Actin-dependent localization of an RNA encoding a cell-fate determinant in yeast.
The cytoplasmic localization of messenger RNA creates an asymmetric distribution of proteins that specify cell fate during development in multicellular eukaryotes. The protein Ash1 is a cell-fate determinant in budding yeast which localizes preferentially to the presumptive daughter nucleus, where it inhibits mating-type switching. Here we show that Ash1 mRNA is localized to the distal tip of daughter buds in post-anaphase cells. Three-dimensional imaging reveals that Ash1 mRNA is assembled into particles that associate with the cell cortex. To achieve this localization, Ash1 mRNA must have its 3' untranslated region and the actin cytoskeleton must be intact. Ash1 mRNA is not localized correctly in the absence of a myosin (Myo4) and is mislocalized to the mother-bud neck in the absence of a regulator of the actin cytoskeleton known as Bnil. We propose that Ash1 mRNA particles are transported into the daughter bud along actin filaments and are anchored at the distal tip. Thus, as in higher eukaryotes, Saccharomyces cerevisiae employs RNA localization to generate an asymmetric distribution of proteins and hence to determine cell fate.


Mutual relationship between stacking and hydrogen bonding in DNA. Theoretical study of guanine-cytosine, guanine-5-methylcytosine, and their dimers.
The mutual relationship between stacking and hydrogen-bonding and the possible influence of stacking in the different behavior of cytosine (C) and 5-methylcytosine (C') in DNA have been studied through complete DFT optimization of different structures of G-C and G-C' dimers (i.e., G-C/C-G and G-C'/C'-G), using four different functionals. Our results show that stacking leads to an increase of the O(6)...H-N(4) hydrogen bond length and to a simultaneous decrease of the N(2)-H...O(2) one, in such a way that both lengths approach each other and, in some cases, an inversion occurs. These results suggest that stacking can be a factor to explain the disparity between theory and experiment on the relative strength of the two lateral hydrogen bonds. Regarding the difference between cytosine and 5-methylcytosine, we have shown that methylation enhances the stacking interactions, mainly due to the increase of polarizability. Methylation also favors the existence of slid structures which can produce local distortions of DNA.


Pulmonary exacerbations in cystic fibrosis.
The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12-month baseline period, data from 11692 patients were compared with data collected during the subsequent 6-month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and >or=6 years of age. The outcome of interest was any antibiotic treatment in the 6-month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients >or=6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients.


Thermodynamic behavior of correlated electron-hole fluids in van der Waals heterostructures.
Coupled two-dimensional electron-hole bilayers provide a unique platform to study strongly correlated Bose-Fermi mixtures in condensed matter. Electrons and holes in spatially separated layers can bind to form interlayer excitons, composite Bosons expected to support high-temperature exciton condensates. The interlayer excitons can also interact strongly with excess charge carriers when electron and hole densities are unequal. Here, we use optical spectroscopy to quantitatively probe the local thermodynamic properties of strongly correlated electron-hole fluids in MoSe2/hBN/WSe2 heterostructures. We observe a discontinuity in the electron and hole chemical potentials at matched electron and hole densities, a definitive signature of an excitonic insulator ground state. The excitonic insulator is stable up to a Mott density of ~0.8 × 1012 cm-2 and has a thermal ionization temperature of ~70 K. The density dependence of the electron, hole, and exciton chemical potentials reveals strong correlation effects across the phase diagram. Compared with a non-interacting uniform charge distribution, the correlation effects lead to significant attractive exciton-exciton and exciton-charge interactions in the electron-hole fluid. Our work highlights the unique quantum behavior that can emerge in strongly correlated electron-hole systems.


Left atrial volume: predictor of atrial fibrillation in patients with degenerative mitral regurgitation.
In patients with mitral regurgitation (MR) due to degenerative mitral valve prolapse (MVP), preoperative atrial fibrillation (AF) has been identified as an independent predictor of survival after surgery for MR. Thus, the determinants of preoperative AF may have critical implications to evaluate the timing of mitral valve repair. The study aim was to investigate the role of left atrial (LA) volume in predicting preoperative AF in patients with severe MR due to degenerative MVP. Sixty-six patients with severe degenerative MR (regurgitant volume > or =60 ml, regurgitant fraction > or =50%, effective regurgitant orifice area > or =0.4 cm(2)) in sinus rhythm (SR) at diagnosis and conservatively managed were eligible for the study. Complete two-dimensional (2-D) echocardiographic and Doppler measurements, including the measurement of maximum LA volume, were performed in all patients. During follow up under conservative management (18.1+/-4.8 months), eight patients (12%) experienced conversion to AF, and 58 remained in SR. The mean LA dimension was 4.0+/-0.5 cm in patients with SR, and 5.1+/-0.8 cm in those who developed AF (p <0.0001). The mean LA volume and LA volume index (indexed to body surface area) were 95 +/-23 ml and 60+/-14 ml/m(2) respectively in patients with SR, and 166+/-66 ml and 104+/-42 ml/m(2) respectively in those who developed AF (both p <0.0001). The optimal cut-off value for LA volume to predict AF conversion was 117.5 ml (sensitivity 88%, specificity 83%), and for LA volume index was 75 ml/m(2) (sensitivity 88%, specificity 88%). LA volume measurement should be considered in patients with degenerative severe MR diagnosed in SR. A LA volume index > or =75 ml/m(2) reflects the risk of subsequent AF, and patients should be closely monitored.


[Genital histoplasmosis. Presentation of a clinical case].
On December 1905 Darling, resident histopathologist on the Panama Channel area, observed a parasite in the large mononuclear cells of different organs. Negroni in 1914 described the first Argentinean case. Lung, oral, nasal, and laryngeal involvement are common. On the other hand, genital involvement is uncommon. The objective of this war is to communicate the case of a patient with genital histoplasmosis. A 60-year-old Argentinian male started two years before with penile lesions and pruritus. Two partial penile resections had been performed in 1999, but pathology reports were not available. The lesions evolved towards ulceration and bleeding. Surgical toilette was carried out. A partial penectomy and glanuloplasty with an original technique were performed. Pathology revealed intracellular and extracellular spherical microorganisms. Morphologically it was histoplasma capsulatum. The histoplasmosis is an endemic mycosis. The infection takes place when inhaling the microconidiae of the fungus filamentous phase. Only a small number of people develop the disease after infection. Diagnosis is made by discovering of 2-3 micron yeasts with Giemsa stain. If a patient from the histoplasmosis endemic area has a granular lesion, a mycotic disease should be considered.


Characterization and in vitro biological effects of ambient air PM10 from a rural, an industrial and an urban site in Sulaimani City, Iraq.
High urban atmospheric pollution is caused by economic and industrial growth, especially in developing countries. The objective of this study was to assess possible relationships between in vitro effects on human alveolar epithelial cells of source-related dust types collected at Sulaimani City (Iraq), and to determine their mineralogical and chemical composition. A passive sampler was used to collect dust particles at a rural, an industrial and an urban sampling site during July and August 2014. The samples were size-fractionated by a low-pressure impactor to obtain respirable dust with aerodynamic diameters of less than 10 μm. The dust was mainly composed of quartz and calcite. Chrysotile fibres (white asbestos) were also found at the urban site. Dust from the industrial and urban sites triggered cytotoxic and genotoxic effects in the cells, whereas only minor effects were observed for the sample from the rural site.


The clinical value of cardiopulmonary exercise testing in the modern era.
Cardiopulmonary exercise testing (CPET) has long been used as diagnostic tool for cardiac diseases. During recent years CPET has been proven to be additionally useful for 1) distinguishing between normal and abnormal responses to exercise; 2) determining peak oxygen uptake and level of disability; 3) identifying factors contributing to dyspnoea and exercise limitation; 4) differentiating between ventilatory (respiratory mechanics and pulmonary gas exchange), cardiovascular, metabolic and peripheral muscle causes of exercise intolerance; 5) identifying anomalies of ventilatory (respiratory mechanics and pulmonary gas exchange), cardiovascular and metabolic systems, as well as peripheral muscle and psychological disorders; 6) screening for coexistent ischaemic heart disease, peripheral vascular disease and arterial hypoxaemia; 7) assisting in planning individualised exercise training; 8) generating prognostic information; and 9) objectively evaluating the impact of therapeutic interventions. As such, CPET is an essential part of patients' clinical assessment. This article belongs to the special series on the "Ventilatory efficiency and its clinical prognostic value in cardiorespiratory disorders", addressed to clinicians, physiologists and researchers, and aims at encouraging them to get acquainted with CPET in order to help and orient the clinical decision concerning individual patients.


Common questions about Barrett esophagus.
Barrett esophagus is a precancerous metaplasia of the esophagus that is more common in patients with chronic reflux symptoms, although it also occurs in patients without symptomatic reflux. Other risk factors include smoking, male sex, obesity, white race, hiatal hernia, and increasing age (particularly older than 50 years). Although Barrett esophagus is a risk factor for esophageal adenocarcinoma, its management and the need for screening or surveillance endoscopy are debatable. The annual incidence of progression to esophageal cancer is 0.12% to 0.33%; progression is more common in patients with high-grade dysplasia and long-segment Barrett esophagus. Screening endoscopy should be considered for patients with multiple risk factors, and those who have lesions with high-grade dysplasia should undergo endoscopic mucosal resection or other endoscopic procedures to remove the lesions. Although the cost-effectiveness is questionable, patients with nondysplastic Barrett esophagus can be followed with endoscopic surveillance. Lowgrade dysplasia should be monitored or eradicated via endoscopy. Although there is no evidence that medical or surgical therapies to reduce acid reflux prevent neoplastic progression, proton pump inhibitors can be used to help control reflux symptoms.


