[A comparative assessment of the results of end-to-end and end-to-side anastomoses in arterial reconstructions of the aorto-iliac segment].
The aim of this study to evaluate comparatively the early and long-term outcome of end-to-end (E-E) vs end-to-side (E-S) anastomoses in arterial reconstructions for aorto-iliac occlusive disease (AIOD). The early and late postoperative results of 150 arterial reconstructions for AIOD are evaluated, covering the period 1990 through 1993. All patients present AIOD II-IV clinical stage, randomized in three groups according to type of arterial reconstruction/anastomosis. Group A consists of 60 patients (pts) undergoing aortobifemoral/biprofunda bypass grafting (Ao-2F/P), with all proximal and distal anastomoses performed in the classical E-S fashion. Group B (40 pts)--Ao-2F/P replacement grafting (RG), with all proximal and distal anastomoses performed E-E, and simultaneous reconstruction of at least one hypogastric artery and/or inferior mesenteric artery (AMI). Group C (50 pts)--Ao2F/P or unilateral aorto-femoral/profunda bypass grafting (Ao-F/P) with EO-S proximal and E-E all distal anastomoses. The aforementioned groups are then compared to 30 pts (group O) free of vascular diseases. All patients are subjected to 18 months average follow-up study (range 6 to 32 months). The postoperative effect, including evaluation of the complete and regional hemodynamics by clinical and Doppler ultrasonography (DS) methods, is assayed. In some cases control angiography is performed as well. The complication rate--restenoses, rethromboses, false aneurysms and amputations--is estimated in percents. Statistically significant higher restenosis and rethrombosis rate is found in group A pts (56 per cent), compared to B (20 per cent) and C (25 per cent) which correlates with the early postoperative results, referred to in the authors' previous study.(ABSTRACT TRUNCATED AT 250 WORDS)


Classification of environmental pollutants for global mobility potential.
The environmental behaviour of global organic contaminants is known to be controlled by the physico-chemical properties of the compounds themselves. The principal component analysis of some physico-chemical properties, particularly relevant in determining mobility potential (vapour pressure, Henry's law constant, water solubility, K(OW), K(OA) and melting point) allows a multivariate approach to a ranking of organic pollutants according to their intrinsic tendency towards mobility, and the definition of four a priori mobility classes for screening purposes. Quantitative structure-property relationships (QSPRs) were used to predict missing values for octanol/air partition coefficients. Finally, a classification method employing theoretical molecular descriptors was used to assign studied chemicals to four mobility classes. The proposed approach assesses, directly and simply, a pollutant's inherent tendency towards mobility using only knowledge of the pollutant's molecular structure; the approach is particularly useful for a preliminary screening and the prioritisation of organic pollutants of emerging environmental concern.


A Qualitative Exploration of Nurses' Information-Gathering Behaviors Prior to Decision Support Tool Design.
Large and readily-available clinical datasets combined with improved computational resources have permitted the exploration of many new research and clinical questions. Predictive analytics, especially for adverse events, has surfaced as one promising application of big data, and although statistical results can be highly accurate, little is known about how nurses perceive this new information and how they might act upon it. Within the context of recognizing patients at risk for cardiopulmonary arrest, this study explored the possibility of incorporating predictive analytics into clinical workflows by identifying nurses' current information gathering activities and perceptions of probability-related terms. We used a qualitative description approach for data collection and analysis in order to understand participants' information gathering behaviors and term perceptions in their own words. We conducted one-on-one interviews and a focus group with a total of 10 direct care bedside nurses and 8 charge nurses. Participants collected information from many sources that we categorized as: Patient, Other People, and Technology. The process by which they gathered information was conducted in an inconsistent order and differed by role. Major themes comprised: (a) attempts to find information from additional sources during uncertainty, (b) always being prepared for the worst-case scenario, and (c) the desire to review more detailed predictions. Use of the words probability, risk, and uncertainty were inconsistent. In an effort to successfully incorporate predictive analytics into clinical workflows, we have described nurses' perceived work practices for gathering information related to clinical deterioration and nurses' beliefs related to probability-based information. Findings from our study could guide design and implementation efforts of predictive analytics in the clinical arena.Jeffery AD, Kennedy B, Dietrich MS, Mion LC, Novak LL. A Qualitative Exploration of Nurses' Information-Gathering Behaviors Prior to Decision Support Tool Design. Appl Clin Inform 2017; 8: 763-778 https://doi.org/10.4338/ACI-2017-02-RA-0033.


A protocol for prospective observational study to determine if non-anaemic iron deficiency worsens postoperative outcome in adult patients undergoing elective cardiac surgery: the IDOCS study.
Pre-operative anaemia has been associated independently with worse outcomes after cardiac surgery in adults and is often caused by absolute or functional iron deficiency. Iron deficiency is a continuum ending with anaemia, and therefore it is plausible that pre-operative early or 'non-anaemic' iron deficiency may also be associated with worse outcomes in patients undergoing cardiac surgery. We have designed a prospective, observational study to determine if there is an association between non-anaemic iron deficiency and worse outcomes after cardiac surgery in adults. Patients without anaemia undergoing elective cardiac surgery will be allocated to an iron-deficient and an iron-replete group based on standard pre-operative blood tests (ferritin, transferrin saturation and C-reactive protein). The primary outcome is days alive and at home on postoperative day 30. The key secondary outcomes are days alive and at home on postoperative day 90 and readmission to acute care. Other secondary outcomes include health-related quality of life questionnaires, quality of postoperative recovery, postoperative complications, changes in haemoglobin concentration, and requirement for allogeneic blood products. The planned study sample size is 240 patients per group, which has 83% power to detect a median difference of 1.25 days in the primary outcome. The study commenced in March 2018, and recently completed recruitment, with data audit and cleaning ongoing. This study will be conducted using a rigorous, prospective observational design; it will provide peak bodies and clinicians with high-quality evidence concerning the associations between non-anaemic iron deficiency and patient-centred outcomes after elective cardiac surgery. Our primary and key secondary outcomes are known to have great importance to clinicians and patients alike and align with the recommendations of the StEP-COMPAC group for outcomes in prospective peri-operative research. The definition used for iron deficiency accounts for both absolute and functional iron deficiency and make use of standard pre-operative blood tests to make this determination, easing the transition of results into clinical practice. The study will be conducted in two relatively high-volume centres in a single high-income country. This limits the generalisability of study results to similar centres. Australian and New Zealand Clinical Trials Registry ( ACTRN12618000185268 ). Registered 5 February 2018.


Doing nothing: adults with disabilities with no daily activities and their siblings.
A significant concern of parents and professionals is that adults with intellectual and developmental disabilities will go without regular educational-vocational activities. The authors examined predictors of such inactivity in individuals with intellectual and developmental disabilities, as well as how inactivity related to their sibling's well-being and the sibling relationship. Participants included 796 siblings of adults with intellectual and developmental disabilities who responded to a web-based survey. Nearly 13% of adults with intellectual and developmental disabilities were without daytime activities; these adults had more emotional-behavioral and health problems, were more underserved by the formal service system, and had parents who were less able to provide care. Although siblings of adults without activities reported more depressive symptoms, worse health, and less close sibling relationships, inactivity no longer predicted these problems after controlling for characteristics that predisposed adults with intellectual and developmental disabilities to have no activities.


Locked nailing of spiral humeral fractures with or without radial nerve entrapment.
The experience of locked nailing of spiral humeral fractures and the perioperative conditions of the radial nerve are reported. The nerve is at risk of entrapment after such a fracture, and severe injury may occur during closed nailing. Among 162 humeral fractures treated by locked nailing, there were 21 spiral fractures: 18 acute fractures, and three delayed unions. The distribution of the fractures was two at the middle and 19 at the distal (1/3). Twelve patients had preoperative radial nerve palsy. All fractures excluding one middle fracture were retrograde nailed, and all patients had radial nerve exploration. Thirteen fractures were locked statically, seven were locked distally and had cerclage wiring, and one was locked distally only. Fisher's exact tests showed that the risk of radial nerve entrapment significantly increased in fractures with varus angulation or resulting from high-energy trauma. All the patients achieved fracture union and regained satisfactory joint functions. The author suggests that in external rotational spiral humeral fractures, radial nerve exploration should be done if nerve entrapment is highly suspected, irrespective of the fracture location or nerve palsy. Locked nailing with transfixing screws or cerclage wire could be a reliable treatment method for these fractures.


Autologous and allogeneic mixed lymphocyte reactions in progressive systemic sclerosis.
The autologous and allogeneic mixed lymphocyte reactions (MLR), observed when peripheral blood mononuclear cells from 20 patients with progressive systemic sclerosis were used, were compared with those of age-, sex-, and race-matched normal controls. Such cells were separated by gradient centrifugation of sheep red blood cell (E) rosettes into stimulator (E- or non-T cell) and responder (E + or T cell) populations. The autologous MLR of both the progressive systemic sclerosis and normal peripheral blood mononuclear cells varied widely but there was no statistical difference between the means of each group. In the allogeneic MLR, proliferation between progressive systemic sclerosis non-T cells and normal T cells was significantly less than that of normal non-T cells and progressive systemic sclerosis T cells (P = 0.001). A decreased autologous MLR, while noted with other autoimmune diseases, was lacking in progressive systemic sclerosis. This suggests a different defect. The differences in the allogeneic MLR also suggest that either progressive systemic sclerosis non-T cells were poor stimulators or T cells associated with this disease were better responders when compared with similarly prepared cell populations from normal individuals. The MLR differences could have also resulted from compositional subset alterations or the sharing of a common antigen. HLA-DR5 was found in 9 of the 17 white patients with progressive systemic sclerosis. Although these individuals were evenly distributed as low, medium, and high responders, this finding showed that some progressive systemic sclerosis non-T cells shared a common antigen.


