[Diabetes and pregnancy].
We tried to summarize our and foreign experience in the field of diabetes and pregnancy Our aim was to detect pregnant women with diabetes mellitus, as well as to introduce screening method for early detection and apply a suitable diet and treatment for these patients. Patients with diabetes and pregnancy were researched for the period of 2007-2014 (70 patients). Introducing a screening method in the second trimester between 24-28 gestational week, applying a suitable diet and treatment lead to better outcome of this disease and to more safe delivery outcome. Future research work will give additional light in this field.


Examining conscious motor processing and the effect of single-task, dual-task and analogy training on walking during rehabilitation by older adults at risk of falling in Hong Kong: Design and methodology of a randomized controlled trial.
Walking is a common activity among older adults. Fallers were discovered to have a higher propensity to conscious motor processing (reinvestment) than age-matched non-fallers, leading to movement disruption, possibly by constraining or interfering with automatic motor control mechanisms. However, gait rehabilitation programs by implicit motor learning methodologies may ameliorate reinvestment propensity while improving gait ability in older adults. One hundred and five older adults, with moderate to high risk of falling, will be recruited from different community centres in Hong Kong to investigate the effect of single-task, dual-task and analogy training (implicit motor learning methodologies) on walking during rehabilitation in the context of reinvestment propensity, balance, walking ability and fear of falling. Participants will be randomly allocated and received 12 training sessions in either a Single-task Walking Group (STWG), a Dual-task Walking Group (DTWG) or an Analogy Walking Group (AGWG). Reinvestment propensity, walking ability, balance and fear of falling will be assessed by the Chinese version Movement Specific Reinvestment Scale (MSRS-C), 10-meter Walk Test, Tinetti Balance Assessment Tool, Timed 'Up & Go' Test (TU&G), Berg Balance Scale (BBS) and 13-item Falls Efficacy Scale (FES-13), respectively at baseline before training (T0), just after completion of all training sessions (T1), and 6 months after completion of all training sessions (T2). Participants' number of falls between T1 and T2 will also be recorded. The results could establish a solid foundation for further development and implementation of a novel and effective gait rehabilitation program in fall prevention for older adults at risk of falling.


Barriers to cervical cancer screening faced by immigrant women in Canada: a systematic scoping review.
The objective of this scoping study is to review the published literature and summarize findings related to barriers experienced by immigrant women in Canada while accessing cervical cancer screening. Electronic databases of peer-reviewed articles and grey literature were searched using comprehensive sets of keywords, without restricting the time period or language. Articles were selected based on the following criteria: (a) the study population consisted of Canadian immigrant women and healthcare providers and other stakeholders serving immigrant women, (b) the research focused on the barriers to accessing cervical cancer screening, and (c) the study was conducted in Canada. Extracted data were grouped and analyzed, resulting in barriers comprised of six themes: economic barriers, cultural barriers, language barriers, healthcare system-related barriers, knowledge-related barriers, and individual-level barriers. Lack of education, low income, preference for a female physician, lack of knowledge, lack of effective communication, and embarrassment were some of the most common barriers mentioned. Immigrant access to health services, including cervical cancer screening, is a complex issue concerning a wide range of barriers. Our findings offer insights into barriers to cervical cancer screening in immigrant communities in Canada that can be used to assist policymakers, healthcare providers, and researchers enhance the health and well-being of these populations by mitigating barriers and improving screening.


An examination of heme action in gene expression: heme and heme deficiency affect the expression of diverse genes in erythroid k562 and neuronal PC12 cells.
The aim of this study was to identify key genes whose expression is altered by heme and heme deficiency in the human erythroleukemia K562 cells and in the NGF-induced rat pheochromocytoma neuronal PC12 cells, respectively. By quantitative RT-PCR, Northern blotting, and Western blotting analyses, we found that the expression of the CDK inhibitors p18 and p21 was upregulated at the early and late stages of heme-induced erythroid differentiation of K562 cells, respectively, while the expression of cyclin D1 was downregulated. Data from succinyl acetone and desferrioxamine treatments suggest that these effects of heme in K562 cells were specific. Further, by microarray expression analysis, we found that inhibition of heme synthesis by succinyl acetone in NGF-induced PC12 cells drastically altered the expression of several groups of important neuronal genes, including the structural genes encoding neurofilament proteins and synaptic vesicle proteins, regulatory genes encoding signaling components beta-arrestin and p38 MAPK, and stress-response genes encoding hsp70. These results show that heme and heme deficiency affect the expression of diverse genes in a cell-type specific manner in mammalian cells, and that heme, although needed at different levels, is critical for both erythropoiesis and neurogenesis. These studies provide insights into how heme may act to control diverse regulatory processes in mammals.


Platelet plug formation in an extracorporeal unit.
Platelet plugs were formed in an extracorporeal unit from flowing venous blood and studied by electron microscopy. The unit consisted of a stainless steel needle threaded into a section of silicone rubber tubing that was constricted to form a slit-like stenosis equivalent in cross-sectional area to an arteriole 100 mu in diameter. Blood was allowed to flow at a steady pressure from an antecubital vein through a collection line and the attached unit until bleeding was stopped by the formation of a platelet plug at the stenosis. Electron microscopy of the plugs showed closely packed aggregated platelets. No fibrin was detected. The formation of a stable plug in the absence of fibrin was considered a measure of the capacity of platelets in hemostasis and thrombosis to aggregate and resist the force of the blood current.


Maternal immunization with a herpes simplex virus type 2 replication-defective virus reduces visceral dissemination but not lethal encephalitis in newborn mice after oral challenge.
Herpes simplex virus (HSV) causes devastating infections in newborns. Maternal immunization is one potential strategy to reduce neonatal HSV disease. Female mice were immunized with an HSV type 2 (HSV-2) replication-defective mutant (HSV-2 dl5-29, which is defective for the genes UL5 and UL29) and then mated. Protection was evaluated in newborn mice after a virulent HSV-2 oral challenge. Heightened neonatal susceptibility was observed to a thymidine kinase-negative HSV-2 strain (HSV-2 186DeltaKpn) that is highly attenuated in adult mice. Maternal immunization with HSV-2 dl5-29 and HSV-2 186DeltaKpn reduced visceral spread of infectious challenge virus in pups after challenge at either 1 day or 1 week of age but did not prevent replication at the site of entry, spread to the central nervous system, or lethal encephalitis. No protection was seen in pups born to mock-immunized mothers or to mothers immunized with a UV-inactivated wild-type HSV-2 strain. Levels of protection correlated with levels of passively transferred maternal HSV-2-specific IgG antibody.


An Efficient Fusion-Based Defogging.
Degradation in visibility is often introduced to images captured in poor weather conditions, such as fog or haze. To overcome this problem, conventional approaches focus mainly on the enhancement of the overall image contrast. However, because of the unspecified light-source distribution or unsuitable mathematical constraints of the cost functions, it is often difficult to achieve quality results. In this paper, a fusion-based transmission estimation method is introduced to adaptively combine two different transmission models. Specifically, the new fusion weighting scheme and the atmospheric light computed from the Gaussian-based dark channel method improve the estimation of the locations of the light sources. To reduce the flickering effect introduced during the process of frame-based dehazing, a flicker-free module is formulated to alleviate the impacts. The systematic assessments show that this approach is capable of achieving superior defogging and dehazing performance, compared with superior defogging and dehazing performance, compared with the state-of-the-art methods, both quantitatively and qualitatively.


Annexin A2 Acts as an Adhesion Molecule on the Endometrial Epithelium during Implantation in Mice.
To determine the function of Annexin A2 (Axna2) in mouse embryo implantation in vivo, experimental manipulation of Axna2 activities was performed in mouse endometrial tissue in vivo and in vitro. Histological examination of endometrial tissues was performed throughout the reproduction cycle and after steroid treatment. Embryo implantation was determined after blockage of the Axna2 activities by siRNA or anti-Axna2 antibody. The expression of Axna2 immunoreactivies in the endometrial luminal epithelium changed cyclically in the estrus cycle and was upregulated by estrogen. After nidatory estrogen surge, there was a concentration of Axna2 immunoreactivities at the interface between the implanting embryo and the luminal epithelium. The phenomenon was likely to be induced by the implanting embryos as no such concentration of signal was observed in the inter-implantation sites and in pseudopregnancy. Knockdown of Axna2 by siRNA reduced attachment of mouse blastocysts onto endometrial tissues in vitro. Consistently, the number of implantation sites was significantly reduced after infusion of anti-Axna2 antibody into the uterine cavity. Steroids and embryos modulate the expression of Axna2 in the endometrial epithelium. Axna2 may function as an adhesion molecule during embryo implantation in mice.


International Life Sciences Institute North America Listeria monocytogenes strain collection: development of standard Listeria monocytogenes strain sets for research and validation studies.
Research and development efforts on bacterial foodborne pathogens, including the development of novel detection and subtyping methods, as well as validation studies for intervention strategies can greatly be enhanced through the availability and use of standardized strain collections. These types of strain collections are available for some foodborne pathogens, such as Salmonella and Escherichia coli. We have developed a standard Listeria monocytogenes strain collection that has not been previously available. The strain collection includes (i) a diversity set of 25 isolates chosen to represent a genetically diverse set of L. monocytogenes isolates as well as a single hemolytic Listeria innocua strain and (ii) an outbreak set, which includes 21 human and food isolates from nine major human listeriosis outbreaks that occurred between 1981 and 2002. The diversity set represents all three genetic L. monocytogenes lineages (I, n = 9; II, n = 9; and III, n = 6) as well as nine different serotypes. Molecular subtyping by EcoRI automated ribotyping and pulsed-field gel electrophoresis (PFGE) with AscI and ApaI separated the 25 isolates in the diversity set into 23 ribotypes and 25 PFGE types, confirming that this isolate set represents considerable genetic diversity. Molecular subtyping of isolates in the outbreak set confirmed that human and food isolates were identical by ribotype and PFGE, except for human and food isolates for two outbreaks, which displayed related but distinct PFGE patterns. Subtype and source data for all isolates in this strain collection are available on the Internet and are linked to the PathogenTracker database (www.pathogentracker.com), which allows the addition of new, relevant information on these isolates, including links to publications that have used isolates from this collection. We have thus developed a core L. monocytogenes strain collection, which will provide a resource for L. monocytogenes research and development efforts with centralized Internet-based data curation and integration.


