Enhancing the effectiveness of alcohol warning labels with a self-affirming implementation intention.
Excess alcohol consumption extorts significant social and economic costs that are increasing despite the presence of mandatory warning labels on packaged alcoholic beverages. We used a novel approach by adding a brief statement based on self-affirmation theory to alcohol warning labels. In two studies (N = 85 and N = 58), we randomized regular wine drinkers recruited from university campuses to complete a wine-pouring task with bottles that had standard labeling or bottles that added a self-affirming implementation intention to the standard labeling. Alcohol consumption, behavioral intention, and self-efficacy were measured premanipulation; message acceptance was measured postmanipulation; and alcohol consumption, behavioral intention, and self-efficacy were measured again at follow-up. In both studies, the self-affirming implementation intention significantly reduced subsequent alcohol consumption (ds = 0.70 and 0.91, respectively). However, message acceptance, behavioral intention, and self-efficacy did not significantly mediate the observed effects. Self-affirming implementation intentions augmented the effect of alcohol warning labels to reduce subsequent alcohol consumption, but-consistent with the broader self-affirmation literature-it was not clear what mediated the effects. Further research is required to examine the effects of self-affirming implementation intentions on other kinds of public health-related labeling. (PsycINFO Database Record


Induction of apoptosis in glioma cells requires cell-to-cell contact with human umbilical cord blood stem cells.
We have previously demonstrated the multipotent nature of human umbilical cord blood stem cells (hUCB). In this study, we have attempted to show the use of hUCB in glioma therapy. We used hUCB enriched in CD44 and CD133 cells for our studies and observed that glioma cells co-cultured with hUCB undergo apoptosis. To prove the role of cell-to-cell contact in the induction of apoptotic events, we used a modified 0.22 microm Boyden's chamber where the upper surface was used to culture glioma cells (SNB19 or U87) or xenografts (4910 or 5310) and the lower surface to culture hUCB. TUNEL assay was carried out to determine the degree of apoptotic induction and we observed that glioma or xenograft cells co-cultured with hUCB had a higher number of TUNEL-positive characteristics (63+/-6%) compared to the controls. Further, we co-cultured glioma cells labeled with lipophilic green fluorescent dye and hUCB labeled with lipophilic red fluorescent dye. FACS analysis of cells collected from the upper and lower surfaces revealed that glioma cells had taken up red fluorescent dye from the stem cells (70+/-3%) when compared to glioma cells co-cultured with fibroblast cells (15+/-4%). The apoptotic events in the glioma and xenograft cells co-cultured with hUCB were also confirmed by Western blot analysis for the cleavage of PARP and activation of caspase 8. In addition, elevated levels of CHK-2 levels and downregulation of MAP2K1 were observed in glioma cells co-cultured with hUCB indicating the DNA damage and decrease in cell survival. Nude mice, intracranially implanted with luciferase-expressing U87 cells followed by implantation of hUCB or human fibroblast cells showed retardation of intracranial tumors in hUCB-implanted mice. Taken together, these results demonstrate that hUCB have therapeutic potential with possible clinical implications.


Function of disintegrin-like/cysteine-rich domains of atrolysin A. Inhibition of platelet aggregation by recombinant protein and peptide antagonists.
Snake venom hemorrhagic metalloproteinase toxins that have metalloproteinase, disintegrin-like and cysteine-rich domains are significantly more potent than toxins with only a metalloproteinase domain. The disintegrin-like domains of these toxins differ from the disintegrin peptides found in crotalid and viperid venoms by the nature of their different disulfide bond structure and, in lieu of the disintegrins' signature Arg-Gly-Asp (RGD) integrin binding sequence, there is an XXCD disulfide-bonded cysteinyl sequence in that region. Due to these apparent differences, the contribution to the overall function of the hemorrhagic metalloproteinases by the disintegrin-like domain has been unknown. In this investigation we have expressed in insect cells the disintegrin-like/cysteine-rich (DC) domains of the Crotalus atrox hemorrhagic metalloproteinase atrolysin A and demonstrated that the recombinant protein (A/DC) can inhibit collagen- and ADP-stimulated platelet aggregation. Using synthetic peptides, we have evidence that the region of the disintegrin-like domain that is positionally analogous to the RGD loop of the disintegrins is the site responsible for inhibition of platelet aggregation. For these synthetic peptides to have significant inhibitory activity, the -RSECD- cysteinyl residue must be constrained by participation in a disulfide bond with another cysteinyl residue. The two acidic amino acids adjacent to the middle cysteinyl residue in these peptides are also important for biological activity. These studies emphasize a functional role for the disintegrin-like domain in toxins and suggest structural possibilities for the design of antagonists of platelet aggregation.


[Vertebral tuberculosis in Gabon. Anatomo-clinical aspects, diagnostic and therapeutic problems, 107 cases from 1976 to 1986].
This retrospective study covers a period of 10.5 years (february 1976 to november 1986). It concerns 107 patients who contracted tuberculous spondylitis and originated from different provinces of Gabon. The authors report their experiences in order to emphasize the frequency of the disease, diagnostic and therapeutic problems. In Gabon, tuberculosis of the spine occupies the third position (3%), after the pulmonary form (90%) and ganglionic form (3.8%). In also represents 83.6% of the osteoarticular tuberculosis. The average age is 22 years, 55% of the patients were less than 20 years. The zone of maximum predilection, in decreasing order, is thoracic spine (36.4%), lumbar spine (33.6%), thoraco-lumbar region (10.3%). The 107 patients totalized 257 vertebral bodies destroyed (an average of 2.4 bodies per patients). On the clinical field the sick seek advice at an advance stage of the disease with gibbosity (38.3%) and neurologic deficits (21.5%). The diagnosis proof often followed the therapeutic results. There were three therapeutic modalities: medical (all patients), surgical (6 patients) and orthopedic (44 patients). The therapeutic indications improved with the available of more material and qualified staff. In children the treatment remains classic. The authors discuss the surgical indications in adults. The therapeutic results in patients treated and followed for over one year were satisfactory. Unfortunately, most patients were lost to follow-up. They suggest public health means of decreasing the frequency of the disease.


Remarkable Response to Olaparib in a Patient with Combined Hepatocellular-Cholangiocarcinoma Harboring a Biallelic BRCA2 Mutation.
Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver malignancy characterized by aggressive behavior and poor prognosis. Radial surgical resection is the standard curative treatment. However, effective therapeutic options for recurrent or metastatic cHCC-CC are still lacking, mainly because of an insufficient understanding of the molecular and genomic alterations of cHCC-CC, preventing the discovery of specialized targeting therapy. Here, we present the case of a patient with metastatic cHCC-CC on first-line treatment of gemcitabine, cisplatin, and nab-paclitaxel. A comprehensive genomic profile revealed four clinically relevant single nucleotide variants (BRCA2, PIK3C2G, RET, and TP53), two amplified genomic regions (CRKL and MAPK1), and 11 heterozygous genomic deletions (BAP1, CDKN2A, PTCH1, TSC1, BRCA2, RB1, RAD51, PALB2, TSC2, SMAD4, and STK11). The patient underwent olaparib treatment and achieved a remarkable and sustained tumor response. Our experience indicates that BRCA2 mutations could be a potential therapeutic target for patients with cHCC-CC.


Balanced Protein-Water Interactions Improve Properties of Disordered Proteins and Non-Specific Protein Association.
Some frequently encountered deficiencies in all-atom molecular simulations, such as nonspecific protein-protein interactions being too strong, and unfolded or disordered states being too collapsed, suggest that proteins are insufficiently well solvated in simulations using current state-of-the-art force fields. To address these issues, we make the simplest possible change, by modifying the short-range protein-water pair interactions, and leaving all the water-water and protein-protein parameters unchanged. We find that a modest strengthening of protein-water interactions is sufficient to recover the correct dimensions of intrinsically disordered or unfolded proteins, as determined by direct comparison with small-angle X-ray scattering (SAXS) and Förster resonance energy transfer (FRET) data. The modification also results in more realistic protein-protein affinities, and average solvation free energies of model compounds which are more consistent with experiment. Most importantly, we show that this scaling is small enough not to affect adversely the stability of the folded state, with only a modest effect on the stability of model peptides forming α-helix and β-sheet structures. The proposed adjustment opens the way to more accurate atomistic simulations of proteins, particularly for intrinsically disordered proteins, protein-protein association, and crowded cellular environments.


The utility of Apc-mutant rats in modeling human colon cancer.
Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.


Understanding Divergent Thermal Conductivity in Single Polythiophene Chains Using Green-Kubo Modal Analysis and Sonification.
We used molecular dynamics simulations and the Green-Kubo modal analysis (GKMA) method as well as sonification to study the modal contributions to thermal conductivity in individual polythiophene chains. The simulations suggest that it is possible to achieve divergent thermal conductivity in individual polythiophene chains of certain lengths, with periodic boundary conditions. Application of the GKMA method further allowed for exact pinpointing of the modes responsible for the anomalous behavior. The analysis showed that transverse vibrations in the plane of the aromatic rings at low frequencies ∼0.05 THz are primarily responsible for the divergence. Within the integration time, one mode in particular exhibits a thermal conductivity contribution greater than 100 W m-1 K-1. Further investigation showed that the divergence arises from persistent correlation between the three lowest frequency modes on chains that have exact multiples of 30 unit cells in length. Sonification of the mode heat fluxes revealed regions where the heat flux amplitude yields a somewhat sinusoidal envelope with a long period similar to the relaxation time. This characteristic in the divergent mode heat fluxes gives rise to the overall thermal conductivity divergence, which strongly supports earlier hypotheses that attribute the divergence to correlated phonon-phonon scattering/interactions as opposed to a lack of scattering/interaction among modes (e.g., infinite relaxation time/ballistic transport).


