Graphene oxide as novel vaccine adjuvant.
To improve antigen immunogenicity and promote long-lasting immunity, vaccine formulations have been appropriately supplemented with adjuvants. Graphene has been found to enhance the presentation of antigens to CD8+ T cells, as well as stimulating innate immune responses and inflammatory factors. Its properties, such as large surface area, water stability, and high aspect ratio, make it a suitable candidate for delivering biological substances. Graphene-based nanomaterials have recently attracted significant attention as a new type of vaccine adjuvants due to their potential role in the activation of immune responses. Due to the limited functionality of some approved human adjuvants for use, the development of new all-purpose adjuvants is urgently required. Research on the immunological and biomedical use of graphene oxide (GO) indicates that these nanocarriers possess excellent physicochemical properties, acceptable biocompatibility, and a high capacity for drug loading. Graphene-based nanocarriers also could improve the function of some immune cells such as dendritic cells and macrophages through specific signaling pathways. However, GO injection can lead to significant oxidative stress and inflammation. Various surface functionalization protocols have been employed to reduce possible adverse effects of GO, such as aggregation of GO in biological liquids and induce cell death. Furthermore, these modifications enhance the properties of functionalized-GO's qualities, making it an excellent carrier and adjuvant. Shedding light on different physicochemical and structural properties of GO and its derivatives has led to their application in various therapeutic and drug delivery fields. In this review, we have endeavored to elaborate on different aspects of GO.


Targeted inhibition of the FGF19-FGFR4 pathway in hepatocellular carcinoma; translational safety considerations.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death and new therapies are urgently required to treat this disease. Recent data suggest that the FGF19-FGFR4 axis may be a key driver in certain forms of HCC, making the pathway an interesting, emerging molecular target for potential therapeutic intervention. A complication is that, outside of malignant disease, FGFR4 plays an important physiological role in the regulation of hepatic bile acid (BA) synthesis. FGF19 signalling via FGFR4 suppresses de novo BA production in the liver, tightly maintaining hepatic and systemic levels of these detergent-like molecules at a physiological threshold and preventing pathological complications of raised BA levels, such as cholestatic liver injury and bile acid diarrhoea. In some cases of HCC, the malignant disease causes bile duct obstruction, preventing BA secretion from the liver and resulting in cholestasis. Here, the role of FGFR4 signalling in both HCC and BA homoeostasis is discussed. The potential effects of therapeutic FGF19-FGFR4 inhibition on human hepatobiliary/gastrointestinal physiology are considered along with the potential safety implications of FGF19-FGFR4 blockade in patients with HCC.


School burnout and heart rate variability: risk of cardiovascular disease and hypertension in young adult females.
Emerging research documents the relationship between school burnout and some indicators of increased cardiovascular risk. Indicators of cardiovascular functioning assessed via ambulatory blood pressure and heart rate variability (HRV) have not been thoroughly explored in this research domain. Therefore, the current study examined relationships between school burnout and indicators of cardiac functioning via 24 h ambulatory blood pressure (BP) and electrocardiogram monitoring in a sample of young adult female undergraduates (N = 88). Two hypotheses were tested: (1) that independent of related negative affective symptomology (depression and anxiety), increased school burnout would be related to greater systolic and diastolic BP, higher low frequency (LF) HRV and lower very low frequency (VLF) HRV, and (2) that lower VLF would be related to greater school burnout independently of LF HRV. Hierarchical multiple regression analyzes showed that school burnout was significantly related to elevated ambulatory BP (systolic and diastolic) and HRV markers of increased cardiac sympathovagal tone. These findings support the hypotheses and suggest that school burnout might be implicated in the development of pre-hypertension or early cardiovascular disease. Study limitations and the need for future longitudinal research are discussed.


Outcomes after Ventral Hernia Repair Using the Rives-Stoppa, Endoscopic, and Open Component Separation Techniques.
Complex ventral hernias remain a challenge for general surgeons despite advances in minimally invasive surgical techniques. This study compares outcomes following Rives-Stoppa (RS) repair, components separation technique with mesh (CST-M) or without mesh (CST), and endoscopic components separation technique (ECST). A retrospective review of patients undergoing open ventral hernia repair between 2006 and 2011 was performed. Analysis included patient demographics, surgical site occurrences, hernia recurrence, hospital readmission, and mortality. The search was limited to open repairs, specifically the RS, CST-M, CST, and ECST with mesh techniques. A total of 362 patients underwent repair with RS (66), CST-M (126), CST (117), or ECST (53). The groups were demographically similar. ECST was more frequently used for patients with a history of two or more recurrences (P < 0.001). The RS method had the lowest rate of recurrence (9.1%) compared with CST and CST-M with 28 and 25 per cent recurrences, respectively (P = 0.011). The RS recurrence rate was not significantly different than ECST (15%). There were no significant differences between groups for surgical site occurrences (P = 0.305), hospital readmission (P = 0.288), or death (P = 0.197). When components separation is necessary for complex ventral hernia repair, ECST is a viable option without added morbidity or mortality.


Myotonic dystrophy in pregnancy. Prenatal, neonatal and maternal considerations.
Five pregnancies occurred in three women with myotonic dystrophy. Four of the five infants had generalized hypotonia, respiratory failure, swallowing difficulties and arthrogryposis; two of the affected infants died despite intensive treatment. The surviving affected children had a gradual improvement in respiratory and swallowing symptoms but have remained hypotonic and developmentally delayed. The fifth infant was entirely normal. Polyhydramnios was the most constant feature of the affected pregnancies. Three of the four affected fetuses weighed less than 2,500 gm. Other obstetric complications were not prominent. Second-trimester amniocentesis and linkage studies have a role in predicting myotonic dystrophy. Real-time ultrasound can be used in the prenatal diagnosis of neonatal myotonic dystrophy.


Soil fertility and biodiversity in organic farming.
An understanding of agroecosystems is key to determining effective farming systems. Here we report results from a 21-year study of agronomic and ecological performance of biodynamic, bioorganic, and conventional farming systems in Central Europe. We found crop yields to be 20% lower in the organic systems, although input of fertilizer and energy was reduced by 34 to 53% and pesticide input by 97%. Enhanced soil fertility and higher biodiversity found in organic plots may render these systems less dependent on external inputs.


Measure for the degree of non-markovian behavior of quantum processes in open systems.
We construct a general measure for the degree of non-Markovian behavior in open quantum systems. This measure is based on the trace distance which quantifies the distinguishability of quantum states. It represents a functional of the dynamical map describing the time evolution of physical states, and can be interpreted in terms of the information flow between the open system and its environment. The measure takes on nonzero values whenever there is a flow of information from the environment back to the open system, which is the key feature of non-Markovian dynamics.


Skull Base Fungal Osteomyelitis: A Case Report and Review of the Literature.
Skull base osteomyelitis (SBO) is an invasive infection refractory to therapy, closely linked with malignant otitis externa (MOE). It is characterized by a mild clinical presentation that can delay cross-sectional imaging considered as the key to revealing it. Skull base osteomyelitis typically affects elderly diabetics and immunocompromised patients (>70 years). It most commonly has an otogenic origin due to an extension of MOE. The prognosis can be very poor without the administration of adequate and timely therapy at an early disease stage. Nowadays, Pseudomonas aeruginosa remains the most common pathogen associated with SBO. Fungi are a rare cause of MOE. This report documents a rare case of otogenic SBO caused by Candida parapsilosis in a diabetic patient, with persistent otologic symptoms as clinical onset and resistance to medical treatment. Fungal MOE has more subtle symptoms and is more aggressive than its bacterial counterpart. When MOE is resistant to antibacterial drugs, this should raise the suspicion of a fungal etiology of MOE. The current guidelines do not exhaustively describe the diagnosis, antifungal drugs of choice, and optimum duration of treatment. The description of these rare clinical cases should help with the multidisciplinary management of this disease in order to optimize the diagnosis and therapeutic protocol.


Vibrational spectra of cyclopentadienylphosphine: infrared and theoretical studies from DFT anharmonic potentials.
Both experimental and theoretical infrared investigations of cyclopentadienylphosphine (CpP) are reported. The infrared spectra (3500-500 cm(-1)) in the gas phase have been recorded at 0.5 cm(-1) resolution. Infrared absorptions bands of the two lowest stable conformers were observed and assigned. Average integrated intensities of isolated and overlapping vibrational bands were also determined experimentally. The vibrational frequencies of the CpP system and its P-dideuterated isotopologue have been calculated by means of density functional theory. The Becke exchange functional and Lee-Yang-Parr correlation functional method with a combination of the two basis sets, namely 6-31+G(d,p) and the correlation-consistent triple-zeta cc-pVTZ set of Dunning, were used. Hybrid B3LYP/B3LYP//cc-pVTZ/6-31+G(d,p) anharmonic frequencies of the fundamental, overtone, and combination transitions were calculated in the 3500-200 cm(-1) area with the use of a variational approach, implemented in the P_Anhar_v1.1 code, to assign the experimental data for each conformer.


Operationalizing biodiversity for conservation planning.
Biodiversity has acquired such a general meaning that people now find it difficult to pin down a precise sense for planning and policy-making aimed at biodiversity conservation. Because biodiversity is rooted in place, the task of conserving biodiversity should target places for conservation action; and because all places contain biodiversity, but not all places can be targeted for action, places have to be prioritized. What is needed for this is a measure of the extent to which biodiversity varies from place to place. We do not need a precise measure of biodiversity to prioritize places. Relative estimates of similarity or difference can be derived using partial measures, or what have come to be called biodiversity surrogates. Biodiversity surrogates are supposed to stand in for general biodiversity in planning applications. We distinguish between true surrogates, those that might truly stand in for general biodiversity, and estimator surrogates, which have true surrogates as their target variable. For example, species richness has traditionally been the estimator surrogate for the true surrogate, species diversity. But species richness does not capture the differences in composition between places; the essence of biodiversity. Another measure, called complementarity, explicitly captures the differences between places as we iterate the process of place prioritization, starting with an initial place. The relative concept of biodiversity built into the definition of complementarity has the level of precision needed to undertake conservation planning.


