Laparoscopic splenectomy plus cholecystectomy for treating hereditary spherocytosis combined with cholelithiasis in siblings.
With the advancements that have been made in the field of minimally invasive surgery, combined laparoscopic procedures are now being performed for treating coexisting abdominal pathologies during the same surgery; this combined surgery thereby offers the maximum benefits to the patients. In this paper we describe how we perform laparoscopic splenectomy plus cholecystectomy at the same time to treat hereditary spherocytosis combined with cholelithiasis in two siblings.


The unfolded protein response as regulator of cancer stemness and differentiation: Mechanisms and implications for cancer therapy.
The unfolded protein response (UPR) is an adaptive mechanism that regulates protein and cellular homeostasis. Three endoplasmic reticulum (ER) membrane localized stress sensors, IRE1, PERK and ATF6, coordinate the UPR in order to maintain ER proteostasis and cell survival, or induce cell death when homeostasis cannot be restored. However, recent studies have identified alternative functions for the UPR in developmental biology processes and cell fate decisions under both normal and cancerous conditions. In cancer, increasing evidence points towards the involvement of the three UPR sensors in oncogenic reprogramming and the regulation of tumor cells endowed with stem cell properties, named cancer stem cells (CSCs), that are considered to be the most malignant cells in tumors. Here we review the reported roles and underlying molecular mechanisms of the three UPR sensors in regulating stemness and differentiation, particularly in solid tumor cells, processes that have a major impact on tumor aggressiveness. Mainly PERK and IRE1 branches of the UPR were found to regulate CSCs and tumor development and examples are provided for breast cancer, colon cancer and aggressive brain tumors, glioblastoma. Although the underlying mechanisms and interactions between the different UPR branches in regulating stemness in cancer need to be further elucidated, we propose that PERK and IRE1 targeted therapy could inhibit self-renewal of CSCs or induce differentiation that is predicted to have therapeutic benefit. For this, more specific UPR modulators need to be developed with favorable pharmacological properties that together with patient stratification will allow optimal evaluation in clinical studies.


A review of psychosocial interventions targeting families of children with cancer.
Psychosocial interventions in families of children with cancer are considered an effective way of empowering family members to tackle the complex hurdles they face. The ability of parents to develop adaptive coping strategies during the child's treatment is not only important to their own mental and physical health, but also to their child's well-being and long-term adjustment with the disease. The aim of this review was to evaluate the existing literature for the period from 2009 to 2017 on psychosocial interventions targeting families of children with cancer. We searched the PubMed database using the following combination of keywords: "cancer AND children AND (intervention OR training) AND (mothers OR primary caregivers OR parents OR fathers OR siblings)." After careful evaluation of 995 papers, 17 full-text papers were found to match our criteria (12 randomized controlled trials and 5 quasi-experimental studies). The quality of the studies was assessed using the Delphi score questionnaire, and the score of the reviewed studies ranged from 3 to 5. The findings suggest that most interventions reduced distress and improved coping strategies among participants. Interventions, mainly cognitive behavioral therapy and problem-solving skills training targeting maternal distress, were associated with improved adjustment outcomes in mothers of children with cancer. Psychosocial interventions are helpful, and efforts should be made to promote them in a larger scale. Protocols should be implemented to ensure that all parents benefit. Computer-assisted methods may provide additional benefit by improving cancer-related knowledge and cancer-related communication.


Secretory leukocyte protease inhibitor promotes differentiation and mineralization of MC3T3-E1 preosteoblasts on a titanium surface.
Mineralized bone matrix constituted with collagenous and non-collagenous proteins was synthesized by osteoblasts differentiated from mesenchymal stem cells. Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor, promotes cell migration and proliferation, and suppresses the inflammatory response. Recent studies reported that SLPI regulates the formation of dentin and mineralization by odontoblasts and increases the adhesion and viability of preosteoblasts on a titanium (Ti) surface. Ti and its alloys are widely used implant materials in artificial joints and dental implants owing to their biocompatibility with bone. Therefore, this study aimed to examine whether SLPI can be an effective molecule in promoting differentiation and mineralization of osteoblasts on a Ti surface. In order to investigate the effects of SLPI on osteoblasts, an MTT assay, PCR, western blotting and Alizarin Red S staining were performed. The results demonstrated that SLPI increased the viability of osteoblasts during differentiation on Ti discs compared with that of the control. The expression levels of SLPI mRNA and protein were higher than that of the control after treatment of osteoblasts with SLPI on Ti discs during differentiation. SLPI increased the formation of mineralized nodules and mRNA expression of alkaline phosphatase, dentin sialophosphoprotein, dentin matrix protein 1, bone sialoprotein, and collagen I in osteoblasts on Ti discs compared with that of the control. In conclusion, SLPI increases the viability and promotes the differentiation and mineralization of osteoblasts on Ti surfaces, suggesting that SLPI is an effective molecule for achieving successful osseointegration between osteoblasts and a Ti surface.


Paclitaxel delivery systems: the use of amino acid linkers in the conjugation of paclitaxel with carboxymethyldextran to create prodrugs.
Paclitaxel was bound via its hydroxyl group to carboxymethyldextran (CMDex, 150 kDa) by means of an amino acid linker; the linker was introduced into the 2'- or 7-hydroxyl group of the paclitaxel through an ester bond. These conjugates--CMDex-2'-paclitaxel and CMDex-7-paclitaxel--were designed to be water-soluble with a paclitaxel content between 6-8% (w/w) with a degree of subsititution (DS) of the CM groups at 0.6 per sugar residue. The release of the paclitaxel from the conjugates was influenced by the hydroxyl group (2'- or 7-) of paclitaxel to which the amino acid linker was introduced, and by what amino acid was used as the linker. In mouse plasma incubated at 37 degrees C for 72 h, the most paclitaxel was released using CMDex-paclitaxel conjugate with 2'gly followed by, in descending order, 2'-ala, 2'-leu, 2'-ile, and 7-gly as the amino linkers. Colon 26, a Taxol resistant cancer, was introduced into mice and the conjugates were intravenously administered by bolus injection for a tumor distribution study, and intermittently intravenously administered for a tumor growth regression study. In both studies the highest amount of paclitaxel release was found in the CMDex-2'-gly-paclitaxel followed by CMDex-2'-ala-paclitaxel, CMDex-2'-leu-paclitaxel and paclitaxel. There was a direct correlation between the amount of paclitaxel released and the observed efficacy. CMDex-2'-ile-paclitaxel and CMDex-7-gly-paclitaxel did not show any anti-tumor activity. These results clearly demonstrate that a CMDex-paclitaxel with an appropriate amino acid linker has significant anti-tumor activity against colon 26, and that these anti-tumor effects appear to correlate with the amounts of paclitaxel released in the tumor.


Lympho-epithelial interactions in the turtle Chrysemys scrypta elegans.
The morphological relationships present in the areas of lymphoid infiltration found in the esophagus in Chrysemys scripta elegans were studied by the use of light and transmission electron microscopy. These infiltrations are widespread and can be observed in the lamina propria and the covering epithelium. Electron microscopy reveals the presence of epithelial cells with differing characteristics at the apex of the lymphoid infiltrations. The introduction of horseradish peroxidase (HRP) into the esophageal lumen revealed that these cells possess a micropinocytotic activity. On the basis of the morphological and experimental results obtained, a hypothesis is advanced of the existence, also in the turtle, of a local system of uptake of extraneous material, which induces local and systemic immunological processes.


Comparison of three in-office bleaching systems based on 35% hydrogen peroxide with different light activators.
To compare in vitro the bleaching effects obtained with and without the use of the various lights on power bleaching systems. 19 groups of five tooth specimens were prepared and allocated randomly to treatments. Only specimens with shade C4 were accepted for the study. Three commercial bleaching products all based on 35% hydrogen peroxide were used with and without four different light sources. Shade assessments were made using a Shade Guide (SG), Shade Vision System (SVS) and chromometer. For SG, all but the light only treatment resulted in measurable improvement in shade ranging from 4.6 to 14.6 shade guide units. Similar findings were apparent with SVS and chromometer. No change was seen in the light only treatments by SVS or SG with very small changes by chromometer. In mean terms with all three gels, least change was noted when there was no light used. For SG, SVS and chromometer data analysis over all treatment groups, excluding light only treatments, revealed highly significant differences. Within bleach product treatment differences were only significant with one gel both with and without light activation. Differences between gels with the same light and no light revealed some significant differences in SG and chromometer data but not SVS. In mean terms the order of efficacy of gels with each light and no light was the same for the majority of data sets.


Reasons of preclusion of living-related donor renal transplants in Oman.
Renal transplant, especially from genetically related living-donors, is associated with excellent results. The security and free will of the donor are of paramount importance. A significant percentage of such transplants are not accomplished for both medical and nonmedical reasons. We looked retrospectively into the causes of nonaccomplishment of renal transplants from living-related donor transplants at our center from January 2006 through June 2008. During this period, 69 and 99 potential renal transplant recipient and donors were investigated. Transplants could be performed only in 35 patients (51%). About 59% of the donors were rejected or declined. Reasons for exclusion were immunologic in 14 donors (14%). Medical and nonmedical conditions precluded donation in 35 donors (35%) and 12 donors (12%). Medical reasons consisted mainly of undiagnosed hypertension, obesity, diabetes mellitus, and renal anomalies. In the recipients, the major reason was option for transplant tourism, occurred in 11 cases (16%). A substantial number of investigated recipients and donors for living-related transplant are not accomplished. The major reasons are medical for the donor and transplant tourism for the recipient.


