug UA-Met significantly inhibited the invasion (∼55.3 ± 2.74%) and migration (∼52.4 ± 1.57%) of TGF-β induced breast cancer MDA-MB-231 and MCF-7 cells in vitro at low concentration of 10 μM. These effects were accompanied by down-regulation of CXCR4, uPA, vimentin, E-cadherin, N-cadherin, and MMP-2/9 proteins expression and regulation of the AMPK/m-TOR signaling pathways as expected from UA and Met. Moreover, UA-Met could reduce the progression of pulmonary metastasis by 4T1 cells (63.4 ± 3.52%) without influencing the glucose blood level in mice. Our study suggests that the codrug UA-Met is safe and effective in preventing cancer metastasis and possibly treatment of cancer.


How friends' involvement in crime affects the risk of offending and victimization.
This article examines how friends' involvement in crime influences such involvement in those around them, as offenders or victims, and the extent to which such friendship effects vary with contact frequency, friendship intimacy, and geographical proximity. To test our hypotheses we used four waves from the Dutch panel survey CrimeNL, which includes ego-centered network measures in each wave for respondents aged between 16 and 45. To test our hypotheses, fixed-effects panel models were employed. The results show that living in close proximity to delinquent friends increases people's own risk of offending, and daily interaction with these friends decreases the risk of victimization. Victimization is also communicated among friends in their daily interactions. These findings stress the need to consider factors that condition how friendships exert influence on the risk of crime involvement.


Has 'lifetime prevalence' reached the end of its life? An examination of the concept.
Many cross-sectional surveys in psychiatric epidemiology report estimates of lifetime prevalence, and the results consistently show a declining trend with age for such disorders as depression and anxiety. In a closed cohort with no mortality, lifetime prevalence should increase or remain constant with age. For mortality to account for declining lifetime prevalence, mortality rates in those with a disorder must exceed those without a disorder by a sufficient extent that more cases would be removed from the prevalence pool than are added by new cases, and this is unlikely to occur across most of the age range. We argue that the decline in lifetime prevalence with age cannot be explained by period or cohort effects or be due to a survivor effect, and are likely due to a variety of other factors, such as study design, forgetting, or reframing. Further, because lifetime prevalence is insensitive to changes in treatment effectiveness or demand for services, it is a parameter that should be dropped from the lexicon of psychiatric epidemiology.


Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents.
Vitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0-18 years of age and to estimate age-dependent reference intervals. Plasma vitamin B12 markers were measured in collected plasma samples of 170 children 0-18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof. Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied. Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency. We analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0-18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.


A sensitive indicator for the severity of COVID-19: thiol
Thiol status is a good reflector of the cellular redox and have vital roles in various cellular signaling pathways. The purpose of the study was to investigate thiol status in patients with SARS-CoV-2 infection. A total of 587 subjects (517 patients/70 healthy controls) were enrolled in the study.The patients were categorized into the groups regarding to the severity of disease (mild, moderate, severe, and critical).Thiol status of all groups were compared. The patients had significantly diminished thiol levels compared to controls. Thiol levels were gradually decreased as the severity of the disease increased. Logistic regression analyses identified that thiol concentrations were an independent risk factor for the disease severity in each phase (mild group OR 0.975, 95%CI 0.965-0.986; moderate group, OR 0.964, 95%CI 0.953-0.976; severe group OR 0.953, 95%CI 0.941-0.965; critical group OR 0.947, 95%CI 0.935-0.960).Thiol test exhibited the largest area under the curve at 0.949, with the highest sensitivity (98.6%) and specificity (80.4%). Depleted thiol status was observed in SARS-CoV-2 infection. Decline of the thiol levels by degrees while the severity of infection increased was closely related to the progression of the disease. This outcome highlights that thiols could be an impressible biomarker for predicting of the severity of COVID-19.


Understanding of Contemporary Regional Sea-Level Change and the Implications for the Future.
Global sea level provides an important indicator of the state of the warming climate, but changes in regional sea level are most relevant for coastal communities around the world. With improvements to the sea-level observing system, the knowledge of regional sea-level change has advanced dramatically in recent years. Satellite measurements coupled with in situ observations have allowed for comprehensive study and improved understanding of the diverse set of drivers that lead to variations in sea level in space and time. Despite the advances, gaps in the understanding of contemporary sea-level change remain and inhibit the ability to predict how the relevant processes may lead to future change. These gaps arise in part due to the complexity of the linkages between the drivers of sea-level change. Here we review the individual processes which lead to sea-level change and then describe how they combine and vary regionally. The intent of the paper is to provide an overview of the current state of understanding of the processes that cause regional sea-level change and to identify and discuss limitations and uncertainty in our understanding of these processes. Areas where the lack of understanding or gaps in knowledge inhibit the ability to provide the needed information for comprehensive planning efforts are of particular focus. Finally, a goal of this paper is to highlight the role of the expanded sea-level observation network-particularly as related to satellite observations-in the improved scientific understanding of the contributors to regional sea-level change.


History of syncope predicts loss of consciousness after head trauma: Retrospective study.
Head trauma may present as transient loss of consciousness (TLOC) currently classified as traumatic in origin, in contrast to non-traumatic forms, such as syncope. Whether past history of syncope predisposes to loss of consciousness after head injury has been poorly studied. A retrospective analysis of data obtained from 818 consecutive patients admitted to Emergency Departments was conducted. Face-to-face semi-structured interviews were performed, where patients' past history of syncope and head injury were explored. Head injury events were stratified as high- or low-energy trauma. Data regarding past syncopal events were explored in regard to number, age at the first occurrence, and syncope circumstances. Multivariate logistic regression model was applied to assess the relationship between loss of consciousness during head injury and past history of syncope. Both past history of non-traumatic TLOC (odds ratio [OR] 3.78; 95% confidence interval [CI] 2.13-6.68, p < 0.001) and high-energy mechanism (OR 3.84; 95% CI 2.35-6.28, p < 0.001) predicted TLOC after head trauma. This relationship was even stronger when past episodes of TLOC were limited to those typical for reflex syncope (OR 4.34; 95% CI 2.34-7.89, p < 0.001). Further, the number of non-traumatic TLOC episodes in the patient's history was also predictive of TLOC after head injury (OR per 1 episode: 1.24; 95% CI 1.04-1.48, p = 0.015). Syncope in a patient's history predicts loss of consciousness after head injury. The clinical importance of this finding merits further investigation.


A survey of pediatric intensive care unit clinician experience with restricted family presence during COVID-19.
Limiting family presence runs counter to the family-centred values of Canadian pediatric intensive care units (PICUs). This study explores how implementing and enforcing COVID-19-related restricted family presence (RFP) policies impacted PICU clinicians nationally. We conducted a cross-sectional, online, self-administered survey of Canadian PICU clinicians to assess experience and opinions of restrictions, moral distress (Moral Distress Thermometer, range 0-10), and mental health impacts (Impact of Event Scale [IES], range 0-75 and attributable stress [five-point Likert scale]). For analysis, we used descriptive statistics, multivariate regression modelling, and a general inductive approach for free text. Representing 17/19 Canadian PICUs, 368 of 388 respondents (94%) experienced RFP policies and were predominantly female (333/368, 91%), English speaking (338/368, 92%), and nurses (240/368, 65%). The mean (standard deviation [SD]) reported moral distress score was 4.5 (2.4) and was associated with perceived differential impact on families. The mean (SD) total IES score was 29.7 (10.5), suggesting moderate traumatic stress with 56% (176/317) reporting increased/significantly increased stress from restrictions related to separating families, denying access, and concern for family impacts. Incongruence between RFP policies/practices and PICU values was perceived by 66% of respondents (217/330). Most respondents (235/330, 71%) felt their opinions were not valued when implementing policies. Though respondents perceived that restrictions were implemented for the benefit of clinicians (252/332, 76%) and to protect families (236/315, 75%), 57% (188/332) disagreed that their RFP experience was mainly positive. Pediatric intensive care unit-based RFP rules, largely designed and implemented without bedside clinician input, caused increased psychological burden for clinicians, characterized as moderate moral distress and trauma triggered by perceived impacts on families.