The effect of short-term administration of (-)-deprenyl and isatin on the expressions of some genes in the mouse brain cortex.
Isatin (indoledione 2,3) is an endogenous indole found in the mammalian brain, peripheral tissues, and body fluids. It exhibits many neurophysiological and neuropharmacological effects. It shares some common molecular targets with (-)-deprenyl, a neuroprotective pharmacological drug. Some isatin effects imply a possible influence of gene expression; however, no isatin-responsive genes have yet been identified. In this study the effects of a three-week administration of isatin (20 mg/kg) or (-)-deprenyl (1 mg/kg) on the expressions of several putative isatin/deprenyl-responsive genes in the mouse cortex were compared using real-time PCR. Both treatments caused similarly significant decreases in superoxide dismutase (SOD) mRNA. Treatment of mice with either drug decreased glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, although only in the deprenyl-treated mice was this significant (p<0.01). No significant changes were found in cortex mRNA content of monoamine oxidase A or monoamine oxidase B. The results suggest that isatin and (-)-deprenyl have some common target genes and this supports the idea that isatin may be an endogenous partial functional agonist of (-)-deprenyl. Since GAPDH mRNA expression is sensitive to the pharmacological treatments, these results also question the applicability of GAPDH as a reference gene in gene expression studies.


Interactions of free and immobilized myelin basic protein with anionic detergents.
The interaction of free and immobilized myelin basic protein (MBP) with sodium deoxycholate (DOC) and sodium dodecyl sulfate (NaDodSO4) was studied under a variety of conditions. Free MBP formed insoluble complexes with both detergents. Analysis of the insoluble complexes revealed that the molar ratio of detergent/MBP in the precipitate increased in a systematic fashion with increasing detergent concentration until the complex became soluble. At pH 4.8, equilibrium dialysis studies indicated that approximately 15 mol of NaDodSO4 could bind to the protein without precipitation occurring. Regardless of the surfactant, however, minimum protein solubility occurred when the net charge on the protein-detergent complex was between +18 and -9. Complete equilibrium binding isotherms of both detergents to the protein were obtained by using MBP immobilized on agarose. The bulk of the binding of both detergents was highly cooperative and occurred at or above the critical micelle concentration. At I = 0.1, saturation levels of 2.09 +/- 0.15 g of NaDodSO4/g of protein and 1.03 /+- 0.40 g of DOC/g of protein were obtained. Below pH 7.0 the NaDodSO4 binding isotherms revealed an additional cooperative transition corresponding to the binding of 15-20 mol of NaDodSO4/mol of protein. Affinity chromatography studies indicated that, in the presence of NaDodSO4 (but not in its absence), [125I]MBP interacted with agarose-immobilized histone, lysozyme, and MBP but did not interact with ovalbumin-agarose. These data support a model in which the detergent cross-links and causes precipitation of MBP-anionic detergent complexes. Cross-linking may occur through hydrophobic interaction between detergents electrostatically bound to different MBP molecules.


Protein Carbamylation in Peritoneal Dialysis and the Effect of Low Glucose Plus Amino Acid Solutions.
Protein carbamylation is a post-translational urea-driven protein modification associated with mortality. Free amino acids (AAs) competitively inhibit protein carbamylation and parenteral AA therapy reduces carbamylation in hemodialysis (HD) patients. Peritoneal dialysis (PD) yields differences in urea clearance and AA balance compared with HD, but the influence of PD and intraperitoneal AA solutions on carbamylation is unclear. Thus, we first measured carbamylated albumin (C-Alb; a marker of carbamylation load) in 100 diabetic HD patients frequency-matched by age, sex, and race to 98 diabetic PD subjects from the IMPENDIA trial, which originally compared the metabolic effects of low-glucose PD solutions (incorporating icodextrin and AAs) to a control group (dextrose-only solutions). We then determined the effects of the AA-enriched PD solutions by measuring the 6-month change in C-Alb within the IMPENDIA cohort by treatment allocation (48 treated vs 50 controls). Peritoneal dialysis patients, when compared with HD patients, had higher baseline urea and higher C-Alb. Among IMPENDIA participants, there was no difference in C-Alb change in either arm, but treated subjects showed a trend towards increased carbamylation. Treated subjects also demonstrated an increase in urea, possibly explaining the carbamylation trend. In summary, carbamylation levels in PD patients appeared higher than in matched HD patients. A regimen of AA and low-glucose PD solutions did not reduce C-Alb in IMPENDIA subjects.


Reconstruction of Undersampled Big Dynamic MRI Data Using Non-Convex Low-Rank and Sparsity Constraints.
Dynamic magnetic resonance imaging (MRI) has been extensively utilized for enhancing medical living environment visualization, however, in clinical practice it often suffers from long data acquisition times. Dynamic imaging essentially reconstructs the visual image from raw (k,t)-space measurements, commonly referred to as big data. The purpose of this work is to accelerate big medical data acquisition in dynamic MRI by developing a non-convex minimization framework. In particular, to overcome the inherent speed limitation, both non-convex low-rank and sparsity constraints were combined to accelerate the dynamic imaging. However, the non-convex constraints make the dynamic reconstruction problem difficult to directly solve through the commonly-used numerical methods. To guarantee solution efficiency and stability, a numerical algorithm based on Alternating Direction Method of Multipliers (ADMM) is proposed to solve the resulting non-convex optimization problem. ADMM decomposes the original complex optimization problem into several simple sub-problems. Each sub-problem has a closed-form solution or could be efficiently solved using existing numerical methods. It has been proven that the quality of images reconstructed from fewer measurements can be significantly improved using non-convex minimization. Numerous experiments have been conducted on two in vivo cardiac datasets to compare the proposed method with several state-of-the-art imaging methods. Experimental results illustrated that the proposed method could guarantee the superior imaging performance in terms of quantitative and visual image quality assessments.


Ultraviolet irradiation increases green fluorescence of dihydrorhodamine (DHR) 123: false-positive results for reactive oxygen species generation.
Dihydrorhodamine (DHR) 123 is a fluorophore commonly used for measuring reactive oxygen species (ROS), often after exposing cells to ultraviolet (UV) irradiation or oxidative burst inducers such as Phorbol 12-myristate 13-acetate (PMA). However, the negative effects of UV irradiation on oxidation of DHR123 itself to green fluorescence rhodamine (R) 123 under different experimental conditions (e.g., different buffers, media, cells, ROS detection techniques) have not been fully appreciated. We determined the effect of UV on DHR123 fluorescence, using a cell-free system, and A549 epithelial cells, NIH/3T3 fibroblast cells, Jurkat T cells, primary human T cells, HL-60 neutrophils and primary human neutrophils. We found that UV irradiation rapidly increases green fluorescence of DHR123 in cell-free solutions. The intensity of green fluorescence increases with increasing amounts of DHR123 and UV exposure. The fluorescence increase was greater in Roswell Park Memorial Institute medium (RPMI) than DMEM media. The presence of DMSO (0-1.25%, v/v) in RPMI further increases the fluorescence signal. Phosphate buffered solution (PBS) and Hanks' Balanced Salt Solution (HBSS) generate considerable background signal with DHR123, and increasing DMSO concentration greatly increases the fluorescence signal in these buffers. However, after UV irradiation the amount of DHR123 that remains unoxidized generates sufficient fluorescence signal to measure the ROS produced by H2O2 and peroxidase in vitro or Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated ROS production within HL-60 neutrophils or primary human neutrophils. We conclude that UV irradiation oxidizes DHR123 to generate Rhodamine 123 (R123) green fluorescence signal, and that the R123 present in the culture supernatant could give erroneous results in plate reader assays. However, flow cytometry and fluorescence microscopy reliably detect ROS in cells such as neutrophils. Overall, avoiding false-positive results when detecting ROS using DHR123 requires selection of, agonists, the correct buffers, media, cell types, and measurement techniques.


Foliar sprays of citric acid and salicylic acid alter the pattern of root acquisition of some minerals in sweet basil (Ocimum basilicum L.).
The effect of foliar application of two levels of citric acid (CA; 0 and 7 mM) and two levels of salicylic acid (SA; 0 and 1 mM) combined with two levels of nutrient solution strength (full strength and half strength) on mineral acquisition by sweet basil were investigated. The experiment was conducted in a randomized block design arrangement with three replications. SA alone reduced the plant height and thickened the stem. Plants supplied with a full strength solution had a ticker stem, produced more biomass, and showed higher values of Fv/Fm. Some changes in the uptake pattern of some nutrients, especially boron and sulfur, were noticed. Higher boron concentrations in leaves were in plants sprayed with a combination of 7 mM CA and 1 mM of SA. Applying combination of CA and SA was more effective than using them individually that suggests an effective synergism between them.


Models for bacteraemia risk prediction. Clinical implications.
Bacteraemia has important consequences for the patient, as it is associated with worse clinical outcomes. On the other hand, unnecessarily obtaining samples for blood cultures increases costs and the workload in the microbiology laboratory. Its diagnosis implies a time delay, but decisions about start antibiotic treatment, discharge, or admits the patient must be taken during the first attention and, therefore, before known the blood cultures results. This manuscript reviews the different strategies based on clinical scores and biomarkers that are useful for predicting bacteraemia and improving initial decision-making.


Towards epitaxial graphene p-n junctions as electrically programmable quantum resistance standards.
We report the fabrication and measurement of top gated epitaxial graphene p-n junctions where exfoliated hexagonal boron nitride (h-BN) is used as the gate dielectric. The four-terminal longitudinal resistance across a single junction is well quantized at the von Klitzing constant [Formula: see text] with a relative uncertainty of 10-7. After the exploration of numerous parameter spaces, we summarize the conditions upon which these devices could function as potential resistance standards. Furthermore, we offer designs of programmable electrical resistance standards over six orders of magnitude by using external gating.


Sonography of autonomous follicular ovarian cysts in precocious pseudopuberty.
Isolated follicular cysts of the ovary without elevated gonadotropin levels can occur as the primary source of early pubertal changes in young girls. To date, cyst excision or oophorectomy have been the treatments of choice. We studied three girls aged 5 to 8 7/12 years who presented with sexual precocity and revealed autonomous functioning ovarian cysts (2.2 to 5.5 cm). Clinical signs subsided following resection of the cyst in one case and after regression of the cyst documented by ultrasonography in the other two cases. On the basis of these three cases, we believe ultrasonography can be valuable in the workup of sexual precocity caused by primary ovarian cysts. Given that the spontaneous resolution of such cysts is possible, close clinical follow-up of unequivocally benign-appearing large ovarian cysts in young girls with pubertal changes deserves consideration.