Analyses of Mitochondrial DNA and Immune Phenotyping Suggest Accelerated T-Cell Turnover in Treated HIV.
HIV infection is associated with premature aging, and mitochondrial integrity is compromised during the aging process. Because mitochondrial toxicity is a consequence of antiretroviral therapies (ARTs), we hypothesized HIV and long-term ART would correlate with immunosenescence and mitochondrial DNA (mtDNA) pathology. Thirteen older HIV-infected individuals (aged >40 years) with virologic suppression (stratified by duration of ART) were compared with 10 uninfected controls well-matched for age. Peripheral blood T-cells were immunophenotyped to measure immune activation, proliferation, and immunosenescence in subsets. mtDNA copies per cell and the relative abundance of mtDNA carrying the "common deletion" (RACD) were quantified by droplet digital polymerase chain reaction. Immune activation was higher in HIV-infected individuals than HIV-uninfected individuals in mature CD4 T-cell subsets (CD4TTM P = 0.025, CD4TEM P = 0.0020) regardless of ART duration. Cell populations from uninfected individuals were more likely to be more senescent populations in mature CD4 T-cell subsets (TTM P = 0.017), and CD8 (CD8TEMRA+ P = 0.0026). No differences were observed in mtDNA or RACD levels in any CD4 T-cell subsets, while CD8TSCM of infected individuals trended to have more mtDNA (P = 0.057) and reduced RACD (P = 0.0025). HIV-infected individuals demonstrated increased immune activation, but reduced senescence in more mature T-cell subsets. Increased mtDNA content and lower RACD in CD8TSCM suggest immune activation driven turnover of these cells in HIV-infected persons.


Sport orientation model for wheelchair basketball athletes.
This study examined the validity of the Sport Orientation Questionnaire (Competitiveness: 13 items, Win Orientation: 6 items, and Goal Orientation: 6 items) in a sample of 195 wheelchair basketball athletes from the USA. Following evidence for sample-specific validity, the measurement model that underlies the questionnaire was examined. A short-form with 15 items for three factors of Competitiveness (7 items), Win Orientation (5 items) and Goal Orientation (3 items) fit the data (X2/df ratio=2.21, NNFI=.892, CFI=.991, RCFI=.935, SRMR=.058, RMSEA=.071). To evaluate the findings further, we cross-validated the short-form by sex. Structural equation modeling indicated there were similar measurement properties and factor structures for the men and women, indicating similar conceptualization of sport orientations. Meaningful comparisons across sex may be undertaken, since both men and women who are wheelchair basketball athletes perceive the three short-form SOQ factors similarly.


Informational Theory of Aging: The Life Extension Method Based on the Bone Marrow Transplantation.
The method of lifespan extension that is a practical application of the informational theory of aging is proposed. In this theory, the degradation (error accumulation) of the genetic information in cells is considered a main cause of aging. According to it, our method is based on the transplantation of genetically identical (or similar) stem cells with the lower number of genomic errors to the old recipients. For humans and large mammals, this method can be realized by cryopreservation of their own stem cells, taken in a young age, for the later autologous transplantation in old age. To test this method experimentally, we chose laboratory animals of relatively short lifespan (mouse). Because it is difficult to isolate the required amount of the stem cells (e.g., bone marrow) without significant damage for animals, we used the bone marrow transplantation from sacrificed inbred young donors. It is shown that the lifespan extension of recipients depends on level of their genetic similarity (syngeneity) with donors. We have achieved the lifespan increase of the experimental mice by 34% when the transplantation of the bone marrow with high level of genetic similarity was used.


Radical salts of bis(ethylenediseleno)tetrathiafulvalene with paramagnetic tris(oxalato)metalate anions.
The synthesis, crystal structure, and physical characterization of five new radical salts formed by the organic donor bis(ethylenediseleno)tetrathiafulvalene (BEST) and the paramagnetic tris(oxalato)metalate anions [M(C2O4)3]3- (M = FeIII and CrIII) are reported. The salts isolated are (BEST)4[M(C2O4)3].PhCOOH.H2O with MIII = Cr (1) or Fe (2) (crystal data: 1, triclinic, space group P(-)1 with a = 14.0999(4) A, b = 15.3464(4) A, c =19.5000(4) A, alpha = 76.711(5) degrees, beta = 71.688(5) degrees, gamma = 88.545(5) degrees, V = 3893.5(2) A3, and Z = 2; 2, triclinic, space group P(-)1 with a = 14.0326(3) A, b =15.1981(4) A, c =19.4106(4) A, alpha = 76.739(5) degrees, beta = 71.938(5) degrees, gamma = 88.845(5) degrees, V = 3824.9(2) A3, and Z = 2), (BEST)4[M(C2O4)3].1.5H2O with MIII = Cr (3) or Fe (4) (crystal data: 3, monoclinic, space group C2/m with a = 33.7480(10) A, b =12.3151(7) A, c = 8.8218(5) A, beta = 99.674(5) degrees, V = 3614.3(3) A3, and Z = 2; 4, monoclinic, space group C2/m with a = 33.659(6) A, b =12.248(2) A, c = 8.759(2) A, beta = 99.74(3) degrees, V = 3558.9(12) A3, and Z = 2), and (BEST)9[Fe(C2O4)3]2.7H2O (5) (crystal data: triclinic, space group P(-)1 with a =12.6993(3) A, b =18.7564(4) A, c = 18.7675(4) A, alpha = 75.649(5) degrees, beta = 107.178(5) degrees, gamma = 79.527(5) degrees, V = 3977.5(3) A3, and Z = 1). The structures of all these salts consist of alternating layers of the organic donors and tris(oxalato)metalate anions. In 1 and 2 the anionic layers contain also benzoic acid molecules H-bonded to the terminal oxygen atoms of the anions. In all salts the organic layers adopt beta-type packings. Along the parallel stacks the donors form dimers in 3 and 4, trimers in 5, and tetramers in 1 and 2. All the compounds are paramagnetic semiconductors with high room-temperature conductivities and magnetic susceptibilities dominated by the Fe- or Cr-containing anions.


Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy.
Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.


Diffusion MRI of cancer: From low to high b-values.
Following its success in early detection of cerebral ischemia, diffusion-weighted imaging (DWI) has been increasingly used in cancer diagnosis and treatment evaluation. These applications are propelled by the rapid development of novel diffusion models to extract biologically valuable information from diffusion-weighted MR signals, and significant advances in MR hardware that has enabled image acquisition with high b-values. This article reviews recent technical developments and clinical applications in cancer imaging using DWI, with a special emphasis on high b-value diffusion models. The article is organized in four sections. First, we provide an overview of diffusion models that are relevant to cancer imaging. The model parameters are discussed in relation to three tissue properties-cellularity, vascularity, and microstructures. An emphasis is placed on characterization of microstructural heterogeneity, given its novelty and close relevance to cancer. Second, we illustrate diffusion MR clinical applications in each of the following three categories: 1) cancer detection and diagnosis; 2) cancer grading, staging, and classification; and 3) cancer treatment response prediction and evaluation. Third, we discuss several practical issues, including selection of image acquisition parameters, reproducibility and reliability, motion management, image distortion, etc., that are commonly encountered when applying DWI to cancer in clinical settings. Lastly, we highlight a few ongoing challenges and provide some possible future directions, particularly in the area of establishing standards via well-organized multicenter clinical trials to accelerate clinical translation of advanced DWI techniques to improving cancer care on a large scale. Level of Evidence: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:23-40.


Evolution of Pediatric Home Mechanical Ventilation Program in Serbia-What Has Changed in the Last Decade.
Home mechanical ventilation (HMV) is a method of treatment in children with sleep-disordered breathing (SDB) and alveolar hypoventilation regardless of primary disease. The goal of the study was to describe the changes in the HMV program in Serbia during the last two decades. Cross-sectional retrospective study included data from the national HMV database from 2001 until 2019. HMV was initiated in clinically stable patients after the failure to wean from mechanical ventilation succeeded acute respiratory deterioration or electively after the confirmation of SDB and alveolar hypoventilation by sleep study or continuous transcutaneous capnometry and oximetry. The study included 105 patients (50 ventilated noninvasively and 55 ventilated invasively via tracheostomy). The median age at the time of HMV initiation was 6.2 years (range: 0.3-18 years). Invasive ventilation had been initiated significantly earlier than noninvasive ventilation (NIV) (p < 0.01), without difference in duration of ventilatory support (p = 0.95). Patients on NIV were significantly older (p < 0.01) than those ventilated invasively (13 and 1.5 years, respectively). Average waiting time on equipment had been shortened significantly-from 6.3 months until 2010 to 1 month at the end of the study (p < 0.01). Only 6.6% of patients had obstructive sleep apnea syndrome (OSAS) requiring HMV. During the study period, 24% patients died, mostly due to uncontrolled infection or progression of underlying disease. Availability and shortened waiting time for the equipment accompanied by advanced overall health care led to substantial improvements in the national HMV program. However, future improvements should be directed to systematic evaluation of SDB in patients with OSAS, early diagnosis of nocturnal hypoventilation, and subsequent timely initiation of chronic ventilation.


Assessing slide coverage by cytoscreeners during the primary screening of cervical smears, using the AxioHOME Microscope system.
We have used the HOME Microscope system to examine the screening patterns of cytotechnologists who undertake the primary screening of cervical smears, in order to measure accuracy of screening against screening time, slide coverage, and mean screening rate. Twelve cytotechnologists engaged routinely on cervical screening volunteered for this study. They were asked to perform primary screening of 10 test slides under normal laboratory conditions in the normal way. Slide coverage and screening time were recorded on the HOME system. Slide maps were prepared and the results analysed. The exercise demonstrated that all primary screeners fail at some point to scan the whole of the slide during primary screening. The maps produced by the HOME system clearly demonstrated that 5 different types of error can occur that lead to incomplete coverage of the slide. Mean slide coverage was 84%, and some individuals averaged only 66% coverage. The results show that there is a major problem in the education of some individual cytotechnologists in slide coverage. This could be rectified by the incorporation of a HOME system into every training centre, and the establishment of a protocol for assessment of slide coverage in competence examinations. Furthermore, the exercise has shown that even those individuals who normally attain a good standard of slide coverage would be able to improve slide coverage given access to the daily use of a HOME Microscope, or a system with equivalent screening/reviewing functionality.


Heart weight and heart weight/body weight coefficient in malnourished adults.
To compare the heart weight and the heart weight/body weight coefficient of adults with and without chronic malnutrition. In an initial case series of 210 autopsies performed in adults, we recorded body and heart weights and calculated the heart weight/body weight coefficients (HW/BW x 100). The exclusion criteria were as follows: positive serology for Chagas' disease, edema, obesity, heart diseases, hepatopathies, nephropathies, and systemic arterial hypertension. Malnutrition was characterized as a body mass index <18.5kg/m2. Differences with p<0.05 were considered significant. Individuals in the malnourished (n=15) and control (n=21) groups were statistically different, respectively, in regard to body mass index (15.9+/-1.7 versus 21.3+/-2.5kg/m2), heart weight (267.3+/-59.8 versus 329.1+/-50.4g), and the HW/BW coefficient (0.64+/-0.12 versus 0.57+/-0.09%). A positive and significant correlation was observed between heart weight and body mass index (r=0.52), and between heart weight and body weight (r=0.65). Malnourished individuals have lighter hearts and a greater HW/BW coefficient than non-malnourished individuals do. These findings indicate a possible preservation of the myocardium in relation to the intensity of weight loss associated with the probable relative increase in cardiac connective tissue and heart blood vessels.