Suppression of class I compensated cell enlargement by xs2 mutation is mediated by salicylic acid signaling.
The regulation of leaf size has been studied for decades. Enhancement of post-mitotic cell expansion triggered by impaired cell proliferation in Arabidopsis is an important process for leaf size regulation, and is known as compensation. This suggests a key interaction between cell proliferation and cell expansion during leaf development. Several studies have highlighted the impact of this integration mechanism on leaf size determination; however, the molecular basis of compensation remains largely unknown. Previously, we identified extra-small sisters (xs) mutants which can suppress compensated cell enlargement (CCE) via a specific defect in cell expansion within the compensation-exhibiting mutant, angustifolia3 (an3). Here we revealed that one of the xs mutants, namely xs2, can suppress CCE not only in an3 but also in other compensation-exhibiting mutants erecta (er) and fugu2. Molecular cloning of XS2 identified a deleterious mutation in CATION CALCIUM EXCHANGER 4 (CCX4). Phytohormone measurement and expression analysis revealed that xs2 shows hyper activation of the salicylic acid (SA) response pathway, where activation of SA response can suppress CCE in compensation mutants. All together, these results highlight the regulatory connection which coordinates compensation and SA response.


Consistency of effects is important in replication: Rejoinder to Mathur and VanderWeele (2019).
In this rejoinder, we discuss Mathur and VanderWeele's response to our article, "Statistical Analyses for Studying Replication: Meta-Analytic Perspectives," which appears in this current issue. We attempt to clarify a point of confusion regarding the inclusion of an original study in an analysis of replication, and the potential impact of publication bias. We then discuss the methods used by Mathur and VanderWeele to conduct an alternative analysis of the Gambler's Fallacy example from our article. We highlight that there are some potential statistical and conceptual differences to their approach compared to what we propose in our article. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Prevention of a Th1 disease by a Th1 cytokine: IL-12 and diabetes in NOD mice.
The effects of interleukin-12 on autoimmune diabetes in nonobese diabetic mice was examined. IL-12 was given, intraperitoneally, to NOD females in two different treatment protocols: three times a week, for 2 weeks beginning at 9 weeks of age and a single weekly injection, for 15 weeks, beginning at 9 weeks of age. A significant decrease in diabetes incidence was observed with multidose/short-term IL-12 treatment. Age of disease onset, however, was unchanged. Weekly administration of IL-12 was more effective in preventing onset of diabetes. Only 20% of female NOD mice become diabetic by 30 weeks of age, with a later age of onset. In spite of the decrease in diabetes incidence, no differences were seen in islet histology with treated mice compared to controls. Furthermore, IL-12 treatment of recipient mice did not prevent induction of diabetes using spleen cells from diabetic mice in adoptive transfer experiments. These observations are in contrast to reported data in which treatment of NOD mice with daily doses of IL-12 exacerbated disease incidence and hastened diabetes onset.


Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities.
Results from a new PET/CT scanner using lutetium-yttrium oxyorthosilicate (LYSO) crystals for the PET component are presented. This scanner, which operates in a fully 3-dimensional mode, has a diameter of 90 cm and an axial field of view of 18 cm. It uses 4 x 4 x 22 mm(3) LYSO crystals arranged in a pixelated Anger-logic detector design. This scanner was designed to perform as a high-performance conventional PET scanner as well as provide good timing resolution to operate as a time-of-flight (TOF) PET scanner. Performance measurements on the scanner were made using the National Electrical Manufacturers Association (NEMA) NU2-2001 procedures to benchmark its conventional imaging capabilities. The scatter fraction and noise equivalent count (NEC) measurements with the NEMA cylinder (20-cm diameter) were repeated for 2 larger cylinders (27-cm and 35-cm diameter), which better represent average and heavy patients. New measurements were designed to characterize its intrinsic timing resolution capability, which defines its TOF performance. Additional measurements to study the impact of pulse pileup at high counting rates on timing, as well as energy and spatial, resolution were also performed. Finally, to characterize the effect of TOF reconstruction on lesion contrast and noise, the standard NEMA/International Electrotechnical Commission torso phantom as well as a large 35-cm-diameter phantom with both hot and cold spheres were imaged for varying scan times. The transverse and axial resolution near the center is 4.8 mm. The absolute sensitivity of this scanner measured with a 70-cm-long line source is 6.6 cps/kBq, whereas scatter fraction is 27% measured with a 70-cm-long line source in a 20-cm-diameter cylinder. For the same line source cylinder, the peak NEC rate is measured to be 125 kcps at an activity concentration of 17.4 kBq/mL (0.47 microCi/mL). The 2 larger cylinders showed a decrease in the peak NEC due to increased attenuation, scatter, and random coincidences, and the peak occurs at lower activity concentrations. The system coincidence timing resolution was measured to be 585 ps. The timing resolution changes as a function of the singles rate due to pulse pileup and could impact TOF image reconstruction. Image-quality measurements with the torso phantom show that very high quality images can be obtained with short scan times (1-2 min per bed position). However, the benefit of TOF is more apparent with the large 35-cm-diameter phantom, where small spheres are detectable only with TOF information for short scan times. The Gemini TF whole-body scanner represents the first commercially available fully 3-dimensional PET scanner that achieves TOF capability as well as conventional imaging capabilities. The timing resolution is also stable over a long duration, indicating the practicality of this device. Excellent image quality is achieved for whole-body studies in 10-30 min, depending on patient size. The most significant improvement with TOF is seen for the heaviest patients.


Discontinuous shear thickening in Brownian suspensions.
Discontinuous shear thickening in dense suspensions naturally emerges from the activation of frictional forces by shear flow in non-Brownian systems close to jamming. Yet, this physical picture is incomplete as most experiments study soft colloidal particles subject to thermal fluctuations. To characterize discontinuous shear thickening in colloidal suspensions, we use computer simulations to provide a complete description of the competition between athermal jamming, frictional forces, thermal motion, particle softness, and shear flow. We intentionally neglect hydrodynamics, electrostatics, lubrication, and inertia, but can nevertheless achieve quantitative agreement with experimental findings. In particular, shear thickening corresponds to a crossover between frictionless and frictional jamming regimes which is controlled by thermal fluctuations and particle softness and occurs at a softness dependent Péclet number. We also explore the consequences of our findings for constant pressure experiments, and critically discuss the reported emergence of "S-shaped" flow curves. Our work provides the minimal ingredients to quantitatively interpret a large body of experimental work on discontinuous shear thickening in colloidal suspensions.


The role of Chinese face in the perpetration of dating partner violence.
This study explored the associations between the perpetration of partner violence and two types of face orientation-protective and acquisitive-in Chinese societies. Data from a convenience sample of 3,388 university students from Hong Kong, Shanghai, and Beijing were analyzed. The participants completed the Protective and Acquisitive Face Orientation (PAFO) Scale Short Form and the Revised Conflict Tactics Scale (CTS2) to measure their face orientations and experience of perpetrating violence against their dating partner. Acquisitive face orientation (AFO) was positively associated with the self-reported perpetration of physical and psychological partner violence. No significant associations were found between protective face orientation (PFO) and partner violence perpetration. Gender differences were found across all types of dating violence. City of residence, age, and SES were also associated with partner violence in specific ways. The findings gave insights on the possible mechanisms between partner violence and the concept of face to be explored in future research.


Two-stage chemical oncogenesis in cultures of C3H/10T1/2 cells.
The initiation and promotion stages of chemical oncogenesis have been demonstrated in cultured C3H/10T1/2 mouse embryo cells. Treatment of the cells with a subeffective concentration of 3-methylcholanthrene, benzo(a)pyrene, or 7,12-dimethylbenz(a)anthracene, followed 4 days later by a nontransforming amount of tetradecanoylphorbol acetate (TPA), phorbol didecanoate, or 4-alpha-phorbol didecanoate, produced transformation. Phorbol was ineffective. TPA did not select for transformed cells. When TPA treatment preceded 3-methylcholanthrene, no enhancement of transformation was observed. When TPA was added immediately after hydrocarbon treatment, there was a significant inhibition of transformation. TPA did not exert promoting activity when the hydrocarbons were in high enough concentrations to produce appreciable transformation. The promoting action of TPA cannot be attributed only to a stimulation of cell division.


Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms.
Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer's long latency and multifactorial etiology make evaluation of these chemicals in humans challenging. For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development. We systematically searched the PubMed database for articles with breast cancer outcomes published in 2006-2016 using terms for 134 environmental chemicals, sources, or biomarkers of exposure. We critically reviewed the articles. We identified 158 articles. Consistent with experimental evidence, a few key studies suggested higher risk for exposures during breast development to dichlorodiphenyltrichloroethane (DDT), dioxins, perfluorooctane-sulfonamide (PFOSA), and air pollution (risk estimates ranged from 2.14 to 5.0), and for occupational exposure to solvents and other mammary carcinogens, such as gasoline components (risk estimates ranged from 1.42 to 3.31). Notably, one 50-year cohort study captured exposure to DDT during several critical windows for breast development (in utero, adolescence, pregnancy) and when this chemical was still in use. Most other studies did not assess exposure during a biologically relevant window or specify the timing of exposure. Few studies considered genetic variation, but the Long Island Breast Cancer Study Project reported higher breast cancer risk for polycyclic aromatic hydrocarbons (PAHs) in women with certain genetic variations, especially in DNA repair genes. New studies that targeted toxicologically relevant chemicals and captured biological hypotheses about genetic variants or windows of breast susceptibility added to evidence of links between environmental chemicals and breast cancer. However, many biologically relevant chemicals, including current-use consumer product chemicals, have not been adequately studied in humans. Studies are challenged to reconstruct exposures that occurred decades before diagnosis or access biological samples stored that long. Other problems include measuring rapidly metabolized chemicals and evaluating exposure to mixtures.


