[Establishment and verification of risk assessment scale for clinical safety medication of aconitine].
Chinese patent medicine containing aconitine is the key in clinical rational drug use. These drugs contain Chuanwu, Caowu or Fuzi, and Aconitum brachypodum with functions of expelling wind-dampness or tonifying Yang, all of which shall be used by strictly following the indications and dosage. However, there are many kinds of such drugs. Not only the unfamiliar knowledge of some Chinese and Western physicians about the characteristics of them, but also the combination of multiple drugs from different clinical departments, would increase the risk of aconitine poisoning. Based on the previous research, this paper proposed three core elements "syndrome differentiation-dosage differentiation-toxicity differentiation" from the prescription review and pharmacy consulting work, and objective and standardized evaluation was used to build a risk assessment scale containing 3 categories, 9 items and 36 indicators with Hulisan Jiaonang and Qufeng Zhitong Jiaonang as the example. This scale was used to evaluate the risk of a therapeutic regimen before and after the implementation. According to the verification of the existing adverse reaction cases, the risk assessment scale can be used to indicate the risk of drug treatment program and identify the risk level of drug treatment status. This paper tried to provide a methodological paradigm for scientific and objective evaluation on the safety of Chinese patent medicines, and help to identify the key links and risk prevention in the rational use by Chinese medicine physicians and pharmacists.


Urologic management of spinal cord injury in children.
This overview of the management of children with spinal cord injury has focused on a program based on bladder dynamics. The bladder is modulated pharmacologically and surgically, if necessary, to create a reservoir that stores urine at low pressure, and emptying is achieved by clean intermittent catheterization. The parent assumes the responsibility for bladder emptying when the child is unable to perform catheterization. Reflex voiding in a balanced fashion is not advocated. The program described not only avoids the deleterious effects of high voiding pressures, it also obviates the wearing of a urinary collection device, which is impractical for most prepubertal boys, and it provides for emptying at predictable intervals in order to make the child more socially acceptable. This approach seems to improve the child's self-image, and it should increase the chances of useful participation in society and a fulfilling life.


Injectable in situ intelligent thermo-responsive hydrogel with glycyrrhetinic acid-conjugated nano graphene oxide for chemo-photothermal therapy of malignant hepatocellular tumor.
Malignant tumor is one of the major diseases with high morbidity and mortality. The purpose of this study is to prepare berberine hydrochloride (BH) in situ thermo-sensitive hydrogel based on glycyrrhetinic acid (GA) modified nano graphene oxide (NGO) (GA-BH-NGO-gel). NGO was taken as the photosensitizer, GA was taken as the target molecule, and BH was taken as the model drug. The physicochemical properties and anti-tumor activity in vivo and in vitro were also studied. This subject could provide a certain theoretical basis for the chemo-photothermal therapy combined treatment of malignant tumor. The release behavior of GA-BH-NGO-gel in vitro presented sustained and temperature-dependent drug release effect. The anti-tumor activity studies in vivo and in vitro had shown that GA-BH-NGO-gel had stronger anti-tumor activity, which could be targeting distributed to the tumor tissues. Moreover, the inhibitory effect of GA-BH-NGO-gel was enhanced when combined with 808 nm of laser irradiation. In this research, the chemo-photothermal combination therapy was applied into the tumor treatment, which may provide certain research ideas for the clinical treatment of malignant tumor.


Glyceroneogenesis is reduced and glucose uptake is increased in adipose tissue from cafeteria diet-fed rats independently of tissue sympathetic innervation.
The pathways of glycerol-3-P (G3P) generation were examined in retroperitoneal (RETRO) and epididymal (EPI) adipose tissues from rats fed a cafeteria diet for 3 wk. The cafeteria diet induced marked increases in body fat mass and in the plasma levels of insulin and triacylglycerol (TAG). RETRO and EPI from cafeteria diet-fed rats had increased rates of norepinephrine turnover (143 and 60%, respectively) and of de novo fatty acid (FA) synthesis (58 and 98%), compared with controls fed a balanced commercial diet. Cafeteria diet feeding induced marked increases in RETRO and EPI in vivo rates of glucose uptake (52 and 51%, respectively), used to evaluate G3P generation via glycolysis, as well as in glycerokinase activity (119 and 36%) and TAG-glycerol synthesis from glycerol (56 and 71%, respectively). In contrast, there was a marked reduction of glyceroneogenesis in RETRO and EPI from cafeteria diet-fed rats, which was evidenced by the significant decreases of P-enolpyruvate carboxykinase (PEPCK-C) activity (48 and 36%) and TAG-glycerol synthesis from pyruvate (45 and 56%, respectively). Denervation of RETRO from cafeteria diet-fed rats reduced the activity of glycerokinase by 50%, but did not affect glucose uptake or PEPCK-C activity and TAG-glycerol synthesis from pyruvate by the tissue. The data show that glyceroneogenesis can also be inhibited to adjust the supply of G3P to the existing rates of FA esterification and TAG synthesis and suggest that this adjustment is made by reciprocal changes in the generation of G3P from glucose via glycolysis and from glyceroneogenesis, independently from G3P production by glycerokinase.


Effects of fentin hydroxide on reproduction of the Japanese quail (Coturnix coturnix japonica).
In a one-generation reproductive study, the fungicidal compound triphenyltin hydroxide (fentin) was administered to adult Japanese quail for 6 weeks at dietary levels of 3 and 30 ppm. Reproduction was significantly impaired in the high-dose group. The principal adverse finding was a marked increase in embryonic mortality, resulting in a lower hatch rate. Furthermore, a reduction in egg production was observed with ongoing duration of treatment. Most of the other reproduction-related parameters were not affected. The in ovo losses are assumed to result from a direct toxic effect of the test substance on chick embryos. At the low dietary level, reproduction was not altered. In contrast to the obvious reproductive toxicity, there was only limited evidence of adverse treatment-related findings in the adult birds. However, because such minor effects as an increase in mean liver weight, which was accompanied by macroscopic liver findings and a decrease in T4 serum concentration, were still seen at 3 ppm, a no-observed-effect level could not be established.


Prediction of thioredoxin and glutaredoxin target proteins by identifying reversibly oxidized cysteinyl residues.
A significant part of cellular proteins undergo reversible thiol-dependent redox transitions which often control or switch protein functions. Thioredoxins and glutaredoxins constitute two key players in this redox regulatory protein network. Both interact with various categories of proteins containing reversibly oxidized cysteinyl residues. The identification of thioredoxin/glutaredoxin target proteins is a critical step in constructing the redox regulatory network of cells or subcellular compartments. Due to the scarcity of thioredoxin/glutaredoxin target protein records in the public database, a tool called Reversibly Oxidized Cysteine Detector (ROCD) is implemented here to identify potential thioredoxin/glutaredoxin target proteins computationally, so that the in silico construction of redox regulatory network may become feasible. ROCD was tested on 46 thioredoxin target proteins in plant mitochondrion, and the recall rate was 66.7% when 50% sequence identity was chosen for structural model selection. ROCD will be used to predict the thioredoxin/glutaredoxin target proteins in human liver mitochondrion for our redox regulatory network construction project. The ROCD will be developed further to provide prediction with more reliability and incorporated into biological network visualization tools as a node prediction component. This work will advance the capability of traditional database- or text mining-based method in the network construction.


Capturing the impact employees have on their coworkers and leaders: a holistic approach on health-specific support behavior from employees.
Support is a valuable resource for ensuring employee health in the workplace. However, research on health-specific support behavior (i.e., support specifically targeting concrete health aspects) has only concentrated on either leader behavior (e.g., healthy leadership styles) or support provided by employees for specific health issues (e.g., healthy eating or smoking cessation). Although the importance of employee health has been well established, the examination of a wider range of potential health-specific support behaviors from employees provided for their colleagues and leaders has been neglected. To understand employee health-specific support behavior, we adapted an existing health-oriented leadership questionnaire to cover support for colleagues (PeerCare) and their leaders (LeaderCare). Capturing the employee perspective with a sample of 347 employees, the results confirmed a delineation of health-oriented scales (factor, convergent, and discriminant validity). By testing health-specific support behavior processes at work, the positive effects of PeerCare on general health were demonstrated. Contrary to expectations, existing health effects are outweighed when leaders provide health-specific support behavior to their employees (StaffCare). However, the results imply that the health-specific support behavior practices of different actors reinforce each other: the effects of StaffCare and PeerCare enhance each other, and StaffCare has a strong influence on LeaderCare. Remarkably, SelfCare has a key role in this process. The open questions and implications regarding the effects of the different health-specific support behavior measurements are discussed.


From Multiscale to Mesoscience: Addressing Mesoscales in Mesoregimes of Different Levels.
This review covers three decades of research on mesoscale phenomena in chemical engineering, from the energy minimization multiscale (EMMS) model specific for gas-solid fluidization to a general principle of compromise in competition between dominant mechanisms, leading to the proposed concept of mesoscience. First, the concept of mesoscales is reviewed with respect to their commonality, diversity, and misunderstanding in different fields. Then, the evolution from the EMMS model to the EMMS principle common to all mesoscales is described to show the rationale of mesoscience referring to both mesoscales and mesoregimes. Finally, the potential universality of mesoscience and its importance, particularly to enable virtual process engineering (VPE) by realizing the consistency of logic and structure between the problem, the model, the software, and the computer, are discussed. The review concludes by illustrating possible case studies to collect more evidence and a potential framework for mesoscience.


Current status and future potential role of exemestane in the treatment of early and advanced breast cancer (Review).
Exemestane is a new oral steroidal aromatase inactivator, active in postmenopausal women with hormonal sensitive breast carcinoma. This drug, at a dosage of 25 mg once daily, was shown to suppress in vivo aromatase activity by 97.9%, with a subsequent reduction superior to 85% of circulating oestrogen level. It exhibits definite antitumor activity at a relatively low daily dose, and is highly potent, highly selective, and well-tolerated. Moreover, for postmenopausal women with metastatic breast cancer, exemestane demonstrated a higher activity and lower toxicity profile when compared to megestrol acetate and tamoxifen in second- and first-line therapy, respectively. New data on exemestane are forthcoming both in the adjuvant and neoadjuvant setting, which could improve the management of early breast cancer in the future.