[The national anti-opium-smoking campaigns across the country in the Republican Period].
Anti-opium-smoking had been the key policy of successive central and local governments from the late Qing Dynasty to the Republican Period. Since the establishment of the Nanjing Provisional Government in January 1912, the Anti-opium-smoking campaign had culminated across the country. Under the support of the government, the "National Anti-Opium Association of China" and "Association of Chinese People Rejecting Opium" were established which made an important contribution to China's anti-opium-smoking campaign.Yunnan, Shaanxi, Heilongjiang, Zhejiang, Shanghai and other local governments also combined with local specific circumstances to make anti-opium-smaking policy for punishing severely the opium cultivation, trade and opium smoking, thus, the overrun of opium began to be brought under an overall control.


Community-Based Participatory Research and Gene-Environment Interaction Methodologies Addressing Environmental Justice among Migrant and Seasonal Farmworker Women and Children in Texas: "From Mother to Child Project"
The "From Mother to Child Project" is a molecular epidemiological study that employs a community- based participatory research (CBPR) approach and gene-environment interaction research to address environmental justice in migrant and seasonal farmworker (MSF) women and children of Mexican origin home-based in Baytown and La Joya, Texas. This paper presents the background and rationale for the study and describes the study design and methodology. Preliminary data showed that MSF women and children in Texas have measurable levels of pesticides in their blood and urine, some of which were banned in the United States decades ago and are possible human carcinogens. Polymorphisms in genes involved in chemical detoxification and DNA repair have been associated with susceptibility to genetic damage and cancer development in populations exposed to environmental toxins. The "From Mother to Child Project" is testing three hypotheses: (1) MSF women and children who are occupationally exposed to pesticides are at higher risk for DNA damage than are non-exposed women and children. (2) Both, the extent of pesticide exposure and type of polymorphisms in chemical detoxification and DNA repair genes contribute to the extent of DNA damage observed in study participants. (3) The mutagenic potency levels measured in the organic compounds extracted from the urine and serum of study participants will correlate with the total concentrations of pesticides and with the measured DNA damage in study participants. The study will enroll 800 participants: 200 MSF mother-child pairs; 200 children (one per family) whose parents have never worked in agriculture, matched with the MSF children by ethnicity, age ± 2 years, gender, and city of residence; and these children's mothers. Personal interviews with the mothers are used to gather data for both mothers and children on sociodemographic characteristics; pesticide exposure at work and home; medical and reproductive history; dietary assessment, and lifestyle factors. Blood and urine samples are collected from each participant and analyzed for (1) organochlorine and organophosphate pesticide levels, (2) genetic polymorphisms of chemical detoxification and DNA repair genes, (3) DNA damage (chromosomal aberrations), and (4) the mutagenic potential of pesticides in the serum and urine. Recruitment and data collection in Baytown is near completion, and over one third of the target population for the La Joya study site.


Mono- and Bis(iminoxolene)iridium Complexes: Synthesis and Covalency in π Bonding.
N-(2,6-Diisopropylphenyl)-4,6-di-tert-butyl-o-iminobenzoquinone (Diso) reacts with the (cyclooctadiene)iridium chloride dimer to form a monoiminoxolene complex, (Diso)Ir(cod)Cl. Reaction of 2 equiv of the iminoquinone with chlorobis(cyclooctene)iridium dimer affords the bis-iminoxolene (Diso)2IrCl. This five-coordinate complex adopts a distorted square pyramidal structure with an apical chloride ligand and undergoes halide exchange to form an air-stable iodide complex. (Diso)2IrCl can be reduced by one electron to form neutral, square planar (Diso)2Ir, while oxidation with PhICl2 gives octahedral trans-(Diso)2IrCl2. The cis isomer can be prepared by air oxidation of (Diso)2IrCl; cis/trans isomerization is not observed even on prolonged heating. Structural and spectroscopic features of the complexes are consistent with the presence of strong, covalent π bonding between the metal and the iminoxolene ligands, with structural data suggesting between 45 and 60% iridium character in the π bonding orbitals, depending on the ancillary ligands. The spectroscopic similarity of (Diso)2Ir and (Diso)2IrCl to their cobalt congeners suggests that the first-row metal complexes likewise have appreciably covalent metal-iminoxolene π bonds.


Recent Advances in the Development and Characterization of Electrochemical and Electrical Biosensors for Small Molecule Neurotransmitters.
Neurotransmitters act as chemical messengers, determining human physiological and psychological function, and abnormal levels of neurotransmitters are related to conditions such as Parkinson's and Alzheimer's disease. Biologically and clinically relevant concentrations of neurotransmitters are usually very low (nM), so electrochemical and electronic sensors for neurotransmitter detection play an important role in achieving sensitive and selective detection. Additionally, these sensors have the distinct advantage to potentially be wireless, miniaturized, and multichannel, providing remarkable opportunities for implantable, long-term sensing capabilities unachievable by spectroscopic or chromatographic detection methods. In this article, we will focus on advances in the development and characterization of electrochemical and electronic sensors for neurotransmitters during the last five years, identifying how the field is progressing as well as critical knowledge gaps for sensor researchers.


Repetitive visual stimulation: a neuropsychological approach to the treatment of cortical blindness.
Cortical visual disturbances can occur after traumatic or ischemic brain lesion. Patients mostly suffer from hemianopia. Different treatment approaches in patients with hemianopia are being debated with respect to their effectiveness. For more severely disabled patients with cortical blindness or residual rudimentary vision (RRV) no systematic therapeutic approaches have been reported. In a case study the positive effects of a recently developed repetitive photic stimulation therapy in a patient with RRV after a bioccipital ischemic infarction are presented. The application of this new therapy over several months, supported by treatment with amphetamines led to a statistically significant improvement of different visual functions and a reoccurrence of visual abilities important in daily life. The pathophysiological basis and possible neurorehabilitative consequences that arise from these results are discussed with respect to similar findings in animal experiments.


Cytogenetic and Molecular Characterization of Eigenmannia aff. desantanai (Gymnotiformes: Sternopygidae): A First Report of System of Sex Chromosomes ZW1W2/ZZ in Gymnotiformes.
Gymnotiformes a monophyletic group of fish endemic to the Neotropics, represent an important component of the freshwater ichthyofauna that presents relevant taxonomic problems. Thus, in view of the morphological complexity involving Eigenmannia (Gymnotiformes) fish species, this study aimed to characterize Eigenmannia aff. desantanai of the upper Paraguay River basin through cytogenetic and molecular analyses, to help in the correct identification and delimitation of species. This study reports a multiple sex system of the type ZW1W2/ZZ, with 2n = 31 for females and 2n = 30 for males. A single pair of chromosomes carrying the nucleolar organizing regions (NORs) was detected. The heterochromatin was colocated in NOR sites and mainly located in the centromeric regions of chromosomes. Besides that, individual sequences COI from the specimens of E. aff. desantanai were obtained, totalizing three haplotypes. The distance p between the haplotypes in E. aff. desantanai, ranged from 0.2% to 7.1%. Species delimitation tests indicated the existence of two possible operational taxonomic units of E. aff. desantanai. Thus, this study reports a new multiple sex system in Gymnotiformes and these specimens previously identified as E. aff. desantanai may belong to two distinct species.


Effect of blood flow rate on subendothelial proliferation in venous autografts used as arterial substitutes.
The effect of augmented and reduced blood flow rates through autogenous vein grafts (AVG) on the histological characteristics of veins used for arterial substitutes was studied in 22 dogs. In each animal autogenous jugular veins were implanted as conduits to replace excised segments of both iliac arteries. In one group (control) blood flow through the AVG conduits was not modified, but in the remaining animals blood flow rate was either augmented by a distal femoral arteriovenous fistula or reduced by a distal arterial stenosis. In the control group in which there was no modification of blood flow, subendothelial proliferative lesions (SEPL) were found in the vein graft, and typical SEPL were found at each anastomosis. However, in those animals in which blood flow was reduced by an average of 44% through the graft, SEPL were more numerous throughout the length of the vein graft, and the anastomotic SEPL were more prominent. In contrast, those animals in which a unilateral distal arteriovenous fistula augmented blood flow through the AVG (average 6.7-fold increase), no SEPL were detected along the length of the graft. Although SEPL were present at the suture lines, the lesions were much less prominent. These findings suggest that the magnitude and distribution of SEPL in AVG are determined, in part, by the rate of blood flow through the graft.


Physicochemical properties and oral bioavailability of ursolic acid nanoparticles using supercritical anti-solvent (SAS) process.
The objective of the study was to prepare ursolic acid (UA) nanoparticles using the supercritical anti-solvent (SAS) process and evaluate its physicochemical properties and oral bioavailability. The effects of four process variables, pressure, temperature, drug concentration and drug solution flow rate, on drug particle formation during SAS process, were investigated. Particles with mean particle size ranging from 139.2±19.7 to 1039.8±65.2nm were obtained by varying the process parameters. The UA was characterised by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, thermal gravimetric analysis, specific surface area, dissolution test and bioavailability test. It was concluded that physicochemical properties and bioavailability of crystalline UA could be improved by physical modification, such as particle size reduction and generation of amorphous state using SAS process. Further, SAS process was a powerful methodology for improving the physicochemical properties and bioavailability of UA.