[Meta-analysis and trial sequential analysis of modified Sangbaipi Decoction for treating acute exacerbation of chronic obstructive pulmonary disease].
The randomized controlled trials about modified Sangbaipi Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) patients were collected from 7 databases( PubMed,CNKI,et al) from the establishment to December 5,2018. All the studies searched were strictly evaluated. Literatures were independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. To systematically review the efficacy of modified Sangbaipi Decoction in treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 25 RCTs involving 1 784 patients were included. According to the results of Meta-analysis,compared with the control groups,the trial group had a higher clinical efficacy in AECOPD patients( RR =1. 18,95%CI[1. 13,1. 22],P = 0),improved pulmonary functions including forced expiratory volume in one second( FEV1,WMD =0. 44,95%CI[0. 01,0. 87],P = 0. 046),and the forced vital capacity( FVC,WMD = 0. 42,95%CI[0. 07,0. 22],P = 0),but no statistical significance in the percentage of forced expiratory volume in one second( FEV1%,P = 0. 067) and the first seconds breathing volume percentage of forced vital capacity( FEV1/FVC,P = 0. 238); it improved the arterial oxygen partial pressure( PaO2,SMD =0. 85,95%CI[0. 41,1. 30],P = 0) and decreased the arterial partial pressure of carbon dioxide( PaCO2,SMD =-0. 94,95% CI[-1. 70,-0. 18],P= 0. 016); and in terms of inflammatory markers,it improved the white blood cell count( WBC,WMD=-0. 94,95%CI[-1. 17,-0. 70],P = 0). The trial sequential analysis showed that the studies included with the improvement of clinical efficacy had passed the conventional and TSA threshold,so as to further confirm the evidence. According to the findings,in addition to conventional Western medicine treatment,modified Sangbaipi Decoction could improve the efficiency in treating acute exacerbation patients with chronic obstructive pulmonary disease,increase PaO2,and decrease PaCO2,with a high safety but no effect on pulmonary function. However,restricted by the low quality of studies included,this conclusion shall be further verified by more high-quality clinical trials.


Using temporal modulation sensitivity to select stimulation sites for processor MAPs in cochlear implant listeners.
Previous studies in our laboratory showed that temporal acuity as assessed by modulation detection thresholds (MDTs) varied across activation sites and that this site-to-site variability was subject specific. Using two 10-channel MAPs, the previous experiments showed that processor MAPs that had better across-site mean (ASM) MDTs yielded better speech recognition than MAPs with poorer ASM MDTs tested in the same subject. The current study extends our earlier work on developing more optimal-fitting strategies to test the feasibility of using a site-selection approach in the clinical domain. This study examined the hypothesis that revising the clinical speech processor MAP for cochlear implant (CI) recipients by turning off selected sites that have poorer temporal acuity and reallocating frequencies to the remaining electrodes would lead to improved speech recognition. Twelve CI recipients participated in the experiments. We found that site selection procedure based on MDTs in the presence of a masker resulted in improved performance on consonant recognition and recognition of sentences in noise. In contrast, vowel recognition was poorer with the experimental MAP than with the clinical MAP, possibly due to reduced spectral resolution when sites were removed from the experimental MAP. Overall, these results suggest a promising path for improving recipient outcomes using personalized processor-fitting strategies based on a psychophysical measure of temporal acuity.


[Effect of iodine-containing thyroid hormones on the histostructure of rat liver under the stress].
Experiments with 130 outbred male rats weighing 220-250 g have show that stress "free swimming in a cage" (FSC) affects the histological structure of the liver as early as in 1 h. FSC occurred in standard plastic cages (5 animals) filled with water to a height of 15 cm and topped with a grid. One hour after FSC (the alarm-stage) caused dystrophy of hepatocytes and increased blood flow to the liver lobules, which also continued at the resistance-stage (48 h after the FSC). At the exhaustion-stage (daily 1-hour stress for 10 days) there were even greater hepatocytes dystrophy, necrosis, and their microcirculatory disturbances in the lobules. The introduction of merkazolil (intragastrically 25 mg/kg for 20 days) per se altered the histostructure of the liver tissue and under stress aggravates the microcirculatory changes, dystrophy and necrosis of the hepatocytes. Small doses of L-thyroxine (intragastrically 1.5-3.0 μg/kg for 28 days) minimized the histological signes of the liver damage at all stages of the stress response. Consequently, the iodine-containing thyroid hormones limit the disturbance of the microstructure of the liver caused by stress.


Impact of sensory integration training on balance among stroke patients: sensory integration training on balance among stroke patients.
This study attempts to investigate the impact that the sensory integration training has on the recovery of balance among patients with stroke by examining the muscle activity and limit of stability (LOS). A total of 28 subjects participated. The subjects were randomly allocated by the computer program to one of two groups: control (CON) group (n=15), sensory integration training (SIT) group (n=13). The research subjects received intervention five days a week for a total of four weeks. The CON group additionally received 30-minute general balance training, while the SIT group additionally received 30-minute sensory integration training. In the muscle activity, the improvement of Erector spinae (ES) and Gluteus medius (GM) was more significant in the SIT group than in the CON group. In the LOS, the improvement of affected side and forward side was significantly higher in the SIT group compared to the CON group. Sensory integration training can improve balance ability of patients with stroke by increasing muscle activity of stance limb muscles such as GM and trunk extensor such as ES along with enhancement of the limit of stability.


Appearance concerns among women with neurofibromatosis: examining sexual/bodily and social self-consciousness.
Neurofibromatosis (NF) 1 and 2 have distinct appearance effects, yet little research has examined patients' appearance concerns. We assessed appearance concerns and self-consciousness, self-esteem, and loneliness among women with NF. Women with NF1 (n = 79) and NF2 (n = 48) completed the Derriford Appearance Scale to assess appearance concerns and sexual/bodily and social self-consciousness, Rosenberg Self-Esteem Scale, and UCLA Loneliness Scale. Women's appearance concerns were coded to determine whether they were NF-related and whether psychosocial factors contributed to the concerns. A total of 85% of women reported appearance concerns, many of which were NF-related and attributed to psychosocial factors. Women with NF1 reported significantly more sexual/bodily self-consciousness but similar levels of social self-consciousness compared with women with NF2. Significantly higher sexual/bodily self-consciousness was found among married/cohabiting women regardless of NF group. Compared with general population norms and breast cancer survivors (BCS), women with NF1 reported significantly greater sexual/bodily and social self-consciousness. Women with NF2 reported less sexual/bodily self-consciousness compared with population norms, yet tended to report greater sexual/bodily self-consciousness than BCS. Women with NF2 reported significantly greater social self-consciousness compared with population norms and BCS. For both NF1 and NF2, higher levels of sexual/bodily and social self-consciousness were related to lower self-esteem and higher levels of social self-consciousness to more loneliness. Appearance concerns are prevalent, and social self-consciousness is high, among women with NF1 and NF2. Women with NF1 compared with NF2 experience more sexual/bodily self-consciousness. Providers should assess the impact of NF on women's self-perceptions and address sexual, body image, and social concerns.


Radiobiological modifiers in clinical radiation oncology: current reality and future potential.
Radiation therapy can successfully ablate tumors. However, the same ionization process that destroys a cancer can also permanently damage surrounding organs resulting in unwanted clinical morbidity. Therefore, modern radiation therapy attempts to minimize dose to normal tissue to prevent side effects. Still, as tumors and normal tissues intercalate, the risk of normal tissue injury often may prevent tumoricidal doses of radiation therapy to be delivered. This paper will review current outcomes and limitations of radiobiological modifiers that may selectively enhance the radiosensitivity of tumors as well as parallel techniques that may protect normal tissues from radiation injury. Future endeavors based in part upon newly elucidated genetic pathways will be highlighted.


Joint stage recognition and anatomical annotation of Drosophila gene expression patterns.
Staining the mRNA of a gene via in situ hybridization (ISH) during the development of a Drosophila melanogaster embryo delivers the detailed spatio-temporal patterns of the gene expression. Many related biological problems such as the detection of co-expressed genes, co-regulated genes and transcription factor binding motifs rely heavily on the analysis of these image patterns. To provide the text-based pattern searching for facilitating related biological studies, the images in the Berkeley Drosophila Genome Project (BDGP) study are annotated with developmental stage term and anatomical ontology terms manually by domain experts. Due to the rapid increase in the number of such images and the inevitable bias annotations by human curators, it is necessary to develop an automatic method to recognize the developmental stage and annotate anatomical terms. In this article, we propose a novel computational model for jointly stage classification and anatomical terms annotation of Drosophila gene expression patterns. We propose a novel Tri-Relational Graph (TG) model that comprises the data graph, anatomical term graph, developmental stage term graph, and connect them by two additional graphs induced from stage or annotation label assignments. Upon the TG model, we introduce a Preferential Random Walk (PRW) method to jointly recognize developmental stage and annotate anatomical terms by utilizing the interrelations between two tasks. The experimental results on two refined BDGP datasets demonstrate that our joint learning method can achieve superior prediction results on both tasks than the state-of-the-art methods. http://ranger.uta.edu/%7eheng/Drosophila/.


Studies of human chorionic gonadotrophin in steroid-primed hypophysectomized rats.
The uptake of [125I]HCG was studied in the ovaries of intact and hypophysectomized (Hypox) Sprague-Dawley rats. The [125I]HCG localized specifically in the ovary of the intact rat, and to a lesser extent, in the ovary of the hypox rat. The concentration of HCG in all other tissues and organs of either sex was negligible. However, the localization of [125I]HCG in the hypox rat was enhanced by the presence of exogenous steroids. The greatest increase in HCG uptake was observed in the rats primed with androgen; while a lesser enhancement was demonstrated in the oestrogen treated rats. Comparison of the ovary-to-body weight ratios revealed that a greater amount of HCG localized in the androgen-primed rats than in the oestrogen treated animals even though the ovaries of the former were smaller. These findings suggest that the hypox rat ovary primed with androgen could provide a highly sensitive animal model for further studies of the HCG cell receptor site in animals free of pituitary influence.