Does pre-enrichment of anodes with acetate to select for Geobacter spp. enhance performance of microbial fuel cells when switched to more complex substrates?
Many factors affect the performance of microbial fuel cells (MFCs). Considerable attention has been given to the impact of cell configuration and materials on MFC performance. Much less work has been done on the impact of the anode microbiota, particularly in the context of using complex substrates as fuel. One strategy to improve MFC performance on complex substrates such as wastewater, is to pre-enrich the anode with known, efficient electrogens, such as Geobacter spp. The implication of this strategy is that the electrogens are the limiting factor in MFCs fed complex substrates and the organisms feeding the electrogens through hydrolysis and fermentation are not limiting. We conducted a systematic test of this strategy and the assumptions associated with it. Microbial fuel cells were enriched using three different substrates (acetate, synthetic wastewater and real domestic wastewater) and three different inocula (Activated Sludge, Tyne River sediment, effluent from an MFC). Reactors were either enriched on complex substrates from the start or were initially fed acetate to enrich for Geobacter spp. before switching to synthetic or real wastewater. Pre-enrichment on acetate increased the relative abundance of Geobacter spp. in MFCs that were switched to complex substrates compared to MFCs that had been fed the complex substrates from the beginning of the experiment (wastewater-fed MFCs - 21.9 ± 1.7% Geobacter spp.; acetate-enriched MFCs, fed wastewater - 34.9 ± 6.7% Geobacter spp.; Synthetic wastewater fed MFCs - 42.5 ± 3.7% Geobacter spp.; acetate-enriched synthetic wastewater-fed MFCs - 47.3 ± 3.9% Geobacter spp.). However, acetate pre-enrichment did not translate into significant improvements in cell voltage, maximum current density, maximum power density or substrate removal efficiency. Nevertheless, coulombic efficiency (CE) was higher in MFCs pre-enriched on acetate when complex substrates were fed following acetate enrichment (wastewater-fed MFCs - CE = 22.0 ± 6.2%; acetate-enriched MFCs, fed wastewater - CE =58.5 ± 3.5%; Synthetic wastewater fed MFCs - CE = 22.0 ± 3.2%; acetate-enriched synthetic wastewater-fed MFCs - 28.7 ± 4.2%.) The relative abundance of Geobacter ssp. and CE represents the average of the nine replicate reactors inoculated with three different inocula for each substrate. Efforts to improve the performance of anodic microbial communities in MFCs utilizing complex organic substrates should therefore focus on enhancing the activity of organisms driving hydrolysis and fermentation rather the terminal-oxidizing electrogens.


Role of IP(3) in modulation of spontaneous activity in pacemaker cells of rabbit urethra.
Isolated interstitial ("pacemaker") cells from rabbit urethra were examined using the perforated-patch technique. Under voltage clamp at -60 mV, these cells fired large spontaneous transient inward currents (STICs), averaging -860 pA and >1 s in duration, which could account for urethral pacemaker activity. Spontaneous transient outward currents (STOCs) were also observed and fell into two categories, "fast" (<100 ms in duration) and "slow" (>1 s in duration). The latter were coupled to STICs, suggesting that they shared the same mechanism, while the former occurred independently at faster rates. All of these currents were abolished by cyclopiazonic acid, caffeine, or ryanodine, suggesting that they were activated by Ca(2+) release. When D-myo-inositol 1,4,5-trisphosphate (IP(3))-sensitive stores were blocked with 2-aminoethoxydiphenyl borate, the STICs and slow STOCs were abolished, but the fast STOCs remained. In contrast, the fast STOCs were more nifedipine sensitive than the STICs or the slow STOCs. These results suggest that while fast STOCs are mediated by a mechanism similar to STOCs in smooth muscle, STICs and slow STOCs are driven by IP(3). These results support the hypothesis that pacemaker activity in the urethra is driven by the IP(3)-sensitive store.


A feasibility study of robot-assisted percutaneous reduction and fixation technique for treating posterolateral depression tibial plateau fractures.
Posterolateral (PL)-depression fractures of the tibial plateau are difficult to manage. The aim of this study was: (1) to present our experience with a novel technique of robot-assisted percutaneous reduction and fixation and (2) to compare it with the traditional percutaneous screw osteosynthesis (PSO) technique for the treatment of PL-depression tibial plateau fractures. The clinical data of patients with PL-depression tibial plateau fractures treated by robot-assisted percutaneous reduction and fixation technique and traditional PSO technique from January 2017 to January 2021 were retrospectively analyzed. Among them, there were 18 cases in the robot-assisted group (RA group) and 23 cases in the PSO group. All fractures were unilateral, closed and fresh PL-depression fractures of the tibial plateau. Patients in the RA group were treated by robot assisted reduction and minimally invasive absorbable screw fixation. The PSO group was treated by closed reduction and percutaneous absorbable screw osteosynthesis. The incision length, operation time, intraoperative blood loss, fluoroscopic times, inpatient time, weight training time and postoperative complications of the two groups were statistically analyzed. The Rasmussen radiological score was used to assess the reduction quality after operation while the Rasmussen functional score was used to evaluate knee joint functions at one year postoperatively. All patients were followed for at least one year. There was no significant difference in demographic information between the two groups (p > 0.05). Compared with the PSO group, the RA group showed less fluoroscopic times and better Rasmussen radiological and functional scores (p < 0.05). Besides, there was no significant difference in the incidence of postoperative complications between the two groups (p > 0.05). The novel robot-assisted percutaneous reduction and fixation technique had the characteristics of less radiation, accurate reduction and fixation. It could accelerate the rehabilitation of patients with PL-depression fractures of the tibial plateau and enable patients to obtain good joint functions.


Self-assembly flexible SERS imprinted membrane based on Ag nanocubes for selective detection of microcystin-LR.
Silver nanocubes monolayer-modified polydimethylsiloxane (Ag NC/PDMS) flexible SERS substrates have been prepared by a three-phase interface self-assembly procedure. The combination of this method with membrane technology brings nanoparticles in close proximity, densely, and regularly arranged in monolayers over a large area, leading to excellent SERS properties. Considering the complexity of practical detection, molecular imprinted polymers (MIPs) were anchored on the surface of SERS substrate and applied to selective detection of microcystin-LR (MC-LR). It is worth mentioning that the SERS imprinted membranes (AP-MIMs) were still clearly detected at a concentration of 0.1 µg·L-1 of MC-LR in drinking water, and the detection limit was as low as 0.0067 µg·L-1. The substrate exhibited excellent uniformity with a relative standard deviation (RSD) of 6.1%. In the presence of interference molecules, AP-MIMs exhibited excellent selectivity for MC-LR. Furthermore, in the spiking and recovery tests of practical lake water samples, the method showed excellent recoveries ranging from 96.47 to 105.31%. It has been demonstrated that the prepared AP-MIMs can be applied to sensitive and specific detection of trace amounts of MC-LR in drinking water.


NDRG1 promotes endothelial dysfunction and hypoxia-induced pulmonary hypertension by targeting TAF15.
Pulmonary hypertension (PH) represents a threatening pathophysiologic state that can be induced by chronic hypoxia and is characterized by extensive vascular remodeling. However, the mechanism underlying hypoxia-induced vascular remodeling is not fully elucidated. By using quantitative polymerase chain reactions, western blotting, and immunohistochemistry, we demonstrate that the expression of N-myc downstream regulated gene-1 (NDRG1) is markedly increased in hypoxia-stimulated endothelial cells in a time-dependent manner as well as in human and rat endothelium lesions. To determine the role of NDRG1 in endothelial dysfunction, we performed loss-of-function studies using NDRG1 short hairpin RNAs and NDRG1 over-expression plasmids. In vitro, silencing NDRG1 attenuated proliferation, migration, and tube formation of human pulmonary artery endothelial cells (HPAECs) under hypoxia, while NDRG1 over-expression promoted these behaviors of HPAECs. Mechanistically, NDRG1 can directly interact with TATA-box binding protein associated factor 15 (TAF15) and promote its nuclear localization. Knockdown of TAF15 abrogated the effect of NDRG1 on the proliferation, migration and tube formation capacity of HPAECs. Bioinformatics studies found that TAF15 was involved in regulating PI3K-Akt, p53, and hypoxia-inducible factor 1 (HIF-1) signaling pathways, which have been proved to be PH-related pathways. In addition, vascular remodeling and right ventricular hypertrophy induced by hypoxia were markedly alleviated in NDRG1 knock-down rats compared with their wild-type littermates. Taken together, our results indicate that hypoxia-induced upregulation of NDRG1 contributes to endothelial dysfunction through targeting TAF15, which ultimately contributes to the development of hypoxia-induced PH.


Deletion of Marek's disease virus large subunit of ribonucleotide reductase impairs virus growth in vitro and in vivo.
Marek's disease virus (MDV), a highly cell-associated lymphotropic alphaherpesvirus, is the causative agent of a neoplastic disease in domestic chickens called Marek's disease (MD). In the unique long (UL) region of the MDV genome, open reading frames UL39 and UL40 encode the large and small subunits of the ribonucleotide reductase (RR) enzyme, named RR1 and RR2, respectively. MDV RR is distinguishable from that present in chicken and duck cells by monoclonal antibody T81. Using recombinant DNA technology we have generated a mutant MDV (Md5deltaRR1) in which RR1 was deleted. PCR amplification of the RR gene in Md5deltaRR1-infected duck embryo fibroblasts (DEF) confirmed the deletion of the 2.4 kb RR1 gene with a resultant amplicon of a 640-bp fragment. Restriction enzyme digests with SalI confirmed a UL39 deletion and the absence of gross rearrangement. The biologic characteristics of Md5deltaRR1 virus were studied in vitro and in vivo. The Md5deltaRR1 replicated in DEF, but significantly slower than parental Md5-BAC, suggesting that RR is important but not essential for replication in fibroblasts. In vivo studies, however, showed that the RR1 deletion virus was impaired for its ability to replicate in chickens. Inoculation of specific-pathogen-free (SPF) chickens with Md5deltaRR1 showed the mutant virus is nonpathogenic and does not induce MD in birds. A revertant virus, Md5deltaRR1/R, was generated with the restored phenotype of the parental Md5-BAC in vivo, indicating that RR is essential for replication of the virus in chickens. Protection studies in SPF chickens indicated that the Md5deltaRR1 virus is not a candidate vaccine against MD.


Failure rates in the hepatocellular carcinoma surveillance process.
Hepatocellular carcinoma (HCC) surveillance is underutilized among patients with cirrhosis. Understanding which steps in the surveillance process are not being conducted is essential for designing effective interventions to improve surveillance rates. The aim of our study was to characterize reasons for failure in the HCC surveillance process among a cohort of cirrhotic patients with HCC. We conducted a retrospective cohort study of cirrhotic patients diagnosed with HCC at a large urban safety-net hospital between 2005 and 2011. Patients were characterized by receipt of HCC surveillance over a two-year period before HCC diagnosis. Among patients without HCC surveillance, we classified reasons for failure into four categories: failure to recognize liver disease, failure to recognize cirrhosis, failure to order surveillance, and failure to complete surveillance despite orders. Univariate and multivariate analyses were conducted to identify predictors of failures. We identified 178 patients with HCC, of whom 20% had undergone surveillance. There were multiple points of failure-20% had unrecognized liver disease, 19% had unrecognized cirrhosis, 38% lacked surveillance orders, and 3% failed to complete surveillance despite orders. Surveillance was more likely among patients seen by hepatologists [OR, 6.11; 95% confidence interval (CI), 2.5-14.8] and less likely in those with alcohol abuse (OR, 0.14; 95% CI, 0.03-0.65). Although a retrospective analysis in a safety-net hospital, our data suggest that only one in five patients received surveillance before HCC diagnosis. There are multiple points of failure in the surveillance process, with the most common being failure to order surveillance in patients with known cirrhosis. Future interventions must target multiple failure points in the surveillance process to be highly effective.


