Key maneuvers for successful correction of a deviated nose in Asians.
The authors present surgical results of 64 Asian patients with deviated nose and introduce important key maneuvers used in the surgery. Sixty-four consecutive patients who underwent corrective rhinoplasty because of a deviated nose were analyzed retrospectively. Approaches and techniques used for the surgery, surgical results, and complications were evaluated. A questionnaire was used to evaluate each patient's functional and esthetic satisfaction. Preoperative and postoperative standardized photographs of the face were evaluated to judge objectively the esthetic outcomes of the surgery. An endonasal approach was used in 44 patients and an open approach was used in 20 patients. Five important key maneuvers to correct the deviation were noted, in the order of frequency: septoplasty, osteotomy, spreader graft, turbinoplasty, and camouflage graft. Additional procedures included augmentation of the dorsum, tip surgery, and hump removal. On a 5-point box scale of 0-4, the patients scored their satisfaction on functional improvements as 3.2+/-0.79 and their esthetic satisfaction as 3.0+/-0.8. The objective evaluation of the appearance showed complete correction in 84.4%, a minimally visible deviation in 10.9%, and a residual deviation but less than before surgery in 4.7%. Aside from residual deviations, complications included a slight depression of the middorsum after spreader graft and a malpositioning of the dorsal cartilage graft. Deviated nose in Asians can be managed successfully by combining key maneuvers that correct specific anatomic abnormalities. Many of these key maneuvers require modifications that take into account the race-specific characteristics of the Asian nose.


Psychophysiological biomarkers of dissociation in psychogenic non-epileptic seizures.
Misdiagnosis of patients with psychogenic non-epileptic seizures (PNES) as having epilepsy is a clinical relevant problem. Considerable problems for the patients, such as unnecessary anticonvulsant medication use and delay of suitable therapy, as well as a considerable economic burden are involved. Furthermore, after the diagnosis of PNES is confirmed, there is a lack of scientific evidence about the most efficient treatment for PNES. Evaluation of contributing factors is necessary. These factors should be implemented in explanatory models for the occurrence of PNES, which should be employed in diagnosis and treatment. Recent evidence suggests a role of deficiencies in neuronal information processing in multiple mental conditions. Although the focus in PNES research over the last two decades primarily has been on differential diagnosis and psychological and environmental factors, abnormalities in psychophysiological characteristics might also be involved in PNES. This review focuses on neurobiological substrates of PNES and dissociation, a trait which is often associated with PNES, to explore whether deviant information processing is involved in the aetiology of PNES. All studies examining the relationship between psychophysiological parameters and PNES have an exploratory character. However, the results suggest that neurophysiological characteristics, such as brain activity as visualized by functional MRI, cardiovascular measurements and neuroendocrine functioning, may be abnormal in patients with PNES. Future investigations should therefore elucidate the exact role of neurophysiological abnormalities in the aetiology of PNES.


NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study.
The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease-free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction = 0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction = 0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively.


Eilatin complexes of ruthenium and osmium. synthesis, electrochemical behavior, and near-IR luminescence.
The synthesis and characterization of new Ru(II) and Os(II) complexes of the ligand eilatin (1) are described. The new complexes [Ru(bpy)(eil)(2)](2+) (2), [Ru(eil)(3)](2+) (3), and [Os(eil)(3)](2+) (4) (bpy = 2,2'-bipyridine; eil = eilatin) were synthesized and characterized by NMR, fast atom bombardment mass spectrometry, and elemental analysis. In the series of complexes [Ru(bpy)(x)(eil)(y)()](2+) (x + y = 3), the effect of sequential substitution of eil for bpy on the electrochemical and photophysical properties was examined. The absorption spectra of the complexes exhibit several bpy- and eil-associated pi-pi and metal-to-ligand charge-transfer (MLCT) transitions in the visible region (400-600 nm), whose energy and relative intensity depend on the number of ligands bound to the metal center (x and y). On going from [Ru(bpy)(2)(eil)](2+) (5) to 2 to 3, the d(pi)(Ru) --> pi(eil) MLCT transition undergoes a red shift from 583 to 591 to 599 nm, respectively. Electrochemical measurements performed in dimethyl sulfoxide reveal several ligand-based reduction processes, where each eil ligand can accept up to two electrons at potentials that are significantly anodically shifted (by ca. 1 V) with respect to the bpy ligands. The complexes exhibit near-IR emission (900-1100 nm) of typical (3)MLCT character, both at room temperature and at 77 K. Along the series 5, 2, and 3, upon substitution of eil for bpy, the emission maxima undergo a blue shift and the quantum yields and lifetimes increase. The radiative and nonradiative processes that contribute to deactivation of the excited level are discussed in detail.


Robust, high-productivity phototrophic carbon capture at high pH and alkalinity using natural microbial communities.
Bioenergy with carbon capture and storage (BECCS) has come to be seen as one of the most viable technologies to provide the negative carbon dioxide emissions needed to constrain global temperatures. In practice, algal biotechnology is the only form of BECCS that could be realized at scale without compromising food production. Current axenic algae cultivation systems lack robustness, are expensive and generally have marginal energy returns. Here it is shown that microbial communities sampled from alkaline soda lakes, grown as biofilms at high pH (up to 10) and high alkalinity (up to 0.5 kmol m-3 NaHCO3 and NaCO3) display excellent (>1.0 kg m-3 day-1) and robust (>80 days) biomass productivity, at low projected overall costs. The most productive biofilms contained >100 different species and were dominated by a cyanobacterium closely related to Phormidium kuetzingianum (>60%). Frequent harvesting and red light were the key factors that governed the assembly of a stable and productive microbial community.


Commentary 2: Sibling Power Dynamics: The Role of Family and Sociocultural Context.
The balance of power and control is an understudied, yet important, aspect of the sibling relationship that is theorized to shift over the course of development from early childhood to young adulthood. The investigations in this issue offer support for this overall progression, but extend prior research by providing a nuanced understanding of sibling power dynamics using different methodologies, analytic approaches, and study designs. Grounded within an ecological framework, directions for future research are offered to expand our understanding of sibling power dynamics in diverse family and sociocultural contexts.


[Programmed cell death: is it only apoptosis?].
Recent reports prove the necessity to modify the classical definitions of cell death. The canonical distinction between apoptosis (defined as programed cell death--PCD) and necrosis (gene independent) in no longer scientifically valid. Furthermore, more than one process mediated by intracellular genetic program has been documented, for example programmed necrosis. Diversity in definitions leads to confusion, particularly regarding specific terminology. Here we present the new unified criteria for the evaluation of cell death mechanisms as proposed by the Nomenclature Committee on Cell Death in recommendations from 2009 and 2012.


Insulin sensitivity in alcoholic cirrhosis.
The amount-of-substance rate of glucose metabolism and its sensitivity to the concentration of insulin was quantified in 10 non-diabetic patients with alcoholic cirrhosis of varying severity, using the 'glucose clamp technique'. Fasting glucose and insulin were 5.4 +/- 0.3 mmol/l and 187 +/- 50 pmol/l (mean +/- SEM), respectively. During the hyperglycaemic clamp (blood glucose at 12.5 mmol/l) the glucose metabolic rate (divided by body mass) was 27 +/- 4 mumol X min-1 X kg-1 at an insulin concentration of 998 +/- 158 pmol/l. Thus the insulin sensitivity of the tissue glucose metabolism was 22 +/- 7 m3 X min-1 X kg-1. During the euglycaemic clamp exogenous insulin was given to a concentration of 574 +/- 72 pmol/l. The resulting glucose metabolic rate was 20 +/- 4 mumol X min-1 X kg-1 and the insulin sensitivity the same as during hyperglycaemia. The calculated systemic delivery rate of insulin (divided by body surface area) was 783 +/- 172 pmol X min-1 X m-2. Fasting glucagon was 32 +/- 5 pmol/ and only partly depressed by glucose or insulin. In comparison with stated relevant control groups cirrhotics exhibit glucose intolerance characterized by decreased sensitivity to insulin, hyperinsulinaemia due to increased release, and hyperglucagonaemia with decreased suppressibility. There was no relation between clinical or biochemical data of the patients and the above results, suggesting that the abnormal glucose metabolism does not depend directly on the decreased liver function but on a disturbed pancreatic-hepatic-peripheral axis.


The stuff that motor chunks are made of: Spatial instead of motor representations?
In order to determine how participants represent practiced, discrete keying sequences in the discrete sequence production task, we had 24 participants practice two six-key sequences on the basis of two pre-learned six-digit numbers. These sequences were carried out by fingers of the left (L) and right (R) hand with between-hand transitions always occurring between the second and third, and the fifth and sixth responses. This yielded the so-called LLRRRL and RRLLLR sequences. Early and late in practice, the keypad used for the right hand was briefly relocated from the front of the participants to 90° at their right side. The results indicate that after 600 practice trials, executing a keying sequence relies heavily on a spatial cross-hand representation in a trunk- or head-based reference frame that after about only 15 trials is fully adjusted to the changed hand location. The hand location effect was not found with the last sequence element. This is attributed to the application of explicit knowledge. The between-hand transitions appeared to induce initial segmentation in some of the participants, but this did not consolidate into a concatenation point of successive motor chunks.