From good health to illness with post-infectious fatigue syndrome: a qualitative study of adults' experiences of the illness trajectory.
Municipal drinking water contaminated with the parasite Giardia lamblia in Bergen, Norway, in 2004 caused an outbreak of gastrointestinal infection in 2500 people, according to the Norwegian Prescription Database. In the aftermath a minor group subsequently developed post-infectious fatigue syndrome (PIFS). Persons in this minor group had laboratory-confirmed parasites in their stool samples, and their enteritis had been cured by one or more courses of antibiotic treatment. The study's purpose was to explore how the affected persons experienced the illness trajectory and various PIFS disabilities. A qualitative design with in-depth interviews was used to obtain first-hand experiences of PIFS. To get an overall understanding of their perceived illness trajectory, the participants were asked to retrospectively rate their functional level at different points in time. A maximum variation sample of adults diagnosed with PIFS according to the international 1994 criteria was recruited from a cohort of persons diagnosed with PIFS at a tertiary Neurology Outpatient Clinic in Western Norway. The sample comprised 19 women and seven men (mean age 41 years, range 26-59). The interviews were fully transcribed and subjected to a qualitative content analysis. All participants had been living healthy lives pre-illness. The time to develop PIFS varied. Multiple disabilities in the physical, cognitive, emotional, neurological, sleep and intolerance domains were described. Everyone more or less dropped out from studies or work, and few needed to be taken care of during the worst period. The severity of these disabilities varied among the participants and during the illness phases. Despite individual variations, an overall pattern of illness trajectory emerged. Five phases were identified: prodromal, downward, turning, upward and chronic phase. All reached a nadir followed by varying degrees of improvement in their functional ability. None regained pre-illness health or personal and professional abilities. The needs of persons with this condition are not met. Early diagnosis and interdisciplinary rehabilitation could be beneficial in altering the downward trajectory at an earlier stage, avoiding the most severe disability and optimising improvement. Enhanced knowledge among health professionals, tailored treatment, rest as needed, financial support and practical help would likely improve prognosis.


Down-regulation of beta3-adrenergic receptor expression in rat adipose tissue during the fasted/fed transition: evidence for a role of insulin.
The beta3-adrenergic receptor (beta3-AR) exerts a central role in the transduction of catecholamine effects in white and brown adipose tissue (WAT and BAT). A recent report has documented that insulin strongly down-regulates beta3-AR expression and catecholamine responsiveness in 3T3-F442A adipocytes [Fève, El Hadri, Quignard-Boulangé and Pairault (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 5677-5681]. In the present report we show that the rise in plasma insulin levels elicited by the fasted/fed transition is associated with a reduction in beta3-AR mRNA levels and beta-adrenergic responsiveness in WAT and BAT. beta3-AR transcripts are also decreased in adipose tissue from animals subjected for 6 h to euglycaemic hyperinsulinaemic glucose clamps. Moreover, insulin acts directly on cultured rat white and brown adipocytes to decrease beta3-AR gene expression and adenylate cyclase activity in response to beta3-AR-selective agonists. These results suggest that there is a close relationship between food intake, plasma insulin levels and beta3-AR expression.


Patchwork of contrasting medication cultures across the USA.
Health in the United States is markedly heterogeneous, with large disparities in disease incidence, treatment choices and health spending. Drug prescription is one major component of health care-reflecting the accuracy of diagnosis, the adherence to evidence-based guidelines, susceptibility to drug marketing and regulatory factors. Using medical claims data covering nearly half of the USA population, we have developed and validated a framework to compare prescription rates of 600 popular drugs in 2334 counties. Our approach uncovers geographically separated sub-Americas, where patients receive treatment for different diseases, and where physicians choose different drugs for the same disease. The geographical variation suggests influences of racial composition, state-level health care laws and wealth. Some regions consistently prefer more expensive drugs, even when they have not been proven more efficacious than cheaper alternatives. Our study underlines the benefit of aggregating massive information on medical practice into a summarized and actionable form.


[Biological agents targeting on pro-inflammatory cytokines].
Biological agents targeting on pro-inflammatory cytokines are developed, and provide a great impact on the medical management of rheumatoid arthritis (RA). Particularly, biologics against tumor necrosis factor(TNF) can not only induce great clinical improvement, but also halt structural damage on the joints. Now chimeric anti-TNFalpha monoclonal antibody, infliximab, full human anti-TNFalpha monoclonal antibody, adalimumab, and TNF receptor II (p75) -IgGFc fusion protein, etanercept, are widely used in the inflammatory disorders including RA. This review article shows the characteristics of these anti-TNF biologics on RA, and summarizes the efficacy as well as the safety of the agents.


[Radioprotective effects of gallic acid on bone marrow cells in mice].
To investigate the radioprotective effect of gallic acid(GA) on mouse bone marrow cells. Healthy male ICR mice were randomly divided into saline control group, GA control group, X-ray irradiation group and GA protection group, with 10 mice in each group. X-ray irradiation group and normal saline control group were given 0.01 mL/g normal saline gavage, GA control group and GA protection group were given 200 mg/kg GA(20 mg/mL) gavage once a day for 14 consecutive days. On the 15 th day, 4 X-ray irradiation groups and 4 GA protection groups were given one-time X-ray irradiation to the whole body of the mice, and the absorbed doses were 1.0, 2.0, 3.0 and 4.0 Gy, respectively. The saline control group and the GA control group were not irradiated. After irradiation, detected the whole blood catalase(CAT), superoxide dismutase(SOD), malondialdehyde(MDA) and micronucleus frequency of polychromatic erythrocyte in bone marrow(MN-PCE), and use flow cytometry to detect bone marrow cell cycle, early apoptosis rate and late apoptosis rate. The CAT activities in the serum of mice in the 1.0, 2.0, 3.0 and 4.0 Gy GA protection groups were 2.13, 1.74, 1.49 and 1.15 U/mL, respectively, which were significantly increased compared with the corresponding X-ray irradiation group(P<0.01). SOD activities were 184.69, 156.92, 139.17 and 107.15 U/mL, which were significantly increased compared with the corresponding X-ray irradiation group(P<0.01). The contents of MDA were 3.92, 4.20, 6.32 and 9.31 nmol/mL, which were significantly lower than those of the corresponding X-ray irradiation group(P<0.05, P<0.01). The bone marrow MN-PCE rate of the mice in the 1.0, 2.0, 3.0 and 4.0 Gy GA protection groups were 4.35‰, 8.00‰, 12.90‰ and 3.80‰, respectively, which were significantly lower than those in the corresponding X-ray irradiation group(P<0.01). The proportions of G_0/G_1 phase cells of bone marrow cells in the 1.0, 2.0, 3.0 and 4.0 Gy GA protection group were 81.00%, 86.28%, 92.04% and 93.15%, respectively, which were significantly reduced compared with the corresponding X-ray irradiation group(P<0.01). The proportions of G_2/M phase cells were 4.51%, 3.05%, 2.35% and 1.81%, which were significantly increased compared with the corresponding X-ray irradiation group(P<0.05, P<0.01). The proportions of S phase cells were 15.32%, 11.36%, 5.96% and 4.92%, which were significantly increased compared with the corresponding X-ray irradiation group(P<0.01). The early apoptosis rate of bone marrow cells of mice in the 1.0, 2.0, 3.0 and 4.0 Gy GA protection groups were 3.32%, 8.96%, 12.11% and 2.26%, respectively, which were significantly reduced compared with the corresponding X-ray irradiation group(P<0.01). The late apoptosis rates of bone marrow cells were 7.21%, 11.73%, 17.11% and 19.36%, which were significantly reduced compared with the corresponding X-ray irradiation group(P<0.05, P<0.01). GA can reduce the oxidative damage, DNA damage and bone marrow cell cycle arrest of the bone marrow cells of radiation-damaged mice, inhibit the apoptosis of bone marrow cells, and have radioprotective effects on the bone marrow cells of mice.


Mature Cardiac Teratoma in an Adult.
The incidental diagnosis in adult age is very unusual and the presence of clinical symptoms is related to its location, which is most commonly intrapericardial. The presence of intramyocardial teratoma lesions is even rarer and has been reported in few publications. The recommendations for the diagnosis and management of a cardiac teratoma depends upon the imaging studies and the pathological report after surgical excision. The prognosis of surgically treated patient is very good and a complete surgical excision is preferred in order to avoid complications.


Antifibrinolytic therapy in the acute period following aneurysmal subarachnoid hemorrhage. Preliminary observations from the Cooperative Aneurysm Study.
Antifibrinolytic therapy remains a controversial issue in the management of subarachnoid hemorrhage (SAH). The relationship of antifibrinolytic therapy with mortality, rebleeding, ischemia, hydrocephalus, and clotting abnormalities was studied in 672 patients in the International Cooperative Study on the Timing of Aneurysm Surgery. The patients with antifibrinolytic therapy had a significantly lower rebleeding rate, but higher rates of ischemic deficits and hydrocephalus. The net result was no difference in mortality in the 1st month following the initial SAH. Further clinical trials are needed to determine the overall effects of antifibrinolytic therapy.


Cancer trial enrollment after state-mandated reimbursement.
Recruitment of patients into cancer research studies is exceedingly difficult, particularly for early phase trials. Payer reimbursement policies are a frequently cited barrier. We examined whether state policies that ensure coverage of routine medical care costs for cancer trial participants are associated with an increase in clinical trial enrollment. We used logistic Poisson regressions to analyze enrollment in National Cancer Institute phase II and phase III Clinical Trials Cooperative Group trials and compared changes in trial enrollment rates between 1996 and 2001 of privately insured cancer patients who resided in the four states that enacted coverage policies in 1999 with enrollment rates in states without such policies. All statistical tests were two-sided. Trial enrollment rates increased in the coverage and noncoverage states by 24.9% (95% confidence interval [CI] = 22.8% to 27.0%) and 28.8% (95% CI = 27.7% to 29.8%) per year, respectively, from 1996 through 2001. After implementation of the coverage policies in 1999 in four states, there was a 21.7% (95% CI = 3.8% to 42.6%) annual increase in phase II trial enrollment in coverage states, compared with a 15.6% (95% CI = 8.8% to 21.8%) annual decrease in noncoverage states (P<.001). After accounting for secular trend, cancer type, and race in multivariable analyses, the odds ratio (OR) for a phase II trial participant residing in a coverage versus a noncoverage state after 1999 was 1.59 per year (95% CI = 1.22 to 2.07; P =.001). In a multivariable analysis of phase III trial participation, there was a decrease in the odds of residing in a coverage state after 1999 (OR = 0.90, 95% CI = 0.84 to 0.98; P =.011). State coverage policies were associated with a statistically significant increase in phase II cancer trial participation and did not increase phase III cancer trial enrollment.