Percutaneous ASD closure of children weighing less than 10 kg.
Background: Traditionally the procedure of percutaneous ASD closure is carried out in children weighing more than 15 kg. The aim of this study was to discuss the success, efficacy and safety of the percutaneous closure of symptomatic ASD in children weighing less than 10 kg.Material and methods: This study was performed in two centres. A total of 44 patients were included. Demographic and angiographic data of these patients were gathered retrospectively from patients' records. Main indications for ASD closure were: failure to thrive, recurrent respiratory infections, bronchopulmonary dysplasia and genetic syndromes.Results: Median weight of patients was 9.0(8.12-9.50) kg. Bodyweight of 22 patients was less than 3 percentiles. In the follow-up, this number was lowered to 9 patients at 12 months. Median age of patients was 18.0(12.0-285) months. Minimum age and weight of patients was 3 months and 4.5 kg, respectively. Median mean pulmonary pressure was 24.0(20.0-29.5). The values of median defect size were measured in Cath lab as 13.0(10.75-15.3) mm. Median device size was 13(9-15) mm. Defect size was evaluated according to body weight and body surface area. The ratio of weight per defect size was 0.65(0.54-0.84) also the ratio of body surface area per defect size was 0.032(0.028-0.04). The ratio of total septum per device diameter was 2.5(2.1-3.1). Types of devices used were Amplatzer Septal Occluder, Cera Flex Septal Occluder, Figulla Flex II Atrial Septal Occluder, Memopart Septal Occluder. All cases were closed successfully, but the device had to be retrieved in one patient after successful positioning because it was detected that device compressed the aorta. No major complications were seen.Conclusion: In the experienced centres, percutaneous ASD closure can be done effectively and safely in symptomatic children weighing less than 10 kg.


QT dispersion in sinus beats and ventricular extrasystoles in normal hearts.
Recent studies have suggested that QT interlead variability (dispersion) on the surface electrocardiogram may have potential as a measure of recovery time dispersion. To test this hypothesis further QT dispersion occurring in sinus beats was compared with that in ventricular extrasystoles. Simultaneous electrocardiograms were recorded at 50 mm/s during sinus rhythm in a drug free state while ventricular extrastimuli were introduced by programmed right ventricular stimulation at different coupling intervals. QT dispersion, defined as the difference between the maximum and minimum QT, was calculated separately for the extrasystoles and preceding and following sinus complexes. To correct for the influence of the number of measurable leads on QT dispersion, an "adjusted" QT dispersion calculated as QT dispersion/square root of the number of measurable leads, was used to compare sinus complexes and extrasystoles. Nine patients were studied who were undergoing electrophysiological study for investigation of palpitation and were found to have electrically normal ventricles. At all coupling intervals tested "adjusted" QT dispersion was significantly greater in the ventricular extrasystoles than in either the preceding or following sinus complexes. For the coupling interval 350 ms, the 95% confidence intervals for the difference between means was 52 to 78 ms (preceding sinus complex) and 56 to 82 ms (following sinus complex) (p less than 0.00001). There was no correlation between the coupling interval and the magnitude of the "adjusted" QT dispersion. These results accord fully with expected differences in ventricular recovery time dispersion and offer further support for the hypothesis that QT dispersion reflects regional variation in ventricular recovery. If substantiated by invasive studies, these findings have wide implications for both the usefulness and the method of QT measurement.


Distribution of hydrolytic activity catalyzes the biotransformation of prednisolone 21-acetate in human skin.
We investigated the distribution of hydrolytic enzymes which metabolize prednisolone 21-acetate (PNA) to prednisolone (PN) in human skin. Km (Michaelis-Menten constant) and Vmax (maximum rate) of hydrolytic enzyme in human skin was 25.1 microM and 0.46 nmol/min/mg protein, respectively. Specific activities of hydrolysis in dermis and epidermis were similar and, in consideration to their thickness, hydrolytic activity in epidermis was 12.1 times higher than in dermis. Moreover, the highest amount of metabolite (PN) was found at 80-120 microm from the skin surface by skin slicing. Therefore, hydrolytic activity which metabolized PNA was distributed in epidermis, especially in the basement membrane area; epidermis borders dermis in this area and the papillary plexus is reached just beneath the dermal papillae. These results suggest that the distribution of hydrolytic activity in human skin may prevent certain substances from entering the systemic circulation in their unhydrolyzed form.


Tafamidis in transthyretin amyloid cardiomyopathy: effects on transthyretin stabilization and clinical outcomes.
Transthyretin (TTR) amyloidosis is a progressive systemic disorder caused by misfolded TTR monomers that cumulatively deposit in the heart and systemically as amyloid. This phase 2 open-label trial evaluated the stabilization of TTR tetramers using 20 mg of tafamidis daily at week 6 (primary end point), month 6, and month 12, as well as safety of tafamidis treatment and efficacy with respect to progression of TTR amyloid cardiomyopathy. Thirty-one wild-type patients (median age, 76.7 years; 93.5% men) with a median disease duration of 55.6 months and mild to moderate heart failure (96.8%; New York Heart Association, classes I-II) were enrolled. Thirty of 31 patients (96.8%) achieved TTR stabilization after 6 weeks and 25 of 28 patients (89.3%) after 12 months. After 12 months of treatment, 3 patients discontinued prematurely, 2 patients died, 7 patients were hospitalized because of cardiovascular events, 20 of 28 patients demonstrated preserved New York Heart Association classification status, but 15 of 31 (48.4%) patients had clinical progression (eg, admission for cardiac failure, atrial fibrillation, and syncope). N-terminal prohormone brain natriuretic peptide levels did not increase significantly over time, troponin I and troponin T increased moderately, and no consistent clinically relevant changes were seen in echocardiographic cardiac assessments. Tafamidis treatment was generally well tolerated although 7 of 31 patients had bouts of diarrhea. Tafamidis treatment effectively achieved and maintained TTR stabilization and was well tolerated. The absence of significant changes in most biochemical and echocardiographic parameters suggests that further evaluation of tafamidis in TTR amyloid cardiomyopathy is warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00694161.


Selectivity in K+ channels is due to topological control of the permeant ion's coordinated state.
The selectivity filter of K+ channels provides specific coordinative interactions between dipolar carbonyl ligands, water, and the permeant cation, which allow for selective flow of K+ over (most importantly) Na+ across the cell membrane. Although a structural viewpoint attributes K+ selectivity to coordination geometry provided by the filter, recent molecular dynamics simulation studies attribute it to dynamic and unique chemical/electrostatic properties of the filter's carbonyl ligands. Here we provide a simple theoretical analysis of K+ and Na+ complexation with water in the context of simplified binding site models and bulk solution. Our analysis reveals that water molecules and carbonyl groups can both provide K+ selective environments if equivalent constraints are imposed on the coordination number of the complex. Absence of such constraints annihilates selectivity, demonstrating that whether a coordinating ligand is a water molecule or a carbonyl group, "external" or "topological" constraints/forces must be imposed on an ion-coordinated complex to elicit selective binding. These forces must inevitably originate from the channel protein, because in bulk water, which, by definition, presents a nonselective medium, the coordination number is allowed to relax to suit the ion. We show that the coordination geometry of K+ channel binding sites is replicated by 8-fold complexation of K+ in both water and simplified binding site models due to dominance of local interactions within a complex and is thus a requirement for topologically constraining the coordination number to a specific value.


Immersive virtual reality health games: a narrative review of game design.
High quality head-mounted display based virtual reality (HMD-VR) has become widely available, spurring greater development of HMD-VR health games. As a behavior change approach, these applications use HMD-VR and game-based formats to support long-term engagement with therapeutic interventions. While the bulk of research to date has primarily focused on the therapeutic efficacy of particular HMD-VR health games, how developers and researchers incorporate best-practices in game design to achieve engaging experiences remains underexplored. This paper presents the findings of a narrative review exploring the trends and future directions of game design for HMD-VR health games. We searched the literature on the intersection between HMD-VR, games, and health in databases including MEDLINE, Embase, CINAHL, PsycINFO, and Compendex. We identified articles describing HMD-VR games designed specifically as health applications from 2015 onwards in English. HMD-VR health games were charted and tabulated according to technology, health context, outcomes, and user engagement in game design. We identified 29 HMD-VR health games from 2015 to 2020, with the majority addressing health contexts related to physical exercise, motor rehabilitation, and pain. These games typically involved obstacle-based challenges and extrinsic reward systems to engage clients in interventions related to physical functioning and pain. Less common were games emphasizing narrative experiences and non-physical exercise interventions. However, discourse regarding game design was diverse and often lacked sufficient detail. Game experience was evaluated using primarily ad-hoc questionnaires. User engagement in the development of HMD-VR health games primarily manifested as user studies. HMD-VR health games are promising tools for engaging clients in highly immersive experiences designed to address diverse health contexts. However, more in-depth and structured attention to how HMD-VR health games are designed as game experiences is needed. Future development of HMD-VR health games may also benefit from greater involvement of end-users in participatory approaches.