Estimation of the ideal ratio of true ileal digestible sulfur amino acids:lysine in 8- to 26-kg nursery pigs.
Four experiments were conducted to determine the ideal ratio of true ileal digestible (TID) sulfur AA to Lys (SAA:LYS) in nursery pigs at two different BW ranges using both DL-Met and 2-hydroxy-4-(methylthio)-butanoic acid (HMTBA) as Met sources. In Exp. 1, 1,549 nursery pigs (Triumph 4 x PIC Camborough 22; initial BW 8.3 +/- 0.08 kg) were allotted to one of nine dietary treatments. The basal diet (Diet 1) was a semicomplex corn-soybean meal-based diet (1.32% TID Lys) with no supplemental HMTBA or DL-Met (47.7% TID SAA:LYS). Diets 2 to 9 consisted of the basal diet supplemented with four equimolar levels of DL-Met or HMTBA (52.7, 57.7, 62.7, and 67.7% TID SAA:LYS). In Exp. 2, 330 nursery pigs (Triumph 4 x PIC Camborough 22; initial BW 11.4 +/- 0.10 kg) were allotted to one of nine dietary treatments. The basal diet (Diet 1) was a corn-soybean meal-based diet (1.15% TID Lys) with no supplemental HMTBA or DL-Met (49% TID SAA:LYS). Diets 2 to 9 consisted of the basal diet supplemented with four equimolar levels of DL-Met or HMTBA (54, 59, 64, and 69% TID SAA:LYS). In Exp. 3, 1,544 nursery pigs (Triumph 4 x PIC Camborough 22; initial BW 12.4 +/- 0.13 kg) were allotted to one of nine dietary treatments as in Exp. 2. In Exp. 4, 343 nursery pigs (Genetiporc; initial BW 12.8 +/- 0.56 kg) were allotted to one of six dietary treatments. The basal diet (Diet 1) was a corn-soybean meal-based diet (1.05% TID Lys) with no supplemental DL-Met (49% TID SAA:LYS). Diets 2 to 5 consisted of the basal diet supplemented with four levels of DL-Met (54, 59, 64, and 69% TID SAA:LYS), and Diet 6 was the basal diet supplemented with one equimolar level of HMTBA to satisfy 59% TID SAA:LYS ratio. In all experiments, increasing the TID SAA:LYS ratio resulted in quadratic improvements in ADG (P < or = 0.09) and G:F (P < or = 0.05). Three different methods were used to estimate the optimal TID SAA:LYS ratio for each experiment. The two-slope broken-line regression model, x-intercept value of the broken-line and quadratic curve, and 95% of upper asymptote across the four experiments indicated that the average optimal TID SAA:LYS ratios were 59.3, 60.1, and 57.7% for ADG and 60.6, 61.7, and 60.1% for G:F, respectively. Thus, the optimal TID SAA:LYS ratio for 8- to 26-kg pigs based on the average value of these three estimates was 59.0% for ADG and 60.8% for G:F.


New Proximal Femoral Compaction Blade Provides Strong Antirotation Stability of the Femoral Head.
This study investigated the mechanical properties of a new rectangular compaction blade and compared this blade with other types of nail. Three types of nail were tested: the Magnum lag screw (Robert Reid Inc, Tokyo, Japan), proximal femoral nail, and Magnum Fid blade (Robert Reid Inc). The nails were inserted into solid rigid polyurethane foam, and the torsional moments were loaded with an Instron testing machine (Instron, Kanagawa, Japan). The force curve was recorded, and the average maximum torque was calculated from this curve. A simulation study was performed with finite element models to determine the mechanism underlying differences in rotational stability. Mechanical testing showed that the new compaction blade had stronger resistance against rotational force than the helical blade and lag screw implants. Finite element analysis also showed that the new compaction blade had stronger resistance to migration of the polyurethane foam cylinder than the other implant types. In addition, the new compaction blade had strong rotational stability. This implant should be useful for the treatment of unstable trochanteric fracture in patients with osteoporosis. [Orthopedics. 2017; 40(3):e491-e494.].


Melanoma. Tumor angiogenesis and human neoplasia.
Transparent hamster-cheek-pouch chambers were used to document angiogenesis induced by implants of human malignant melanoma. Capillary proliferation was observed with direct implantation of melanoma fragments and with tumor implants place on microporous membrane filters. The pattern of capillary neovascularization was recorded and correlated with clinical and histopathologic parameters.


Marine mammal cell cultures: To obtain, to apply, and to preserve.
The world's oceans today have become a place for the disposal of toxic waste, which leads to the degradation of marine mammal habitats and populations. Marine mammal cell cultures have proven to be a multifunctional tool for studying the peculiarities of the cell physiology and biochemistry of these animals as well as the destructive effects of anthropogenic and natural toxicants. This review describes the sources of marine mammal live tissues and the methods required for establishing cell cultures, their use, and long-term storage. Approaches to conserving rare animal species by applying cell biology methodologies are also discussed.


Molecular dynamics simulation of glycine zwitterion in aqueous solution.
A classical molecular dynamics method was used to study the modifications of the solution structure and the properties of glycine zwitterion in aqueous solution due to the increase of glycine zwitterion concentration and the incorporation of Na(+) and Cl(-) ions to the solution. The glycine zwitterion had fundamentally a hydrophilic behavior at infinite dilution, establishing around six hydrogen bonds with the water molecules that surrounded it, which formed a strong hydration layer. Because of the increase of glycine zwitterion concentration, the hydration structure became more compact and the quantity of water molecules bound to this molecule decreased. The Na(+) ion bound to the CO(2) group of glycine, while the Cl(-) ion bound mainly to the NH(3) group of this molecule. The integration of the ions to the hydration layer of the glycine zwitterion produced modifications in the orientational correlation between atoms of glycine zwitterion and water that surrounded them and an increase of the approaches between the glycine zwitterion molecules. The incorporation of ions to the solution also produced changes in the water-water orientational correlation. Decreases of the water-water hydrogen bonds and diffusion coefficient of all molecules were observed when the glycine zwitterion concentration increased and when the ions were incorporated to the solution.


Changes in the monitoring and oversight practices of not-for-profit hospital governing boards 1989-2005: evidence from three national surveys.
Despite the legal and practical importance of monitoring and oversight of management by hospital governing boards, there is little empirical evidence of how hospital boards fulfill these roles and the extent to which these practices have changed over time. We utilize data from three national surveys of hospital governance to examine how oversight and monitoring practices in public and private not-for-profit (NFP) hospital boards have changed over time. Findings suggest that board relations with CEOs in NFP hospitals display important but potentially contradictory patterns. On the one hand, NFP hospital boards appear to be exercising more stringent oversight of management and hospital performance. On the other hand, management is more actively involved with governance matters with less separation of board and management. This general pattern varies by the dimension of oversight and monitoring practice and by specific characteristics of NFP hospitals.


Electronic Traps and Their Correlations to Perovskite Solar Cell Performance via Compositional and Thermal Annealing Controls.
Herein, underlying factors for enabling efficient and stable performance of perovskite solar cells are studied through nanostructural controls of organic-inorganic halide perovskites. Namely, MAPbI3, (FA0.83MA0.17)Pb(I0.83Br0.17)3, and (Cs0.10FA0.75MA0.15)Pb(I0.85Br0.15)3 perovskites (abbreviated as MA, FAMA, and CsFAMA, respectively) are examined with a grain growth control through thermal annealing. FAMA- and CsFAMA-based cells result in stable photovoltaic performance, while MA cells are sensitively dependent on the perovskite grain size dominated by annealing time. Micro-/nanoscopic features are comprehensively analyzed to unravel the origin that is directly correlated to the cell performance with the applications of electronic-trap characterizations such as photoconductive noise microscopy and capacitance analyses. It is revealed that CsFAMA has a lower trap density compared to MA and FAMA through the analyses of 1/ f noises and trapping/detrapping capacitances. Also, an open-circuit voltage ( Voc) change is correlated to the variation of trap states during the shelf-life test: FAMA and CsFAMA cells with the negligible change of Voc over weeks exhibit trap states shifting toward the band edge, although the power-conversion efficiencies are clearly reduced. The origins that critically affect the solar cell performance through the characterizations of shallow/deep traps with additional mobile defects in the perovskite and interfaces are discussed.


High active local levels of vancomycin without nephrotoxicity released from impacted bone allografts in 20 revision hip arthroplasties.
Cancellous bone can act as a delivery vehicle for vancomycin without impairment of graft incorporation. However, local and systemic antibiotic levels, biological activity of vancomycin, interaction with antibiotic-loaded cement, and also nephrotoxicity of these composites have not yet been studied clinically. Blood, drainage and urine samples of 20 consecutive patients undergoing revision total hip arthroplasties with impaction grafting technique utilizing 1 g of vancomycin per femoral head were studied. Plain PMMA cement was used in 10 cases, while PMMA with gentamycin was used in 5 cases and tobramycin was used in the remaining 5 cases. Biological activity of vancomycin was studied using kinetic killing curves in three ATCC organisms (methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosas). Quantification was done with fluorescent polarized immunoassay. Renal function was evaluated with preoperative and postoperative urea and creatinine. Local active bactericidal levels of vancomycin reached 1400 microg/mL (average 5-point level = 367 microg/mL) without nephrotoxicity. Vancomycin was present in urine until the fifteenth day. Both aminoglycosides in the cement had activity against Pseudomonas aeruginosas. Local levels of vancomycin were 35 times greater than the highest levels reported with vancomycin-loaded PMMA. A synergistic effect was observed between vancomycin released from impacted allografts and aminoglycoside-loaded PMMA.


Production of swainsonine by fungal endophytes of locoweed.
Consumption of locoweeds, legumes endemic in arid western USA, has long been associated with locoism, a disease of ruminant animals. To explore the relationship between fungi associated with locoweed and locoweed toxicity, 11 locoweed populations from various sites in New Mexico were assessed for endophytic fungi. Endophytes were isolated from the leaves, stems, seeds, and flowers of eight populations of the toxic locoweeds Astragalus mollissimus, Oxytropis lambertii, and O. sericea. Fungal cultures grew very slowly and sporadically produced subcylindrical conidia with very dark transverse septa. All cultured endophytes produced the alkaloid swainsonine, which causes locoism. Endophyte-infected locoweed populations produced swainsonine, and the swainsonine level of endophyte strains in vitro was highly correlated with the swainsonine level of their host plant populations. The rDNA ITS from mycelia from four endophyte isolates and beta-tubulin encoding regions from mycelia of 18 fungal endophyte isolates were amplified using PCR and the nucleic acid sequences were analyzed. The nucleic acid sequences of the beta-tubulin encoding regions were essentially identical among all the endophytes regardless of plant genus and locations. Morphological evidence and sequence analysis of the ITS region suggest that the endophytes are most closely related to Embellisia. However, with the paucity of Embellisia species represented in sequence databases, precise taxonomic placement will await further study.