Fast and Efficient Genome Editing of Human FOXP3+ Regulatory T Cells.
FOXP3+ regulatory T cells (Tregs) are central for maintaining peripheral tolerance and immune homeostasis. Because of their immunosuppressive characteristics, Tregs are a potential therapeutic target in various diseases such as autoimmunity, transplantation and infectious diseases like COVID-19. Numerous studies are currently exploring the potential of adoptive Treg therapy in different disease settings and novel genome editing techniques like CRISPR/Cas will likely widen possibilities to strengthen its efficacy. However, robust and expeditious protocols for genome editing of human Tregs are limited. Here, we describe a rapid and effective protocol for reaching high genome editing efficiencies in human Tregs without compromising cell integrity, suitable for potential therapeutic applications. By deletion of IL2RA encoding for IL-2 receptor α-chain (CD25) in Tregs, we demonstrated the applicability of the method for downstream functional assays and highlighted the importance for CD25 for in vitro suppressive function of human Tregs. Moreover, deletion of IL6RA (CD126) in human Tregs elicits cytokine unresponsiveness and thus may prevent IL-6-mediated instability of Tregs, making it an attractive target to potentially boost functionality in settings of adoptive Treg therapies to contain overreaching inflammation or autoimmunity. Thus, our rapid and efficient protocol for genome editing in human Tregs may advance possibilities for Treg-based cellular therapies.


[Experimental study of the anabolic activity of 6-ketoderivatives of certain natural sapogenins].
It is shown that 6-ketoderivatives of natural sapogenins, viz. agigenin, diosgenin and alliogenin, display the anabolic activity and do not manifest any androgenic properties. The compoud IV/(25 R)-5alpha-spirostan-2alpha, 3beta, 5alpha-triol-6-OH/produces an accelerated gain of weight in rats, and also an increase in the weight of the liver, heart, kidneys, musculus tibiliasis anterior and augments the total amount of protein therein. All of the above-mentioned changes become more pronounced with the study substance introduced to young animals. Castration of sexually immature rats greatly mitigates the anabolic effect of the compound IV.


Intestinal cytomegalovirus infection in patients hospitalized for exacerbation of inflammatory bowel disease: a 10-year tertiary referral center experience.
This 10-year retrospective cohort study aims to determine the prevalence and risk factors of cytomegalovirus (CMV) infection in inpatients with exacerbated inflammatory bowel disease (IBD). All patients admitted to the Department of Gastroenterology of the University Hospital Heidelberg for IBD exacerbation between January 2004 and June 2013 were enrolled. To identify the risk factors of CMV infection, infected individuals were compared with those with excluded infection. Among 297 patients with exacerbated IBD, 21 had confirmed CMV infection and 79 had excluded CMV infection, whereas the remaining patients had not been sufficiently tested for CMV. Taking into account only sufficiently tested individuals, the prevalence of CMV infection was 22.7% in ulcerative colitis and 16.0% in Crohn's disease. The occurrence of CMV infection was associated with the following variables at admission: age of 30 years or more [odds ratio (OR) 14.29; P=0.004], disease duration less than 60 months (OR 7.69; P=0.011), a blood leukocyte count less than 11/nl (OR 4.49; P=0.041), and immunosuppressive therapy (OR 6.73; P=0.0129). CMV-positive patients remained in the hospital longer than noninfected patients (P=0.0009). In the CMV-positive cohort, a 66-year-old woman died of CMV pneumonia and sepsis, whereas there was no death in the CMV-negative cohort. Immunuosuppressive therapy and age older than 30 years were identified as the main risk factors for the development of CMV infection in exacerbated IBD. Because of the risk of death, diagnostics of CMV infection should especially be initiated in older patients on immunosuppressive therapy.


Correlates of sexual activity and inconsistent condom use among high-school girls in Dominica.
To determine factors associated with sexual activity and inconsistent condom use among high-school girls in Dominica. A cross-sectional study was conducted at five high-schools in Dominica in 2000 to assess behaviour that may put high-school girls at risk for HIV The main outcome variable, sexual activity, was defined as vaginal or anal sex, and inconsistent condom use defined as none to infrequent condom use. The convenience sample consisted of 204 girls (median age 16 years). Forty-one per cent (41%) of girls reporting at least one episode of sexual activity. Sexual intercourse was associated with past sexual coercion (OR = 7.2, 95% CI 2.4, 21.8), oral sex (OR = 8.0, 95% CI 3.0, 21.0) and smoking marijuana (OR = 8.2, 95% CI 2.9, 23.0). Among sexually active girls, 59% were inconsistent condom users. Variables associated with inconsistent condom use were being coerced (OR 2.8, 95% CI 0.9, 8.2) and low socio-economic status (OR 3.3, 95% CI 1.1, 9.6). Sexual activity and inconsistent condom use occur frequently among high-school girls in Dominica. Therefore, strategies directed at delaying the onset of sexual activities such as providing accurate and age-appropriate information on sexuality in the context of the economic and social conditions of their daily lives, and increasing condom use are important in HIV prevention in this population.


Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.
The efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) is limited due to drug resistance and cardiotoxic effects. Preclinical studies have shown that statin induces apoptosis and decreases breast cancer cell growth. This study aims to evaluate the role of statin in combination with fluorouracil, adriamycin, and cyclophosphamide (FAC) therapy in LABC patients. We undertook a randomized, double-blinded, placebo-controlled trial in two centers of Indonesia. Patients were randomly assigned to FAC plus simvastatin (40 mg/day orally) or FAC plus placebo (40 mg/day) for 21 days. The FAC regimen was repeated every 3 weeks. We evaluated the clinical response, pathological response, and toxicities. The objective response rate (ORR) for FAC plus simvastatin was 90% (95% confidence interval [CI], 0.99 to 1.67) by per-protocol analysis. No complete responses (CR) were recorded, but there were 48 partial responses. No significant difference was observed between the two groups with the ORR (p=0.103). The pathological CR rate was 6.25% (2 in simvastatin group and 1 in placebo group). Adverse events in both arms were generally mild, mainly consisted of myotoxicity. Human epidermal growth factor receptor 2 (HER2) expression was a factor related to the success of therapeutic response (odds ratio, 4.2; 95% CI, 1.121 to 15.731; p=0.033). This study suggests that simvastatin combined with FAC shows improvements in ORR and pathological response in patients with LABC. Although no statistically significant difference was documented, there was a trend for better activity and tolerability. The addition of 40 mg simvastatin may improve the efficacy of FAC in LABC patients with HER2 overexpression.


Release and uptake rates of 5-hydroxytryptamine in the dorsal raphe and substantia nigra reticulata of the rat brain.
Fast scan cyclic voltammetry with carbon fiber electrodes has been used to investigate the dynamics of the neurotransmitter 5-hydroxytryptamine (5-HT) in the extracellular fluid of two brain regions: the dorsal raphe and the substantia nigra reticulata. The method used previously was shown to be optimized to allow the time course of 5-HT concentration changes to be measured rapidly. Measurements were made in slices prepared from the brains of rats with the carbon fiber electrode inserted into the tissue and a bipolar stimulating electrode placed on the slice surface. Identification of 5-HT as the detected substance in both regions was based on voltammetric, anatomical, physiological, and pharmacological evidence. Autoradiography using [3H]paroxetine revealed highest 5-HT transporter binding densities in the regions in which voltammetric measurements were made. Evaluation of the pharmacological actions of tetrodotoxin and tetrabenazine, as well as the effects of calcium removal, suggested that 5-HT storage was vesicular and that the release process was exocytotic. The effects of fluoxetine (0.5 microM) were typical of a competitive uptake inhibitor, changing Km with little effect on Vmax. Release of 5-HT was found to be maximal with wide (2-ms) stimulus pulses in both regions, as expected for release from small unmyelinated processes, and to increase linearly with the number of pulses when high frequencies (100 Hz) were used. At lower frequencies, the concentration observed was a function of both release and uptake. Kinetic simulations of the data revealed that the major difference in 5-HT neurotransmission between the two regions was that release and uptake rates are twice as large in the dorsal raphe ([5-HT] per pulse = 100 +/- 20 nM, Vmax = 1,300 +/- 20 nM/s for dorsal raphe; [5-HT] per pulse = 55 +/- 7 nM, Vmax = 570 +/- 70 nM/s for substantia nigra reticulata). When normalized to tissue content, uptake rates in both regions were identical and similar to rates previously reported for dopamine in dopamine terminal regions. Nonetheless, compared with dopaminergic transmission in terminal regions such as the striatum, the absolute clearance rates in the substantia nigra reticulata and dorsal raphe were lower, resulting in a longer lifetime of 5-HT in the extracellular fluid and allowing long-range interactions.


Green fluorescent protein as a scaffold for intracellular presentation of peptides.
Peptide aptamers provide probes for biological processes and adjuncts for development of novel pharmaceutical molecules. Such aptamers are analogous to compounds derived from combinatorial chemical libraries which have specific binding or inhibitory activities. Much as it is generally difficult to determine the composition of combinatorial chemical libraries in a quantitative manner, determining the quality and characteristics of peptide libraries displayed in vivo is problematical. To help address these issues we have adapted green fluorescent protein (GFP) as a scaffold for display of conformationally constrained peptides. The GFP-peptide libraries permit analysis of library diversity and expression levels in cells and allow enrichment of the libraries for sequences with predetermined characteristics, such as high expression of correctly folded protein, by selection for high fluorescence.