miR-21 promotes dengue virus serotype 2 replication in HepG2 cells.
Infection with the mosquito transmitted dengue virus (DENV) remains a significant worldwide public health problem. While the majority of infections are asymptomatic, infection can result in a range of symptoms. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through repression or degradation of mRNAs. To understand the contribution of miRNAs to DENV 2 replication, we screened a number of candidate miRNAs for variations in expression levels during DENV 2 infection of HepG2 (liver) cells. Seven miRNAs were identified as differentially expressed, and one, miR-21, was differentially expressed at all time points examined. Interestingly, miR-21 was also differentially regulated in DENV 2 infection under conditions of antibody dependent enhancement of infection, and in direct Zika virus infection, but not in DENV 4 infection. The role of miR-21 during DENV infection was further examined by treating HepG2 cells with an anti-miR-21 (AMO-21) before DENV infection. The results showed a significant reduction in DENV 2 production, clearly suggesting that miR-21 plays a key role in DENV 2 replication. To further confirm the role of miR-21 in DENV infection, a peptide nucleic acid-21 (PNA-21) construct with a nucleotide sequence complementary to AMO-21, was co-administered with AMO-21 as an AMO-21/PNA-21 complex followed by DENV 2 infection. The results showed that AMO-21 significantly reduced DENV 2 titer, PNA-21 significantly increased DENV 2 titer and the combined AMO-21/PNA-21 showed no difference from non-treated infection controls. Taken together, the results show that miR-21 promotes DENV 2 replication, and this mechanism could serve as a possible therapeutic intervention point.


[Reliability of low platelet counts--comparison of microscopic counts with automated hematology analyzer XE-2100].
Sysmex XE-2100 is an automated hematological analyzer with excellent features that can count platelets by both impedance and optical fluorescent method. Particularly, it is notable that platelet counts by optical fluorescent method (PLT-O) are automatically adopted when platelet counts by impedance method (PLT-I) are less than 50 x 10(3)/microl or platelets have abnormal distribution. We compared PLT-I with PLT-O, and also with microscopic counts, using the samples with thrombocytopenia. Regarding reproducibility, mean coefficient of variation values were 5.3% in both PLT-I and PLT-O, when no flags of "PLT Abn Distribution" appeared in the samples with thrombocytopenia. Coefficient of variation values was 10.4% in PLT-I and 5.9% in PLT-O, when flags of "PLT Abn Distribution" appeared in the sample with thrombocytopenia. Correlation among the data obtained by PLT-I, PLT-O and microscopic counts were excellent. When a large difference was observed between PLT-I and PLT-O, PLT-O was more closely consistent with microscopic counts. PLT-O was useful compared with PLT-I, and this system was considered to measure platelet counts more correctly in the samples with thrombocytopenia. Thus, it was suggested that reliable platelet counts could be reported even in the samples with thrombocytopenia by switching system in XE-2100.


Cholera toxin B-subunit prevents activation and proliferation of human CD4+ T cells by activation of a neutral sphingomyelinase in lipid rafts.
The inhibition of human CD4+ T lymphocyte activation and proliferation by cholera toxin B-subunit (CTB) is a well-established phenomenon; nevertheless, the exact mechanism remained unclear. In the present study, we propose an explanation for the rCTB-induced inhibition of CD4+ T lymphocytes. rCTB specifically binds to GM1, a raft marker, and strongly modifies the lipid composition of rafts. First, rCTB inhibits sphingomyelin synthesis; second, it enhances phosphatidylcholine synthesis; and third, it activates a raft-resident neutral sphingomyelinase resembling to neutral sphingomyelinase type 1, thus generating a transient ceramide production. We demonstrated that these ceramides inhibit protein kinase Calpha phosphorylation and its translocation into the modified lipid rafts. Furthermore, we show that rCTB-induced ceramide production activate NF-kappaB. Combined all together: raft modification in terms of lipids, ceramide production, protein kinase Calpha inhibition, and NF-kappaB activation lead to CD4+ T cell inhibition.


Changing Student Perception of an Online Integrated Structured Clinical Examination During the COVID-19 Pandemic.
The COVID-19 pandemic has created a hiatus in in-person clinical assessments due to safety and logistical concerns. We aimed to evaluate student perception and utility of an online Integrated Structured Clinical Examinations (ISCEs) during the pandemic. Final-year medical students from a single institution were offered an online mock ISCE through a student-to-student ("near-peer") teaching-programme. A questionnaire-based cross-sectional study was conducted pre- and post-online mock ISCE. Sixty-four students completed the study. Pre- and post-data showed an increase in confidence (p<0.0001), less worry regarding the online format (p<0.0001) and less anxiety about excelling in ISCEs (p<0.001). Students felt that having done the mock, an online format would more positively affect their overall performance (p=0.007). This study demonstrates a positive change in student perception and confidence in online ISCEs. Online ISCEs are thus feasible, though sole reliance on this format may provide an incomplete assessment of student's overall clinical competency.


Research about suppression effect and auditory processing in individuals who stutter.
To verify the auditory processing abilities and occurrence of the suppression effect of Otoacoustic Emissions (OAE) in individuals who stutter. The study sample comprised 15 adult individuals who stutter, aged 18-40 years, with stuttering severity ranging from mild to severe, paired according to gender, age, and schooling with individuals without speech complaint or disorder. All participants underwent conventional clinical evaluation, specific stuttering assessment, and basic (audiometry, imitanciometry, and measurement of acoustic reflexes) and specific (auditory processing evaluation and measurement of suppression effect of OAEs) audiological assessments. Data were statistically analyzed with application of the Fisher's Exact Test and the Mann-Whitney Test. The group of individuals who stutter (Study Group - SG) presented higher incidence of auditory processing disorders. The auditory processing assessments used to differentiate the groups of stutterers and non-stutterers (Control Group - CG) were the Nonverbal Dichotic Test and the Frequency Pattern Test. The SG presented higher incidence of absence of suppression effect of OAEs, indicating abnormal functioning of the efferent medial olivocochlear system. The auditory processing abilities investigated in this study differentiate individuals who stutter from non-stutterers, with greater changes in the first. Functioning of the efferent medial olivocochlear system showed a deficit in stutterers, indicating difficulties in auditory discrimination, especially in the presence of noise.


Phylogeography of Daphnia magna Straus (Crustacea: Cladocera) in Northern Eurasia: Evidence for a deep longitudinal split between mitochondrial lineages.
Species with a large geographic distributions present a challenge for phylogeographic studies due to logistic difficulties of obtaining adequate sampling. For instance, in most species with a Holarctic distribution, the majority of studies has concentrated on the European or North American part of the distribution, with the Eastern Palearctic region being notably understudied. Here, we study the phylogeography of the freshwater cladoceran Daphnia magna Straus, 1820 (Crustacea: Cladocera), based on partial mitochondrial COI sequences and using specimens from populations spread longitudinally from westernmost Europe to easternmost Asia, with many samples from previously strongly understudied regions in Siberia and Eastern Asia. The results confirm the previously suspected deep split between Eastern and Western mitochondrial haplotype super-clades. We find a narrow contact zone between these two super-clades in the eastern part of Western Siberia, with proven co-occurrence in a single lake in the Novosibirsk region. However, at present there is no evidence suggesting that the two mitochondrial super-clades represent cryptic species. Rather, they may be explained by secondary contact after expansion from different refugia. Interestingly, Central Siberia has previously been found to be an important contact zone also in other cladoceran species, and may thus be a crucial area for understanding the Eurasian phylogeography of freshwater invertebrates. Together, our study provides an unprecedented complete, while still not global, picture of the phylogeography of this important model species.


A novel pathogenic missense ADAMTS17 variant that impairs secretion causes Weill-Marchesani Syndrome with variably dysmorphic hand features.
Weill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and ectopia lentis. Brachydactyly and joint stiffness appear less commonly in patients with WMS4 caused by pathogenic ADAMTS17 variants. Here, we investigated a large family with WMS from Newfoundland, Canada. These patients displayed core WMS features, but with proportionate hands that were clinically equivocal for brachydactyly. Whole exome sequencing and autozygosity mapping unveiled a novel pathogenic missense ADAMTS17 variant (c.3068 G > A, p.C1023Y). Sanger sequencing demonstrated variant co-segregation with WMS, and absence in 150 population matched controls. Given ADAMTS17 involvement, we performed deep phenotyping of the patients' hands. Anthropometrics applied to hand roentgenograms showed that metacarpophalangeal measurements of affected patients were smaller than expected for their age and sex, and when compared to their unaffected sibling. Furthermore, we found a possible sub-clinical phenotype involving markedly shortened metacarpophalangeal bones with intrafamilial variability. Transfection of the variant ADAMTS17 into HEK293T cells revealed significantly reduced secretion into the extracellular medium compared to wild-type. This work expands understanding of the molecular pathogenesis of ADAMTS17, clarifies the variable hand phenotype, and underscores a role for anthropometrics in characterizing sub-clinical brachydactyly in these patients.


How tetraspanins shape endothelial and leukocyte nano-architecture during inflammation.
Tetraspanins are ubiquitous membrane proteins that induce local membrane curvature and hence co-ordinate cell-to-cell contacts. This review highlights their role in inflammation, which requires control of the nano-architecture of attachment sites between endothelial cells and leukocytes. The active role of endothelial cells in preparing for transmigration of leukocytes and determining the severity of an inflammation is often underscored. A clear hint to endothelial pre-activation is their ability to protrude clustered adhesion proteins upward prior to leukocyte contact. The elevation of molecular adhesive platforms toward the blood stream is crucially dependent on tetraspanins. In addition, leukocytes require tetraspanins for their activation. The example of the B-cell receptor is referenced in some detail here, since it provides deeper insights into the receptor-coreceptor interplay. To lift the role of tetraspanins from an abstract model of inflammation toward a player of clinical significance, two pathologies are analyzed for the known contributions of tetraspanins. The recent publication of the first crystal structure of a full-length tetraspanin revealed a cholesterol-binding site, which provides a strong link to the pathophysiological condition of atherosclerosis. Dysregulation of the inflammatory cascade in autoimmune diseases by endothelial cells is exemplified by the involvement of tetraspanins in multiple sclerosis.