Effective phosphate removal for advanced water treatment using low energy, migration electric-field assisted electrocoagulation.
A migration electric-field assisted electrocoagulation (MEAEC) system was developed to increase phosphate removal from domestic wastewater, with reduced energy consumption, using a titanium charging (inert) electrode and a sacrificial iron anode. In the MEAEC, an electric field was applied between the inert electrode (titanium) and an air cathode to drive migration of phosphate anions towards the sacrificial anode. Current was then applied between the sacrificial anode (Fe or Al mesh) and the air cathode to drive electrocoagulation of phosphate. A MEAEC with the Fe electrode using primary clarifier effluent achieved 98% phosphate removal, producing water with a total phosphorus of 0.3 mg/L with <6 min total treatment time (five cycles; each 10 s inert electrode charging, and 1 min electrocoagulation), at a constant current density of 1 mA/cm2. In the absence of the 10 s charging time, electrocoagulation required 15 min for the same removal. With an aluminum anode and the same phosphorus removal, the MEAEC required 7 cycles (7 min total treatment, 1 min 10 s total charging), while conventional electrocoagulation required 20 min. The energy demand of Fe-MEAEC was only 0.039 kWh/m3 for 98% phosphate removal, which was 35% less than with the Al-MEAEC of 0.06 kWh/m3, and 28% less than that previously obtained using an inert graphite electrode. Analysis of the precipitate showed that a less porous precipitate was obtained with the Al anode than with the Fe anode. The phosphorus in precipitate of Fe-MEAEC was identified as PO43- and HPO42-, while the Fe was present as both Fe2+ and Fe3+. Only HPO42- and Al3+ were identified in the precipitate of the Al-MEAEC. These results indicated that the MEAEC with a titanium inert charging electrode and iron anode could achieve the most efficient phosphate removal with very low energy demands, compared to previous electrochemical approaches.


[Transcriptome analysis of Pichia pastoris in response to ethanol stress].
Effective expression of pIFN-α in recombinant Pichia pastoris was conducted in a 5 L fermentor. Ethanol accumulation during the late glycerol feeding period inhibited heterologous protein expression. Comparative transcriptome analysis was thus performed to compare the gene transcription profiles of Pichia pastoris KM71H in high and low ethanol concentration environments. The results showed that during the glycerol cultivation stage, 545 genes (265 up-regulated and 280 down-regulated) were differentially expressed with ethanol stress. These genes were mainly involved in protein synthesis, energy metabolism, cell cycle and peroxisome metabolism. During the methanol induction stage, 294 genes (171 up-regulated and 123 down-regulated) were differentially expressed, which were mainly related to methanol metabolism, amino acid metabolism and protein synthesis. Ethanol stress increased protein misfolding and reduced structural integrity of ribosome and mitochondria during cultivation stage, and led to the failure of endoplasmic reticulum stress removal and damaged amino acid metabolism during induction stage in Pichia pastoris.


Altitudinal and spatial signature of persistent organic pollutants in soil, lichen, conifer needles, and bark of the southeast Tibetan Plateau: implications for sources and environmental cycling.
The southeast Tibetan Plateau (TP) of China is characterized by mountain-valley topography and is usually the main channel for the warm and humid airstream from South Asia caused by the Indian monsoon. In this study, it is hypothesized that some semivolatile organic pollutants such as organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) can be transported from the densely populated and intensely agricultural Indian Subcontinent via the Indian monsoon and then cold-trapped by the mountains of the southeast TP. Samples of soils, lichens, conifer barks, and needles were collected from five transects to investigate the accumulation patterns of OCPs and PAHs in this region. The OCP concentrations were found to generally increase with increasing altitude in transects 1, 3, and 4, while such trends were insignificant in most cases for PAHs. Total organic carbon/lipid based normalization of concentrations does not strengthen the correlations with altitude in most cases. Chemical concentration ratios in soils of forest areas to clearing sites without forest cover (F/C) showed significantly positive correlation with log K(oa) and negative correlation with log K(aw) of PAHs, suggesting that the role of forests as a filter and forest soil as a final sink are more pronounced for more lipophilic compounds. A lower α-/γ-HCH ratio and higher ratios of DDT/DDE and o,p'-DDT/p,p'-DDT compared with the technical products suggest the usage of lindane (γ-HCH), DDT, and dicofol in neighboring countries. The suitability of using different sample matrices (soil, lichen, conifer bark, and needles) as passive air samplers in remote regions is evaluated.


The decagonal AlCuRh quasicrystal modelled with five atomic surfaces - high-temperature X-ray diffraction data analysis.
Five datasets of high-temperature X-ray diffraction performed upon the decagonal phase of AlCuRh are used to derive the temperature-related structural changes. Two sets of atomic structure refinements are conducted, with four and five atomic surfaces, respectively. The fifth atomic surface emerges as a consequence either of the transition to a tiling with different local isomorphism than the Penrose tiling or of the structure being phason disordered. The correlation of the occupancy of the fifth atomic surface with the thermal dependence of the lattice constants is 80%. In addition, the structural refinement with five atomic surfaces allowed a better agreement with the experimental data to be obtained, compared with the model with four atomic surfaces.


Resistance of paroxysmal nocturnal hemoglobinuria cells to the glycosylphosphatidylinositol-binding toxin aerolysin.
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder caused by a somatic mutation of the PIGA gene. The product of this gene is required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; therefore, the phenotypic hallmark of PNH cells is an absence or marked deficiency of all GPI-anchored proteins. Aerolysin is a toxin secreted by the bacterial pathogen Aeromonas hydrophila and is capable of killing target cells by forming channels in their membranes after binding to GPI-anchored receptors. We found that PNH blood cells (erythrocytes, lymphocytes, and granulocytes), but not blood cells from normals or other hematologic disorders, are resistant to the cytotoxic effects of aerolysin. The percentage of lysis of PNH cells after aerolysin exposure paralleled the percentage of CD59(+) cells in the samples measured by flow cytometry. The kinetics of red blood cell lysis correlated with the type of PNH erythrocytes. PNH type III cells were completely resistant to aerolysin, whereas PNH type II cells displayed intermediate sensitivity. Importantly, the use of aerolysin allowed us to detect PNH populations that could not be detected by standard flow cytometry. Resistance of PNH cells to aerolysin allows for a simple, inexpensive assay for PNH that is sensitive and specific. Aerolysin should also be useful in studying PNH biology.


Nitrogen-Enriched Conjugated Polymer Enabled Metal-Free Carbon Nanozymes with Efficient Oxidase-Like Activity.
Metal-free carbon nanozymes could be promising with the unique features of intrinsic catalytic ability, structure diversity, and strong tolerance to acidic/alkaline media. However, to date, the study of metal-free carbon nanozymes fell far behind metal-based nanomaterials, in which, the majority reported much more peroxidase-like activity than other enzyme-mimicking behavior (e.g., oxidase). Thus, the exploit of high-performance carbon nanozymes is of importance but challenging. In this work, the nitrogen-rich conjugated polymer (Aza-CPs) with rigid network structure is utilized as precursor to yield N-doped carbon material QAU-Z1 in high yield via a direct pyrolysis method. Surprisingly, QAU-Z1 stood out in oxidase-like behavior, which significantly outperformed the control materials GNC-900 and QAU-Z2 with nucleobase or conjugated small molecule as precursor, respectively. More importantly, it is a crucial revelation that the catalytic performance is closely related to the change of zeta potential for carbon nanozyme during the substrate 3,3',5,5'-tetramethylbenzidine oxidation process, as well as its catalytical capacity to O2 , which could be insightful to understand the inherent mechanism. This work not only presents the potential of conjugated polymers in constructing highly efficient carbon nanozyme, but also reveals the vital role of interaction mode between the nanozyme and substrate in the catalytic performance.


Review of Intravenous Lipid Emulsion Therapy.
Intravenous fat emulsion (IVFE) is an important source of calories and essential fatty acids for patients receiving parenteral nutrition (PN). Administered as an individual infusion or combined with PN, the fats provided by IVFE are vital for cellular structural function and metabolism. The affinity of some medications to lipids has led to the use of IVFE as a treatment for any lipophilic drug overdose. This article will explain the available formulations of IVFE, administration, and maintenance issues, as well as the risks and benefits for various applications.


The relationship between medical impairments and arithmetic development in children with cerebral palsy.
Arithmetic ability was tested in children with cerebral palsy without severe intellectual impairment (verbal IQ >or= 70) attending special (n = 41) or mainstream education (n = 16) as well as control children in mainstream education (n = 16) throughout first and second grade. Children with cerebral palsy in special education did not appear to have fully automatized arithmetic facts by the end of second grade. Their lower accuracy and consistently slower (verbal) response times raise important concerns for their future arithmetic development. Differences in arithmetic performance between children with cerebral palsy in special or mainstream education were not related to localization of cerebral palsy or to gross motor impairment. Rather, lower accuracy and slower verbal responses were related to differences in nonverbal intelligence and the presence of epilepsy. Left-hand impairment was related to slower verbal responses but not to lower accuracy.


Pickering Emulsions Stabilized by an Alkyl Chain-Bridged Lignin-Based Polymer without Additives and Organic Solvents.
In this article, an alkyl chain-bridged lignin polymer was prepared from our previous study. Then, an ultrafiltration method was used to classify the polymer into three fractions with a narrow molecular weight distribution. These three fractions were used to prepare novel Pickering emulsions without additives and organic solvents. The results show that the Pickering emulsion with fraction-3 of the highest molecular weight shows the best result compared with the other two fractions, and the Pickering emulsion is formed of droplets. The influence of oil-water ratios and fraction-3 dosages on the Pickering emulsions was also investigated in our study. The results show that the diameter of the droplets increases with increasing oil proportion and decreases with increasing lignin-based polymer dose. UV spectroscopy shows that the prepared Pickering emulsions have strong absorption properties from 300 to 800 nm, which will be expected to be applied in cosmetics, especially in sunscreen creams. Finally, the Pickering emulsion was also used to deliver ibuprofen, and the results showed that the embedding rate was as high as 10%. It is suggested that the Pickering emulsion stabilized by lignin-based polymers can be used for drug delivery. This will provide a potential research idea for high-value applications of lignin.


[Fluconazole in the treatment of vaginitis caused by Candida albicans].
The authors verified the local activity and tolerance of the antimycotic drug Fluconazole in 125 cases of women suffering from clinical diagnosed vulvovaginitis caused by Candida albicans. Results were positive with regard to the efficacy and safety of the treatment.


