Impact of whole genome amplification on analysis of copy number variants.
Large-scale copy number variants (CNVs) have recently been recognized to play a role in human genome variation and disease. Approaches for analysis of CNVs in small samples such as microdissected tissues can be confounded by limited amounts of material. To facilitate analyses of such samples, whole genome amplification (WGA) techniques were developed. In this study, we explored the impact of Phi29 multiple-strand displacement amplification on detection of CNVs using oligonucleotide arrays. We extracted DNA from fresh frozen lymph node samples and used this for amplification and analysis on the Affymetrix Mapping 500k SNP array platform. We demonstrated that the WGA procedure introduces hundreds of potentially confounding CNV artifacts that can obscure detection of bona fide variants. Our analysis indicates that many artifacts are reproducible, and may correlate with proximity to chromosome ends and GC content. Pair-wise comparison of amplified products considerably reduced the number of apparent artifacts and partially restored the ability to detect real CNVs. Our results suggest WGA material may be appropriate for copy number analysis when amplified samples are compared to similarly amplified samples and that only the CNVs with the greatest significance values detected by such comparisons are likely to be representative of the unamplified samples.


Absence of Intermediates in the BINOL-Derived Mg(II)/Phosphate-Catalyzed Desymmetrizative Ring Expansion of 1-Vinylcyclobutanols.
The catalyzed desymmetrizative ring expansion of alkenylcyclobutanols promoted by halofunctionalization of the alkene moiety with N-bromosuccinimide has been experimentally and computationally studied. The reaction yields highly enantioenriched cyclopentanones bearing two all-carbon quaternary stereocenters, one of them being generated in the rearrangement of the cyclobutane ring and the other by enantioselective desymmetrization. The reaction is competitive with the formation of a spiroepoxide, but it turns completely selective toward the cyclopentanone when a chiral bisphosphonium magnesium salt is employed as a catalyst. Mechanistic studies support the formation of an ion pair leading to a complex with only a unit of phosphoric acid, which is the resting state of the catalytic cycle. Calculations reproduce in an excellent way the observed reactivity and predict the effect exerted by the substituents of the aromatic ring linked to the double bond. The computational studies also revealed the reaction as a highly asynchronous concerted process taking place as one kinetic step but in two stages: (i) halogenation of the double bond and (ii) rearrangement of the cyclobutane. No intermediates are present in the reaction as energy minima. The experimental scope of the reaction further confirms the predictions for the observed reactivity and selectivity.


Emerging Infectious Diseases in Pregnancy.
It has been recognized for centuries that pregnant women have unique susceptibilities to many infectious diseases that predispose them to untoward outcomes compared with the general adult population. It is thought a combination of adaptive alterations in immunity to allow for the fetal allograft combined with changes in anatomy and physiology accompanying pregnancy underlie these susceptibilities. Emerging infectious diseases are defined as those whose incidence in humans has increased in the past two decades or threaten to increase in the near future. The past decade alone has witnessed many such outbreaks, each with its own unique implications for pregnant women and their unborn fetuses as well as lessons for the health care community regarding response and mitigation. Examples of such outbreaks include, but are not limited to, severe acute respiratory syndrome, the 2009 H1N1 pandemic influenza, Ebola virus, and, most recently, the Zika virus. Although each emerging pathogen has unique features requiring specific considerations, there are many underlying principles that are shared in the recognition, communication, and mitigation of such infectious outbreaks. Some of these key principles include disease-specific delineation of transmission dynamics, understanding of pathogen-specific effects on both mothers and fetuses, and advance planning and contemporaneous management that prioritize communication among public health experts, clinicians, and patients. The productive and effective working collaboration among the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine has been a key partnership in the successful communication and management of such outbreaks for women's health care providers and patients alike. Going forward, the knowledge gained over the past decade will undoubtedly continue to inform future responses and will serve to optimize the education and care given to pregnant women in the face of current and future emerging infectious disease outbreaks.


[The diagnostic value of TEOAE-glycerine test in patients with vertigo on the first attack].
To investigate the diagnostic value of transiently evoked otoacoustic emissions (TEOAE) combined with glycerine test in patients with vertigo on the first attack. PTT and TEOAE-glycerine test were conducted on the 28 patients who suffered the first attack of vertigo without hearing loss, tinnitus or a sensation of fullness in the ear. At the same time, history and clinical manifestation of the patients were not supportive for the non-Meniere's disease. Among the 28 cases, four of them had nothing changed on the PTT and TEOAE parameters after glycerol administration, all of the indexes were in the normal range. Among the 20 positive cases in the TEOAE-glycerine test (unilateral ear 16 cases, bilateral ears 4 cases), TEOAE for 2 cases were not evoked before glycerol administration, while it was evocable after glycerol administration. For the positive ears, all of the parameters of TEOAE were lower than those in the normal standard before and after glycerol administration; there were 4 positive cases in the PTT glycerine test, however, both TEOAE were not evoked before and after glycerol administration. TEOAE-glycerine test can be used as a routine method for the early diagnosis of Meniere's disease and differentiating diagnosis in the patients who suffer vertigo on the first attack with normal hearing.