Immunomodulatory Activity of MicroRNAs: Potential Implications for Multiple Myeloma Treatment.
Multiple myeloma (MM) is an incurable plasma cell neoplasm accounting for about 10% of all hematologic malignancies. Recently, emerging evidence is disclosing the complexity of bone marrow interactions between MM cells and infiltrating immune cells, which have been reported to promote proliferation, survival and drug resistance of tumor cells. MicroRNAs (miRNAs) are small non-coding RNA molecules with regulatory functions in the cell, whose expression has predictive and prognostic value in different malignancies. MiRNAs are gaining increasing interest due to their capability to polarize the immune-response through different mechanisms, which include the molecular reprogramming of immune cells. This characteristic, together with the antitumor activity of miRNA mimics or inhibitors, make the miRNA network an attractive area of investigation for novel anti-MM therapeutic approaches. In this review, we will discuss the recent advances in the understanding of the interplay between MM cells and bone marrow resident immune cells, with special focus on the molecular and functional changes induced by miRNA network modulation. We will finally indicate potential targets for therapeutic intervention.


What was the immediate impact on population health of the recent fall in hormone replacement therapy prescribing in England? Ecological study.
The publication in 2002 of the women's health initiative (WHI) trial revealed long-term risks and benefits of hormone replacement therapy (HRT). Increased cardiovascular disease, venous thromboembolism and breast cancer risks outweighed benefits on hip fracture, colorectal and endometrial cancer. We investigated whether the subsequent 50% fall in HRT use in England impacted on population rates of these outcomes. Time-series analysis of hospital admissions, incidence and mortality amongst women aged 50-69, England 1997-2006. There was no relationship between reduced HRT prescribing after 2002 and trends in breast cancer, colorectal cancer or hip fracture. Amongst 50-59 year olds, the annual percentage change in venous thromboembolism hospitalizations fell from 0.0% [95% confidence interval (CI): -2.3 to 2.3%] between 1997 and 2000 to -5.7% (-7.7 to -3.6%) between 2000 and 2006 (P-value = 0.001); the annual change in endometrial cancer mortality increased from 0.7% (-3.2 to 4.8%) between 1997 and 2003 to 11.0% (0.2 to 22.9%) after 2003 (P-value = 0.07); and previously falling acute myocardial infarction hospitalizations (annual change: -6.8%) and stroke (-3.0%) stabilized (-0.4%) or increased (+0.8%), respectively, around 2001 (P < 0.0001). Although rates of venous thromboembolism (decline) and endometrial cancer mortality (increase) changed in line with WHI findings, the decline in venous thromboembolism may have started before 2002 and increased fatal endometrial cancers could be a chance finding.


Bioaccumulation of Some Heavy Metals in the Liver Flukes Fasciola hepatica and F. gigantica.
Heavy metals tend to bioaccumulate in living organisms, and their accumulation has been a major concern. As mammals are known to excrete heavy metals via their bile, it seems to be very promising to analyse metal burdens of parasites that infect the biliary tree such as liver flukes of the genus Fasciola. The present study was carried out to evaluate F. hepatica and F. gigantica as bioaccumulators of heavy metals, and to estimate their use as sensitive markers of environmental pollution with heavy metals. A total of 36 slaughtered buffaloes (26 infected and 10 controls) collected from the slaughter-house of Tanta City, Egypt were used. Samples of muscle and liver tissues were taken from each buffalo. A total of 44 adult Fasciola flukes were collected from the 26 infected buffaloes. Quantification of some heavy metals (Cd, Cr, Cu, Pb and Zn) in samples was carried out using electrothermal atomic absorption spectrometry. Results revealed different concentrations of heavy metals in different host tissues. The adult flukes were classified into F. hepatica (n = 25) and F. gigantica (n = 19). The bio-concentration factor (BCF) of Cr was significantly higher in F. hepatica (P = 0.0465) while BCF of Zn was significantly higher in F. gigantica (P = 0.0189). A comparative study between the two species as regards the BCF was never done before. The obtained results indicate the possibility of use of Fasciola flukes as markers of environmental pollution with some heavy metals.


A diagnostic electronic reporting framework proposal using preassigned automated coded phrases.
Radiologists daily diagnose a large number of Chest X-rays and it is crucial that these reports are appropriately recorded, meaningfully indexed, carefully stored, easily retrieved, shared and printed. The absence of organized reports' storage does not permit their direct and easy retrieval, while after almost a year the report is perished and not even readable (handwritten or typed). The scope of this paper is to evaluate and propose the use of preassigned automated-coded phrases for the chest X-ray electronic reporting in a Radiology Department. The research included 9,252 typed reports, using the proposed method and 949 hand written reports (later typed or not), which were used to compare between the time being spent in reporting with either method. The results proved that even if the method could not be applied fully, there was a 90% reduction of the time being spent by the radiologists and secretarial staff in a Radiology Department, thereby facilitating the typing and management of the electronic archives. In addition, it was found that the reprinting due to addendums/discrepancies, when the proposed method was used, was reduced fourfold, when compared to the previously used methods. In conclusion, the consistent application of preassigned automated-coded reporting can be time saving, cost effective and environmentally friendly saving paper and ink.


[Effect of regulatory light chains of myosin on aggregation of its subfragment-1].
Chymotryptic (Ch-Cl) and Mg(2+)-papain subfragments 1 of (Mg-Cl) skeletal myosin has been studied. Mg-Cl is known to differ from Ch-Cl by the presence of the regulatory light chain (RLC) and elongated heavy chain including C-end hinge segment. Experimental data prove the decisive part of coordination bondings with bivalent cations in stabilization of RLV on myosin head hinge segment. Hydrophobic interactions are also significant that is evidenced by the intensive aggregation between subfragment Mg-Cl molecules, after RLC dissociation.


A phenotype resembling the Clouston syndrome with deafness is associated with a novel missense GJB2 mutation.
Mutations in GJB2 (connexin26) are associated with skin disorders and deafness. The Clouston syndrome (MIM129500) is associated with mutations in GJB6 (connexin30). Here, we describe a patient suffering from a Clouston-syndrome-like phenotype of thin hair, deafness, nail dystrophy, and mild erythrokeratoderma, caused by a novel spontaneous missense mutation in GJB2. The heterozygous mutation in codon 42, AAC>AAG, changes asparagine to lysine (N14K). Interestingly, this asparagine is near two of the residues mutated in Keratitis-like ichthyosis deafness (KID) syndrome (G12R and S17F), yet the phenotype associated with N14K strongly differs from the KID phenotype. Instead, there is a clear phenotypic overlap with syndromes associated with connexin26 or 30 mutations. Our finding suggest that careful audiological evaluation of patients suffering from Clouston-syndrome-like phenotypes is warranted and expand the spectrum of connexin26-associated disease.


Chemical conversion of mouse fibroblasts into functional dopaminergic neurons.
Ectopic expression of lineage-specific transcription factors facilitates the conversion of mammalian somatic cells into dopaminergic (DA) neurons, which is a promising strategy for cell therapy of Parkinson's disease (PD). However, this approach still has some drawbacks limiting its clinical application due to the potential risks of integrating vectors into the host genome. Therefore, it is critical to seek a more desired approach to generate DA neurons derived from mammalian somatic cells. Here, we report that mouse embryonic fibroblasts (MEFs) can be efficiently converted into DA neurons by using small molecules along with specific growth factors. These neuron-like cells generate DA neuronal morphology, and acquire immunocytochemical and calcium imaging special for neuronal electrophysiological profile. More importantly, these converted cells can secrete dopamine, indicating that they are functionally similar to DA neurons. Taken together, our study might provide a promising cell source for treating PD by using chemical approach without introduction of exogenous transcription factors.


Development and initial assessment of the medication user self-evaluation (MUSE) tool.
Using patient-reported data to supplement claims-based indicators may be helpful in identifying Medicare beneficiaries likely to benefit from medication therapy management (MTM) services. Our objective was to develop and initially assess a patient medication user self-evaluation (MUSE) tool to identify Medicare Part D beneficiaries who would benefit from a comprehensive medication review. A random sample of 225 patient medication profiles was created from a survey of Medicare beneficiaries; the survey also included demographic characteristics, responses to adherence questions, and reported symptoms. Three clinical pharmacists used the patient profiles to make judgments regarding the likelihood (low, moderate, or high) that each patient would benefit from an MTM visit in the next 3 months. A total of 150 cases were used for model calibration, and 75 were used for validation. Ordinal logistic regression models were fit to predict the likelihood of benefit from an MTM visit by using different combinations of potential MUSE items. Final model selection was based on the Akaike information criterion and the percent agreement between model prediction and expert judgments in the validation data. Measures considered for inclusion in the MUSE tool were related to medication use, medical conditions, and health care utilization. The final MUSE items incorporated number of medications, number of physicians, number of pharmacies, number of hospitalizations in the past 6 months, having forgotten to take medications, cost-related problems, and number of medical conditions. The 7-item MUSE tool could be used in targeting MTM services, such as comprehensive medication reviews, among Medicare beneficiaries.


New Complexes of Antimony(III) with Tridentate O,E,O-Ligands (E = O, S, Se, Te, NH, NMe) Derived from N-Methyldiethanolamine.
We synthesized a series of new antimony(III) compounds by reaction of Sb(OEt)3 with organic ligands of the type E(CH2-CH2-OH)2, with E = NH, NMe, O, S, Se, and Te. The synthesized compounds have the general composition [E(CH2-CH2-O)2]Sb(OEt). For comparison, the compound (O-CH2-CH2-S)Sb(OEt) was prepared. All compounds are characterized using NMR, IR, and Raman spectroscopy. The molecular structures of the products reveal the formation of chelate complexes, wherein the ligand molecules coordinate as tridentate O,E,O-ligands to the antimony atom. Dimer formation in the solid state allows the antimony atoms to reach pentacoordination. Quantum chemical calculations including topological analysis of electron density reveal that there are polar shared bonds between antimony and the oxygen atoms bound to antimony. The interactions between the donor atom E and the Sb atom and the interactions in the dimers can be characterized as Van der Waals interactions. The reactivity of [MeN(CH2-CH2-O)2]Sb(OEt) was investigated as an example. For this purpose, the compound reacted with a range of organic compounds such as carboxylic acids and carboxylic anhydrides and small molecules like CO2 and NH3. This study establishes a new and easy accessible class of antimony(III) compounds, provides new insights into the chemistry of antimony compounds and opens up new opportunities for further research in this field.