Computer-Assisted Cognitive-Behavior Therapy for Depression in Primary Care: Systematic Review and Meta-Analysis.
To examine evidence for the effectiveness of computer-assisted cognitive-behavior therapy (CCBT) for depression in primary care and assess the impact of therapist-supported CCBT versus self-guided CCBT. A search for randomized studies of CCBT compared to control groups for treating depression in primary care settings was conducted using Ovid MEDLINE, PsycINFO, PubMed, and Scopus. We extracted the following information from the studies that met inclusion criteria: mean depression rating scale scores before and after treatment, number of patients, type of control group and CCBT program, therapist support time and method of support, and treatment completion rate. Meta-analyses compared differences between posttreatment mean scores in each condition, as well as mean scores at follow-up. Study quality and possible bias also were assessed. Eight studies of CCBT for depression in primary care met inclusion criteria. The overall effect size was g = 0.258, indicating a small but significant advantage for CCBT over control conditions. Therapist support was provided in 4 of the 8 studies. The effect size for therapist-supported CCBT was g = 0.372-a moderate effect. However, the effect size for self-guided CCBT was g = 0.038, indicating little effect. Implementation of therapist-supported CCBT in primary care settings could enhance treatment efficiency, reduce cost, and improve access to effective treatment for depression. However, evidence to date suggests that self-guided CCBT offers no benefits over usual primary care.


Parenting Stress and Social Style in Mothers and Fathers of Children with Autism Spectrum Disorder: A Cross-Cultural Investigation in Italy and Japan.
Parents of children with autism spectrum disorder (ASD) face unique challenges, which may affect parenting functioning. However, little is known about gender and cultural variations in parenting stress and styles in these families. The aims of this study were to investigate: (1a) the differences in parenting stress and (1b) social style between Italian and Japanese mothers and fathers of children with ASD; (2) the predictive role of culture, sociodemographic, and child's characteristics on parenting stress; (3) the predictors of the social parenting style, including parenting stress dimensions. The study involved 92 Italians and 89 Japanese parents of school-age children (5-12 years) with ASD who completed the Parenting Stress Index and the Parenting Style Questionnaire. Results revealed that Japanese parents showed higher parenting stress and less engagement in social style than Italians. Across cultures, mothers used more social style than fathers. Being Japanese and having a child with greater ASD severity predicted higher levels of parenting stress. We also found that country, parent's gender, and stress related to the dysfunctional interaction were significant predictors of parenting social style. Our findings highlight the importance of a cross-cultural approach to better understand the experiences and needs of mothers and fathers of children with ASD.


Prediction of vibrational spectra of polysaccharides-simulated IR spectrum of cellulose based on density functional theory (DFT).
The continuing developments of electronic structure methods may provide insight into the vibrational spectroscopy of polysaccharides, which was not accessible to older works on this subject. The present work shows for the first time how main features of cellulose infrared spectra can be predicted and assigned using simple single chain models of cellulose combined with density functional theory prediction of their vibrational properties. The results provide a more informed basis for assigning cellulose IR bands and may resolve some of the challenges associated with the molecular origin of "marker" bands, which are commonly used to measure properties such as crystallinity or crystalline forms. The theoretical approach can be seen as a first-order approximation, which can be further improved.


Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: absence of structural mutations in five patients with Brody disease.
Sarcolipin (SLN) is a low-molecular-weight protein that copurifies with the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase (SERCA1). Genomic DNA and cDNA encoding human sarcolipin (SLN) were isolated and characterized and the SLN gene was mapped to chromosome 11q22-q23. Human, rabbit, and mouse cDNAs encode a protein of 31 amino acids. Homology of SLN with phospholamban (PLN) suggests that the first 7 hydrophilic amino acids are cytoplasmic, the next 19 hydrophobic amino acids form a single transmembrane helix, and the last 5 hydrophilic amino acids are lumenal. The cytoplasmic and transmembrane sequences are not well conserved among the three species, but the lumenal sequence is highly conserved. Like SERCA1, SLN is highly expressed in rabbit fast-twitch skeletal muscle, but it is expressed to a lower extent in slow-twitch muscle and to an even lower extent in cardiac muscle, where SERCA2a and PLN are highly expressed. It is expressed in only trace amounts in pancreas and prostate. SLN and PLN genes resemble each other in having two small exons, with their entire coding sequences lying in exon 2 and a large intron separating the two segments. Brody disease is an inherited disorder of skeletal muscle function, characterized by exercise-induced impairment of muscle relaxation. Mutations in the ATP2A1 gene encoding SERCA1 have been associated with the autosomal recessive inheritance of Brody disease in three families, but not with autosomal dominant inheritance of the disease. A search for mutations in the SLN gene in five Brody families, four of which were not linked to ATP2A1, did not reveal any alterations in coding, splice junction or promoter sequences. The homozygous deletion of C438 in the coding sequence of ATP2A1 in Brody disease family 3, leading to a frameshift and truncation following Pro147 in SERCA1, is the fourth ATP2A1 mutation to be associated with autosomal recessive Brody disease.


[Molecular characterization of Japanese encephalitis virus isolated from Gansu province in 2008].
To sequence PrM and E gene of the Japanese encephalitis virus isolated from Gansu province in 2008 and analysis the genotype of new JEV isolates and the molecular characterization of E gene. Computer software was used to analyze nucleic acid sequence and deduced amino acid sequence, and draw phylogenetic trees, including ClustalX2.09, MegAlign and Mega4. The six JEV strains were clustered in genotype I. 87.5%-87.9% identity in nucleotide sequence and 96.8%-97.2% identity in amino acid sequence were found in E gene when compared with the vaccine strain SA14-14-2. Eleven common amino acid differences were observed in E protein between new isolates and the vaccine strain. Genotype I JEVs were isolated from mosquitoes collected in Gansu province. The amino acid difference occurred in sites that were not the key ones affecting the antigenic of JEV.


[Distribution of HIV-1 subtypes in Guangxi Zhuang Autonomous Region, 2008-2009].
To understand the distribution of HIV-1 subtypes in Guangxi Zhuang Autonomous Region. 294 participants who were infected by HIV-1 in 2008 - 2009 and residing in 13 cities in Guangxi were enrolled into this study. Epidemiological information showed that heterosexual transmission was the main transmitting route. 1584 bp full length gag gene, 3147 bp full length pol gene and 558 bp env (C2V3) fragments were amplified by using RT-PCR and then directly sequenced. NCBI genotyping tool and Mega 5.03 software were used to determine the HIV subtypes. Simplot and Recombinant HIV-1 Drawing Tool were used for the analysis of recombination. A total of 739 sequences, including 270 gag, 246 pol and 223 env (C2V3), were successfully obtained from 294 plasma specimens. Genotypes of HIV from 272 participants were determined. CRF01_AE was found the dominant (77.6%), followed by CRF08_BC (10.7%) and CRF07_BC (7.4%). 7 unique recombinant forms, 4 subtype B (B') and 1 subtype G were also identified. No significant difference on the distribution of subtypes among different regions and ethnics was found. Among the 7 unknown recombinant forms, 6 strains were mosaic B and/or C fragments with CRF01_AE genome as the backbone, while one strain originated from CRF07_BC and CRF08_BC. Currently, CRF01_AE was found the major subtype of HIV epidemic in Guangxi. New recombinant forms with CRF01_AE as backbones had been emerging, which called for serious attention.


Noise-improved signal detection in cat primary visual cortex via a well-balanced stochastic resonance-like procedure.
Adding noise to a weak signal can paradoxically improve signal detection, a process called 'stochastic resonance' (SR). In the visual system, noise might be introduced by the image jitter resulting from high-frequency eye movements, like eye microtremor and microsaccades. To test whether this kind of noise might be beneficial or detrimental for cortical signal detection, we performed single-unit recordings from area 17 of anaesthetized cats while jittering the visual stimulus in a frequency and amplitude range resembling the possible range of eye movements. We used weak, sub- and peri-threshold visual stimuli, on top of which we superimposed noise with variable jitter amplitude. In accordance with the typical SR effect, we found that small noise levels actually increased the signal-to-noise ratio (SNR) of previously weak cortical visual responses, while originally strong responses were little affected or even reduced. Above a certain noise level, the SNR dropped a little, but not as a result of increased background activity - as would be proposed by SR theory - but because of a lowered response to signal and noise. Therefore, it seems that the ascending visual pathway optimally utilizes signal detection improvement by a SR-like process, while at the same time preventing spurious noise-induced activity and keeping the SNR sufficiently high.


[How to do an endovenous ablation of varicose veins].
Minimally invasive endovenous therapies for treatment of varicosis are a well established alternative to the classical surgical approach. Based on an example of radiofrequency ablation (Venefit(®)) of the great saphenous vein and foam sclerotherapy of the side branches this article shows the step-by-step implementation of the procedure. Tips and tricks for starters with the procedure are given.


Intestinal transplantation.
In contrast to other solid organ transplantations slow progress has been seen in introducing intestinal transplantation (IT) from an experimental level to clinical practice. In nine years less than 200 transplantations have been performed worldwide with a three-years, survival of approximately 40%. The main problem of IT is immunological. Large amounts of lymphatic tissues transplanted along with the intestinal graft increase the risk of acute rejection and necessitate high doses of immunosuppressive regimens liable of inducing serious side-effects. The immunocompromized recipient is vulnerable to various infections, particularly cytomegalovirus (CMV) enteritis of the graft. However, improved results are expected after introducing modern potent immunosuppressive drugs such as combination of tacrolimus and mycophenolic acid. Emphasized antiviral prophylaxis and treatment, improved preservation and prevention of ischaemia reperfusion injury are other means presently available to obtain better results after intestinal transplantation in the near future. Intestinal transplantation is becoming the treatment of choice in intestinal failure when total parenteral nutrition (TPN) fails for one reason or an other.


Acute olanzapine-induced akathisia and dystonia in a patient discontinued from fluoxetine.
The patient with acute extrapyramidal signs and symptoms presents a significant clinical challenge. We present the case of a young man who developed an acute akathisia and dystonia after inadvertent overdose of olanzapine (Zyprexa) in the setting of a recent discontinuation of fluoxetine. The receptor chemistry and mechanisms pertinent to his presentation are reviewed. An analysis of the literature indicates that a broad incidence range is cited for the extrapyramidal effects of these medications. We suggest a diagnostic and therapeutic approach to the undifferentiated patient presenting with extrapyramidal signs and symptoms. The possibility of neuroleptic malignant syndrome (NMS), serotonin syndrome (SS), tricyclic overdose, and cocaine abuse should be considered in a patient with extrapyramidal signs and symptoms, given the potential for complications. An emphasis is placed on the need for carefully verbalized discharge instructions to avoid a potential untoward outcome.