Responses of tree growth, leaf area and physiology to pavement in Ginkgo biloba and Platanus orientalis.
Trees growing on paved lands endure many environmental stresses in the urban environment. However, the morphological and physiological mechanisms underlying tree adaptation to pavement in the field are less known. In this study, we investigated 40 sites where Ginkgo biloba and Platanus orientalis grow on adjacent pairs of paved and vegetated plots in parks and roadsides in Beijing, China. Relative to the vegetated land, the mean increments in the diameter at breast height and height in the paved land were significantly decreased by 44.5% and 31.9% for G. biloba and 31.7% and 60.1% for P. orientalis, respectively. These decreases are related to both the decrease in assimilation products due to the reductions in leaf area, leaf total nitrogen content, and chlorophyll content and the increase in energy cost due to the synthesis of more soluble sugar and proline for mitigating stress. The increase in leaf soluble sugar content, proline content, and δ13C indicated that trees could adapt to the paved land through the regulation of osmotic balance and the enhancement of water-use efficiency. Piecewise structural equation models showed that trees growing on the paved land are stressed by compounding impacts of the leaf morphological and physiological changes. Therefore, it is critical to explore the complex response of plant morphological and physiological traits to the pavement-induced stress for improving tree health in urban greening.


Nasal and bronchoalveolar lavage fluid cytokines in early cystic fibrosis.
Cytokine levels in nasal and lower airways in young cystic fibrosis (CF) patients were compared with those in controls. Nasal (NLF) and bronchoalveolar (BALF) lavage fluids were obtained from children with or without CF who were undergoing bronchoscopy for clinical indications. In NLF, neither inflammatory cells nor cytokine concentrations differed between patients and controls. However, interleukin (IL)-8 levels in infected BALF from children with CF were markedly elevated compared with levels in infected and uninfected controls, even after standardization of IL-8 concentrations to bacterial counts. BALF IL-6 was modestly elevated in infected CF patients compared with uninfected but not infected controls; IL-10 did not differ among the groups. NLF and BALF IL-8 levels were not significantly correlated. Excessive airway inflammation in early CF thus appears to be confined to the lower respiratory tract, and IL-8 levels are markedly increased in children with CF compared with control children with a bacterial infection of the lower airways.


The Human Plasma Proteome Draft of 2017: Building on the Human Plasma PeptideAtlas from Mass Spectrometry and Complementary Assays.
Human blood plasma provides a highly accessible window to the proteome of any individual in health and disease. Since its inception in 2002, the Human Proteome Organization's Human Plasma Proteome Project (HPPP) has been promoting advances in the study and understanding of the full protein complement of human plasma and on determining the abundance and modifications of its components. In 2017, we review the history of the HPPP and the advances of human plasma proteomics in general, including several recent achievements. We then present the latest 2017-04 build of Human Plasma PeptideAtlas, which yields ∼43 million peptide-spectrum matches and 122,730 distinct peptide sequences from 178 individual experiments at a 1% protein-level FDR globally across all experiments. Applying the latest Human Proteome Project Data Interpretation Guidelines, we catalog 3509 proteins that have at least two non-nested uniquely mapping peptides of nine amino acids or more and >1300 additional proteins with ambiguous evidence. We apply the same two-peptide guideline to historical PeptideAtlas builds going back to 2006 and examine the progress made in the past ten years in plasma proteome coverage. We also compare the distribution of proteins in historical PeptideAtlas builds in various RNA abundance and cellular localization categories. We then discuss advances in plasma proteomics based on targeted mass spectrometry as well as affinity assays, which during early 2017 target ∼2000 proteins. Finally, we describe considerations about sample handling and study design, concluding with an outlook for future advances in deciphering the human plasma proteome.


Metastatic intracerebral choriocarcinoma in a teenager.
Intracerebral metastatic carcinoma is one of the most common tumors of the central nervous system. Intracerebral choriocarcinoma, however, is rare, but may occur as the initial manifestation of choriocarcinoma. This case report describes the treatment and outcome of a teenager with metastatic intracerebral choriocarcinoma.


The impact of lymph node dissection and positive lymph nodes on cancer-specific mortality in contemporary pT2-3 non-metastatic renal cell carcinoma treated with radical nephrectomy.
To assess the effect of lymph node dissection (LND), number of removed nodes (NRN), and number of positive nodes (NPN), on cancer-specific mortality (CSM) in contemporary vs historical patients with pT2-3 Nany M0 renal cell carcinoma (RCC) treated with radical nephrectomy (RN). Within the Surveillance, Epidemiology, and End Results database (2001-2013), we identified patients with non-metastatic pT2-3 Nany RCC who underwent RN with or without LND. Kaplan-Meier analyses and multivariable Cox regression models with propensity score weighting for inverse probability of treatment were used. Of 25 357 patients, 24.8% underwent LND (2001-2007: 3 167 patients vs 2008-2013: 3 133 patients). The median NRN was 3 (interquartile range [IQR]: 1-7). Positive nodes were identified in 17.1%: 9.3% of pT2 and 21.6% of pT3 patients, who underwent LND. The median NPN was 2 (IQR: 1-3). In multivariable models, LND did not decrease CSM (hazard ratio [HR] 1.29; P < 0.001). LND extent, defined as NRN, did not decrease CSM (HR 0.94; P = 0.3). Finally, multivariable models testing the effect of NPN showed increased CSM in pT3 but not in pT2 patients (HR 1.29 and 1.58, P = 0.02 and P = 0.1, respectively). NRN exerted a protective effect on CSM in patients with positive nodes (HR 0.98; P = 0.007). In contemporary and historical patients LND or its extent do not protect from CSM. However, the NPN increases the rate of CSM in pT3 patients. Consequently, LND and its extent appear to have little if any therapeutic value in pT2-3 Nany M0 patients, besides its prognostic impact. High-risk non-metastatic patients may represent a target population for a multi-institutional prospective trial.