[Tension-type headache].
Tension-type headache is the most common type of primary headache. Life time prevalence of tension-type headache in general population ranges from 30 to 78%. It is the least studied of the primary headache disorders, despite the fact that it has the highest socio-economic impact. In the new 'The International Classification of Headache Disorders', tension-type headache is divided into episodic and chronic subtypes. The exact mechanisms of tension -type headache are not known. Peripheral pain mechanisms are most likely to play a role in episodic headache, whereas central pain mechanisms play a more important role in chronic tension-type headache. Treatments of tension-type headache include not only medication but also the physical therapy. In many uncertain cases there is overuse of medication. Two months after medication overuse has ceased, chronic tension-type should be diagnosed.


Ultrastructural basis of impulse propagation failure in a nonbranching axon.
The morphological basis of intermittent conduction failure in the excitor axon innervating the crayfish opener and stretcher muscles was investigated using the electron microscope. The connective tissue component of the sheath surrounding the axon was found consistently to be thinner in the region at which blocking occurs than in control regions located one cm either proximally or distally, at which blocking does not occur. Otherwise in these regions differences in the width of the periaxonal spaces, the length or width of the mesaxons, the density of mitochondria, the width of the adaxonal glial cell layer, or the structure of lamination of the sheath are not observed. Because of the thinner connective tissue component of the sheath in the joint region, neighboring axons are distributed more densely around the excitor, and the volume of the extracellular space is reduced. The possibility that the reduced extracellular space might allow excessive accumulation of potassium during repetitive discharge, causing conduction block, is discussed. Alternative mechanisms consistent with this morphology are also considered.


Passive immunization with monoclonal antibodies against herpes simplex virus glycoproteins protects mice against herpetic ocular disease.
The effects of passive immunization with specific monoclonal antibodies against herpes simplex virus glycoproteins gB, gC, gD, and gE on the course of herpetic keratitis, survival and the establishment of latency in an outbred mouse model are described. A total of nine monoclonal antibodies were tested in these experiments. Passive immunization at 24 or 48 hours post-inoculation had little effect on the severity of the initial epithelial infection of the cornea, but blocked dissemination of the virus to the central nervous system and periocular tissues and prevented development of blepharitis, iritis and stromal keratitis. Additional studies are needed to characterize these monoclonal antibodies in greater detail, and to define the mechanism of these protective effects.


The Asbestos Ban in Korea from a Grassroots Perspective: Why Did It Occur?
In 2009, asbestos was finally banned in Korea, about 70 years after the first opening of asbestos mines under Japanese control. After having presented the history of asbestos industry, together with its regulations and health effects over time, we constructed narrative analyses of how the asbestos issue under the prevailing risk system was managed by whom and for what purpose, to provide context for the change. We could identify five different phases: laissez-faire, politico-technical, economic-managerial, health-oriented cultural, and human rights-based post-cultural risk systems. The changes leading to the asbestos ban evolved over different phases, and each phase change was necessary to reach the final ban, in that, without resolving the previous issues by examining different categories of potential alternatives, either the final ban was not possible or, even if instituted, could not be sustained. An asbestos ban could be introduced when all the alternatives to these issues, including legitimate political windows, economic rationalizations, health risk protections, and human rights sensitivities, were available. We think the alternatives that we had were not in perfect shape, but in more or less loosely connected forms, and hence we had to know how to build solidarities between different stakeholders to compensate for the imperfections.


[Mesenteric venous thrombosis].
Mesenteric venous thrombosis (MVT) is a serious though rare abdominal disease. MVT often takes a subacute course with non-specific symptoms. The absence of simple and precise diagnostic tools result in delayed start of treatment and high mortality. Through information retrieval we have here given an overview of the incidence, etiology, pathophysiology, symptomatology, diagnosis, treatment and prognosis of MVT.


Effects of perceived disability on persuasiveness of computer-synthesized speech.
Are perceptions of computer-synthesized speech altered by the belief that the person using this technology is disabled? In a 2 x 2 factorial design, participants completed an attitude pretest and were randomly assigned to watch an actor deliver a persuasive appeal under 1 of the following 4 conditions: disabled or nondisabled using normal speech and disabled or nondisabled using computer-synthesized speech. Participants then completed a posttest survey and a series of questionnaires assessing perceptions of voice, speaker, and message. Natural speech was perceived more favorably and was more persuasive than computer-synthesized speech. When the speaker was perceived to be speech-disabled, however, this difference diminished. This finding suggests that negatively viewed assistive technologies will be perceived more favorably when used by people with disabilities.


Experimental investigation of double-groove grating satisfying total internal reflection condition.
We experimentally demonstrate a TiO(2) double-groove grating coupler with two different groove widths on a SiO(2) substrate in the visible region. Tolerance investigations based on Bloch-mode profiles in the grating and coupling strengths between the Bloch modes and diffraction orders reveal that the transmission performance is robust when one of the paired ridges is narrow enough (60 nm and less) considering a typical nanofabrication accuracy. Moreover, the ridge shape affects weakly the transmission performance due to the non-resonance operation of our dielectric device. Such tolerance investigations together with current nanofabrication technology enable us to accomplish a 70% efficiency for coupling the normal incident light into the + 1st order transmission diffraction satisfying the total internal reflection condition at a 640 nm wavelength of operation.


All-optical self-referencing measurement of vectorial optical arbitrary waveform.
We propose the Vectorial E-field Characterization Through all-Optical and self-Referenced (VECTOR) method to characterize vectorial optical arbitrary waveform with up to 100% duty cycle, which is free of ambiguity, iteration, radio-frequency or external optical reference, restriction on repetition rate, and requirement of external interferometric stabilization. The feasibility of VECTOR is experimentally verified by different waveforms created by a phase-modulated CW comb source and a built-in polarization line-by-line pulse shaper.


Physiotherapy-led arthroplasty review clinic: a preliminary outcomes analysis.
With the rising demand for Orthopaedics in the healthcare sector, service delivery innovations need to be explored to accommodate the increasing workload. Senior Musculoskeletal Physiotherapists have the specialised skills in the assessment of musculoskeletal conditions to determine the impact of surgery on patient outcomes. The aim of the present study was to compare outcomes between a physiotherapy-led arthroplasty review clinic (PT clinic) and the traditional model of orthopaedic surgeon review (OS clinic) after hip and knee replacement. This study was a retrospective case-controlled audit using a comprehensive database. Twenty-four patients who had a hip arthroplasty and 52 patients who had a knee arthroplasty were reviewed solely by the PT clinic at 3, 6 and 12 months after surgical reviews. These patients were matched 1:2 against patients seen only by the OS clinic. The outcome measures included International Knee Score (IKS), Harris Hip Score (HHS) and the Short Form (SF)-12. There were no significant differences in HHS or SF-12 scores for patients after hip arthroplasty. Significant differences for knee arthroplasty were observed favouring the PT clinic; IKS, PT clinic 147.6 (37.07), OS clinic 135.4 (35.68), P≤0.01, and physical component of the SF-12, PT clinic 41.98 (10.45), OS clinic 37.20 (10.44), P<0.01. Implementation of a physiotherapy-led arthroplasty review clinic appears to be a safe and effective service alternative to reviews conducted by orthopaedic surgeons. WHAT IS KNOWN ABOUT THE TOPIC?: Osteoarthritis (OA) is a leading cause of musculoskeletal pain and disability and the burden of the disease is rapidly increasing. Joint arthroplasty surgery is the mainstay of treatment for people with end-stage OA; it is a high-cost, high-volume procedure that dominates surgical wait lists around Australia. Long-term follow up is encouraged by the Arthroplasty Society of Australia and endorsed by the Australian Orthopaedics Association, but it is acknowledged that it is impossible to achieve this with solely orthopaedic surgeon reviews, an issue that is only going to worsen with the increased demand for surgery. Physiotherapists have become involved in many advanced scope roles within public health care, and emerging research suggests that patients are highly satisfied with their care in these types of clinics. WHAT DOES THIS PAPER ADD?: Although it has been shown that patients are satisfied in physiotherapy-led advanced clinics, there is a paucity of evidence in the outcomes of patients attending these clinics. Implementation of a physiotherapy-led arthroplasty review clinic demonstrated that outcome measures in this patient cohort were not compromised and, following knee joint arthroplasty, may even be improved. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?: The findings of this study indicate that joint review clinics involving physiotherapists acting in an advanced scope role are unlikely to compromise patient outcomes. The use of this role substitution on a broader scale can be recommended.


Splenic abscess caused by Shigella flexneri and Bacteroides fragilis.
We report a case of splenic abscess from which only Shigella flexneri (serotype 1a) and Bacteroides fragilis were isolated. The patient was a 59-year-old diabetic female who displayed minimal gastrointestinal symptoms. The S. flexneri isolate was resistant to chloramphenicol and tetracycline. The possible synergistic relationship between the two organisms is discussed.


para-Selective C-H Borylation of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis.
para-Selective C-H borylation of benzamides and pyridines has been achieved by cooperative iridium/aluminum catalysis. A combination of iridium catalysts commonly employed for arene C-H borylation and bulky aluminum-based Lewis acid catalysts provides an unprecedented strategy for controlling the regioselectivity of C-H borylation to give variously substituted (hetero)arylboronates, which are versatile synthetic intermediates for complex multi-substituted aromatic compounds.


[Patient safety in Sweden].
This article describes the patient safety work in Sweden and the cooperation between the Nordic countries in the area of patient safety. It depicts the national infrastructure, methods and partners in patient safety work as well as the development in key areas. Since 2000, the interest in patient safety and quality issues has significantly increased. A national study (2009) showed that more than 100,000 patients (8.6 %) experienced preventable harm in hospitals. Since 2007, all Swedish counties and regions work on the "National commitment for increased patient safety" to systematically minimize adverse events in the healthcare system. Also, a national strategy for patient safety has been proposed based on a new law regulating the responsibility for patient safety (2011) and a zero vision in terms of preventable harm and adverse events. The Nordic collaboration in this field currently focuses on the development of indicators and quality measurement with respect to nosocomial infections, harm in inpatient somatic care, patient safety culture, hospital mortality and polypharmacy in the elderly. The Nordic collaboration is driven by the development, exchange and documentation of experiences and evidence on patient safety indicators. The work presented in this article is only a part of the Swedish and the Nordic efforts related to patient safety and provides an interesting insight into how this work can be carried out.


Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid organ transplant recipients.
The implications of the findings from clinical studies and pharmacokinetic analyses of the antiviral agent valganciclovir for dosing of the drug to prevent cytomegalovirus (CMV) disease in solid organ transplant recipients are reviewed. Valganciclovir, an oral prodrug of ganciclovir, is as effective as oral ganciclovir for preventing CMV disease, although prophylaxis with either agent may delay CMV disease. Dosage reduction is required for both drugs in patients with renal impairment to prevent high plasma ganciclovir concentrations and toxicity. A valganciclovir dosage of 900 mg/day is required in patients with normal renal function, especially those at high risk for CMV disease, to provide adequate systemic ganciclovir exposure. Some studies suggest that a lower dosage might suffice for patients at a low risk for CMV disease. Valganciclovir dosing should be based on renal function to avoid toxicity.


Psychometric Properties of the Italian Version of the Leader Member Exchange Scale (LMX-7): A Validation Study.
For decades, scholars have studied leader-member exchange (LMX) relationships to understand and explain the effects of leadership on follower attitudes and performance outcomes within work settings. One available instrument to measure these aspects is the LMX-7 scale. This measurement has been widely used in empirical studies, but its psychometric properties have been poorly explored. The aim of this study was to test the psychometric characteristics (content, structural and construct validity, and reliability) of the Italian version of the LMX-7 scale and to support its cultural adaptation. We used a cross-sectional multi-center design. The forward-backward translation process was used to develop the Italian version of the scale. The scale was administered through an online survey to 837 nurses and nurse managers working in different settings. The factorial structure was tested using both exploratory and confirmatory factor analyses (EFA and CFA), and reliability was evaluated using Cronbach's alpha. For the construct validity, we used hypothesis testing and differentiation by known groups. The Italian version of the LMX-7 scale presented one dimension. All the psychometric tests performed confirmed its validity and suggested its usefulness for future research.


Green fluorescent protein as a novel marker and reporter system in Helicobacter sp.
In order to be able to study gene regulation in single, live Helicobacter pylori bacteria in vitro or in contact with host cells, we established the green fluorescent protein gene gfp from Aequorea victoria as a reporter gene for use with Helicobacter species. We describe here the construction of genomic transcriptional fusions of the promoterless gfp gene with the flaA and flaB promoters of H. pylori. We have also constructed a Mini-Tn3-km-gfp transposon to be used for shuttle transposon mutagenesis in H. pylori and H. mustelae. A marker strain with wild-type phenotype, carrying multiple plasmid-borne copies of gfp under the control of the H. pylori flaB promoter, was constructed for studies of bacterial distribution and transmission in animal models.


The effect of days on feed and zilpaterol hydrochloride supplementation on feeding behavior and live growth performance of Holstein steers.
This experiment was designed to study the effect of days on feed (d 225-533) and zilpaterol hydrochloride (ZH) supplementation on Holstein steer ( = 110) performance and feeding behavior as part of a serial slaughter trial. Steers were randomly assigned to 1 of 11 harvest groups with 10 steers ( = 5 control and = 5 ZH; ZH at 8.33 mg/kg diet) harvested each 28 d. Steers were weighed every 28 d (d 225, 253, 281, 309, 337, 365, 393, 421, 449, 477, 505, and 533); individual daily meal consumption data for each steer were recorded using GrowSafe technology. In the pretreatment period, dry matter intake expressed a negative quadratic relationship with days on feed (DOF) {DMI = -5.7120 + (0.08370 x DOF)- (0.00011 x DOF); Adj. = 0.2574; RMSE = 0.25 75; 0.01}. A linear increase in BW ( < 0.01) occurred during the pretreatment 308 d period from 466 to 844 kg, {BWend = 137.61 + (1.4740 x DOF); Adj. = 0.8819; RMSE = 37.06; < 0.01}, whereas ADG and G:F decreased linearly. Dry matter intake per meal exhibited a quadratic relationship over days on feed and peaked ( < 0.01) during d 365 to 392 at 1.065 kg coinciding with the highest numerical daily DMI (11.19 kg). Daily consumption visit duration differed ( < 0.01) during the 308 d period, with a low of 52.29 min (d 337-364) and a high of 55.59 min (d 365-392). Consumption rate peaked at 714 g/min (d 337-364) and exhibited a quadratic relationship to DOF. The difference ( < 0.04) in DMI between control and ZH treated cattle across all 11 harvest groups averaged 0.575 kg. Moreover, ZH treatment resulted in decreased ( 0.01) DMI per meal event of 0.093 kg. Gain to feed tended to improve ( = 0.06) with ZH treatment by 0.017 kg gain per kg feed relative to the control cattle. Daily bunk, consumption, and meal visit durations were influenced by ZH during the 20 d treatment period ( = 0.01); the average difference between control and ZH supplemented cattle over the 308 d trial was 9.09, 8.71, and 11.39 min per d, respectively. The data collected in this trial indicate live growth performance and feeding behavior were impacted by both DOF and ZH supplementation.


Biological behavior and cell properties of new AKR lymphoma malignancy variants.
The AKR lymphoma-leukemia is a T lymphocyte neoplasm, most suitable as a model for human T cell malignancies. We have been interested in the process of tumor progression in the AKR lymphoma system. In the present study, two newly isolated variants, the TAU-42 and TAU-44, were characterized with respect to their biological behavior, by comparing them to a previously studied low-malignancy variant, the TAU-39. While the TAU-44 variant formed large s.c. local tumors, the TAU-42 variant formed only small growths or none at all. The TAU-42 lymphoma was found to have the highest malignant potential: it displayed very marked dissemination to spleen, lymph nodes, liver and lungs. The TAU-44 variant had an intermediate degree of metastatic potential but presented a predilection for spread to lymph nodes and spleen and was sometimes found to metastasize to peculiar organs, such as heart and pancreas. Cells derived from the different lymphoma variants varied in their immunophenotype: the highly malignant variant cells expressed more CD4 antigen than the low-malignancy one. The opposite was observed with regard to CD8. The variant cells also differed in their migrating capacity, the more malignant one exhibiting a higher motile activity. Studies on the tumor progression model of AKR lymphoma might contribute to the elucidation of the features determining the aggressiveness of T lymphocytic malignancies.


[Considerations on limits and profits of registries].
The article collects the summary of the discussion occurred in the setting of PRIER II, in the session dedicated to the taxonomy of registries. Shown below, some specific contributions by health professionals working at the regional departments, which deal with registries, as well as the contribution on the same subject by specialists working at some pharmaceutical companies. In particular, after the presentation summarized in the article by prof. Giuseppe Costa1, the contributions, respectively by a representative of the Emilia-Romagna Region, of a health and hospital service and by the PRIER II workgroup, are following. Finally, a collective work with all participants to the working group took place to focus on all the issues considered to be crucial in defining clinical registries. At the same discussion table, institutional representatives of the regulatory national and regional branch were also invited to take into consideration the points of view of all public and private registry users, in particular in their benefits, limits and purposes. Going through the discussion on a specific check list and deepening a number of statements identified by the working group, a list of key points, essential to characterize each clinical registry, was produced.


Assessment of the antinociceptive and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea.
Context: Since there is still a great need to search for plant species with antinociceptive and anti-inflammatory activities, Diploptropis purpurea (Rich.) Amshoff (Fabaceae) is studied for the first time. Objective: This evaluates the analgesic and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea (MEDP). Material and methods: The anti-inflammatory and analgesic effects of MEDP of D. purpurea were evaluated in vivo. The antinociceptive activity was assessed in CD1 male mice were treated by oral gavage with 500 mg/kg of MEDP 30 min before submitting to acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Paws oedema induced by carrageenan, histamine or serotonin were performed in male Sprague-Dawley rats to determinate the anti-inflammatory activity. Results: Oral administration of MEDP produced significant antinociceptive effects on the inflammatory phase in the formalin test [12.0 s versus 72.5 s in carboxymethyl cellulose (CMC) control group]. MEDP produced an analgesic effect in the hot-plate model, although the effect was modest compared to tramadol (40 and 60%, respectively). The oral administration of MEDP in a dose of 500 mg/kg showed maximum inhibition (75.1%) after 0.5 h in carrageenan-induced oedema, but it did not modify histamine or serotonin-induced oedemas. Discussion and conclusion: In the peripheral nociception model, acetic acid-induced abdominal writhing, the MEDP did not show a protective effect, but its analgesic effects were evident in the inflammatory phase of the formalin test and in the hot-plate model. These results show that the anti-inflammatory effect was accompanied by a reduction in the perception of painful stimuli.


Risk evaluation of outcome of vitreous surgery for proliferative diabetic retinopathy based on vitreous level of vascular endothelial growth factor and angiotensin II.
To ascertain whether measurement of the vitreous fluid levels of vascular endothelial growth factor (VEGF) or angiotensin II (Ang II) could predict the outcome of vitreous surgery in patients with proliferative diabetic retinopathy (PDR). A prospective observational case study was performed in 61 consecutive patients (61 eyes) with PDR who underwent vitreoretinal surgery. Vitreous fluid samples were obtained during surgery. The VEGF level in vitreous fluid and plasma was determined by enzyme linked immunosorbent assay, while the Ang II level was measured by radioimmunoassay. Patients were prospectively followed for 6 months and the postoperative outcome was analysed by logistic regression analysis. No improvement and/or progression of PDR was seen in 15 (25%) of the 61 eyes. Vitreous levels of VEGF and Ang II were significantly higher in eyes with progression of PDR than in eyes with regression of PDR (p = 0.0044, and p = 0.0178, respectively). Multivariate logistic regression analysis showed that the vitreous VEGF level increased along with the progression of PDR after vitreous surgery (odds ratio 2.48, p = 0.0008). A high vitreous fluid VEGF level is associated with a significant risk of postoperative progression of PDR. The vitreous level of VEGF at the time of surgery may be a useful predictor of the outcome.