A Comprehensive Assessment of Blood Transfusions in Elective Thyroidectomy Based on 180,483 Patients.
To assess the incidence, risk factors, and complications of blood transfusions (BTs) in elective thyroidectomy patients. A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program. Adult patients who underwent elective thyroidectomy from 2005 to 2019 were divided into two cohorts based on whether they received BT or not. Multivariable binary logistic regression models were used to identify risk factors of BT and its impact on postoperative complications. Of 180,483 patients, 0.13% received BT. Risk factors for BT included underweight body mass index (BMI) (adjusted odds ratio [OR] 3.179, 95% confidence interval [CI] 1.444-6.996), bleeding disorders (OR 2.121, 95% CI 1.149-3.913), anemia (OR 4.730, 95% CI 3.472-6.445), preoperative transfusion (OR 7.230, 95% CI 1.454-35.946), American Society of Anesthesiology physical statuses 3-5 (OR 3.103, 95% CI 2.143-4.492), operative time >150 min (OR 4.390, 95% CI 1.996-9.654), and inpatient thyroidectomy (OR 5.791, 95% CI 3.816-8.787). In addition, transfusion was independently associated with any postoperative complication, non-infectious, cardiac, pulmonary, renal, vascular, or infectious complications, surgical site infection, sepsis, septic shock, wound disruption, pneumonia, unplanned reoperation, prolonged length of stay, and mortality. Recognition of risk factors of BT is imperative to identify at-risk patients and reduce transfusions by controlling modifiable risk factors such as anemia, operative time, and BMI. In cases where transfusions are still indicated, surgeons should optimize care to prevent or adequately manage transfusion-associated complications. 3 Laryngoscope, 132:2078-2084, 2022.


Inside SWISS-2DPAGE database.
Several two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) databases have been established and updated for more than 15 years. Only recently have developments of computer networks and high-speed transfer protocols provided the required tools for sharing comprehensive and hypermedia 2-D PAGE databases. This publication describes the SWISS-2DPAGE database structure. Proteins present in samples of human tissue, cells, cell lines and body fluids are assembled and described in an accessible uniform format. SWISS-2DPAGE can be freely accessed through the World-Wide Web (WWW) network on the ExPASy molecular biology server.


Endothelin-1 induces endothelial barrier failure in the cat hindlimb.
Our purpose was to see whether endothelin- (ET) 1 could produce a change in the endothelial membrane barrier to protein in skeletal muscle. Previous studies in other tissues have suggested that ET-1 affects this barrier, but the measurement methods used could not exclude vascular protein extravasation due to microvascular pressure changes or the effects of changes in perfused capillary surface area. We measured the protein sieving coefficient, a specific measure of the permeability of the membrane to protein, in the isolated, perfused cat hindlimb preparation. The integral-mass balance method determined this coefficient from the changes in hematocrit and plasma protein concentration induced by a period of transvascular fluid filtration. The data clearly indicate that ET-1 produces a dose (1-20 nM) dependent increase in permeability indicative of barrier dysfunction. Hence, elevated ET levels may contribute to the perivascular edema, hemoconcentration, and impaired tissue perfusion found in systemic inflammatory response syndromes and related diseases.


The selective estrogen receptor alpha agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: a phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazine.
Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor alpha (ERalpha) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity. A 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding, proof-of-concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28). Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial. The observed lack of clinical benefit in RA patients treated with an ERalpha agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ERalpha-mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs.


Visual alignment from the midline: a declining developmental trend in normal, strabismic, and monocularly enucleated children.
Children, 1.8 to 5.0 years of age, were asked to sight through a tube at targets. There were three groups tested: children with normal binocular vision, children with strabismus, and children with one eye enucleated. The younger normal and strabismic patients placed the tube midway between the two eyes. Surprisingly, the younger enucleated children also placed the tube at the midline. This "Cyclops effect" diminished as the children grew older, with a transition to sighting monocularly by the age of 4 years. The tendency to align with the midline by the younger children, regardless of the degree of their binocular vision, presumably is a natural response to a cyclopean projection center in the midline. As children mature, they learn to meet the demands of monocular preference tasks by aligning objects in front of one eye.


Molecular analysis of the mitochondrial markers COI, 12S rDNA and 16S rDNA for six species of Iranian scorpions.
Annually, 1.2 million humans are stung by scorpions and severely affected by their venom. Some of the scorpion species of medical importance have a similar morphology to species with low toxicity. To establish diagnostic tools for surveying scorpions, the current study was conducted to generate three mitochondrial markers, Cytochrome Oxidase I (COI gene), 12S rDNA and 16S rDNA for six species of medically important Iranian scorpions: Androctonus crassicauda, Hottentotta saulcyi, Mesobuthus caucasicus, M. eupeus, Odontobuthus doriae, and Scorpio maurus. Phylogenetic analyses of the obtained sequences corroborated the morphological identification. For the first time, 12S rDNA sequences are reported from Androctonus crassicauda, Hottentotta saulcyi, Mesobuthus caucasicus and M. eupeus and also the 16S rDNA sequence from Hottentotta saulcyi. We conclude that the mitochondrial markers are useful for species determination among these medically important species of scorpions.


Complete Genome Sequence of a UL96 Mutant Cytomegalovirus Towne-BAC (Bacterial Artificial Chromosome) Isolate Passaged in Fibroblasts To Allow Accumulation of Compensatory Mutations.
Here, we present the complete genome sequence of a cytomegalovirus Towne-BAC (bacterial artificial chromosome) isolate that we first genetically engineered to mutate the UL96 gene and then serially passaged in human fibroblasts to allow for the accumulation of compensatory mutations. A total of 17 single-base substitutions were discovered in the passaged genome compared to the reference sequence (KF493877).


Screening for heart disease: C-reactive protein versus coronary artery calcium.
The Framingham model has become the standard to assess future risk of coronary artery disease. Several nontraditional risk factors have been suggested to improve risk stratification to provide a new algorithm for predicting coronary heart disease (CHD). Two factors with the most available data include C-reactive protein (CRP) and coronary artery calcification (CAC). CRP, a well-established biomarker of inflammation, has shown very inconsistent data to predict CHD, and no study to date shows improvement in the C-statistic; in addition, reclassification is modest (<10% of patients are reclassified to higher or lower risk categories). CAC seems to hold a greater promise in the prediction of CHD and demonstrates a stronger relationship to future cardiac events, with all studies demonstrating improvement in the C-statistic when added to the Framingham risk score. Measurement of CAC consistently provides reclassification of patients more accurately to the Framingham risk model. Only four studies have evaluated both CAC and CRP in the same cohort for future cardiovascular events, but all of these showed significant prediction for coronary artery disease using CAC and no significant prediction ability for CRP. Current review of the literature available suggests CAC to be more relevant in evaluating CHD in a clinical setting. Given the higher cost of CAC scanning compared with CRP, cost-effectiveness studies are still needed.


Active case finding of tuberculosis: historical perspective and future prospects.
Despite a history of remarkable scientific achievements in microbiology and therapeutics, tuberculosis (TB) continues to pose an extraordinary threat to human health. Case finding and treatment of TB disease are the principal means of controlling transmission and reducing incidence. This review presents a historical perspective of active case finding (ACF) of TB, detailing case detection strategies that have been used over the last century. This review is divided into the following sections: mass radiography, house-to-house surveys, out-patient case detection, enhanced case finding, high-risk populations and cost-effectiveness. The report concludes with a discussion and recommendations for future case finding strategies. Understanding the strengths and weaknesses of these methods will help inform and shape ACF as a TB control policy in the twenty-first century.


Ecstasy: commodity or disease?
This article evaluates past work on heroin and crack cocaine epidemics by comparing it with the increase in Ecstasy use in the late 1990s. First of all, the authors make the case that there was, in fact, a dramatic increase in Ecstasy use in the late 1990s. Following that is a review of the rise and fall of several different Ecstasy scenes beginning in the 1960s. The most recent rise, in the late 1990s, requires a broadening of the theory of epidemics to include longer historical waves of change, so we do that by reviewing work on post World War II trends in social disconnection and consumerism. We then shift to a marketing rather than a public health framework and look at the nature of the Ecstasy "product," both its good and bad characteristics. Finally, we describe the narrative mechanism, developed in our earlier work, that plausibly explains why use rose when it did, given the needs of the market. The article concludes by discussing the changes this case motivates for our theory, particularly in light of globalized and normalized drug use that at the moment appears to be the current context for illicit drug use.


Arsenic in Mexican children exposed to contaminated well water.
This cross-sectional study measures the arsenic level in school children exposed to contaminated well water in a rural area in México. Arsenic was measured in hair by hydride generation atomic absorption spectrophotometry. Overall, 110 children were included (average 10 years-old). Among 55 exposed children, mean arsenic level on hair was 1.3 mg/kg (range <0.006-5.9). All unexposed children had undetectable arsenic levels. The high level of arsenic in water was associated to the level in hair. However, exposed children drank less well water at school or at home than unexposed children, suggesting that the use of contaminated water to cook beans, broths or soups may be the source of arsenic exposure.