Deterministic Scheme for Two-Dimensional Type-II Dirac Points and Experimental Realization in Acoustics.
Low-energy electrons near Dirac/Weyl nodal points mimic massless relativistic fermions. However, as they are not constrained by Lorentz invariance, they can exhibit tipped-over type-II Dirac/Weyl cones that provide highly anisotropic physical properties and responses, creating unique possibilities. Recently, they have been observed in several quantum and classical systems. Yet, there is still no simple and deterministic strategy to realize them since their nodal points are accidental degeneracies, unlike symmetry-guaranteed type-I counterparts. Here, we propose a band-folding scheme for constructing type-II Dirac points, and we use a tight-binding analysis to unveil its generality and deterministic nature. Through realizations in acoustics, type-II Dirac points are experimentally visualized and investigated using near-field mappings. As a direct effect of tipped-over Dirac cones, strongly tilted kink states originating from their valley-Hall properties are also observed. This deterministic scheme could serve as a platform for further investigations of intriguing physics associated with various strongly Lorentz-violating nodal points.


Over-the-counter pill provision: evidence from Jamaica.
Although many countries allow over-the-counter distribution of oral contraceptives, doubt remains about whether such provision is safe for the user. The greatest concern is whether women with contraindications for use are given access to the pill. Clearly, women without such contraindications should be given access to it and be offered adequate information about its correct use. In 15 pharmacies in Jamaica, mystery clients approached pharmacists to determine their willingness to sell oral contraceptives and to solicit information from them about correct use of the method. In addition to data from mystery-client observations, interviews were conducted with 78 pharmacists and with 524 pharmacy customers who bought oral contraceptives, providing complementary information about knowledge of, attitudes toward, and experiences with the method. Analysis of the combined findings suggests that over-the-counter provision of oral contraceptives is a safe, practical, and effective method of distribution in Jamaica.


Sperm-mediated gene transfer: effect on bovine in vitro embryo production.
The technique of sperm-mediated gene transfer (SMGT) can be used to delivery exogenous DNA into the oocyte. However, it has low repeatability and produces inconsistent results. In order to optimize this technique, it is necessary to study the mechanism by which DNA enters the sperm cell and integrates in the sperm genome. Furthermore, studies must focus in the maintenance of sperm cell viability and function. The aim of this study was to evaluate different SMGT protocols of sperm electroporation or capacitation (CaI) aiming to maintain sperm viability in the production of bovine embryos in vitro. Frozen-thawed semen was divided in two experimental groups (electroporation or CaI) and one control group (non-treated cells). For the electroporation method, five different voltages (100, 500, 750, 1000 or 1500 V) with 25 μF capacitance were used. For CaI treatment, combinations of two CaI concentrations (250 nM or 500 nM), two incubation periods of sperm cells with CaI (1 or 5 min) and two incubation periods that mimicked time of sperm cell interaction with exogenous DNA molecules (1 or 2 h) were evaluated. According to our data, electroporation and CaI treatments do not prevent sperm penetration and oocyte fertilization and can be an alternative method to achieve satisfactory DNA delivery in SMGT protocols.


[The theory of biomembrane elasticity].
The dielectric permeability of the different layers of biological membrane were investigated. The objects taken into account included a lipid bilayer, membrane proteins and external covers formed by clumps of protein chains. The distribution of electric fields and the values of electrostatic forces of membrane elastic layers stretching was found in such membrane.


[Single-photon emission computed tomography in diagnosis of left ventricular post-infarction aneurysm].
To assess value of single-photon emission computed tomography with (99m)Tc-sestamibi ((99m)Tc MIBI SPECT) for detection of post-infarction left ventricular aneurysm in patients with coronary artery disease. Fifty nine patients were operated upon because of coronary heart disease. In 27 patients with post-infarction left ventricular aneurysm modified Dor operation (aneurysmectomy with endoventricular circular patch plasty reconstruction) was performed. In 24 patients with extended cardiosclerosis direct myocardial revascularization was conducted. Comparison of (99m)Tc MIBI SPECT data obtained at rest and during dobutamine stress test revealed some diagnostic features characteristic of patients with left ventricular post-infarction aneurysm. Quantitative and qualitative assessment of viability of myocardium in basal and "borderline" zones influenced not only the volume of revascularization, it was important for preliminary determination of post-infarction left ventricular aneurysm resection level, selection of type of plasty, prognostication of complications in immediate and remote postoperative periods.


[Umbilical cord blood from an unrelated donor as source for stem cell transplantations in inborn errors of metabolism].
In certain inborn errors of metabolism, an allogeneic stem cell transplantation is able to prevent disease progression. This is only possible when the stem cell transplantation (SCT) is performed early in life, before cerebral involvement has occurred. In addition to bone marrow and peripheral blood, unrelated umbilical cord blood appears to be an effective stem cell source as well. Important advantages of umbilical blood as stem cell source are: the time between diagnosis and SCT can be considerably reduced; there is a greater chance of finding a suitable donor and the risk of graft-versus-host disease and viral transmission is decreased. By far the most common disease in the group of inborn metabolic errors for which SCTs are performed is Hurler's disease. In these patients, the percentage of successful transplantations is considerably higher after the use ofunrelated cord blood than when bone marrow or peripheral blood is used as a stem cell source. In addition, donor chimerism occurred significantly more often in those patients who had received unrelated umbilical cord blood. There are also potential disadvantages attached to the use of umbilical blood as stem cell source: the possibility of only one donation per donor and less adaptive immunity following umbilical blood SCT with an increased risk of reactivation of a previous viral infection. However, these disadvantages are less applicable to young children with inborn errors of metabolism. The improvement of transplantation techniques and the availability of this new stem cell source could improve the success rate of this procedure and consequently the prognosis of these severely affected patients.