Is there a genomically imprinted social brain?
Imprinted genes (IGs) are expressed or silenced according to their parent-of-origin. These genes are known to play a role in regulating offspring growth, development and infant behaviors such as suckling and ultrasonic calls. In adults, neurally expressed IGs coordinate several behaviors including maternal care, sex, feeding, emotionality, and cognition. However, despite evidence from human psychiatric disorders and evolutionary theory that maternally and paternally expressed genes should also regulate social behavior, little empirical data from mouse research exists. This paper discusses data from a recent study (Garfield et al., 2011) that the IG Grb10 governs unique aspects of mouse social behavior and interprets the relevance of these findings for the future of this field.


Phenotypic Detection of Hemin-Inducible Trimethoprim-Sulfamethoxazole Heteroresistance in Staphylococcus aureus.
Trimethoprim-sulfamethoxazole (SXT) is a valuable second-line antimicrobial agent to treat methicillin-resistant Staphylococcus aureus infections. Discrepancies between various antibiotic susceptibility testing (AST) methods for SXT susceptibility in S. aureus have been described. Here, we describe a hemin-inducible heteroresistance phenotype in S. aureus. We compared the results of the Vitek 2 AST on a set of 95 S. aureus clinical isolates with broth microdilution, disk diffusion using standard Mueller-Hinton agar, and disk diffusion using Mueller-Hinton agar supplemented with 5% horse blood (MHF). To investigate the potential clinical relevance of SXT heteroresistance, an in vivo Galleria mellonella infection assay was performed. All Vitek 2 SXT-susceptible (n = 17) isolates were concordant with AST results by other methods applied in this study. In 32/78 (41%) of Vitek 2 SXT-resistant isolates, we observed a heteroresistant growth phenotype on MHF. The heteroresistance phenotype was associated with the presence of dfr genes, encoding trimethoprim resistance. The addition of a hemin-impregnated disk in a double disk diffusion method on standard Mueller-Hinton agar was able to induce growth in the SXT zone of inhibition. An in vivo infection assay with G. mellonella suggested that the SXT heteroresistance phenotype resulted in lethality similar to that of the SXT-resistant phenotype. In this study, we describe a novel hemin-inducible heteroresistance phenotype in S. aureus. This heteroresistance phenotype may be missed by standard AST methods but can be detected by performing disk diffusion using Mueller-Hinton agar supplemented with 5% horse blood, commonly used for AST of fastidious organisms. This phenomenon may partly explain the discrepancies of AST methods in determining SXT resistance in S. aureus. IMPORTANCE Staphylococcus aureus is one of most important pathogens in clinical medicine. Besides its virulence, the acquisition or emergence of resistance toward antibiotic agents, in particular to beta-lactam antibiotics (methicillin-resistant S. aureus [MRSA]), poses a major therapeutic challenge. Trimethoprim-sulfamethoxazole (SXT) is one of the effective antimicrobial agents of last resort to treat MRSA infections. Here, we report the detection of a SXT-heteroresistant phenotype which is inducible by hemin and can be detected using Mueller-Hinton agar supplemented with horse blood. Heteroresistance describes the presence or emergence of resistant subpopulations, which may potentially lead to inaccurate antibiotic susceptibility testing results and influence the success of antibiotic therapy.


The fertilising potential of manure-based biogas fermentation residues: pelleted vs. liquid digestate.
Spreading of manure on agricultural soils is a main source of ammonia emissions and/or nitrate leaching. It has been addressed by the European Union with the Directives 2001/81/EC and 91/676/EEC to protect the environment and the human health. The disposal of manure has therefore become an economic and environmental challenge for farmers. Thus, the conversion of manure via anaerobic digestion in a biogas plant could be a sustainable solution, having the byproducts (solid and liquid digestates) the potential to be used as fertilizers for crops. This work aimed at characterizing and assessing the effect of digestates obtained from a local biogas plant (Biogas Wipptal, Gmbh), either in the form of liquid fraction or as a solid pellet on: (i) the fertility of the soils during an incubation experiment; (ii) the plant growth and nutritional status of different species (maize and cucumber). Moreover, an extensive characterization of the pellet was performed via X-ray microanalytical techniques. The data obtained showed that both digestates exhibit a fertilizing potential for crops, depending on the plant species and the fertilizer dose: the liquid fraction increases the shoot fresh weight at low dose in cucumber, conversely, the solid pellet increases the shoot fresh weight at high dose in maize. The liquid digestate may have the advantage to release nutrients (i.e. nitrogen) more rapidly to plants, but its storage represents the main constraint (i.e. ammonia volatilization). Indeed, pelleting the digestates could improve the storability of the fertilizer besides enhancing plant nutrient availability (i.e. phosphate and potassium), plant biomass and soil biochemical quality (i.e. microbial biomass and activity). The physical structure and chemical composition of pellet digestates allow nutrients to be easily mobilized over time, representing a possible source of mineral nutrients also in long-term applications.


[Biometric studies in the cytological diagnosis of soft tissue tumors].
Introducing of quantitative signs (the number of cells on the given area, size of cells, nuclei, optic and spectral characteristics) makes the cytologic diagnosis much more objective. Karyometric studies conducted by the author (the determination of nuclei volume) on cytological smears, obtained from 16 patients with soft tissue tumors, indicated some difference in nuclei size of various histotypes. The studies have evidenced that the method of karyometry associated with cytophotometry will offer the pre-conditions for using karyometry in the practice of pathocytologists and facilitate the finding of algorithms for computing analysis of soft tissue neoplasms.


Influence of accompanied encounters on patient-centeredness with older patients.
To conduct a pilot study to examine physician patient interaction when elderly patients are accompanied during a medical visit. This was a study in which 30 patients were randomly assigned to be accompanied (13) or unaccompanied (17) during a regular medical visit to their physician. Visits were tape recorded, transcribed, and coded with the Measure of Patient-Centered Communication (MPCC) and with the Rochester Participatory Decision-Making Scale (RPAD). We found no differences between the number of words spoken in accompanied versus unaccompanied visits, comparing patients alone with patients and companions combined. Physicians spoke longer without interruption in accompanied encounters (39.9 vs 78.6 words per speech turn). There were no differences in the level of MPCC or in the level of participatory decision making between the 2 types of visits. In accompanied visits, patients introduced most of the concerns and physicians discussed concerns with patients more than with companions. Previously reported differences in accompanied versus unaccompanied visits may reflect patients' preferences for being accompanied, the role they wish their companion to play, and the patients' health status. Being accompanied by a family member or friend does not result in less attention being paid to patients' concerns.


Health promoting properties of blueberries: a review.
With the strengthening of the link between diet and health, several foodstuffs have emerged as possessing potential health benefits such as phenolic rich fruits and vegetables. Blueberries, along with other berries, given their flavonoid and antioxidant content have long since been considered as a particularly interesting health promoting fruit. Therefore, the present work aimed to compile the existing evidences regarding the various potential benefits of blueberry and blueberry based products consumption, giving particular relevance to in vivo works and epidemiological studies whenever available. Overall, the results demonstrate that, while the evidences that support a beneficial role of blueberry and blueberry extracts consumption, further human based studies are still needed.


Heterocarbon nanosheets incorporating iron phthalocyanine for oxygen reduction reaction in both alkaline and acidic media.
Heterocarbon nanosheets incorporating iron phthalocyanine (FP-NCNs-SP) have been successfully synthesized by a facile one-pot solution plasma process at high repetition frequency. It was found that the Fe-N4 catalytic active sites could be preserved on the FP-NCNs-SP without degradation. The FP-NCNs-SP also possessed large surface area, good conductivity and high degree of graphitization. Electrochemical evaluations demonstrated that NCNs-SP had excellent electrocatalytic activity and selectivity toward oxygen reduction reaction (ORR) in alkaline medium through a direct four-electron pathway. Although the significant improvement in ORR activity was clearly observed in acidic medium, it was much poorer than in alkaline medium. We believe that the results presented in this work will shed light on the advanced synthesis and design of ORR electrocatalysts at room temperature with an abundance of catalytically active sites and high ORR performance.


Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a condition characterized by systemic low-grade inflammation that could increase the production of nitric oxide (NO), of which arginine is the sole precursor. Arginine is derived from the breakdown of protein and through the conversion of citrulline to arginine (de novo arginine production). Our objective was to study whole-body arginine and citrulline and related metabolism in stable COPD patients. With the use of stable isotope methodology, we studied whole-body arginine and citrulline rates of appearance, de novo arginine (citrulline-to-arginine flux) and NO (arginine-to-citrulline flux) production, protein synthesis and breakdown rates, and plasma amino acid concentrations in a heterogeneous group of patients with moderate-to-severe COPD [n = 23, mean ± SE age: 65 ± 2 y, forced expiratory volume in 1 s (FEV1): 40% ± 2% of predicted], and a group of healthy older adults (n = 19, mean ± SE age: 64 ± 2 y, FEV1: 95% ± 4% of predicted). Although plasma arginine and citrulline concentrations were comparable between COPD patients and controls, whole-body arginine (P = 0.015) and citrulline (P = 0.026) rates of appearance were higher in COPD patients and related to a 57% greater de novo arginine production (P < 0.0001). Despite a higher whole-body arginine clearance in COPD patients (P < 0.0001), we found no difference in NO production. In stable patients with moderate-to-severe COPD, endogenous arginine production is upregulated to support a higher arginine utilization that is unrelated to whole-body NO production. This trial was registered at clinicaltrials.gov as NCT01173354 and NCT01172314.


Association of expression levels of pluripotency/stem cell markers with the differentiation outcome of Wharton's jelly mesenchymal stem cells into insulin producing cells.
Recently, there has been much attention towards generation of insulin producing cells (IPCs) from stem cells, especially from Wharton's jelly mesenchymal stem cells (WJ-MSCs). However, generation of mature IPCs remains a challenge. Assessment of generation of IPCs was usually done by examining β-cell markers, however, assessment of pluripotency/stem cell markers drew less attention. Therefore, the purpose of this study was to investigate the levels of pluripotency/stem cell markers during differentiation of WJ-MSCs into IPCs and the association of these levels with differentiation outcomes. WJ-MSCs were isolated, characterized then induced to differentiate into IPCs using three different protocols namely A, B and C. Differentiated IPCs were assessed by the expression of pluripotency/stem cell markers, together with β-cell markers using qRT-PCR, and functionally by measuring glucose stimulated insulin secretion. Differentiated cells from protocol A showed lowest expression of pluripotency/stem cell markers and relatively best GSIS. However, protocol B showed concomitant expression of pluripotency/stem cell and β-cell markers with relatively less insulin secretion as compared to protocol A. Protocol C failed to generate glucose-responsive IPCs. In conclusion, sustained expression of pluripotency/stem cell markers could be associated with the incomplete differentiation of WJ-MSCs into IPCs. A novel finding for which further investigations are warranted.


The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases through Cannabinoid System Modulation-Evidence from In Vivo Studies.
Neurological disorders such as neurodegenerative diseases or traumatic brain injury are associated with cognitive, motor and behavioural changes that influence the quality of life of the patients. Although different therapeutic strategies have been developed and tried until now to decrease the neurological decline, no treatment has been found to cure these pathologies. In the last decades, the implication of the endocannabinoid system in the neurological function has been extensively studied, and the cannabinoids have been tried as a new promising potential treatment. In this study, we aimed to overview the recent available literature regarding in vivo potential of natural and synthetic cannabinoids with underlying mechanisms of action for protecting against cognitive decline and motor impairments. The results of studies on animal models showed that cannabinoids in traumatic brain injury increase neurobehavioral function, working memory performance, and decrease the neurological deficit and ameliorate motor deficit through down-regulation of pro-inflammatory markers, oedema formation and blood-brain barrier permeability, preventing neuronal cell loss and up-regulating the levels of adherence junction proteins. In neurodegenerative diseases, the cannabinoids showed beneficial effects in decreasing the motor disability and disease progression by a complex mechanism targeting more signalling pathways further than classical receptors of the endocannabinoid system. In light of these results, the use of cannabinoids could be beneficial in traumatic brain injuries and multiple sclerosis treatment, especially in those patients who display resistance to conventional treatment.


Treatment of vaginal candidosis with fluconazole.
In patients with vulvovaginal mycosis systemic treatment is being discussed for eradication of possible fungal reservoirs, therefore, the efficacy and toleration of fluconazole, a triazole-derivative, has been investigated in the course of an open, comparative study. 104 patients with clinical, microscopic and cultural evidence of vaginal mycosis were included, 53 of whom were treated with a single dose of 150 mg of fluconazole and 51 patients daily received local treatment with 50 mg of econazole over a period of 6 days. The results regarding clinical efficacy were comparable for both preparations. At follow-up visits 4 to 10 d and 30 to 45 d post therapy the mycological as well as the subjective cure rates were similar. However, there was a higher mycological cure rate in the rectum of fluconazole patients which was statistically verifiable. This enables the elimination of rectal fungal infection as a source of homologous reinfection.


Refined control of cell stemness allowed animal evolution in the oxic realm.
Animal diversification on Earth has long been presumed to be associated with the increasing extent of oxic niches. Here, we challenge that view. We start with the fact that hypoxia (<1-3% O2) maintains cellular immaturity (stemness), whereas adult stem cells continuously-and paradoxically-regenerate animal tissue in oxygenated settings. Novel insights from tumour biology illuminate how cell stemness nevertheless can be achieved through the action of oxygen-sensing transcription factors in oxygenated, regenerating tissue. We suggest that these hypoxia-inducible transcription factors provided animals with unprecedented control over cell stemness that allowed them to cope with fluctuating oxygen concentrations. Thus, a refinement of the cellular hypoxia-response machinery enabled cell stemness at oxic conditions and, then, animals to evolve into the oxic realm. This view on the onset of animal diversification is consistent with geological evidence and provides a new perspective on the challenges and evolution of multicellular life.


Outcome of post-term pregnancy: a matched-pair case-control study.
Matched-case control study was performed to assess perinatal mortality and feto-maternal morbidity related to the post-term pregnancy. 124 patients who delivered after 42 weeks of pregnancy were matched by age and parity with a control group of patients who delivered at term. Perinatal mortality and neonatal morbidity, as well as maternal morbidity were analyzed in both groups and differences tested for statistical significance. There was no statistically significant difference in perinatal mortality between the two groups (1 vs. 0; p>0.05). A statistically significant difference was found in the umbilical cord blood sample base excess after delivery in the post-term group. Cesarean section rate was higher in the post-term group (-6.1 vs. -4.9, p<0.05). If spontaneous labor occurred, there were no statistically significant differences in any of the analyzed parameters between the groups (p>0.05). Post-term pregnancy was related to higher maternal and neonatal morbidity, but the risks were biased by higher induction of labor rate and more frequent monitoring resulting in a higher intervention rate.


Biologically Inspired Object Tracking Using Center-Surround Saliency Mechanisms.
A biologically inspired discriminant object tracker is proposed. It is argued that discriminant tracking is a consequence of top-down tuning of the saliency mechanisms that guide the deployment of visual attention. The principle of discriminant saliency is then used to derive a tracker that implements a combination of center-surround saliency, a spatial spotlight of attention, and feature-based attention. In this framework, the tracking problem is formulated as one of continuous target-background classification, implemented in two stages. The first, or learning stage, combines a focus of attention (FoA) mechanism, and bottom-up saliency to identify a maximally discriminant set of features for target detection. The second, or detection stage, uses a feature-based attention mechanism and a target-tuned top-down discriminant saliency detector to detect the target. Overall, the tracker iterates between learning discriminant features from the target location in a video frame and detecting the location of the target in the next. The statistics of natural images are exploited to derive an implementation which is conceptually simple and computationally efficient. The saliency formulation is also shown to establish a unified framework for classifier design, target detection, automatic tracker initialization, and scale adaptation. Experimental results show that the proposed discriminant saliency tracker outperforms a number of state-of-the-art trackers in the literature.