Multifunctional Resonance Bridge-Mediated Dynamic Modulation of Perovskite Films For Enhanced Intrinsic Stability of Photovoltaics.
The improving intrinsic stability, determining the life span of devices, is a challenging task in the industrialization of inverted perovskite solar cells. The most important prerequisite for boosting intrinsic stability is high-quality perovskite films deposition. Here, a molecule, N-(2-pyridyl)pivalamide (NPP) is utilized, as a multifunctional resonance bridge between poly(triarylamine) (PTAA) and perovskite film to regulate the perovskite film quality and promote hole extraction for enhancing the device intrinsic stability. The pyridine groups in NPP couple with the phenyl groups in PTAA through π-π stacking to improve hole extraction capacities and minimize interfacial charge recombination, and the resonance linkages (NCO) in NPP dynamically modulate the perovskite buried defects through strong PbO bonds based on the fast self-adaptive tautomerization between resonance forms (NCO and N+ CO- ). Because of the combined effect of the reduction defect density and improved energy level in the perovskite buried interfaces as well as the optimized crystal orientation in perovskite film enabled by the NPP substrate, the devices based on NPP-grown perovskite films show an efficiency approaching 20% with negligible hysteresis. More impressively, the unencapsulated device displays start-of-the-art intrinsic photostability, operating under continuous 1-sun illumination for 2373 h at 65 °C without loss of PCE.


Polarity establishment by Cdc42: Key roles for positive feedback and differential mobility.
Cell polarity is fundamental to the function of most cells. The evolutionarily conserved molecular machinery that controls cell polarity is centered on a family of GTPases related to Cdc42. Cdc42 becomes activated and concentrated at polarity sites, but studies in yeast model systems led to controversy on the mechanisms of polarization. Here we review recent studies that have clarified how Cdc42 becomes polarized in yeast. On one hand, findings that appeared to support a key role for the actin cytoskeleton and vesicle traffic in polarity establishment now appear to reflect the action of stress response pathways induced by cytoskeletal perturbations. On the other hand, new findings strongly support hypotheses on the polarization mechanism whose origins date back to the mathematician Alan Turing. The key features of the polarity establishment mechanism in yeasts include a positive feedback pathway in which active Cdc42 recruits a Cdc42 activator to polarity sites, and differential mobility of polarity "activators" and "substrates."


Breast engorgement and galactorrhea after preventing premature contractions with ritodrine.
Breast engorgement and galactorrhea were observed in many patients receiving ritodrine treatment to delay labor due to premature contractions. In an attempt to understand the causes for these phenomena, serum prolactin, progesterone, estradiol and estriol excretion were measured in 11 women. No statistical difference was found in these parameters after ritodrine administration. It can thus be assumed that breast engorgement and galactorrhea after ritodrine treatment are unrelated to changes in these hormones but might be mediated by some other factors or probably by the premature contractions themselves.


[Community ecology of Acanthopanax giraldii in west Sichuan plateau].
To study the community characteristics of Acanthopanax giraldii and its role and adaptability in the community. The methods of community ecology were used to investigate vegetation composition in different sample plots and the number of the clumps and clonal ramets. The importance value of species and biodiversity index of each plot was calculated. The life form spectra in different community were counted. The chi-square test was applied to analyze the dependence degree of A. giraldii to other main shrub species in the community. The investigation had showed that A. giraldii community could be divided into three types. The number of A. giraldii population in each type had great difference. Statistical analysis had shown that there's no correlation between the growth of A. giraldii with biodiversity and no significant interspecific association between A. giraldii and other main shrub species in the community yet. The population growth of A. giraldii was sensitive to Sunshine. A. giraldii maybe has the biological characteristics for artificial planting as a single population.


Global analysis of gene expression patterns in developing mouse neocortex using serial analysis of gene expression.
Molecular inventories of the developing mouse neocortex before and after birth were generated using the global gene expression profiling tool serial analysis of gene expression (SAGE). Libraries were generated from embryonic day 15 and postnatal day 1 mouse neocortex and more than 40,000 tags were collected (20,211 and 22,001 tags, representing 11,706 and 12,402 transcripts, respectively). Comparison of the two libraries resulted in the identification of 321 transcripts that were differentially expressed (P < 0.05). Differential expression was independently verified for selected genes by Northern blotting, and in situ hybridization revealed spatial expression patterns in the neocortex. Differentially expressed transcripts included genes known to be important in neocortical development (e.g., brain factor 1, neuroD2, and Id2), genes not previously associated with neocortical development (such as brahma-related gene 1, receptor for activated C-kinase I, hypermethylated in cancer 2, and Evi9), and genes of unknown identity or function.


Towards substrate-independent age estimation of blood stains based on dimensionality reduction and k-nearest neighbor classification of absorbance spectroscopic data.
The age determination of blood traces provides important hints for the chronological assessment of criminal events and their reconstruction. Current methods are often expensive, involve significant experimental complexity and often fail to perform when being applied to aged blood samples taken from different substrates. In this work an absorption spectroscopy-based blood stain age estimation method is presented, which utilizes 400-640nm absorption spectra in computation. Spectral data from 72 differently aged pig blood stains (2h to three weeks) dried on three different substrate surfaces (cotton, polyester and glass) were acquired and the turnover-time correlations were utilized to develop a straightforward age estimation scheme. More precisely, data processing includes data dimensionality reduction, upon which classic k-nearest neighbor classifiers are employed. This strategy shows good agreement between observed and predicted blood stain age (r>0.9) in cross-validation. The presented estimation strategy utilizes spectral data from dissolved blood samples to bypass spectral artifacts which are well known to interfere with other spectral methods such as reflection spectroscopy. Results indicate that age estimations can be drawn from such absorbance spectroscopic data independent from substrate the blood dried on. Since data in this study was acquired under laboratory conditions, future work has to consider perturbing environmental conditions in order to assess real-life applicability.


Meta-analysis of vitamin D receptor polymorphisms and pulmonary tuberculosis risk.
Several case-control studies performed in populations where the incidence of tuberculosis (TB) is high have examined genetic susceptibility to TB. The Vitamin D receptor (VDR) gene is a good candidate, because it influences immune response, and associations between TaqI and FokI polymorphisms in the VDR gene and pulmonary TB risk have been found. Furthermore, if a relationship between these polymorphisms and TB risk is confirmed this will be important evidence pointing to vitamin D as a potential preventive agent for TB. We carried out a systematic review and meta-analysis, and found that results were inconclusive and studies were underpowered.


Solvation of Methyl Lactate in Water: Molecular Dynamics Studies.
Methyl lactate (ML), a chiral α-hydroxy ester, has been probed widely to understand the competition between two types of intramolecular H-bonds in solvents of different polarities. Recent experimental and high-level quantum chemical studies have revealed the predominant existence of ML-water insertion complexes over addition complexes in aqueous solution. Although the stability of monohydrate insertion conformer was studied accurately, ab initio quantum chemical calculations failed to predict the most stable dihydrate conformer in analogy with the experimental spectroscopic search. Atomistic molecular dynamics simulations of aqueous solution of methyl lactate predict that the population and lifetime of different H-bonded ML-water addition complexes are dictated by their interaction energies. Although the population of dihydrate insertion complexes is higher than that of the monohydrate complexes, the lifetime of the former is smaller than the latter, which is in good agreement with the experimental result. The nature of intramolecular H-bonds within a methyl lactate molecule in aqueous solution is opposite to that in the gas phase due to the solvation process in water by intermolecular H-bonding interactions.


Analysis of injected cement volume and clinical outcomes following kyphoplasty for vertebral compression fractures.
It has been suggested that greater volumes of cement injected during kyphoplasty correlate with improved vertebral body height restoration and kyphotic angulation correction. However, there is little evidence tying cement volume to patient outcomes. Here, we analyzed the association between cement volume and outcome utilizing indices of pain, disability, and quality of life. One hundred and thirty-six patients undergoing kyphoplasty were analyzed retrospectively. The total volume of bone cement injected was recorded intraoperatively for each patient; the average total cement volume was 5.44 cc. Pre- and postoperative outcome indices were documented, using the visual analog scale (VAS), Roland-Morris disability index (RMDI), and the EuroQol 5 Dimension instrument (EQ5D). Pearson's correlations and linear regression models were derived for the association of total cement volume with each of the patient outcome measures. This was a retrospective cohort study. The average change in VAS, RMDI, and EQ5D scores for all patients was -6.8, +8.3, and +0.41, respectively. For VAS, RMDI, and EQ5D improvements, neither Pearson's correlations nor multiple linear regression models revealed a correlation or an association with total cement volume. For patients undergoing kyphoplasty, outcomes were not associated with the total injected cement volume; all had a significant reduction in pain and most exhibited decreased disability with improved quality of life.


Use of Blood-soaked Cellulose Filter Paper for Measuring Carbon and Nitrogen Stable Isotopes.
We explored the use of filter paper soaked in whole blood for measuring carbon (C) and nitrogen (N) stable isotopes, often used in feeding ecology or diet studies, to better understand drivers of exposure to contaminants. Our results showed no statistically or biologically relevant differences in C and N stable isotope measures between our gold standard (whole blood with anticoagulant) and eluates from processed, blood-soaked filter paper. Our data supported the effectiveness of using filter paper for assessing C and N stable isotopes in blood to address feeding ecology and other uses. The ease of sampling and processing should allow blood-soaked filter paper to be used in sampling of live (e.g., captured, stranded) and lethally taken (e.g., hunter-killed) wild vertebrates.


Naphthodithiophenediimide (NDTI): synthesis, structure, and applications.
A straightforward synthesis of α,β-unsubstituted and α-halogenated naphtho[2,3-b:6,7-b']dithiophenediimides (NDTIs) is described. Electrochemical and optical studies of N,N-dioctyl-NDTI demonstrate that the compound has a low-lying LUMO energy level (4.0 eV below the vacuum level) and a small HOMO-LUMO gap (~2.1 eV). With its interesting electronic and optical properties, in addition to its planar structure, NDTI is a promising building block for the development of novel π-functional materials. In fact, it afforded n-channel, p-channel, and ambipolar materials, depending on the molecular modification.