A systematic review of frontal lobe volume in autism spectrum disorder revealing distinct trajectories.
Frontal lobe volume has been extensively researched in individuals with Autism spectrum disorder (ASD), though findings are yet to be summarised to explain the developmental trends of frontal lobe volume. The aim of the present study is to consolidate all existing frontal lobe volume and age data of autistic individuals below 30 years of age, and compare this data to non-autistic (N-ASD) controls. Following a systematic review, frontal lobe volume data were obtained from seven papers. Raw data, or the means and standard deviations of frontal lobe volume, and age, were obtained from the studies giving 372 autistic and 190 N-ASD participants. Data were plotted and analysed. Findings revealed that regression lines of fit for ASD (R2Linear = 0.33; R2Quadratic = 0.52) and N-ASD (R2Linear = 0.14; R2Quadratic = 0.39) were significantly different by diagnosis (linear p = 0.002, quadratic p = 0.02) with quadratic models providing significantly better fit within ASD (p < 0.001) and N-ASD (p < 0.001). Additional analyses revealed that frontal lobe volume was greater in autistic individuals than N-ASD between two and four years (F(1,31) = 12.965, p < 0.005, η2 = 0.291). In the present study, there were distinct developmental trends for frontal lobe volume between ASD and N-ASD.


Irofulven (6-hydroxymethylacylfulvene, MGI 114)-induced apoptosis in human pancreatic cancer cells is mediated by ERK and JNK kinases.
Pancreatic carcinoma resists chemotherapeutic mediation of apoptosis. Irofulven (MGI 114, 6-hydroxymethylacylfulvene) is a novel illudin S analogue that we have shown to induce caspase-mediated apoptosis in pancreatic carcinoma cell lines. Westem blot analysis and kinase assays were used to demonstrate the activation of Erk 1/2 and JNK1 kinases following Irofulven administration in the presence and absence of selective kinase inhibitors. Irofulven activates JNK1 and Erk1/2, but not p38. The addition of the MAPK inhibitors, SB202190 and PD98059 (targeting JNK1 and Erk1/2 activation, respectively), prevents kinase activation and blocks Irofulven-induced activation of caspases -3, -7, -8 and -9. Blockade of either JNK1 or Erk1/2 results in a 50% decrease in apoptosis in MiaPaCa-2 cells treated with Irofulven. Our data demonstrated that JNK1 and Erk1/2 are activated by Irofulven treatment and that blockade of either MAPK subfamily decreases apoptosis by rendering Irofulven incapable of inducing caspase activation.


Repair of left ventricular pseudoaneurysm with the triple patch technique (Empanada Patch).
Left ventricular pseudoaneurysm is a rare but serious complication of myocardial infarction that requires urgent intervention to avoid unpredictable fatal rupture. Surgical repair aims at excluding the aneurysmal area with a patch to preserve the left ventricular geometry. Here, we present a case of successful repair of inferobasal left ventricular pseudoaneurysm using a modified triple patch technique ('Empanada Patch').


Association of the CD226 Ser(307) variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis.
The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361. The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 × 10(-5) . The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti-topoisomerase I antibody-positive, and SSc-related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42-2.43), P = 5.15 × 10(-6) , OR 1.82 (95% CI 1.38-2.40), P = 2.16 × 10(-5) , and OR 1.61 (95% CI 1.25-2.08), P = 2.73 × 10(-4) , respectively. CD226 expression was not significantly influenced by CD226 rs763361 genotypes whatever the T cell subtype investigated. Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.


Benchmarking density functional tight binding models for barrier heights and reaction energetics of organic molecules.
Density Functional Tight Binding (DFTB) models are two to three orders of magnitude faster than ab initio and Density Functional Theory (DFT) methods and therefore are particularly attractive in applications to large molecules and condensed phase systems. To establish the applicability of DFTB models to general chemical reactions, we conduct benchmark calculations for barrier heights and reaction energetics of organic molecules using existing databases and several new ones compiled in this study. Structures for the transition states and stable species have been fully optimized at the DFTB level, making it possible to characterize the reliability of DFTB models in a more thorough fashion compared to conducting single point energy calculations as done in previous benchmark studies. The encouraging results for the diverse sets of reactions studied here suggest that DFTB models, especially the most recent third-order version (DFTB3/3OB augmented with dispersion correction), in most cases provide satisfactory description of organic chemical reactions with accuracy almost comparable to popular DFT methods with large basis sets, although larger errors are also seen for certain cases. Therefore, DFTB models can be effective for mechanistic analysis (e.g., transition state search) of large (bio)molecules, especially when coupled with single point energy calculations at higher levels of theory. © 2017 Wiley Periodicals, Inc.


Identification of active transposon dTok, a member of the hAT family, in rice.
Recent completion of the sequencing of the rice genome has revealed that it contains >40% repetitive sequences, most of which are related to inactive transposable elements. During the molecular analysis of the floral organ number 1/multiple pistil 2 (fon1/mp2) mutant, we identified an active transposable element dTok0 that was inserted at the kinase domain of FON1, a homolog of CLAVATA1. Insertion of the element into FON1 generated an 8 bp duplication of its target sites, which is one of the major characteristics of the hAT family of transposons. The dTok0 element was actively transposed out of the FON1 gene, leaving 5-8 bp footprints. Reinsertion into a new location was observed at a low frequency. Analysis of the genome sequence showed that the rice cultivar 'Nipponbare' contains 25 copies of dTok elements; similar numbers were present in all the Oryza species examined. Because dTok0 does not encode a transposase, enzyme activity should be provided in trans. We identified a putative autonomous transposon, Tok1 that contains an intact open reading frame of the Ac-like transposase.


Supramolecular networks of 10-(2-hydroxyethyl)acridin-9(10H)-one and 10-(2-chloroethyl)acridin-9(10H)-one.
Both 10-(2-hydroxyethyl)acridin-9(10H)-one, C15H13NO2, and 10-(2-chloroethyl)acridin-9(10H)-one, C15H12ClNO, have monoclinic (P21/c) symmetry and supramolecular three-dimensional networks. But the differences in the intermolecular interactions displayed by the hydroxy group and the chlorine substituent lead to stronger intermolecular π-stacking interactions and hydrogen bonding, and hence a significantly higher melting point for the former.


Modeling the population lens effect in thermal lens spectrometry.
We report a theoretical model and experimental results for laser-induced lensing in solids. The model distinguishes and quantifies the contributions from population and thermal effects. Laser-induced lensing in ytterbium-doped fluorozirconate glass ZBLAN:Yb(3+) is measured, and the thermal and optical properties obtained from analyzing the data with the proposed model agree well with published values. Photothermal techniques are used extensively for the investigation of laser and laser-cooling materials, and the model developed here enables the interpretation of convoluted laser-induced lensing signals that have contributions from different sources.


Comparison of eosinophil densities in oral mucosal lichen planus and lichenoid drug reactions.
The eosinophil density in various tissue compartments in oral mucosal lichen planus and oral mucosal lichenoid drug reactions was studied using a variety of staining methods and histomorphometry. No significant differences were found, indicating that the presence of eosinophils cannot be used as a reliable histologic criterion for establishing a diagnosis of oral mucosal lichenoid drug reactions.


Fhit down-regulation is an early event in pancreatic carcinogenesis.
Aberrant Fhit expression characterizes a large proportion of primary pancreatic ductal adenocarcinomas (PDACs), but fragmentary information is available on Fhit expression during the phenotypic changes of pancreatic ductal epithelium during multistep transformation. We assessed Fhit expression by immunohistochemistry in two different multistep pancreatic carcinogenic processes: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). We considered 105 surgically treated PDACs/IPMNs and selected 30 samples of non-neoplastic pancreatic parenchyma, 50 PanIN lesions, 30 IPMNs, 15 IPMNs with associated invasive carcinoma, and 60 adenocarcinomas. Normal pancreatic ducts and surrounding acinar cells consistently showed moderate to strong Fhit immunoreactivity. Significant down-regulation of Fhit expression was observed in association with increasing severity of dysplastia/neoplastia in both carcinogenic processes. This was further confirmed by studying multiple lesions obtained from the same surgical specimen. Of 60 PDACs, only 14 showed Fhit expression comparable to normal pancreatic ductal epithelium, while the remainder (77%) showed clearly negative or reduced Fhit expression. This study demonstrates that Fhit down-regulation is an early event in both multistep carcinogenic processes leading to PDAC.


Solitary pulmonary nodules and masses: a meta-analysis of the diagnostic utility of alternative imaging tests.
The purpose was to assess the clinical utility of diagnostic tests for identifying malignancy within a solitary pulmonary nodule (SPN), and to create a nomogram or "look-up" table using clinical data and non-invasive radiology (positive) test results to estimate post-test probability of malignancy. Studies that examined computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT) for the evaluation of SPN. Two reviewers independently abstracted data and assessed study quality. Study-specific and overall positive likelihood ratios (LRs) for each diagnostic test confirming a diagnosis of malignancy and negative LR for each diagnostic test excluding a diagnosis of malignancy within an SPN were calculated. Forty-four of 242 articles were included. Positive LRs for diagnostic tests were: CT 3.91 (95% confidence interval 2.42, 5.40), MRI 4.57 (3.03, 6.1), PET 5.44 (3.56, 7.32) and SPECT 5.16 (4.03, 6.30). Negative LRs were: CT 0.10 (0.03, 0.16), MRI 0.08 (0.03, 0.12), PET 0.06 (0.02, 0.09) and SPECT 0.06 (0.04, 0.08). Differences in performance for all tests were negligible; therefore, the clinician may confidently use any of the four tests presented in further evaluating an SPN. Given the low cost and prevalence of the technology, SPECT appears to be the leading choice for additional testing in SPN evaluation.