Slip to π Ru: structural distortions due to metal-iminoxolene π bonding.
Both pseudo-octahedral and pseudo-square pyramidal bis-iminoxolene complexes trans-(Diso)2RuCl2 and trans-(Diso)2Ru(PPh3) are structurally distorted, with the ruthenium atom slipping off the twofold axis of the idealized coordination polyhedra. These distortions take place because they allow or enhance π interactions between ruthenium and the iminoxolene π orbitals.


Effect of combinations of morphine, dexmedetomidine and maropitant on the electroencephalogram in response to acute electrical stimulation in anaesthetized dogs.
This study was conducted to compare the efficacy of combinations of morphine, dexmedetomidine and maropitant in preventing the changes in electroencephalographic (EEG) indices of nociception in anaesthetized dogs subjected to a noxious electrical stimulus. In a crossover study, eight healthy adult dogs were randomly allocated to four groups: Mor: morphine 0.6 mg/kg; Dex + Mor: morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; Maro + Mor: morphine 0.3 mg/kg + maropitant 1 mg/kg; and Dex + Maro + Mor: morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Following intramuscular administration of test drugs in a minimal anaesthesia model, a supramaximal electrical stimulus (50 V at 50 Hz for 2 s) was applied and the EEG data were recorded. There were significant increases (p < .05) in the poststimulus median frequency (F50) only in groups Mor and Maro + Mor. Dex + Mor group had a significantly lower change in F50 and F95 compared to all other treatment groups. There was no correlation of the changes in EEG frequencies with blood plasma concentration of the drugs during and after noxious stimulation. Combination of dexmedetomidine and morphine was most effective in abolishing the changes in EEG indices in response to a noxious stimulus indicating a supra-additive interaction between these two drugs.


Heart failure-induced brain myelin changes and differences between sexes.
Heart failure (HF) leads to brain injury in autonomic, respiratory, mood, and cognitive control sites, revealed as tissue volume loss, altered metabolites, and impaired diffusion tissue properties. The extent of myelin changes in HF and variations within sexes are unclear. Our aim was to examine regional brain subcortical and white matter myelin integrity in HF patients over control subjects, as well as differences between sexes using T1- and T2-weighted clinical images. We acquired T1- and T2-weighted images from 63 HF patients and 129 controls using a 3.0-Tesla MRI scanner. Using T1- and T2-weighted images, ratio maps were computed, normalized to a common space, smoothed, and compared between groups (ANCOVA; covariates: age and sex; SPM12, false discovery rate, p < .010), as well as between male versus female HF (ANCOVA; covariate: age; SPM12, uncorrected p < .005). Multiple brain areas in HF showed decreased myelin integrity, including the amygdala, hippocampus, cingulate, insula, cerebellum, prefrontal cortices, and multiple white matter areas, compared to controls. Female HF patients showed more brain injuries in the parietal, prefrontal and frontal, hippocampus, amygdala, pons, cerebellar, insula, and corpus callosum compared to male HF patients. HF subjects showed compromised subcortical and white matter myelin integrity, especially in sites regulating autonomic, respiratory, mood, and cognition, with more changes in females over males. These findings provide a structural basis for the enhanced symptoms identified in female over male HF patients with similar disease severity.


Treatment of Fournier's Gangrene With Vacuum-assisted Closure Therapy as Enhanced Recovery Treatment Modality.
Fournier's gangrene is an uncommon, but extremely serious condition of necrotizing, soft tissue infection. There is a great debate regarding the management of larger defects and wound closure, with various techniques being described in the current literature. We aimed to present the surgical management of extensive Fournier's gangrene treated successfully with Vacuum-assisted closure (VAC) therapy, a novel approach to treatment algorithm that can lead to a paradigm shift. A 66-year-old male patient with Fournier's gangrene was treated with extensive surgical debridement, protective colostomy and VAC therapy. After initial extensive surgical debridement, VAC therapy significantly improved the clinical and aesthetic condition of the patient. VAC therapy in Fournier's gangrene patients may be a safe and effective technique with favorable clinical outcomes, by improving and enhancing wound healing and recovery.


Photoredox Approach to N-Acyl-N'-aryl-N,N'-aminals Using Enamides and Their Conversion to γ-Lactams.
A photoredox catalytic approach to synthetically valuable N-acyl-N'-aryl-N,N'-aminals is described. This method uses the addition of a radical precursor to enamides, with subsequent interception of the cationic iminium intermediate with an arylamine. The reaction has been shown to be compatible with electron-rich and electron-deficient arylamines, and moderate to good levels of diastereoselectivity can be attained using a chiral enamide. Furthermore, the N-acyl-N'-aryl-N,N'-aminal reaction products can be readily cyclized, providing a novel synthetic route to valuable γ-lactams.


[Human mycobacterial infections: impact of host genetic factors].
Humans are exposed worldwide to a variety of environmental mycobacteria (EM) and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. Although rarely pathogenic, poorly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. M. tuberculosis and M. leprae are more virulent, causing tuberculosis, and leprosy, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. There is now accumulating evidence that the large interindividual variability of clinical outcome results in part from variability in the human genes that control host defense. We review here in current knowledge about genetic predisposition to common (leprosy and tuberculosis) and rare (BCG and EM infections) mycobacterial infections.


An E2 enzyme Ubc11 is required for ubiquitination of Slp1/Cdc20 and spindle checkpoint silencing in fission yeast.
For ordered mitotic progression, various proteins have to be regulated by an ubiquitin ligase, the anaphase-promoting complex or cyclosome (APC/C) with appropriate timing. Recent studies have implied that the activity of APC/C also contributes to release of mitotic checkpoint complexes (MCCs) from its target Cdc20 in the process of silencing the spindle assembly checkpoint (SAC). Here we describe a temperature-sensitive mutant (ubc11-P93L) in which cell cycle progression is arrested at mitosis. The mutant grows normally at the restrictive temperature when SAC is inactivated, suggesting that the arrest is not due to abnormal spindle assembly, but rather due to prolonged activation of SAC. Supporting this notion, MCCs remain bound to APC/C even when SAC is satisfied. The ubc11 (+) gene encodes one of the two E2 enzymes required for progression through mitosis in fission yeast. Remarkably, Slp1 (a fission yeast homolog of Cdc20), which is degraded in an APC/C-dependent manner, stays stable throughout the cell cycle in the ubc11-P93L mutant lacking the functional SAC. Other APC/C substrates, in contrast, were degraded on schedule. We have also found that a loss of Ubc4, the other E2 required for progression through mitosis, does not affect the stability of Slp1. We propose that each of the two E2 enzymes is responsible for collaborating with APC/C for a specific set of substrates, and that Ubc11 is responsible for regulating Slp1 with APC/C for silencing the SAC.


Signal Amplification Gains of Compressive Sampling for Photocurrent Response Mapping of Optoelectronic Devices.
Spatial characterisation methods for photodetectors and other optoelectronic devices are necessary for determining local performance, as well as detecting local defects and the non-uniformities of devices. Light beam induced current measurements provide local performance information about devices at their actual operating conditions. Compressed sensing current mapping offers additional specific advantages, such as high speed without the use of complicated experimental layouts or lock-in amplifiers. In this work, the signal amplification advantages of compressed sensing current mapping are presented. It is demonstrated that the sparsity of the patterns used for compressive sampling can be controlled to achieve significant signal amplification of at least two orders of magnitude, while maintaining or increasing the accuracy of measurements. Accurate measurements can be acquired even when a point-by-point scan yields high noise levels, which distort the accuracy of measurements. Pixel-by-pixel comparisons of photocurrent maps are realised using different sensing matrices and reconstruction algorithms for different samples. The results additionally demonstrate that such an optical system would be ideal for investigating compressed sensing procedures for other optical measurement applications, where experimental noise is included.


West Nile virus neuroinvasive disease.
Since 1999, there have been nearly 20,000 cases of confirmed symptomatic West Nile virus (WNV) infection in the United States, and it is likely that more than 1 million people have been infected by the virus. WNV is now the most common cause of epidemic viral encephalitis in the United States, and it will likely remain an important cause of neurological disease for the foreseeable future. Clinical syndromes produced by WNV infection include asymptomatic infection, West Nile Fever, and West Nile neuroinvasive disease (WNND). WNND includes syndromes of meningitis, encephalitis, and acute flaccid paralysis/poliomyelitis. The clinical, laboratory, and diagnostic features of these syndromes are reviewed here. Many patients with WNND have normal neuroimaging studies, but abnormalities may be present in areas including the basal ganglia, thalamus, cerebellum, and brainstem. Cerebrospinal fluid invariably shows a pleocytosis, with a predominance of neutrophils in up to half the patients. Diagnosis of WNND depends predominantly on demonstration of WNV-specific IgM antibodies in cerebrospinal fluid. Recent studies suggest that some WNV-infected patients have persistent WNV IgM serum and/or cerebrospinal fluid antibody responses, and this may require revision of current serodiagnostic criteria. Although there is no proven therapy for WNND, several vaccines and antiviral therapy with antibodies, antisense oligonucleotides, and interferon preparations are currently undergoing human clinical trials. Recovery from neurological sequelae of WNV infection including cognitive deficits and weakness may be prolonged and incomplete.


[Effectiveness of a health education class to increase fish intake evaluated by serum fatty acid compositions].
For prevention of cardiovascular disease, we recommended increased fish intake for 50 middle-aged women and men of 40-83 years old at a three-month community-based health education program in an inland farming community. The effectiveness of the education program was evaluated by examining changes in serum lipids and serum fatty acid compositions. For comparison, we selected 48 men and women of 38-82 years old did not participated in the program. Before education, there was no significant difference in the dietary frequency of fish, meat, egg and dishes prepared with oil, mean values of serum lipids or serum fatty acid compositions except for saturated fatty acid, gamma-linolenic acid, dihomo-gamma-linolenic acid and alpha-linolenic acid. After three months, the frequency of fish intake of one or more times per day increased from 33% to 43% in the education group while the frequency of fish intake did not change in the control group. In the education group, serum n3 polyunsaturated fatty acid composition increased from 8.8% to 10.6%. This fatty acid increase was primarily observed in eicosapentaenoic acid and docosahexaenoic acid. The n3/n6 ratio increased from 0.21 to 0.31. In the control group, no change was observed in n3 polyunsaturated fatty acids. This study suggests that the community-based dietary education increased fish intake and serum n3 polyunsaturated fatty acids in women and men of 40 years old or older.