Melatonin protects sperm cells of Capoeta trutta from toxicity of titanium dioxide nanoparticles.
In this study, it was aimed to determine the protective effects of melatonin (0.01, 0.1, and 1 mM) against 10 mg/L titanium dioxide nanoparticles (TiO2-NPs) on kinematic and oxidative indices in the sperm cells of Capoeta trutta. Therefore, TiO2 nanoparticles were synthesized primarily within the scope of the study. The synthesized nanoparticles were characterized by structurally different techniques. Then, melatonin and TiO2 were applied to Capoeta trutta sperm cells by in vitro. According to our data, all doses of melatonin showed protective effects on all velocities of sperm cells such as the straight line velocity (VSL), the curvilinear velocity (VCL), and the angular path velocity (VAP) against TiO2-NPs, while 0.1 and 1 mM doses of melatonin improved the VSL value. Although TiO2-NPs increased total glutathione (tGSH), malondialdehyde (MDA) lipid peroxidation, and superoxide dismutase (SOD) compared to the control group, there were positive treatment effects for all doses of melatonin on antioxidant capacity of sperm cells. At the end of this research, it is suggested that over 0.1 mM dose of melatonin improves the velocity of sperm cells and it plays a protective role against the toxic effects of TiO2-NPs.


Custom acetabular prosthesis for total hip replacement: A case report in a dog with acetabular bone loss after femoral head and neck ostectomy.
To describe the application of a custom acetabular prosthesis (CAP) for total hip replacement (THR) in a dog 20 months after femoral head and neck ostectomy (FHNO). Case report. A 10-year-old, male, castrated, Labrador retriever with progressive lameness and pain after FHNO. Acetabular bone stock was assessed as insufficient for conventional THR, so a biflanged CAP was designed and three-dimensionally printed in titanium to bridge the bone defect. The CAP had a porous surface for long-term biologic fixation on the backside and was anchored to the ilium and ischium with screws. A polyethylene cup was cemented into the CAP, and a bolted cementless femoral stem was inserted. The loss of the conventional anatomic landmarks complicated intraoperative orientation and led to eccentric reaming and 5-mm malalignment of the CAP. Reduction of the prosthetic joint was difficult because of periarticular fibrosis, loss of functional muscle length, and thickness of the CAP, and intraoperative shortening of the stem neck was required. Postoperative complications included sciatic neurapraxia, which resolved with time and conservative management. Absence of pain and improvement of range of motion were observed at clinical examination 12 months after surgery; however, moderate hind limb lameness persisted due to muscle tension. No evidence of implant loosening was noted on radiographs acquired 24 months after surgery. Femoral head and neck ostectomy with poor functional outcome was ameliorated by using a CAP in this dog. Use of a CAP can be considered to treat acetabular defects in dogs.


Complications of T-tube drainage of the common bile duct.
The complications associated with T-tube drainage of the common bile duct following biliary surgery were studied prospectively. A high rate of complications especially associated with T-tube removal was found. Biliary leakage and bacteraemia were the two main problems though in most cases caused minimal clinical upset. Alternatives to T-tube drainage are discussed. It is suggested that if T-tubes are to be used broad spectrum antibiotic cover should be employed at the time of removal.


Observations on intramammary infection and somatic cell counts in cows treated with recombinant bovine somatotropin.
Data were collected on udder health variables as part of a study of the effects of recombinant bovine somatotropin on production in lactating dairy cows. Milk samples, obtained at three intervals during the study, were assessed for their somatic cell count and bacteriological culture result. There was an increase in the prevalence of infection at mid-lactation in the 20.6 and 41.2 mg per day treatment groups as compared to the controls. There was no difference detected in the mean cell count between groups from the samples collected pretrial, mid-lactation, or late lactation. However, analysis of the individual cow Dairy Herd Improvement somatic cell count data showed a difference between groups which was most evident in mid-lactation.


Interventions to reduce dependency in personal activities of daily living in community-dwelling adults who use homecare services: protocol for a systematic review.
There is a growing demand for services whereby individuals receive assistance from care workers for personal care within the home. This has led to the development of re-ablement or restorative homecare services that provide time-limited input aimed at reducing dependency in personal activities of daily living, and preventing or delaying the need for further homecare support. However, little is currently known about how such interventions are configured, or how they may affect individuals' ability to carry out personal care independently. We will seek to identify studies that compare an intervention designed to reduce dependency in personal activities of daily living with routine input or usual care as the control. We will include randomised controlled trials, nonrandomised controlled trials, and controlled before and after studies. We will also include interrupted time series studies. We shall search electronic databases in addition to searching for ongoing and unpublished studies, and where appropriate will contact key authors. Two reviewers will independently screen articles for inclusion; will assess risk of bias using quality assessment tools; and will carry out data extraction using pre-prepared forms. Any disagreements, at any stage, will be resolved by discussion and the involvement of a third reviewer if needed. We will produce a narrative summary of the results. A meta-analysis will be conducted if sufficient data are available of appropriate quality and comparability. The findings from this review will inform future practice within homecare re-ablement services; will inform policy decisions about the structure, organisation and content of such services; and will identify areas where further research is warranted. This review protocol has been registered on the PROSPERO database (CRD42013004163).