Disruption of the interaction of alpha-synuclein with microtubules enhances cell surface recruitment of the dopamine transporter.
Mutations in alpha-synuclein have been implicated in the genesis of Parkinson's disease. A probable normative function of alpha-synuclein is the maintenance of dopamine homeostasis, partly through a negative modulation of dopamine transporter (DAT) activity, by reducing its level at the cell surface. To study the possible involvement of the microtubular network in the alpha-synuclein-dependent trafficking of DAT, we treated cotransfected cells and primary mesencephalic neurons with either colchicine, vinblastine, or nocodazole, each of which disrupts microtubules or affects microtubule dynamics. Treatment of both types of cells with vinblastine, colchicine, or nocodazole reversed alpha-synuclein-mediated inhibition of DAT activity, resulting in an increased rate of dopamine uptake and and increased level of extracellular dopamine-induced oxidative stress, with accelerated cell death. Treatment with these agents also reversed the alpha-synuclein-induced decrease in levels of cell surface-associated DAT. This effect of colchicine, vinblastine, or nocodazole was not linked to a disruption of formation of the alpha-synuclein-DAT complex but paradoxically caused an increased level of interaction between these proteins. Both alpha-synuclein and DAT co-immunoprecipitated with both alpha- and beta-tubulins, in both transfected cells and rat primary mesencephalic dopaminergic neurons, suggesting heteromeric complex formation between these various proteins. Treatment with the microtubule depolymerizing agents disrupted the heteromeric protein complex between either alpha-synuclein or the DAT, and alpha- or beta-tubulins. These results indicate a previously unappreciated role of microtubules in the modulation of DAT trafficking, and provide insight into a novel mechanism by which alpha-synuclein regulates DAT activity, by tethering the transporter to the microtubular network.


Impact of nap length, nap timing and sleep quality on sustaining early morning performance.
The study examined how nap length, nap timing and sleep quality affect early morning performance (6:00 to 8:00). Twelve students participated in a simulated nightshift schedule (22:00 to 8:00) where the length and timing of nocturnal naps were manipulated (0:00-1:00, 0:00-2:00, 4:00-5:00 and 4:00-6:00). A performance test battery was administered consisting of a psychomotor vigilance test, a logical reasoning test, and a visual analogue scale for subjective fatigue and sleepiness. The results showed that a 120-min nap sustained early morning performance better than a 60-min nap. Taking a nap earlier or later did not affect the neurobehavioral performance tests, although participants slept more efficiently during naps later in the night shift. A negative effect of a nocturnal nap during the night shift on subsequent daytime and nocturnal sleep was not observed in the sleep architecture. It still remains unclear whether slow wave sleep plays an important role in sustaining early morning performance. In terms of work safety and sleep health, the results suggest that a longer and later nap is beneficial during night shifts.


Longitudinal examination of American National Adult Reading Test (AMNART) performance in dementia of the Alzheimer type (DAT): validation and correction based on degree of cognitive decline.
The American National Adult Reading Test (AMNART) was constructed to provide a valid and stable estimate of premorbid verbal IQ (VIQ) in dementing individuals. However, recent studies have brought into question its validity in patients with dementia of the Alzheimer type (DAT). The present study was designed to longitudinally assess the validity of the AMNART in 40 DAT patients and 40 demographically matched normal control (NC) subjects. The results showed that VIQ estimates for patients with DAT were significantly lower than those of NC subjects and declined significantly over time with increasing dementia severity as measured by the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). An MMSE-based correction factor was derived for the DAT group which allows for the effective estimation of premorbid VIQ in these patients.


AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy.
Conventional targeted therapies for the treatment of cancer have limitations, including the development of acquired resistance. However, novel alternatives have emerged in the form of targeted therapies based on AB toxins. These biotoxins are a diverse group of highly poisonous molecules that show a nanomolar affinity for their target cell receptors, making them an invaluable source of ligands for biomedical applications. Bacterial AB toxins, in particular, are modular proteins that can be genetically engineered to develop high-affinity therapeutic compounds. These toxins consist of two distinct domains: a catalytically active domain and an innocuous domain that acts as a ligand, directing the catalytic domain to the target cells. Interestingly, many tumor cells show receptors on the surface that are recognized by AB toxins, making these high-affinity proteins promising tools for developing new methods for targeting anticancer therapies. Here we describe the structure and mechanisms of action of Diphtheria (Dtx), Anthrax (Atx), Shiga (Stx), and Cholera (Ctx) toxins, and review the potential uses of AB toxins in cancer therapy. We also discuss the main advances in this field, some successful results, and, finally, the possible development of innovative and precise applications in oncology based on engineered recombinant AB toxins.


Attentional bias toward negative stimuli in PTSD: an eye-tracking study.
Research on biased processing of aversive stimuli in posttraumatic stress disorder (PTSD) has produced inconsistent results between response time (RT) and eye-tracking studies. Recent RT-based results of dot-probe studies showed no attentional bias (AB) for threat while eye-tracking research suggested heightened sustained attention for this information. Here, we used both RT-based and eye-tracking measures to explore the dynamics of AB to negative stimuli in PTSD. Twenty-three individuals diagnosed with PTSD, 23 trauma-exposed healthy controls, and 23 healthy controls performed an emotional dot-probe task with pairs of negative and neutral scenes presented for either 1 or 2 s. Analyses included eye movements during the presentation of the scenes and RT associated with target localization. There was no evidence for an AB toward negative stimuli in PTSD from RT measures. However, the main eye-tracking results revealed that all three groups showed longer dwell times on negative pictures than neutral pictures at 1 s and that this AB was stronger for individuals with PTSD. Moreover, although AB disappeared for the two groups of healthy controls with prolonged exposure, it persisted for individuals with PTSD. PTSD is associated with an AB toward negative stimuli, characterized by heightened sustained attention toward negative scenes once detected. This study sheds light on the dynamics of AB to negative stimuli in PTSD and encourages us to consider optimized therapeutic interventions targeting abnormal AB patterns.


Insulin secretion and sensitivity during oral glucose tolerance test in Korean lean elderly women.
Impaired glucose tolerance (IGT) and type 2 diabetes including undiagnosed isolated postchallenge hyperglycemia (IPH) are common in the elderly. The aim of this study was to investigate the insulin secretion and sensitivity in Korean elderly lean diabetic women. Forty-one lean women aged 65-88 years took 2 hr oral glucose tolerance test (OGTT) and were stratified according to the WHO criteria (normal glucose tolerance [NGT], n=20; IGT, n=6; and type 2 diabetics, n=15 including seven IPH). HbA1c and fructosamine progressively increased from the NGT to the diabetic subjects (p=0.006 and p=0.001, respectively). Compared with subjects with NGT, the insulinogenic index, a marker of early insulin secretion and the AUC(ins), a marker of total insulin secretion, decreased significantly in diabetic group [0.53 (-0.44 -1.45) vs. 0.18 (0.00 -1.11), p=0.03 and 306+/-165 vs. 199+/-78 pmol/L, p=0.02 respectively]. A significant difference was found in the AUC(c-peptide) among each group (221+/-59 vs. 206+/-34 vs. 149+/-51 pmol/L, p=0.001 for each). The homeostasis model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, was not different among the groups. We conclude that compared with NGT subjects, elderly lean women with diabetes have impaired oral glucose-induced insulin secretion but have relatively preserved insulin sensitivity. This suggests that insulin resistance is not necessarily an essential component of Korean elderly lean diabetic women.


PPACA and Low-Income People Living with HIV: 2014 Qualified Health Plan Enrollment in a Medicaid Nonexpansion State.
People living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) often are uninsured or underinsured, and they may benefit from the Patient Protection and Affordable Care Act (PL 111-148) and its improved access to medical care. Safety net programs, such as AIDS Drug Assistance Programs (ADAP) funded through the Ryan White HIV/AIDS Program, which serve low-income people living with HIV, are incorporating Patient Protection and Affordable Care Act Marketplace-qualified health plans (QHPs) and helping to fund patients' participation. This changing landscape differs from state to state, and one main element contributing to the differing situations is whether a state elected to expand Medicaid. This review examines QHP enrollment of ADAP clients in Virginia, a Medicaid nonexpansion state, and explores some issues that affect people living with HIV in other Medicaid nonexpansion states. Virginia is a leader in the shift of ADAP healthcare delivery from direct medication provision to purchasing QHPs. Virginia ADAP clients accounted for approximately 2% of ADAP clients nationally, but they represent 17% of ADAP clients enrolled in QHPs nationwide. Ensuring good HIV care of the ADAP population is important to each patient's personal longevity, the public health, and the efficient use of healthcare dollars. As healthcare delivery models shift, the effects on patients and health outcomes achieved should be monitored, particularly for chronic diseases such as HIV.


Deletion of AIF1 but not of YCA1/MCA1 protects Saccharomyces cerevisiae and Candida albicans cells from caspofungin-induced programmed cell death.
Caspofungin was the first member of a new class of antifungals called echinocandins to be approved by a drug regulatory authority. Like the other echinocandins, caspofungin blocks the synthesis of β(1,3)-D-glucan of the fungal cell wall by inhibiting the enzyme, β(1,3)-D-glucan synthase. Loss of β(1,3)-D-glucan leads to osmotic instability and cell death. However, the precise mechanism of cell death associated with the cytotoxicity of caspofungin was unclear. We now provide evidence that Saccharomyces cerevisiae cells cultured in media containing caspofungin manifest the classical hallmarks of programmed cell death (PCD) in yeast, including the generation of reactive oxygen species (ROS), the fragmentation of mitochondria, and the production of DNA strand breaks. Our data also suggests that deleting AIF1 but not YCA1/MCA1 protects S. cerevisiae and Candida albicans from caspofungin-induced cell death. This is not only the first time that AIF1 has been specifically tied to cell death in Candida but also the first time that caspofungin resistance has been linked to the cell death machinery in yeast.