The GuLF STUDY: A Prospective Study of Persons Involved in the Deepwater Horizon Oil Spill Response and Clean-Up.
The 2010 Deepwater Horizon disaster led to the largest ever marine oil spill. Individuals who worked on the spill were exposed to toxicants and stressors that could lead to adverse effects. The GuLF STUDY was designed to investigate relationships between oil spill exposures and multiple potential physical and mental health effects. Participants were recruited by telephone from lists of individuals who worked on the oil spill response and clean-up or received safety training. Enrollment interviews between 2011 and 2013 collected information about spill-related activities, demographics, lifestyle, and health. Exposure measurements taken during the oil spill were used with questionnaire responses to characterize oil exposures of participants. Participants from Gulf states completed a home visit in which biological and environmental samples, anthropometric and clinical measurements, and additional health and lifestyle information were collected. Participants are being followed for changes in health status. Thirty-two thousand six hundred eight individuals enrolled in the cohort, and 11,193 completed a home visit. Most were young (56.2% ≤ 45 years of age), male (80.8%), lived in a Gulf state (82.3%), and worked at least 1 day on the oil spill (76.5%). Workers were involved in response (18.0%), support operations (17.5%), clean-up on water (17.4%) or land (14.6%), decontamination (14.3%), and administrative support (18.3%). Using an ordinal job exposure matrix, 45% had maximum daily total hydrocarbon exposure levels ≥ 1.0 ppm. The GuLF STUDY provides a unique opportunity to study potential adverse health effects from the Deepwater Horizon oil spill.


Translocation of an erythroid-specific hypersensitive site in deletion-type hereditary persistence of fetal hemoglobin.
Hereditary persistence of fetal hemoglobin (HPFH) can involve large deletions which eliminate the 3' end of the beta-like globin gene cluster and more than 70 kilobases (kb) of flanking DNA. Blot hybridization revealed a DNase I-hypersensitive site extending from 1.1 to 1.4 kb downstream of the HPFH-1 3' deletion endpoint. The site was found in normal fetal and adult nucleated erythroid cells and in two erythroleukemia cell lines but not in nonerythroid cells and tissues. Simian virus 40 core enhancer-like sequences were found nonrandomly distributed within the boundaries of the site, which is contained in a fragment of known enhancer activity (E. A. Feingold and B. G. Forget, Blood, in press). A second hypersensitive site was found 0.5 kb upstream of the HPFH-1 3' deletion endpoint but was not erythroid specific. A third site, most prominent in fetal liver-derived erythroid cells, was found 1 kb upstream of the HPFH-2 deletion endpoint. As predicted by the locations of the deletion endpoints, the first two sites were translocated to within 12 kb of the A gamma gene in erythroid colonies derived from an HPFH-2 heterozygote and in hybrid mouse-human erythroid cells carrying the HPFH-2 deletion chromosome. Further analysis of this region showed that it was DNase I sensitive in erythroid and myeloid cells, indicating that it resides in an open chromatin domain. These observations suggest that alterations of chromatin structure flanking the fetal globin genes may contribute to abnormal gene regulation in deletion-type HPFH.


Investigation of the cooperative structure of Fc fragments from myeloma immunoglobulin G.
The cooperative structure of Fc fragments prepared from myeloma human IgG1 was studied using scanning microcalorimetry and fluorescence at pH 4.2-8.0. It was shown that the first to be melted are CH2 domains whose interaction with each other is rather weak, while that with CH3 domains is strong. Then CH3 domains which form a single cooperative block are melted. The data for the structure of the Fc fragment in solution agree with the X-ray data according to which the interaction between CH2 domains is mediated by the carbohydrate moiety while the two CH3 domains are strongly associated. The presence of intensive CH2-CH3 interaction is a distinctive feature of the state of the Fc fragment in the given pH region as compared to that at pH <4.1 [Tischenko, V. M., et al. (1982) Eur. J. Biochem. 126, 517-521; Ryazantsev, S., et al. (1990) Eur. J. Biochem. 190, 393-399]. First, cis interactions greatly increase the free energy of the native structure stabilization in CH2 domains. Second, they decrease this energy for CH3 domains when compared to the state of the latter at pH 3.8 or within the Fc' fragment (the dimer of CH3 domains). The temperature and enthalpy of melting of CH2 domains coincide in all the samples studied despite heterogeneity of the carbohydrate moiety. Thus, it may be postulated that the conservative part of CH2 domains makes a cardinal contribution to the interaction of these domains with the carbohydrate moiety.


"Slow walking with turns" increases quadriceps and erector spinae muscle activity.
[Purpose] To maintain an independent lifestyle, older adults should improve muscle strength and mass, or aerobic capacity. A new exercise pattern, called slow walking with turns, which incorporates turning as an extra load additional to walking. The purpose of this study was to measure oxygen consumption during exercise and muscle activity while turning. [Subjects and Methods] Recreationally active volunteers participated. The participants performed 20 turns per minute while walking back and forth over distances of 1.5 to 3.5 m. We measured oxygen consumption, heart rate, and rating of perceived exertion and performed electromyography during the exercise. [Results] The metabolic equivalents of the exercise were 4.0 ± 0.4 to 6.3 ± 4.0 Mets. Activity was significantly greater in the vastus medialis, vastus lateralis, and erector spinae during the turn phase of slow walking with turns than during the stance phase of treadmill walking. [Conclusion] These findings suggest that slow walking with turns may help to preserve the muscle strength and mass of the trunk and lower limbs that are needed to maintain an independent lifestyle. Slow walking can be performed easily by older people, and in slow walking with turns, the exercise intensity can be adjusted as required for each individual.


Rational Design of a Lanthanide-Based Complex Featuring Different Single-Molecule Magnets.
The rational synthesis of the 2-{1-methylpyridine-N-oxide-4,5-[4,5-bis(propylthio)tetrathiafulvalenyl]-1H-benzimidazol-2-yl}pyridine ligand (L) is described. It led to the tetranuclear complex [Dy4(tta)12(L)2] (Dy-Dy2-Dy) after coordination reaction with the precursor Dy(tta)3⋅2 H2O (tta(-) = 2-thenoyltrifluoroacetonate). The X-ray structure of Dy-Dy2-Dy can be described as two terminal mononuclear units bridged by a central antiferromagnetically coupled dinuclear complex. The terminal N2O6 and central O8 environments are described as distorted square antiprisms. The ac magnetism measurements revealed a strong out-of-phase signal of the magnetic susceptibility with two distinct sets of data. The high- and low-frequency components were attributed to the two terminal mononuclear single-molecule magnets (SMMs) and the central dinuclear SMM, respectively. A magnetic hysteresis loop was detected at very low temperature. From both structural and magnetic points of view, the tetranuclear SMM Dy-Dy2-Dy is a self-assembly of two known mononuclear SMMs bridged by a known dinuclear SMM.


The molecular epidemiology of Stenotrophomonas maltophilia bacteraemia in a tertiary referral hospital in the United Arab Emirates 2000-2004.
Stenotrophomonas maltophilia is recognised as an important cause of nosocomial infection, especially in immunocompromised patients, resulting in significant morbidity and mortality. The treatment of S. maltophilia infection presents a therapeutic challenge. The precise modes of transmission of S. maltophilia in the hospital environment are not known and such knowledge is essential to target interventions to prevent spread. There are few published data on the patterns of nosocomial infection in the United Arab Emirates (UAE). A recent study showed that S. maltophilia is an established cause of bloodstream infection in Tawam Hospital in the UAE. Little is known about its epidemiology in the hospital. We describe the clinical characteristics of 25 episodes of S. maltophilia bacteraemia which occurred from 2000-2004. The strains were characterised using pulsed field gel electrophoresis (PFGE). All episodes were hospital-acquired and malignancy and central venous catheters were predisposing factors. Catheter-associated infection comprised 88% infection. Catheter removal was important for the successful management of catheter-associated infection. The results of PFGE suggested that there were as many strains as patients. S. maltophilia strains isolated from the same patient had indistinguishable PFGE profiles. PFGE is a valid and reproducible typing method for S. maltophilia. The precise sources and modes of spread of S. maltophilia in the hospital are still not known. Knowledge that person to person transmission was not a major mode of transmission enabled infection control interventions for S. maltophilia to be targeted more effectively.


Lupus nephritis: from pathogenesis to targets for biologic treatment.
Lupus nephritis is an organ manifestation of systemic autoimmunity. Current treatment algorithms are still based on unselective immunosuppressive drugs. There is hope that highly selective biological drugs could be as or even more effective but less toxic. A profound understanding of the pathogenesis of lupus nephritis is necessary to identify the optimal molecular targets. PubMed and www.clincialtrials.gov were searched using 'lupus nephritis' as the key word. The pathogenesis of lupus nephritis is based (1) on the mechanisms that lead to loss of tolerance against nuclear autoantigens, i.e. systemic lupus, and then (2) on the mechanisms of immune complex-induced intrarenal inflammation. Systemic lupus develops when genetic variants allow autoimmunization against nuclear autoantigens, e.g. by impairing lymphocyte depletion via apoptosis, opsonization, and rapid phagocytic clearance. This allows endogenous nucleic acids to directly activate Toll-like receptors on dendritic cells or B cells, a process that drives IFN-α-driven immunity, antigen presentation, and the activation of autoreactive lymphocyte subsets. Activation of B cells and their maturation to plasma cells promotes autoantibody production and subsequent immune complex glomerulonephritis. Complement and numerous proinflammatory cytokines drive the inflammatory process that can cause kidney injury, scarring, and chronic kidney disease. Systemic lupus is more a variable syndrome than a single disorder based on heterogeneous genetic variants and complex aberrant immune alterations. This makes it less likely that a single specific biological drug will be as efficient as currently used unselective immunosuppressive drugs. Autoantibody production and intrarenal immune complex formation are the hallmark of lupus nephritis. However, kidney injury and scarring also result from local amplification of tissue inflammation. Therefore, a combination of unselective immunosuppressive and biological drugs that block immune cell recruitment or proinflammatory cytokines may be promising to improve disease outcomes in lupus nephritis.