Acuity and colour vision changes post intravitreal dexamethasone implant injection in patients with diabetic macular oedema.
To evaluate changes in colour vision following intravitreal injection of Dexamethasone implant (Ozurdex) in patients with diabetic macular oedema (DMO). Both red-green (RG) and yellow-blue (YB) chromatic sensitivity were assessed using the Colour Assessment & Diagnosis (CAD) test which isolates the use of colour signals and provides age-corrected, statistical limits for normal trichromats. To determine whether colour changes and visual acuity (VA) post-treatment relate to central sub-field retinal thickness (CST). Fourteen patients with DMO who were undergoing treatment with Ozurdex were recruited for this study. RG and YB colour thresholds were measured using the CAD test, best corrected visual acuity was assessed using the ETDRS chart and CST was measured using spectral domain optical coherence tomography (SD-OCT). All tests were performed monocularly at baseline and 24 weeks post injection. All patients (n = 14 eyes), had significant loss of RG and YB chromatic sensitivity at baseline (p<0.05). The mean age was 56 ± 9.5 years. The age specific, monocular, upper normal limits for a 56 year old subject are 2.66 for RG and 2.85 for YB. In this study, the measured, pre injection thresholds (mean±SD) were 22.6 ± 11.3 for RG and 16.2 ± 3.76 for YB. There was significant improvement in RG threshold post injection (i.e., 19.2 ± 10.8 (p<0.05)). No significant changes were found in the YB thresholds with corresponding mean and range values of: 15.8 ± 4.6 (p = 0.23). CST pre-treatment was 542 ±135 μm. After treatment and by week 24 the CST values decreased to 435 ±127 μm. RG colour thresholds provide a sensitive measure of functional change in diabetic subjects with macular oedema. The YB system is damaged severely in the DMO patients studied and shows little or no recovery post treatment. The improvement in VA and particularly in RG colour vision correlate well with the measured decrease in CST. The results suggest that the improvement in the RG chromatic sensitivity can provide a useful biomarker for monitoring the efficacy of treatment in DMO.


A sequence upstream from the coding region is required for the transcription of the 7SK RNA genes.
We have isolated and characterized two recombinant lambda phages containing sequences homologous to 7SK RNA which code for a RNA 330 nucleotides long in an "in vitro" transcription system. S1 mapping of the transcript shows that this RNA corresponds to the 7SK RNA obtained from human cells, indicating that the two recombinant phages contain genes coding for 7SK RNA. The transcription of these genes is polymerase III dependent. Sequences upstream from the start of transcription are essential for "in vitro" synthesis of 7SK RNA, suggesting that internal promoter elements, if present, are not sufficient to support the synthesis of 7SK RNA. A region of homology with the upstream sequences of the genes for U6 RNA, 7SL RNA and Bombyx mori alanine tRNA is found within 50 bp from the transcription start point. Within the homologous region a motif common to the four genes is a "TATA"-like box, placed at position -30 to -25 of the 7SK RNA gene, which is typical of the polymerase II promoter region.


[Interaction of microorganisms with solids].
The paper generalizes data from literature dedicated to microorganisms interaction with solids. This interaction is widely spread in nature and considerably affects physiological activity of microbial populations. The role of physical, chemical and biological factors in this process is analyzed. It is noted that under certain conditions the hydrophobic forces are the basic factor in this interaction. The role of the cell surface components in this process is discussed.


Ripple (approximately 200-Hz) oscillations in temporal structures.
Spontaneous network oscillations near 200 Hz have been described in the hippocampus and parahippocampal regions of rodents and humans. During the last decade the characteristics and the mechanisms behind these field "ripples" have been studied extensively, mainly in rodents. They occur during rest or slow-wave sleep and provide a very fast, short-lasting (approximately 50 msec) rhythmic and synchronous activation of specific projection cells and interneurons. Ripples are frequently triggered by a massive synaptic activation from the hippocampal CA3 subfield, which is called a sharp wave. Recent evidence suggests that ripples have a specific task in memory processing-namely, that they convey information stored in the hippocampus to the cortex where it can be preserved permanently. Network mechanisms involved in ripple oscillations may be relevant for understanding pathologic synchronization processes in temporal lobe epilepsy.


Biosynthesis and processing of class II histocompatibility antigens.
The class II major histocompatibility antigens at the cell surface exist as heterodimers of alpha and beta subunits. During biosynthesis, these subunits are associated with a third chain, the invariant (I) or I chain. Association with the I chain occurs early in biosynthesis in the rough endoplasmic reticulum and persists during transport through the Golgi apparatus. One of the two alpha subunit N-linked oligosaccharides and the single beta subunit N-linked oligosaccharide are converted to the complex form during Golgi transit. In the human system, both I chain N-linked oligosaccharides can also be processed to the complex form, and at least two O-linked oligosaccharides can be added to the I chain. At some point during transit to the cell surface, class II antigens associate with a proteoglycan bearing chondroitin sulfate side chains. Complexes containing alpha, beta and I chain subunits and the associated proteoglycan accumulate in human B-cell lines treated with the ionophore monensin, an inhibitor of Golgi transport, suggesting that this may be a biosynthetic intermediate in class II antigen transport and assembly. Prior to cell surface expression of class II antigens, the exocytic pathway which they follow intersects the endocytic route, followed by certain ligands internalized by receptor-mediated endocytosis. The I chain appears to dissociate from mature class II alpha, beta dimers prior to their cell surface expression but following the intersection of the exocytic and endocytic pathways.


Silver impregnation method for neurons and myelinated axons of acult central nervous system.
A new method has been developed for silver impregnation of neurons and myelinated axons in the cerebral cortex of the adult dog. By this method principal types of neurons including pyramidal, stellate, fusiform, horizontal neurons of Layer I, and special auditory neurons are colored black with a clear background, while myelinated fibers in the same piece of tissue are colored yellow. The yellow hue appears limited to the myelin sheath. Meyelinated axons of all sizes in the molecular layer, radial bundles, and deep tangential strata accept the stain. Comparison with data from other experiments indicates that osmium tetroxide inhibits the yellow staining of the myelinated axons, and that formaldehyde promotes such staining in conjunction with ammonium ions and sucrose.


SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab‑resistant ovarian cancer model.
Ovarian cancer is one of the most common gynecologic cancers and the leading cause of mortality in women worldwide. HER2/neu is overexpressed in various types of cancers and is most commonly associated with decreased survival. Trastuzumab is a humanized anti-HER2 monoclonal antibody for the treatment of HER2-positive breast cancers. However, primary and/or acquired resistance occurs in up to 62% patients during the first year of treatment. Vascular endothelial growth factor (VEGF) is a well‑known angiogenesis factor involved in many physiological and pathological processes. Its significance has been implicated in promoting tumor growth and metastasis via angiogenesis. In the present study, we demonstrated that the upregulation of SP1 enhanced expression of VEGF promoting the angiogenesis and migration of trastuzumab-resistant ovarian cancer cell line SKOV3-T. Our in vitro and in vivo results both gave evidence that the SP1-VEGF axis was responsible for the enhanced malignancy, angiogenesis and migration in the acquired trastuzumab-resistant ovarian cancer cell model.


Circulating catecholamines and sympathetic activity after head injury.
Plasma norepinephrine (NE) and dopamine beta-hydroxylase (DBH) levels were measured during the first 7 days after head injury in 48 patients. Blood pressure, pulse, temperature, and Glasgow coma score (GCS) were recorded at the time of sampling for each patient, and the relationships of these to NE and DBH were examined. In patients with multiple trauma, NE levels were usually elevated, regardless of the GCS. In patients with head injury alone, however, NE was proportional to GCS. Alert patients after a brief loss of consciousness (GCS, 14) had normal NE levels. Those in coma had levels as high as 7 times normal. Blood pressure, pulse, and temperature were found to be elevated proportionally to elevations in plasma NE in patients with head injury. The finding of elevated plasma NE in patients with severe head injury raises the possibility of adverse effects of sympathetic hyperactivity in patients with severe head injury, including hypermetabolism, cardiovascular abnormalities, and direct effects of catecholamines on the damaged central nervous system.


Intussusception in a preterm neonate; a very rare, major intestinal problem--systematic review of cases.
Intussusception is an extremely rare disorder in preterm infants and it is often misdiagnosed as necrotizing enterocolitis. We report a case of intussusception in a 30-day-old preterm infant of 26 weeks of gestational age and a birthweight of 610 g who was diagnosed via abdominal ultra sonography. A systematic review of the literature was performed and reports on 23 previous cases were found. The presence of recognizable causes of intussusception in preterms, such as Meckel's diverticulum, bowel polypus, etc. was very infrequent. Comorbidity before and after intussusception is heterogeneous and related to prematurity. The intussusception is predominantly located in the small bowel (91.6%)--ileal or jejunal. The condition is misdiagnosed as NEC and managed conservatively until clinical deterioration occurs. A definitive diagnosis is thus established during abdominal surgery, which is usually delayed an average of 9.5 days from the onset of symptoms. Our case illustrates the capability of abdominal ultrasonography to establish early diagnosis of intussusception in the premature newborn.


The spatial-temporal characteristics of type I collagen-based extracellular matrix.
Type I collagen abounds in mammalian extracellular matrix (ECM) and is crucial to many biophysical processes. While previous studies have mostly focused on bulk averaged properties, here we provide a comprehensive and quantitative spatial-temporal characterization of the microstructure of type I collagen-based ECM as the gelation temperature varies. The structural characteristics including the density and nematic correlation functions are obtained by analyzing confocal images of collagen gels prepared at a wide range of gelation temperatures (from 16 °C to 36 °C). As temperature increases, the gel microstructure varies from a "bundled" network with strong orientational correlation between the fibers to an isotropic homogeneous network with no significant orientational correlation, as manifested by the decaying of length scales in the correlation functions. We develop a kinetic Monte-Carlo collagen growth model to better understand how ECM microstructure depends on various environmental or kinetic factors. We show that the nucleation rate, growth rate, and an effective hydrodynamic alignment of collagen fibers fully determines the spatiotemporal fluctuations of the density and orientational order of collagen gel microstructure. Also the temperature dependence of the growth rate and nucleation rate follow the prediction of classical nucleation theory.