Knowledge, attitudes, and practices regarding antiretroviral management, reproductive health, sexually transmitted infections, and sexual risk behavior among perinatally HIV-infected youth in Thailand.
More than 30% of perinatally HIV-infected children in Thailand are 12 years and older. As these youth become sexually active, there is a risk that they will transmit HIV to their partners. Data on the knowledge, attitudes, and practices (KAP) of HIV-infected youth in Thailand are limited. Therefore, we assessed the KAP of perinatally HIV-infected youth and youth reporting sexual risk behaviors receiving care at two tertiary care hospitals in Bangkok, Thailand and living in an orphanage in Lopburi, Thailand. From October 2010 to July 2011, 197 HIV-infected youth completed an audio computer-assisted self-interview to assess their KAP regarding antiretroviral (ARV) management, reproductive health, sexual risk behaviors, and sexually transmitted infections (STIs). A majority of youth in this study correctly answered questions about HIV transmission and prevention and the importance of taking ARVs regularly. More than half of the youth in this study demonstrated a lack of family planning, reproductive health, and STI knowledge. Girls had more appropriate attitudes toward safe sex and risk behaviors than boys. Although only 5% of the youth reported that they had engaged in sexual intercourse, about a third reported sexual risk behaviors (e.g., having or kissing boy/girlfriend or consuming an alcoholic beverage). We found low condom use and other family planning practices, increasing the risk of HIV and/or STI transmission to sexual partners. Additional resources are needed to improve reproductive health knowledge and reduce risk behavior among HIV-infected youth in Thailand.


Active-learning strategies in computer-assisted drug discovery.
High-throughput compound screening is time and resource consuming, and considerable effort is invested into screening compound libraries, profiling, and selecting the most promising candidates for further testing. Active-learning methods assist the selection process by focusing on areas of chemical space that have the greatest chance of success while considering structural novelty. The core feature of these algorithms is their ability to adapt the structure-activity landscapes through feedback. Instead of full-deck screening, only focused subsets of compounds are tested, and the experimental readout is used to refine molecule selection for subsequent screening cycles. Once implemented, these techniques have the potential to reduce costs and save precious materials. Here, we provide a comprehensive overview of the various computational active-learning approaches and outline their potential for drug discovery.


Massive spontaneous suprachoroidal hemorrhage in a young woman with cystic fibrosis and diabetes mellitus on anticoagulants.
To report a case of massive spontaneous suprachoroidal hemorrhage in a young woman with cystic fibrosis and proliferative diabetic retinopathy on anticoagulant therapy. Single case report. A 24-year-old woman with cystic fibrosis and diabetes mellitus developed a massive spontaneous suprachoroidal hemorrhage in the left eye after two months of warfarin therapy and recent treatment with heparin. Fundus examination and B-scan ultrasonography of the left eye revealed a hemorrhagic choroidal detachment. Elevated intraocular pressure was controlled with brimonidine, but four months later the left eye ceased to perceive light. Massive spontaneous suprachoroidal hemorrhage (SSCH) is a rare event that occurs almost exclusively in patients of advanced age. To our knowledge, this is the youngest patient with SSCH described in the literature. Regardless of age or other medical conditions, anticoagulant therapy appears to be a strong risk factor. SSCH carries a poor visual prognosis with or without surgical intervention.


Computer-assisted statistical analyses of enzyme and ribosomal DNA electrophoretic polymorphism in Yersinia.
The intra- and inter-species differentiation of 90 strains of Yersinia belonging to six species were studied independently by computer-assisted statistical analysis of data from enzyme electrophoretic polymorphism and ribosomal DNA (rDNA) restriction fragment length polymorphism. Two correspondence analyses (CA) demonstrated the concordance between the bacterial classification obtained from enzymatic and genomic data. This concordance was reinforced by an algorithm of the correspondence established between the two dendrograms drawn from previous computations. Comparison of CA with similarity analysis (also called "numerical taxonomy") indicated that the intra- and inter-species differentiation obtained by the two methods are similar. The advantage of CA is that it gives a synthetic geometrical representation of the results (factorial planes), displaying both the main features of the clusters of strains (location and dispersion) and their essential character (i.e.: enzyme electrophoretic variant, rDNA fragment size).


The suture fixation of levonorgestrel-releasing intrauterine device using the hysteroscopic cold-knife surgery system: an original method in treatment of adenomyosis.
To introduce an effective approach using the hysteroscopic cold-knife surgery system (HCSS) for suture fixation of the levonorgestrel-releasing intrauterine device (LNG-IUD) in patients with adenomyosis. Video description of the surgical procedures to demonstrate the detailed technique. The study was reviewed and approved by the institutional review board of Hangzhou Women's Hospital. Maternity hospital. A 39-year-old woman diagnosed with adenomyosis had endured 7 years of severe dysmenorrhea and 4 years of heavy menstrual bleeding. She had a past medical history that was significant for expulsion of an LNG-IUD. Transvaginal ultrasonography revealed that her uterus was enlarged by adenomyosis. She insisted on preserving fertility potential. We proceeded with the HCSS and the uterine cavity was found enlarged significantly. In consideration of the patient's strong desire for maintaining fertility options, the fixation of the LNG-IUD on the intrauterine posterior wall with an Ethibond suture was performed successfully through an endoscopic needle driver and a knot-pushing device. Proficient endoscopic suturing is the key to the technique. Informed consent was obtained from the patient. Feasibility and value of using the HCSS to fix an LNG-IUD for treatment of adenomyosis. The LNG-IUD was fixed successfully by the HCSS with an Ethibond suture on the posterior wall of the uterus within 30 minutes, and the intraoperative blood loss was 2 mL. The patient was discharged 24 hours postoperatively without any adverse perioperative complications. At the one-year follow-up, the patient reported obvious relief of her dysmenorrhea and menorrhagia and no more experience with expulsion. Ultrasound demonstrated normal position of the IUD at 1, 3, 6, and 12 months postoperatively. Hysteroscopy presents a clear visual field to locate and fix the IUD. In patients with adenomyosis suffering from dysmenorrhea or excessive menstrual blood loss, suture fixation of the LNG-IUD using the HCSS can be a minimally invasive and effective alternative for treating adenomyosis, especially in patients who have previously expelled an LNG-IUD, preventing the risk of expulsion.


Male adolescents' concern about a physical examination conducted by a female.
This descriptive study measured degree of concern of 45 healthy male adolescents aged 13 to 17 from three private physicians' offices when they were told that their complete physical examination might be conducted by a female examiner. Degree was measured on a 20-item Likert-type instrument on which areas of concern were categorized as body image, identity, independence, and relatedness. Concern scores were obtained in each of the four categories, and a total concern score was determined. Relationships between the independent variable, age of the participants, and the dependent variables, concerns (body image, identity, independence, relatedness, and total concerns), were determined by Pearson correlations. Relationships were additionally determined between a second independent variable, Tanner stage of physiological sexual development, and the dependent variables. Partial correlation was used to determine relationships between Tanner stage and concerns while holding age constant. As age increased, concerns decreased, and no significant relationship was found between Tanner stage and concerns. Age was such a contributing factor affecting concerns that when partialed out, no significant relationship between Tanner stage and concerns remained. Because female clinicians might expect to seen more concern in younger adolescent males, research is required on how to reduce these concerns.


A controlled clinical trial with De-Nol (tripotassium dicitrato bismuthate) in patients with gastric ulcer.
The efficacy of local-acting De-Nol liquid (tripotassium dicitrato bismuthate) was investigated in patients with endoscopically verified gastric ulcer. In a prospective-type clinical trial, 16 outpatients received De-Nol and 24 outpatients received an antacid mixture (sodium bicarbonate, calcium carbonate, magnesium trisilicate in equal parts). The period of study was 4 weeks, the endoscopy being performed on the 14th and 28th day after commencement of treatment. We Registration was made of the degree of ulcer healing (ulcer is healed, or not healed but reduced by 50%, or slightly healed, or unchanged), the degree of pain (0 = none, 1 = slight, 2 = moderate, 3 = severe), body weight, different biochemical and haematological examinations, side-effects and some other parameters. Of those patients given De-Nol treatment, the ulcer healed in 69% within four weeks, as compared with 33% of those given antacid therapy. There was also a significant (p less than 0.001, p less than 0.02) difference between the two groups in the size of the ulceration which remained and in the decrease of pain. Side-effects were not recorded. These data suggest the beneficial effect of De-Nol liquid in the treatment of patients with gastric ulceration.


Flow cytometric analysis of primary lung carcinomas and their lymph node metastases.
Specimens of primary lung carcinomas and lymph node metastases from the same 18 patients were investigated by means of flow cytometry. The number of DNA stemlines, DNA indices, the proportion of diploid cells in the tumors and the distribution of the cell cycle phases were compared. In 10 patients DNA stemlines and DNA indices were identical in primary tumors and metastases. In two cases the DNA indices were doubled in metastases. In 6 cases the primary tumors contained two abnormal DNA stemlines and their metastases contained only one aneuploid stemline. Gross differences between primary tumors and lymph node metastases with regard to the proportion of cell cycle phases could not be found. The large variation between primary tumors and lymph node metastases with regard to DNA stemlines indicates that flow cytometric analysis of lymph nodes gives only limited information about the primary tumors.


A Review of Structure Engineering of Strain-Tolerant Architectures for Stretchable Electronics.
Stretchable electronics possess significant advantages over their conventional rigid counterparts and boost game-changing applications such as bioelectronics, flexible displays, wearable health monitors, etc. It is, nevertheless, a formidable task to impart stretchability to brittle electronic materials such as silicon. This review provides a concise but critical discussion of the prevailing structural engineering strategies for achieving strain-tolerant electronic devices. Not only the more commonly discussed lateral designs of structures such as island-bridge, wavy structures, fractals, and kirigami, but also the less discussed vertical architectures such as strain isolation and elastoplastic principle are reviewed. Future opportunities are envisaged at the end of the paper.


Fragile X-Associated Tremor/Ataxia Syndrome: From Molecular Pathogenesis to Development of Therapeutics.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells. Besides these CGG-mediated mechanisms, recent studies have shed light on additional mechanisms of pathogenesis, such as the antisense transcript ASFMR1, mitochondrial dysfunction, DNA damage from R-loop formation and 5-hydroxymethylcytosine (5hmC)-mediated epigenetic modulation. Here we summarize the recent progress towards understanding the etiology of FXTAS and provide an overview of potential treatment strategies.