Maternal insulin resistance in pregnancy is associated with fetal fat deposition: findings from a longitudinal study.
Newborns exhibit substantial variation in fat mass accretion over gestation. These individual differences in newborn adiposity extend into infancy and childhood and relate to subsequent risk of obesity and metabolic dysregulation. Maternal glucose homeostasis in pregnancy has been proposed as an underlying mechanism; however, the timing in gestation when maternal glucose regulation influences the progression of fetal fat deposition remain unclear. This study aimed to investigate the cross-sectional and longitudinal association of maternal insulin resistance in early, mid, and late pregnancy with fetal fat deposition in uncomplicated pregnancies. We hypothesized that maternal insulin resistance at early, mid, and late gestation is positively associated with fetal fat deposition, and that the magnitude of the association is greater for the mid and late gestation measures than for the early gestation measure. In a longitudinal study of 137 low-risk pregnancies, a fasting maternal blood sample was obtained and fetal ultrasonography was performed at ≈ 12, 20, and 30 weeks' gestation. Maternal insulin resistance was quantified using the homeostasis model assessment of insulin resistance (fasting insulin×fasting glucose/405). Estimated fetal adiposity was calculated by integrating measurements of cross-sectional arm and thigh percentage fat area and anterior abdominal wall thickness. The associations between maternal homeostasis model assessment of insulin resistance and estimated fetal adiposity and estimated fetal weight were determined by multiple linear regression adjusted for potential confounding factors including maternal age, parity, race and ethnicity, prepregnancy body mass index, gestational weight gain per week, fetal sex, and gestational age at assessments. Maternal homeostasis model assessment of insulin resistance at ≈ 12, 20, and 30 weeks was 2.79±1.79 (±standard deviation), 2.78±1.54, and 3.76±2.30, respectively. Homeostasis model assessment of insulin resistance at 20 weeks was positively associated with estimated fetal adiposity at 20 weeks (r=0.261; P=.005). Homeostasis model assessment of insulin resistance at 20 weeks (r=0.215; P=.011) and 30 weeks (r=0.285; P=.001) were also positively associated with estimated fetal adiposity at 30 weeks. These relationships remained significant after adjustment for confounding factors. There was no significant correlation between homeostasis model assessment of insulin resistance and estimated fetal weight at 20 and 30 weeks' gestation. In low-risk pregnancies, maternal insulin resistance at mid and late but not early pregnancy is significantly associated with fetal adiposity but not with fetal weight. Maternal insulin resistance in mid-gestation could provide a basis for risk identification and interventions that target child adiposity.


Domino synthesis of protochromic "ON-OFF-ON" luminescent 2-styryl quinolines.
The microwave-assisted coupling-isomerization reaction (MACIR) opens a straightforward domino access to 2-styryl quinolines in good to excellent yields. The push-pull character of these lumophores can be enhanced by placing a dimethyl amino group as an auxochrome in the para-position of the styryl moiety whereas anti-auxochromes are located in the 6-position of the quinoline part. The optical absorption and emission properties of the compounds were studied in solvents of different polarity and at various pH. The pronounced proto- and solvochromicity of the absorption and emission properties qualify them as luminescent pH sensors with "ON-OFF-ON" emission profiles triggered by pH variation over a broad pH range. The electronic structure of the chromophores is rationalized by DFT calculations.


Glass-Fiber-based MR-safe Guidewire for MR Imaging-guided Endovascular Interventions: In Vitro and Preclinical in Vivo Feasibility Study.
Purpose To evaluate glass-fiber-based guidewires that are safe for magnetic resonance (MR) imaging-guided endovascular interventions by using a phantom and an in vivo swine model. Materials and Methods MR imaging-safe guidewires were made from micropultruded glass and/or aramid fibers and epoxy resin with diameters of 0.89 mm (0.035 inch) for standard and stiff guidewires and 0.36 mm (0.014 inch) for micro guidewires. MR imaging visibility and mechanical properties were assessed in a pulsatile flow model. After approval was obtained from the institutional animal care and use committee, MR imaging guidewires were evaluated for standard endovascular procedures in nine pigs. Real-time steady-state free-precession sequences were used for MR imaging-guided catheterization, balloon dilation, and stent implantation into aorto-iliac/visceral arteries and the vena cava (temporal resolution, five images per second; and spatial resolution, 150-mm field of view, and 128 × 128 matrix) with a 1.5-T clinical imager. Visualization with the guidewires was rated on a four-point scale, handling was rated on a three-point scale, and catheterization times for different vessel regions were determined by two interventional radiologists. Afterward, handling ratings and catheterization times were obtained for standard nitinol guidewires during x-ray-based fluoroscopy. Cannulation times, signal intensity in each vessel region, and visualization and handling ratings were measured for the MR imaging guidewires. Bland-Altman analysis was performed for inter- and intraobserver variability of cannulation time. Spearman rank correlation was used to compare handling of MR imaging guidewires and standard nitinol guidewires. Results MR imaging guidewires were characterized by good to excellent visibility, with a continuous artifact of 2 mm in diameter and 4 × 8-mm ball-shaped tip marker. Stiffness, flexibility, and guidance reflected comparable times for all in vitro and in vivo procedures with both the MR imaging and standard nitinol guidewires. Standard and micro MR imaging guidewires were most suitable for the iliac crossover maneuver. Phantom visceral artery cannulation was easier with standard and micro MR imaging guidewires. The stiff MR imaging guidewire provided the best support for cannulation of the swine aorta and vena cava. All interventional procedures were performed successfully without complications. Conclusion Preliminary results showed that the use of glass-fiber-based guidewires for evaluation of MR imaging-guided endovascular interventions is technically feasible and safe in a swine model, and potentially, in humans. © RSNA, 2017 Online supplemental material is available for this article.


Prophylactic use of myelopoietic growth factors in children after myelosuppressive and myeloablative therapy.
Judicious use of myelopoietic colony-stimulating factors is not well defined and is the source of ongoing controversy in the pediatric patient population. Prophylactic colony-stimulating factors may provide little clinically relevant benefits in children with hematologic malignancies or solid tumors after myelosuppressive chemotherapy. Although several studies demonstrated that recombinant human granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor accelerate neutrophil engraftment after myeloablative therapy and stem cell transplantation, their use did not alter morbidity or mortality after stem cell transplantation and has been associated with delayed platelet engraftment. Large prospective randomized multicenter studies are necessary to demonstrate an improvement in infectious complications, duration of hospitalization, overall survival, and cost-benefit ratio with the prophylactic use of myelopoietic growth factors after myelosuppressive or myeloablative chemotherapy in children and adolescents. Additional pediatric studies comparing the safety, efficacy, and cost effectiveness of granulocyte colony-stimulating factor versus granulocyte macrophage colony-stimulating factor are needed.


Reaching out to retirees.
The numbers pertaining to the approaching demographic boom in health-care-related expenditures are eye-popping: Health-related financial products to help retiring baby boomers deal with out-of-pocket costs alone will generate up to 80 billion dollars in revenues and 8-12 billion dollars in pre-tax profits by 2014. But health insurers will have to refocus their efforts if they want to take full advantage of this opportunity. (For more, see "Turning Subscribers Into Customers: The Future Is Now" in the July/August issue, the first in this two-part series.) Two areas are critical: product innovation to provide comprehensive solutions that meet seniors' needs more effectively, and advice-based distribution that creates privileged customer relationships.


Input transformation by dendritic spines of pyramidal neurons.
In the mammalian brain, most inputs received by a neuron are formed on the dendritic tree. In the neocortex, the dendrites of pyramidal neurons are covered by thousands of tiny protrusions known as dendritic spines, which are the major recipient sites for excitatory synaptic information in the brain. Their peculiar morphology, with a small head connected to the dendritic shaft by a slender neck, has inspired decades of theoretical and more recently experimental work in an attempt to understand how excitatory synaptic inputs are processed, stored and integrated in pyramidal neurons. Advances in electrophysiological, optical and genetic tools are now enabling us to unravel the biophysical and molecular mechanisms controlling spine function in health and disease. Here I highlight relevant findings, challenges and hypotheses on spine function, with an emphasis on the electrical properties of spines and on how these affect the storage and integration of excitatory synaptic inputs in pyramidal neurons. In an attempt to make sense of the published data, I propose that the raison d'etre for dendritic spines lies in their ability to undergo activity-dependent structural and molecular changes that can modify synaptic strength, and hence alter the gain of the linearly integrated sub-threshold depolarizations in pyramidal neuron dendrites before the generation of a dendritic spike.


The effect of transforming growth factor-beta on mouse mesangial cell proliferation.
The factors which regulate mesangial cell growth are of importance in determining the cellular lesions of nephritis. In this communication, we report that transforming growth factor-beta (TGF-beta) exerts a suppressive effect on mesangial cell 3H-thymidine uptake. Furthermore, TGF-beta antagonizes the mitogenic effect of epidermal growth factor (EGF) on DNA synthesis. The concomitant presence of TGF-beta in the cell cultures is not required for its effect since cells pretreated with the substance and rinsed of it showed suppressed 3H-thymidine uptake and did not respond to EGF. The effect of TGF-beta can also be demonstrated on cells committed to proliferate by the prior addition of EGF. The results of the study have relevance to the mechanisms underlying the histologic lesions of immune-mediated nephritis.


Comparison of Ticagrelor Versus Clopidogrel on Cerebrovascular Microembolic Events and Platelet Inhibition during Transcatheter Aortic Valve Implantation.
The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during transcatheter aortic valve implantation (TAVI) are unknown. Our aim was to evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events in patients undergoing TAVI. Patients scheduled for TAVI were randomized previous to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions. Among 90 patients randomized, 6 had an inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p <0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension, aortic valve calcium content, procedural ACT, and pre-implantation balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95% CI: [-335.7, -176.5]) fewer total procedural HITS than patients on clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10, 74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p <0.001, and correlated significantly with procedural HITS (r = 0.5, p <0.05). In conclusion, ticagrelor resulted in fewer procedural HITS, compared with clopidogrel, in patients undergoing TAVI, while achieving greater platelet inhibition.