Zeolite Nanoparticles Loaded with 2-Methoxystradiol as a Novel Drug Delivery System for the Prostate Cancer Therapy.
The estrogen metabolite 2-methoxyestradiol (2ME) is a promissory anticancer drug mainly because of its pro-apoptotic properties in cancer cells. However, the therapeutic use of 2ME has been hampered due to its low solubility and bioavailability. Thus, it is necessary to find new ways of administration for 2ME. Zeolites are inorganic aluminosilicates with a porous structure and are considered good adsorbents and sieves in the pharmaceutical field. Here, mordenite-type zeolite nanoparticles were loaded with 2ME to assess its efficiency as a delivery system for prostate cancer treatment. The 2ME-loaded zeolite nanoparticles showed an irregular morphology with a mean hydrodynamic diameter of 250.9 ± 11.4 nm, polydispersity index of 0.36 ± 0.04, and a net negative surface charge of -34 ± 1.73 meV. Spectroscopy with UV-vis and Attenuated Total Reflectance Infrared Fourier-Transform was used to elucidate the interaction between the 2ME molecules and the zeolite framework showing the formation of a 2ME-zeolite conjugate in the nanocomposite. The studies of adsorption and liberation determined that zeolite nanoparticles incorporated 40% of 2ME while the liberation of 2ME reached 90% at pH 7.4 after 7 days. The 2ME-loaded zeolite nanoparticles also decreased the viability and increased the mRNA of the 2ME-target gene F-spondin, encoded by SPON1, in the human prostate cancer cell line LNCaP. Finally, the 2ME-loaded nanoparticles also decreased the viability of primary cultures from mouse prostate cancer. These results show the development of 2ME-loaded zeolite nanoparticles with physicochemical and biological properties compatible with anticancer activity on the human prostate and highlight that zeolite nanoparticles can be a good carrier system for 2ME.


Attenuation, safety, and efficacy of an infectious bronchitis virus GA98 serotype vaccine.
In 1998, novel strains of infectious bronchitis virus (IBV) were identified in chickens from the southeastern United States and classified as a new serotype designated Georgia 98 (GA98). Because of the widespread nature of the GA98 virus in the southeastern United States and the lack of adequate protection with the DE072 vaccine, we developed a specific vaccine for the GA98 serotype. The GA98/0470/98 isolate of IBV was passaged in embryonating chicken eggs 70 times, and attenuation of the virus was determined in specific-pathogen-free chicks. Pass 70 of the GA98/0470/98 strain of IBV when given at 1 day of age by coarse spray and at 14 days of age in the drinking water at 1 x 10(4.5) 50% embryo infectious dose/bird protected against the homologous GA98 challenge as well as provided good protection against the DE072-type virus. In addition, the vaccine was shown to be adequately attenuated and safe at a 10x dosage.


A comparison of anthropometry, biochemical variables and plasma amino acids among centenarians, elderly and young subjects.
Aging health is associated with nutritional changes which are not well understood and were therefore evaluated in this study by comparing the nutritional status of centenarians and elderly (in their 70s) relative to young subjects. The participants were 27 young subjects (10 males, 17 females), 40 healthy elderly (20 males, 20 females) and 32 centenarians (9 males, 23 females). The activities of daily living (ADL), height, weight, body mass index (BMI), biochemical variables (total protein, albumin, triglycerides as well as total, HDL, LDL and VLDL cholesterol) and plasma amino acid profiles were evaluated. Compared with young subjects, lower (p<0.05) height, weight, total protein, albumin and albumin/globulin (A/G) ratio and total cholesterol for centenarians and height, albumin and A/G ratio for elderly were observed in both genders. Total cholesterol of male centenarians was lower than in young and elderly subjects and total and LDL cholesterol concentrations of female elderly were higher than those of young and centenarian subjects. However, the cholesterol concentrations of all the centenarians were within the reference range. The ratios of essential amino acids to nonessential amino acids were significantly lower (p<0.05) in the centenarians than the young subjects. Clear changes in individual amino acids with aging were lower (p<0.05) branched chain amino acids and methionine and higher proline and cystine, which are similar to the amino acid profiles in liver deterioration. The results suggest that the centenarians had poor nutritional status, which may be due to their decreased metabolism and the possibility that only short, slender individuals with low lipids, protein and essential amino acids are those that tend to survive to be centenarians.


Scaling analysis of anomalous Hall resistivity in the Co2TiAl Heusler alloy.
A comprehensive magnetotransport study including resistivity (ρ xx ), isothermal magnetoresistance, Hall resistivity (ρ xy ) and magnetization have been carried out at different temperatures on the Co2TiAl Heusler alloy. Co2TiAl alloy shows a paramagnetic to ferromagnetic (FM) transition below the Curie temperature (T C) ∼ 125 K. In the FM region, resistivity and magnetoresistance reveal a spin flip electron-magnon scattering and the Hall resistivity unveils the anomalous Hall resistivity. Scaling of anomalous Hall resistivity with resistivity establishes the extrinsic scattering process responsible for the anomalous Hall resistivity; however skew scattering is the dominant mechanism compared to the side-jump contribution. A one to one correspondence between magnetoresistance and side-jump contribution to anomalous Hall resistivity verifies the electron-magnon scattering being the source of side-jump contribution to the anomalous Hall resistivity.


Developmental-behavioral initiation of evolutionary change.
The traditional approach to evolutionary psychology relies entirely on natural selection as the cause of the evolution of adaptations. Exclusive reliance on natural selection overlooks the fact that changes in development are a necessary prerequisite for evolutionary change. These developmental changes provide the material for natural selection to work on. In the neo-Darwinian scenario, the mechanisms of evolution are mutation or genetic recombination, selection, migration, and eventual reproductive isolation. In the spirit of evolutionary pluralism, the author describes a different 3-stage scenario in which migration (the invasion of new niches or habitats) may occur without mutation or genetic recombination and selection first initiating a change in genes or gene frequencies.


Osteochondritis dissecans of the elbow managed by Herbert screw fixation.
Seven patients (eight elbows) with osteochondritis dissecans were treated with cancellous bone grafts and internal fixation of the fragment using a Herbert screw. Average follow-up was 32 months. All patients were pain-free and returned to previous sporting activities. The postoperative range of motion of the elbow increased by an average of 18 degrees. Radiographs showed complete reossification of the capitular cyst and normally contoured joint surface.


The Role of Strain in the Homoaromatization of Semibullvalenes.
The low activation barrier to the Cope rearrangement of semibullvalenes has been attributed to the inherent ring-strain of this nucleus. Appropriate, Dewar-Hoffmann, substitution of semibullvalene results in the stabilization of the transition state and a further lowering of the Cope barrier. An alternative proposal for lowering/eliminating this barrier is the use of strain to destabilize the localized semibullvalene. Using density functional and Hartree-Fock calculations, we predict that additionally straining the semibullvalene nucleus, by small ring annelations, will lead to a lowering of the Cope barrier and ultimately to ground state neutral homoaromatics.


[Analysis of solvent residues in raw material drug of glimepiride by head-space sampling-capillary gas chromatography].
An analytical method for the solvent residues in the raw material drug of glimepiride has been established by head-space sampling capillary gas chromatography. General evaluation was made for the distribution of organic residual solvents in glimepiride samples from 8 different domestic manufacturers. Based on the evaluation-test results and the information provided by manufacturers, 14 target solvents were ascertained including acetone, ethyl acetate, methanol, isopropanol, ethanol, chloroform, toluene, 1,4-dioxane, pyridine, chlorobenzene, ether, dichloromethane, n-hexane and benzene. The target solvents were divided into two groups for baseline separation according to their column-retention specificity. Acetone, ethyl acetate, methanol, isopropanol, ethanol, chloroform, toluene, 1,4-dioxane, pyridine and chlorobenzene were separated on a Supelco-Wax capillary column with acetonitrile as internal standard, while ether, dichloromethane, n-hexane and benzene were determined on a Supelco OVI-G43 capillary column with butanone as internal standard. Linear responses were obtained for the 14 residual solvents in their respective concentration ranges (r = 0.99167-0.99997, n = 8), and the limits of detection were 0.2-13.5 microg/g. The inter-day reproducibilities, measured as relative standard deviations (RSDs), were 0.6%-9.2% (n = 3). The average recoveries of three concentration levels were 86.3%-104.1% with the RSD of 0.2%-5.3% (n = 16). The developed method is simple, sensitive, and accurate for the residual solvent analysis in glimepiride samples.


Transport implications resulting from internal redistribution of arsenic and iron within constructed soil aggregates.
Soils are an aggregate-based structured media that have a multitude of pore domains resulting in varying degrees of advective and diffusive solute and gas transport. Consequently, a spectrum of biogeochemical processes may function at the aggregate scale that collectively, and coupled with solute transport, determine element cycling in soils and sediments. To explore how the physical structure impacts biogeochemical processes influencing the fate and transport of As, we examined temporal changes in speciation and distribution of As and Fe within constructed aggregates through experimental measurement and reactive transport simulations. Spherical aggregates were made with As(V)-bearing ferrihydrite-coated sand inoculated with Shewanella sp. ANA-3; aerated solute flow around the aggregate was then induced. Despite the aerated aggregate exterior, where As(V) and ferrihydrite persist as the dominant species, anoxia develops within the aggregate interior. As a result, As and Fe redox gradients emerge, and the proportion of As(III) and magnetite increases toward the aggregate interior. Arsenic(III) and Fe(II) produced in the interior migrate toward the aggregated exterior and result in coaccumulation of As and Fe(III) proximal to preferential flow paths as a consequence of oxygenic precipitation. The oxidized rind of aggregates thus serves as a barrier to As release into advecting pore-water, but also leads to be a buildup of this hazardous element at preferential flow boundaries that could be released upon shifting geochemical conditions.


Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion under intraoperative neuromonitoring: A case report.
Traditional open discectomy and intervertebral fusion surgery is the common strategy for lumbar disc herniation (LDH). However, it has the disadvantages of long recovery time and severe paravertebral soft tissue injury. Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion (ZELIF), as a novel minimally invasive surgical technique for LDH, has the advantages in quicker recovery, less soft tissue destruction, shorter hospital stays and less pain. We report a novel technique of ZELIF under intraoperative neuromonitoring (INM) for the treatment of LDH. A 51-year-old male presented to our hospital with left lower extremity pain and numbness for 1 year. Lumbar disc herniation (LDH). This patient was treated with Zina percutaneous screw fixation combined with endoscopic neural decompression, endplate preparation, and intervertebral fusion through Kambin's triangle. Each step of the operation was performed under INM. The follow-up period lasted 12 months; the hospitalization lasted 4 nights; the blood loss volume was 65 ml, and the time of operation was 266 min. INM showed no neurological damage during the surgery. No surgical complications, including neurological deterioration, cage migration, non-union, instrumentation failure or revision operation, were observed during the follow-up period. Visual Analogue Scale (VAS) score reduced from 7 to 1; the Oswestry Disability Index (ODI) decreased from 43 to 14; the EQ-5D score was 10 preoperatively and 15 at the final follow-up visit; the Physical Component Summary of the 36-Item Short Form Health Survey (SF-36) was 48 preoperatively and 49 at the last follow up visit; the SF-36 Mental Component Summary was 47 before surgery and decreased to 41 postoperatively. ZELIF under INM may represent a feasible, safe and effective alternative to endoscopic intervertebral fusion and percutaneous screw fixation, for decompressing the lumbar's exiting nerve root directly with minimal invasion in selected patients.