Using evolutionary changes to achieve species-specific inhibition of enzyme action--studies with triosephosphate isomerase.
Many studies that attempt to design species-specific drugs focus on differences in the three-dimensional structures of homologous enzymes. The structures of homologous enzymes are generally well conserved especially at the active site, but the amino-acid sequences are often very different. We reasoned that if a non-conserved amino acid is fundamental to the function or stability of an enzyme from one particular species, one should be able to inhibit only the enzyme from that species by using an inhibitor targeted to that residue. We set out to test this hypothesis in a model system. We first identified a non-conserved amino acid (Cys14) whose integrity is important for catalysis in triosephosphate isomerase (TIM) from Trypanosoma brucei. The equivalent residues in rabbit and yeast TIM are Met and Leu, respectively. A Cys14Leu mutant of trypanosomal TIM had a tendency to aggregate, reduced stability and altered kinetics. To model the effects of a molecule targeted to Cys14, we used methyl methanethiosulfonate (MMTS) to derivatize Cys14 to a methyl sulfide. This treatment dramatically inhibited TIMs with a Cys residue at a position equivalent to Cys14, but not rabbit TIM (20% inhibition) or yeast TIM (negligible inhibition), which lack this residue. Cys14 of trypanosomal TIM is a non-conserved amino acid whose alteration leads to loss of enzyme structure and function. TIMs that have a cysteine residue at position 14 could be selectively inhibited by MMTS. This approach may offer an alternative route to species-specific enzyme inhibition.


Prevalence of inducible clindamycin resistance in gram positive organisms in a tertiary care centre.
Gram positive organisms are one of the leading pathogens causing skin and soft tissue infections. For these infections, clindamycin is a useful alternate drug in penicillin-allergic patients. This study was conducted to investigate the prevalence of erythromycin-induced clindamycin resistance in gram positive organisms in the southern part of the country. A total of 522 consecutive clinical isolates from blood, CSF, sputum, throat, pus, and urine were collected between November 2006 and April 2007 and tested for erythromycin resistance and inducible clindamycin resistance. There was a relatively higher incidence of inducible clindamycin resistance among the MRSA isolates. We conclude, therefore, that clindamycin is not a suitable alternative antibiotic for use in staphylococcal skin and soft tissue infections.


Molecular chemisorption on passivated and defective boron doped silicon surfaces: a "forced" dative bond.
We investigate the adsorption mechanism of a single trans 4-pyridylazobenzene molecule (denoted by PAB) on a doped boron Si(111)√3×√3R30° surface (denoted by SiB) with or without boron-defects, by means of density functional theory calculations. The semiempirical approach proposed by Grimme allows us to take the dispersion correction into account. The role of the van der Waals correction in the adsorption geometries and energies is presented. In particular, two adsorption configurations are electronically studied. In the first one, the molecule is parallel to the surface and interacts with the SiB surface via the -N=N- bond. In the presence of a boron-defect, a Si-N chemical bond between the molecule and the surface is then formed, while electrostatic or/and van der Waals interactions are observed in the defectless surface. In the second adsorption configuration, the molecule presents different orientations with respect to the surface and interacts via the nitrogen atom of the pyridyl part of the PAB molecule. If the molecule is perpendicular to the perfect SiB surface, the lone-pair electrons associated with the heterocyclic nitrogen atom fill the empty dangling bond of a silicon adatom via a dative bond. Finally, in the presence of one boron-defect, the possibility of a "forced" dative bond, corresponding to a chemical bond formation between the PAB molecule and the silicon electron occupied dangling bond, is emphasized.


Prognostic values of E2F mRNA expression in human gastric cancer.
Gastric cancer (GC) is the second most frequent cause of cancer-related mortality in the world, with Eastern Asia having the highest incidence rates. E2F is a family of transcription factor proteins that has a variety of functions, which include control of cell cycle, cell differentiation, DNA damage response and cell death. E2F transcription factors are divided into two subfamilies: transcription activators (E2F transcription factors 1 (E2F1), 2 (E2F2) and 3a (E2F3a)) and repressors (E2F3b, E2F transcription factors 4 (E2F4), 5 (E2F5), 6 (E2F6), 7 (E2F7) and 8 (E2F8)). Studies have demonstrated that E2F had prognostic significance in a number of cancers. However, the entirety of the prognostic roles of E2F mRNA expression in GC has not yet been apparently determined. In the present study, the prognostic value of individual family members of E2F mRNA expression for overall survival (OS) was evaluated by using online Kaplan-Meier Plotter (KM Plotter) database. Our result demonstrated that high expressions of three family members of E2F (E2F1, E2F3, E2F4) mRNA were significantly associated with unfavourable OS in all GC patients. However, increased expressions of E2F2, E2F5, E2F6 and E2F7 were significantly associated with favourable OS, especially for higher clinical stages in GC patients. These results provided a better insight into the prognostic functions of E2F mRNA genes in GC. Although the results should be further verified in clinical trials, our findings may be a favourable prognostic predictor for the development of newer therapeutic drugs in the treatment of GC.


Nodular Sclerosing Mesenteritis: An Occasional Finding Mimicking a Spindle Cell Tumor.
BACKGROUND The term "sclerosing mesenteritis" includes a spectrum of rare idiopathic diseases involving the small and/or large bowel. It appears as a diffuse, localized, or multinodular thickening of the mesentery, with a variable degree of chronic non-specific inflammation, fat necrosis, and fibrosis. CASE REPORT Here, we report a case of 83-year-old woman with symptoms of intestinal occlusion, vomiting, and abdominal pain. Radiographic examinations showed air fluid levels in right and left quadrants and in the mesogastric site, while computed tomography (CT) documented a strangulated inguinal hernia with ileal obstruction. Based on clinical examination and radiologic findings, the patient underwent surgery for inguinal hernia reduction. The examination of viscera revealed 2 tracts of ileum with ischemic signs and covered by fibrin; thus, the 2 intestinal loops were resected. Histological examination revealed chronic non-specific inflammation of the whole intestinal wall, including the subserosa in the resected tract of proximal ileum, while the distal ileal loop (not herniated tract) showed a subserosal fibrous nodule of 2 cm in greatest diameter, composed of a proliferation of spindle cells haphazardly arranged in a collagenized stroma. The diagnosis of sclerosing mesenteritis was rendered. CONCLUSIONS The present case shows the possibility of an incidental diagnosis during another intervention such as hernia surgery. Pathologists should be aware of this disease to avoid confusion with aggressive tumors such as intra-abdominal desmoid-type fibromatosis and gastrointestinal stromal tumor.


Rational Design and Synthesis of 3-Morpholine Linked Aromatic-Imino-1H-Indoles as Novel Kv1.5 Channel Inhibitors Sharing Vasodilation Effects.
Atrial fibrillation (AF) is the most common clinical sustained arrhythmia; clinical therapeutic drugs have low atrial selectivity and might cause more severe ventricle arrhythmias while stopping AF. As an anti-AF drug target with high selectivity on the atrial muscle cells, the undetermined crystal structure of Kv1.5 potassium channel impeded further new drug development. Herein, with the simulated 3D structure of Kv1.5 as the drug target, a series of 3-morpholine linked aromatic amino substituted 1H-indoles as novel Kv1.5 channel inhibitors were designed and synthesized based on target-ligand interaction analysis. The synthesis route was practical, starting from commercially available material, and the chemical structures of target compounds were characterized. It was indicated that compounds T16 and T5 (100 μM) exhibited favorable inhibitory activity against the Kv1.5 channel with an inhibition rate of 70.8 and 57.5% using a patch clamp technique. All compounds did not exhibit off-target effects against other drug targets, which denoted some selectivity on the Kv1.5 channel. Interestingly, twelve compounds exhibited favorable vasodilation activity on pre-contracted arterial rings in vitro using KCl or phenylephrine (PE) by a Myograph. The vasodilation rates of compounds T16 and T4 (100 μM) even reached over 90%, which would provide potential lead compounds for both anti-AF and anti-hypertension new drug development.


Analysis of progression of reticular pseudodrusen by spectral domain-optical coherence tomography.
To analyze reticular pseudodrusen progression using spectral domain-optical coherence tomography (SD-OCT). Thirty-three consecutive patients (48 eyes) underwent SD-OCT using the eye-tracked follow-up protocol 24 ± 2 months after baseline examination. Each pair of B-scans (only one per eye was evaluated among those showing pseudodrusen progression) was compared with respect to pseudodrusen appearance and retinal layer structure. Stage 1 pseudodrusen was defined as granular material between the RPE and the inner segment/outer segment (IS/OS), stage 2 as mounds of material sufficient to alter the contour of the IS/OS, stage 3 as thicker material adopting a conical appearance and breaking through the IS/OS, and stage 4 as fading of the material because of reabsorption and migration within the inner retinal layers. A total of 78 pseudodrusen (detected on the 48 analyzed B-scans, and counting for a mean of 2.3 pseudodrusen per scan) showed progression over a mean of 23.9 ± 1.2 months. All 58 pseudodrusen (100%) graded as stage 1 at baseline examination progressed to stage 2. Thirteen of 16 pseudodrusen (81.3%) graded as stage 2 at baseline examination progressed to stage 3, and three (18.7%) progressed to stage 4. All four pseudodrusen (100%) graded as stage 3 at baseline examination progressed to stage 4. Among pseudodrusen that were stage 3 or 4 at follow-up (n = 20), 100% had IS/OS disruption whereas 12.1% (n = 7) had IS/OS disruption at stage 1 or 2 (n = 58) (OR, 1.736; 95% CI, 1.02-2.43). The frequency of stage changes over time suggest that reticular pseudodrusen are dynamic pathologic structures.


Cloning and sequence determination of a gene encoding an osmotin-like protein from strawberry (Fragaria X ananassa Duch.).
Osmotin and osmotin-like proteins (OLPs) are pathogenesis-related (PR) proteins, whose synthesis is normally stimulated upon infection of plants by pathogens. A strawberry genomic clone containing an osmotin-like protein (OLP) gene was isolated and sequenced. This clone contains an open reading frame of 681 nucleotides without any intron. The predicted amino acid sequence of the protein shares high degrees of homology with a number of other OLPs and related proteins, of which several are known to have antifungal activities. Southern hybridization analysis of strawberry genomic DNA suggested that the OLP is coded by a multi-gene family. Results from reverse transcriptase-polymerase chain reaction indicated that this OLP gene is expressed in uninfected strawberry plants.