Identification of biomarkers for physical frailty and sarcopenia through a new multi-marker approach: results from the BIOSPHERE study.
Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy. Two-hundred community-dwellers, 100 with PF&S and 100 non-physically frail, non-sarcopenic (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 serum analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel) analysis. Separate SO-CovSel models were constructed for the whole study population and for the two genders. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet-derived growth factor BB, heat shock protein 72 (Hsp72), myeloperoxidase, and α-aminobutyric acid defined the profile of nonPF&S participants. Gender-specific SO-CovSel models identified a "core" biomarker profile of PF&S, characterized by higher serum levels of aspartic acid and Hsp72 and lower concentrations of macrophage inflammatory protein 1β, with peculiar signatures in men and women.SO-CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.


Both conserved signals on mammalian histone pre-mRNAs associate with small nuclear ribonucleoproteins during 3' end formation in vitro.
Pre-mRNA substrates containing sequences from human and mouse histone genes are accurately processed in a HeLa cell nuclear extract to generate mature 3' termini. When in vitro processing reactions containing either human histone H3 or mouse histone H3 transcripts are treated with RNase T1 and probed with antibodies specific for the Sm protein determinants or for the trimethylguanosine cap structure unique to the U RNAs present in small nuclear ribonucleoproteins, RNA fragments that encompass the site of 3' end formation on the pre-mRNA transcript are selectively recovered. Several different interactions are detected: at time zero, the protected region contains the upstream conserved hairpin loop structure; at later times during the reaction, protection extends beyond the site of 3' end formation to include the downstream conserved sequence element and the 5' cap of the transcript is bound as well. Possible interactions between Sm small nuclear ribonucleoproteins and these conserved sequence elements in histone pre-mRNAs are discussed.


Versatile Neuromorphic Modulation and Biosensing based on N-type Small-molecule Organic Mixed Ionic-Electronic Conductors.
The ion/chemical-based modulation feature of organic mixed ionic-electronic conductors (OMIECs) are critical to advancing next generation bio-integrated neuromorphic hardware. Despite achievements with polymeric OMIECs in organic electrochemical neuronal synapse (OENS). However, small molecule OMIECs based OENS has not yet been realized. Here, for the first time, we demonstrate an effective materials design concept of combining n-type fused all-acceptor small molecule OMIECs with subtle side chain optimization that enables robustly and flexibly modulating versatile synaptic behavior and sensing neurotransmitter in solid or aqueous electrolyte, operating in accumulation modes. By judicious tuning the ending side chains, the linear oligoether and butyl chain derivative gNR-Bu exhibits higher recognition accuracy for a model artificial neural network (ANN) simulation, higher steady conductance states and more outstanding ambient stability, which is superior to the state-of-art n-type OMIECs based OENS. These superior artificial synapse characteristics of gNR-Bu can be attributed to its higher crystallinity with stronger ion bonding capacities. More impressively, we unprecedentedly realized n-type small-molecule OMIECs based OENS as a neuromorphic biosensor enabling to respond synaptic communication signals of dopamine even at sub-μM level in aqueous electrolyte. This work may open a new path of small-molecule ion-electron conductors for next-generation ANN and bioelectronics.


A Rare Case of Obstructive Shock due to Cardiac Tamponade in a Term Pregnancy.
Obstructive shock due to cardiac tamponade is a rare, life-threatening occurrence in the peripartum period. Etiologies include preeclampsia, infection, autoimmune conditions, and malignancy. Early recognition of the underlying disease process allows for multidisciplinary treatment and a favorable outcome. A 33-year-old presented for cardiac tamponade identified in the peripartum period. She was diagnosed with preeclampsia with severe features immediately prior to her repeat cesarean delivery and received magnesium prophylaxis. Postoperatively, she developed hypotension, tachycardia, and shortness of breath and was found to have a pericardial effusion with tamponade physiology. She underwent pericardial drain placement which was initially successful. However, she had recurrent symptomatic tamponade and thus a pericardial window was performed resulting in improvement of her symptoms. Workup revealed pericardial inflammation possibly secondary to a viral source, and she was successfully treated with anti-inflammatory therapy. We hypothesize that this patient's cardiac tamponade was caused by inflammatory pericarditis exacerbated by severe preeclampsia. Preeclampsia is a disease characterized by cardiovascular remodeling and fluid shifts in other compartments and thus is theorized to have contributed to this patient's effusion. Cardiac tamponade should be considered in the differential for any parturient presenting with hypotension and shortness of breath.


Survival of glass fiber post restorations over 5 years.
To evaluate the survival of glass fiber reinforced composite post (GFP) restorations and to identify risk factors for restoration failure. GFPs of three consecutively placed post systems, two tapered and one parallel-sided, were adhesively luted and the core was built with a resin composite. Teeth served as abutment teeth according to the prosthetic treatment plan. 149 GFP in 121 patients (age: 53 +/- 15 year; 50 men; 71 women) were followed for 5-79 months (mean +/- SD: 50 +/- 21 months). Cox proportional hazards models were used to evaluate the association between several clinical variables and the failure rate. After exclusion of endodontic failures (n = 3), significantly higher failure rates were found for restorations of anterior teeth compared to posterior teeth (hazard regression (HR): 2.8; 95% confidence interval (CI): 1.4; 5.8; P = 0.004). Restorations in teeth with no proximal contacts compared to at least one proximal contact, single crowns compared to fixed partial dentures and less than two remaining cavity walls had a HR of 2.4 (CI: 0.8-7.1), 2.4 (CI: 0.6-8.7), and 1.5 (CI: 0.6-3.8), respectively. However, these correlations were not statistically significant (P > 0.05).