[ND YAG laser impact for creating a pupil].
Using the energy of Nd YAG laser for creating a pupil and achievement of best functional and esthetic effect. For creating a pupil in membranous cataract and pupillar membranes we used Nidek Nd YAG laser in 53 eyes with pseudophakia, senile and traumatic aphakia. We used individual method of approach in each eye. In some of the eyes a complex of laser treatment: membranectomy, iridectomy, anterior vitreolysis in several treatments. We defined the average power of the laser beam and the average number of applications for attaining best results. The creation of pupil plan was connected with the immediate improvement of the visual acuity. In 41 of the eyes (77.35%) it reached value between 0.4 and 1.0. The IOP was compensated up to the 24th hour with local beta-block. The use of the Nd YAG laser energy for creating a pupil is uninvasive, modern, spare microsurgical method. An excellent functional and esthetic effect was achieved and no adjacent tissue was damaged while using it in closed eye ball conditions.


[Syncopes in children and adolescents].
Syncopes are frequent in the pediatric age group. The majority of these events are benign and are so called neurocardiogenic syncopes. In a minority of affected children, a cardiac pathology is the underlying cause, these cases need to be recognized promptly as almost all of the underlying cardiac causes are potentially fatal conditions. Usually detailed history of syncopal events allows for differentiation between neurocardiogenic and other causes of syncope. In case the physical examination is normal, a simple ECG as the only additional laboratory test is adequate. Other laboratory tests are performed on the basis of suspicious findings in both history and physical examination. The typical neuricardiogenic syncopes rarely require medication in childhood, usually addressing some behavioural aspects with the patient are sufficient as only therapeutic measures.


[A robot-assisted system YunSRobot for soft endoscopy: the first trial of upper gastrointestinal endoscopy on human volunteers].
Objective: To evaluate robot-assisted system YunSRobot to perform oesophagogastroduodenoscopy(EGD) in simulation model and human volunteers. Methods: The YunSRobot was invented for soft endoscopy by our team. In this trial, gastroenterologists operated the double handles of YunSRobot to perform EGD endoscopy with Olympus GIF-H 260 in simulation model Lm103 of Koken Japan and human volunteers. The operating time, lumenal anatomic exposure, man-machine interaction and other parameters were recorded and compared with manual endoscopy. Results: In the endoscopy on model, each of four doctors performed 5 procedures of EGD by YunSRobot and traditional manual endoscopy, respectively. The average time of one procedure was (626.4±120.7) seconds in the robot group and (241.5±24.7) seconds in the manual group, the operating time in robot group was more than that in manual endoscopy group. (t=14.0, P<0.001). However, the robotic manipulation time of the four endoscopists was significantly shortened from the first case to the fifth case with ((783.5±154.8)s, (667.75±85.1)s, (582.0±74.7)s, (555.0±28.9)s, (543.8±29.7)s, F=15.353, P=0.03). In the endoscopy on human, three physicians operated the EGD endoscopy in 21 volunteers, each physician performed seven volunteers by YunSRobot and traditional manual endoscopy respectively. The average time of each procedure in the robot group and the manual endoscopy group was (875.6±179.8) vs (378.8±80.4)s, the operating time in robot group was also more than that in manual endoscopy group (t=10.278, P<0.001). Like the endoscopy on model, the robotic manipulation time by the three operators was significantly reduced from the first case to the seventh cases ((954.7±62.1)s, (936.7±116.9)s, (968.7±227.1)s, (1 008.0±229.4)s, (876.7±110.5)s, (735.0±149.2)s, (649.3±81.0)s, F=3.79, P=0.024). All endoscopic anatomy of EGD were clearly and skillfully observed including esophgus, cardia, fundus, body, gastric angle, antrum, pylorus, first and second parts of duodenum, and papilla in both groups. In all procedures, there were no complications. Conclusions: The soft endoscopy robot YunSRobot is competent to conduct endoscopy of EGD on human. Presently the initial learning time of YunSRobot for EGD is longer than that of experienced manual endoscopy. The learning curve shows that the time of robot manipulation reduces rapidly in the initial procedures. It indicates that YunSRobot system has user-friendly functions and is easy to master.


Differential Phenotypes of Myeloid-Derived Suppressor and T Regulatory Cells and Cytokine Levels in Amnestic Mild Cognitive Impairment Subjects Compared to Mild Alzheimer Diseased Patients.
Alzheimer disease (AD) is the most prevalent form of dementia although the underlying cause(s) remains unknown at this time. However, neuroinflammation is believed to play an important role and suspected contributing immune parameters can be revealed in studies comparing patients at the stage of amnestic mild cognitive impairment (aMCI) to healthy age-matched individuals. A network of immune regulatory cells including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) maintains immune homeostasis but there are very few data on the role of these cells in AD. Here, we investigated the presence of these cells in the blood of subjects with aMCI and mild AD (mAD) in comparison with healthy age-matched controls. We also quantitated several pro- and anti-inflammatory cytokines in sera which can influence the development and activation of these cells. We found significantly higher levels of MDSCs and Tregs in aMCI but not in mAD patients, as well as higher serum IL-1β levels. Stratifying the subjects based on CMV serostatus that is known to influence multiple immune parameters showed an absence of differences between aMCI subjects compared to mAD patients and healthy controls. We suggest that the increase in MDSCs and Tregs number in aMCI subjects may have a beneficial role in modulating inflammatory processes. However, this protective mechanism may have failed in mAD patients, allowing progression of the disease. This working hypothesis obviously requires testing in future studies.


Developing Sustainable Agriculture Systems in Medicinal and Aromatic Plant Production by Using Chitosan and Chitin-Based Biostimulants.
Chitosan is illustrated in research as a stimulant of plant tolerance and resistance that promotes natural defense mechanisms against biotic and abiotic stressors, and its use may lessen the amount of agrochemicals utilized in agriculture. Recent literature reports indicate the high efficacy of soil or foliar usage of chitin and chitosan in the promotion of plant growth and the induction of secondary metabolites biosynthesis in various species, such as Artemisia annua, Curcuma longa, Dracocephalum kotschyi, Catharanthus roseus, Fragaria × ananassa, Ginkgo biloba, Iberis amara, Isatis tinctoria, Melissa officinalis, Mentha piperita, Ocimum basilicum, Origanum vulgare ssp. Hirtum, Psammosilene tunicoides, Salvia officinalis, Satureja isophylla, Stevia rebaudiana, and Sylibum marianum, among others. This work focuses on the outstanding scientific contributions to the field of the production and quality of aromatic and medicinal plants, based on the different functions of chitosan and chitin in sustainable crop production. The application of chitosan can lead to increased medicinal plant production and protects plants against harmful microorganisms. The effectiveness of chitin and chitosan is also due to the low concentration required, low cost, and environmental safety. On the basis of showing such considerable characteristics, there is increasing attention on the application of chitin and chitosan biopolymers in horticulture and agriculture productions.


An Ecologic Study of Trends in the Prevalence of Myopia in Chinese Adults in Singapore Born from the 1920s to 1980s.
This study aimed to investigate secular trends in the prevalence of myopia over 6 decades (from the 1920s to 1980s) in Chinese adults in Singapore. Parental myopia prevalence was estimated using a parent-completed questionnaire in paediatric cohorts that included: 1) The Singapore Cohort Of Risk factors for Myopia (SCORM), 2) The Strabismus, Amblyopia and Refractive Error in Singaporean Children (STARS), and 3) The Growing Up in Singapore Towards healthy Outcomes (GUSTO). Published estimates for myopia prevalence from 5 adult studies in Singapore were reviewed. Secular trends in the prevalence of myopia were correlated with changes in the education system. The prevalence of parental myopia in SCORM (n = 2943), STARS (n = 4938), and GUSTO (n = 1072) was 47.8%, 53.4%, and 73.4%, respectively; corresponding calendar years these parents might have started schooling were 1966, 1973, and 1983 (born in 1960, 1967, and 1977), respectively. Mean age of parents was 41.3, 40.1, and 33.4 years, respectively. Prevalence of myopia in adult studies in persons who started elementary school in 1928, 1934, 1938, 1939, 1942, 1948, 1952, 1958, 1962, 1972, 1982, and 1995 were 36.4%, 39.7%, 30.0%, 31.5%, 33.0%, 26.4%, 32.5%, 48.7%, 39.4%, 52.0%, 82.2%, and 85.9%, respectively. During the past few decades, the prevalence of myopia increased rapidly, especially in persons who started elementary school after the 1980s (born after 1970). The education system was expanded after Singapore's independence in 1965, and the new education system was introduced in 1978. These changes, together with increasing intensive schooling, may have contributed to the increase in myopia prevalence.


On the link between shadow economy and carbon dioxide emissions: an analysis of homogeneous groups of countries.
In the framework of an environmental Kuznets curve, the linkage between shadow economy and carbon dioxide (CO2) emissions was evaluated for 145 countries from 1991 to 2017. In assessing the effect of the shadow economy on CO2 emissions, we used panel quantile regression, panel fixed effects, and panel smooth transition regression as estimation methods. In addition, to deal with parameter heterogeneity, we resorted to the procedure of Lin and Ng (2012). We found two country groups that share homogeneous parameters. No environmental Kuznets curve was found for the set of all countries. Nevertheless, one was found for each of the homogeneous parameter country groups. This result supports different turning points for different groups of countries. Shadow economy contributed to reducing CO2 emissions in group 1 and aggravated it in group 2. Manufacturing was revealed to be statistically significant for the countries of group 1. Fossil fuel rents increased the CO2 emissions, mainly in group 2. Urbanization contributed to the hike of CO2 emissions in both country groups but much more intensely for group 1. Evidence of a tendency for decreasing CO2 emissions was also found, reflecting the efficiency gains over time.


Catheterization Laboratory Activation Time in Patients Transferred With ST-Segment-Elevation Myocardial Infarction: Insights From the Mission: Lifeline STEMI Accelerator-2 Project.
Catheterization laboratory (cath lab) activation time is a newly available process measure for patients with ST-segment-elevation myocardial infarction requiring inter-hospital transfers for primary percutaneous coronary intervention that reflects inter-facility communication and urgent mobilization of interventional laboratory resources. Our aim was to determine whether faster activation is associated with improved reperfusion time and outcomes in the American Heart Association Mission: Lifeline Accelerator-2 Project. From April 2015 to March 2017, treatment times of 2063 patients with ST-segment-elevation myocardial infarction requiring inter-hospital transfer for primary percutaneous coronary intervention from 12 regions around the United States were stratified by cath lab activation time (first hospital arrival to cath lab activation within [timely] or beyond 20 minutes [delayed]). Median cath lab activation time was 26 minutes, with a delayed activation observed in 1241 (60.2%) patients. Prior cardiovascular or cerebrovascular disease, arterial hypotension at admission, and black or Latino ethnicity were independent factors of delayed cath lab activation. Timely cath lab activation patients had shorter door-in door-out times (40 versus 68 minutes) and reperfusion times (98 versus 135 minutes) with 80.1% treated within the national goal of ≤120 minutes versus 39.0% in the delayed group. Cath lab activation within 20 minutes across a geographically diverse group of hospitals was associated with performing primary percutaneous coronary intervention within the national goal of ≤120 minutes in >75% of patients. While several confounding factors were associated with delayed activation, this work suggests that this process measure has the potential to direct resources and practices to more timely treatment of patients requiring inter-hospital transfer for primary percutaneous coronary intervention.