Intramolecular electron transfer within a covalent, fixed-distance donor-acceptor molecule in an ionic liquid.
Intramolecular photoinduced charge separation and recombination within the donor-acceptor molecule 4-(N-pyrrolidino)naphthalene-1,8-imide-pyromellitimide, 5ANI-PI, are studied using ultrafast transient absorption spectroscopy in the room-temperature ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide [EMIM][Tf2N]. The rate constants of both photoinduced charge separation and charge recombination for 5ANI-PI in [EMIM][Tf2N] are comparable to those observed in pyridine, which has a static dielectric constant similar to that of [EMIM][Tf2N] but a viscosity that is nearly 2 orders of magnitude lower than that of [EMIM][Tf2N]. The electron-transfer dynamics of 5ANI-PI in [EMIM][Tf2N] are compared to those in pyridine as a function of temperature and are discussed in the context of recently reported ionic liquid solvation studies.


Masting in wind-pollinated trees: system-specific roles of weather and pollination dynamics in driving seed production.
Masting, the highly variable production of synchronized large seed crops, is a common reproductive strategy in plant populations. In wind-pollinated trees, flowering and pollination dynamics are hypothesized to provide the mechanistic link for the well-known relationship between weather and population-level seed production. Several hypotheses make predictions about the effect of weather on annual pollination success. The pollen coupling hypothesis predicts that weather and plant resources drive the flowering effort of trees, which directly translates into the size of seed crops through efficient pollination. In contrast, the pollination Moran effect hypothesis predicts that weather affects pollination efficiency, leading to occasional bumper crops. Furthermore, the recently formulated phenology synchrony hypothesis predicts that Moran effects can arise because of weather effects on flowering synchrony, which, in turn, drives pollination efficiency. We investigated the relationship between weather, airborne pollen, and seed production in common European trees, two oak species (Quercus petraea and Q. robur) and beech (Fagus sylvatica) with a 19-yr data set from three sites in Poland. Our results show that warm summers preceding flowering correlated with high pollen abundance and warm springs resulted in short pollen seasons (i.e., high flowering synchrony) for all three species. Pollen abundance was the best predictor for seed crops in beech, as predicted under pollen coupling. In oaks, short pollen seasons, rather than pollen abundance, correlated with large seed crops, providing support for the pollination Moran effect and phenology synchrony hypotheses. Fundamentally different mechanisms may therefore drive masting in species of the family Fagacae.


GENETIC DUTIES.
Most of our genetic information does not change, yet the results of our genetic tests might. Labs reclassify genetic variants in response to advances in genetic science. As a result, a person who took a test in 2010 could take the same test with the same lab in 2020 and get a different result. However, no legal duty requires labs or physicians to inform patients when a lab reclassifies a variant, even if the reclassification communicates clinically actionable information. This Article considers the need for such duties and their potential challenges. In so doing, it offers much-needed guidance to physicians and labs, who may face liability, and to courts, which will hear these cases.


A comparative investigation on subspace dimension determination.
It is well-known that constrained Hebbian self-organization on multiple linear neural units leads to the same k-dimensional subspace spanned by the first k principal components. Not only the batch PCA algorithm has been widely applied in various fields since 1930s, but also a variety of adaptive algorithms have been proposed in the past two decades. However, most studies assume a known dimension k or determine it heuristically, though there exist a number of model selection criteria in the literature of statistics. Recently, criteria have also been obtained under the framework of Bayesian Ying-Yang (BYY) harmony learning. This paper further investigates the BYY criteria in comparison with existing typical criteria, including Akaike's information criterion (AIC), the consistent Akaike's information criterion (CAIC), the Bayesian inference criterion (BIC), and the cross-validation (CV) criterion. This comparative study is made via experiments not only on simulated data sets of different sample sizes, noise variances, data space dimensions, and subspace dimensions, but also on two real data sets from air pollution problem and sport track records, respectively. Experiments have shown that BIC outperforms AIC, CAIC, and CV while the BYY criteria are either comparable with or better than BIC. Therefore, BYY harmony learning is a more preferred tool for subspace dimension determination by further considering that the appropriate subspace dimension k can be automatically determined during implementing BYY harmony learning for the principal subspace while the selection of subspace dimension k by BIC, AIC, CAIC, and CV has to be made at the second stage based on a set of candidate subspaces with different dimensions which have to be obtained at the first stage of learning.


[Malunited juvenile fractures in the foot region].
Between 1971 and 1990 we treated 121 juvenile patients up to 14 years of age with fractures of the ankle joint and foot in the department of trauma surgery at Hannover Medical School. A total of 128 fractures were treated in these patients, excluding toe fractures. The distribution of fractures as referred to the anatomical-functional planes was as follows: Tibia-talar joint 69; talus 8; calcaneus 6; Chopart joint 5; Lisfranc joint 4 and metatarsal area 36. Clinical and radiological follow-up investigations were possible a mean of 8.7 years post trauma for all talar and calcaneal fractures, for 7 out of 9 Chopart/Lisfranc injuries and for 7 out of 35 of metatarsal fractures. In the case of talus fractures our results suggest that it is to restore the original length of the talus bone (medial column); this is important to prevent collapse of the longitudinal arch with subsequent early arthritis. The rare cases of sustained intraarticular damage to calcaneal fractures should be treated as in adults, i.e. by open, anatomical reconstruction. In children, Chopart/Lisfranc 2 fracture dislocations only occur if high-energy trauma is present (runover trauma in 4 out of 9 cases). Optimal treatment again is comparable to that in adults: open, anatomical reduction with Kirschner-wires followed by temporary, tibio-tarsal transfixation; this is important since no compensatory mechanisms develop if a subluxation is present after reduction. Metatarsal fractures often occur along the first and fifth rays and have a good prognosis. Conservative treatment is justified, since, according to our results, even in intraarticular fractures of the metatarsal head good remodeling to fragments occurs.


Software used in emergency medical services.
Management of documentation in emergency medical services poses specific challenges due to its mode of operation. Electronic aids are already being used in this field. This article identifies four key systems: documentation management software, software for diagnostic devices, software for county emergency dispatches and navigational software. Each county emergency services provider in the Czech Republic is now equipped with all aforementioned systems. Most of these providers are also able to perform remote ECG consultations.


Mediators of change in physical activity following an intervention in primary care: PACE.
The current study evaluated the construct validity of a physical activity intervention in primary care by testing whether the intervention changed hypothesized mediators and whether changes in the mediators were associated with behavior change. Matched physician offices were nonrandomly assigned to intervention or control. Apparently healthy, sedentary, adult patients (N = 255) were recruited from physician offices. The intervention was brief, behaviorally based counseling by physicians, plus a telephone follow-up 2 weeks later. Assessments of physical activity and mediators were collected at baseline and at 4- to 6-week follow-up. Hypothesized mediators were processes of change, self-efficacy, and social support for exercise. Patients who were counseled improved significantly more than those in the control group on behavioral and cognitive processes of change. Other changes in mediators were nonsignificant. Behavioral processes of change and self-efficacy made significant contributions to the multiple regression model explaining self-report and objective measures of physical activity. The intervention affected some of the targeted mediators of physical activity change. Two of three mediator variables were associated with changes in physical activity regardless of experimental condition and other variables. The construct validity of the intervention was partially supported.


The pluripotent genome in three dimensions is shaped around pluripotency factors.
It is becoming increasingly clear that the shape of the genome importantly influences transcription regulation. Pluripotent stem cells such as embryonic stem cells were recently shown to organize their chromosomes into topological domains that are largely invariant between cell types. Here we combine chromatin conformation capture technologies with chromatin factor binding data to demonstrate that inactive chromatin is unusually disorganized in pluripotent stem-cell nuclei. We show that gene promoters engage in contacts between topological domains in a largely tissue-independent manner, whereas enhancers have a more tissue-restricted interaction profile. Notably, genomic clusters of pluripotency factor binding sites find each other very efficiently, in a manner that is strictly pluripotent-stem-cell-specific, dependent on the presence of Oct4 and Nanog protein and inducible after artificial recruitment of Nanog to a selected chromosomal site. We conclude that pluripotent stem cells have a unique higher-order genome structure shaped by pluripotency factors. We speculate that this interactome enhances the robustness of the pluripotent state.


Efficacy of cyclophosphamide, doxorubicin, and cisplatin for adenoid cystic carcinoma, and their relationship with the pre-chemotherapy tumor growth rate.
While surgical resection is the treatment of choice for adenoid cystic carcinoma (ACC), patients with metastasis and those who cannot undergo surgery receive palliative chemotherapy. However, the role of palliative chemotherapy is not clear yet. This study aimed to evaluate the efficacy of chemotherapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) for patients with ACC; and to analyze the relationship between the pre-chemotherapy tumor growth rate (P-TGR) and treatment outcomes in patients with the recurred metastatic unresectable ACC. We retrospectively analyzed the clinical data and treatment outcomes of patients who diagnosed ACC and treated with CAP chemotherapy. Response evaluation was performed using computed tomography (CT) images obtained before and after chemotherapy according to the RECIST 1.1. P-TGR was defined as the difference of the sum of the largest diameter of the target lesion per unit of time between the pre-baseline and baseline CT images. Fourteen patients with ACC who were treated with CAP were enrolled. Median patient age was 49 years, and the patients received a median of 5 CAP treatment cycles. Two patients achieved partial response (PR) and 10 patients showed stable disease. Response rate was 14.3%, and the disease control rate was 85.7%. Median progression-free survival was 5.7 months (95% CI: 4.3 to not reached) and the median overall survival was 23.4 months (95% CI: 12.9 to not reached). A low P-TGR was associated with a good response to CAP (correlation coefficient, 0.56). Palliative CAP chemotherapy demonstrated a modest anti-cancer effect for ACC. A low P-TGR was associated with a good response to CAP chemotherapy.


[Characteristics of Partial Denitrification in Biofilm System].
As an intermediate form of microbial denitrification, nitrite serves as a key substrate for anaerobic ammonium oxidation (ANAMMOX). This study investigated the partial dentification (PD) characteristics and the coupling feasibility of PD+ANAMMOX in the biofilm system, using a moving bed biofilm reactor which was operated for 120 days. After 40 days of operation with a C/N ratio of 3.0 and filling fraction of 20%, the nitrate-to-nitrite transformation ratio (NTR) reached (69.38±3.53)%, and enzymatic assays indicated that the activities of nitrate reductase (NAR) had increased from 0.03 to 0.45 μmol·(min·mg)-1 while the activities of nitrite reductase (NIR) had decreased from 0.18 to 0.02 μmol·(min·mg)-1. Illumina high-throughput sequencing analysis revealed that the proportion of genus of Thauera bacteria to total microorganism increased from 0.3% (d1) to 37.27% (d64). Finally, the effluent had a total nitrogen (TN) concentration of (6.41±1.50) mg·L-1, indicating a total nitrogen removal ratio of (88.16±2.71)% and confirming the feasibility of PD+ANAMMOX in the biofilm system.