Hypoxia-sensitive long noncoding RNA CASC15 promotes lung tumorigenesis by regulating the SOX4/β-catenin axis.
Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles in enabling malignant cells to survive under hypoxic stress. However, the molecular crosstalk between lncRNAs and hypoxia signaling cascades in non-small cell lung cancer (NSCLC) remains largely elusive. Firstly, we identified differentially expressed lncRNA cancer susceptibility candidate 15 (CASC15) as associated with NSCLC based on bioinformatic data. The clinical significance of CASC15 in lung cancer was investigated by Kaplan-Meier survival analysis. Then, we modulated CASC15 expression in NSCLC cell lines by RNAi. CCK-8 and transwell assays were carried out to examine the effects of CASC15 on proliferation and migration of NSCLC cells. Upstream activator and downstream targets of CASC15 were validated by luciferase reporter assay, qRT-PCR, Western blotting, and chromatin immunoprecipitation (ChIP). Lastly, RNA in situ hybridization (RNA-ISH) and immunohistochemistry (IHC) were performed to confirm the genetic relationships between CASC15 and related genes in clinical samples. CASC15 was highly expressed in NSCLC tissues and closely associated with poor prognosis. Loss-of-function analysis demonstrated that CASC15 was essential for NSCLC cell migration and growth. Mechanistic study revealed that CASC15 was transcriptionally activated by hypoxia signaling in NSCLC cells. Further analysis showed that hypoxia-induced CASC15 transactivation was mainly dependent on hypoxia-inducible factor 1α (HIF-1α) and hypoxia response elements (HREs) located in CASC15 promoter. CASC15 promotes the expression of its chromosomally nearby gene, SOX4. Then SOX4 functions to stabilize β-catenin protein, thereby enhancing the proliferation and migration of NSCLC cells. HIF-1α/CASC15/SOX4/β-catenin pathway was activated in a substantial subset of NSCLC patients. HIF-1α/CASC15/SOX4/β-catenin axis plays an essential role in the development and progression of NSCLC. The present work provides new evidence that lncRNA CASC15 holds great promise to be used as novel biomarkers for NSCLC. Blocking the HIF-1α/CASC15/SOX4/β-catenin axis can serve as a potential therapeutic strategy for treating NSCLC.


Pseudomonas exotoxin-mediated delivery of exogenous antigens to MHC class I and class II processing pathways.
Peptides associated with class II MHC molecules are normally derived from exogenous proteins, whereas class I MHC molecules normally associate with peptides from endogenous proteins. We have studied the ability of Pseudomonas exotoxin A (PE) fusion proteins to deliver exogenously added antigen for presentation by both MHC class I and class II molecules. A MHC class II-restricted antigen was fused to PE; this molecule was processed in a manner typical for class II-associated antigens. However, a MHC class I-restricted peptide fused to PE was processed by a mechanism independent of proteasomes. Furthermore, we also found that the PE fusion protein was much more stable in normal human plasma than the corresponding synthetic peptide. We believe that effective delivery of an antigen to both the MHC class I and class II pathways, in addition to the increased resistance to proteolysis in plasma, will be important for immunization.


The biological functions of low-frequency vibrations (phonons) 5. A phenomenological theory.
Low-frequency internal motions of a biomacromolecule are thought to possess significant biological function from the dynamic point of view. In this paper, a general phenomenological theory is established by which it is clearly verified that low-frequency resonance plays a central role in the energy transmission required during the cooperative interaction between subunits in a protein oligomer. According to the present theory, it is found that the energy transmission between a pair of diagonal subunits in a protein oligomer with a polygon arrangement is the most efficient, so as to in a sense further predict that after a ligand is bound to a subunit by random collision, its diagonal subunit in the same protein oligomer will possess the greatest probability of binding with the next ligand. Furthermore, based on the concept of the 'resonance-controlled trigger' derived from the phenomenological theory, it is feasible to estimate the lower time limit of allosteric transition from one subunit to the other. Such a time limit depends on the dominant low-frequency mode of each subunit, the ratio of the coupling force constant to the corresponding inherent force constant, as well as the geometrical arrangement of subunits in a protein oligomer. So far none of the allosteric transitions observed in proteins has exceeded the time limit as defined here, indicating a logical consistency between our theory and the experiments.


Functional aspects of drusen regression in age-related macular degeneration.
To investigate the functional implications of macular soft drusen regression in AMD eyes. Patients were selected from a large ongoing collection of clinical data at Moorfields Eye Hospital. Phenotyping based on standard colour fundus images was performed according to the system defined by the International Classification for ARM, by certified graders masked to the main aim of the study. Fundus autofluorescence (FA) was recorded using a Heidelberg Retina Angiograph 2. Where drusen regression was confirmed by independent grading, the patient was invited for photopic and scotopic fine matrix mapping (FMM). Phenotype and functional data were analysed for correlations between fundus appearance, autofluorescence and retinal sensitivity. Fundus and FA images of 960 patients were screened, soft drusen regression was detected in 34 cases, and 14 patients agreed to participate in the study, ranging in age from 52 to 84 years (median 72). The mean follow-up period was 5.9 years (range 2.8-14.4 years). FMM showed generalised threshold elevation relative to normal controls both under photopic and scotopic conditions. Scotopic sensitivity loss exceeded photopic loss in all cases. Sensitivity loss over areas with drusen or regressed drusen did not differ significantly from that over non-drusen areas. Macular soft drusen may fade or disappear without detectable ophthalmoscopic, FA or psychophysical signs of local dysfunction. This phenomenon is a potential source of misclassification. The prognosis for cases with true regression of drusen compared with those without needs to be considered in future studies on AMD.