Adsorption and photocatalyzed oxidation of methylated arsenic species in TiO2 suspensions.
Monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) are used as herbicides in the agriculture industry. We have demonstrated that MMA and DMA are readily degraded upon TiO2 photocatalysis. DMA is oxidized to MMA as the primary oxidation product, which is subsequently oxidized to inorganic arsenate, As(V). The adsorption of MMA and DMA on Ti02 surface was measured as a function of initial arsenic concentration and solution pH. The pH of the solution influences the adsorption and photocatalytic degradation to a similar degree, due to the speciation of the arsenic substrates and surface charge of TiO2 as a function of pH. The mineralization of MMA and DMA by TiO2 photocatalysis follows the Langmuir-Hinshelwood kinetic model. Addition of tert-butyl alcohol, a hydroxyl radical scavenger, during TiO2 photocatalysis dramatically reduces the rate of degradation, indicating that *OH is the primary oxidant. For dilute solutions, TiO2 may also be applicable as an absorbent for direct removal of a variety of arsenic species, namely As(III), As(V), MMA, and DMA, all of which are strongly adsorbed, thus eliminating the need for a multistep treatment process.


Retinal protection from acute glaucoma-induced ischemia-reperfusion injury through pharmacologic induction of heme oxygenase-1.
To investigate the protective effects of cobalt protoporphyrin (CoPP), a potent heme oxygenase (HO)-1 inducer, in a rat model of ischemia-reperfusion injury and to document the possible antiapoptotic and anti-inflammatory mechanisms underlying the protection. Rats pretreated with intraperitoneal injection of CoPP (5 mg/kg) were subjected to retinal ischemia by increases in intraocular pressure to 130 mm Hg for 60 minutes. The protective effects of CoPP were evaluated by determining the morphology of the retina, counting the survival of retinal ganglion cells (RGCs), and measuring apoptosis in retinal layers. In addition, expressions of HO-1, caspase-3, p53, Bcl-xL, monocyte chemoattractant protein (MCP)-1, and inducible nitric oxide synthase (iNOS) were documented by Western blot analysis. Detection of HO-1, NF-kappaB, and CD68 protein in the retina was performed by immunohistochemistry or immunofluorescence. Pharmacologic induction of HO-1 by CoPP led to HO-1 expression in the full retinal layer. HO-1 overexpression alleviated apoptosis in the retina, preserved RGCs, and attenuated the reduction of inner retinal thickness after ischemia-reperfusion injury. Concurrently, overexpression of HO-1 was associated with inhibition of caspase-3, p53, NF-kappaB, and iNOS and with increased expression of Bcl-xL. Meanwhile, the anti-inflammatory effect of HO-1 was related to reduction in the recruitment of macrophage infiltration in the retina through the suppression of MCP-1. These beneficial effects of HO-1 induced by CoPP were diminished by the HO-1 inhibitor ZnPP. Overexpression of HO-1 by pharmacologic induction protected the retina from subsequent cellular damage caused by ischemia-reperfusion injury through antiapoptotic and anti-inflammatory effects.


[Combination chemotherapy with methotrexate, vincristine, cis-platinum, cyclophosphamide, adriamycin, and bleomycin: MVP-CAB for disseminated urological cancer].
Twenty-eight evaluable patients with disseminated measurable malignancies of the genitourinary organs except testicular cancer were treated with MVP-CAB, between May 1985 and June 1988. Chemotherapy was given at 3 to 4 week intervals, as follows. On day 1, methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg/body were administered. On day 2, cis-platinum 50 mg/m2, on day 1 to 3, prednisolone 20 mg/body were also administered. The administration of bleomycin and adriamycin were limited to 90 mg/body and 400 mg/m2. The median age was 59 years. The median follow-up duration was 11 months. The primary lesions were urothelial tract cancer (19 patients), malignant lymphoma (1 patient), renal cell adenocarcinoma, penile cancer, prostatic adenocarcinoma, and leiomyosarcoma (2 patients each). CR was observed in 2 patients, and PR in 11 patients with urothelial tract cancer. The overall response rate was 68% (13/19). The response rates in primary and metastatic lesions were 56% (5/9) in primary, 73% (8/11) in lymph node, 71% (5/7) in lung, 67% (2/3) in liver, and 20% (1/5) in bone. The median duration of survival in the responders was 13.5 months, and in the non-responders was 5 months. The 1 year survival rate by Kaplan-Meier method was 70% in responders. On the other hand, the longest survival time in non-responders was 9 months. Marked improvement of survival time was noted in the responders. PR was observed in 1 patient with malignant lymphoma, prostatic adenocarcinoma, and leiomyosarcoma in each. The main toxic effect of MVP-CAB was bone marrow suppression. Leucopenia (WBC less than 4,000/mm3) was noted in 24 patients (86%), and 16 patients (57%) had a WBC count nadir below 2,000/mm3. Thrombocytopenia (plt less than 10 x 10(4)/mm3) was noted in 10 patients (36%). However, there were no deaths due to the bone marrow suppression.


Spatial microscopic modeling of collective movements in multi-robot systems: Design choices and calibration.
Despite the strong increase in available computational power enabling an unprecedented level of realism in simulation, modeling robotic systems at higher abstraction level remains crucial to efficiently design robot controllers and analyze their properties. This is especially true for multi-robot systems, with their high computational complexity due to the numerous interactions among individual robots. While multiple contributions in the literature have proposed approaches leading to highly abstracted and therefore computationally efficient models, often such abstractions have been obtained with strong assumptions on the underlying spatiality of the system behavior (e.g., well-mixed system, diffusive system). In this work, we address the modeling of an arbitrary collective movement involving the displacement of a robot ensemble along a certain trajectory overlapped with continuous interactions among the robotic members. Without loss of generality, we have focused our modeling effort on a flocking case study, as a prominent and well-known example of collective movement. We investigate our case study at the microscopic level while leveraging a more faithful submicroscopic model (implemented through a high-fidelity robotic simulator) as ground-truth. More specifically, we illustrate multiple choices for designing and calibrating such microscopic models, so that their faithfulness with the underlying submicroscopic model of the same physical system is preserved. Such effort has produced concrete implementations of three different microscopic models for the same case study, all taking into account the spatiality of the collective movement. We find that all three microscopic models produce quantitatively accurate estimations for our flocking case study. As they rely on different underlying assumptions and modeling techniques, the choice between them is a trade-off between the computational cost, the modeling effort, the metrics considered to evaluate their faithfulness, and the subsequent usage (e.g., control design, system property analysis, control code prototyping).


Hapten-specific B cell repertoire probed by hybridoma technology: selection and characterization of representative clonotypes from the antibody-forming cell pool.
In the course of this study, more than 3000 phthalate-specific antibody-forming cell hybrids were identified using the hybridoma technology. With the aid of a rapid screening assay and an extensive library of phthalate analogs, it was possible to assign selected hapten-specific clones to one of 11 distinct fine-specificity sets. This compartmentalization of the phthalate-specific hybridomas has made it possible to focus attention upon a single manageable portion of the phthalate-specific repertoire. Fourteen clones from a single fine-specificity set were selected for further immunochemical characterization. Five of these clones were found to secrete an antibody that was indistinguishable in isoelectric focusing. Affinity-purified, high-resolution anti-idiotype antibodies were prepared with specificity for the antibodies produced by one of these clones (i.e., 4C7). A major portion of the serologically defined private idiotype (4C7 IdI) was shown to be associated with the ligand-combining site. Our results indicate that the five clones that share a common spectrotype also express the 4C7 IdI. Two other independently derived clones from two distinct fusions also share this idiotype. The 4C7 IdI was also identified in affinity-purified anti-phthalate antibodies derived from a pool of phthalate-immune serum (conventional antibody) and from affinity-purified antibodies derived from a pool of serum from unimmunized BALB/c mice (natural antibody). The 4C7 IdI is thus considered to represent a repeating clonotype in the phthalate-specific repertoire of BALB/c mice, and will serve as one of several useful clonal markers that are being developed for studies of the mechanism regulating idiotype expression.


Hospital Nurses' Competencies in Disaster Situations: A Qualitative Study in the South of Brazil.
Introduction Hospital nurses play a key role in the aftermath of the occurrence of disasters and need specific competencies to work in these situations. From a global perspective, few models exist that focus on disaster nursing. This study aimed to identify hospital nurses' competencies in disaster situations. A qualitative, descriptive, exploratory study was developed using focus groups as a method of data collection. Three meetings were held from June through September 2012 with nurses who worked at a hospital used as reference for disaster situations in the South of Brazil. Thematic analysis of collected data generated the competencies. For statement standardization, a format consistent with a verb, a noun, and a complement was adopted. The group validated 17 competencies, which were organized according to the phases of emergency management described by the World Health Organization (WHO) and classified in domain areas of management, health care, communication, and education. The competencies identified in this study can contribute to the education and practice of nurses in the hospital ambience, strengthening its capacity to face disaster situations.


Generation of inhibitory DNA aptamers against human hepatocyte growth factor.
Hepatocyte growth factor (HGF), a multifunctional cytokine, can act on many cell types. It is involved in cancer growth and metastasis by enhancing the motility of cancer cells and stimulating angiogenesis. The development of effective inhibitors for HGF is an important issue in cancer therapy. In this study, we isolated DNA aptamers against human HGF using the systematic evolution of ligands by exponential enrichment method. The selected DNA aptamers had a highly conserved consensus sequence, and could be divided into two major classes (classes I and II). The consensus motif of classes I and II might contribute to the formation of a hairpin loop structure and a G-quartet structure, respectively. These DNA aptamers bound to human HGF with high affinity and specificity. The dissociation constants of typical aptamers H38-15 and H38-21, representative of the two classes, were calculated to be approximately 20 nM. H38-15 and H38-21 inhibited the biological activities of HGF including the stimulation of scattering, migration, and invasion of pancreatic cancer KP-3 cells. Furthermore, both aptamers inhibited HGF-induced tube formation by human umbilical vein endothelial cells. These results suggested that the isolated DNA aptamers will be useful as therapeutic and diagnostic reagents for cancers.