[Development of osteoplastic gene-activated 3D matrices based on adenoviral vectors].
Gene therapy is one of the most promising approaches in regenerative medicine for the restoration of extensive bone defects in dentistry and maxillofacial surgery. Matrices obtained using three-dimensional printing from bioresorbable polymers, impregnated with adenoviral constructs with genes for osteoinductive factors, can ensure safe and effective formation of bone tissue. To study the properties of three-dimensional matrices based on polylactic-co-glycolic acid and adenoviral constructs with the GFP gene in vitro. The matrices were obtained by antisolvent three-dimensional printing. Transduction efficiency was assessed by fluorescence microscopy and flow cytometry. The cytocompatibility of the matrices was assessed by the MTT test and by staining cells with fluorescent dyes. Matrices based on polylactic-co-glycolic acid have high cytocompatibility on adipose tissue-derived mesenchymal stem cells. Impregnation of adenoviral vectors with the green fluorescent protein gene in 3D matrices ensures the release of viral particles within a week, maintaining their high transducing ability. The developed method for obtaining gene-activated matrices can serve as the basis for the creation of effective osteoplastic materials for bone regeneration.


Genome-wide characterisation and analysis of bHLH transcription factors related to tanshinone biosynthesis in Salvia miltiorrhiza.
Salvia miltiorrhiza Bunge (Labiatae) is an emerging model plant for traditional medicine, and tanshinones are among the pharmacologically active constituents of this plant. Although extensive chemical and pharmaceutical studies of these compounds have been performed, studies on the basic helix-loop-helix (bHLH) transcription factors that regulate tanshinone biosynthesis are limited. In our study, 127 bHLH transcription factor genes were identified in the genome of S. miltiorrhiza, and phylogenetic analysis indicated that these SmbHLHs could be classified into 25 subfamilies. A total of 19 sequencing libraries were constructed for expression pattern analyses using RNA-Seq. Based on gene-specific expression patterns and up-regulated expression patterns in response to MeJA treatment, 7 bHLH genes were revealed as potentially involved in the regulation of tanshinone biosynthesis. Among them, the gene expression of SmbHLH37, SmbHLH74 and SmbHLH92 perfectly matches the accumulation pattern of tanshinone biosynthesis in S. miltiorrhiza. Our results provide a foundation for understanding the molecular basis and regulatory mechanisms of bHLH transcription factors in S. miltiorrhiza.


Self-locomotion and spatial language and spatial cognition: insights from typical and atypical development.
Various studies have shown that occurrence of locomotion in infancy is correlated with the development of spatial cognitive competencies. Recent evidence suggests that locomotor experience might also be important for the development of spatial language. Together these findings suggest that locomotor experience might play a crucial role in the development of linguistic-cognitive spatial skills. However, some studies indicate that, despite their total deprivation of locomotor experience, young children with spinal muscular atrophy (SMA) have the capacity to acquire and use rich spatial representations including good spatial language. Nonetheless, we have to be cautious about what the striking performances displayed by SMA children can reveal on the link between motor and spatial development, as the dynamics of brain development in atypically developing children are different from typically developing children.


Partial purification and properties of guinea-pig liver polynucleotide phosphorylase.
1. Polynucleotide phosphorylase has been isolated and partially purified from crude preparations of guinea-pig liver nuclei. 2. The enzyme is particulate and associated with RNA and lipids characteristic of membranes. 3. It has phosphorolysis and exchange activities, but the latter may be due to a contaminating enzyme. 4. The phosphorolysis activity is dependent on bivalent cations, preferably Mg(2+), has a pH optimum between 8.6 and 9.2 and is inhibited by potassium chloride and sodium chloride. 5. The enzyme catalyses phosphorolysis of poly A, poly C, poly U, rRNA and tRNA. Poly G is only phosphorolysed to a very small extent and DNA is not a substrate. 6. The enzyme appears to lack nucleoside diphosphate polymerization activity.


Sensitivity of a new commercial enzyme-linked immunospot assay (T SPOT-TB) for diagnosis of tuberculosis in clinical practice.
Diagnosis of active and latent tuberculosis (TB) remains a challenge; however, over the last few years, a new approach based on detecting Mycobacterium tuberculosis-specific T cells has shown much promise. In particular, there is substantial published evidence showing that the detection of ESAT-6- and CFP-10-specific T cells using the ex vivo enzyme-linked immunospot technique is a marked improvement over the existing tuberculin skin test. This technique, which detects gamma interferon-producing T cells, is now available as the commercial assay T SPOT-TB (Oxford Immunotec, Oxford, UK). In the present study, the usefulness of the T SPOT-TB test for diagnosis of TB in "real-world" clinical practice was investigated. Ninety patients of a southern German referral centre for TB with confirmed or suspected TB were randomly selected for this study. The results of the T SPOT-TB test were compared with the results of conventional diagnostic tools. The T SPOT-TB test detected 70 of 72 patients with pulmonary or extrapulmonary TB, indicating a sensitivity of 97.2% (95% confidence interval, 90.3-99.7). For 45 of these patients, tuberculin skin test (TST) results were also available. Only 40 (89%) of these 45 patients were positive in the TST compared to all 45 (100%) in the T SPOT-TB test (p=0.056). Among 12 of 90 patients for whom active TB disease was ruled out, the T SPOT-TB test was negative for 11 (92%), allowing the rapid exclusion of TB in patients suspected to have active TB disease. The T SPOT-TB test is a sensitive assay for detection of TB and represents a useful addition to the diagnostic algorithm available for detecting TB in low-incidence settings.


Polymer Colloids: Moving beyond Spherical Particles.
When thinking about colloidal particles, the fist image that comes into mind is that of tiny little polystyrene spheres with a narrow size distribution. While spherical polymer colloids are one of the workhorses of colloid science, scientists have been working on the development of progressively advanced strategies to move beyond particles with spherical shapes, and prepared polymer colloids with more complex morphologies. This short review aims at providing a summary of these developments, focusing primarily on methods applicable to submicron particles, with an eye towards their applications and some discussion about advantages and drawbacks of the various approaches.


Comparative study of skin phototoxicity with three drugs by an in vivo mouse model.
Photosafety evaluation is becoming important during the drug development process in pharmaceutical companies. Both in vitro and in vivo test systems have been developed for the evaluation of phototoxic potential of chemicals. In the present study, we conducted an in vivo phototoxicity test using BALB/c mice. The mice were treated with sparfloxacin, lomefloxacin, or a quinoline derivative orally followed by the irradiation of simulated sunlight, and resulting phototoxic reactions of the ears were assessed. Sparfloxacin and lomefloxacin, but not the quinoline derivative, are well known to cause photoirritation in humans. All three drugs exhibited positive reaction in the 3T3 neutral red uptake phototoxicity test (3T3 NRU PT). In the in vivo test, sparfloxacin and lomefloxacin exhibited positive skin reaction in mice, but the quinoline derivative did not. The results of in vivo phototoxicity test in the mice coincided with phototoxic potential of these drugs in humans. The exposure levels of sparfloxacin or lomefloxacin at the minimum effective dose that exhibited phototoxic reaction in the mice were comparable with those in humans treated with the recommended therapeutic dose.


Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia.
Naked mole rats are among the most hypoxia-tolerant mammals identified and live in chronic hypoxia throughout their lives. The physiological mechanisms underlying this tolerance, however, are poorly understood. Most vertebrates hyperventilate in acute hypoxia and exhibit an enhanced hyperventilation following acclimatization to chronic sustained hypoxia (CSH). Conversely, naked mole rats do not hyperventilate in acute hypoxia and their response to CSH has not been examined. In this study, we explored mechanisms of plasticity in the control of the hypoxic ventilatory response (HVR) and hypoxic metabolic response (HMR) of freely behaving naked mole rats following 8-10 days of chronic sustained normoxia (CSN) or CSH. Specifically, we investigated the role of the major inhibitory neurotransmitter γ-amino butyric acid (GABA) in mediating these responses. Our study yielded three important findings. First, naked mole rats did not exhibit ventilatory plasticity following CSH, which is unique among adult animals studied to date. Second, GABA receptor (GABAR) antagonism altered breathing patterns in CSN and CSH animals and modulated the acute HVR in CSN animals. Third, naked mole rats exhibited GABAR-dependent metabolic plasticity following long-term hypoxia, such that the basal metabolic rate was approximately 25% higher in normoxic CSH animals than CSN animals, and GABAR antagonists modulated this increase.


Clinical awareness of intra-abdominal hypertension and abdominal compartment syndrome in 2007.
There has been an exponentially increasing interest in intra-abdominal hypertension (IAH). The aim of this review is to evaluate the evolution in clinical awareness of this syndrome. A PubMed (U.S. National Library of Medicine) search and a ScienceDirect (Elsevier B.V.) search of recent literature were performed in order to assess clinical awareness of IAH and abdominal compartment syndrome (ACS). In total, 489 articles and 8 clinical surveys have been identified. The results of the landmark papers and the surveys will be briefly discussed in this review. Clinical awareness of ACS is steadily increasing. It is time to pay attention to ACS, but further, it is time to move forward with therapeutic bundles in a multi-centered, outcome trial on IAH/ACS therapy in order to elevate IAH/ACS management to an international standard of care.


NF-κB p65 serine 467 phosphorylation sensitizes mice to weight gain and TNFα-or diet-induced inflammation.
The NF-κB family of transcription factors is essential for an effective immune response, but also controls cell metabolism, proliferation and apoptosis. Its broad relevance and the high connectivity to diverse signaling pathways require a tight control of NF-κB activity. To investigate the control of NF-κB activity by phosphorylation of the NF-κB p65 subunit, we generated a knock-in mouse model in which serine 467 (the mouse homolog of human p65 serine 468) was replaced with a non-phosphorylatable alanine (S467A). This substitution caused reduced p65 protein synthesis and diminished TNFα-induced expression of a selected group of NF-κB-dependent genes. Intriguingly, high-fat fed S467A mice displayed increased locomotor activity and energy expenditure, which coincided with a reduced body weight gain. Although glucose metabolism or insulin sensitivity was not improved, diet-induced liver inflammation was diminished in S467A mice. Altogether, this study demonstrates that phosphorylation of p65 serine 467 augment NF-κB activity and exacerbates various deleterious effects of overnutrition in mice.