Acute intermittent porphyria: general aspects with focus on pain.
Despite medical advances, the diagnosis and management of acute intermittent porphyria continues to be challenging. Acute pain is one of the most important clinical manifestations in acute intermittent porphyria, but management and pain assessment have been poorly studied in these patients. The lack of information and evidence based recommendations regarding these topics in the medical literature is certainly surprising. Furthermore, pain management is discussed based on extrapolating concepts adopted for other pain syndromes. An important arsenal of medications, including reportedly safe opioid and non-opioid analgesics, is available for use in this type of patient. In addition to conducting an extensive review of the current literature, the present article aims to show the general aspects of a disease that generates a challenge for the clinician, emphasizing what is related to pain as a cardinal symptom and to create awareness about the need for studies supporting the development of guidelines, based on evidence obtained from analgesic management in patients presenting with this disorder. A systematic assessment directed at understanding the physiopathological processes underlying acute pain combined with a stepwise approach to pain management with safe opioid and non-opioid drugs constitutes the fundamental basis for a successful pain management program in patients with acute intermittent porphyria.


A pseudo-outbreak of influenza A associated with use of laboratory stock strain.
In November 1982, when influenza type A(H3N2) viruses were spreading in the United States, influenza A(H1N1) viruses were reportedly isolated from 10 hospitalized patients in New Mexico, only two of whom had influenza-like illnesses. Reference stock influenza A/Fort Monmouth (FM)/1/47(H1N1) virus had been used to prepare fluorescent antibody test slides in the laboratory reporting the isolates. After investigation, it was concluded that the isolates from the patients' cultures were a result of laboratory contamination. When an unexpected cluster of unusual virus isolates is reported, the possibility of laboratory contamination should be considered.


Molecular interactions between ribosomal proteins. Evidence for specificity of interaction between isolated proteins.
The proteins S2, S3, S5, and S10 from the 30S ribosomal subunit of Escherichia coli was studied by analytical ultracentrifugation to characterize them in solution and to determine whether isolated protein-protein interactions exist. Such interactions, if specific, may therefore bear some relationship to the spatial organization of the subunit structure. It was found that protein S2 self-associates to a slight extent and that solution mixtures of S2 and S3 contain only enough dimeric species to account for the S2 dimer. Hence, no observable interaction was detected between S2 and S3. Solution mixtures of proteins S5 and S10 revealed a species of molecular weight greater than either protein. The proposal is that S5 and S10 interact with an association equilibrium constant of 7.6 X 10(-5) M-1 at 3 degrees in a Tris buffer at pH 7.4. It was also shown that solution with a 1:1:1 mixture by mass, of S2, S5, and S10 contained a species possessing a molecular weight consistent with a simple ternary complex of the three proteins.


Noninvasive Fetal Electrocardiography in the Diagnosis of Long QT Syndrome: A Case Series.
Early detection and monitoring for malignant arrhythmias is fundamental to prenatal care in long QT syndrome (LQTS). Recently, we studied the feasibility of isolating the fetal electrocardiogram (fECG) and measuring electrocardiographic intervals with a noninvasive fECG device using blind source separation with reference signal. Our aim was to evaluate the ability of fECG to diagnose LQTS. We identified 3 cases of clinically suspected LQTS based on fetal echocardiogram (2 had sinus bradycardia, 1 had second-degree atrioventricular block with negative maternal anti-SSA/SSB antibody titers). With institutional review board approval, these patients were prospectively enrolled for fECG acquisition. Offline post-processing generated fECG waveforms and calculated QT intervals. Case 1 and 3 had a maternal history of LQTS. Two of the three fetuses with suspected LQTS had confirmed LQTS by postnatal ECG and genetic testing. FECG was able to identify a prolonged corrected QT interval in both cases. One of these also had fetal magnetocardiography (fMCG), which yielded similar findings to the fECG. The third fetus had a normal fECG; fMCG and postnatal ECG were also normal. In 3 cases, fECG findings corroborated the diagnosis of LQTS. Noninvasive fECG may offer a novel method for fECG that is portable and more clinically accessible.


DGW1, encoding an hnRNP-like RNA binding protein, positively regulates grain size and weight by interacting with GW6 mRNA.
Grain size and weight determine rice yield. Although numerous genes and pathways involved in regulating grain size have been identified, our knowledge of post-transcriptional control of grain size remains elusive. In this study, we characterize a rice mutant, decreased grain width and weight 1 (dgw1), which produces small grains. We show that DGW1 encodes a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family protein and preferentially expresses in developing panicles, positively regulating grain size by promoting cell expansion in spikelet hulls. Overexpression of DGW1 increases grain weight and grain numbers, leading to a significant rise in rice grain yield. We further demonstrate that DGW1 functions in grain size regulation by directly binding to the mRNA of Grain Width 6 (GW6), a critical grain size regulator in rice. Overexpression of GW6 restored the grain size phenotype of DGW1-knockout plants. DGW1 interacts with two oligouridylate binding proteins (OsUBP1a and OsUBP1b), which also bind the GW6 mRNA. In addition, the second RRM domain of DGW1 is indispensable for its mediated protein-RNA and protein-protein interactions. In summary, our findings identify a new regulatory module of DGW1-GW6 that regulates rice grain size and weight, providing important insights into the function of hnRNP-like proteins in the regulation of grain size.


Analysis of natural killer cells in patients with aplastic anemia.
We have analyzed natural killer (NK) cells in 43 patients with severe aplastic anemia, using cytotoxicity assays and microfluorometry with monoclonal antibodies, prior to and after treatment with antithymocyte globulin (ATG). Before treatment, natural killer cell activity (NKa) in both peripheral blood and bone marrow was markedly decreased in 76% of patients as compared with normal controls. Although we have measured low NKa in patients receiving large numbers of blood transfusions (means = 150 U of RBCs), six aplastic patients had low NKa in the absence of transfusions, and the average number of transfusions in the total population was low (means = 24). Purification of larger granular lymphocytes (LGLs) from peripheral blood of aplastic anemia patients failed to recover significant NKa. Most of these large granular lymphocytes showed few azurophilic granules. NKa was appropriately enhanced in these patients samples by exposure of mononuclear cells to either interleukin 2 (IL-2) or interferon (IFN). Analysis of peripheral blood phenotypic markers showed that cells bearing Leu 7 antigen were in the normal range in aplastic anemia (means = 12% +/- 2%; normal = 16% +/- 2%), but there was a deficiency of Leu 11+ cells (means = 8% +/- 2%; normal = 15% +/- 2%). The number of Leu 11+ cells was well correlated with NKa. In 13 of 22 patients treated with ATG, NKa returned to the normal range, and recovery of NKa was correlated to hematopoietic recovery. Our results suggest that deficient NKa is an intrinsic feature of aplastic anemia, and that the circulating cells in this disease are of the pre-NK cell stage.


Utility of FDG PET/CT in Patient with Synchronous Breast and Colon Cancer.
The most common malignancy in women is breast cancer, and the second one is colon cancer. Synchronous breast and colon cancers are rare. Here, we reported a 60-year-old woman with a left breast mass for six months. Biopsy revealed an invasive ductal carcinoma. She underwent 2-[Fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan for evaluation of the extent of the disease. FDG PET/CT revealed an advanced left breast cancer with multiple metastases in both regional and distant lymph nodes (in left axilla level I/II, lower paratracheal region, and right lung hilum), bilateral lungs, and axial and proximal appendicular skeletons. An early staged synchronous colon cancer was detected incidentally on FDG PET/CT images. After endoscopic mucosal resection of colon cancer, she received palliative chemotherapy for breast cancer with a marked therapeutic response. The disease status of post-treated breast cancer remained relatively stationary for more than one year. Brain metastasis was noted afterward. Nevertheless, there was no evidence of colon cancer recurrence throughout her breast cancer disease course.


Macroscopic and histological investigation of guanaco footpads (Lama guanicoe, Müller 1776).
The surface of guanaco footpads is characterized by hairless skin with up to 4-mm-thick stratum corneum that protects from abrasion. The horny layer is pliable and elastic, and ensures firm contact with irregular ground. It is padded with a particular structure of the subcutaneous layer, the digital cushion. The flat cushions of each of the two digits are of elongated ovate shape, each about 45-mm long, up to 20-mm wide, and 8-mm thick. The cushions are lined by a 1-2-mm-thick capsule that resembles a tunica albuginea. The capsule consists of coarse collagen fibers, with elastic fibers absent. The cushion capsule and dermis approach each other, and fuse along a line that runs parallel to the longitudinal axes of cushion and digit. Loose connective tissue rich in elastic fibers and acidic glycosaminoglycans separates dermis and cushion capsule lateral to the narrow interconnecting zone. The cushion capsule encloses cloudy yellowish, gelatinous material. Microscopy shows bundles of elastic fibers in abundant mucinous matrix. Tightly gathered elastic bundles adjoin the inner surface of the capsule. Rough cords of elastic fibers branch out from there and traverse to the opposite side. The cushion is pressed flat, and elastic fibers are stretched when bearing weight. With relief of load, elastic fibers contract and reset the cushion's shape. Contractile cells are absent. A resistant capsule and easily malleable mucinous contents establish the functioning as a gel pad. Mucinous connective tissue between elastic fiber bundles contains abundant basophilic matrix. Hyaluronan, chondroitin sulfate, and dermatan sulfate are main matrix constituents. Spindle-shaped or stellate fibroblasts contain vimentin, S100 protein, and neuron specific enolase. Moprhology, staining characteristics and synthesis activities of these cells meet the criteria to be classified as myxoid cells. The connective tissue in guanaco digital cushions represents myxoid tissue.


The Institutional Approach for Modeling the Evolution of Human Societies.
Artificial life is concerned with understanding the dynamics of human societies. A defining feature of any society is its institutions. However, defining exactly what an institution is has proven difficult, with authors often talking past each other. This article presents a dynamic model of institutions, which views them as political game forms that generate the rules of a group's economic interactions. Unlike most prior work, the framework presented here allows for the construction of explicit models of the evolution of institutional rules. It takes account of the fact that group members are likely to try to create rules that benefit themselves. Following from this, it allows us to determine the conditions under which self-interested individuals will create institutional rules that support cooperation-for example, that prevent a tragedy of the commons. The article finishes with an example of how a model of the evolution of institutional rewards and punishments for promoting cooperation can be created. It is intended that this framework will allow artificial life researchers to examine how human groups can themselves create conditions for cooperation. This will help provide a better understanding of historical human social evolution, and facilitate the resolution of pressing societal social dilemmas.