Is gluteus medius injured in patients treated with a trochanter tip entry intramedullary nail? Clinical, electrophysiological and functional outcomes.
This study aims to assess the functional outcomes, static-dynamic postural stability of patients and evaluate electromyographic activity of gluteus medius (GMed) muscle during gait and spatiotemporal parameters of gait in patients after antegrade intramedullary nailing (IMN) of femoral shaft fractures with trochanter tip entry. Sixteen patients (15 males, 1 female; mean age 34.8±15.2 years; range, 18 to 58 years) who were treated with an antegrade trochanteric IMN between January 2009 and July 2013 and eight healthy male controls (mean age 39.3±9.8 years; range, 27 to 57 years) were included in this retrospective study. Muscle strength, static and dynamic postural stability and fall risk were evaluated. In addition, spatiotemporal parameters of gait were assessed using a validated wireless inertial sensing device and a wireless electromyography (EMG) device was used to measure electromyographic activity of GMed muscle in both groups. There were significant differences in muscle strength, functional and dynamic balance test scores between operated and intact sides (one-leg hop test score p=0.009, balance test scores p<0.001-0.033). There were significant differences in functional and quality of life physical function test scores between groups (one-leg hop test score p=0.014). However, no significant differences were found in EMG results, dynamics balance, and statics postural stability test scores between groups (p>0.05). After isolated femur fracture, patients treated with antegrade trochanteric IMN demonstrated good static and dynamic stability and poor functional outcomes compared to controls. In conclusion, patients with antegrade trochanteric IMN have good balance but poor functional performance; however, further studies are needed to find out the primary reason for these results.


A review on inorganic nanostructure self-assembly.
In recent years, there has been a growing interest in the self-assembly process for the fabrication of micro- and nano-scale structures for various device applications. The success of these applications requires the development of a versatile assembly process for producing large area ordered arrays. In this article, we review recent advances, particularly related to photonic material and device applications, based on self-assembly processes, with the focus on the processes for inorganic structure self assembly. We first discuss major forces guiding the particle self-assembly in the wet coating technology. Then we review device applications and recent advances based on three kinds of wet coating technologies, including dip coating, spin coating and convective coating. Finally, a conclusion will be given, with discussions given on future perspectives.


Involvement of the major glycoprotein (gp43) of Paracoccidioides brasiliensis in attachment to macrophages.
The yeast form of Paracoccidioides brasiliensis, the causative agent of a deep mycosis in humans, is known to be phagocytized by, and to multiply inside, macrophages. In this work we describe the involvement of gp43, a major antigenic protein of P. brasiliensis, in the initial steps of attachment of the fungus to macrophages. Anti-gp43 F(ab) polyclonal fragments were capable of inhibiting phagocytosis in a concentration-dependent manner. Sheep red blood cells sensitized with purified gp43 were more endocytized than SRBC alone, and this process was also inhibited by anti-gp43 F(ab) fragments. Inhibition tests indicated the involvement of fucose and mannose residues in the phagocytosis of the fungus and of SRBC-gp43 by macrophages. Taken together, these results suggest that gp43 may be involved in the adherence and uptake of the fungus by murine peritoneal macrophages, and that this binding may be dependent on monosaccharide residues that are part of the gp43 glycoprotein.


Environmental predictors of drinking and drinking-related problems in young adults.
We examined relationships among drinking norms, peer alcohol use, alcohol availability, drinking location, alcohol consumption, and drinking-related problems among young adult drinkers. The specific objectives of our study were to assess the relative contribution of normative and physical environmental factors to drinking and drinking consequences. Subjects were 3,095 young adults, aged eighteen to twenty years old who participated in the Communities Mobilizing for Change on Alcohol Project baseline survey. Alcohol consumption (i.e., number of drinks on the last occasion) and drinking consequences served as dependent variables. Multiple linear regression was used to identify predictors of alcohol consumption, and logistic regression was employed to identify predictors of drinking consequences. Drinking norms and peer alcohol use were positively related to alcohol consumption and to drinking consequences. Drinking in a public setting was positively related to alcohol consumption, but not to drinking-related problems. Findings suggest that policies and programs that alter the normative and physical environment surrounding drinking may reduce alcohol consumption and subsequent problems in young adults.


Identification and analysis of chemical constituents and rat serum metabolites in Suan-Zao-Ren granule using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with multiple data processing approaches.
Suan-Zao-Ren granule is widely used to treat insomnia in China. However, because of the complexity and diversity of the chemical compositions in traditional Chinese medicine formula, the comprehensive analysis of constituents in vitro and in vivo is rather difficult. In our study, an ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and the PeakView® software, which uses multiple data processing approaches including product ion filter, neutral loss filter, and mass defect filter, method was developed to characterize the ingredients and rat serum metabolites in Suan-Zao-Ren granule. A total of 101 constituents were detected in vitro. Under the same analysis conditions, 68 constituents were characterized in rat serum, including 35 prototype components and 33 metabolites. The metabolic pathways of main components were also illustrated. Among them, the metabolic pathways of timosaponin AI were firstly revealed. The bioactive compounds mainly underwent the phase I metabolic pathways including hydroxylation, oxidation, hydrolysis, and phase II metabolic pathways including sulfate conjugation, glucuronide conjugation, cysteine conjugation, acetycysteine conjugation, and glutathione conjugation. In conclusion, our results showed that this analysis approach was extremely useful for the in-depth pharmacological research of Suan-Zao-Ren granule and provided a chemical basis for its rational.


Positive identification of UV-generated, non-hydrogen-bonded isomers of o-hydroxybenzaldehyde and o-hydroxyacetophenone.
Non-hydrogen-bonded isomers were photogenerated by UV (lambda > 335 nm) irradiation of o-hydroxybenzaldehyde (salicylaldehyde) and o-hydroxyacetophenone monomers isolated in low-temperature Ar matrixes. These photoisomerizations were found to be photoreversible. Upon shorter wavelength (lambda > 235 nm or lambda > 270 nm) UV irradiation, the initial forms of the compounds (with intramolecular hydrogen bonds) were partially repopulated. The structures of the photogenerated non-hydrogen-bonded isomers of both compounds were positively identified by comparison of their IR spectra with the spectra theoretically calculated [at the DFT(B3LYP)/6-311++G(2d,p) level] for all possible non-hydrogen-bonded isomers of the studied compounds. The experimental IR spectra of the photoproducts generated from o-hydroxybenzaldehyde and o-hydroxyacetophenone are very well reproduced only by the theoretical spectra predicted for the isomers with both OH and formyl (or acetyl) groups rotated by 180 degrees, with respect to the initial, most stable hydrogen-bonded conformer. Excellent agreement between experiment and theoretical prediction provides a basis for a very reliable identification of the photoproduced isomers of o-hydroxybenzaldehyde and o-hydroxyacetophenone.


Socioeconomic status in relation to Parkinson's disease risk and mortality: A population-based prospective study.
Little is known about the role of socioeconomic status in relation to Parkinson's disease (PD) risk, and no study has investigated whether the impact of socioeconomic status on all-cause mortality differs between individuals with and without PD.In this population-based prospective study, over 4.6 million Swedish inhabitants who participated in the Swedish census in 1980 were followed from 1981 to 2010. The incidence rate of PD and incidence rate ratio were estimated for the association between socioeconomic status and PD risk. Age-standardized mortality rate and hazard ratio (HR) were estimated for the association between socioeconomic status and all-cause mortality for individuals with and without PD.During follow-up, 66,332 incident PD cases at a mean age of 76.0 years were recorded. Compared to individuals with the highest socioeconomic status (high nonmanual workers), all other socioeconomic groups (manual or nonmanual and self-employed workers) had a lower PD risk. All-cause mortality rates were higher in individuals with lower socioeconomic status compared with high nonmanual workers, but relative risks for all-cause mortality were lower in PD patients than in non-PD individuals (e.g., for low manual workers, HR: 1.12, 95% confidence interval [CI]: 1.09-1.15 for PD patients; HR: 1.36, 95% CI: 1.35-1.36 for non-PD individuals).Individuals with lower socioeconomic status had a lower PD incidence compared to the highest socioeconomic group. Lower socioeconomic status was associated with higher all-cause mortality among individuals with and without PD, but such impact was weaker among PD patients.


Characterization of peripheral and central sensitization after dorsal root ganglion intervention in patients with unilateral lumbosacral radicular pain: a prospective pilot study.
Quantitative sensory testing (QST) has been used to predict the outcome of epidural steroid injections in lumbosacral radicular pain and has the potential to be an important tool in the selection of appropriate treatment (such as epidural steroid injections vs surgery) for patients with chronic radicular pain. In addition, QST assists in identification of the pain pathways of peripheral and central sensitization in selected groups of patients. Twenty-three patients were given dorsal root ganglion (DRG) infiltration with local anaesthesia and steroid ('DRG block'), and those who demonstrated at least 50% pain relief were offered pulsed radiofrequency (PRF) to the DRG. Questionnaires and QST scores were measured before the DRG blocks and at 1 week and 3 months after their procedure. Those who received PRF also answered questionnaires and underwent QST measurements at 1 week and 3 months after their procedure. There was a significant increase in pressure pain threshold scores after DRG blocks. A reduced conditioned pain modulation response was seen before DRG, which increased after the procedure. Ten out of 23 patients underwent PRF to the DRG, and an increase in pressure pain threshold scores after PRF was observed. The conditioned pain modulation response was maintained in this group and increased after PRF. The study demonstrates that patients with unilateral radicular low back pain who receive dorsal root ganglion interventions show changes in pressure pain thresholds and conditioned pain modulation that are consistent with a 'normalization' of peripheral and central sensitization.