Mycoplasma synoviae has two distinct phase-variable major membrane antigens, one of which is a putative hemagglutinin.
Mycoplasma synoviae is a major pathogen of poultry, causing synovitis and respiratory infection. A cluster of 45- to 50-kDa membrane proteins is immunodominant in strain WVU-1853. Four distinct proteins were identified in this cluster by high-pressure liquid chromatography. Monoclonal antibodies and monospecific antisera against each established that they fell into two groups, MSPA and MSPB, each containing two members distinguishable by a difference in hydrophobicity. A 25- to 30-kDa membrane protein (MSPC) was shown to be antigenically related to the MSPB proteins. Considerable variation in the size and expression of MSPA and MSPB was observed among different strains of M. synoviae. Examination of expression in colonies of strain WVU-1853 established that both MSPA and MSPB (and MSPC) were phase variable. Immunostaining of MSPB (and MSPC) with monoclonal antibodies exhibited quantal variation, with three distinct levels observed between and within colonies. Hemadsorption by M. synoviae colonies was also found to be phase variable, with some colonies exhibiting sectorial expression of hemadsorption. Monospecific antisera against MSPA inhibited hemagglutination, but neither monoclonal antibodies nor monospecific antisera against MSPB could inhibit hemagglutination. However, loss of the capacity to hemadsorb by individual clones was associated with loss of expression of both MSPA and MSPB. These findings have elucidated the complexity of structure, function, and expression of the 45- to 50-kDa membrane protein cluster of M. synoviae, and they suggest that all members of the cluster may be involved in adhesion.


Fecundity-survival trade-offs and parental risk-taking in birds.
Life history theory predicts that parents should value their own survival over that of their offspring in species with a higher probability of adult survival and fewer offspring. We report that Southern Hemisphere birds have higher adult survival and smaller clutch sizes than Northern Hemisphere birds. We subsequently manipulated predation risk to adults versus offspring in 10 species that were paired between North and South America on the basis of phylogeny and ecology. As predicted, southern parents responded more strongly to reduce mortality risk to themselves even at a cost to their offspring, whereas northern parents responded more strongly to reduce risk to their offspring even at greater risk to themselves.


Association of salivary flow rates with maximal bite force.
Mean salivary secretion and bite force decrease with advancing age. Previous studies have shown that salivary flow rates are influenced by mastication. In the present study, we examined the relationship between salivary flow rates and maximal bite force in a community-based sample of men and women 35 years of age or older. Salivary flow rates for unstimulated whole and unstimulated submandibular/sublingual (SMSL) saliva as well as citrate-stimulated parotid and SMSL saliva were measured in 399 subjects. Bite force was assessed with a bilateral force transducer. Pearson correlation analysis yielded significant positive correlations between bite force and flow rates for unstimulated whole saliva (r = 0.24, p < 0.0001), stimulated parotid saliva (r = 0.13, p < 0.03), unstimulated SMSL (r = 0.14, p < 0.0001), and stimulated SMSL (r = 0.16, p < 0.003). When adjusted for age and gender, the partial correlations between bite force and salivary flow rates remained significant for unstimulated whole saliva (r = 0.10, p < 0.05), stimulated parotid saliva (r = 0.13, p < 0.02), and stimulated SMSL saliva (r = 0.14, p < 0.006). Subjects were divided into four groups based on their maximal bite force score (low, medium low, medium high, and high). For each saliva type, the flow rate of the high-bite-force group was significantly greater than that of the low-bite-force group as well as that of the medium-high-bite-force group. These results confirm an age-related decrease in bite force and salivary flow rates and show that, regardless of age or gender, bite force is correlated with salivary flow.


Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine.
A revamped interest in the study of hallucinogens has recently emerged, especially with regard to their potential application in the treatment of psychiatric disorders. In the last decade, a plethora of preclinical and clinical studies have confirmed the efficacy of ketamine in the treatment of depression. More recently, emerging evidence has pointed out the potential therapeutic properties of psilocybin and LSD, as well as their ability to modulate functional brain connectivity. Moreover, MDMA, a compound belonging to the family of entactogens, has been demonstrated to be useful to treat post-traumatic stress disorders. In this review, the pharmacology of hallucinogenic compounds is summarized by underscoring the differences between psychedelic and nonpsychedelic hallucinogens as well as entactogens, and their behavioral effects in both animals and humans are described. Together, these data substantiate the potentials of these compounds in treating mental diseases.


Variable-Volume Kinetic Model to Estimate Absolute Blood Volume in Patients on Dialysis Using Dialysate Dilution.
Long- and short-term adverse outcomes in hemodialysis (HD) have been associated with intradialytic hypotension, a common HD complication and significant cause of morbidity. It has been suggested that knowledge of absolute blood volume (ABV) could be used to significantly improve treatment outcomes. Different dilution-based protocols have been proposed for estimating ABV, all relying on the classic mono-exponential back-extrapolation algorithm (BEXP). In this paper, we introduce a dialysate dilution protocol and an estimation algorithm based on a variable-volume, two-compartment, intravascular blood water content kinetic model (VVKM). We compare ABV estimates derived using the two algorithms in a dialysate dilution study including three arterio-venous (AV) and three central-venous (CV) access patients, and multiple bolus injection tests (3-5) within each of several (2-6) HD treatments. The distribution of differences between ABV estimated from the two methods showed negligible systematic difference between the mean values of ABVs estimated from the BEXP and VVKM algorithms, however, the VVKM estimates were 53% and 42% more precise for the CV and AV patients, respectively. Good agreement was observed between measured and VVKM-estimated blood water concentration with the root-mean-square error (RMSE) less than 0.02 kg/kg (2%) and 0.03 kg/kg (3%) for AV and CV patients, respectively. The dilution protocol and the new VVKM-based estimation algorithm offer a noninvasive, inexpensive, safe, and practical approach for ABV estimation in routine HD settings.