Integrated Bioinformatic Analysis Identifies TIPIN as a Prognostic Biomarker in Hepatocellular Carcinoma.
Gene expression and DNA methylation analyses have long been used to identify cancer markers. However, a combination analysis of the gene expression and DNA methylation has yet to be performed to identify potential biomarkers of hepatocellular carcinoma (HCC). By matching gene expression profiles and promoter methylation data in The Cancer Genome Atlas (TCGA), genes with discrepant expression as well as genes with differential promoter methylation were identified. High-expression genes with low promoter methylation were defined as epigenetically induced (EI), while low-expression genes with high promoter methylation were defined as epigenetically suppressed (ES). The human protein interaction network was further integrated to construct the EI/ES gene interaction network, and the key genes in the subnet were identified as potential HCC biomarkers. The expression differences and prognostic values were verified in TCGA and Gene Expression Omnibus (GEO) databases, as well as with tissue chip technology. Four key genes were identified: TIPIN, RBM15B, DUSP28, and TRIM31, which demonstrated the differential gene expression and prognostic value in TCGA and GEO databases. Tissue microarray analysis (TMA) revealed that TIPIN levels were altered in HCC. The upregulated TIPIN expression was associated with worse overall survival. Univariate and multivariate analyses showed that the TIPIN expression was an independent predictor of HCC. TIPIN might be a potential novel prognostic biomarker for HCC.


Combining Statistical Tools and Ecological Assessments in the Study of Biodeterioration Patterns of Stone Temples in Angkor (Cambodia).
Biodeterioration is a major problem for the conservation of cultural heritage materials. We provide a new and original approach to analyzing changes in patterns of colonization (Biodeterioration patterns, BPs) by biological agents responsible for the deterioration of outdoor stone materials. Here we analyzed BPs of four Khmer temples in Angkor (Cambodia) exposed to variable environmental conditions, using qualitative ecological assessments and statistical approaches. The statistical analyses supported the findings obtained with the qualitative approach. Both approaches provided additional information not otherwise available using one single method. Our results indicate that studies on biodeterioration can benefit from integrating diverse methods so that conservation efforts might become more precise and effective.


Features of central serous chorioretinopathy presenting at a tertiary care hospital in Lahore.
To evaluate the clinical, angiographic and optical coherence tomographic features of central serous chorioretinopathy in patients presenting at a tertiary care centre in Lahore. The observational study was conducted at the Layton Rehmatulla Benevolent Trust Eye and Cancer Hospital Lahore from July 15, 2010 to December 15, 2011. Patients who had received prior treatment for the condition and allergy to fluorescein were excluded. There were 86 eyes of 64 adult patients with central serous chorioretinopathy. The following data was recorded: history, signs and symptoms, best corrected visual acuity, fundus fluorescein angiography, and central macular thickness measurement with optical coherence tomography. Data was analyzed using SPSS 17. Mean age of patients who presented during the study duration was 39.52 +/- 8.85 years.There were 53 (82.8%) males and 11(17.2%) females. Of the total, 42 (65.6%) cases had unilateral and 22 (34.4%) cases had bilateral involvement. Chronic central serous chorioretinopathy was seen in 27 (42.2%) cases while 37 (57.8%) cases were acute presentations. Retinal pigment epithelial detachment was observed in 29 (45.3%) cases. On fundus fluorescein angiography, there were 62 (72.1%) eyes that showed ink blot pattern. Median visual acuity at presentation was 0.25. Median central macular thickness at presentation was 550.5micro. Central serous chorioretinopathy in the study sample was associated with pigment epithelial detachment, bilateral involvement, and presence of systemic diseases.


Subtypes of hypertension and risk of stroke in rural Chinese adults.
Hypertension is a definitive risk factor for stroke. We examined the associations between hypertension subtypes and stroke incidence in rural Chinese adults. We conducted a prospective study in a sample of 38,949 rural Chinese adults aged ≥35 years and free from stroke at baseline. The subtypes of hypertension were defined as isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), systolic and diastolic hypertension (SDH), and managed hypertension (MHT). The relative risks of stroke with the subtypes of hypertension, compared with normotensive subjects, were estimated using the Cox model after adjusting for age, sex, and other confounders. The prevalence of hypertension was as follows: SDH = 18.6%, ISH = 10.2%, IDH = 5.8%, and MHT = 0.4%. During a total of 168,023 person-years of follow-up, 858 subjects developed stroke. The incidence rate per 100,000 person-years of overall first-ever stroke was 510.6. The SDH group was at the highest risk of stroke among all the hypertensive subjects. The hazard ratio was 2.13 (95% confidence interval (CI) = 1.78-2.55) for all stroke, 2.74 (95% CI = 2.08-3.60) for hemorrhagic stroke, and 1.92 (95% CI = 1.50-2.45) for ischemic stroke. SDH patients warrant the most attention for prevent of stroke. However, ISH and IDH are also independent predictors of stroke. The risk factors for stroke, especially hypertension, were not controlled in the rural population we studied. More aggressive efforts to control the risk factors for stroke in rural areas are needed.


MED1 Deficiency in Macrophages Accelerates Intimal Hyperplasia via ROS Generation and Inflammation.
Mediator complex subunit 1 (MED1) is a component of the mediator complex and functions as a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Previously, we showed that MED1 in macrophages has a protective effect on atherosclerosis; however, the effect of MED1 on intimal hyperplasia and mechanisms regulating proinflammatory cytokine production after macrophage MED1 deletion are still unknown. In this study, we report that MED1 macrophage-specific knockout (MED1 ΔMac) mice showed aggravated neointimal hyperplasia, vascular smooth muscle cells (VSMCs), and macrophage accumulation in injured arteries. Moreover, MED1 ΔMac mice showed increased proinflammatory cytokine production after an injury to the artery. After lipopolysaccharide (LPS) treatment, MED1 ΔMac macrophages showed increased generation of reactive oxygen species (ROS) and reduced expression of peroxisome proliferative activated receptor gamma coactivator-1α (PGC1α) and antioxidant enzymes, including catalase and glutathione reductase. The overexpression of PGC1α attenuated the effects of MED1 deficiency in macrophages. In vitro, conditioned media from MED1 ΔMac macrophages induced more proliferation and migration of VSMCs. To explore the potential mechanisms by which MED1 affects inflammation, macrophages were treated with BAY11-7082 before LPS treatment, and the results showed that MED1 ΔMac macrophages exhibited increased expression of phosphorylated-p65 and phosphorylated signal transducer and activator of transcription 1 (p-STAT1) compared with the control macrophages, suggesting the enhanced activation of NF-κB and STAT1. In summary, these data showed that MED1 deficiency enhanced inflammation and the proliferation and migration of VSMCs in injured vascular tissue, which may result from the activation of NF-κB and STAT1 due to the accumulation of ROS.


Effect of the cervical flexion angle during smart phone use on muscle fatigue of the cervical erector spinae and upper trapezius.
[Purpose] The purpose of this study was to examine the influence of the cervical flexion angle when using a smart phone on muscle fatigue of the cervical erector spinae (CES) and upper trapezius (UT). [Subjects] This study recruited 12 healthy adults. [Methods] Each subject sat on a chair, with his/her back against the wall and held a smart phone with both hands. Fatigue of the neck and shoulder muscles at different cervical flexion angles (0°, 30°, and 50°) was measured by electromyography. The following muscles were assessed: the right upper trapezius (RtUT), left upper trapezius (LtUT), right cervical erector spinae (RtCES), and left cervical erector spinae (LtCES). A cervical range of motion instrument was attached to the subjects' heads to measure the cervical angle during the experiment. [Results] The RtUT and LtUT showed the highest muscle fatigue at a cervical flexion angle of 50° and the lowest fatigue at an angle of 30°. There was no significant difference in the muscle fatigue of the RtCES and LtCES at any of the cervical flexion angles. [Conclusion] UT muscle fatigue depends on the cervical flexion angle when using a smart phone.


Inhibition of natural killer cell activity by oral administration of theophylline.
Asthmatic patients have a low incidence of malignancies, and this is possibly due to higher NK cell activity in this population. Because theophylline is used widely in this population, we evaluated the influence of theophylline on NK cell activity in vitro and in vivo. The NK cell activity was significantly inhibited by direct addition of concentrations of aminophylline that exceeded 5 x 10(-5) M. To test whether such an effect can be observed in vivo, we administered one sustained-release tablet of theophylline (400 to 500 mg twice daily) to five normal volunteers for seven days. Significant inhibition of NK activity was noted after administration (mean percentage of inhibition, 41.3 percent), but the serum concentrations observed gave a mean value of 2 x 10(-5) M, which was lower than that yielding the same degree of inhibition by direct addition in vitro (about 20 x 10(-5) M). These results suggest that long-term theophylline therapy may inhibit NK cell activity, and thus more information would be needed to determine the position of such therapy in the management of asthmatic patients.


Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function.
The mitogen-activated protein kinase-activated protein kinase-5 (MK5) resides predominantly in the nucleus of resting cells, but p38(MAPK), extracellular signal-regulated kinases-3 and -4 (ERK3 and ERK4), and protein kinase A (PKA) induce nucleocytoplasmic redistribution of MK5. The mechanism by which PKA causes nuclear export remains unsolved. In the study reported here we demonstrated that Ser-115 is an in vitro PKA phosphoacceptor site, and that PKA, but not p38(MAPK), ERK3 or ERK4, is unable to redistribute MK5 S115A to the cytoplasm. However, the phospho-mimicking MK5 S115D mutant resides in the cytoplasm in untreated cells. While p38(MAPK), ERK3 and ERK4 fail to trigger nuclear export of the kinase dead T182A and K51E MK5 mutants, S115D/T182A and K51E/S115D mutants were able to enter the cytoplasm of resting cells. Finally, we demonstrated that mutations in Ser-115 affect the biological properties of MK5. Taken together, our results suggest that Ser-115 plays an essential role in PKA-regulated nuclear export of MK5, and that it also may regulate the biological functions of MK5.