Apigenin blocks IKKα activation and suppresses prostate cancer progression.
IKKα has been implicated as a key regulator of oncogenesis and driver of the metastatic process; therefore is regarded as a promising therapeutic target in anticancer drug development. In spite of the progress made in the development of IKK inhibitors, no potent IKKα inhibitor(s) have been identified. Our multistep approach of molecular modeling and direct binding has led to the identification of plant flavone apigenin as a specific IKKα inhibitor. Here we report apigenin, in micro molar range, inhibits IKKα kinase activity, demonstrates anti-proliferative and anti-invasive activities in functional cell based assays and exhibits anticancer efficacy in experimental tumor model. We found that apigenin directly binds with IKKα, attenuates IKKα kinase activity and suppresses NF-ĸB/p65 activation in human prostate cancer PC-3 and 22Rv1 cells much more effectively than IKK inhibitor, PS1145. We also showed that apigenin caused cell cycle arrest similar to knockdown of IKKα in prostate cancer cells. Studies in xenograft mouse model indicate that apigenin feeding suppresses tumor growth, lowers proliferation and enhances apoptosis. These effects correlated with inhibition of p-IKKα, NF-ĸB/p65, proliferating cell nuclear antigen and increase in cleaved caspase 3 expression in a dose-dependent manner. Overall, our results suggest that inhibition of cell proliferation, invasiveness and decrease in tumor growth by apigenin are mediated by its ability to suppress IKKα and downstream targets affecting NF-ĸB signaling pathways.


Seroepidemiology of toxoplasmosis in pregnant women and detection of infection acquired during pregnancy in Cotonou, Benin.
Assessing the prevalence of toxoplasmosis in pregnant women and the associated risk factors is the first step in defining policy for the prevention of congenital toxoplasmosis in a given population. An epidemiological study was conducted during prenatal consultations at the CHU-MEL of Cotonou (Benin) between September 2018 and April 2021 and recruited 549 pregnant women to determine the seroprevalence and potential factors associated with Toxoplasma gondii infection. Toxoplasma gondii IgG/IgM antibodies were detected using an enzyme-linked fluorescence assay (ELFA) technique, an IgG avidity test and an IgG/IgM comparative Western blot to diagnose the maternal toxoplasmosis serological status, the possibility of an infection acquired during pregnancy and congenital infection, respectively. Concomitantly, the participants answered a questionnaire investigating potential risk factors. Toxoplasmosis seroprevalence was estimated at 44.4% (95% CI 40.3-48.6) and the factors significantly associated with T. gondii seropositivity were: age over 30 years, multigravid women and contact with cats. The possibility of an infection acquired during the periconceptional period or the first trimester of pregnancy concerned six women [1.1% (95% CI 0.5-2.0)]. However, due to the low rate of serological controls in seronegative women, a significant proportion of women first tested during the 3rd trimester of pregnancy, and an insufficient sample size, the incidence of primary infection during pregnancy could not be determined. No cases of congenital transmission occurred in the newborns from the suspected cases of primary infection.


A Dual-Function Na2 SO4 Template Directed Formation of Cathode Materials with a High Content of Sulfur Nanodots for Lithium-Sulfur Batteries.
The sulfur content in carbon-sulfur hybrid using the melt-diffusion method is normally lower than 70 wt%, which greatly decreases the energy density of the cathode in lithium-sulfur (Li-S) batteries. Here, a scalable method inspired by the commercialized production of Na2 S is used to prepare a hierarchical porous carbon-sulfur hybrid (denoted HPC-S) with high sulfur content (≈85 wt%). The HPC-S is characterized by the structure of sulfur nanodots naturally embedded in a 3D carbon network. The strategy uses Na2 SO4 as the starting material, which serves not only as the sulfur precursor but also as a salt template for the formation of the 3D carbon network. The HPC-S cathode with such a high sulfur content shows excellent rate performance and cycling stability in Li-S batteries because of the sulfur nanoparticles, the unique carbon framework, and the strong interaction between them. The production method can also be readily scaled up and used in practical Li-S battery applications.


Medical therapy of unstable angina pectoris.
The pathophysiologic mechanisms responsible for the clinical syndrome known as unstable angina pectoris are complex but provide a framework for a rational medical approach to this ischemic condition. The combined use of nitrates, beta-blockers, calcium antagonists, antiplatelet agents, and anticoagulants has been shown to reduce recurrent ischemia, and the latter therapies have reduced the incidence of progression to myocardial infarction and death. A rational risk stratification scheme, which utilizes the presenting symptoms, electrocardiographic, and anatomic information to identify patients for whom additional revascularization procedures are warranted, is presented.


[Prevalence of obesity and its association with dietary patterns: a cohort study among Tibetan pastoralists in Qinghai Province].
Objectives: To explore obesity prevalence and its association with dietary patterns among Tibetan pastoralists during the urbanization transition in Qinghai Province. Methods: Using an open cohort study design, 1 003 subjects were enrolled at baseline in 2018, 599 were followed up, and 1 012 were newly recruited in 2022. A total of 1 913 adults over 18 years were included in the study, and a questionnaire survey and health examination were conducted. Factor analysis was used to identify dietary patterns, and a mixed-effects model was used to analyze the association between dietary patterns and obesity. Results: From 2018 to 2022, the prevalence rates of overweight, obesity, and central obesity were 27.6%, 33.8%, and 54.6%, respectively. Age-sex-standardized prevalence of obesity and central obesity increased. Three dietary patterns were identified: the modern pattern was characterized by frequent consumption of pork, poultry, processed meat, fresh fruits, sugary drinks, salty snacks, etcetera; the urban pattern was characterized by frequent consumption of refined carbohydrates, beef and mutton, vegetables and eggs, etcetera; and pastoral pattern featured frequent consumption of tsamba, Tibetan cheese, buttered/milk tea, and whole-fat dairy products. After adjusting for demographic characteristics, socioeconomic status, and lifestyle factors, compared with the T1, subjects in the T3 of urban pattern scores were more likely to be overweight (OR=2.09, 95%CI: 1.10-3.95) and overweight/obese (OR=1.23, 95%CI: 1.00-1.51), whereas those in the T3 of pastoral pattern scores had a lower risk of overweight (OR=0.45, 95%CI: 0.24-0.84), obesity (OR=0.81, 95%CI: 0.69-0.95), overweight/obesity (OR=0.75, 95%CI: 0.61-0.91) and central obesity (OR=0.58, 95%CI: 0.38-0.89). Conclusions: Prevalence of obesity and central obesity was high among Tibetan pastoralists during the urbanization transition. Urban dietary pattern was a risk factor for overweight and overweight/obesity, whereas pastoral dietary pattern was a protective factor for overweight, obesity, overweight/obesity, and central obesity. Tailored interventions are needed to improve local people's health.


Understanding barriers to hepatitis C virus care and stigmatization from a social perspective.
A large body of literature emphasizes the relationship between stigma and adverse health outcomes and health access measures. For people living with hepatitis C virus (HCV), stigma is a defining feature given the association of HCV with the socially demonized practice of injection drug use. However, there is little literature that specifically examines stigma as a barrier to HCV care and treatment. This review argues that the relationship between the person living with HCV and their health worker can work to ameliorate the effects of stigma. We draw on an emerging literature that examines the positive association between a patient's "trust" in their health worker and outcomes such as increased healthcare utilization and reduced risk behaviors. We investigate a growing body of health services research that acknowledges the importance of stigma and demonstrates ways to build positive, enabling relationships between patient, health worker, and health setting.


Citizens, Patients and Policy: A Challenge for Australia's National Electronic Health Record.
Australia will implement a personally controlled electronic health record (PCEHR) over the next three to five years. Development of an e-health policy framework to support this initiative has involved healthcare providers and patients, but the discussion appears to have bypassed non-patient citizens. There is a risk that this omission may result in difficulties with implementation and uptake of the new system.


Spatiotemporal analysis of indigenous and imported dengue fever cases in Guangdong province, China.
Dengue fever has been a major public health concern in China since it re-emerged in Guangdong province in 1978. This study aimed to explore spatiotemporal characteristics of dengue fever cases for both indigenous and imported cases during recent years in Guangdong province, so as to identify high-risk areas of the province and thereby help plan resource allocation for dengue interventions. Notifiable cases of dengue fever were collected from all 123 counties of Guangdong province from 2005 to 2010. Descriptive temporal and spatial analysis were conducted, including plotting of seasonal distribution of cases, and creating choropleth maps of cumulative incidence by county. The space-time scan statistic was used to determine space-time clusters of dengue fever cases at the county level, and a geographical information system was used to visualize the location of the clusters. Analysis were stratified by imported and indigenous origin. 1658 dengue fever cases were recorded in Guangdong province during the study period, including 94 imported cases and 1564 indigenous cases. Both imported and indigenous cases occurred more frequently in autumn. The areas affected by the indigenous and imported cases presented a geographically expanding trend over the study period. The results showed that the most likely cluster of imported cases (relative risk = 7.52, p < 0.001) and indigenous cases (relative risk = 153.56, p < 0.001) occurred in the Pearl River Delta Area; while a secondary cluster of indigenous cases occurred in one district of the Chao Shan Area (relative risk = 471.25, p < 0.001). This study demonstrated that the geographic range of imported and indigenous dengue fever cases has expanded over recent years, and cases were significantly clustered in two heavily urbanised areas of Guangdong province. This provides the foundation for further investigation of risk factors and interventions in these high-risk areas.


Stochastic modeling of gene positive autoregulation networks involving signal molecules.
Positive autoregulation in gene regulation networks has been shown in the past to exhibit stochastic behavior, including stochastic bistability, in which an initially uniform cell population develops into two distinct subpopulations. However, positive autoregulation is often mediated by signal molecules, which have not been considered in prior stochastic analysis of these networks. Here we propose both a full model of such a network that includes a signal molecule, and a simplified model in which the signal molecules have been eliminated through the use of two simplifications. The simplified model is amenable to direct mathematical analysis that shows that stochastic bistability is possible. We use stochastic Petri networks for simulating both types of models. The simulation results show that 1), the stochastic behavior of the two models is similar; and 2), that the analytical steady-state distribution of the simplified model matches well the transient results at times equal to that of a cell generation. A discussion of the simplifications we used in the context of the results indicates the importance of the signal molecule number as a factor determining the presence of bistability. This is further supported from a deterministic steady-state analysis of the full model that is shown to be a useful indicator of potential stochastic bistability. We use the regulation of SdiA in Escherichia coli as an example, due to the importance of this protein and of the signal molecule, a bacterial autoinducer, that is involved. However, the use of kinetic parameter values representing typical cellular activities make the conclusions applicable to other signal-mediated positive autoregulation networks as well.