The negative social network: when friends are foes.
In this study, three factors appear to influence significantly whether a child in foster care would be returned to the parent. The factors proved to be the number of persons in the parent's home, the number of friends in the neighborhood, and the frequency with which the parent saw those friends.


Fascin in Gynecological Cancers: An Update of the Literature.
Fascin is an actin-binding protein that is encoded by the FSCN1 gene (located on chromosome 7). It triggers membrane projections and stimulates cell motility in cancer cells. Fascin overexpression has been described in different types of human cancers in which its expression correlated with tumor growth, migration, invasion, and metastasis. Moreover, overexpression of fascin was found in oncovirus-infected cells, such as human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), disrupting the cell-cell adhesion and enhancing cancer progression. Based on these findings, several studies reported fascin as a potential biomarker and a therapeutic target in various cancers. This review provides a brief overview of the FSCN1 role in various cancers with emphasis on gynecological malignancies. We also discuss fascin interactions with other genes and oncoviruses through which it might induce cancer development and progression.


Influence of the fetal bovine serum proteins on the growth of human osteoblast cells on graphene.
The influence of single-layer graphene produced by chemical vapor deposition on human osteoblast cells under different conditions was studied. Measurements probed the ability of cells to adhere and proliferate on graphene compared with SiO(2)/Si substrates and standard tissue culture plastic when cells were incubated for the first 2 h in the presence or the absence of fetal bovine serum (FBS), thus influencing the initial, direct interaction of cells with the substrate. It was found that after 48 h of human osteoblast incubation on graphene films, there were a comparable number of cells of a similar size irrespective of the presence or the absence of serum proteins. On the other hand, a strong initial influence through the presence of FBS proteins on cell number and cell size was observed in the case of the SiO(2)/Si substrate and control plastic. Thus, our study showed that the initial presence/absence of FBS in the medium does not determine cell fate in the case of a graphene substrate, which is very unusual and different from the behavior of cells on other materials.


Colovaginal and colovesical fistulae: the diagnostic paradigm.
Colovaginal and colovesical fistulae (CVF) are relatively uncommon conditions, most frequently resulting from diverticular disease or colorectal cancer. A high suspicion of a CVF can usually be obtained from an accurate clinical history. Demonstrating CVF radiologically is often challenging, and patients frequently undergo a multitude of investigations prior to definitive management. The aim of this study was to develop an algorithm for the investigation of suspected CVF in order to improve diagnosis and subsequent management. Thirty-seven patients from a single NHS Trust with a diagnosis of colovaginal or colovesical fistula were included in the study. Clinical records and imaging were reviewed retrospectively, and data on demographics, symptoms, investigations, management and outcome were collated. A total of 87.5% patients with a colovesical fistula presented with pathognomic symptoms of faecaluria or pneumaturia. The commonest aetiologies were diverticular disease (72.9%), colonic and gynaecological neoplasia (10.8% each). Computerised tomography (CT) was the most frequently performed investigation (91.9%) and was most sensitive in detecting the fistula (76.5%) and underlying aetiology (94.1%). Colonoscopy was most sensitive in detecting an underlying colonic malignancy (100%). Resectional surgery was performed in 62.1% of cases, although morbidity and 1-year mortality was significant, with rates of 21.7 and 17.4%, respectively. The diagnosis of CVF is predominately a clinical one, and patients with a suspected CVF are over-investigated. Investigations should be focused on determining aetiology rather than demonstrating the fistulous tract itself. We propose that, in the majority of cases, CT and lower gastrointestinal endoscopy should suffice.


Capsaicin and Proton Differently Modulate Activation Kinetics of Mouse Transient Receptor Potential Vanilloid-1 Channel Induced by Depolarization.
The transient receptor potential vanilloid type 1 (TRPV1) channel is a non-selective cation channel expressed with transient receptor potential ankyrin type 1 (TRPA1) in small and medial size neurons of the dorsal root ganglions and trigeminal ganglions. TRPV1 is activated by capsaicin, thermal stimuli higher than 43°C, mechanical stress, and protons (H+). Although the TRPV1 channel does not have positively charged residues at regular intervals on its transmembrane segments, alterations in membrane potential also affect the state of TRPV1 channel. In the presence of capsaicin, voltage-dependent probability of opening of the TRPV1 channel and its kinetics have been examined, but the characteristics in the low pH remain unclear. To understand the voltage-dependency of the TRPV1 channel activation, we recorded capsaicin- and proton-induced mouse TRPV1 channel currents in a heterologous expression system. Outward current evoked by depolarizing square pulses in the presence of capsaicin or protons was fitted to a two-exponential function with a time-independent component. The voltage-dependent changes in amplitude of the three components displayed shallow curves and the changes in their ratio to the total current display similar tendencies in the presence of capsaicin and under the low pH. However, the fast and slow time constants in the presence of capsaicin were respectively 5- and 8-fold lower than those obtained under low pH conditions. These results suggest that the TRPV1 channel slowly drives the feed-forward cycle of pain sensation, and capsaicin and protons differently modulate the voltage-dependent TRPV1 channel gating.


Semantic similarity and machine learning with ontologies.
Ontologies have long been employed in the life sciences to formally represent and reason over domain knowledge and they are employed in almost every major biological database. Recently, ontologies are increasingly being used to provide background knowledge in similarity-based analysis and machine learning models. The methods employed to combine ontologies and machine learning are still novel and actively being developed. We provide an overview over the methods that use ontologies to compute similarity and incorporate them in machine learning methods; in particular, we outline how semantic similarity measures and ontology embeddings can exploit the background knowledge in ontologies and how ontologies can provide constraints that improve machine learning models. The methods and experiments we describe are available as a set of executable notebooks, and we also provide a set of slides and additional resources at https://github.com/bio-ontology-research-group/machine-learning-with-ontologies.


Overexpression of Wild-Type Human Alpha-Synuclein Causes Metabolism Abnormalities in Thy1-aSYN Transgenic Mice.
Parkinson's disease is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, pathological accumulation of alpha-synuclein and motor symptoms, but also by non-motor symptoms. Metabolic abnormalities including body weight loss have been reported in patients and could precede by several years the emergence of classical motor manifestations. However, our understanding of the pathophysiological mechanisms underlying body weight loss in PD is limited. The present study investigated the links between alpha-synuclein accumulation and energy metabolism in transgenic mice overexpressing Human wild-type (WT) alpha-synuclein under the Thy1 promoter (Thy1-aSYN mice). Results showed that Thy1-aSYN mice gained less body weight throughout life than WT mice, with significant difference observed from 3 months of age. Body composition analysis of 6-month-old transgenic animals showed that body mass loss was due to lower adiposity. Thy1-aSYN mice displayed lower food consumption, increased spontaneous activity, as well as a reduced energy expenditure compared to control mice. While no significant change in glucose or insulin responses were observed, Thy1-aSYN mice had significantly lower plasmatic levels of insulin and leptin than control animals. Moreover, the pathological accumulation of alpha-synuclein in the hypothalamus of 6-month-old Thy1-aSYN mice was associated with a down-regulation of the phosphorylated active form of the signal transducer and activator of transcription 3 (STAT3) and of Rictor (the mTORC2 signaling pathway), known to couple hormonal signals with the maintenance of metabolic and energy homeostasis. Collectively, our results suggest that (i) metabolic alterations are an important phenotype of alpha-synuclein overexpression in mice and that (ii) impaired STAT3 activation and mTORC2 levels in the hypothalamus may underlie the disruption of feeding regulation and energy metabolism in Thy1-aSYN mice.