Differentiating anxiety-panic disorders from psychologic dental anxiety.
It has always been believed that fear and anxiety of dental treatment was a simple continuum of experience that occurs in mild, moderate, or severe form. Past and present studies that attempt to both trace etiology and measure it reflect this view. The numerous studies that are concerned with methods of management are based on this accepted philosophy regarding the etiology of dental fear and anxiety. To a large extent, this may be true. However, there are some notable exceptions, and it is these cases that present the greatest management problem. Omitting the symptoms of fear and anxiety related to physical illness, drug withdrawal, or major mental illness, they present anxiety as a unidimensional learned problem usually conditioned by externally negative forces or experiences. They postulate that the fear and anxiety seen is due to a variety of factors. The interpretation of the definitions of fear, anxiety, and phobias by many in the profession that are presented in this issue also reflect the view that fear, anxiety, and phobias are learned or conditioned responses. This single-minded view has determined much of our understanding and subsequent management of this problem in dentistry.


Probucol inhibits hydrogen peroxide to induce apoptosis of vascular smooth muscle cells.
The aim of this study was to investigate the effect of the antioxidant probucol on hydrogen peroxide (H2O2)-induced vascular smooth muscle cell (VSMC) apoptosis. H2O2 (1 mmol/l) was used as the VSMC apoptosis-inducing agent, and 100, 10 and 1 µmol/l probucol concentrations were incubated with cells for 6 h. The cell apoptosis was observed using Annexin V-FITC, TUNEL and Hoechst 33258 staining methods. H2O2 promoted VSMC apoptosis, ASK-1 protein expression increased and Trx-l protein expression decreased. Probucol reduced H2O2-induced apoptosis in a dose-dependent manner; while ASK-1 protein expression decreased, Trx-1 protein expression increased. Probuco1 is capable of antagonizing the H2O2-induced apoptosis in VSMCs, which may be related to the decrease in ASK-1 protein expression and the increase in Trx-1 protein expression.


Efficacy of nickel-titanium memory alloy in the treatment of multiple rib fracture combined with sternal fracture.
Clinical efficacy and complications of nickel-titanium memory alloy in the treatment of multiple rib fractures combined with sternal fractures was investigated. A retrospective analysis of 123 patients with multiple rib fractures combined with sternal fractures admitted to First People's Hospital of Fuzhou from January 2013 to December 2015 was performed, including study group (treated with internal fixation by the nickel-titanium memory alloy, n=68) and control group (treated with internal fixation by partial pressure bandage, n=55). Μean arterial pressure (MAP), heart rate (HR), and visual analogue pain score (VAS) of the two groups before and after treatment were compared and analyzed. No significant difference in MAP, HR and VAS scores between groups was detected before treatment (P>0.05). After treatment, MAP score of study group was significantly higher, and HR and VAS scores were significantly lower (P<0.05). Μethod of internal fixation by the nickel-titanium memory alloy, with better efficacy than the traditional method of internal fixation by partial pressure bandage and less postoperative complications in the treatment of flail chest caused by multiple rib fractures combined with sternal fractures, is worthy of clinical application and promotion.


Preparation of hydroxyapatite coated porous carbon nanofibres for DEX loading and enhancing differentiation of BMSCs.
The proliferation and differentiation of bone mesenchymal stem cells (BMSCs) in vitro are the key properties of bone tissue engineering for biomaterials. In this study, hydroxyapatite (HA) coated porous carbon nanofibres (PCNFs) were prepared to load dexamethasone (DEX) and further improve the differentiation ability of the BMSCs. Various characterisations were applied to reveal the DEX loading efficacy and biocompatibility, especially the differentiation strength. The results showed that HA could be successfully coated on the PCNFs by pretreating the surface using PEG conjugation. With an increase of HA, the particle diameter increased and the DEX loading decreased. In vitro experiments proved higher cell viability, alkaline phosphatase (ALP) activity, calcium nodule secretion ability and the RUNX2 protein expression, indicating that the as-prepared was of great biocompatibility and optimised osteoconductivity, which was attributed to the componential imitation to natural bone and the accelerated BMSCs differentiation. Consequently, the novel DEX loaded and HA coated PCNFs can provide potential applications in bone tissue regeneration.


Spiral CT with 3D reconstruction in children requiring reoperation for failure of chest wall growth after pectus excavatum surgery. Preliminary observations.
Pectus excavatum is the most common congenital chest wall deformity. Extensive corrective surgery prior to age 3 may disturb chest wall growth and result in a constricted thorax. We describe our surgical and radiologic experience with eight such cases, paying particular attention to the role of spiral computed tomography (CT) with 3D reconstruction in patient management. Spiral CT was performed on children who had developed restrictive chest walls following pectus excavatum surgery. These children then underwent a unique operation to elevate the sternum and attempt to correct their restrictive chest wall defects. In several cases, postoperative spiral CT was performed. Spiral CT with 3D reconstruction defined the orientation of the ribs and costal cartilages and their relationship to the sternum, allowing exact preoperative measurement of the bony rib cage and guiding individualized operative correction. Computed thoracic volumes in select cases correlated well with subjective patient reports of increased exercise capacity. Repair of pectus excavatum defects prior to age 3 may result in constrictive thoracic abnormalities. Surgical correction can increase thoracic volume and improve prospects for normal thoracic function. Three-dimensional reconstruction of spiral CT data is useful in both preoperative and postoperative evaluation.


Interplay between the phosphatase PHLPP1 and E3 ligase RNF41 stimulates proper kinetochore assembly via the outer-kinetochore protein SGT1.
Kinetochores link chromosomes to spindle microtubules and are essential for accurate chromosome segregation during cell division. Kinetochores assemble at the centromeric region of chromosomes as a multiprotein complex. However, the molecular mechanisms of kinetochore assembly have not yet been fully elucidated. In this study, we identified pleckstrin homology domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) as a regulatory phosphatase that facilitates proper kinetochore assembly. We found that PHLPP1 interacted with the essential outer-kinetochore protein SGT1 and stabilized its protein levels. Loss of PHLPP1 from cells led to SGT1 degradation and thereby caused defective kinetochore assembly. We also found that the ring finger protein 41 (RNF41) as an E3 ligase ubiquitinated and degraded SGT1 in a phosphorylation-dependent manner. PHLPP1 dephosphorylated SGT1 at four conserved residues (Ser-17, Ser-249, Ser-289, and Thr-233) and thereby prevented SGT1 from associating with RNF41, in turn, countering SGT1 degradation. Importantly, depletion of RNF41 or expression of a non-phosphorylatable SGT1 mutant rescued the kinetochore defects caused by the loss of PHLPP1. Taken together, our results suggest that PHLPP1 plays an important role in the assembly of kinetochores by counteracting RNF41-mediated SGT1 degradation.


The Transcription Factor Foxg1 Promotes Optic Fissure Closure in the Mouse by Suppressing Wnt8b in the Nasal Optic Stalk.
During vertebrate eye morphogenesis, a transient fissure forms at its inferior part, known as the optic fissure. This will gradually close, giving rise to a healthy, spherical optic cup. Failure of the optic fissure to close gives rise to an ocular disorder known as coloboma. During this developmental process, Foxg1 is expressed in the optic neuroepithelium, with highest levels of expression in the nasal optic stalk. Foxg1-/- mutant mice have microphthalmic eyes with a large ventral coloboma. We found Wnt8b expression upregulated in the Foxg1-/- optic stalk and hypothesized that, similar to what is observed in telencephalic development, Foxg1 directs development of the optic neuroepithelium through transcriptional suppression of Wnt8b To test this, we generated Foxg1-/-;Wnt8b-/- double mutants of either sex and found that the morphology of the optic cup and stalk and the closure of the optic fissure were substantially rescued in these embryos. This rescue correlates with restored Pax2 expression in the anterior tip of the optic fissure. In addition, although we do not find evidence implicating altered proliferation in the rescue, we observe a significant increase in apoptotic cell density in Foxg1-/-;Wnt8b-/- double mutants compared with the Foxg1-/- single mutant. Upregulation of Wnt/β-catenin target molecules in the optic cup and stalk may underlie the molecular and morphological defects in the Foxg1-/- mutant. Our results show that proper optic fissure closure relies on Wnt8b suppression by Foxg1 in the nasal optic stalk to maintain balanced apoptosis and Pax2 expression in the nasal and temporal edges of the fissure.SIGNIFICANCE STATEMENT Coloboma is an ocular disorder that may result in a loss of visual acuity and accounts for ∼10% of childhood blindness. It results from errors in the sealing of the optic fissure (OF), a transient structure at the bottom of the eye. Here, we investigate the colobomatous phenotype of the Foxg1-/- mutant mouse. We identify upregulated expression of Wnt8b in the optic stalk of Foxg1-/- mutants before OF closure initiates. Foxg1-/-;Wnt8b-/- double mutants show a substantial rescue of the Foxg1-/- coloboma phenotype, which correlates with a rescue in molecular and cellular defects of Foxg1-/- mutants. Our results unravel a new role of Foxg1 in promoting OF closure providing additional knowledge about the molecules and cellular mechanisms underlying coloboma formation.


Oncolytic vesicular stomatitis virus induces apoptosis via signaling through PKR, Fas, and Daxx.
Matrix (M) protein mutants of vesicular stomatitis virus (VSV) are promising oncolytic agents for cancer therapy. Previous research has implicated Fas and PKR in apoptosis induced by other viruses. Here, we show that dominant-negative mutants of Fas and PKR inhibit M protein mutant virus-induced apoptosis. Most previous research has focused on the adapter protein FADD as a necessary transducer of Fas-mediated apoptosis. However, the expression of dominant-negative FADD had little effect on the induction of apoptosis by M protein mutant VSV. Instead, virus-induced apoptosis was inhibited by the expression of a dominant-negative mutant of the adapter protein Daxx. These data indicate that Daxx is more important than FADD for apoptosis induced by M protein mutant VSV. These results show that PKR- and Fas-mediated signaling play important roles in cell death during M protein mutant VSV infection and that Daxx has novel functions in the host response to virus infection by mediating virus-induced apoptosis.


Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1, mitigates interferon-α-accelerated lupus nephritis in mice.
Neutrophils have been implicated in initiating and perpetuating systemic lupus erythematosus and the resultant kidney damage in lupus nephritis (LN) patients, in part through an excessive release of neutrophil serine proteases (NSPs). NSP zymogens are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation and released by mature neutrophils in response to inflammatory stimuli. Thus, a potential strategy to attenuate disease progression in LN would be to inhibit DPP1. We tested whether brensocatib, a highly selective and reversible DPP1 inhibitor, could mitigate LN progression in an interferon-alpha (IFNα)-accelerated NZB/W F1 mouse model. To confirm brensocatib's pharmacodynamic effect on NSPs in this mouse strain, repeated dose studies were conducted for 7 and 14 days in naïve NZB/W F1 mice via oral gavage twice a day. Brensocatib at 2 and 20 mg/kg/day achieved a significant reduction in bone marrow NSP activities after 7 days of daily administration. To initiate LN disease progression, the mice were injected with an IFNα-expressing adenovirus. After 2 weeks, three brensocatib doses (or vehicle) were administered for 6 more weeks. Throughout the 8-week study, brensocatib treatment (20 mg/kg/day) significantly reduced the occurrence of severe proteinuria compared to the vehicle control. Brensocatib treatment also entailed a significant reduction in the urine albumin-to-creatinine ratio, indicating decreased kidney damage, as well as a significant reduction in blood urea nitrogen level, suggesting improved renal function. Based on kidney histopathology analysis, brensocatib treatment significantly lowered both the renal tubular protein score and the nephropathy score compared to the vehicle group. A trend towards reduced glomerulonephritis score with brensocatib treatment was also observed. Lastly, brensocatib significantly reduced LN mouse kidney infiltration by various inflammatory cells. In conclusion, these results suggest that brensocatib alters disease progression in LN mice and warrant further evaluation of DPP1 inhibition in LN.


Modelling and structural characteristics analysis of gene networks for prostate cancer.
Analysing structure of gene networks is an important way to understand regulatory mechanisms of organism at the molecular level. In this work, gene mutual information networks are constructed based on gene expression profiles in prostate tissues with and without cancer. In order to contrast structural difference of normal and diseased networks, curves of four structural parameters are given with the change of thresholds. Then threshold discrimination intervals and discrimination weights are defined. A method of finding structural key genes with significant degree-difference is proposed. The finding of key genes will help the biomedical scientists to further research the pathogenesis of prostate cancer. Finally randomisation test is performed to prove that these structural parameters can distinguish normal and prostate cancer in their structures compared with these results in real data.


Ultrafast van der Waals diode using graphene quantum capacitance and Fermi-level depinning.
Graphene, with superior electrical tunabilities, has arisen as a multifunctional insertion layer in vertically stacked devices. Although the role of graphene inserted in metal-semiconductor junctions has been well investigated in quasi-static charge transport regime, the implication of graphene insertion at ultrahigh frequencies has rarely been considered. Here, we demonstrate the diode operation of vertical Pt/n-MoSe2/graphene/Au assemblies at ~200-GHz cutoff frequency (fC). The electric charge modulation by the inserted graphene becomes essentially frozen above a few GHz frequencies due to graphene quantum capacitance-induced delay, so that the Ohmic graphene/MoSe2 junction may be transformed to a pinning-free Schottky junction. Our diodes exhibit much lower total capacitance than devices without graphene insertion, deriving an order of magnitude higher fC, which clearly demonstrates the merit of graphene at high frequencies.


Signal sampling and propagation through multiple cell layers in the retina: modeling and analysis with multirate filtering.
The retina is a multilayered structure. Each layer consists of one or more classes of cell, each at its own density and with its own anatomic and physiologic properties. Signals converge from many cells in one layer onto single cells in another layer, and a signal from a single cell diverges to many cells in the next layer. In this methods paper we develop a general approach to retinal analysis and modeling that incorporates multiple cell classes, their densities, and related anatomic properties. The method is based on multirate filtering, a branch of signal processing in which signals of different sampling rates are manipulated. By drawing a correspondence between cell density and signal sampling rate, we define multirate models that incorporate different cell densities, convergence, divergence, variation in dendritic field shape, cell-to-cell variation in synaptic weights, and other anatomic features. We develop the multirate approach and apply it to the cat cone-->cone bipolar CBb1-->on-beta ganglion cell pathway as an example. We calculate the spatial frequency responses of the CBb1 and on-beta cells based on the cone spatial frequency response and find that the attenuation of high frequencies in the cones prevents aliasing that would otherwise occur in CBb1 and on-beta cells. We compare the calculations with cat psychophysics. We show that the optics of the cat eye are insufficient in themselves for the prevention of aliasing in these cells; additional attenuation by the cone-cone gap junctions and the cone aperture is necessary. By including this postreceptoral filtering, we demonstrate that the highest spatial frequency that can be passed by the retina without aliasing is determined not always only by the densities of cones, bipolar cells, and ganglion cells but also by the synaptic and the dendritic weighting between these cells.


Anti-asthmatic effect of pitavastatin through aerosol inhalation is associated with CD4+ CD25+ Foxp3+ T cells in an asthma mouse model.
Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-A) reductase, and studies have shown that statins also have anti-inflammatory and immunomodulatory properties. The purpose of this study was to investigate the anti-asthmatic effects of pitavastatin, a type of statin, in an asthma mouse model. Mice were sensitized and challenged with ovalbumin (OVA) to establish the asthma model. These mice were then treated with inhaled pitavastatin (5 mg/kg) or dexamethasone (2 mg/kg), the latter of which served as a positive control. The results of the study showed that pitavastatin reduced allergen-induced increases in airway resistance and alleviated bronchial tube thickness and goblet cell hyperplasia in lung tissues. In addition, the results showed that pitavastatin inhibited OVA-induced increases in eosinophil counts and total inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and increased the percentage of CD4+ CD25+ Foxp3+ Treg in the BALF of asthmatic mice. IL-4 and IL-17 levels were decreased, whereas IFN-γ levels were significantly increased in the BALF of pitavastatin-treated mice compared with the BALF of OVA-challenged mice. These results suggest that pitavastatin has potential as a therapy for allergic airway disease and that its effects are associated with its ability to regulate CD4+ CD25+ Foxp3+ T cell counts.


Usnic Acid Induces Cycle Arrest, Apoptosis, and Autophagy in Gastric Cancer Cells In Vitro and In Vivo.
BACKGROUND Usnic acid (UA), a secondary metabolite, is mainly derived from certain lichen species. Growing evidence suggests that UA has antitumor, anti-oxidative, anti-inflammatory, and other activities in a variety of cancer cells. However, the antitumor effect of UA in gastric cancer cells (GC) is unclear. The aim of this investigation was to assess the antitumor effect of UA in GC cells in vitro and in vivo, and to explore the underlying mechanisms. MATERIAL AND METHODS Cell proliferation was measured by CCK8 assay, the arrest of cell cycle was assessed by flow cytometry, and cellular apoptosis was observed via Hoechst 33258 staining assay. Expression levels of apoptosis-related proteins (activated caspase-3 and PARP, Bax, Bcl2) and autophagy-associated proteins (LC3-II and p62) were verified through Western blot analysis. H&E staining and immunohistochemistry were carried out in the subcutaneously implanted BGC823 tumor model in a nude mouse experiment. RESULTS In vitro, we demonstrated that UA was significantly effective in inducing morphological changes, inhibiting the cell proliferation dose- and time-dependently, arresting the cell cycle phase, promoting cancer cellular apoptosis, and inducing autophagy activity. In vivo, compared to mice treated with 5-FU alone, UA treatment was significantly more effective in suppressing the tumor growth without affecting body weight, and in regulating the amount of Bax and Bcl2 in tumor tissues. CONCLUSIONS UA induces cell cycle arrest and autophagy and exerts anti-proliferative and apoptotic effects by modulating expression of apoptosis-related proteins in stomach neoplasm cells, and has a better antitumor effect compared to 5-Fu in the xenograft model.


Commentary: irrational exuberance for the aging in place of vulnerable low-income older homeowners.
This commentary argues that one-size-fits-all aging in place solutions will often not be in the best interests of low-income and frail older homeowners in the United States. This contrarian view runs counter to the reported preferences of this group, various private-sector activities, and U.S. public policies that are increasingly funding home and community-based care. The particular focus is on low-income elderly homeowners living in the oldest housing stock in the country who have demographic characteristics putting them at greater risk of having both unmet care and housing needs, which in turn have spillover effects on their neighborhoods. These vulnerable homeowners would be better served if they relocated to more affordable, easier to maintain, and better designed smaller owned units or rental properties or to planned affordable seniors' rental housing complexes that can offer both light and heavy care. Such residential moves are often not feasible, however, because of the shortage of these housing arrangements.


A rapid procedure for routine double staining of cartilage and bone in fetal and adult animals.
A simple, rapid procedure for dual staining of cartilage and bone in rodents, particularly in late gestation, has been developed for routine use. The procedure involves rapid, complete skinning of fresh eviscerated specimens following a 30 sec immersion in a 70 C water bath. The unfixed specimen is stained in a mixture of 0.14% Alcian blue and 0.12% alizarin red S in ethanol and glacial acetic acid. Specimens are then macerated in 2% KOH, cleared and hardened in 1:1 glycerin and distilled water, and stored in pure glycerin. Rapid staining of cartilage only is done in a mixture of 0.08% Alcian blue, glacial acetic acid, and ethanol, with subsequent maceration, clearing, and hardening as in the double staining procedure. Rapid staining of bone only, concurrent with maceration of soft tissue, can be done by placing fresh, unskinned specimens in a diluted mixture of alizarin red S in 2% KOH, with subsequent clearing and hardening in 1:1 distilled water and glycerin. Good quality fetal specimens can be prepared for examination by any of these procedures in a minimum of 11/2-2 days as compared to a minimum of 4-5 days for other procedures. Double stained specimens can be examined for abnormalities of the cartilage as well as bone.


Maternal stress and development of infant attention to threat-related facial expressions.
Attentional biases to threat-related stimuli, such as fearful and angry facial expressions, are important to survival and emerge early in development. Infants demonstrate an attentional bias to fearful facial expressions by 5-7 months of age and an attentional bias toward anger by 3 years of age that are modulated by experiential factors. In a longitudinal study of 87 mother-infant dyads from families predominantly experiencing low income, we examined whether maternal stress and depressive symptoms were associated with trajectories of attentional biases to threat, assessed during an attention disengagement eye-tracking task when infants were 6-, 9-, and 12-month old. By 9 months, infants demonstrated a generalized bias toward threat (both fearful and angry facial expressions). Maternal perceived stress was associated with the trajectory of the bias toward angry facial expressions between 6 and 12 months. Specifically, infants of mothers with higher perceived stress exhibited a greater bias toward angry facial expressions at 6 months that decreased across the next 6 months, compared to infants of mothers with lower perceived stress who displayed an increased bias to angry facial expressions over this age range. Maternal depressive symptoms and stressful life events were not associated with trajectories of infant attentional bias to anger or fear. These findings highlight the role of maternal perceptions of stress in shaping developmental trajectories of threat-alerting systems.