[INTERDEPENDENCY BETWEEN ZINC AND THYROID GLAND: THE DISCUSSION IS TO BE CONTINUED].
Both hypothyroidism and zinc deficiency have been diagnosed over a long time. The endemic character of both disorders inspired an investigation into the relationship between these two phenomena. Zinc has a role in multiple metabolic processes; therefore, zinc depletion may lead to a serious and prolonged illness. It is well known that changes of zinc levels may correlate with changes in thyroid functions and vice versa. Nevertheless, despite this evidence, thyroid dysfunction does not always improve after zinc supplementation, even in cases of low zinc levels. This review reveals the complexity of the relationship between hypothyroid and zinc deficiency and discusses the options for evaluation and treatment of this mutual relationship.


Rh(III)-catalyzed C-H activation with allenes to synthesize conjugated olefins.
Rh(III)-catalyzed C-H activation with allenes produces highly unsaturated conjugated olefins. The reaction is applicable to both olefin and arene C(sp(2))-H and is compatible with a variety of functional groups. The products can be further transformed into other important skeletons through Diels-Alder reaction and intramolecular transesterification.


The influence of migration on secular trends in sex ratios at birth in cuba in the past fifty years.
Secular trends have been found in the male-female ratio at birth (M/F: male births divided by total births) in various countries and this ratio is anticipated to approximate 0.515. Annual national data for male and female live births in Cuba with contingency tables were obtained from the World Health Organisation and analysed. There were 3 736 718 male and 3 534 270 female births (1960-96). Births declined steadily over the entire period. The male-female ratio at birth remained relatively stable over the period 1960-1985 with significant sharp dips for the years 1966, 1980 and 1985. There was a sharp rise in M/F from 1966 to 1969, another rise after 1985, a steep drop to 1989, and then a sharp rise once more after 1993 (all p < 0.0001). The single year dips are associated with the passage of laws in the United States of America (USA) that facilitated Cuban entry to the USA. The increases in M/F tended to be associated with a skew toward an efflux from Cuba that was predominantly male. This paralleled the situation in the Second World War where a surplus of women left behind led to an increase in M/F in belligerent countries. To the author's knowledge, this is the first report of migration influencing M/F.


Assessment of drivers of spatial genetic variation of a ground-dwelling bird species and its implications for conservation.
In modern wildlife ecology, spatial population genetic methods are becoming increasingly applied. Especially for animal species in fragmented landscapes, preservation of gene flow becomes a high priority target in order to restore genetic diversity and prevent local extinction. Within Central Europe, the Alps represent the core distribution area of the black grouse, Lyrurus tetrix. At its easternmost Alpine range, events of subpopulation extinction have already been documented in the past decades. Molecular data combined with spatial analyses can help to assess landscape effects on genetic variation and therefore can be informative for conservation management. Here, we addressed whether the genetic pattern of the easternmost Alpine black grouse metapopulation system is driven by isolation by distance or isolation by resistance. Correlative ecological niche modeling was used to assess geographic distances and landscape resistances. We then applied regression-based approaches combined with population genetic analyses based on microsatellite data to disentangle effects of isolation by distance and isolation by resistance among individuals and subpopulations. Although population genetic analyses revealed overall low levels of genetic differentiation, the ecological niche modeling showed subpopulations to be clearly delimited by habitat structures. Spatial genetic variation could be attributed to effects of isolation by distance among individuals and isolation by resistance among subpopulations, yet unknown effects might factor in. The easternmost subpopulation was the most differentiated, and at the same time, immigration was not detected; hence, its long-term survival might be threatened. Our study provides valuable insights into the spatial genetic variation of this small-scale metapopulation system of Alpine black grouse.


Improving the availability of vaccines in primary healthcare facilities in South Africa: is the time right for a system redesign process?
An uninterrupted supply of vaccines at different supply chain levels is a basic component of a functional immunization programme and care service. There can be no progress toward achieving universal health coverage and sustainable development without continuous availability of essential medicines and vaccines in healthcare facilities. Shortages of vaccines, particularly at health facility level is an issue of grave concern that requires urgent attention in South Africa. The causes of vaccine stock-outs are multifactorial and may be linked to a broader systems issue. These factors include challenges at higher levels such as delays in the delivery of stock from the pharmaceutical depot; health facility level factors, which include a lack of commitment from healthcare workers and managers; human resource factors, such as, staff shortages, and lack of skilled personnel. Therefore, there is a compelling need to address the factors associated with shortages of vaccines in health facilities. This paper highlights the challenges of vaccine availability in South Africa, the associated factors, the available interventions, and recommended interventions for the expanded programme on immunization in South Africa. We propose a system redesign approach as a potentially useful intervention.


The Snapping Elbow Syndrome as a Reason for Chronic Elbow Neuralgia in a Tennis Player - MR, US and Sonoelastography Evaluation.
Ulnar neuropathy is the second most common peripheral nerve neuropathy after median neuropathy, with an incidence of 25 cases per 100 000 men and 19 cases per 100 000 women each year. Skipping (snapping) elbow syndrome is an uncommon cause of pain in the posterior-medial elbow area, sometimes complicated by injury of the ulnar nerve. One of the reason is the dislocation of the abnormal insertion of the medial triceps head over the medial epicondyle during flexion and extension movements. Others are: lack of the Osboune fascia leading to ulnar nerve instability and focal soft tissue tumors (fibromas, lipomas, etc). Recurrent subluxation of the nerve at the elbow results in a tractional and frictional neuritis with classical symptoms of peripheral neuralgia. As far as we know snapping triceps syndrome had never been evaluated in sonoelastography. A 28yo semi-professional left handed tennis player was complaining about pain in posterior-medial elbow area. Initial US examination suggest golfers elbow syndrome which occurs quite commonly and has a prevalence of 0.3-0.6% in males and 0-3-1.1% in women and may be associated (approx. 50% of cases) with ulnar neuropathy. However subsequently made MRI revealed unusual distal triceps anatomy, moderate ulnar nerve swelling and lack of medial epicondylitis symptoms. Followed (second) US examination and sonoelastography have detected slipping of the both ulnar nerve and the additional band of the medial triceps head. Snapping elbow syndrome is a poorly known medical condition, sometimes misdiagnosed as the medial epicondylitis. It describes a broad range of pathologies and anatomical abnormalities. One of the most often reasons is the slipping of the ulnar nerve as the result of the Osborne fascia/anconeus epitrochlearis muscle absence. Simultaneously presence of two or more "snapping reasons" is rare but should be always taken under consideration. There are no sonoelastography studies describing golfers elbow syndrome, additional triceps band and ulnar neuritis. Our data suggest that the sonoelastography signs are similar to those seen in well described lateral epicondylitis syndrome, Achilles tendinitis and medial nerve neuralgia.


Variation in Licensed Nurse Staffing Characteristics by State Requirements in Residential Care.
Research on licensed nurses in assisted living and residential care communities (RCCs) is sparse compared to that on licensed nurses in nursing homes. RCCs are state-regulated; thus, staffing requirements vary considerably. The current study analyzed variation in characteristics of licensed nurses by state-specific requirements for licensed nurses in RCCs. A significantly higher percentage of RCCs with one or more RNs (68.87%) and licensed practical nurses (LPNs) or licensed vocational nurses (LVNs) (56.85%) were found among states with licensed nurse requirements compared to states with no such requirements (37.35% and 29.08%, respectively; p < 0.05). LPN/LVN hours were higher among RCCs in states with licensed nurse requirements compared to RCCs in states with no such requirements (17 minutes and 8 minutes, respectively; p < 0.05). The findings provide the first evidence of variation in characteristics of licensed nurses by state-specific requirements for licensed nurses. [Res Gerontol Nurs. 2019; 12(1):27-33.].


Broadband terahertz antireflective microstructures on quartz crystal surface by CO2 laser micro-processing.
Anti-reflection (AR) coating is a critical technology and an ongoing challenge for terahertz systems. The subwavelength structure (SWS) is an effective AR method, whereas the current manufacturing techniques, such as chemical etching and ultrafast laser processing, are low-efficient and low-quality for processing structures at the hundred-micron scale on hard brittle materials. We present a study of broadband SWSs directly ablated on the surface of quartz crystal by precisely controlled CO2 laser pulses, instead of commonly used ultra-fast lasers. The processing time of SWS can be shortened by two orders of magnitude compared with that by ultra-fast laser pulses. The SWS samples exhibit excellent AR properties with maximum transmittance of 97% at 0.71 THz, peak transmittance improvement of 13.5%, and optimal efficiency spectrum of 0.28-1.21 THz with transmittance >90%. The AR properties of SWS samples are in agreement with the simulated expectation and exist over a wide range of incidence angles up to ∼40°. The imaging of an object using SWS as the substrate shows an obvious improvement in imaging quality. We present an efficient and practical way to improve the transmission of optical components of materials, such as quartz crystal, alumina, and sapphire, in the terahertz band.


Efficiency of passive sampling by adsorbents.
The efficiency of passive samplers can be influenced strongly by the adsorption isotherm. In this study calculations of sampling efficiency were made in terms of dimensionless variables for adsorption controlled by the Langmuir, Freundlich, and Dubinin-Radushkevich isotherms, respectively. Of particular importance is that for the latter isotherm, which is often followed by activated charcoal for the adsorption of solvent vapors, passive sampling may remain highly efficient until a significant fraction of the capacity of the adsorbent has been utilized.