Binding of monoclonal antibody to protein antigen in fluid phase or bound to solid supports.
Rat monoclonal antibody (MoAb) to fragment D (FgD) of human fibrinogen was used to characterize the direct binding of antibody to protein in solution or bound to solid supports. Purified IgG, F(ab')2 and Fab' were prepared from ascites fluid of hybridoma 104-14B which is a fusion product of spleen cells from a rat immunized with FgD and the mouse myeloma cell line, P3-X63-Ag8. Two-dimensional electrophoresis of radioiodinated antibody preparations demonstrated the presence of hybrid immunoglobulin molecules, but only structures having rat heavy and rat light chains had active antibody combining sites. The affinity constant for IgG as well as F(ab')2 and Fab', 6 X 10(9) M-1, was identical when tested using fluid phase antigen (125I-labeled FgD). Affinity constants determined for direct binding of iodinated IgG using FgD immobilized on solid supports showed a slight dependence on the antigen concentration used in the measurement. These values ranged from 0.5 X 10(9) M-1 at high antigen concentrations (1.3 X 10(-7) M) to 9 X 10(9) M-1 at low antigen concentration (1.3 X 10(-10) M). Binding constants for F(ab')2 and Fab' gave similar results indicating that binding was homogeneous and univalent. The capacity of solid state antigen to bind antibody varied with the method used to bind FgD to the solid support. FgD bound directly to polystyrene plates was least efficient at binding labeled antibody; FgD bound to plates through intermediate carriers poly(L-lysine) was only slightly more efficient, while antigen bound to Sepharose beads by cyanogen bromide activation was the most active.


Senescence (ageing) @ 2011.
Ageing, also called as senescence, is one of the most complex, intrinsic, biological processes of growing older and resulting into reduced functional ability of the organism. Telomerase, environment, low calorie diets, free radicals, etc., are all believed to affect this ageing process. A number of genetic components of ageing have been identified using model organisms. Genes, mainly the sirtuins, regulate the ageing speed by indirection and controlling organism resistance to damages by exogenous and endogenous stresses. In higher organisms, ageing is likely to be regulated, in part, through the insulin/insulin-like growth factor 1 pathway. Besides this, the induction of apoptosis in stem and progenitor cells, increased p53 activity, and autophagy is also thought to trigger premature organismal ageing. Ageing has also been shown to upregulate expression of inflammatory mediators in mouse adipose tissue. The understanding of pathophysiology of ageing over the past few years has posed tremendous challenges for the development of anti-ageing medicine for targeted therapy. Future research areas must include targeted role of systemic inflammatory markers such as C-reactive protein and interleukin 6 and other biochemical and genetic studies including gene signaling pathways, gene microarray analysis, gene modulation, gene therapy, and development of animal/human models for potential therapeutic measures and evaluations.


In Planta Functional Analysis and Subcellular Localization of the Oomycete Pathogen Plasmopara viticola Candidate RXLR Effector Repertoire.
Downy mildew is one of the most destructive diseases of grapevine, causing tremendous economic loss in the grape and wine industry. The disease agent Plasmopara viticola is an obligate biotrophic oomycete, from which over 100 candidate RXLR effectors have been identified. In this study, 83 candidate RXLR effector genes (PvRXLRs) were cloned from the P. viticola isolate "JL-7-2" genome. The results of the yeast signal sequence trap assay indicated that most of the candidate effectors are secretory proteins. The biological activities and subcellular localizations of all the 83 effectors were analyzed via a heterologous Agrobacterium-mediated Nicotiana benthamiana expression system. Results showed that 52 effectors could completely suppress cell death triggered by elicitin, 10 effectors could partially suppress cell death, 11 effectors were unable to suppress cell death, and 10 effectors themselves triggered cell death. Live-cell imaging showed that the majority of the effectors (76 of 83) could be observed with informative fluorescence signals in plant cells, among which 34 effectors were found to be targeted to both the nucleus and cytosol, 29 effectors were specifically localized in the nucleus, and 9 effectors were targeted to plant membrane system. Interestingly, three effectors PvRXLR61, 86 and 161 were targeted to chloroplasts, and one effector PvRXLR54 was dually targeted to chloroplasts and mitochondria. However, western blot analysis suggested that only PvRXLR86 carried a cleavable N-terminal transit peptide and underwent processing in planta. Many effectors have previously been predicted to target organelles, however, to the best of our knowledge, this is the first study to provide experimental evidence of oomycete effectors targeted to chloroplasts and mitochondria.


Condensation transition in polydisperse hard rods.
We study a mass transport model, where spherical particles diffusing on a ring can stochastically exchange volume v, with the constraint of a fixed total volume V= sum(i=1) (N)v(i), N being the total number of particles. The particles, referred to as p-spheres, have a linear size that behaves as v(i) (1/p) and our model thus represents a gas of polydisperse hard rods with variable diameters v(i) (1/p). We show that our model admits a factorized steady state distribution which provides the size distribution that minimizes the free energy of a polydisperse hard-rod system, under the constraints of fixed N and V. Complementary approaches (explicit construction of the steady state distribution on the one hand; density functional theory on the other hand) completely and consistently specify the behavior of the system. A real space condensation transition is shown to take place for p>1; beyond a critical density a macroscopic aggregate is formed and coexists with a critical fluid phase. Our work establishes the bridge between stochastic mass transport approaches and the optimal polydispersity of hard sphere fluids studied in previous articles.


Fenestrated Endografts for Complex Abdominal Aortic Aneurysm Repair.
Since the introduction of fenestrated endovascular aneurysm repair (FEVAR) in 1996, great advances have been made in endograft development. Custom-made and off-the-shelf fenestrated and branched endografts have been used to treat patients with complex abdominal aortic and thoraco-abdominal aneurysms. Most experience has been gained with the Cook Zenith® fenestrated endograft (Cook Medical Inc., Limerick, Ireland). The Cook Zenith® endograft is customized with fenestrations, (fixed) inner or outer branches, or a combination of them, to cover a wide range of complex aneurysms. There are limitations to the number, location, and size of the fenestrations and to the maximal angulation of the aorta. Because the production of a custom-made fenestrated endograft takes several weeks, and is therefore not available for emergency cases, off-the-shelf fenestrated endograft were developed. One of these grafts was the Endologix Ventana™ (Endologix, Inc., Irvine, California). This endograft was withdrawn from enrollment due to a high reintervention rate. Vascutek Ltd. developed the custom-made Vascutek Fenestrated Anaconda™ endograft (Vascutek Ltd., Inchinnan, Scotland) to treat patients where other endografts were not suitable-like in a more tortuous aorta with an angulation up to 90°. Additionally, the unsupported proximal body enables a high number and large size of fenestrations if needed. First reports of custom-made fenestrated and (inner and outer) branched JOTEC E-xtra DESIGN ENGINEERING (JOTEC GmbH, Hechingen, Germany) for aortic aneurysms seem promising, but larger series need to be reported to be able to draw conclusions. Both custom-made Cook Zenith® and Vascutek Fenestrated Anaconda™ endografts have good reported clinical outcomes with a perioperative mortality between 4.1 and 6.7% and a reintervention rate of <10% at one year. Knowledge on the long-term outcome of both devices is still limited.


Pressurized liquid extraction of ginger (Zingiber officinale Roscoe) with bioethanol: an efficient and sustainable approach.
To develop an efficient green extraction approach for recovery of bioactive compounds from natural plants, we examined the potential of pressurized liquid extraction (PLE) of ginger (Zingiber officinale Roscoe) with bioethanol/water as solvents. The advantages of PLE over other extraction approaches, in addition to reduced time/solvent cost, the extract of PLE showed a distinct constituent profile from that of Soxhlet extraction, with significantly improved recovery of diarylheptanoids, etc. Among the pure solvents tested for PLE, bioethanol yield the highest efficiency for recovering most constituents of gingerol-related compounds; while for a broad concentration spectrum of ethanol aqueous solutions, 70% ethanol gave the best performance in terms of yield of total extract, complete constituent profile and recovery of most gingerol-related components. PLE with 70% bioethanol operated at 1500 psi and 100 °C for 20 min (static extraction time: 5 min) is recommended as optimized extraction conditions, achieving 106.8%, 109.3% and 108.0% yield of [6]-, [8]- and [10]-gingerol relative to the yield of corresponding constituent obtained by 8h Soxhlet extraction (absolute ethanol as extraction solvent).


Learning Activity as a Means of Developing Theoretical Thinking Capacities.
The main purpose of this article is to discuss the development of capacities linked to theoretical thinking during the formation process of Learning Activity in students of the early years of elementary school. It considers some elements which could form the basis for thinking about teaching activity as a means of conducting students toward that development. It starts from the hypothesis that the development of the capacities of analysis, reflection, and mental planning depends, essentially, on the systematic organization of the principles and ways of action of the students on the theoretical contents in their learning process. The hypothesis further states that Learning Activity is the most appropriate way to organize pedagogical work for the development of methods of action that would enable students to achieve new higher psychological formations and develop new ways of thinking and acting in the learning environment. The theoretical study was carried out through locating, gathering, analyzing, synthesizing, and reframing the theorical ideas contained in publications, texts, articles, and books by authors of the Cultural-Historical Theory. The study places emphasis on Learning Activity as an adequate way to develop psychic neoformations in school-age children, since their organization, based on the solution of learning tasks through learning actions, is the source of the development of analysis, reflection, and mental planning skills, as constituent parts of theoretical thinking in school-age children.