The Feasibility of Hand-assisted Laparoscopic and Laparoscopic Multivisceral Resection Compared With Open Surgery for Locally Advanced Colorectal Cancer.
The role of hand-assisted laparoscopic and pure laparoscopic surgery for locally advanced colorectal cancer invading or adhering to neighboring organs is controversial. This study evaluated the safety and feasibility of laparoscopic multivisceral resection for colorectal cancer. This study included 201 patients who underwent multivisceral resection for locally advanced colorectal cancer from January 2007 to December 2013 in the Department of General Surgery, Henan Provincial Hospital. Perioperative outcomes and long-time outcomes were compared among hand-assisted laparoscopic, laparoscopic and open resections. Estimated blood loss, wound length, time to the first flatus, and postoperative hospital stay were significantly less or shorter in the hand-assisted laparoscopic surgery (HALS) and laparoscopic surgery group than in open surgery (OS) group. There were no significant differences in tumor size, retrieved lymph nodes, and R0 resection rate of the primary tumor among the 3 groups. Surgeries started as laparoscopic surgery were completed in that manner 76.6% of the time with 10.6% being converted to OS and 12.8% converted to HALS and there were only 2 conversions (2.2%) to OS in the HALS group. No significant difference was noted for overall morbidity rate and reoperation rate among the 3 groups. The overall observed 5-year survival rate was 60.5% in the laparoscopic group, 55.4% in the HALS group, and 47.7% in the open group. There was no significant difference among the 3 groups in the 5-year survival rate. Hand-assisted laparoscopic and pure laparoscopic multivisceral resection for locally advanced colorectal cancer is safe and feasible in selected patients. HALS can be used judiciously to reduce the rate of conversion to an open procedure and may be a better alternative for laparoscopic approach.


FGF8-like1 and FGF8-like2 encode putative ligands of the FGF receptor Htl and are required for mesoderm migration in the Drosophila gastrula.
Mesoderm migration in the Drosophila gastrula depends on the fibroblast growth factor (FGF) receptor Heartless (Htl). During gastrulation Htl is required for adhesive interactions of the mesoderm with the ectoderm and for the generation of protrusive activity of the mesoderm cells during migration. After gastrulation Htl is essential for the differentiation of dorsal mesodermal derivatives. It is not known how Htl is activated, because its ligand has not yet been identified. We performed a genome-wide genetic screen for early zygotic genes and identified seven genomic regions that are required for normal migration of the mesoderm cells during gastrulation. One of these genomic intervals produces upon its deletion a phenocopy of the htl cell migration phenotype. Here we present the genetic and molecular mapping of this genomic region. We identified two genes, FGF8-like1 and FGF8-like2, that encode novel FGF homologs and were only partially annotated in the Drosophila genome. We show that FGF8-like1 and FGF8-like2 are expressed in the neuroectoderm during gastrulation and present evidence that both act in concert to direct cell shape changes during mesodermal cell migration and are required for the activation of the Htl signaling cascade during gastrulation. We conclude that FGF8-like1 and FGF8-like2 encode two novel Drosophila FGF homologs, which are required for mesodermal cell migration during gastrulation. Our results suggest that FGF8-like1 and FGF8-like2 represent ligands of the Htl FGF receptor.


Hygiene versus fertiliser: the use of human excreta in agriculture--a Vietnamese example.
The use of human excreta as fertiliser in agriculture is a common practice in parts of South East Asia benefiting production but at the same time a risk factor for increased helminth infections. This paper describes the hygienic handling of human excreta for use in agriculture in Central Vietnam from a practical farming perspective presenting the farmers perceived health risks and benefits of its use. Further, in the study findings are discussed relating to the new Vietnamese guidelines for the use of human excreta in agriculture to their implications on an on-farm context. A total of 471 households in five communes responded to a structured questionnaire. This survey was supplemented by focus group discussions, key informant interviews and participant observations. More than 90% of the surveyed households used their own excreta as fertiliser and a total of 94% composted the excreta before use, either inside or outside the latrine. However, due to the prevailing design of the latrine and the three annual cropping seasons, it was found that for a minimum of one cultivation season per year 74% of the households will have only 3-4 months for composting before the input is needed in production, which is short of the 6 months stipulated in the national guidelines. The community associated great benefits from using human excreta in agriculture, especially if composted, and did not associate risks with the use of composted excreta if it was dry and lacked odour. It is recommended that the guidelines be revised and attempts made to identify ways of reducing the time needed to ensure the die-off of helminth eggs, including the use of pH regulators, such as an increased use of lime in the latrines.


Effects of tetrathiomolybdate on copper metabolism in healthy volunteers and in patients with Wilson disease.
In Wilson Disease (WD), copper accumulates in the liver and brain causing disease. Bis-choline tetrathiomolybdate (TTM) is a potent copper chelator that may have a lower risk of inducing paradoxical neurological worsening than conventional therapy for neurologic WD. To better understand the mode of action of TTM, we investigated the effects of TTM on copper absorption and biliary excretion. In a double-blind randomized setting, hepatic 64Cu activity after orally administered 64Cu was examined by PET/CT in 16 healthy volunteers before and after 7 days of TTM treatment (15 mg/d) or placebo. Oral 64Cu was administered 1 h after final TTM dose. Changes in hepatic 64Cu activity reflected changes in intestinal 64Cu uptake. Additionally, in four WD patients, distribution of 64Cu in venous blood, liver, gallbladder, kidney, and brain were followed after i.v. 64Cu dosing for up to 68 hours before and after seven days of TTM (15 mg/d), using PET/MRI. Increased gallbladder 64Cu activity was taken as evidence of increased biliary 64Cu excretion. In healthy subjects TTM reduced intestinal 64Cu uptake by 82% 15 hours after the oral 64Cu dose. In WD patients, gallbladder 64Cu activity was negligible before and after TTM, while TTM effectively retained 64Cu in the blood, significantly reduced hepatic 64Cu activity at all time points and significantly reduced cerebral 64Cu activity 2 h after the intravenous 64Cu dose. While we did not show an increase in biliary excretion of 64Cu following TTM administration, we demonstrated that TTM effectively inhibited most intestinal 64Cu uptake and retained 64Cu in the blood stream, limiting 64Cu exposure to organs like the liver and the brain. Bis-choline tetrathiomolybdate (TTM) is an investigational copper chelator for treatment of Wilson Disease. In animal studies of Wilson Disease models, TTM has been shown to facilitate biliary copper excretion. In the present human study, TTM surprisingly did not facilitate biliary copper excretion but instead reduced intestinal copper uptake to a clinically significant degree. Our study improves the understanding of human copper metabolism and the mechanism of action of TTM. Data is presented from two clinical trials:Absorption study: EudraCT 2020-005832-31Excretion study: EudraCT 2021-000102-25.


Idiopathic thrombocytic purpura.
Oncology nurses often see patients with nononcologic disorders. Idiopathic thrombocytic purpura (ITP), a platelet disorder, is one such example. Being both an emergent condition as well as a chronic one, nurses will need to assess patients with ITP for bleeding and conduct extensive patient education about the disease process and treatment options.


Laparoscopic radical nephrectomy.
Although open nephrectomy is the standard of care for localized renal-cell carcinoma, the significant postoperative pain and lengthy convalescence have encouraged the use of laparoscopy, which can yield similar 2- to 5-year survival rates. Either a transperitoneal or a retroperitoneal approach may be used, and sometimes, they are combined. Generally, the technique is limited to tumors <10 cm, but larger tumors can be removed. Nitrous oxide is avoided as an anesthetic agent. The dissection follows accepted oncologic principles: in situ renal dissection within Gerota's fascia, early ligation of the renal vessels, and careful removal of the specimen to prevent tumor spillage. Dissection of the hilum is facilitated by a PEER retractor and an Endoholder. On average, patients having laparoscopic radical nephrectomy return to normal activities approximately 4.5 weeks sooner than those having open surgery, a fact not taken into account in cost analyses. Laparoscopic nephrectomy may offer a special benefit in patients with known metastatic disease, as interleukin-2 administration can be started a month earlier than after open surgery. There may also be immunologic benefits of minimally invasive v open surgery. The technique and instruments continue to evolve, and cost-effectiveness should continue to improve.


Modifications to the Standard Sit-and-Reach Flexibility Protocol.
To present several modifications of the standard sit-and-reach protocol. Many exercises designed to increase strength and aerobic capacity tend to decrease the flexibility of the erector spinae and hamstrings musculature. Less-than-ideal flexibility in these soft tissues may increase the risk of injury during training, competition, or activities of daily living. The most widely used measures of flexibility have been either the stand-and-reach or the sit-and-reach, but both are limited to a single measure. Using the new multitest flexometer, we were able to take 6 flexibility measures beyond the stand-and-reach test: standard active sit-and-reach, standard passive sit-and-reach, modified active sit-and-reach with external rotators slackened, modified passive sit-and-reach with external rotators slackened, modified active sit-and-reach with the hamstrings, gastrocnemii, and external rotators slackened, and modified passive sit-and-reach with the hamstrings, gastrocnemii, and external rotators slackened. This modified sit-and-reach protocol allows the indirect assessment of the influence of the 4 major muscle groups that affect sit-and-reach scores: erector spinae, hip rotators, hamstrings, and gastrocnemii.


Distinguishing subtypes in primary progressive aphasia: application of the Sydney language battery.
Primary progressive aphasia (PPA) comprises three main subtypes, varying in clinical features, patterns of brain atrophy, and underlying pathology. Differentiation of these variants is important for treatment and planning; however, simple, effective cognitive tests to aid diagnosis are lacking. This study introduces a new language battery - the SYDBAT (Sydney Language Battery) - to assist clinicians. Fifty-seven PPA patients and 54 age- and education-matched healthy controls were compared on naming, repetition, word comprehension, and semantic association subtests. Significant group differences were found for all tasks, reflecting different language profiles for each group. Using discriminative function analysis, 80% of PPA cases were correctly classified from three SYDBAT scores, from which a simple diagnostic algorithm was defined. The SYDBAT is a fast and simple tool which provides a valuable adjunct to clinicians diagnosing PPA.