Addressing malnutrition in young children in South Africa. Setting the national context for paediatric food-based dietary guidelines.
Despite various national nutrition and primary healthcare programmes being initiated in South Africa over the last decade, child health has deteriorated. This is seen by the rise in infant and child mortality rates, the high prevalence of preventable childhood diseases, e.g. diarrhoea and lower respiratory tract infections, and the coexistence of under-nutrition along with HIV/AIDS. Poor dietary intake, food insecurity and poor quality of basic services prevail within this precarious causal web. The national Integrated Nutrition Programme is a comprehensive nutrition strategy that focuses on children below 6 years old, at-risk pregnant and lactating women, and those affected by communicable and non-communicable diseases. Focus areas relevant to pre-school children include disease-specific nutrition treatment, support and counselling; growth monitoring and promotion (GMP); micronutrient malnutrition control; breastfeeding promotion, protection and support; contributions to household food security; nutrition interventions among HIV-infected children; and nutrition promotion, education and advocacy. Progress towards this includes the Baby-Friendly Hospital Initiative; mandatory fortification of maize meal and wheat flour with multiple micronutrients; vitamin A supplementation coverage and mandatory iodization of salt by legislation; the provision of free road-to-health charts for GMP; and the National School Nutrition Programme. Since 2003, the basis of the nutrition education strategy has been the locally developed food-based dietary guidelines (FBDGs), directed at adults and school-going children. This review sketches the backdrop to and motivation for the introduction of specifically targeted paediatric FBDGs, for mothers and caregivers of children from birth to age 7 years, as a national initiative.


[Neurosis and hypertensive disease].
An interrelationship between neurotic and psychosomatic pathologies was analysed. Experimental modelling of psychosomatic diseases suggested a combined action of the neurotization and destabilizing of regulatory mechanisms of a corresponding visceral system. In contrast to a neurosis with hypertensive syndrome, an obvious suppression of the vascular system's self-regulatory mechanism was revealed in subjects with initial stages of hypertensive disease (PAH and HD-1). The data obtained suggested a hypothesis of different mechanisms for formation of a neurosis and hypertensive disease.


Durvillaea antarctica: A Seaweed for Enhancing Immune and Cardiometabolic Health and Gut Microbiota Composition Modulation.
Durvillaea antarctica is the seaweed that is the most consumed by the Chilean population. It is recognized worldwide for its high nutritional value in protein, vitamins, minerals, and dietary fiber. This is a narrative review in which an extensive search of the literature was performed to establish the immunomodulator, cardiometabolic, and gut microbiota composition modulation effect of Durvillaea antarctica. Several studies have shown the potential of Durvillaea antarctica to function as prebiotics and to positively modulate the gut microbiota, which is related to anti-obesity, anti-inflammatory, anticancer, lipid-lowering, and hypoglycemic effects. The quantity of Bacteroides was negatively correlated with that of inflammatory monocytes and positively correlated with the levels of several gut metabolites. Seaweed-derived polysaccharides modulate the quantity and diversity of beneficial intestinal microbiota, decreasing phenol and p-cresol, which are related to intestinal diseases and the loss of intestinal function. Additionally, a beneficial metabolic effect related to this seaweed was observed, mainly promoting the decrease in the glycemic levels, lower cholesterol levels and cardiovascular risk. Consuming Durvillaea antarctica has a positive impact on the immune system, and its bioactive compounds provide beneficial effects on glycemic control and other metabolic parameters.


Long-Term Weight Loss Effects of a Behavioral Weight Management Program: Does the Community Food Environment Matter?
This study examined whether community food environments altered the longer-term effects of a nationwide behavioral weight management program on body mass index (BMI). The sample was comprised of 98,871 male weight management program participants and 15,385 female participants, as well as 461,302 and 37,192 inverse propensity-score weighted matched male and female controls. We measured the community food environment by counting the number of supermarkets, convenience stores, and fast food restaurants within a 1-mile radius around each person's home address. We used difference-in-difference regression models with person and calendar time fixed effects to estimate MOVE! effects over time in sub-populations defined by community food environment attributes. Among men, after an initial decrease in BMI at 6 months, the effect of the program decreased over time, with BMI increasing incrementally at 12 months (0.098 kg/m², p < 0.001), 18 months (0.069 kg/m², p < 0.001), and 24 months (0.067 kg/m², p < 0.001). Among women, the initial effects of the program decreased over time as well. Women had an incremental BMI change of 0.099 kg/m² at 12 months (p < 0.05) with non-significant incremental changes at 18 months and 24 months. We found little evidence that these longer-term effects of the weight management program differed depending on the community food environment. Physiological adaptations may overwhelm environmental influences on adherence to behavioral regimens in affecting longer-term weight loss outcomes.


An unbiased iterative group registration template for cortical surface analysis.
Accurate alignment of explicit surface representations of human cerebral cortices is necessary in order to compare local individual differences in cortical morphometric measurements (thickness, surface area, gyrification, etc.) in both normal and clinical populations. This paper presents a methodology for developing unbiased, high resolution iterative registration templates from a group of 222 subject hemispheres and shows that the resulting template provides better alignment of a separate set of test data than single-subject templates. It demonstrates that between 30 and 50 subjects are required to generate a stable iterative template. It also explores the way in which fold variants in registration templates affect the quality of registration. Finally, it shows that hemisphere-specific group registration templates systematically better register subject hemispheres of the same laterality, underlining the need to develop templates free of hemisphere bias for asymmetry analysis.


Pulmonary epithelial permeability in ARDS and cardiogenic pulmonary oedema.
Clearance of inhaled 99mTechnetium-labelled diethylene triamine pentacetate (99mTc-DTPA) from the lung, an index of pulmonary alveolar epithelial permeability (PAEP), was measured in 13 patients with cardiogenic interstitial pulmonary oedema (CIPO) and in 7 patients with adult respiratory distress syndrome (ARDS). Thirty-five normal subjects (22 nonsmokers and 13 smokers) were evaluated as controls. Half-time clearance (t0.5) values in ARDS patients (mean +/- SD: 15 +/- 2 min) were significantly lower than in CIPO patients (62 +/- 9 min). This PAEP increase in ARDS was impressive, even in comparison to heavy smokers. Loss of the PAEP vertical gradient (apical PAEP greater than base PAEP) was observed in both cardiogenic and ARDS lungs and among smokers.


[Ethics and long-term nutritional support in children].
Since its outset, parenteral nutrition has led to deep ethical thinking. These interrogations have increased over the last 30 years when faced with the problems brought about by the concept of intestinal failure and parenteral nutrition dependence, by the quality of life of these children and the endeavors to wean them from this artificial nutrition at the price of major therapeutic innovation. Thirty years later, regulated programs of home parenteral nutrition and of intestinal (and liver) transplantation instigate new ethical interrogations. It is the expert's responsibility to take these points into account when making strategic choices which he will then discuss with the families.


Scattering-induced changes in the degree of polarization of a stochastic electromagnetic plane-wave pulse.
The scattering of a stochastic electromagnetic plane-wave pulse on a deterministic spherical medium is investigated. An analytical formula for the degree of polarization (DOP) of the scattered field in the far zone is derived. Letting pulse duration T(0) → ∞, our formula can be applied to study the scattering of a stationary stochastic electromagnetic light wave. Numerical results show that the DOP of the far zone field is closely determined by the size of the spherical medium when the incident field is a stochastic electromagnetic plane-wave pulse. This is much different from the case when the incident field is a stationary stochastic electromagnetic light wave, where the DOP of the far zone field is independent of the size of the medium. One may obtain the information of the spherical medium by measuring the scattering-induced changes in the DOP of a stochastic electromagnetic plane-wave pulse.


Unraveling the inhibition mechanism of cyanidin-3-sophoroside on polyphenol oxidase and its effect on enzymatic browning of apples.
The hunt for anti-browning agents in the food and agricultural industries aims to minimize nutritional loss and prolong post harvest storage. In the present study, the effect of cyanidin-3-sophoroside (CS) from Garcinia mangostana rind, on polyphenol oxidase (PPO) activity was investigated. The non-competitive inhibition mode of CS was determined by Lineweaver Burk plot. CS forms a ground-state complex by quenching the intrinsic fluorescence of PPO. The static quenching was temperature-dependent with an activation energy of 4.654±0.1091kJmol-1 to withstand the disruption of amino acid residues of the enzyme binding site. The enzyme conformational change was validated by 3D fluorescence and CD spectrum. Docking (binding energy -8.124kcal/mol) and simulation studies confirmed the binding pattern and stability. CS decreased PPO activity and browning index of fresh cut apples and prolonged the shelf life. Thus, CS appears to be a promising anti-browning agent to control enzymatic browning.


Bioactive Peptide of Marine Origin for the Prevention and Treatment of Non-Communicable Diseases.
Non-communicable diseases (NCD) are the leading cause of death and disability worldwide. The four main leading causes of NCD are cardiovascular diseases, cancers, respiratory diseases and diabetes. Recognizing the devastating impact of NCD, novel prevention and treatment strategies are extensively sought. Marine organisms are considered as an important source of bioactive peptides that can exert biological functions to prevent and treatment of NCD. Recent pharmacological investigations reported cardio protective, anticancer, antioxidative, anti-diabetic, and anti-obesity effects of marine-derived bioactive peptides. Moreover, there is available evidence supporting the utilization of marine organisms and its bioactive peptides to alleviate NCD. Marine-derived bioactive peptides are alternative sources for synthetic ingredients that can contribute to a consumer's well-being, as a part of nutraceuticals and functional foods. This contribution focus on the bioactive peptides derived from marine organisms and elaborates its possible prevention and therapeutic roles in NCD.


Structure of a physiologically based biokinetic model for use in 14C and organically bound tritium dosimetry.
Physiologically based biokinetic (PBBK) dosimetry models for beta emitters such as 3H and 14C must include rapid turnover compartments which, while they may be minor in terms of dose commitment, can dominate bioassay measurements at early times after intake. In this paper, a consistent PBBK model structure will be described for use in dose assessments for organic 14C and organically bound tritium (OBT), and also for 14CO2, based on the literature of human carbon metabolism, and on direct measurements of human excretion. CO3/HCO3- is a central compartment in carbon metabolism. The 14CO2 biokinetic model described in ICRP Publication 80 for the calculation of dose coefficients was found to omit early components of excretion necessary for the accurate interpretation of bioassay results. Recommendations on the requirements on dosimetry models for intakes of 14C and OBT are made.