Misconceptions about case-mix payments for nursing homes.
Despite the increasing use of case-mix payment systems for skilled and intermediate nursing home care (at least 10 state Medicaid programs have adopted or are considering adopting such a system), misconceptions about such systems still exist. Unless these inaccurate perceptions are corrected, a state may adopt a system that fails to realize its goals. Some of these misconceptions include the beliefs that case-mix payment systems: Apply to all nursing homes costs; Will benefit hospital-based facilities; Will resolve the access problems of heavy care public patients; Will result in higher statewide payment rates because patient characteristics are factored directly into the calculations. In fact, case-mix adjustments are applied only to costs that can be traced directly to patients' impairments. Nursing services and some ancillary services are dependent on case mix, while administrative and support services are largely independent of case mix. Capital costs usually can be ignored in formulating the case-mix adjustment. Although hospital-based facilities frequently have sicker patients than freestanding facilities, studies show that only a portion of the cost differential is explained by case-mix differences. In the case of heavy-care patients, some believe that case-mix payment systems will resolve access problems by paying higher rates in response to the higher treatment costs. Access may not improve, however, if the new rates are lower than those paid by comparable private patients. Perhaps a loosening in the certificate-of-need process will also be needed to resolve the access problem.(ABSTRACT TRUNCATED AT 250 WORDS)


Leveraging Prior Knowledge to Recover Characteristic Immune Regulatory Motifs in Gulf War Illness.
Potentially linked to the basic physiology of stress response, Gulf War Illness (GWI) is a debilitating condition presenting with complex immune, endocrine and neurological symptoms. Here we interrogate the immune response to physiological stress by measuring 16 blood-borne immune markers at 8 time points before, during and after maximum exercise challenge in n = 12 GWI veterans and n = 11 healthy veteran controls deployed to the same theater. Immune markers were combined into functional sets and the dynamics of their joint expression described as classical rate equations. These empirical networks were further informed structurally by projection onto prior knowledge networks mined from the literature. Of the 49 literature-informed immune signaling interactions, 21 were found active in the combined exercise response data. However, only 4 signals were common to both subject groups while 7 were uniquely active in GWI and 10 uniquely active in healthy veterans. Feedforward mediation of IL-23 and IL-17 by IL-6 and IL-10 emerged as distinguishing control elements that were characteristically active in GWI versus healthy subjects. Simulated restructuring of the regulatory circuitry in GWI as a result of applying an IL-6 receptor antagonist in combination with either a Th1 (IL-2, IFNγ, and TNFα) or IL-23 receptor antagonist predicted a partial rescue of immune response elements previously associated with illness severity. Overall, results suggest that pharmacologically altering the topology of the immune response circuitry identified as active in GWI can inform on strategies that while not curative, may nonetheless deliver a reduction in symptom burden. A lasting and more complete remission in GWI may therefore require manipulation of a broader physiology, namely one that includes endocrine oversight of immune function.


Structure and enzymic activity of ribonuclease-A esterified at glutamic acid-49 and aspartic acid-53.
The dimethyl ester of bovine pancreatic ribonuclease-A (dimethyl RNAase-A), the initial product of esterification of RNAase-A in anhydrous methanolic HCl, was isolated in a homogeneous form. The two carboxy functions esterified in this derivative are those of glutamic acid-49 and aspartic acid-53. There were no changes in the u.v.-absorption spectral characteristics, the accessibility of the methionine residues, the resistance of the protein to proteolysis by trypsin and the antigenic behaviour of RNAase-A as a result of the esterification of these two carboxy groups. Dimethyl RNAase-A exhibited only 65% of the specific activity of RNAase-A, but still had the same K(m) value for both RNA and 2':3'-cyclic CMP. However, the V(max.) was decreased by about 35%. On careful hydrolysis of the methyl ester groups at pH9.5, dimethyl RNAase-A was converted back into RNAase-A. Limited proteolysis of dimethyl RNAase-A by subtilisin resulted in the formation of an active RNAase-S-type derivative, namely dimethyl RNAase-S, which was chromatographically distinct from dimethyl RNAase-A and had very nearly the same enzymic activity as dimethyl RNAase-A. Fractionation of dimethyl RNAase-S by trichloroacetic acid yielded dimethyl RNAase-S-protein and dimethyl RNAase-S-peptide, both of which were inactive by themselves but regenerated dimethyl RNAase-S when mixed together. Dimethyl RNAase-A-peptide was identical with RNAase-S-peptide. RNAase-S-protein could be generated from dimethyl RNAase-S-protein by careful hydrolysis of the methyl ester groups at pH9.5. The interaction of dimethyl RNAase-S-protein with RNAase-S-peptide appears to be about 4-fold weaker than that between the RNAase-S-protein and RNAase-S-peptide. Conceivably, the binding of the S-peptide ;tail' of dimethyl RNAase-A with the remainder of the molecule is similarly weaker than that in RNAase-A, and this brings about subtle changes in the geometrical orientation of the active-site amino acid residues of these modified methyl ester derivatives. It is suggested that these changes could be responsible for the generation of the catalytically less-efficient RNAase-A and RNAase-S molecules (dimethyl RNAase-A and dimethyl RNAase-S respectively).


[A neuritogenic compound from Tremella fuciformis].
To search for low-molecular-weight neuritogenic compounds from the traditional Chinese medicine (TCM). An extract library of TCM was prepared. Targeted isolation guided by biological screening led to the discovery of compound 1, and its structure was elucidated by analysis of spectroscopic methods and comparison of spectroscopic data with these reported from the literature. A neuritogenic compound 1, 3-O-beta-D-glucopyranosyl-22E, 24R-5alpha, 8alpha-epidioxyergosta-6, 22-diene, was isolated and identified from the methanol extract of T. fuciformis. This compound showed a significant neuritogenic activity against PC12 cells at 3 micromol x L(-1)). Methonal extract of T. fuciformis and targeted compound 1 both showed significant neuritogenic activity against PC12 cells. These results suggested that the extract and compound 1 might be used to prevent and treat neurodegenerative disease such as Alzheimer's disease.


Imbalanced neural responsivity to risk and reward indicates stress vulnerability in humans.
Trauma-related psychopathology has been associated with an intense emotional reaction to stressful event. Emotional responses have evolved to signal the presence of risks to be avoided or of rewards to be approached in the environment. Thus, individuals' sensitivity to signals of risk and reward may affect the level of stress vulnerability. Stress, however, can modify these sensitivities as well. In the current functional magnetic resonance imaging (fMRI) study, we prospectively probed the neural correlates of such sensitivities in 24 healthy soldiers by using an interactive game that encompasses risky and rewarding intervals both pre-exposure and post-exposure to stressful military service. As expected, risky and rewarding intervals elicited selective responses in the amygdala and nucleus accumbens (Nacc), respectively. Furthermore, increased post-traumatic stress disorder symptoms post-exposure (i.e., stress vulnerability) corresponded to greater amygdala's response to risk both pre-exposure and post-exposure and to decreased NAcc response to reward only post-exposure. By combining these regional responsivities post-exposure, we accurately identified all the most vulnerable soldiers. Imbalanced neural responsivity to risk and reward following exposure to stress may therefore constitute a marker for stress vulnerability. Such identification of vulnerability biomarkers can aid future diagnostic and therapeutic efforts by allowing early detection of vulnerability as well as follow up on patient's treatment progression.


The function of microRNAs, small but potent molecules, in human prostate cancer.
Prostate cancer is one of the most significant cancers of men all over the world. The microRNAs (miRNAs) possess crucial functions in pathogenesis of the disease and its gain of androgen independency. The miRNAs are small, approximately 18-24 nucleotides, non-coding, endogenously synthesized RNAs that regulate gene expression post-transcriptionally. They are found in viruses, plants, and animal cells. The miRNAs have critical functions in gene expression and their dysregulation may cause tumor formation and progression of several diseases. Here, we have reviewed the most current literature to elucidate the function of miRNAs in human prostate cancer. We believe that this will help investigators not only working in prostate cancer, but also studying the miRNAs in other diseases to delineate the functions of miRNAs implicated in human prostate cancer development and progression.