Purification, crystallization and preliminary crystallographic studies of plant S-adenosyl-L-homocysteine hydrolase (Lupinus luteus).
By degrading S-adenosyl-L-homocysteine, which is a byproduct of S-adenosyl-L-methionine-dependent methylation reactions, S-adenosyl-L-homocysteine hydrolase (SAHase) acts as a regulator of cellular methylation processes. S-Adenosyl-L-homocysteine hydrolase from the leguminose plant yellow lupin (Lupinus luteus), LlSAHase, which is composed of 485 amino acids and has a molecular weight of 55 kDa, has been cloned, expressed in Escherichia coli and purified. Crystals of LlSAHase in complex with adenosine were obtained by the hanging-drop vapour-diffusion method using 20%(w/v) PEG 4000 and 10%(v/v) 2-propanol as precipitants in 0.1 M Tris-HCl buffer pH 8.0. The crystals were tetragonal, space group P4(3)2(1)2, with unit-cell parameters a = 122.4, c = 126.5 A and contained two protein molecules in the asymmetric unit, corresponding to the functional dimeric form of the enzyme. Atomic resolution (1.17 A) X-ray diffraction data have been collected using synchrotron radiation.


Minimally invasive guided bone regeneration.
Guided bone regeneration (GBR) is indicated when there is a volume deficiency of the residual ridge that prohibits implantation or optimal implant installation for esthetic and functional needs. Our objective is to describe a new minimally invasive GBR and report its clinical application in several patients. A vertical incision is made mesial to the augmentation zone. The periosteum is initially elevated with a miniature chisel, and then through a series of sequential balloon inflations. This yields a tunnel with adequate space for membrane insertion, decortication, and grafting with substitute bone and platelet rich fibrin (PRF) filling. Primary closure is obtained by 2 or 3 simple interrupted sutures. Vertical and horizontal gains were measured on computerized tomography obtained before and 5 to 6 months after the procedure. Eleven patients were treated with this procedure. There were no significant adverse events. The range of vertical gain was 2.4 to 5.1 mm, while horizontal gain measured 1.3 to 3.9 mm. Implants were successfully placed in 6 patients.


Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas.
Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.


[Development of a perceived social support scale: for a Japanese population].
Social support is increasingly attracting interest in as a factor in epidemiological research of disease risks. However, at present, few methods for measuring social support that can be credited as having reliability and validity exist in Japan. Therefore a perceived social support scale was developed in relation to a population study of a town in Fukuoka prefecture. A method for measuring functional support from several external sources was designed consisting of a self-administered test provided with only two available response options--yes & no. Pretests were conducted twice in order to evaluate content validity and adjust the number of determinants and resulted in spouse, family members, and friends being selected to be primary sources of support. A factor analysis was applied to select 10 conditions with high internal consistency for each of the sources. Responses were scored 0 or 1, for 'no' or 'yes,' respectively. Subsequently each set of 10 variables was summed into an index ranking social support conditions for each of the three sources. The three highest ranking indicators from each of the respective sources were then integrated into a single comprehensive total social support score of the individuals. The inquiry method was applied on 277 adults, aged from 40 to 69 years, in the town. Intercorrelation between the indicators of support derived from the three sources was low and coefficients of reliability ranged from 0.892 to 0.978. The score of each set of the 10 variables were incorporated into a principal components analysis in order to determine factorial validity. All of the first factor loadings of the items measuring support from both spouse and family were greater than 0.7 and high eigenvalues were obtained. Therefore the methods applied to spouse and family were considered adequate to measure a given construct. The items measuring support from friends were divided into two factors, emotional support and tangible support.


The possibility of using celiac trunk branches as coronary artery bypass grafts.
The internal mammary artery has proved to be superior to the saphenous vein for coronary artery bypass grafting, because of its arterial nature and closer approximation in size to the coronary arteries. But the internal mammary artery cannot reach the posterior surface of the heart as a pedicled graft. Two suitable intra-abdominal grafts can reach that surface, viz. the right gastroepiploic artery and the splenic artery. In experiments on eight dogs (weight 9-13.5 kg), the gastroepiploic artery was found to be too small for coronary artery anastomosis, and therefore the splenic artery was used. The size approximation with coronary artery (diameter less than 1 mm) was good. Four dogs survived the month of the study. In two of them the anastomosis was patent, in another the splenic artery was patent despite occlusion of the anastomosis, and in the fourth dog both anastomosis and graft were thrombosed. The possibility of using visceral arterial grafts in coronary surgery is discussed.


Unpacking cesarean in rural Bangladesh: Who, what, when, and where.
Bangladesh has experienced an alarming increase in birth through cesarean over the last decade. In this article, we examine rural Bangladeshi women's reporting of why they underwent cesarean, who proposed the cesarean, and when in the process, the decision for a surgical birth was made. We conducted a cross-sectional household survey of 2299 women in Kushtia district. Of these, 1233 who gave birth through cesarean completed a supplemental questionnaire. Descriptive statistics were used to report cesarean rates, which were disaggregated by sociodemographic characteristics and by antenatal care contacts with health services. We analyzed women's reported reasons for having a cesarean, when the decision was taken, and who proposed the intervention. Over half (54%) of women gave birth through cesarean. The proportion of cesareans was significantly higher among women with higher educational attainment, higher socioeconomic status, and increased antenatal care during pregnancy, particularly if this care was sought in private facilities (P < .05). Women reported that health service providers primarily proposed the cesarean (73%), followed by family members (21%) and finally, the birthing person themselves (6%). With respect to the reasons for cesarean, 34% of women reported nonmedical reasons (convenience and avoidance of labor pain), and 44% mentioned only medical reasons. Over half of the women reported that the decision to undergo a cesarean was made on the day of birth. Women in rural Bangladesh often report avoidable reasons for cesarean. Better regulation of cesarean services in both public and private health services, as well as improved counseling of women with respect to cesarean indications and their consequences, is recommended.


The detection, diagnosis, and impact of cognitive impairment among inpatients aged 65 years and over in an Irish general hospital - a prospective observational study.
The diagnosis of dementia remains inadequate, even within clinical settings. Data on rates and degree of impairment among inpatients are vital for service planning and the provision of appropriate patient care as Ireland's population ages. Every patient aged 65 years and over admitted over a two-week period was invited to participate. Those who met inclusion criteria were screened for delirium then underwent cognitive screening. Demographic, functional, and outcome data were obtained from medical records, participants, and family. Consent to participate was obtained from 68.6% of the eligible population. Data for 143 patients were obtained. Mean age 78.1 years. 27.3% met criteria for dementia and 21% had mild cognitive impairment (MCI). Only 41% of those with dementia and 10% of those with MCI had a previously documented impairment. Between-group analysis showed differences in length of stay (p = 0.003), number of readmissions in 12 months (p = 0.036), and likelihood of returning home (p = 0.039) between the dementia and normal groups. MCI outcomes were similar to the normal group. No difference was seen for one-year mortality. Effects were less pronounced on multivariate analysis but continued to show a significant effect on length of stay even after controlling for demographics, personal and family history, and anxiety and depression screening scores. Patients with dementia remained in hospital 15.3 days longer (p = 0.047). A diagnosis is the single biggest contributing factor to length of stay in our regression model. Cognitive impairment is pervasive and under-recognized in the acute hospital and impacts negatively on patient outcomes.


Reducing the oral contrast dose in CT colonography: evaluation of faecal tagging quality and patient acceptance.
To evaluate the minimal iodine contrast medium load necessary for an optimal computed tomography colonography tagging quality. Faecal occult blood test positive patients were randomly selected for one of three iodine bowel preparations: (1) 3 × 50 ml meglumine ioxithalamate (45 g iodine), (2) 4 × 25 ml meglumine ioxithalamate (30 g iodine); or (3) 3 × 25 ml (22.5 g iodine) meglumine ioxithalamate. Two experienced readers assessed the tagging quality per colonic segment on a five-point scale and the presence of adherent stool. Also semi-automatic homogeneity measurements were performed. Patient acceptance was assessed with questionnaires. Of 70 eligible patients, 45 patients participated (25 males, mean age 62 years). Each preparation group contained 15 patients. The quality of tagging was insufficient (score 1-2) in 0% of segments in group 1; 4% in group 2 (p<0.01 versus group 1); and 5% in group 3 (p=0.06 versus group 1). In group 1 in 11% of the segments adherent stool was present compared with 49% in group 2 and 41% in group 3 (p<0.01, group 2 and 3 versus group 1). Homogeneity was 85, 102 (p<0.01), and 91 SD HU (p=0.26) in groups 1, 2, and 3, respectively. In group 1 two patients experienced no burden after contrast agent ingestion compared to one patient in group 2 and nine patients in group 3 (p=0.017). A dose of 3 × 50 ml meglumine ioxithalamate is advisable for an optimal tagging quality despite beneficial effects on the patient acceptance in patients receiving a lower dose.


Downregulation of calbindin 1, a calcium-binding protein, reduces the proliferation of osteosarcoma cells.
Osteosarcoma is the most common type of primary malignant bone tumor and has a high propensity to metastasize to the lungs and bones. Calbindin 1 (CALB1) is a constituent Ca2+ binding protein, which can prevent apoptotic death in several cell types induced through various pro-apoptotic signaling pathways. To investigate whether CALB1 is implicated in the tumor growth of human osteosarcoma, two different short hairpin RNAs (shRNAs) against CALB1 were used for CALB1-knockdown in osteosarcoma U2OS cells. The U2OS cells were divided into three groups: Two groups with CALB1 knockdown (CALB1-shRNA 1 and CALB1-shRNA 2) and one control group (Con-shRNA). Reverse transcription-quantitative polymerase chain reaction and western blot analysis confirmed that the CALB1-shRNA 1- and 2-infected cells exhibited significantly lower levels of CALB1 gene and protein expression compared with the Con-shRNA group. The proliferation and colony formation abilities were significantly inhibited in CALB1-deficient U2OS cells compared with the control, as measured using an MTT assay and crystal violet staining. Flow cytometry revealed that the number of CALB1-shRNA 2-injected cells was increased in the G0/G1 and G2/M phases, but decreased in the S phase, compared with the control group. The assessment of apoptosis and necrosis using Annexin V/7-aminoactinomycin D demonstrated that there was a significantly higher percentage of necrotic, early apoptotic, and late apoptotic cells, but a significantly lower percentage of viable cells in U2OS cells with CALB1-knockdown compared with the control group. In conclusion, CALB1 contributes to protecting osteosarcoma cells from apoptosis and provides a potential novel target for gene therapy to treat patients with osteosarcoma.