Isolation and Purification of Ascorbate Oxidase from Acremonium sp. HI-25.
A screening test was undertaken to isolate microorganisms that produced ascorbate oxidase. The enzyme activity was found in a culture filtrate of a fungal strain (HI-25), newly isolated from a soil sample. Based on the morphological characteristics, this isolate was identified as Acremonium sp. From the examinations of cultural conditions, optimum conditions for enzyme production were found; strain HI-25 was aerobically cultured by a jar fermenter at 25°C in a medium containing 5% glycerol, 2% defatted soybeans, 0.1% monosodium L-glutamate, 0.1% KH2PO4, 0.02% MgSO4 ·7H2O, and 0.01% KCl, pH 6.0. After cultivation, an ascorbate oxidase was purified from the culture filtrate by an ammonium sulfate fractionation, column chromatographies on DEAE-cellulose and Butyl-Toyopearl, and gel filtration twice on Sephadex G-100. The purification was 850-fold with an activity yield of 8.8%. The purified enzyme gave a single band on SDS polyacrylamide gel electrophoresis, and had a molecular weight of 80,000 by SDS polyacrylamide gel electrophoresis and 76,000 by native gel filtration. This enzyme was most active at pH 4.0, 45°C, and was most stable between pH 6.0-10.0 and at temperatures below 60°C.


Results of operative correction of grade IIB tibialis posterior tendon dysfunction.
The prevalence of tibialis posterior tendon dysfunction (PTTD) is estimated to be as high as 3% to 4% in Western populations, and it is one of the most commonly misdiagnosed conditions of the foot and ankle. Clinical and radiological outcomes were assessed in grade IIB PTTD treated with a medializing calcaneal osteotomy, lateral column lengthening, flexor digitorum longus transfer, and tendo-Achilles lengthening. The clinical and radiological findings recorded were the SF-36 score on physical function and mental health, midfoot and hindfoot American Orthopaedic Foot and Ankle Society (AOFAS) clinical scores, the midfoot and visual analog pain scores, as well as the radiological measurements of the hindfoot calcaneal pitch, talo-first metatarsal angle, and medial cuneiform height. The time points of assessment were preoperatively, 6 months postoperatively, and 24 months postoperatively by an examiner different from the operating surgeon. The SF-36 score on physical function (mean difference of 8.7 and 8.2, respectively), AOFAS midfoot score (mean difference of 29.6 and 15.3, respectively), AOFAS ankle-hindfoot score (mean difference of 23.2 and 14.3, respectively), midfoot visual analog pain score (mean difference of 4.0 and 1.2), and the ankle and hindfoot visual analog score (mean difference of 3.6 and 1.6) all had significant reduction from the preoperative to the 24-month postoperative time point (P < .001). Radiologically, there was also correction of the deformity associated with PTTD. The hindfoot calcaneal pitch was corrected from 8.4 degrees to 18.7 degrees. The talo-first metatarsal angle was corrected from 14.0 degrees to 1.3 degrees, and the medial cuneiform height was corrected from 10.3 mm to 20.4 mm at 24 months postoperatively. Grade IIB PTTD treated with a medializing calcaneal osteotomy, lateral column lengthening, flexor digitorum longus transfer, and tendo-Achilles lengthening demonstrated statistical significant improvement in hindfoot and midfoot AOFAS scores, SF-36 physical function scores, as well as visual analog scores. The complications were minimal. We advocate the combination of these procedures as being successful for the treatment of grade IIB PTTD. Longer term follow-up is needed to determine if these improvements plateau, improve, or deteriorate. Level IV, retrospective case series.


Effect of 2-deoxy-D-glucose on gellan gum biosynthesis by Sphingomonas paucimobilis.
2-Deoxy-D-glucose (2-DG) is a non-metabolizable glucose analogue and competitive inhibitor of glycolysis. Effect of 2-DG on gellan gum biosynthesis by Sphingomonas paucimobilis ATCC31461 were studied in this research. The concentration and the addition time of 2-DG significantly affected the biomass and gellan gum accumulation. The maximum gellan gum yield of 20.78 g/L was obtained with the addition of 50 µg/L of 2-DG at 24 h. The mechanism of 2-DG addition favoring to gellan production was revealed by determining the activities of key enzymes. Results indicated that 2-DG addition increased the activities of glucosyltransferase and inhibited UDP-glucose pyrophosphorylase activity. The result indicated that 2-DG inhibited glycolysis and changed metabolic driving force to activate gellan gum biosynthesis metabolism pathways.


A prospective cohort study of partner testing for herpes simplex virus and sexual behavior during pregnancy.
We investigated whether serotesting sexual partners of pregnant women for herpes simplex virus (HSV) improves adherence to safer-sex practices. A total of 287 HSV-2-seronegative pregnant women were recruited, and their partners were invited for HSV serologic testing. On the basis of test results, women were placed into 4 groups: those at risk for HSV-2 infection, those at risk for HSV-1 infection, those whose partner was not tested, and those not at risk for HSV infection. Women received safer-sex counseling and completed diaries of sexual activity. Women in HSV-2-serodiscordant couples (ie, those in relationships in which they were at risk for HSV-2 acquisition) reported a smaller percentage of days with unprotected genital sex acts as compared to women who were not at risk (2% vs 8%; relative risk [RR], 0.3 [95% confidence interval {CI}, .1-.8]; P = .002) and to women whose partners' HSV status was unknown (2% vs 11%; RR, 0.2 [95% CI, .1-.8]; P = .02). Women in HSV-1-serodiscordant couples showed no difference in the frequency of genital sex acts, unprotected genital sex acts, or oral sex acts as compared to those not at risk and to those whose partners' status was unknown. Pregnant women at known risk of HSV-2 acquisition by partner serotesting were less likely to engage in unprotected genital sex acts than HSV-2-seronegative women with partners who were negative or not tested.


Infrared spectroscopy of the solid phases of ammonia.
Thin films of solid ammonia (NH(3) and ND(3)) have been characterized using low temperature (25-110 K) Fourier-transform infrared (FTIR) spectroscopy, and the three solid phase (amorphous, metastable, and crystalline) spectra are reported. This work has been motivated by confusion in the literature about the metastable and crystalline phases as a result of an early erroneous report by Staats and Morgan [(J. Chem. Phys. 31, 553 (1959)]. Although the crystalline phase has subsequently been reported correctly, the metastable phase has not been described in the literature in detail. The unique characteristics of the metastable phase, reported here for the first time, include multiple peaks in the nu(2) and nu(3) regions and peak intensities that are dependent on the deposition temperature. This behavior may be the result of (a) preferential molecular orientations in the solid, or (b) exciton splitting due to different crystal shapes in the solid. The amorphous and metastable phases of deuterated ammonia are also reported for the first time.


Photochemical Activation of Electrospun In2O3 Nanofibers for High-Performance Electronic Devices.
Electrospun metal oxide nanofibers have been regarded as promising blocks for large-area, low-cost, and one-dimensional electronic devices. However, the electronic devices based on electrospun nanofibers usually suffer from poor performance and inferior viability. Here, we report an efficient photochemical process using UV light generated by a high-pressure mercury lamp to promote the electrical performance of the nanofiber-based electronic devices. Such UV treatment can lead to strong photochemical activation of electrospun nanofibers, and therefore, a stable adherent nanofiber network and electronic-clean interface were formed. By use of UV treatment, high-performance indium oxide (In2O3) nanofiber based field-effect transistors (FETs) with highly efficient modulation of electrical characteristics have been successfully fabricated. To reduce the operating voltage and further improve the device performance, the In2O3 nanofiber FETs based on solution-processed high-k AlOx dielectrics were integrated and investigated. The as-fabricated In2O3/AlOx FETs exhibit superior electrical performance, including a high mobility of 19.8 cm2 V-1 s-1, a large on/off current ratio of 106, and high stability over time and cycling. The improved performance of the UV-treated FETs was further confirmed by the integration of the electrospun In2O3/AlOx FETs into inverters. This work presents an important advance toward the practical applications of electrospun nanofibers for functional electronic devices.


Research Ethics in the European Influenzanet Consortium: Scoping Review.
Influenzanet was launched in several European countries to monitor influenza-like illness during flu seasons with the help of volunteering participants and Web-based technologies. As in the case of developing fields, ethical approaches are not well developed in the collection, processing, and analysis of participants' information. Existing controversies and varying national ethical regulations can, thus, hamper efficient cross-border research collaboration to the detriment of quality disease surveillance. This scoping review characterizes current practices on how ethical, legal, and social issues (ELSIs) pertinent to research ethics are handled by different Influenzanet country groups to analyze similarities and identify the need for further harmonization of ethical approaches. A literature search was carried out on PubMed, Web of Science, Global Digital Library on Ethics, and Bioethics Literature Database to identify ELSIs for Influenzanet country platforms. Only English-language papers were included with publication dates from 2003 to 2017. Publications were screened for the application of bioethics principles in the implementation of country platforms. Additional publications gathered from the Influenzanet Consortium website, reference screening, and conference proceeding were screened for ELSIs. We gathered 96 papers from our search methodology. In total, 28 papers that mentioned ELSIs were identified and included in this study. The Research Ethics Committee (REC) approvals were sought for recruiting participants and collecting their data in 8 of 11 country platforms and informed e-consent was sought from participants in 9 of 11 country platforms. Furthermore, personal data protection was ensured throughout the Consortium using data anonymization before processing and analysis and using aggregated data. Epidemics forecasting activities, such as Influenzanet, are beneficial; however, its benefits could be further increased through the harmonization of data gathering and ethical requirements. This objective is achievable by the Consortium. More transparency should be promoted concerning REC-approved research for Influenzanet-like systems. The validity of informed e-consent could also be increased through the provision of a user friendly and standard information sheet across the Consortium where participants agree to its terms, conditions, and privacy policies before being able to fill in the questionnaire. This will help to build trust in the general public while preventing any decline in participation.