Inconsistent retrospective self-reports of childhood sexual abuse and their correlates in the general population.
Epidemiological research on childhood sexual abuse (CSA) and its consequences in adult life mainly relies on retrospective reports. This study explores their consistency and the correlates of inconsistent CSA self-reports in a random population sample. A stratified subsample of 2,462 subjects (selected from a large-scale (N = 34,267) representative sample of Dutch adults aged 40 and beyond) participated in a two-phase online questionnaire survey on extra-familial CSA which was conducted on a four- to six-week interval. Subjects reporting CSA were overrepresented. Participants with consistent and inconsistent responses were compared with regard to demographics, family background, abuse severity, and clinical characteristics. Potential correlates of inconsistency were identified using logistic regression analysis. An additional questionnaire (Phase III) administered to inconsistent respondents explored possible reasons for their inconsistency. Of the 1,992 respondents who had reported extra-familial CSA during Phase I, 707 (35.5%) denied this in Phase II. Of the 2,462 respondents in Phase II, 727 (29.5%; 9.2% when considering sample stratification) gave a discrepant answer to the extra-familial sexual abuse item compared to their answers given in Phase I. Reports of less severe abuse, intra-familial CSA, and early parental separation predicted inconsistency. Reasons provided for inconsistency varied from misunderstanding (e.g., reporting intra-familial CSA rather than extra-familial CSA) to emotional motives (e.g., embarrassment, being overwhelmed) or practical considerations (e.g., lack of privacy while filling out the questionnaire). Inconsistent self-reports of extra-familial sexual abuse occur on a substantial scale and are associated with less severe forms of abuse (lack of salience) or classification difficulties (perpetrator being a family member or not). Consistency tests and probing for clarifications or corrections should be routinely conducted in order to increase the quality of CSA epidemiological research.


Quantum Engineering of a Low-Entropy Gas of Heteronuclear Bosonic Molecules in an Optical Lattice.
We demonstrate a generally applicable technique for mixing two-species quantum degenerate bosonic samples in the presence of an optical lattice, and we employ it to produce low-entropy samples of ultracold ^{87}Rb^{133}Cs Feshbach molecules with a lattice filling fraction exceeding 30%. Starting from two spatially separated Bose-Einstein condensates of Rb and Cs atoms, Rb-Cs atom pairs are efficiently produced by using the superfluid-to-Mott insulator quantum phase transition twice, first for the Cs sample, then for the Rb sample, after nulling the Rb-Cs interaction at a Feshbach resonance's zero crossing. We form molecules out of atom pairs and characterize the mixing process in terms of sample overlap and mixing speed. The dense and ultracold sample of more than 5000 RbCs molecules is an ideal starting point for experiments in the context of quantum many-body physics with long-range dipolar interactions.


Alcohol withdrawal-induced change in lipoprotein(a): association with the growth hormone/insulin-like growth factor-I (IGF-I)/IGF-binding protein-1 (IGFBP-1) axis.
Lipoprotein(a) [Lp(a)] is an important risk factor for cardiovascular disease. Alcohol is one of the few nongenetic factors that lower Lp(a) levels, but the metabolic mechanisms of this action are unknown. Alcohol inhibits the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. Alcohol might also affect IGF-binding protein-1 (IGFBP-1), which is an acute inhibitor of IGF-I. We studied how alcohol withdrawal affects Lp(a) levels and the GH/IGF-I/IGFBP-1 axis. Male alcohol abusers (n=27; 20 to 64 years old) were monitored immediately after alcohol withdrawal for 4 days. Twenty-six healthy men, mainly moderate drinkers, served as control subjects. Fasting blood samples were drawn to determine Lp(a), IGF-I, and IGFBP-1 (by ELISA, RIA, and immunoenzymometric assay, respectively). Nocturnal (12 hours) urine collection was performed in 9 alcoholics and 11 control subjects for GH analyses (RIA). The groups were similar in age and body mass index. Lp(a), GH, and IGF-I tended to be lower and IGFBP-1 higher in the alcoholics immediately after alcohol withdrawal than in the control subjects. During the 4-day observation in alcoholics, Lp(a) levels increased by 64% and IGF-I levels by 41%, whereas IGFBP-1 levels decreased by 59% (P<.001 after ANOVA for all comparisons). Urinary GH levels tended to decline. The increase in Lp(a) correlated inversely with the changes in IGFBP-1 (r= -.63, P<.001, n=27) and GH (r=-.70, P<.05, n=9), but not with IGF-I. In multiple regression analysis, the main predictors for the increase in Lp(a) were IGFBP-1 and urinary GH. In conclusion, alcohol withdrawal induces interrelated and potentially atherogenic changes in Lp(a) and IGFBP-1 levels.


An ionic-polymer-metallic composite actuator for reconfigurable antennas in mobile devices.
In this paper, a new application of an electro-active-polymer for a radio frequency (RF) switch is presented. We used an ionic polymer metallic composite (IPMC) switch to change the operating frequency of an inverted-F antenna. This switch is light in weight, small in volume, and low in cost. In addition, the IPMC is suitable for mobile devices because of its driving voltage of 3 volts and thickness of 200 μm. The IPMC acts as a normally-on switch to control the operating frequency of a reconfigurable antenna in mobile phones. We experimentally demonstrated by network analysis that the IPMC switch could shift its operating frequency from 1.1 to 2.1 GHz, with return losses of than -10 dB at both frequencies. To minimize electrolysis and maximize the operation time in air, propylene carbonate electrolyte with lithium perchlorate (LiClO₄) was applied inside the IPMC. The results showed that when the IPMC was actuated over three months at 3.5 V, the tip displacement fell by less than 10%. Therefore, an IPMC actuator is a promising choice for application to a reconfigurable antenna.


Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990-2015: Systematic review and meta-analysis.
Comorbidity between substance use disorders (SUDs) and bipolar disorder (BD) is highly prevalent to the extent it may almost be regarded the norm. This systematic review and meta-analysis aimed to estimate the prevalence rates of SUDs in treatment seeking patients diagnosed with BD in both inpatient and outpatient settings. A comprehensive literature search of Medline, EMBASE, psychINFO and CINAHL databases was conducted from 1990 to 2015. Prevalence of co-morbid SUDs and BD were extracted and odds ratios (ORs) were calculated using random effects meta-analysis. There were 151 articles identified by electronic searches that yielded 22 large, multi-site studies and 56 individual studies describing comorbid rates of SUDs amongst community dwelling, BD inpatients or outpatients. The SUDs with the highest prevalence in BD were alcohol use (42%) followed by cannabis use (20%) and other illicit drug use (17%). Meta-analysis showed males had higher lifetime risks of SUDs compared to females. BD and comorbid SUDS were associated with earlier age of onset and slightly more hospitalisations than non-users. The results do not take into account the possibility that individuals may have more than one comorbid disorder, such as having more than one SUD, anxiety disorder, or other combination. Some of the meta-analyses were based on relatively few studies with high rates of heterogeneity. Most included studies were cross-sectional and therefore causality cannot be inferred. This systematic review shows comorbidity between SUDs and bipolar illness is highly prevalent in hospital and community-based samples. The prevalence of SUDs was similar in patients with bipolar I and bipolar II disorders. This study adds to the literature demonstrating that SUDs are common in BD and reinforces the need to provide better interventions and properly conducted treatment trials to reduce the burden conferred by comorbid SUD and BD.


Parkinson's disease diffusion MRI is not affected by acute antiparkinsonian medication.
A prior longitudinal study demonstrates that free-water diffusion magnetic resonance imaging (dMRI) tracks progression in the substantia nigra (Ofori et al., 2015b). Here, we test the acute effects of antiparkinsonian medication on this established imaging progression marker for the first time. Fifteen PD patients underwent dMRI OFF and ON-medication one day apart. ON-medication, patients were tested approximately 45 min after their usual dose of antiparkinsonian medication. OFF-medication, patients were tested after not taking antiparkinsonian medication for > 12 h. OFF and ON-medication was counter-balanced across subjects. For dMRI, we computed free-water and free-water corrected fractional anisotropy (FAt) within the following regions: caudate, putamen, substantia nigra, and subthalamic nucleus. ON-medication significantly reduced parkinsonian motor symptoms compared with OFF-medication (p < 0.001). dMRI measures (free-water and FAt) were not different between the OFF and ON-medication conditions. Administration of an acute does of anti-parkinsonian medication in PD does not affect free-water and FAt in key nigrostriatal structures. Free-water and FAt biomarkers reflect the chronic state of the nigrostriatal circuit, and therefore are potential viable biomarkers for disease-modifying therapeutic studies in PD.


Mathematics and the surgeon.
The surgeon uses elementary mathematics just as much as any other educated layman. In his professional life, however, much of the knowledge and skill on which he relies has had a mathematical strand in its development, possibly woven into the supporting disciplines such as physics, chemistry, biology, and bioengineering. The valves and limitations of mathematical models are examined briefly in the general medical field and particularly in relation to the surgeon. Arithmetic and statistics are usually regarded as the most immediately useful parts of mathematics. Examples are cited, however, of medical postgraduate work which uses other highly advanced mathematical techniques. The place of mathematics in postgraduate and postexperience teaching courses is touched on. The role of a mathematical consultant in the medical team is discussed.


Marijuana use among the adolescent children of high-risk drug-abusing fathers.
This study examines marijuana use among children of male drug abusers. Subjects were 83 African-American and European-American male drug abusers, of whom the majority were injection drug users, and their children. Thirty-one of the fathers were HIV-positive and 52 were HIV-negative. Using logistic regression analyses, we explored cross-sectionally the relationship between four psychosocial domains (ie, paternal attributes, adolescent problem behaviors, father-adolescent relations, and environment) and adolescent marijuana use. The father's use of illegal drugs and his failure to cope adaptively predicted adolescent marijuana use, while a close father-child bond predicted less adolescent marijuana use. Adolescent problem behaviors predicted an increased likelihood of marijuana use. Furthermore, hierarchical regression analysis demonstrated that the adolescent's problem behavior mediated the associations between both the father-adolescent relationship and environmental factors with adolescent marijuana use. Reducing the risk factors and enhancing the protective factors within each of the domains could help reduce marijuana use among the adolescent children of drug-abusing fathers. Moreover, if a father is a drug abuser, it is important to help him establish a close bond with his child in order to help attenuate the influence of his drug use on the child's marijuana use.