Design of biomimetic habitats for tissue engineering with P-15, a synthetic peptide analogue of collagen.
In tissues, collagen forms the scaffold for cell attachment and migration, and it modulates cell differentiation and morphogenesis by mediating the flux of chemical and mechanical stimuli. We are constructing biomimetic environments by immobilizing a collagen-derived high-affinity cell-binding peptide P-15 in three-dimensional (3-D) templates. The cell-binding peptide can be expected to transduce mechanical forces. In their physiological environment, periodontal ligament fibroblasts (PDLF) are subject to significant mechanical forces. We have examined the behavior of human PDLF in culture on particulate bovine anorganic bone mineral (ABM) coated with P-15 (ABM-P-15). Greater numbers of cells associated with ABM-P-15 compared to ABM alone. Higher levels of incorporation of radiolabeled precursors in DNA and protein were consistent with the presence of larger numbers of cells on ABM-P-15 compared to ABM cultures. Scanning electron microscopic examination showed that cultures on ABM-P-15 generated highly oriented 3-D colonies of elongated cells and formed copious amounts of fibrous as well as membranous matrix reminiscent of ligamentous structures. PDLF cultured on ABM formed sparse monolayers with little order and a meager matrix. Alizarin Red stained the matrix of particle associated cells and inter-particle cellular bridges in P-15-associated cultures, indicating mineralization. 3-D colony formation and ordering of cells along with increased mineralization suggests that the coupling of cells to the ABM matrix through P-15 may provide a biomimetic environment permissive for cell differentiation and morphogenesis. Our studies suggest that ABM-P-15 templates may be effective as endosseous grafts, and, when seeded with PDLF, these matrices may serve as tissue engineered substitutes for autologous bone grafts.


Machine learning for a sustainable energy future.
Transitioning from fossil fuels to renewable energy sources is a critical global challenge; it demands advances - at the materials, devices and systems levels - for the efficient harvesting, storage, conversion and management of renewable energy. Energy researchers have begun to incorporate machine learning (ML) techniques to accelerate these advances. In this Perspective, we highlight recent advances in ML-driven energy research, outline current and future challenges, and describe what is required to make the best use of ML techniques. We introduce a set of key performance indicators with which to compare the benefits of different ML-accelerated workflows for energy research. We discuss and evaluate the latest advances in applying ML to the development of energy harvesting (photovoltaics), storage (batteries), conversion (electrocatalysis) and management (smart grids). Finally, we offer an overview of potential research areas in the energy field that stand to benefit further from the application of ML.


ED-PALS: A Comprehensive Palliative Care Service for Oncology Patients in the Emergency Department.
The American College of Emergency Physicians has identified early palliative care referral for patients with advanced cancer as a key competent of the Choosing Wisely campaign. To study the feasibility of a new 3-way model of care between emergency department (ED), hospital palliative care department, and inpatient/home hospice. This was a prospective, descriptive study that included oncology patients who attended the hospital ED over a 3-year period from January 2015 to December 2017. The inclusion criteria were as follows: (1) presence of metastatic cancer with either; (2) any 1 of the following symptoms: pain, dyspnea, nausea and vomiting, delirium, or swelling; or (3) potential care difficulties (requiring home hospice care or inpatient hospice). A total of 340 patients were referred from the ED. Mean age was 72 years, 59% were males and 41% females, and the majority (88%) were Chinese. The most common cancers were lung 89 (26%), colorectal 71 (21%), and hepatobiliary cancer 49 (14%). The most common symptoms on Edmonton Symptom Assessment Scale scoring were pain (34%), poor appetite (31%), and dyspnea (26%). This tripartite model of palliative care, hospice, and ED collaboration allows earlier access to palliative care in the ED and direct admissions to the palliative care unit and comfort care rooms. The ED patients who did not need admission were also attended to in the palliative care "Hot Clinics" within a week with home hospice help. Patients who required inpatient hospice care were directly admitted there from the ED.


Knowledge, attitudes and practice preference regarding drug prescriptions of resident dental doctors: A quantitative study.
There has been an increasing need to examine undergraduate dental education in prescribing to confirm whether it is establishing the goal of producing safe and rational prescribers. Prescribing by dental doctors after graduation is influenced by a variety of factors: the different teaching approaches of the professors at the clinics and in the pharmacology course, fellow colleagues and even the information provided by the pharmaceutical industry. The aim of this study was to assess the prescription knowledge, attitude, preference and common errors made by junior resident dental doctors in the dental department of two medical colleges and hospitals in India. Dental graduates (n = 70) who served as junior resident doctors at dental departments and graduated from various dental colleges in India, participated in the study. A survey was conducted among 70 junior resident dental doctors in the dental department, applying a previously validated questionnaire consisting of open-ended questions. The knowledge, attitude and practice preference of resident doctors regarding drug prescription and common errors made by them were analyzed and reviewed. The most frequent response to each question was considered the most significant. The most common reason for prescribing medication was infection (n = 33, 47.14%) and the most widely prescribed antibiotic was amoxicillin (n = 29, 41.42%). The most frequent error reported by resident doctors was lack of knowledge about drug posology (n = 31, 44.28%). Maximum number of junior doctors acquired the information for prescribing drugs from their faculty (n = 33, 47.14%). Around 45.71% dental doctors had no knowledge about the WHO Guide to Good Prescribing. About 50- 60% doctors had knowledge about the dose, frequency, duration and route of administration of the drug prescribed. While prescribing drugs to the patient, 25.71% doctors explain the disease and treatment properly to the patient; 24.28% doctors do not criticize other doctors, and 10% doctors address the patient by name. The results of this study indicate that resident dental doctors' knowledge, attitudes and behavior about the drug prescription need to be improved. More studies are needed to determine whether this issue affects the quality of patient care and the effectiveness and safety of treatments.


Excitotoxic lesions of the rhinal cortex in the baboon differentially affect visual recognition memory, habit memory and spatial executive functions.
To specify the functional role of the rhinal cortex, baboons with bilateral excitotoxic lesions of the rhinal cortex (RH group) were tested on a series of computerized memory and learning tasks. Preoperatively, they were trained to and then tested on a delayed nonmatching-to-sample (DNMS) task with trial-unique stimuli. Postoperatively, this visual recognition memory task was given twice. As compared to a sham-operated group, the RH group showed good retention of rule learning and were unimpaired on the Delay memory subtest. Performance on the List Length memory subtest was, however, severely impaired at both postoperative evaluations, with a significant negative correlation between cognitive performance and neuronal loss in rhinal areas. Visual habit memory and spatial working memory were assessed postoperatively only, using a concurrent discrimination learning task and both a delayed-response task (with a two- and four-location choice) and a delayed alternation task, respectively. The RH group was unimpaired on the first two tasks and was even faster than the controls in learning the delayed-response task with four locations. Finally, most RH baboons failed to learn the delayed alternation task within the limits of testing. These results indicate that neuronal loss in the rhinal cortex is sufficient to impair visual recognition memory, and extend the implication of this area to spatial executive functions. Furthermore, the observation of impaired recognition memory and executive processes with preserved procedural memory and retrograde memory suggests that damage to the rhinal cortex probably participates in the cognitive deficits typical of the early stages of Alzheimer's disease.


Stimulation with autologous lymphoblastoid cell lines: lysis of Epstein-Barr virus-positive and -negative cell lines by two phenotypically distinguishable effector cell populations.
Human lymphocytes, stimulated in vitro for 6 days with x-irradiated or glutaraldehyde-treated autologous Epstein-Barr (EB) virus-transformed lymphoblastoid cell lines (LCL), are cytotoxic for autologous and allogeneic EB+ LCLs as well as for several EB- cell lines that are also susceptible to lysis by interferon-activated natural killer (NK) cells. To determine whether the apparent nonspecific lysis mediated by LCL-stimulated cells is due to a mixture of effector cells directed against different target cells, advantage was taken of our recent finding that monoclonal antibody OKT8 reacts with human cytotoxic T lymphocytes but not with NK cells or NK-like cells generated in mixed leukocyte cultures. The depletion of OKT8+ cells from LCL-stimulated cultures by treatment with OKT8 and complement abolished or markedly depleted cytotoxicity against all EB+ target cells tested, whereas cytotoxicity against EB-, NK-sensitive cell lines including K562, MOLT-4 and HSB-2 was not or only minimally reduced. These results indicate that stimulation with autologous LCL results in the generation of OKT8+ cytotoxic T lymphocytes that lyse EB virus-transformed LCL and OKT8- NK-like cells that lyse EB-, NK-sensitive cells.


Chemokine orchestration of autoimmune thyroiditis.
Chemokines are low-molecular-weight proteins that attract leukocytes and other cell types, via interaction with G protein-coupled receptors. Chemokines control leukocyte migration not only during inflammatory processes, but also throughout ontogeny and differentiation of lymphoid tissues. They have been involved in the pathogenesis of numerous diseases, such as human immunodeficiency virus infection, allergy, atherosclerosis, cancer, and autoimmunity. The number of studies focusing on chemokine biology is expanding exponentially. For example, searching PubMed for the terms "thyroid" and "chemokine" retrieved 1 article in 1980s, 18 articles in 1990s, and 81 articles from 2000 to July 2007. This review will focus on studies analyzing the role of chemokine in autoimmune thyroiditis (Graves' disease and Hashimoto's thyroiditis), performed in both patients and experimental animals. The goal is to emphasize how a better understanding of chemokine biology has advanced our knowledge of the pathogenesis of autoimmune thyroiditis.