Small-spot intensity-modulated proton therapy and volumetric-modulated arc therapies for patients with locally advanced non-small-cell lung cancer: A dosimetric comparative study.
To compare dosimetric performance of volumetric-modulated arc therapy (VMAT) and small-spot intensity-modulated proton therapy for stage III non-small-cell lung cancer (NSCLC). A total of 24 NSCLC patients were retrospectively reviewed; 12 patients received intensity-modulated proton therapy (IMPT) and the remaining 12 received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTV) on averaged 4D-CTs. The dose-volume-histograms (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases of each field per fraction. DVH indices were compared using Wilcoxon rank sum test. Compared with VMAT, IMPT delivered significantly lower cord Dmax , heart Dmean , and lung V5 Gy[ RBE ] with comparable CTV dose homogeneity, and protection of other OARs. In terms of plan robustness, the IMPT plans were statistically better than VMAT plans in heart Dmean , but were statistically worse in CTV dose coverage, cord Dmax , lung Dmean , and V5 Gy[ RBE ] . Other DVH indices were comparable. The IMPT plans still met the standard clinical requirements with interplay effects considered. Small-spot IMPT improves cord, heart, and lung sparing compared to VMAT and achieves clinically acceptable plan robustness at least for the patients included in this study with motion amplitude less than 11 mm. Our study supports the usage of IMPT to treat some lung cancer patients.


Association between zinc nutritional status and glycemic control in individuals with well-controlled type-2 diabetes.
Interest in healthy properties of food and nutrients as co-adjuvant in type-2 diabetes therapy has increased in recent years. Zinc supplementation trials have shown improvements in glycemic control in these patients, although it seems dependent on zinc status of the individuals. The objective of this study was to evaluate the relationship between zinc nutritional status and glucose homeostasis in patients with type-2 diabetes. Eighty patients with well controlled type-2 diabetes were recruited and clinical, anthropometric and dietary evaluations were performed. One week after, insulin sensitivity and beta cell function were assessed by a modified Frequently Sampled Intravenous Glucose Tolerance Test. Zinc status was assessed by plasma zinc and the size of rapidly Exchangeable Zinc Pool (EZP); zinc intake was also determined. Glucagon concentration was evaluated in a subsample of 36 patients. Patients presented a normal zinc status although zinc intake was lower than recommended. Overall, no associations were observed between zinc status and glycemic control markers. Nevertheless, positive correlations were observed between EZP and fasting insulin concentration (ρ = 0.393, p = 0.021) and HOMA-IR (ρ = 0.386, p = 0.024) in women, and between plasma zinc concentration and HbA1c (ρ = 0.342, p = 0.020) in men. No significant associations were found between zinc status and glycemic control parameters in patients with well-controlled type 2 diabetes and normal zinc status, although low-degree gender-dependent associations were observed. Further research is required to assess the role of zinc status in zinc deficient patients.


Dehydrin MtCAS31 promotes autophagic degradation under drought stress.
Drought stress seriously affects crop yield, and the mechanism underlying plant resistance to drought stress via macroautophagy/autophagy is not clear. Here, we show that a dehydrin, Medicago truncatula MtCAS31 (cold acclimation-specific 31), a positive regulator of drought response, plays a key role in autophagic degradation. A GFP cleavage assay and treatment with an autophagy-specific inhibitor indicated that MtCAS31 participates in the autophagic degradation pathway and that overexpressing MtCAS31 promotes autophagy under drought stress. Furthermore, we discovered that MtCAS31 interacts with the autophagy-related protein ATG8a in the AIM-like motif YXXXI, supporting its function in autophagic degradation. In addition, we identified a cargo protein of MtCAS31, the aquaporin MtPIP2;7, by screening an M. truncatula cDNA library. We found that MtPIP2;7 functions as a negative regulator of drought response. Under drought stress, MtCAS31 facilitated the autophagic degradation of MtPIP2;7 and reduced root hydraulic conductivity, thus reducing water loss and improving drought tolerance. Taken together, our results reveal a novel function of dehydrins in promoting the autophagic degradation of proteins, which extends our knowledge of the function of dehydrins.Abbreviations: AIM: ATG8-interacting motif; ATG: autophagy-related; ATI1: ATG8-interacting protein1; BiFC: Biomolecular fluorescence complementation; CAS31: cold acclimation-specific 31; ConcA: concanamycin A; DSK2: dominant suppressor of KAR2; ER: endoplasmic reticulum; ERAD: ER-associated degradation; NBR1: next to BRCA1 gene 1; PM: plasma membrane; PIPs: plasma membrane intrinsic proteins; TALEN: transcription activator-like effector nuclease; TSPO: tryptophan-rich sensory protein/translocator; UPR: unfolded protein response; VC: vector control.


A 68-year-old with cranial nerve neuropathies and a troponin rise.
In this case study, we summarise the inpatient investigations and management of a 68-year-old woman with Takotsubo cardiomyopathy secondary to a Varicella zoster encephalitis and the difficulties inherent with making this diagnosis. She presented with evolving cranial nerve neuropathies, which started with a vagal nerve mononeuritis and eventually included left-sided sensorineural hearing loss and a facial nerve palsy. These symptoms were concomitant with a variety of cardiac abnormalities, including fast atrial fibrillation and electrocardiographic changes. We summarise some of the current understanding of Takotsubo cardiomyopathy and the criteria for its diagnosis. Although left ventricular apical ballooning has been described in association with severe infections and states of high stress, we have not seen it reported in association with a Varicella zoster encephalitis.


The prevalence and predictors of anxiety and depression in adolescents with heart disease.
To evaluate the prevalence and contributory factors of depression and anxiety in adolescents with heart disease. A cohort of adolescents was recruited from an ambulatory cardiology clinic at a tertiary center and from such clinics run privately. Questionnaires included the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Life Orientation Test-Revised, and Sense of Coherence-13. A total of 119 adolescents aged 12-20 years were recruited. Most of the participants (90%) had congenital heart disease. Nearly all (98%) were in New York Heart Association Functional Classification class I. Approximately one-half of the participants had had previous surgeries and/or catheter interventions. Eleven patients (9%) were above the cut-off score for likely depression, and 32 (27%) had likely anxiety. A feeling of optimism was the most significant factor in reducing anxiety and depression, followed by good social support and a strong sense of coherence (multiple regressions, β = -0.38, -0.2, -0.17, respectively). Depression and anxiety were found to be common in a relatively well adolescent population with heart disease. None of those affected had been clinically assessed and appropriately treated by a mental health professional. Protective factors against depression and anxiety need be developed as well as appropriate assessment and intervention.


A structural perspective on nuclear receptors as targets of environmental compounds.
Nuclear receptors (NRs) are members of a large superfamily of evolutionarily related transcription factors that control a plethora of biological processes. NRs orchestrate complex events such as development, organ homeostasis, metabolism, immune function, and reproduction. Approximately one-half of the 48 human NRs have been shown to act as ligand-regulated transcription factors and respond directly to a large variety of endogenous hormones and metabolites that are generally hydrophobic and small in size (eg, retinoic acid or estradiol). The second half of the NR family comprises the so-called orphan receptors, for which regulatory ligands are still unknown or may not exist despite the presence of a C-terminal ligand-binding domain, which is the hallmark of all NRs. Several chemicals released into the environment (eg, bisphenols, phthalates, parabens, etc) share some physicochemical properties with natural ligands, allowing them to bind to NRs and activate or inhibit their action. Collectively referred to as endocrine disruptors or endocrine-disrupting chemicals (EDCs), these environmental pollutants are highly suspected to cause a wide range of developmental, reproductive, neurological, or metabolic defects in humans and wildlife. Crystallographic studies are revealing unanticipated mechanisms by which chemically diverse EDCs interact with the ligand-binding domain of NRs. These studies thereby provide a rational basis for designing novel chemicals with lower impacts on human and animal health. In this review, we provide a structural and mechanistic view of endocrine disrupting action using estrogen receptors α and β, (ERα/β), peroxisome proliferator activated receptor γ (PPARγ), and their respective environmental ligands as representative examples.