In silico modeling-based new alternative methods to predict drug and herb-induced liver injury: A review.
New approach methods (NAMs) have been developed to predict a wide range of toxicities through innovative technologies. Liver injury is one of the most extensively studied endpoints due to its severity and frequency, occurring among populations that consume drugs or dietary supplements. In this review, we focus on recent developments of in silico modeling for liver injury prediction using deep learning and in vitro data based on adverse outcome pathways (AOPs). Despite these models being mainly developed using datasets generated from drug-like molecules, they were also applied to the prediction of hepatotoxicity caused by herbal products. As deep learning has achieved great success in many different fields, advanced machine learning algorithms have been actively applied to improve the accuracy of in silico models. Additionally, the development of liver AOPs, combined with big data in toxicology, has been valuable in developing in silico models with enhanced predictive performance and interpretability. Specifically, one approach involves developing structure-based models for predicting molecular initiating events of liver AOPs, while others use in vitro data with structure information as model inputs for making predictions. Even though liver injury remains a difficult endpoint to predict, advancements in machine learning algorithms and the expansion of in vitro databases with relevant biological knowledge have made a huge impact on improving in silico modeling for drug-induced liver injury prediction.


Factors Predicting Renal Function Outcome after Augmentation Cystoplasty.
We determined the cause of renal deterioration after augmentation cystoplasty (AC). Twenty-nine adult patients with refractory bladder dysfunction and who underwent ileocystoplasty from 2004 to 2015 were studied. Patients with a decline in glomerular filtration rate (GFR) after augmentation were reviewed. The primary outcome was to determine the factors that might lead to deterioration of estimated GFR. Median follow-up was 7.0 ± 2.6 years. Significant bladder capacity, end filling pressure, and bladder compliance were achieved from median 114 ± 53.6 to 342.1 ± 68.3 ml (p = .0001), 68.5 ± 19.9 to 28.2 ± 6.9 cm H2O (p = .0001), and 3.0 ± 2.1 to 12.8 ± 3.9 (p = .0001), respectively. Renal function remained stable and improved in 22 (76%) patients from median eGFR 135 ± 81.98 to 142.82 ± 94.4 ml/min/1.73 m2 (p = .160). Significant deterioration was found in 7 (24%) patients from median eGFR 68.25 ± 42 to 36.57 ± 35.33 (p = .001). The causes of renal deterioration were noncompliance to self-catheterization (2 patients), posterior urethral valve/dysplastic kidneys (2 patients), and reflux/infection (2 patients). On multivariate analysis, recurrent pyelonephritis (OR 3.87, p = 0.0155) and noncompliance (OR 30.78, p = 0.0156) were significant. We concluded that AC is not the cause of progression to end-stage renal disease in patients with renal insufficiency.


Cost-effectiveness of endoscopic ultrasonography in the evaluation of proximal rectal cancer.
Clinical trials demonstrate the superiority of preoperative over postoperative radiotherapy (XRT) in diminishing rates of local recurrence of transmurally infiltrating (T3/4) rectal tumors. The dosage and cost of preoperative XRT are less than postoperative XRT. The economic and health impact of transrectal endoscopic ultrasound (EUS) on rectal cancer management has not been described. The aim of this study was to apply a decision analysis model to compare the cost-effectiveness of three staging strategies in the evaluation of nonmetastatic proximal rectal cancer: abdominal and pelvic CT versus abdominal CT plus EUS versus abdominal CT plus pelvic magnetic resonance imaging. A decision model was designed using DATA Version 3.5 (TreeAge Software, Williamstown, MA), taking as entry criteria nonmetastatic proximal rectal cancer as determined by abdominal CT. In each arm, detection of transmural invasion prompted preoperative XRT. Baseline probabilities were varied through plausible ranges using sensitivity analysis. Cost inputs were based on Medicare professional plus facility fees. Endpoints were cost of treatment per patient and tumor recurrence-free rates. Cost-effectiveness (cost per prevention of local recurrence) and incremental cost-effectiveness ratios were calculated. For proximal rectal tumors, evaluation with abdominal CT plus EUS is the most cost-effective approach ($24,468/yr) compared with abdominal CT plus pelvic magnetic resonance imaging ($24,870) and CT alone ($26,076). Both the magnetic resonance imaging- and CT-only approaches were dominated (i.e., more costly and less effective). Abdominal CT plus EUS is the most cost-effective staging strategy for nonmetastatic proximal rectal cancer. Staging strategies incorporating EUS improve treatment allocation by achieving more accurate T staging, thereby optimizing the benefit of preoperative XRT to more advanced tumors.


Metabolism of R- and S-warfarin by CYP2C19 into four hydroxywarfarins.
Coumadin (R/S-warfarin) is a highly efficacious and widely used anticoagulant; however, its highly variable metabolism remains an important contributor to uncertainties in therapeutic responses. Pharmacogenetic studies report conflicting findings on the clinical relevance of CYP2C19. A resolution to this controversy is impeded by a lack of de tailon the potential role of CYP2C19 in warfarin metabolism. Consequently, we assessed the efficiency of CYP2C19 metabolism of R- and S-warfarin and explored possible contributions in the liver using in vitro methods. Recombinant CYP2C19 metabolized R- and S-warfarin mainly to 6-, 7-, and 8-hydroxywarfarin, while 4'-hydroxywarfarin was a minormetabolite. Over all R-warfarin metabolism was slightly more efficient than that for S-warfarin. Metabolic pathways thatproduce R-6-, 7-, and 8-hydroxywarfarin in human liver microsomal reactions correlated strongly with CYP2C19 Smephenytoinhydroxylase activity. Similarly, CYP1A2 activity toward phenacetin correlated with formation of R-6 and 7-hydroxywarfarin such that R-8-hydroxywarfarin seems unique to CYP2C19 and possibly a biomarker. In following, CYP2C19 likely impacts R-warfarin metabolism and patient response to therapy. Intriguingly, CYP2C19 may contributeto S-warfarin metabolism in patients, especially when CYP2C9 activity is compromised due to drug interactions orgenetic polymorphisms.


Hydrogen-bonding interactions in acetic acid monohydrates and dihydrates by density-functional theory calculations.
Equilibrium structures and the respective binding energies of acetic acid monohydrates and dihydrates have been determined by density-functional theory calculations with different basis sets, including 6-31+G(3d,p), 6-311++G(d,p), and 6-311++G(3df,3pd). Given that the C=O and OH groups in acetic acid provide the predominant hydrogen-bonding interactions with water, six stable conformer structures have been found each for the monohydrate and syn-dihydrate. Of the three syn- and three anti-conformers of acetic acid with water, the most stable monohydrate structure is found to be that of the syn-conformer bonding with water in a cyclic double H-bonded geometry. Similarly, the syn-conformer bonding with two water molecules in a cyclic double H-bonded geometry has also been determined to be the most stable among the six plausible structures for the syn-dihydrate. Frequency analysis of the stable conformers has been performed and the vibrational spectra of the most stable monohydrate and dihydrate structures are compared with the experimental gas-phase and matrix data. Furthermore, the calculated binding energies between an acetic acid and a water molecule for both monohydrate and dihydrate are larger than that between two water molecules, which supports our recent experimental observation of coevaporation of acetic acid with water upon annealing acetic acid on ice.


Modal analysis of annual runoff volume and sediment load in the Yangtze river-lake system for the period 1956-2013.
This study focuses on detecting trends in annual runoff volume and sediment load in the Yangtze river-lake system. Times series of annual runoff volume and sediment load at 19 hydrological gauging stations for the period 1956-2013 were collected. Based on the Mann-Kendall test at the 1% significance level, annual sediment loads in the Yangtze River, the Dongting Lake and the Poyang Lake were detected with significantly descending trends. The power spectrum estimation indicated predominant oscillations with periods of 8 and 20 years are embedded in the runoff volume series, probably related to the El Niño Southern Oscillation (2-7 years) and Pacific Decadal Oscillation (20-30 years). Based on dominant components (capturing more than roughly 90% total energy) extracted by the proper orthogonal decomposition method, total change ratios of runoff volume and sediment load during the last 58 years were evaluated. For sediment load, the mean CRT value in the Yangtze River is about -65%, and those in the Dongting Lake and the Poyang Lake are -92.2% and -87.9% respectively. Particularly, the CRT value of the sediment load in the channel inflow of the Dongting Lake is even -99.7%. The Three Gorges Dam has intercepted a large amount of sediment load and decreased the sediment load downstream.


The 'Surprise question' in heart failure: a prospective cohort study.
The Surprise Question (SQ) is a prognostic screening tool used to identify patients with limited life expectancy. We assessed the SQ's performance predicting 1-year mortality among patients in ambulatory heart failure (HF) clinics. We determined that the SQ's performance changes according to sex and other demographic (age) and clinical characteristics, mainly left ventricular ejection fraction (LVEF) and the New York Heart Association (NYHA) functional classifications. We conducted a prospective cohort study in two HF clinics. To assess the performance of the SQ in predicting 1-year mortality, we calculated the sensitivity, specificity, positive and negative likelihood ratios, and the positive and negative predictive values. To illustrate if the results of the SQ changes the probability that a patient dies within 1 year, we created Fagan's nomograms. We report the results from the overall sample and for subgroups according to sex, age, LVEF and NYHA functional class. We observed that the SQ showed a sensitivity of 85% identifying ambulatory patients with HF who are in the last year of life. We determined that the SQ's performance predicting 1-year mortality was similar among women and men. The SQ performed better for patients aged under 70 years, for patients with reduced or mildly reduced ejection fraction, and for patients NYHA class III/IV. We consider the tool an easy and fast first step to identify patients with HF who might benefit from an advance care planning discussion or a referral to palliative care due to limited life expectancy.


Refractory hypotension induced by Sheehan syndrome with pituitary crisis: A case report.
The present study reported on an unusual case of refractory hypotension induced by Sheehan syndrome with pituitary crisis and explored the causes and treatment of hypotension in hypopiptuitarism. Refractory hypotension is a rare and severe complication of longstanding hypopituitarism induced by Sheehan syndrome with pituitary crisis. A 48-year-old Chinese woman with pituitary crisis due to Sheehan syndrome developed refractory hypotension and received longstanding vasopressor blood pressure support and hormone replacement therapy. Besides normalized blood pressure, echocardiography over 3 months revealed partial reversibility of her cardiac function with hormone replacement therapy. Consistent numerous studies reviewed, hormone replacement therapy may improve cardiac function in patients with cardiomyopathy linked to Sheehan syndrome. A retrospective study of 77 cases with hypopituitarism encountered at Qilu Hospital of Shandong University (Jinan, China) was also performed and the incidence rate of hypotension was analyzed, revealing that the present case was the first of refractory hypotension induced by Sheehan syndrome with pituitary crisis at this institution in 16 years.