Diversifying residents' outpatient psychiatry experience: a contemporary model for academic outpatient psychiatry clinics.
A diversified, outpatient experience is an important part of psychiatric training, yet challenging to attain. We describe a multiple, subspecialty psychiatry clinic model for 3rd year psychiatry residents. Evaluation findings based on its initial implementation indicated improved resident supervision, better therapeutic alliance and an overall increase in satisfaction. This model facilitates resident exposure to diverse patients and treatment modalities as well as faculty development of expertise. It also promotes academic training excellence.


Impact of LiBOB additive on cycle-performance degradation of lithium mono-chelated borate electrolytes: minimize the crosstalk-derived deterioration.
Novel electrolyte systems are required to further improve the performance and ensure the safety of lithium-ion batteries. Lithium-monochelated borates with trifluoromethylated ligands are used as electrolytes for lithium-ion batteries (LIBs) with a lithium bis(oxalato)borate (LiBOB) additive. The capacity decay and extremely high resistance after the cycle test at 60 °C are dramatically suppressed by the addition of LiBOB. Half-cell measurements, X-ray photoelectron spectroscopy (XPS), and electrochemical impedance spectroscopy (EIS) suggested that the reductive decomposition products of the electrolytes at the negative electrode significantly increased the resistance at the positive electrode, which originated from the crosstalk of the decomposition species formed at the negative electrode. Further analysis confirmed the importance of the LiBOB-derived solid electrolyte interphase (SEI) at the negative electrode, which suppressed the formation of crosstalk species at the negative electrode and effectively suppressed the increase in resistance of the positive electrode. This study provides a reliable and promising approach for designing high-performance electrolytes with lithium borate and emphasizes the importance of considering the reactions occurring at both electrodes to improve battery performance.


Safety and immunogenicity of 26-valent group a streptococcus vaccine in healthy adult volunteers.
Group A streptococcus (GAS) causes illness ranging from uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic shock, and rheumatic fever. Attempts to develop an M protein-based vaccine have been hindered by the fact that some M proteins elicit both protective antibodies and antibodies that cross-react with human tissues. New molecular techniques have allowed the previous obstacles to be largely overcome. The vaccine is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that contain N-terminal peptides from streptococcal protective antigen and M proteins of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty healthy adult subjects received intramuscular 26-valent GAS vaccine (400 microg) at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and immunogenicity using assays for tissue cross-reactive antibodies, type-specific M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M protein antibodies. The incidence of local reactogenicity was similar to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject developed evidence of rheumatogenicity or nephritogenicity, and no induction of human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic peptides evoked a >4-fold increase in the geometric mean antibody titer over baseline. The mean log2 fold-increase in serum antibody titer (+/- standard error of the mean) for all 27 antigens was 3.67 +/- 0.21. A significant mean log2 reduction in streptococcal bacterial counts in serum samples obtained after immunization was seen in opsonization assays for all M serotypes. On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptococcal disease.


The Clinical Importance of Periodic Leg Movements in Sleep.
Periodic leg movements during sleep (PLMS) are commonly found in patients with restless leg syndrome (RLS), but they may occur in other sleep disorders and several medical conditions. Their prevalence increases with age, but they can also be observed in children. During the last decades, very active research has been devoted to determine and understand the pathophysiology, associated events, and clinical significance of PLMS. This chapter tries to sum up the most relevant PLMS-related findings, focusing on the relationship between PLMS and the cardiovascular system, in order to understand the clinical implication of this complex motor phenomenon. PLMS have been associated with sympathetic overactivity, namely surges in nocturnal blood pressure and heart rate, without modification in global autonomic balance. Also, PLMS have been related to inflammatory cellular pathways, with elevated level of inflammatory markers, which are associated with cardiovascular risk. The PLMS-related modulation of the autonomic system and of inflammation may increase cardiovascular and cerebrovascular risk in subjects with frequent PLMS. Moreover, also, comorbidities associated with PLMS may play a synergic role in worsening the cardiovascular risk and the consequent mortality and morbidity. Furthermore, little is known about pathophysiological correlates in children with PLMS and their chronic implication on the cardiovascular and cerebrovascular systems. A few studies have suggested that treating PLMS with dopaminergic drugs may reduce their associated sympathetic overactivity and modify disease progression. Definitely, further research is needed to assess the clinical impact of PLMS, associated or not with RLS, and above all the long-term impact of treating PLMS on cardiovascular risk, morbidity, and mortality.


New iron-based mixed-polyanion cathodes for lithium and sodium rechargeable batteries: combined first principles calculations and experimental study.
New iron-based mixed-polyanion compounds Li(x)Na(4-x)Fe(3)(PO(4))(2)(P(2)O(7)) (x = 0-3) were synthesized, and their crystal structures were determined. The new compounds contained three-dimensional (3D)sodium/lithium paths supported by P(2)O(7) pillars in the crystal. First principles calculations identified the complex 3D paths with their activation barriers and revealed them as fast ionic conductors. The reversible electrode operation was found in both Li and Na cells with capacities of one-electron reaction per Fe atom, 140 and 129 mAh g(-1), respectively. The redox potential of each phase was ∼3.4 V (vs Li) for the Li-ion cell and ∼3.2 V (vs Na) for the Na-ion cell. The properties of high power, small volume change, and high thermal stability were also recognized, presenting this new compound as a potential competitor to other iron-based electrodes such as Li(2)FeP(2)O(7), Li(2)FePO(4)F, and LiFePO(4).


Cyclic hair-loss and regrowth in transgenic mice overexpressing an intermediate filament gene.
We have produced transgenic mice containing up to 250 copies of a sheep wool intermediate filament keratin gene to study the effect of its expression on hair structure and development. Several transgenic lines expressed the gene and in the one containing 250 transgenes, a pattern of hair-loss and regrowth was stably established. Successive waves of hair growth follow periods of denuding like the natural progression of hairs in the mouse hair cycle. By in situ hybridization we have shown that the sheep transgenes are expressed at the correct stage in mouse hair development and at a high level. The transgenic hairs contain not only an elevated level of intermediate filament keratin protein but also a decreased level of the filament-associated proteins. This imbalance disrupts the normal ordered array of these proteins in the cells of the hair cortex and leads to weakened fibres which are prematurely lost.


Left ventricular free-wall rupture that occurred during a cardiopulmonary exercise test.
Although exercise testing has become a standard procedure before discharge for patients with acute coronary syndrome, a fatal accident during the test is extremely rare. A 60-year-old man was admitted for a non-ST-segment elevation myocardial infarction. A coronary angiogram showed stenosis at the distal lesion of the circumflex, and a balloon angioplasty was performed. His recovery was smooth, and a cardiopulmonary exercise test was performed 5 days after admission. At 2.5 metabolic equivalents, he suddenly went into cardiac arrest, and percutaneous cardiopulmonary support was initiated. Echocardiography revealed the presence of a large amount of pericardial effusion, and emergency cardiac surgery was performed to repair the free-wall rupture. This highlights the importance of careful monitoring of patients with percutaneous coronary intervention during cardiopulmonary exercise testing.


DNA-Aptamer Raised against Receptor for Advanced Glycation End Products Improves Survival Rate in Septic Mice.
Despite remarkable scientific advances in the understanding of molecular mechanisms for sepsis, therapeutic options are far from satisfactory. High mobility group box 1 (HMGB1), one of the ligands of receptor for advanced glycation end products (RAGE), is a late mediator of lethality in septic mice. We have recently found that the DNA-aptamer raised against RAGE (RAGE-aptamer) significantly blocks experimental diabetic nephropathy and melanoma growth and metastasis. We examined the effects of RAGE-aptamer on sepsis score, survival rate, and inflammatory and oxidative stress responses in serum, peripheral monocytes, kidneys and livers of lipopolysaccharide- (LPS-) injected mice, and on LPS-exposed THP-1 cells. RAGE-aptamer inhibited the binding of HMGB1 to RAGE in vitro. RAGE-aptamer significantly (P = 0.002) improved sepsis score at 8 hours after LPS injection and survival rate at 24 hours (P < 0.01, 70%) in septic mice compared with LPS+vehicle- or LPS+control-aptamer-treated mice. RAGE-aptamer treatment significantly decreased expression of p-NF-κB p65, an active form of redox-sensitive transcriptional factor, NF-κB and gene or protein expression of TNF-α, IL-1β, IL-6, and HMGB1 in serum, peripheral monocytes, and kidneys of septic mice in association with the reduction of oxidative stress and improvement of metabolic acidosis, renal and liver damage. LPS-induced oxidative stress, inflammatory reactions, and growth suppression in THP-1 cells were significantly blocked by RAGE-aptamer. Our present study suggests that RAGE-aptamer could attenuate multiple organ damage in LPS-injected septic mice partly by inhibiting the inflammatory reactions via suppression of HMGB1-RAGE interaction.


Strengthening sociometric prediction: scientific advances in the assessment of children's peer relations.
This study assessed the strength of sociometric classification in the prediction of concurrent sociobehavioral adjustment. Differential adjustment for subgroups of unclassified children were also examined. Participants were 881 fifth graders (ages 9 to 12). Classification strength (CS) and unclassified subgroups were determined through newly developed algorithms. CS added significantly to the prediction of all areas of adjustment. For example, highly rejected children were at extreme risk for victimization whereas highly controversial children were most likely to be bullies and relationally aggressive. Unclassified subgroups were found to exhibit adjustment problems mirroring those of their extreme status group counterparts. Findings support that increasing the sensitivity of sociometric measurement results in both greater predictive strength and enhanced understanding of underlying social processes.