[A new method of calibration and positioning in quantitative analysis of multicomponents by single marker].
This paper aims to establish a new method of calibration and positioning in quantitative analysis of multicomponents by single marker (QAMS), using Shuanghuanglian oral liquid as the research object. Establishing relative correction factors with reference chlorogenic acid to other 11 active components (neochlorogenic acid, cryptochlorogenic acid, cafferic acid, forsythoside A, scutellarin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, baicalin and phillyrin wogonoside) in Shuanghuanglian oral liquid by 3 correction methods (multipoint correction, slope correction and quantitative factor correction). At the same time chromatographic peak was positioned by linear regression method. Only one standard uas used to determine the content of 12 components in Shuanghuanglian oral liquid, in stead of needing too many reference substance in quality control. The results showed that within the linear ranges, no significant differences were found in the quantitative results of 12 active constituents in 3 batches of Shuanghuanglian oral liquid determined by 3 correction methods and external standard method (ESM) or standard curve method (SCM). And this method is simpler and quicker than literature methods. The results were accurate and reliable, and had good reproducibility. While the positioning chromatographic peaks by linear regression method was more accurate than relative retention time in literature. The slope and the quantitative factor correction controlling the quality of Chinese traditional medicine is feasible and accurate.


Thrombin peptide (TP508) promotes adipose tissue-derived stem cell proliferation via PI3 kinase/Akt pathway.
A synthetic peptide representing the receptor-binding domain of human thrombin (TP508) promotes angiogenesis and accelerates wound healing in animal models. However, the mechanisms underlying the therapeutic effects of TP508 have not been clearly defined. In this study, we set out to determine whether TP508 could stimulate stem cell proliferation. Adipose tissue-derived stem cells (ASCs) were incubated with TP508 (5 microg/ml) and cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation. Our data showed that TP508 treatment significantly stimulated BrdU incorporation in ASCs (p < 0.01). The increased BrdU incorporation induced by TP508 was abolished by the PI3 kinase (PI3K) inhibitor LY294002 at 50 microM. Western blot analysis of ASCs revealed increased phosphorylation of Akt in response to TP508 when compared to unstimulated controls. These results indicate that TP508 exerts proliferative effects on ASCs via the PI3K/Akt pathway.


A Computational Drug Repositioning Approach for Targeting Oncogenic Transcription Factors.
Mutations in transcription factor (TF) genes are frequently observed in tumors, often leading to aberrant transcriptional activity. Unfortunately, TFs are often considered undruggable due to the absence of targetable enzymatic activity. To address this problem, we developed CRAFTT, a computational drug-repositioning approach for targeting TF activity. CRAFTT combines ChIP-seq with drug-induced expression profiling to identify small molecules that can specifically perturb TF activity. Application to ENCODE ChIP-seq datasets revealed known drug-TF interactions, and a global drug-protein network analysis supported these predictions. Application of CRAFTT to ERG, a pro-invasive, frequently overexpressed oncogenic TF, predicted that dexamethasone would inhibit ERG activity. Dexamethasone significantly decreased cell invasion and migration in an ERG-dependent manner. Furthermore, analysis of electronic medical record data indicates a protective role for dexamethasone against prostate cancer. Altogether, our method provides a broadly applicable strategy for identifying drugs that specifically modulate TF activity.


Iron supplementation until 6 months protects marginally low-birth-weight infants from iron deficiency during their first year of life.
Low-birth-weight (LBW) infants (<2500 g) have an increased risk of iron deficiency (ID) during their first 6 months of life. The optimal dose and duration of iron supplementation to LBW infants are, however, unknown. The objective of the present study was to investigate the long-term effect on iron status and growth in marginally LBW (2000-2500 g) infants, of iron supplements given until 6 months of life. In a randomized controlled trial, 285 healthy marginally LBW infants received 0, 1, or 2 mg · kg(-1) · day(-1) of iron supplements from 6 weeks to 6 months of age. At 12 months and 3.5 years of life we measured length, weight, head circumference, and indicators of iron status (hemoglobin, ferritin, mean corpuscular volume, and transferrin saturation) and assessed the prevalence of iron depletion, functional ID, and ID anemia. At 12 months of age, there was a significant difference in ferritin between the groups (P = 0.006). Furthermore, there was a significant difference in the prevalence of iron depletion (23.7%, 10.6%, and 6.8%, respectively, in the placebo, 1-mg, and 2-mg groups, P = 0.009) and similar nonsignificant trends for functional ID and ID anemia. At 3.5 years of life there were no significant differences in iron status and the mean prevalence of iron depletion was 3.2%. Anthropometric data were not affected by the intervention. Iron supplements with 2 mg · kg(-1) · day(-1) until 6 months of life effectively reduces the risk of ID during the first 12 months of life and is an effective intervention for preventing early ID in marginally LBW infants.


An investigation of the relationship between ethnicity and success in a BSc (Hons) Physiotherapy degree programme in the UK.
To explore the potential relationship between ethnicity and achievement within undergraduate physiotherapy education. A retrospective analysis of assessment marks awarded for academic and clinical modules. A London University offering undergraduate physiotherapy education. Four hundred forty-eight undergraduate students enrolled onto the Physiotherapy honours degree programme between 2005 and 2009. Marks awarded following academic or clinical assessment. These were modelled through multivariable regression analysis to evaluate the relationship between marks awarded and ethnicity. Differences were noted between ethnic categories in final programme success and across academic and clinical modules. Our multivariable analysis demonstrated students from Asian backgrounds had decreased odds of succeeding compared with white British students (adjusted OR 0.43 95%CI 0.24, 0.79 P=0.006), as had Black students (adjusted OR 0.42 95%CI 0.19, 0.95 P=0.036) and students from Other ethnic backgrounds (adjusted OR 0.41 95%CI 0.20, 0.87 P=0.020). This analysis of undergraduate physiotherapy students illustrated a persistent difference in attainment between students from white British and those from BME backgrounds. Heterogeneity in academic outcomes both within and between minority ethnic groups was illustrated. This study not only reinforces the need to consider ethnicity within physiotherapy education but also raises further questions about why physiotherapy students from BME groups perform less well than their white British peers.


The diabetic foot: pathogenesis and clinical evaluation.
Foot ulcers are one of the major complications of diabetes. They have a poor tendency to heal, which may result in long-term in-hospital treatment and/or amputation. The foot in diabetic patients is the crossroads of several pathological processes, in which almost all components of the lower extremity are involved: skin, subcutaneous tissue, muscles, bones, joints, blood vessels, and nerves. An understanding of these processes is necessary for the development and application of preventative and management strategies. In this article the pathogenesis of the major abnormalities in the diabetic foot are described, the pathways to ulceration are summarized, and a systematic evaluation of a diabetic patient with a foot ulcer is given.


[Dairy product consumption in France].
The French are among the biggest European consumers of dairy products. Characterized by a negative trend during the last 10 to 15 years, the French market shows relatively low liquid milk and high cheese and yogurt consumption. Consumption varies with age, gender, and the type of product.


TDMA-based dual-mode communication for mobile wireless sensor networks.
Small highly mobile robots, and in particular micro air vehicles (MAVs), are well suited to the task of exploring unknown indoor environments such as buildings and caves. Such a task imposes a number of requirements on the underlying communication infrastructure, with differing goals during various stages of the mission. This work addresses those requirements with a hybrid communications infrastructure consisting of a stationary mesh network along with the mobile nodes. The combined network operates in two independent modes, coupling a highly efficient, low duty cycle, low throughput mode for routing and persistent sensing with a burst mode for high data rate communication. By strategically distributing available frequency channels between the mobile agents and the stationary nodes, the overall network provides reliable long-term communication paths while maximizing data throughput when needed.


Non-enzymatic N-acetylation of Lysine Residues by AcetylCoA Often Occurs via a Proximal S-acetylated Thiol Intermediate Sensitive to Glyoxalase II.
Acetyl coenzyme A (AcCoA), a key intermediate in mitochondrial metabolism, N-acetylates lysine residues, disrupting and, in some cases, regulating protein function. The mitochondrial lysine deacetylase Sirtuin 3 (Sirt3) reverses this modification with benefits reported in diabetes, obesity, and aging. We show that non-enzymatic lysine N-acetylation by AcCoA is greatly enhanced by initial acetylation of a cysteine residue, followed by SN-transfer of the acetyl moiety to a nearby lysine on mitochondrial proteins and synthetic peptides. The frequent occurrence of an S-acetyl intermediate before lysine N-acetylation suggests that proximity to a thioester is a key determinant of lysine susceptibility to acetylation. The thioesterase glyoxalase II (Glo2) can limit protein S-acetylation, thereby preventing subsequent lysine N-acetylation. This suggests that the hitherto obscure role of Glo2 in mitochondria is to act upstream of Sirt3 in minimizing protein N-acetylation, thus limiting protein dysfunction when AcCoA accumulates.


Comparative studies of 5 alpha-reductase inhibitors within MCF-7 human breast cancer cells.
We have compared the inhibitory effects of six synthetic steroid analogs (17 beta-carboxy-4-androsten-3-one benzylanilide (VP-1), 17 alpha-acetoxy-6-methylene-4-pregnene-3,20-dione (VP-2), 6-methylene-4-pregnene-3,20-dione (VP-3), 17 beta-acetoxy-6-methylene-4-androsten-3-one (VP-4), 17 beta-acetoxy-16,16-dimethyl-6-methylene-4-androsten-3-one (VP-5), and 3 beta-hydroxy-16-methylene-5-androsten-17-one (VP-6) ) upon 5 alpha-reductase activity within MCF-7 human breast cancer cells and rat prostate. Enzyme assays were performed by quantifying the amounts of [3H]5 alpha-androstan-3 alpha-17 beta-diol and/or [3H]dihydrotestosterone formed from 40 nM [3H]testosterone within each system. Five microM concentrations of VP-2 and VP-3 inhibited prostatic 5 alpha-reductase by 55 and 65%, respectively, whereas the other analogs showed little activity. In contrast, each of the six analogs was active against MCF-7 homogenate 5 alpha reductase activity. VP-2 and VP-4 demonstrated approx 65 and 70% inhibitions, respectively, whereas the other four compounds inhibited enzyme activity by 40-55% in this system. These results suggest that rat prostate and MCF-7 cells contain different 5 alpha-reductase isozymes. When these agents were examined for 5 alpha-reductase inhibitory activity following 1 h preincubations with intact MCF-7 cultures, VP-1 and 3 demonstrated potencies similar to those in MCF-7 homogenate. The other compounds, however, were far less active under these conditions. Longer culture preincubations (16 h) were associated with substantially increased VP-6 potency, moderate increases for VP-4 and 5, but no change in VP-2 activity. Additional studies examining the abilities of these agents to bind to MCF-7 androgen receptor (AR) and progesterone receptor (PR) revealed moderate AR binding activities of VP-2, 3, and 4, and substantial PR binding for VP-2 and 3. Finally, VP-4 failed to inhibit estrogen-dependent MCF-7 PR synthesis, suggesting that it has no androgenic activity despite its ability to interact with MCF-7 AR.


Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders.
Single-nucleotide polymorphisms in genes involved in lipoprotein and adipocyte metabolism may explain why dyslipidemia and lipoatrophy occur in some but not all antiretroviral therapy (ART)-treated individuals. We evaluated the contribution of APOC3 -482C-->T, -455T-->C, and 3238C-->G; epsilon 2 and epsilon 4 alleles of APOE; and TNF -238G-->A to dyslipidemia and lipoatrophy by longitudinally modeling >2600 lipid determinations and 2328 lipoatrophy assessments in 329 ART-treated patients during a median follow-up period of 3.4 years. In human immunodeficiency virus (HIV)-infected individuals, the effects of variant alleles of APOE on plasma cholesterol and triglyceride levels and of APOC3 on plasma triglyceride levels were comparable to those reported in the general population. However, when treated with ritonavir, individuals with unfavorable genotypes of APOC3 and [corrected] APOE were at risk of extreme hypertriglyceridemia. They had median plasma triglyceride levels of 7.33 mmol/L, compared with 3.08 mmol/L in the absence of ART. The net effect of the APOE*APOC3*ritonavir interaction was an increase in plasma triglyceride levels of 2.23 mmol/L. No association between TNF -238G-->A and lipoatrophy was observed. Variant alleles of APOE and APOC3 contribute to an unfavorable lipid profile in patients with HIV. Interactions between genotypes and ART can lead to severe hyperlipidemia. Genetic analysis may identify patients at high risk for severe ritonavir-associated hypertriglyceridemia.


The Value of the Apolipoprotein B/Apolipoprotein A1 Ratio in Predicting the Rapid Progression of Non-Culprit Coronary Lesions in Acute Coronary Syndrome in Patients with Diabetes Mellitus after Percutaneous Coronary Intervention.
This study aims to assess the predictive value of the apolipoprotein B (ApoB) /apolipoprotein A1 (ApoA1) ratio in acute coronary syndrome (ACS) in patients with diabetes mellitus (DM) for the rapid progression (RP) of non-culprit coronary lesions (NCCLs) after percutaneous coronary intervention (PCI) and observe the effect of the ApoB/ApoA1 ratio on major adverse cardiac events (MACE).A total of 175 patients with DM presenting with ACS who received a PCI and an average 13-month follow-up coronary angiography (CAG) were enrolled from January 2015 to December 2020. According to the CAG, the patients were divided into the RP group and the non-RP group. MACE was defined as a composite of death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization from unstable or progressive angina at the end of a 24-month follow-up.The low-density lipoprotein cholesterol (LDL-C), ApoB, ApoB/ApoA1 ratio, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio levels at baseline were significantly higher in the RP group than in the non-RP group. The ApoA1 level at baseline in the non-RP group was significantly higher than in the RP group. The predictive significance of the ApoB/ApoA1 ratio (area under the curve (AUC) = 0.712) for the RP of NCCLs was significantly higher than those of ApoA1, ApoB, LDL-C/HDL-C ratio (AUC = 0.628, AUC = 0.640, and AUC = 0.620, respectively). A higher ApoB/ApoA1 ratio and the RP of NCCLs were significantly associated with the occurrence of MACE.The ApoB/ApoA1 ratio was an effective clinical indicator for the RP of NCCLs after PCI in patients with DM presenting with ACS. The high ApoB/ApoA1 ratio and the RP of NCCLs were two risks for MACE.


Effect of adenomyosis on prognosis of patients with endometrial cancer.
Our goal was to contrast the prognoses of patients with endometrial cancer who had adenomyosis against those that did not. All patients who had received surgical staging for hysterectomy-based endometrial cancer had their medical data retrospectively examined. The analysis covered 397 patients, who were split into two groups depending on the presence of adenomyosis. Comparisons were made between patients covering type of surgery, histopathology, endometrial cancer stage, lymphovascular space invasion, presence of biochemical or histochemical markers, adjuvant therapy, presence of adenomyosis in the myometrial wall, and outcomes in terms of overall survival and disease-free survival. There is no statistically significant difference in the 5-year disease-free survival or overall survival rates between endometrial cancer patients with and without adenomyosis. This is based on comparisons of tumor stage, tumor diameter, histological type and grade of tumor, myometrial invasion, lymphovascular space invasion, and biochemical markers that affect the course of the disease. The median follow-up times were 61 months for the adenomyosis-positive group and 56 months for the group without adenomyosis. Coexisting adenomyosis in endometrial cancer has no bearing on survival rates and is not a prognostic factor.


Use of gold nanoparticles to detect water uptake in vascular plants.
Direct visualization of water-conducting pathways and sap flows in xylem vessels is important for understanding the physiology of vascular plants and their sap ascent. Gold nanoparticles (AuNPs) combined with synchrotron X-ray imaging technique is a new promising tool for investigating plant hydraulics in opaque xylem vessels of vascular plants. However, in practical applications of AuNPs for real-time quantitative visualization of sap flows, their interaction with a vascular network needs to be verified in advance. In this study, the effect of AuNPs on the water-refilling function of xylem vessels is experimentally investigated with three monocot species. Discrepancy in the water uptakes starts to appear at about 20 min to 40 min after the supply of AuNP solution to the test plant by the possible gradual accumulation of AuNPs on the internal structures of vasculature. However conclusively, it is observed that the water-refilling speeds in individual xylem vessels are virtually unaffected by hydrophilically surface-modified AuNPs (diameter ∼20 nm). Therefore, the AuNPs can be effectively used as flow tracers in the xylem vessels in the first 20∼30 min without any physiological barrier. As a result, AuNPs are found to be useful for visualizing various fluid dynamic phenomena occurring in vascular plants.


Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.
Breast cancer (BC) and ovarian cancer (OC) are among the most common and deadly cancers affecting women worldwide. Both are complex diseases with marked heterogeneity. Despite the induction of screening programs that increase the frequency of earlier diagnosis of BC, at a stage when the cancer is more likely to respond to therapy, which does not exist for OC, more than 50% of both cancers are diagnosed at an advanced stage. Initial therapy can put the cancer into remission. However, recurrences occur frequently in both BC and OC, which are highly cancer-subtype dependent. Therapy resistance is mainly attributed to a rare subpopulation of cells, named cancer stem cells (CSC) or tumor-initiating cells, as they are capable of self-renewal, tumor initiation, and regrowth of tumor bulk. In this review, we will discuss the distinctive markers and signaling pathways that characterize CSC, their interactions with the tumor microenvironment, and the strategies they employ to evade immune surveillance. Our focus will be on identifying the common features of breast cancer stem cells (BCSC) and ovarian cancer stem cells (OCSC) and suggesting potential therapeutic approaches.


A Scoping Review of Social Support Research among Refugees in Resettlement: Implications for Conceptual and Empirical Research.
This study reviewed social support research with refugees in resettlement by assessing the scope of scholarship and examining methodological approaches, definitions, theoretical frameworks, domains, and sources of support. The scoping review followed a systematic approach that retained 41 articles for analysis. The findings indicate that refugee resettlement studies seldom conceptualizes social support as a central focus, defines the concept, draws from related theory, or examines multifaceted components of the construct. The review nevertheless yielded promising findings for future conceptual and empirical research. The analysis identified a wide range of relevant domains and sources of social support, laying the foundation for a socio-ecological model of social support specific to refugee experiences in resettlement. The findings also indicate an imperative to examine and theorize social support vis-à-vis diverse groups as a main outcome of interest, in connection to a range of relevant outcomes, and longitudinally in recognition of the temporal processes in resettlement.


Prosocial Motivation: Inferences From an Opaque Body of Work.
Because motivations for prosocial actions typically are unclear, sometimes even to actors but especially for observers, it is difficult to study prosocial motivation. This article reviews research that provides evidence regarding children's motives for prosocial behaviors. First, we present a heuristic model to classify motives on the dimension of reflecting altruistic (with the ultimate goal of benefiting another) to egoism (the ultimate goal of benefiting the self) goals; in addition, we briefly discuss classifying motives based on a continuum of morality. Next, we review findings indicating the existence of a number of different motives in our model and briefly discuss developmental issues, when possible. Future directions for the study of prosocial motivation are proposed.


On the structural regularity in nucleobases and amino acids and relationship to the origin and evolution of the genetic code.
To explore how chemical structures of both nucleobases and amino acids may have played a role in shaping the genetic code, numbers of sp2 hybrid nitrogen atoms in nucleobases were taken as a determinative measure for empirical stereo-electronic property to analyze the genetic code. Results revealed that amino acid hydropathy correlates strongly with the sp2 nitrogen atom numbers in nucleobases rather than with the overall electronic property such as redox potentials of the bases, reflecting that stereo-electronic property of bases may play a role. In the rearranged code, five simple but stereo-structurally distinctive amino acids (Gly, Pro, Val, Thr and Ala) and their codon quartets form a crossed intersection "core". Secondly, a re-categorization of the amino acids according to their beta-carbon stereochemistry, verified by charge density (at beta-carbon) calculation, results in five groups of stereo-structurally distinctive amino acids, the group leaders of which are Gly, Pro, Val, Thr and Ala, remarkably overlapping the above "core". These two lines of independent observations provide empirical arguments for a contention that a seemingly "frozen" "core" could have formed at a certain evolutionary stage. The possible existence of this codon "core" is in conformity with a previous evolutionary model whereby stereochemical interactions may have shaped the code. Moreover, the genetic code listed in UCGA succession together with this codon "core" has recently facilitated an identification of the unprecedented icosikaioctagon symmetry and bi-pyramidal nature of the genetic code.