A theoretic analysis of the effect of pulmonary vasodilation on pulmonary venous pressure: implications for inhaled nitric oxide therapy.
Although the use of inhaled nitric oxide offers certain advantages over more traditional pulmonary vasodilators, concerns have emerged because of reports of acute pulmonary edema during nitric oxide administration in patients with chronic heart failure. It is unclear whether the pulmonary vasodilating action of nitric oxide could, by itself, cause venous pressures to rise in the lung and why patients with preexisting chronic heart failure are at greatest risk for the development of pulmonary edema during inhaled nitric oxide therapy. The cardiovascular system was modeled as time-varying elastances; the pulmonary and systemic vascular systems were each modeled as a series of resistive and compliance elements. Protocols were devised to examine the effects of a decrease in pulmonary vascular resistance on pulmonary venous pressure under different conditions of contractile state and volume status. Under all conditions studied, pulmonary venous pressure increased as pulmonary vascular resistance decreased. Increases in pulmonary venous pressure were caused by volume shifts between pulmonary arterial and venous compartments. These volume shifts were accentuated by high volume status. The impact of alterations in contractile state was minimal. Pulmonary vasodilation by itself can lead to an increase in pulmonary venous pressure that is mediated by shifts of blood between arterial and venous compartments of the pulmonary bed. Furthermore, impairment in ventricular contractile state by itself has relatively little effect on pulmonary venous pressure. The magnitude of the increase in pulmonary venous pressure is largely determined by the volume status and the initial value of pulmonary vascular resistance.


Phase behavior of an extended surfactant in water and a detailed characterization of the dilute and semidilute phases.
The formation of microemulsions with triglycerides under ambient conditions has been a challenge for scientists for many decades. For this reason, so-called extended surfactants were developed that contained hydrophilic/lipophilic linkers to stretch further into the oil and water phase, and enhance the solubility of triglycerides in water. Currently, only limited information about the properties of these surfactants and its behavior in water is available. Therefore, in this work, mixtures of a chosen extended surfactant (C(12-14)-PO(16)-EO(2)-SO(4)Na, X-AES) with H(2)O/D(2)O over the whole concentration range were studied by optical microscopy. A schematic phase diagram has been obtained, which shows two isotropic liquid phases at the lowest and highest surfactant concentrations. Furthermore, between the isotropic solutions, four liquid-crystalline phases occur: a hexagonal phase (H(1)), a lamellar phase (L(alpha)) with a change in birefringence, a bicontinuous cubic phase (V(2)), and a reverse hexagonal phase (H(2)). The structure of the micellar solution (L(1)) was determined by cryo-TEM, dynamic light scattering, and (1)H NMR, which gave information about the size, the aggregation number, and the area per molecule of the micelles. Liquid-crystal formation occurs from the micellar solution in two different ways. The first route appeared by increasing the temperature, going from an L(1) to an L(alpha) phase. By increasing the surfactant concentration (at low temperatures), a second route showed a transition from L(1) to H(1). In addition, the effect of sodium chloride on the cloud point of the extended surfactant was examined, indicating that small amounts of NaCl have no influence on the phase behavior. The monolayer behavior of the extended surfactant at the air-water interface was also determined. Despite its water solubility, an isotherm on the water subphase was found, showing slow kinetics of the molecules to go into the bulk. Thus, the determination of the cmc of the extended surfactant using conventional methods was found to be impossible.


Structural changes with aging in cortical bone of the human tibia.
Structural modifications are considered to play a significant role in the age-related alterations of bone quality and strength. Senescent compact bone is characterized by an increasing heterogeneity of aspects, including high numbers of lowly mineralized osteons as well as the presence of osteons with hypermineralized lamellae or with a notched haversian canal wall, and of double-zone osteons. These latter three types of osteons are different from the structures involved in the haversian remodeling. In the present study, blocks of midshaft tibia from 7 young men (18-39 years), 14 aged men (50-92 years) and 15 aged women (57-96 years) were embedded in methyl methacrylate in order to perform microradiographic and histomorphometric analysis of undecalcified sections. The intracortical porosity was higher in the aged men than in the young ones, as were the numbers of haversian structures and, to a lesser extent, the diameters of the haversian canals. The aged women showed the same tendency, with cortical porosity still higher than in the men. The osteons with hypermineralized lamellae, those with a notched canal and the double-zone osteons appear to constitute large subgroups of the total haversian population, even in the early adult life. Among them, only the osteons with a notched canal wall increased in frequency with age. The 3 types are much more numerous than the structures involved in the typical haversian remodeling. The correlations between their frequencies as well as their significant topographic association corroborates the hypothesis that the hypermineralized lamellae may crumble down because of their excessive brittleness, giving rise to the haversian canals with notched walls. These enlarged canals could be refilled by bone apposition and result in the double-zone osteons. The 3 types of osteons could constitute different steps of one mechanism of bone desintegration and repair occurring very progressively, which might contribute to modify the bone quality and to increase the intracortical porosity.


The active site topology of Aspergillus niger endopolygalacturonase II as studied by site-directed mutagenesis.
Strictly conserved charged residues among polygalacturonases (Asp-180, Asp-201, Asp-202, His-223, Arg-256, and Lys-258) were subjected to site-directed mutagenesis in Aspergillus niger endopolygalacturonase II. Specific activity, product progression, and kinetic parameters (K(m) and V(max)) were determined on polygalacturonic acid for the purified mutated enzymes, and bond cleavage frequencies on oligogalacturonates were calculated. Depending on their specific activity, the mutated endopolygalacturonases II were grouped into three classes. The mutant enzymes displayed bond cleavage frequencies on penta- and/or hexagalacturonate different from the wild type endopolygalacturonase II. Based on the biochemical characterization of endopolygalacturonase II mutants together with the three-dimensional structure of the wild type enzyme, we suggest that the mutated residues are involved in either primarily substrate binding (Arg-256 and Lys-258) or maintaining the proper ionization state of a catalytic residue (His-223). The individual roles of Asp-180, Asp-201, and Asp-202 in catalysis are discussed. The active site topology is different from the one commonly found in inverting glycosyl hydrolases.


Role of angiotensin-converting enzyme inhibitors in congestive heart failure.
Conventional therapy for congestive heart failure (CHF) includes sodium-restricted diet, diuretics, digitalis, vasodilators, and short-term intravenous administration of beta-adrenergic agonists during episodes of decompensation. A specific class of vasodilators, the angiotensin-converting enzyme inhibitors, has recently gained predominance in the treatment of congestive heart failure. The primary mechanism of action is to reduce production of angiotensin II by competitive inhibition of the enzyme that converts angiotensin I into angiotensin II. Reduced levels of angiotensin II, in turn, promote vasodilation and lower aldosterone production. The benefits of angiotensin-converting enzyme inhibitor therapy in chronic congestive heart failure have been demonstrated by improvement in left ventricular performance, exercise capacity, functional status (using New York Heart Association classification), and survival.


Mayo, Myriad, America Invents Act and BPCIA: how has the United States biopharmaceutical market been affected?
This paper discusses how the United States biopharmaceutical market has been affected by recent changes in patent law resulting from United States legislations (Biologics Price Competition and Innovation Act and the Leahy-Smith America Invents Act) and Supreme Court precedents (Mayo Collaborative Services v. Prometheus Laboratories, Inc. and Molecular Pathology v. Myriad Genetics). The authors interviewed eight key opinion leaders from the United States knowledgeable in biopharmaceuticals, including industry veterans, patent counsel, senior scientists and jurists. This paper summarizes the opinions of the key opinion leaders. This paper explains the impact of these Supreme Court decisions - i.e., broadening the exceptions to patent eligibility for law of nature and natural phenomenon - on biopharmaceutical innovations and provides future perspectives.


The cyclicality of government health expenditure and its effects on population health.
Scholars have raised concerns that cutbacks on government health expenditure (GHE) during recessions may jeopardise population health. The present research investigates the extent to which population health outcomes are affected by responses of GHE to business cycles, i.e., cyclicality of GHE. We estimate GHE cyclicality by regressing detrended GHE on detrended gross domestic product (GDP). Our analysis of data for 1995 through 2014 from 135 developing countries shows that mean cyclicality is 0.61, or that a one percent deviation from the GDP trend is positively correlated with a 0.61 percent deviation from the GHE trend. Further, countries in which GHE is less procyclical appear to have shorter life expectancies and higher adult mortality rates. These results suggest that reducing procyclicality of GHE by protecting GHE in bad times may generate substantial health gains. Importantly, our results show that increasing the weight of social security funds in health budgets, and improving institutional quality, can be critical to breaking the procyclical pattern of GHE.


High-risk gestational trophoblastic neoplasia at Gujarat Cancer and Research Institute: thirteen years of experience.
To evaluate and analyze the results of chemotherapy (EMA-CO [etoposide, methotrexate, actinomycin D-cyclophosphamide, vincristine]) in high-risk gestational trophoblastic neoplasia (GTN). A total of 97 women with high-risk GTN were evaluated for a period of 13 years (1995-2008). All women received EMA-CO as a first-line chemotherapy. EMA-EP (etoposide, methotrexate, actinomycin and cisplatinum), PVB (cisplatin, vinblastine and bleomycin), and BEP (bleomycin, etoposide and cisplatin) were the chemotherapies used as second-line therapy in women who experienced resistance to primary chemotherapy. Intrathecal methotrexate was given in women with brain metastasis and also as prophylaxis in pulmonary metastasis. Eleven women had brain metastasis and received cranial radiotherapy. The most common toxicity was hematologic. . Of 97 women, 78 (80.4%) were evaluable and 19 (19.6%) were lost to follow-up with incomplete treatment. Of the 78 patients, 6 women developed resistance and had progression of disease. Seven women had died (5 due to disease, 2 due to chemotherapy toxicity). Overall 65 of the 78 (83.3%) women achieved remission. Of the 78 women, 66.7% (52/78) had complete remission with first-line chemotherapy, and an additional 16.6% (13/78) achieved remission with second-line chemotherapy, resulting in a total of 83.3% (65/78) attaining remission. A total of 46% (30/ 65) had follow-up of > 3 years, and 32.4% (21/65) had follow-up of 1-3 years. Three of 9 women with brain metastasis achieved remission. Sixty percent (39/65) resumed normal menstrual function (had remission for at least 2 years). Twelve women became pregnant since the completion of the chemotherapy, with 10 live births of healthy infants without any congenital abnormalities. High-risk GTNs are highly curable if properly treated, and patients can anticipate a normal future reproductive outcome. EMA-CO remains the preferred chemotherapy for management.