Review and Long-Term Outcomes of Cruciate Ligament Reconstruction versus Conservative Treatment in Siblings with Congenital Anterior Cruciate Ligament Aplasia.
There is no consensus on the best treatment for anterior cruciate ligament hypoplasia or aplasia. To our knowledge, no comparative study between operative and conservative treatment of this condition has ever been performed. Conservative treatment is a viable alternative to surgery for ACL aplasia. Two siblings were examined at our outpatient clinic. The male patient underwent bilateral ACL reconstruction, while his sister was treated conservatively. Our results show a worse long-term outcome for the operative patient. At her last follow-up, the female patient treated conservatively showed subjective improvement in stability and gait. A review of the literature shows inconsistent outcomes after reconstruction in contrast to reports with cruciate ligament agenesis that did not undergo reconstruction with acceptable to good outcomes. Cruciate reconstruction should be reserved for cases of impaired articular instability, objectively manifest in the frequency of giving-way episodes. Treatment depends on the patient's condition and expectations. Surgery should therefore only be suggested after proper patient counseling.


Reconstructing Early Industrial Contributions to Legacy Trace Metal Contamination in Southwestern Pennsylvania.
Early industrial trace metal loadings are poorly characterized but potentially substantial sources of trace metals to the landscape. The magnitude of legacy contamination in southwestern Pennsylvania, the cradle of North American fossil fuel industrialization, is reconstructed from trace metal concentrations in a sediment core with proxies including major and trace metal chemistry, bulk density, and magnetic susceptibility. Trace metal chemistry in this sediment record reflects 19th and 20th century land use and industry. In particular, early 19th century arsenic loadings to the lake are elevated from pesticides used by early European settlers at a lakeside tannery. Later, sediment barium concentrations rise, likely reflecting the onset of acidic mine drainage from coal operations. Twentieth century zinc, cadmium, and lead concentrations are dominated by emissions from the nearby, infamous Donora Zinc Works yet record both the opening of a nearby coal-fired power plant and amendments to the Clean Air Act. The impact of early industry is substantial and rivals more recent metal fluxes, resulting in a significant potential source of contaminated sediments. Thus, modern assessments of trace metal contamination cannot ignore early industrial inputs, as the potential remobilization of legacy contamination would impact ecosystem and human health.


Decision-making on the use of antimicrobial prophylaxis for dental procedures: a survey of infectious disease consultants and review.
There is debate concerning use of antibiotic prophylaxis before invasive dental procedures for patients at risk of acquiring distant site infection (DSI). We determined the opinions and practices of infectious disease consultants (IDCs) regarding antimicrobial prophylaxis to prevent DSIs that result from invasive dental procedures by conducting a survey of the 797 members of the Infectious Diseases Society of America Emerging Infections Network (477 members [60%] responded). Ninety percent of respondents closely follow the American Heart Association guidelines for antibiotic prophylaxis for patients with valvular heart disease who undergo invasive dental procedures. In contrast, few IDCs recommend prophylaxis for patients with lupus erythematosus, poorly controlled diabetes mellitus, dialysis catheters or shunts, cardiac pacemakers, or ventriculoperitoneal shunts. Twenty-five percent to forty percent of respondents recommended prophylaxis for prosthetic vascular grafts, orthopedic implants, or chemotherapy-induced neutropenia. We conclude that IDCs differ considerably in their assessment of the need for prophylaxis for patients who have noncardiac risk factors for DSI. These differences underscore the need for definitive studies to delineate appropriate candidates for antimicrobial prophylaxis in dental practice.


[Drug susceptibility and homologous analysis on Corynebacterium striatum strains isolated from inpatients].
To explore the molecular epidemiological features and in vitro susceptibility profile of Corynebacterium striatum strains isolated from different sites of inpatients, and further provide new data and idea for clinicians to better get knowledge of the clinical significance of Corynebacterium striatum. Fourty-five strains of Corynebacterium striatum isolated from different sites of inpatients from November, 2013 to March, 2014 in Affiliated hospital of Inner Mongolian medical university, and microdilution method was employed to do in vitro antibiotics susceptibility test. Saline-cotton swab method was used to sample the surrounding environmental surfaces for Corynebacterium striatum carrying patients, and suspected colonies were further identified and in vitro drug susceptibility test were performed. Pulsed Field Gel Electrophoresis(PFGE) method was used to do molecular typing for 41 isolates of Corynebacterium striatum. Fourty-five isolates of Corynebacterium striatum strains were mainly isolated from neurosurgical unit(21 isolates), respiratory unit(8 isolates) and intensive care unit(8 isolates), 39 isolates of which were isolated from lower respiratory tract. The 45 isolates presented an aggregate distribution in the following 3 months, which were December 2013, January 2014 and February 2014.In vitro antibiotics susceptibility test showed that MIC90 for penecillin, erythromycin, tetracycline, ciprofloxacin and clindamycin were 64 µg/ml or higher and the MIC90 for gentamicin, vancomycin and rifampicin were all 0.5 µg/ml. Only one isolate was sensitive to all of the antibiotics tested, except clindamycin. PFGE typing results showed that 41 isolates were divided into 7 genotypes, among which 0002 type and 0006 type were the predominant types and accounted for 63% (26/41) and 22% (9/41), respectively. The isolates from different patients showed high homology, which were isolated from the same unit during the same periods.For surrounding surfaces sampling, Corynebacterium striatum isolating rate was 40% (8/20). The isolates from environmental surfaces and those from the corresponding patients showed identical drug susceptibility profiles. Corynebacterium striatum isolated from inpatients show multi-drug resistant profile, and different isolates from different patients are highly homologous. Specific units, such as neurosurgery unit, respiratory unit and intensive care unit, should reevaluate the clinical significance of Corynebacterium striatum and its relationship with clinical treatment measures supplemented.


[Study on thermostability and photo-isomerization of trans-resveratrol by high performance liquid chromatography and liquid chromatography-electrospray ionization-mass spectrometry].
The thermostability and photo-isomerization reaction mechanism of trans-resveratrol were studied by using high performance liquid chromatography (HPLC) and liquid chromatography-electrospray ionization-mass spectrometry ( LC-ESI-MS). A reversed-phase Hypersil-ODS column was used with the mobile phase consisting of 60/40 methanol-water, with addition of 0.05% trifluoroacetic acid for HPLC, and 0.1% formic acid and 5 mmol/L ammonium formate for LC-ESI-MS, at a flow rate of 0.5 mL/min. Diode array detection was set at 300 nm and the injection volume was 20 or 10 microL. Mass spectrometric conditions were in the negative mode. The results of thermostability test under 4, 20 and 40 degrees C indicated that the concentration of trans-resveratrol, after storage for 600 h, was decreased slightly under 4 degrees C, decreased by 5% under 20 degrees C, and 10% under 40 degrees C. In addition, the photo-isomerization reaction of trans- and cis-resveratrol under 254 nm and 365 nm UV irradiation was investigated by LC-ESI-MS, showing that the isomerization is based on p-status, and that some secondary reactions are radical induced.


High salt intake down-regulates colonic mineralocorticoid receptors, epithelial sodium channels and 11β-hydroxysteroid dehydrogenase type 2.
Besides the kidneys, the gastrointestinal tract is the principal organ responsible for sodium homeostasis. For sodium transport across the cell membranes the epithelial sodium channel (ENaC) is of pivotal relevance. The ENaC is mainly regulated by mineralocorticoid receptor mediated actions. The MR activation by endogenous 11β-hydroxy-glucocorticoids is modulated by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Here we present evidence for intestinal segment specific 11β-HSD2 expression and hypothesize that a high salt intake and/or uninephrectomy (UNX) affects colonic 11β-HSD2, MR and ENaC expression. The 11β-HSD2 activity was measured by means of 3H-corticosterone conversion into 3H-11-dehydrocorticosterone in Sprague Dawley rats on a normal and high salt diet. The activity increased steadily from the ileum to the distal colon by a factor of about 3, an observation in line with the relevance of the distal colon for sodium handling. High salt intake diminished mRNA and protein of 11β-HSD2 by about 50% (p<0.001) and reduced the expression of the MR (p<0.01). The functionally relevant ENaC-β and ENaC-γ expression, a measure of mineralocorticoid action, diminished by more than 50% by high salt intake (p<0.001). The observed changes were present in rats with and without UNX. Thus, colonic epithelial cells appear to contribute to the protective armamentarium of the mammalian body against salt overload, a mechanism not modulated by UNX.


The use of correlation and regression methods in optometry.
Correlation and regression are two of the statistical procedures most widely used by optometrists. However, these tests are often misused or interpreted incorrectly, leading to erroneous conclusions from clinical experiments. This review examines the major statistical tests concerned with correlation and regression that are most likely to arise in clinical investigations in optometry. First, the use, interpretation and limitations of Pearson's product moment correlation coefficient are described. Second, the least squares method of fitting a linear regression to data and for testing how well a regression line fits the data are described. Third, the problems of using linear regression methods in observational studies, if there are errors associated in measuring the independent variable and for predicting a new value of Y for a given X, are discussed. Finally, methods for testing whether a non-linear relationship provides a better fit to the data and for comparing two or more regression lines are considered.


Heterophile antibody interference with thyroid assay.
Immunoassays are one of the main methods of measuring thyroid hormones. They are prone to interference. Interference of the immunoassays has been increasingly recognized as a problem because it may lead to misinterpretation of results resulting in unnecessary investigation and wrong course of treatment. We describe a patient who had interference in her thyroid function measurements (free T4, free T3 and TSH) during the course of treatment for Graves' disease.