Desmoplastic neurotropic malignant melanoma.
Desmoplastic neurotropic malignant melanoma is a rare spindle cell variant of malignant melanoma. This chapter reviews its clinical presentation; histologic, immunohistochemical, and ultrastructural features; differential diagnosis; and critical therapeutic issues.


Increasing calcium from deficient to adequate concentration in diets for gestating sows decreases digestibility of phosphorus and reduces serum concentration of a bone resorption biomarker.
The objective of this experiment was to test the hypothesis that the concentration of Ca in diets fed to late gestating sows affects the apparent total tract digestibility (ATTD) and retention of Ca and P, serum concentrations of Ca and P, hormones, and blood biomarkers for bone formation and resorption. Thirty-six sows (average parity = 2.8) were housed in metabolism crates from day 91 to day 104 of gestation and fed 1 of 4 experimental diets containing 25, 50, 75, or 100% of the requirement for Ca. All diets met the requirement for P. The initial 5 d of each period were the adaptation period, which was followed by 4 d of quantitative collection of feces and urine. At the end of the collection period, a blood sample was collected from all sows. Results indicated that feed intake, weights of dried fecal and urine samples, and the ATTD of DM were not affected by dietary Ca, but ATTD of Ca increased (quadratic, P < 0.05) as Ca in diets increased. Urine Ca output was not affected by dietary Ca, but Ca retention increased (quadratic, P < 0.05) as Ca intake increased. Fecal P output increased (linear, P < 0.001) as dietary Ca increased, which resulted in a linear decrease (P < 0.001) in the ATTD of P. Urine P output also decreased (linear, P < 0.001) as dietary Ca increased, but P retention increased (linear, P < 0.05). Regressing the apparent total tract digestible Ca against dietary Ca intake resulted in a regression line with a slope of 0.33, indicating that true total tract digestibility of Ca in calcium carbonate was 33%. Serum concentrations of Ca and P and estrogen, calcitonin, and parathyroid hormone were not affected by dietary Ca. Serum concentration of carboxyterminal cross-linked telopeptide of type I collagen (CTX-I) decreased (linear, P < 0.05) as dietary Ca increased, which is a result of reduced bone resorption as dietary Ca increased. Serum bone-specific alkaline phosphatase tended to decrease (linear, P < 0.10) as Ca in diets increased, but the concentration of osteocalcin (OC) in serum was not affected by dietary Ca. The ratio between OC and CTX-I tended to increase (P < 0.10) as dietary Ca increased, which indicated that there was more bone formation than resorption in sows as dietary Ca increased. In conclusion, P digestibility in late gestating sows decreased, but retention of P increased, as dietary Ca increased from inadequate to adequate levels and blood biomarkers for bone resorption changed as Ca and P retention increased.


Community Wise: Development of a Model to Address Oppression in Order to Promote Individual and Community Health.
Communities with histories of oppression have shown great resilience. Yet few health interventions focus on structural oppression as a contributor to health problems in these communities. This paper describes the development and active ingredients of Community Wise, a unique behavioral-health intervention designed to reduce substance use frequency, related health risk behaviors, and recidivism among individuals with a history of incarceration and substance abuse residing in distressed and predominantly African American communities. Community Wise, developed through the collaborative efforts of a board of service providers, researchers, consumers, and government officials, is a 12-week group intervention that aims to address behavioral-health problems by raising critical consciousness in distressed communities.


Soil chamber method for determination of drip-applied fumigant behavior in bed-furrow agriculture: application to chloropicrin.
To overcome the environmental impacts of soil fumigant use, emission reduction strategies such as tarping can be adopted. There is a need to experimentally quantify the effectiveness of such strategies, preferably in a low-cost manner. We report the design and initial testing of a laboratory soil chamber approach for quantifying the soil distribution and emissions of fumigants from bed-furrow agricultural systems. As far as possible, field conditions (e.g., soil type, bulk density, moisture content temperature) were maintained in the experiments. In studying the drip application of chloropicrin using this system, very good data reproducibility was observed between replicates, allowing confidence in the experimental design. For control chambers, high emissions, around 60% (of the total added), were observed due to the near-surface (5 cm depth) application. When the soil beds were tarped using high-density polyethylene (HDPE) or semi-impermeable film (SIF), emissions were reduced to around 40% due to an accumulation of chloropicrin below the tarp. The approach offers an inexpensive potential alternative to studying fumigant emissions from bed-furrow systems in the field and suggests that less permeable tarps would be required to drastically reduce chloropicrin emissions.


Systematic approach to diagnosing suspected Creutzfeldt-Jakob disease.
Evaluation of rapidly progressive dementia (RPD) is usually challenging. In most cases, patients progress to dementia in weeks to months, and the differential diagnosis is broad. In this case, a woman in her 60s presented with a 1-month history of episodic vertigo, cognitive decline, ataxia and myoclonus. Cerebrospinal fluid total tau was markedly elevated, which was helpful in establishing the diagnosis and discussing prognosis/end-of-life measures with the patient's family. This case summarises a stepwise diagnostic approach for patients with RPD and highlights recent literature on biomarkers of Creutzfeldt-Jakob disease and autoimmune encephalitis.


Evaluating Neighborhood, Social, and Genetic Influences on Precursors of Alcohol Use Risk Behavior in African American Adolescents.
Background: Using a socioecological framework, we examined neighborhood and social stressors in concert with genetic risk for alcohol dependence in relation to externalizing behaviors, important precursors to alcohol-related problems. Methods: We used data from African American adolescents and their caregivers in the Gene, Environment, and Neighborhood Initiative, a subsample of the Mobile Youth and Poverty Study. Participants for the current analyses included 112 adolescents who reported ever having at least one full drink of alcohol. Empirical Bayes scores were used to estimate neighborhood-level violence and transitions. Multivariate models tested main effects and then interactions of family stressors, discrimination, and genetic risk with the neighborhood variables. Results: In the main effects model, adolescent externalizing behaviors were positively associated with greater family stressors, more racial discrimination experiences, and genetic liability, while neighborhood variables were nonsignificant. We found three significant interactions. Specifically, the joint effects of neighborhood violence and transitions and between these neighborhood variables and family stressors were significantly associated with externalizing behaviors. Conclusions: Our findings suggest genetic liability and complex interactions between neighborhood context and social stressors are important contributors that should be considered in the development of early prevention programs for adolescents who live in economically disadvantaged areas.


Cytokinins play opposite roles in lateral root formation, and nematode and Rhizobial symbioses.
We used the cytokinin-responsive Arabidopsis response regulator (ARR)5 gene promoter fused to a beta-glucuronidase (GUS) reporter gene, and cytokinin oxidase (CKX) genes from Arabidopsis thaliana (AtCKX3) and maize (ZmCKX1) to investigate the roles of cytokinins in lateral root formation and symbiosis in Lotus japonicus. ARR5 expression was undetectable in the dividing initial cells at early stages of lateral root formation, but later we observed high expression in the base of the lateral root primordium. The root tip continues to express ARR5 during subsequent development of the lateral root. These results suggest a dynamic role for cytokinin in lateral root development. We observed ARR5 expression in curled/deformed root hairs, and also in nodule primordia in response to Rhizobial inoculation. This expression declined once the nodule emerged from the parent root. Root penetration and migration of root-knot nematode (RKN) second-stage larvae (L2) did not elevate ARR5 expression, but a high level of expression was induced when L2 reached the differentiating vascular bundle and during early stages of the nematode-plant interaction. ARR5 expression was specifically absent in mature giant cells (GCs), although dividing cells around the GCs continued to express this reporter. The same pattern was observed using a green fluorescent protein (GFP) reporter driven by the ARR5 promoter in tomato. Overexpression of CKX genes rendered the transgenic hairy roots resistant to exogenous application of the cytokinin [N6-(Delta2 isopentenyl) adenine riboside] (iPR). CKX roots have significantly more lateral roots, but fewer nodules and nematode-induced root galls per plant, than control hairy roots.


Optical chaotic data-selection logic operation with the fast response for picosecond magnitude.
We investigate the evolution of nonlinear dynamic behaviors of two polarization components (x-PC and y-PC), as well as the interplay of polarization bistability, frequency detuning and injection strength in the vertical cavity surface emitting laser with optical injection. Specifically, by encoding two logic inputs and one clock input in the amplitude of the light from a sampled grating distributed Bragg reflector laser, and by decoding two output logic responses from the x-PC and y-PC emitted by the laser, we demonstrate two parallel data-selection computing. The correct logic output encoded in two emitted PCs response for as short as 100 ps bit time and the response bit time of the correct logic output encoded in the y-PC may be 67 ps by the optimization of the injection strength. The probability of a correct response is controlled by the interplay of the bit time, the injection strength and noise strength, and is equal to 1 in a wide region of the injection strength and noise strength. The chaotic data-selection computing in an optically VCSEL offer interesting perspectives for applications where noise is unavoidable and fast switching is required.


Few-layer nanoplates of Bi 2 Se 3 and Bi 2 Te 3 with highly tunable chemical potential.
A topological insulator (TI) represents an unconventional quantum phase of matter with insulating bulk band gap and metallic surface states. Recent theoretical calculations and photoemission spectroscopy measurements show that group V-VI materials Bi(2)Se(3), Bi(2)Te(3), and Sb(2)Te(3) are TIs with a single Dirac cone on the surface. These materials have anisotropic, layered structures, in which five atomic layers are covalently bonded to form a quintuple layer, and quintuple layers interact weakly through van der Waals interaction to form the crystal. A few quintuple layers of these materials are predicted to exhibit interesting surface properties. Different from our previous nanoribbon study, here we report the synthesis and characterizations of ultrathin Bi(2)Te(3) and Bi(2)Se(3) nanoplates with thickness down to 3 nm (3 quintuple layers), via catalyst-free vapor-solid (VS) growth mechanism. Optical images reveal thickness-dependent color and contrast for nanoplates grown on oxidized silicon (300 nm SiO(2)/Si). As a new member of TI nanomaterials, ultrathin TI nanoplates have an extremely large surface-to-volume ratio and can be electrically gated more effectively than the bulk form, potentially enhancing surface state effects in transport measurements. Low-temperature transport measurements of a single nanoplate device, with a high-k dielectric top gate, show decrease in carrier concentration by several times and large tuning of chemical potential.