Structural dependence of silver nanowires on polyvinyl pyrrolidone (PVP) chain length.
The effect of the chain length of polyvinyl pyrrolidone (PVP) on the structures of silver nanowires (AgNWs) is explored in this study. It was found in the experiments that PVP, when serving as a capping agent, has a great impact on the morphology and structure of AgNWs. By means of a series of experiments and the inquiry of the growth mechanism, the critical minimum PVP chain length for the successful formation of uniform nanowires was discovered, below which only nanoparticles or short nanorods can be obtained. Surprisingly, a core-shell structure of a nanowire with a polycrystal was observed when PVP with a very long chain length was employed in the processing.


Tubercular Nodular Episcleritis: A Case Report.
Tuberculosis (TB) is an infectious disease caused by the acid-fast bacillus Mycobacterium tuberculosis and is an important cause of death worldwide. Tuberculosis most commonly affects the lungs, but has many extrapulmonary manifestations as well, including intraocular involvement. Tubercular nodular episcleritis is a very rare presentation and no such case in an adult male has been reported in the literature. Herein, we present the very first case of tubercular nodular episcleritis in a 30-year-old Indian male.


Performance of statistical methods for meta-analysis when true study effects are non-normally distributed: A simulation study.
Meta-analysis (MA) is a statistical methodology that combines the results of several independent studies considered by the analyst to be 'combinable'. The simplest approach, the fixed-effects (FE) model, assumes the true effect to be the same in all studies, while the random-effects (RE) family of models allows the true effect to vary across studies. However, all methods are only correct asymptotically, while some RE models assume that the true effects are normally distributed. In practice, MA methods are frequently applied when study numbers are small and the normality of the effect distribution unknown or unlikely. In this article, we discuss the performance of the FE approach and seven frequentist RE MA methods: DerSimonian-Laird, Q-based, maximum likelihood, profile likelihood, Biggerstaff-Tweedie, Sidik-Jonkman and Follmann-Proschan. We covered numerous scenarios by varying the MA sizes (small to moderate), the degree of heterogeneity (zero to very large) and the distribution of the effect sizes (normal, skew-normal and 'extremely' non-normal). Performance was evaluated in terms of coverage (Type I error), power (Type II error) and overall effect estimation (accuracy of point estimates and error intervals).


Anemia in men with advanced prostate cancer: incidence, etiology, and treatment.
Anemia associated with advanced prostate cancer is a common occurrence. This article reviews the incidence and examines the various causes of this condition, including androgen deprivation, nutritional decline, bone marrow infiltration, treatment-related toxicity, and the chronic inflammatory state. Treatment of anemia in men with advanced prostate cancer is also discussed. In patients with limited bone marrow reserve, blood transfusions may be the only effective treatment.


A Study of 24 Patients with Colistin-Resistant Gram-negative Isolates in a Tertiary Care Hospital in South India.
As the use of colistin to treat carbapenem-resistant Gram-negative infections increases, colistin resistance is being increasingly reported in Indian hospitals. Retrospective chart review of clinical data from patients with colistin-resistant isolates (minimum inhibitory concentration >2 mcg/ml). Clinical profile, outcome, and antibiotics that were used for treatment were analyzed. Twenty-four colistin-resistant isolates were reported over 18 months (January 2014-June 2015). A history of previous hospitalization within 3 months was present in all the patients. An invasive device was used in 22 (91.67%) patients. Urine was the most common source of the isolate, followed by blood and respiratory samples. Klebsiella pneumoniae constituted 87.5% of all isolates. Sixteen (66.6%) were considered to have true infection, whereas eight (33.3%) were considered to represent colonization. Susceptibility of these isolates to other drugs tested was tigecycline in 75%, chloramphenicol 62.5%, amikacin 29.17%, co-trimoxazole 12.5%, and fosfomycin (sensitive in all 4 isolates tested). Antibiotics that were used for treatment were combinations among the following antimicrobials-tigecycline, chloramphenicol, fosfomycin, amikacin, ciprofloxacin, co-trimoxazole, and sulbactam. Among eight patients who were considered to have colonization, there were no deaths. Bacteremic patients had a significantly higher risk of death compared to all nonbacteremic patients (P = 0.014). Colistin resistance among Gram-negative bacteria, especially K. pneumoniae, is emerging in Indian hospitals. At least one-third of isolates represented colonization only rather than true infection and did not require treatment. Among patients with true infection, only 25% had a satisfactory outcome and survived to discharge. Fosfomycin, tigecycline, and chloramphenicol may be options for combination therapy.


Expression of rat NADPH-cytochrome P-450 reductase cDNA in Saccharomyces cerevisiae.
A full-length cDNA for rat NADPH-cytochrome P-450 reductase was cloned by the procedure of Okayama and Berg (1982) from hepatic poly(A)RNA prepared from phenobarbital-induced rats. Both cDNA and amino acid sequences agreed with the sequences reported by Porter and Kasper (1985) except for four single base differences. Three expression plasmids were constructed by insertion of the reductase cDNA between yeast alcohol dehydrogenase I (ADH) promoter and terminator regions. Plasmids pARF1 and pTRF2 were constructed with slightly different lengths between the ADH promoter and the initiation codon; on introduction into Saccharomyces cerevisiae AH22 cells, they synthesized about 1 X 10(3) and 5 X 10(3) reductase protein molecules per cell, respectively. A third plasmid, pARM1, containing a cytochrome P-450MC cDNA expression unit located between two reductase cDNA expression units synthesized 4 X 10(5) cytochrome P-450MC hemoprotein and 1 X 10(4) reductase protein molecules per cell. The cellular extracts of the AH22/pARM1 strain, which synthesized both rat enzymes, showed higher cytochrome c reductase and cytochrome P-450MC-dependent 7-ethoxycoumarin O-deethylation activities as compared to extracts of the AH22/pAMC1 strain, which synthesized only rat cytochrome P-450MC. 7-Ethoxycoumarin O-deethylation activity in the cellular extract of AH22/pARM1 strain was partly inhibited by the addition of anti-rat reductase IgG. In addition, whole AH22/pARM1 cells exhibited higher monooxygenase activity toward acetanilide and 7-ethoxycoumarin than control AH22/pAMC1 cells. These results indicated that a functional electron-transport chain consisting of rat NADPH-cytochrome P-450 reductase and rat cytochrome P-450MC was constructed in S. cerevisiae cells.


Longitudinal radiographic study of crestal bone levels adjacent to non-submerged dental implants.
To investigate changes in alveolar crestal bone levels adjacent to dental implants prior to and after functional loading, dental radiographs of 103 implants from consecutively treated patients were taken at four time-points: immediately after surgical insertion, at 3-6 months after surgery, at 12 months, and at 24 months after surgery. A computer-assisted method was used to measure the percent of bone change (%BC) relative to the shoulder-apex length of the implants at mesial and distal sites. Differences in the mean rates of %BC between the pre-loading period (3-6 months post-surgery) and the post-loading periods PLP1 and PLP2 (6-12 months and 12-24 months post-surgery, respectively) were evaluated. Rates of % BC during PRE, PLP1, and PLP2 were also determined for locations (maxilla or mandible) and types (screw or press-fit). Significantly higher rates of % bone loss per month were found for all implants during PRE compared with PLP1 and PLP2, and during PLP1 compared with PLP2. During PRE, maxillary implants had a significantly higher rate of bone loss compared with mandibular implants. During PLP1, mandibular implants showed some further loss, whereas maxillary implants exhibited a small but significant gain. No significant difference was found during PLP2. Bone loss adjacent to press-fit implants was significantly higher than that adjacent to the screw type during PRE, while no difference was found during the post-loading periods.


Tailored surface-enhanced Raman nanopillar arrays fabricated by laser-assisted replication for biomolecular detection using organic semiconductor lasers.
Organic semiconductor distributed feedback (DFB) lasers are of interest as external or chip-integrated excitation sources in the visible spectral range for miniaturized Raman-on-chip biomolecular detection systems. However, the inherently limited excitation power of such lasers as well as oftentimes low analyte concentrations requires efficient Raman detection schemes. We present an approach using surface-enhanced Raman scattering (SERS) substrates, which has the potential to significantly improve the sensitivity of on-chip Raman detection systems. Instead of lithographically fabricated Au/Ag-coated periodic nanostructures on Si/SiO2 wafers, which can provide large SERS enhancements but are expensive and time-consuming to fabricate, we use low-cost and large-area SERS substrates made via laser-assisted nanoreplication. These substrates comprise gold-coated cyclic olefin copolymer (COC) nanopillar arrays, which show an estimated SERS enhancement factor of up to ∼ 10(7). The effect of the nanopillar diameter (60-260 nm) and interpillar spacing (10-190 nm) on the local electromagnetic field enhancement is studied by finite-difference-time-domain (FDTD) modeling. The favorable SERS detection capability of this setup is verified by using rhodamine 6G and adenosine as analytes and an organic semiconductor DFB laser with an emission wavelength of 631.4 nm as the external fiber-coupled excitation source.


[Neurological crisis in type 1 hereditary thyrosinemia].
Type 1 hereditary thyrosinemia is a recessive autosomic disease arising from a deficit of fumarylacetoacetate hydrolase enzyme. Neurological changes are similar to those of intermittent acute porphyria, with no biological warning markers nor treatment other than that of symptoms. We present 2 patients suffering several sudden crises of peripheral neuropathy, with other signs of "neurological crisis" occurring at times. We conclude that neurological signs of the diseases are frequent and severe and that, in our limited experience, early liver transplant is the only way of preventing them.