Effects of oral hyposensitization therapy with nickel on haemoglobin and haematocrit values in sensitized patients.
Nickel deficiency leads to reduced iron content in organs and to reduced hemoglobin levels and haematocrit counts. We carried out a clinical trial of oral hyposensitization therapy with low doses of nickel on a group of 20 patients affected by systemic allergy to this sensitizer element and with a chronic relapsing low hemoglobin level and haematocrit count. We obtained interesting results on maintaining these values in treated patients.


Gender differences in the associations between age trends of social media interaction and well-being among 10-15 year olds in the UK.
Adolescents are among the highest consumers of social media while research has shown that their well-being decreases with age. The temporal relationship between social media interaction and well-being is not well established. The aim of this study was to examine whether the changes in social media interaction and two well-being measures are related across ages using parallel growth models. Data come from five waves of the youth questionnaire, 10-15 years, of the Understanding Society, the UK Household Longitudinal Study (pooled n = 9859). Social media interaction was assessed through daily frequency of chatting on social websites. Well-being was measured by happiness with six domains of life and the Strengths and Difficulties Questionnaire. Findings suggest gender differences in the relationship between interacting on social media and well-being. There were significant correlations between interacting on social media and well-being intercepts and between social media interaction and well-being slopes among females. Additionally higher social media interaction at age 10 was associated with declines in well-being thereafter for females, but not for males. Results were similar for both measures of well-being. High levels of social media interaction in early adolescence have implications for well-being in later adolescence, particularly for females. The lack of an association among males suggests other factors might be associated with their reduction in well-being with age. These findings contribute to the debate on causality and may inform future policy and interventions.


Molecules-in-molecule estimation of the extent of localization of Kekuléan substructures in polycyclic aromatic hydrocarbons.
This article first revises graph-theoretical (local aromaticity and overall molecular) indices, introduced by M. Randić in 1975, for benzenoid hydrocarbons and somewhat improves them for computer enumeration. This goes beyond total Kekulé structure enumeration, yielding an index calculation useful for the quantitative estimation of localization of different Kekuléan substructures (including ethylene-, benzene-, annulene-, and radialene-units). This may be viewed as a "molecules-in molecule" approach to polycyclic aromatic hydrocarbons within the context of graph theoretical partitioning.


History of chronic toxicity and animal carcinogenicity studies for pharmaceuticals.
During the 20th century, as drug products were being developed to treat both known and emerging human diseases and conditions, determining the safety of these new chemicals became of increasing importance and necessity. For a time, the safety of use in human populations was of question, let alone whether the drug product was truly effective. As such, US and international regulatory agencies have played a major role in establishing standardized testing to evaluate the safety and efficacy of drug products. Pharmacologic and toxicologic evaluation of a new drug in animals is an important part of the pharmaceutical development process prior to its first-time use in humans, as well as its potential chronic use in affected populations. Just as both science and technology have evolved over the past century and further, so have the guidelines that have been put forth to adequately and efficiently evaluate the toxicity of new drugs and their subsequent safety in humans. This review summarizes the historical highlights of the conduct of drug safety evaluations in animals, particularly with regard to chronic toxicity and carcinogenicity assessments, and how we have progressed to our current standards and protocols to ensure safe use of drug products in human populations.


Susceptibility to quantum dot induced lung inflammation differs widely among the Collaborative Cross founder mouse strains.
Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity. Male mice from 8 genetically diverse inbred strains (the Collaborative Cross founder strains) were exposed to CdSe-ZnS core-shell QDs stabilized with an amphiphilic polymer. QD treatment resulted in significant increases in the percentage of neutrophils and levels of cytokines present in bronchoalveolar lavage fluid (BALF) obtained from NOD/ShiLtJ and NZO/HlLtJ mice relative to their saline (Sal) treated controls. Cadmium measurements in lung tissue indicated strain-dependent differences in disposition of QDs in the lung. Total glutathione levels in lung tissue were significantly correlated with percent neutrophils in BALF as well as with lung tissue Cd levels. Our findings indicate that QD-induced acute lung inflammation is mouse strain dependent, that it is heritable, and that the choice of mouse strain is an important consideration in planning QD toxicity studies. These data also suggest that formal genetic analyses using additional strains or recombinant inbred strains from these mice could be useful for discovering potential QD-induced inflammation susceptibility loci.


Study of antiretroviral drug-resistant HIV-1 genotypes in northern Thailand: role of mutagenically separated polymerase chain reaction as a tool for monitoring zidovudine-resistant HIV-1 in resource-limited settings.
As the number of HIV-1-infected individuals receiving antiretroviral drugs has been rapidly increasing in developing countries, there is an urgent need for drug resistance genotype information of non-B subtype HIV-1 and for the establishment of a practical system of monitoring drug-resistant viruses. This study first sequenced the reverse transcriptase region of HIV-1 in 112 infected individuals who had been treated with zidovudine (AZT)/didanosine or AZT/zalcitabine as dual therapy at a government hospital in northern Thailand and then compared the above sequence method with mutagenically separated polymerase chain reaction (MS-PCR) for detecting M41L and K70R mutations. Concordant rates of detecting M41L and K70R mutations by the 2 methods were 96.9% (93/96) and 92.7% (89/96), respectively. The M41L and K70R MS-PCR could detect 86.4% of AZT-resistant strains with any resistance mutation, which was determined by the sequencing method. Then 292 drug-naive individuals were screened for the presence of drug-resistant HIV-1 by the MS-PCR assay and it was found that 2 individuals (0.7%) carried viruses with either the M41L or K70R mutation. It is feasible to test a large number of samples with MS-PCR, which is sensitive, cheap, and easy to perform and does not require sophisticated equipment. The M41L and K70R MS-PCR is potentially a useful tool to monitor the spread of AZT-resistant HIV-1 in resource-limited countries.


Persistent droplet motion in liquid-liquid dewetting.
When a nonvolatile liquid film dewets from a partly compatible liquid substrate, the advancing dewetting front leaves behind droplets formed through a Rayleigh instability mechanism at its rim. We have found that these droplets continue to move in the direction of the dewetting front for extended periods (of order one day) with an initial droplet velocity varying linearly with the droplet size, and a displacement varying logarithmically with time. We attribute this persistent motion to a transient surface tension gradient on the substrate liquid surface trailing the dewetting front.


A practical guide to carrying out skin-prick allergy testing.
Skin-prick testing is one of the cheapest and most widely available methods for diagnosing allergies. With ever-increasing numbers of nurses performing the tests in nurse-led clinics, it is essential that the procedure is fully understood and carried out correctly, particularly in terms of patient safety. This article discusses the indications, contraindications, advantages and disadvantages of skin-prick testing and details how to carry out the procedure.


Genotypes of 2579 patients with phenylketonuria reveal a high rate of BH4 non-responders in Russia.
Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). Furthermore, numerous studies on BH4-sensitive PAH deficiency have been conducted. To date, BH4, a cofactor of PAH, has not been used to treat PKU in Russia.Genotype data of patients with PKU can be used to predict their sensitivity to BH4 therapy. A cohort of 2579 patients with PKU from Russia was analyzed for 25 common PAH gene mutations using custom allele-specific multiplex ligation-dependent probe amplification-based technology. A mutation detection rate of 84.1% chromosomes was accomplished. Both pathogenic alleles were identified in 73.1% of patients. The most frequent pathogenic variants were p.Arg408Trp (50.9%), p.Arg261Gln (5.3%), p.Pro281Leu (3.5%), IVS12+1G>A (3.1%), IVS10-11G>A (2.6%), and p.Arg158Leu (2.4%). The exact boundaries of a PAH exon 5 deletion were defined as EX5del4154ins268 (c.442-2913_509+1173del4154ins268). Severe phenotypes prevailed in the cohort, and classical PKU was observed in 71.8% cases. Due to the genotype-based prediction, 55.9% of the probands were non-responders to the BH4-treatment, and 20.2% were potential responders. Analysis of genotype data is useful to predict BH4 response in PKU patients. The high rate of non-responders among Russian patients was due to the high allele frequency of severe PAH mutations.


Toward radioguided surgery with β- decays: uptake of a somatostatin analogue, DOTATOC, in meningioma and high-grade glioma.
A novel radioguided surgery (RGS) technique for cerebral tumors using β(-) radiation is being developed. Checking for a radiotracer that can deliver a β(-) emitter to the tumor is a fundamental step in the deployment of such a technique. This paper reports a study of the uptake of (90)Y-DOTATOC in meningiomas and high-grade gliomas (HGGs) and a feasibility study of the RGS technique in these types of tumor. Estimates were performed assuming the use of a β(-) probe under development with a sensitive area 2.55 mm in radius to detect 0.1-mL residuals. Uptake and background from healthy tissues were estimated on (68)Ga-DOTATOC PET scans of 11 meningioma patients and 12 HGG patients. A dedicated statistical analysis of the DICOM images was developed and validated. The feasibility study was performed using full simulation of emission and detection of the radiation, accounting for the measured uptake and background rate. All meningioma patients but one with an atypical extracranial tumor showed high uptake of DOTATOC. In terms of feasibility of the RGS technique, we estimated that by administering a 3 MBq/kg activity of radiotracer, the time needed to detect a 0.1-mL remnant with 5% false-negative and 1% false-positive rates is less than 1 s. Actually, to achieve a detection time of 1 s the required activities to administer were as low as 0.2-0.5 MBq/kg in many patients. In HGGs, the uptake was lower than in meningiomas, but the tumor-to-nontumor ratio was higher than 4, which implies that the tracer can still be effective for RGS. It was estimated that by administering 3 mBq/kg of radiotracer, the time needed to detect a 0.1-mL remnant is less than 6 s, with the exception of the only oligodendroma in the sample. Uptake of (90)Y-DOTATOC in meningiomas was high in all studied patients. Uptake in HGGs was significantly worse than in meningiomas but was still acceptable for RGS, particularly if further research and development are done to improve the performance of the β(-) probe.