Age and sex differences of controlled force exertion measured by a computer-generated quasi-random target-pursuit system.
This study examined age and sex differences of controlled force exertion measured by a computer-generated quasi-random target-pursuit system in 207 males and 249 females aged 15 to 86 years. The participants matched submaximal grip exertion of their dominant hand to changing demand values, appearing as a moving quasi-random waveform on the display of a personal computer. They performed the test three times with 1-min intervals (one trial was 40 sec). The total sum of the percent of differences between the demand value and the grip exertion value for 25 sec was used as an evaluation parameter. The errors in controlled force exertion tended to increase constantly with age in both sexes. Significant linear regressions were identified, but there was no significant difference in the rate of increase in both sexes. Analysis of variance showed nonsignificant sex differences among means, except for those in individuals older than 60 years; significant differences between means in the groups older than the 40 yr.-old age group and the 20-24 yr.-old group were found in both sexes. Controlled force exertion did not show a significant sex difference and decreased gradually with age in both sexes, but decreased remarkably after 40 years of age.


Molecular mimicry by Trypanosoma cruzi: the F1-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide.
Antigenic mimicry by Trypanosoma cruzi antigens that share epitopes with mammalian tissues may drive autoreactive B- or T-cell clones to expand and cause autoimmune pathogenesis. We have been studying one of these antigens, F1-160, a 160-kDa protein on the surface of T. cruzi that antigenically mimics a 48-kDa protein found in mammalian axonal and myenteric plexus cells. The F1-160 antigen has been characterized by cloning and expression of T. cruzi DNA encoding F1-160 in Escherichia coli. Recombinant peptides from various regions of the F1-160 gene were expressed and used to compete with affinity-purified polyclonal anti-F1-160 antibodies binding to nerve. Recombinant 48-amino acid peptide (48X) derived from expression of base pairs 611-761 of the DNA sequence completely inhibited anti-F1-160 binding to nerve. Recombinant peptides expressed from DNA lacking this region did not inhibit anti-F1-160 binding to nerve. Three peptides were synthesized to encompass the 48X peptide, a 12-amino acid peptide and two 18-amino acid peptides. The 12-amino acid peptide TPQRKTTEDRPQ (12X), corresponding to bases 615-651, completely inhibited the binding of anti-F1-160 antibodies to nerve at a concentration of 80 ng/ml (30 microM). The two 18-residue peptides did not inhibit, even at 10 micrograms/ml. Thus, the epitope of F1-160 crossreactive with nervous tissue can be mapped to a 12-amino acid peptide. Some humans with T. cruzi infection make antibodies to F1-160 and to the 48X and 12X peptides. Control sera from uninfected persons did not react with these antigens. Anti-48X antibodies, immunoselected from human serum with 48X peptide, bind to human nerve axons. This demonstrates that some individuals infected with T. cruzi make antibodies to the F1-160 epitope crossreactive with nervous tissues.


Fine-needle aspiration biopsy cytology of cutaneous calcinosis in a 74-year-old woman with dermatomyositis on methotrexate therapy: a case report.
Cutaneous calcinosis (CC) occurs in a variety of rheumatic diseases. Fine needle aspiration biopsy (FNAB) may be used in the office setting to evaluate such soft tissue lesions. For patients on methotrexate (MTX) therapy, methotrexate nodulosis (MN) should be considered in the differential diagnosis. A 74-year-old Caucasian woman with adult-onset dermatomyositis (ADM) on MTX therapy presented for evaluation of a right breast mass and multiple soft tissue nodules. FNABs of the right breast mass and a left upper extremity nodule both demonstrated benign calcified material. Six months later, the patient returned for evaluation of the persistent right breast mass and repeat FNAB revealed adenocarcinoma. Concurrently, a right hip soft tissue nodule was aspirated, demonstrating benign crystalline debris. MTX therapy was discontinued, and the patient subsequently underwent a lumpectomy of the right breast 1 month after FNAB diagnosis, displaying infiltrative ductal carcinoma. Of note, 2 months after her lumpectomy, MTX therapy was restarted and the patient continues to have adequate control of ADM symptoms with persistent, clinically benign soft tissue calcifications. Performing FNAB on soft tissue lesions can obviate needless tissue biopsies of CC in appropriate rheumatology patients, thus avoiding the risks and complications associated with more invasive procedures.


Residual household waste: from pay-per-bag to pay-per-kilogram. An evaluation study for Flanders.
To be in line with the polluter-pays principle, an increasing number of Flemish municipalities have introduced a weight-based pricing system for residual household waste. Municipalities using this new pricing scheme are keen to ascribe decreasing waste production to the introduction of the new system. In order to evaluate the real impact of the weight-based pricing, an extension to the standard difference-in-differences evaluation techniques is proposed. The main idea is to use historical observations on waste production to determine which version of the difference-in-differences technique is most suitable to assess the impact of a policy action on waste quantities. The method is easy to apply, which makes it a very useful tool for both scientists and policy makers. Surprisingly, empirical results for Flanders indicate that, on average, municipalities using the weight-based system do not perform better than other municipalities.


Implications for eicosapentaenoic acid- and docosahexaenoic acid-derived resolvins as therapeutics for arthritis.
Omega-3 polyunsaturated fatty acids are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases. Indeed, dietary supplementation with omega-3 polyunsaturated fatty acids has proved efficacious in reducing joint pain, morning stiffness and nonsteroidal anti-inflammatory drugs usage in rheumatoid arthritis patients. However, the mechanisms by which omega-3 polyunsaturated fatty acids exert their beneficial effects have not been fully explored. Seminal discoveries by Serhan and colleagues have unveiled a novel class of bioactive lipid mediators that are enzymatically biosynthesized in vivo from omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), termed resolvins, protectins and maresins. These bioactive pro-resolving lipid mediators provide further rationale for the beneficial effects of fish-oil enriched diets. These endogenous lipid mediators are spatiotemporally biosynthesized to actively regulate resolution by acting on specific G protein-coupled receptors (GPCRs) to initiate anti-inflammatory and pro-resolving signals that terminate inflammation. In this review, we will discuss the mechanism of actions of these molecules, including their analgesic and bone-sparing properties making them ideal therapeutic agonists for the treatment of inflammatory diseases such as rheumatoid arthritis.


Cost-effectiveness analysis of rituximab versus natalizumab in patients with relapsing remitting multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory disease in which the myelin sheaths of the nerve cells in the brain and spinal cord, which are responsible for communication, are destroyed and cause physical signs and symptoms. According to studies, anti-CD20 monoclonal antibodies have significant results in the treatment of this disease. Thus, the aim of the present study was to determine the cost-effectiveness of rituximab against natalizumab in the patients with RRMS in southern Iran in 2020. This is an economic evaluation including cost-effectiveness analysis in which the Markov model with a lifetime horizon was used. The study sample consisted of 120 patients randomly selected from among those referred to the MS Association and the Special Diseases Unit of Shiraz University of Medical Sciences. In this study, the costs were collected from a societal perspective, and the outcomes were obtained in the form of Quality Adjusted Life Years (QALY) and the mean relapse rate. The TreeAge pro 2020 and Excel 2016 software were used for data analysis. The comparative study of rituximab and natalizumab showed that the patients receiving rituximab had lower costs ($ 58,307.93 vs. $ 354,174.85) and more QALYs (7.77 vs. 7.65). In addition, the incidence of relapse by rituximab was lower compared to natalizumab (1.15 vs. 2.57). The probabilistic one-way sensitivity analysis showed the robustness of the results. The scatter plots also showed that rituximab was more cost-effective for the patients in 100% of the simulations for the threshold of < $ 37,641. According to the results of this study, rituximab had higher cost-effectiveness than natalizumab. Therefore, it could be a priority for RRMS patients compared to natalizumab because it reduced treatment costs and increased effectiveness.


Incidence and significance of FLT3-ITD and NPM1 mutations in patients with normal karyotype acute myeloid leukaemia.
Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic progenitor cells. Approximately half of all adult AML patients have a normal karyotype (NK-AML) and an intermediate risk prognosis. To determine the incidence and prognostic significance of NPM1 and FLT3-ITD mutations in a population of patients with NK-AML. FLT3-ITD and NPM1 mutation status was retrospectively sought in presentation samples from 44 NK-AML patients. FLT3-ITD and NPM1 mutations were detected in 45.5 and 54.5% of patients, respectively, allowing stratification according to genotype. FLT3-ITD and NPM1 mutation status can be defined in NK-AML. Prospective screening for these mutations is advocated in all NK-AML patients, as the genotype is of clinical importance when considering treatment options including stem cell transplantation.


Comparison of clinical outcomes of conbercept versus ranibizumab treatment for retinopathy of prematurity: a multicentral prospective randomised controlled trial.
To compare the recurrence rate and surgical complications of retinopathy of prematurity (ROP) between patients treated with intravitreal injection of conbercept (IVC) and intravitreal injection of ranibizumab (IVR) within 6 months. A multicentral prospective, randomised controlled trial was applied from May 2017 to February 2019 for the infants diagnosed as aggressive posterior-ROP, zone I or posterior zone II treatment-requiring ROP by binocular indirect ophthalmoscope and RetCam3. These infants were assigned to randomly receive either intravitreal injection of 0.25 mg conbercept or 0.25 mg ranibizumab. The recurrence rate, fundus fluorescence angiography (FFA) and surgical complications were examined during the follow-up period of 6 months. Recurrent eyes were retreated by laser or another intravitreal injection within the 72 hours. A total of 30 infant patients (60 eyes) underwent IVC and 30 patients (60 eyes) underwent IVR. A total of 10 eyes (16.67%) in the IVC group and 14 eyes (23.34%) in the IVR group developed recurrence. There was no significant statistical difference in the recurrence rate between the two groups (χ2=0.83, p=0.36). The postmenstrual age (PMA) at first injection was (34.60±3.47) weeks in IVC and (35.14±1.76) in IVR group. In recurrent cases, the mean PMA at second treatment were (43.31±3.85) and (43.43±3.89) weeks in the IVC and IVR group, respectively. The period between two treatments was (8.71±6.62) for the IVC and (8.29±2.56) weeks for the IVR group. All these results showed no significant statistical difference between these two groups. The fluorescein leakage were observed in the eyes of recurrent infants by FFA. There were no other complications in the two groups except for complicated cataract in three eyes. Both IVC and IVR are effective therapies for the treatment of ROP. Conbercept is a new option for treating ROP.