Alexithymia in schizophrenia.
Changes in emotional and social behavior are considered to be amongst the most common and debilitating consequences of schizophrenia. However, little is known of the effects of schizophrenia on alexithymia, which refers to impairment in aspects of understanding emotions. In the current study, participants with schizophrenia (n = 29) and nonclinical controls (n = 30) completed self-report and performance-based measures of this construct, in addition to measures of cognitive functioning, clinical symptomatology, and negative affect. The results indicated that individuals with schizophrenia showed increased alexithymia as indexed by the performance task, with these difficulties related to cognitive functioning, and the specific clinical symptom of alogia. However, although the correlation between self-reported alexithymia and negative affect in the schizophrenia group was congruent with prior empirical research and theory, there were no group differences in perceived levels of alexithymia. It is suggested that alexithymia may not be affected per se in schizophrenia (as indicated by the lack of group differences on the self-report measure of this construct), but that schizophrenia-related difficulties do emerge in contexts where cognitive demands are incremented.


[The ethical challenges of health policies in Benin].
Over the past two decades, new challenges in public health have sparked renewed interest in health policy ethics in the world. But in Africa in general and Benin in particular, public health ethics as an approach of intervention, remains embryonic. By aiming the well-being of the population, the health policy in Benin is implicitly ethics. But it is too focused on medical logic and operates at the expense of ethics-oriented approach, clearly expressed in terms of strategies assessed by an independent body before, during and after their implementation, based on the relevance, the efficiency, the equity, the transparency, the social justice... In a context of lack of access to information sources or credible knowledge, health policies recipients do not seem able to exercise their autonomy.


Clinical parameters in T1N0M0 lower lip squamous cell carcinoma.
This retrospective study was carried out to asses the clinical outcome of T1 (i.e., tumor 2 cm or less at greatest dimension) squamous cell carcinoma of the lower lip (SCCLL) and verify the impact of some clinical parameters on prognosis. Fifty-seven patients with histologically proven T1 SCCLL were analyzed. Fifty-two patients were never treated before admission, whereas five (8.8%) had a second radical resection of the primary tumor location; none had neck nodes (i.e., N0) or distant metastasis (i.e., M0). The global disease-specific survival rate at 32 months was 100%, irrespective of grading and type of surgery, and thus no differences were statistically detected. Therefore, we concluded that radical tumor resection is a viable procedure for T1 SCCLL, irrespectively of grading. In addition, a second surgery on the primary tumor location is possible and has effectiveness on survival. Finally, neck dissection is not necessary in cases of T1 SCCLL.


Effector mechanisms of human monocyte-mediated tumor cytotoxicity in vitro: parameters of induction of cytotoxins from peripheral blood monocytes isolated by counterflow elutriation.
Human peripheral blood monocytes, isolated in high purity by centrifugal counterflow elutriation from normal donors, were stimulated in vitro to release cell toxins, herein termed human monocyte toxin(s) (HMT). Bacterial lipopolysaccharide, the lipophilic 6-O-stearoyl derivative of muramyl dipeptide, and 4 beta-phorbol-12 beta-myristate-13 alpha-acetate served as effective induction signals. Induction involved a sequence of transcription, translation, and secretion, all necessary for HMT synthesis and release into the supernatant as determined by blocking of these functions with the drugs actinomycin D, cycloheximide, and monensin, respectively; HMT levels reached a peak within 4-6 h and thereafter declined. The levels of HMT produced varied considerably from donor to donor; one parameter causing this variability appeared to be the plateletapheresis history of the donor. Monocytes from donors subjected to pheresis for the first time were responsive to induction signals immediately after adherence and could not be brought to a higher state of priming for HMT production by further in vitro culture for up to 9 days, with or without recombinant human gamma-interferon. In contrast, monocytes from donors who had recently undergone pheresis (up to 1 wk earlier) were poorly responsive initially to triggering with lipopolysaccharide; however, these cells could be brought to a highly primed state for HMT production by a combination of culture in vitro for several days and a subsequent 24-h exposure to recombinant gamma-interferon (0.1-1.0 units/ml). These primed cells could then be effectively triggered by lipopolysaccharide to release HMT. HMT was found to be cytotoxic (cytostatic/cytolytic) for human and murine tumor cells in vitro.


Effect of clindamycin on neutrophil killing of gram-negative periodontal bacteria.
Periodontal diseases are infections of the tissues supporting the dentition. Recognition that relatively specific microfloras are associated with distinct clinical forms of periodontal disease has prompted the use of antimicrobial agents as adjuncts in periodontal therapy. Clindamycin is one of several antibiotics known to concentrate in bioactive form in neutrophils and to potentiate phagocyte bactericidal activity against certain bacteria. Neutrophils appear to play a key role in host defense against periodontopathic gram-negative bacteria. In the present study, we evaluated the effect of preincubation of neutrophils with therapeutically achievable concentrations of clindamycin upon subsequent in vitro bactericidal activity against three species of gram-negative periodontal bacteria, including Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga ochracea. In each instance, clindamycin neither enhanced nor inhibited the kinetics of bactericidal activity at low bacterium-neutrophil multiplicities. Further, this antibiotic had no demonstrable effect upon neutrophil bactericidal capacity, as assessed at bacterium-neutrophil ratios as high as 50:1. Our results indicate that clindamycin does not potentiate neutrophil bactericidal activity against the species of gram-negative periodontal organisms tested.


Use of the Fluocinolone Acetonide Intravitreal Implant for the Treatment of Noninfectious Posterior Uveitis: 3-Year Results of a Randomized Clinical Trial in a Predominantly Asian Population.
The fluocinolone acetonide (FA) intravitreal implant 0.59 mg (Retisert(®), Bausch + Lomb, Rochester, NY, USA) provides sustained release of FA directly to the vitreous cavity over a prolonged period of time. The purpose of this study was to evaluate the safety and efficacy of a 0.59- and 2.1-mg FA intravitreal implant in patients with noninfectious posterior uveitis. A prospective, multicenter, randomized, double-masked, dose-controlled study was performed. Patients were randomized to the 0.59- or 2.1-mg FA implant surgically placed in the vitreous cavity through a pars plana incision and were evaluated at visits through 3 years. Patients with bilateral disease had the more severely affected eye implanted. Outcomes included uveitis recurrence rate, best-corrected visual acuity (BCVA), use of adjunctive therapy, and safety. A total of 239 patients, predominantly Asian, were implanted (n = 117, 0.59-mg implant; n = 122, 2.1-mg implant). Approximately 80% of patients had bilateral disease. Recurrence rates for implanted eyes decreased from 42.3% during the 1-year pre-implantation period to 25.9% during the 3-year post-implantation period (P = 0.0003) and increased for nonimplanted fellow eyes from 19.8 to 59.7% (P < 0.0001). More implanted eyes gained ≥3 lines of BCVA compared to nonimplanted fellow eyes (P ≤ 0.0046); and implanted eyes required less adjunctive systemic therapy and fewer periocular injections (P < 0.0001). Elevations of intraocular pressure (≥10 mm Hg) were frequent in implanted eyes (67.8%, 0.59-mg implant; 71.3%, 2.1-mg implant); nearly all (94.9%) phakic implanted eyes required cataract surgery. The FA intravitreal implant significantly reduced uveitis recurrence rates and led to improvements in visual acuity and reductions in adjunctive therapy. Lens clarity and intraocular pressure require monitoring.


Stereoacuity in the periphery is limited by internal noise.
It is well-established that depth discrimination is finer in the fovea than the periphery. Here, we study the decline in depth discrimination thresholds with distance from the fovea using an equivalent noise analysis to separate the contributions of internal noise and sampling efficiency. Observers discriminated the mean depth of patches of "dead leaves" composed of ellipses varying in size, orientation, and luminance at varying levels of disparity noise between 0.05 and 13.56 arcmin and visual field locations between 0° and 9° eccentricity. At low levels of disparity noise, depth discrimination thresholds were lower in the fovea than in the periphery. At higher noise levels (above 3.39 arcmin), thresholds converged, and there was little difference between foveal and peripheral depth discrimination. The parameters estimated from the equivalent noise model indicate that an increase in internal noise is the limiting factor in peripheral depth discrimination with no decline in sampling efficiency. Sampling efficiency was uniformly low across the visual field. The results indicate that a loss of precision of local disparity estimates early in visual processing limits fine depth discrimination in the periphery.


Role of dominant versus non-dominant hand position during uninterrupted chest compression CPR by novice rescuers: a randomized double-blind crossover study.
Previous research has suggested improved quality of chest compressions when the dominant hand was in contact with the sternum. However, the study was in health care professionals and during conventional chest compression-ventilation CPR. The aim of this study was to test the hypothesis, in null form, that the quality of external chest compressions (ECC) in novice rescuers during 5min of uninterrupted chest compression CPR (UCC-CPR) is independent of the hand in contact with the sternum. Confirmation of the hypothesis would allow the use of either hand by the novice rescuers during UCC-CPR. Fifty-nine first year public heath students participated in this randomised double-blind crossover study. After completion of a standard adult BLS course, they performed single rescuer adult UCC-CPR for 5 min on a recording Resusci Anne. One week later they changed the hand of contact with the sternum while performing ECC. The quality of ECC was recorded by the skill meter for the dominant and non-dominant hand during 5 min ECC. The total number of correct chest compressions in the dominant hand group (DH), mean 183+/-152, was not statistically different from the non-dominant hand group (NH), mean 152+/-135 (P=0.09). The number of ECC with inadequate depth in the DH group, mean 197+/-174 and NH group, mean 196+/-173 were comparable (P=0.1). The incidence of ECC exceeding the recommended depth in the DH group, mean 51+/-110 and NH group, mean 32+/-75 were comparable (P=0.1). Although there is a trend to increased incidence of correct chest compressions with positioning the dominant hand in contact with the sternum, it does not reach statistical significance during UCC-CPR by the novice rescuers for 5 min.