Varicella zoster antibodies after herpes zoster, varicella and multiple sclerosis.
We previously showed that Manitoba Hutterites seek physician care for varicella zoster virus infection significantly less than non-Hutterites. The current study was undertaken to measure varicella zoster virus seroprevalence for Hutterite and non-Hutterite controls. Blood was obtained from 315 Hutterites and 259 similar age and sex controls at the time of blood donations to The Canadian Red Cross Society. The controls were from the same or a contiguous postal code area and were collected at the same time as the Hutterite samples. The immune status of the specimens was determined by the ELISA method (enzyme linked immunosorbent assay). Twenty-eight per cent of 315 Hutterites had no immunity and an additional 25% had only marginal immunity. Among the 259 controls, 10% had no immunity and an additional 10% had only marginal immunity (p < .0001). Manitoba Hutterites have significantly decreased seroprevalence to varicella zoster virus infection. This study of serum varicella zoster virus antibodies verifies a previous population based study that demonstrated the relative rarity of varicella and herpes zoster among a particular population group.


Etiology of bacterial vaginosis and polymicrobial biofilm formation.
Microorganisms in nature rarely exist in a planktonic form, but in the form of biofilms. Biofilms have been identified as the cause of many chronic and persistent infections and have been implicated in the etiology of bacterial vaginosis (BV). Bacterial vaginosis is the most common form of vaginal infection in women of reproductive age. Similar to other biofilm infections, BV biofilms protect the BV-related bacteria against antibiotics and cause recurrent BV. In this review, an overview of BV-related bacteria, conceptual models and the stages involved in the polymicrobial BV biofilm formation will be discussed.


MicroRNA-5p and -3p co-expression and cross-targeting in colon cancer cells.
Two mature miRNA species may be generated from the 5' and 3' arms of a pre-miRNA precursor. In most cases, only one species remains while the complementary species is degraded. However, co-existence of miRNA-5p and -3p species is increasingly being reported. In this work, we aimed to systematically investigate co-expression of miRNA-5p/3p in colon cancer cells in a genome-wide analysis, and to examine cross-targeting of the dysregulated miRNAs and 5p/3p species. Four colon cancer cell lines were examined relative to two normal colon tissues. Of the 1,190 miRNAs analyzed, 92 and 36 were found to be up- or down-regulated, respectively, in cancer cells. Nineteen co-expressed miRNA-5p/3p pairs were further identified suggesting frequent 5p/3p co-accumulation in colon cancer cells. Of these, 14 pairs were co-up-regulated and 3 pairs were co-down-regulated indicating concerted 5p/3p dysregulation. Nine dysregulated miRNA pairs fell into three miRNA gene families, namely let-7, mir-8/200 and mir-17, which showed frequent cross-targeting in the metastasis process. Focusing on the let-7d-5p/3p pair, the respectively targeted IGF1R and KRAS were shown to be in a reverse relationship with expression of the respective miRNA, which was confirmed in transient transfection assays using let-7d mimic or inhibitor. Targeting of KRAS by let-7d was previous reported; targeting of IGF1R by let-7d-5p was confirmed in luciferase assays in this study. The findings of let-7d-5p/3p and multiple other miRNAs targeting IGF1R, KRAS and other metastasis-related factors suggest that 5p/3p miRNAs contribute to cross-targeting of multiple cancer-associated factors and processes possibly to evade functional abolishment when any one of the crucial factors are inactivated. miRNA-5p/3p species are frequently co-expressed and are coordinately regulated in colon cancer cells. In cancer cells, multiple cross-targeting by the miRNAs, including the co-existing 5p/3p species, frequently occurs in an apparent safe-proof scheme of miRNA regulation of important tumorigenesis processes. Further systematic analysis of co-existing miRNA-5p/3p pairs in clinical tissues is important in elucidating 5p/3p contributions to cancer pathogenesis.


Structure of inorganic pyrophosphatase from Helicobacter pylori.
Inorganic pyrophosphatase (PPase) is a ubiquitous cytosolic enzyme which catalyzes the hydrolysis of inorganic pyrophosphate (PPi) to orthophosphate (Pi). The crystal structure of inorganic pyrophosphatase from Helicobacter pylori (H-PPase) has been solved by MAD and refined to an R factor of 20.6% at 2.6 A resolution. The crystallographic asymmetric unit contains a homohexameric H-PPase arranged as a dimer of trimers. While most of the structural elements of PPases are highly conserved in H-PPase, some unique structural features are localized in the flexible loops near the active site, suggesting that the structural flexibility of these loops is required for the catalytic efficiency of PPase.


Association between anemia and outcome in patients hospitalized for acute heart failure syndromes: findings from Beijing Acute Heart Failure Registry (Beijing AHF Registry).
Whether the anemia increases the risk of mortality in patients with acute heart failure (AHF) remains unclear. This study aims to explore the relationship between anemia and outcomes in patients with AHF including subgroup analysis. This study included 3279 patients with hemoglobin available from the Beijing Acute Heart Failure Registry (Beijing AHF Registry) study. The primary endpoint was all-cause mortality in 1 year, and the secondary endpoint was 1-year all-cause events including all-cause death and readmission. Logistic regression models were applied to describe related variables of anemia in patients with AHF. Multivariate Cox proportional hazards models described associations of anemia with clinical outcomes in the overall cohort and subgroups. 45.4% of the patients were found anemic. They were older and had more comorbidities than non-anemic patients. Variables including older age, female, chronic kidney dysfunction (CKD), lower hematocrit, lower albumin, with loop diuretics applied, without beta-blockers, angiotensin-converting enzyme inhibitors /angiotensin receptor blockers (ACEIs/ARBs) and spironolactone applied in the emergency department (ED) were associated with anemia in AHF patients. Anemic patients had higher 1-year mortality (38.4% vs. 27.2%, p < 0.0001) and 1-year events rates (63.2% vs. 56.7%, p < 0.0001). After adjusted for covariates, anemia was associated with the increase of 1-year mortality (hazard ratio [HR] 1.278; 95% confidence interval [CI] 1.114-1.465; p = 0.0005) and 1-year events (HR 1.136; 95% CI 1.025-1.259; p = 0.0154). The severer anemia patients had higher risks both of 1-year mortality and events. In the subgroup analysis, the independent associations of anemia with 1-year mortality were shown in the subgroups including age < 75 years, male, body mass index < 25 kg/m2 and BMI ≥ 25 kg/m2, New York Heart Association (NYHA) functional class I-II and NYHA functional class III-IV, with and without cardiovascular ischemia, heart rate (HR) < 100 bpm and HR ≥ 100 bpm, systolic blood pressure (SBP) < 120 mmHg and SBP ≥ 120 mmHg, left ventricular ejection fraction (LVEF) < 40% and LVEF ≥ 40%, serum creatinine (Scr) < 133 umol/l, and with diuretics use, with and without beta-blockers use, without ACEIs/ARBs use in the ED. Anemia is associated with older age, female, CKD, volume overload, malnutrition, with loop diuretics, without beta-blockers, ACEIs/ARBs and spironolactone administration, and higher mortality and readmission in AHF. The risk associations are particular significantly obvious in younger, male, overweight, preserved LVEF, lower Scr, with diuretics and beta-blockers, without ACEIs/ARBs administration subgroups.Clinical trial No. ChiCTR-RIC-17014222.


Structural and Thermo-Mechanical Properties of Poly(ε-caprolactone) Modified by Various Peroxide Initiators.
The modification of poly(ε-caprolactone) (PCL) was successfully conducted during reactive processing in the presence of dicumyl peroxide (DCP) or di-(2-tert-butyl-peroxyisopropyl)-benzene (BIB). The peroxide initiators were applied in the various amounts of 0.5 or 1.0 pbw (part by weight) into the PCL matrix. The effects of the initiator type and its concentration on the structure and mechanical and thermal properties of PCL were investigated. To achieve a detailed and proper explication of this phenomenon, the decomposition and melting temperatures of DCP and BIB initiators were measured by differential scanning calorimetry. The conjecture of the branching or cross-linking of PCL structure via used peroxides was studied by gel fraction content measurement. Modification in the presence of BIB in PCL was found to effectively increase gel fraction. The result showed that the cross-linking of PCL started at a low content of BIB, while PCL modified by high DCP content was only partially cross-linked or branched. PCL branching and cross-linking were found to have a significant impact on the mechanical properties of PCL. However, the effect of used initiators on poly(ε-caprolactone) properties strongly depended on their structure and content. The obtained results indicated that, for the modification towards cross-linking/branching of PCL structure by using organic peroxides, the best mechanical properties were achieved for PCL modified by 0.5 pbw BIB or 1.0 pbw DCP, while the PCL modified by 1.0 pbw BIB possessed poor mechanical properties, as it was related to over cross-linking.


Proatherogenic oxidized low-density lipoprotein/β2-glycoprotein I complexes in arterial and venous disease.
OxLDL/β2GPI complexes have been implicated in the initiation and progression of atherosclerosis and associated with disease severity and adverse outcomes. We investigate the significance of anti-oxLDL/β2GPI antibodies and oxLDL/β2GPI complexes in patients with arterial and idiopathic venous disease. A cohort of 61 arterial disease patients, 32 idiopathic venous disease patients, and 53 healthy controls was studied. Because statins influence oxLDL/β2GPI, these complexes were analyzed on subjects not taking statins. Arterial and venous groups expressed higher levels of IgG anti-oxLDL/β2GPI antibodies than controls without any other significant clinical association. OxLDL/β2GPI complexes were significantly elevated in arterial (0.69 U/mL, P = 0.004) and venous disease (0.54 U/mL, P = 0.025) than controls (0.39 U/mL). Among arterial diseases, oxLDL/β2GPI was 0.85 U/mL for carotid artery disease, 0.72 U/mL for peripheral artery disease, and 0.52 U/mL for abdominal aortic aneurysm. There was a significant association with male gender, age, hypertension, and history of thrombosis. Subjects with oxLDL/β2GPI above the median (0.25 U/mL) were more likely to have arterial (OR 4.5, P = 0.004) or venous disease (OR 4.1, P = 0.008). Multivariate regression indicated that males (P = 0.021), high cholesterol (P = 0.011), and carotid disease (P = 0.023) were significant predictors of oxLDL/β2GPI. The coexistence of oxLDL/β2GPI in arterial and venous disease may suggest a common oxidative mechanism that independently predicts carotid artery disease.