Memristive device based learning for navigation in robots.
Biomimetic robots have gained attention recently for various applications ranging from resource hunting to search and rescue operations during disasters. Biological species are known to intuitively learn from the environment, gather and process data, and make appropriate decisions. Such sophisticated computing capabilities in robots are difficult to achieve, especially if done in real-time with ultra-low energy consumption. Here, we present a novel memristive device based learning architecture for robots. Two terminal memristive devices with resistive switching of oxide layer are modeled in a crossbar array to develop a neuromorphic platform that can impart active real-time learning capabilities in a robot. This approach is validated by navigating a robot vehicle in an unknown environment with randomly placed obstacles. Further, the proposed scheme is compared with reinforcement learning based algorithms using local and global knowledge of the environment. The simulation as well as experimental results corroborate the validity and potential of the proposed learning scheme for robots. The results also show that our learning scheme approaches an optimal solution for some environment layouts in robot navigation.


Enhancing Intercellular Coordination: Rewiring Quorum Sensing Networks for Increased Protein Expression through Autonomous Induction.
While inducing agents are often used to redirect resources from growth and proliferation toward product outputs, they can be prohibitively expensive on the industrial scale. Previously, we developed an autonomously guided protein production system based on the rewiring of E. coli's native quorum sensing (QS) signal transduction cascade. Self-secreted autoinducer, AI-2, accumulated over time and actuated recombinant gene expression-its design, co-opting the collective nature of QS-mediated behavior. We recently demonstrated that desynchronization of autoinduced intercellular feedback leads to bimodality in QS activation. In this work, we developed a new QS-enabled system with enhanced feedback to reduce cell heterogeneity. This narrows the population distribution of protein expression, leading to significant per cell and overall increases in productivity. We believe directed engineering of cell populations and/or cell consortia will offer many such opportunities in future bioprocessing applications.


The Nonclinical Assessment of Trans-1,3,3,3-tetrafluoropropene (HFO-1234ze (E)), a Near Zero Global Warming Potential Propellant for Use in Metered Dose Inhalation Products.
HFO-1234ze (E) is proposed as a near zero global warming propellant for use in metered dose inhaled (MDI) products. This paper describes the non-clinical safety assessment in mice, rats, and dogs and supplements previously reported data (genetic toxicology, short-term toxicology, and reproductive toxicology). In all species, HFO-1234ze (E) was only detectable in blood for a short period after dosing with no evidence of accumulation. HFO-1234ze (E) was without any toxicological effects at very high doses in subchronic (13-week mouse) and chronic (39-week dog) studies. Chronic (26-week) administration to rats at very high doses was associated with an exacerbation of rodent progressive cardiomyopathy, a well-documented background finding in rodents. In a 2-generation study, extremely high doses were associated with the early euthanasia of some lactating female rats. This finding was considered to be significantly influenced by a state of negative energy balance, reflecting the specific vulnerability of rats during lactation. These findings are considered to not pose a risk to humans with typical MDI use given they occurred at doses which far exceed those expected in patients. Overall, the nonclinical safety data for HFO-1234ze (E) support its further development as an MDI propellant.


SCC-MPGCN: self-attention coherence clustering based on multi-pooling graph convolutional network for EEG emotion recognition.
The emotion recognition with electroencephalography (EEG) has been widely studied using the deep learning methods, but the topology of EEG channels is rarely exploited completely. In this paper, we propose a self-attention coherence clustering based on multi-pooling graph convolutional network (SCC-MPGCN) model for EEG emotion recognition. The adjacency matrix is constructed based on phase-locking value to describe the intrinsic relationship between different EEG electrodes as graph signals. The graph Laplacian matrix is obtained from the adjacency matrix and then is fed into the graph convolutional layers to learn the generalized features. Moreover, we propose a novel graph coarsening method called SCC, using the coherence to cluster the nodes. The benefits are that the dimensionality of adjacency matrix can be reduced and the global information can be achieved from the raw data. Meanwhile, a MPGCN block is introduced to learn the generalized features of emotional states. The fully-connected layer and a softmax layer are adopted to derive the final classification results. We carry out the extensive experiments on DEAP dataset and the results show that the proposed method has better classification results than the state-of-the-art methods with the ten-fold cross-validation. And the model achieves the emotion recognition performance with a mean accuracy of 96.37%, 97.02%, 96.72% on valence, arousal, and dominance dimension, respectively.


Zone-dependent changes in human vertebral trabecular bone: clinical implications.
We have previously shown that there are pronounced age-related changes in human vertebral cancellous bone density and microarchitecture. However, the magnitude of these changes seemed to be dependent on zone location in the vertebral body-the central third vs. the areas adjacent to the endplates. The aim of the present study was, therefore, to investigate whether such zone-specific differences could be identified by static histomorphometric measures. The material comprised 48 individuals (24 women aged 19-97 years, and 24 men aged 23-95 years). Three of the women had a known fracture of the L-2. From each L-2, thick frontal sections of half of the vertebra were embedded undecalcified in methylmethacrylate, cut into 10-microm-thick sections, and stained with aniline blue. The sections were scanned into a computer, and classic static histomorphometry was performed on the images. The histomorphometry was performed on both the whole section and on the separate zones (central and sub-endplate zone). The results showed that trabecular bone volume, trabecular number, and connectivity density decreased significantly faster with age, whereas marrow space star volume increased significantly faster with age in the zones adjacent to the endplates than in the central zone. The other histomorphometric measures showed no zone specificity in relation to aging. However, trabecular thickness and trabecular separation were both higher at all ages in the central zone than in the sub-endplate zone, although this was significant only for trabecular separation. The described differences might have significant clinical implications concerning quantitative computed tomography (QCT) scanning, X-ray analyses, and assessment of fracture liability in the human spine, but the underlying pathogenesis is still not known. This study shows that the human vertebral body can be described as two distinct zones with very specific age-related changes in density and microstructure. This zone-specificity is important for the correct interpretation of clinical data.


Association of toll-like receptor 4, 5 and 10 polymorphisms with Helicobacter pylori-positive peptic ulcer disease in a center in Jordan.
Helicobacter pylori infection is widespread, affecting about 50% of the global population. Polymorphisms in host genes such as the toll-like receptor 4 (TLR4) might affect the susceptibility and severity of infection and treatment success. Investigate the susceptibility and severity of H pylori infection with host TLR4 (rs11536889, rs4986790, rs200109652, rs10759932), TLR5 (rs5744174, rs2072493, rs746250566), TLR10 (rs559182335, rs10004195) polymorphisms. Analytical, cross-sectional. Endoscopy clinic at tertiary care center. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues collected from H pylori-infected patients and healthy individuals. The single nucleotide polymorphisms (SNPs) within the targeted TLR genes were genotyped to assess the genetic association of various SNPs with disease severity. Effect of genotype distribution on H pylori infection. 250 peptic ulcer patients and 217 controls. The TLR10 genotype showed no significant association with H pylori infection except for rs10004195 (T>A) (P=.002). The genotype frequency of Rs5744174 in TLR5 had a significant association with the presence of H pylori infection (P=.046, OR=0.52). Except for gender (P=.022), there were no significant associations between clinical and demographic variables and SNPs relating to the severity of the H pylori infections. Our findings are consistent with differences in severity of H pylori infection due to TLR SNPs in different ethnic groups. Understanding differences in genetic susceptibility could help in classifying patients and matching patients with various treatment options on a genetic basis. Lack of H pylori pathogenicity features assessment. None.


Radioactivity in environmental samples taken in the Sellafield and Ravenglass areas of West Cumbria, 1977-1982.
Terrestrial foodstuffs and other materials of agricultural importance have been analyzed for fission products and actinides discharged in waste from the Sellafield processing works in west Cumbria . Results obtained between 1977 and 1982 are summarized and it is concluded that the internal radiation exposure of the general public due to consumption of locally produced food in no instance amounts to more than a small fraction of recommended limits. Deposition of seaborne sediment is shown to be the main route by which radionuclides of Sellafield origin reach grazing land bordering a nearby tidal estuary.


[Availability, consumption of alcoholic beverages and alcohol-related mortality in Italy].
On the basis of the W.H.O. guide lines the relevant parameters for the study of alcoholism in Italy have been identified. The production and utilization of alcoholic substances is very high, then appears to have reached a plateau about ten years ago. Likewise, consumption has not increased since a few years. Hospital admissions for symptoms related to alcoholism are no more available after the closure of all mental hospitals in 1978. Alcohol-related deaths seem to be stable, as well as cause specific death rates for cirrhosis .


Treatment of cannabis use disorders: a review of the literature.
Cannabis is the most widely used illicit drug in the United States. Despite the fact that there are large numbers of people with cannabis dependence, relatively little attention has been paid to the treatment of this condition. This article seeks to critically review the existing literature about the various psychosocial and pharmacologic treatments of cannabis dependence. We begin with a discussion of the early treatment literature which draws primarily from anecdotal experience and open, uncontrolled trials and proceed through two recent, large, randomized controlled trials of psychotherapies for the treatment of cannabis dependence. We conclude that while a number of psychotherapies have been found to be effective in treating this disorder, with the exception of adding vouchers to reinforce negative urine toxicology screens, no form of psychotherapy has been found to be more effective than any other. In addition, we review the only two clinical pharmacotherapy trials for cannabis dependence as well as the pre-clinical laboratory pharmacotherapy trials in cannabis dependent individuals. We also review pertinent dual-diagnosis pharmacotherapy trials and discuss potential future directions in treatment research for the pharmacotherapy of cannabis dependence.