New insights into the bioactivity of peptides from probiotics.
Probiotics are unique bacteria that offer several therapeutic benefits to human beings when administered in optimum amounts. Probiotics are able to produce antimicrobial substances, which stimulate the body's immune responses. Here, we review in detail the anti-infective peptides derived from probiotics and their potential immunomodulatory and anti-inflammatory activities, including a major role in cross-talk between probiotics and gut microbiota under adverse conditions. Insights from the engineered cell surface of probiotics may provide novel anti-infective therapy by heterologous expression of receptor peptides of bacterial toxins. It may be possible to use antigenic peptides from viral pathogens as live vaccines. Another possibility is to generate antiviral peptides that bind directly to virus particles, while some peptides exert anti-inflammatory and anticancer effects. Some extracellular polymeric substances might serve as anti-infective peptides. These avenues of treatment have remained largely unexplored to date, despite their potential in generating powerful anti-inflammatory and anti-infective products.


Safety and efficacy of rivastigmine in patients with Alzheimer's disease not responding adequately to donepezil: an open-label study.
Switching patients with Alzheimer's disease from one cholinesterase inhibitor to another represents a viable option for patients not responding to current therapy. The objective of this large U.S.-based study was to evaluate the safety and efficacy of a treatment switch to rivastigmine in patients not responding adequately to or declining on treatment with donepezil. In this 26-week, prospective, open-label, single-arm, multicenter study conducted from April 24, 2003, to June 25, 2004, patients with mild-to-moderate Alzheimer's disease (DSM-IV-TR criteria) who were not responding to donepezil were treated with rivastigmine 3-12 mg/day. Safety and tolerability were measured by the occurrence of adverse events and patient disposition. Treatment effects on global functioning were assessed using the Clinical Global Impression of Change (CGIC) scale. Two hundred seventy patients with a mean age of 78.5 (SD = 7.56) years and a mean duration of dementia of 3.5 (SD = 2.06) years were included in the study. Sixty-nine percent of patients completed the study with 17.8% discontinuing due to adverse events. Eighty-three percent of patients reported at least 1 adverse event, with the most frequently occurring adverse events affecting the gastrointestinal system (54%). The majority of patients were reported to have either improvement or no decline on the CGIC. A limitation of the study is that the interpretation of the results is based on an overall completion rate of 69%. Immediately switching patients from donepezil to rivastigmine without a washout period was safe and well tolerated in the current study. Additionally, these results suggest that patients not responding adequately to or declining while taking donepezil may improve or stabilize after switching to rivastigmine.


Codevelopment of well-being and self-esteem in romantic partners: Disentangling the effects of mutual influence and shared environment.
Common sense suggests that romantic partners tend to be interdependent in their well-being and self-esteem. The authors tested the degree to which codevelopment in romantic partners (i.e., development in similar directions) is due to mutual influence between partners or due to the effects of shared environment, using longitudinal data from 5 samples of couples (N = 4,116 participants). The samples included dating, cohabiting, and married couples, with a broad age range covering young adulthood to old age. The authors used a longitudinal version of the actor-partner interdependence model and examined measures of well-being (life satisfaction, positive affect, negative affect, and depression) and self-esteem. After conducting the study-level analyses, we meta-analytically aggregated the findings across studies. The results showed significant mutual influence between partners in life satisfaction, positive affect, negative affect, and depression, and significant effects of shared environment on life satisfaction, positive affect, negative affect, depression, and self-esteem. The findings suggest that both mutual influence and shared environment account for codevelopment of well-being in romantic partners. In contrast, only shared environment but not mutual influence contributes to the partners' codevelopment of self-esteem. The findings have important implications because they show that the level of well-being of a person's relationship partner has long-term influence on the person's own well-being. (PsycINFO Database Record


Phenotypic variations in wolf-hirschhorn syndrome.
Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder caused by terminal deletion of the short arm of chromosome 4. The clinical picture includes growth retardation, severe mental retardation, characteristic "Greek helmet" like face, seizures and midline defects in the brain, heart, palate and genitalia. Recently-used molecular techniques increase the number of diagnosed cases due to the detection of smaller deletions. The severity of the clinical presentation is variable depending on the haploinsufficiency of genes in a deleted region. We present six children with WHS with variable clinical appearance. The assessment of several elements (facial dysmorphism, mental retardation, additional congenital anomalies) provided classification into minor, mild or severe forms. Three of the children had a visible cytogenetic deletion on chromosome 4p, two had microdeletions detected with fluorescent in situ hybridization (FISH), and one child with a less characteristic clinical picture had a mosaic type of the deletion. Correlation between the clinical presentation and the length of the deleted region was confirmed.


Volumetric formulation for a class of kinetic models with energy conservation.
We analyze a volumetric formulation of lattice Boltzmann for compressible thermal fluid flows. The velocity set is chosen with the desired accuracy, based on the Gauss-Hermite quadrature procedure, and tested against controlled problems in bounded and unbounded fluids. The method allows the simulation of thermohydrodyamical problems without the need to preserve the exact space-filling nature of the velocity set, but still ensuring the exact conservation laws for density, momentum, and energy. Issues related to boundary condition problems and improvements based on grid refinement are also investigated.


"Panic-attack disorders". Clinical and biological correlates.
A large group of patients suffer anxiety and phobic disorders which although are somewhat difficult to separate from other nosologic entities solely on clinical grounds, are having their borders with these disorders more keenly defined through our increased knowledge regarding various biological correlates. The main biological correlates: family history, incidence of mitral valve prolapse, response to specific pharmacological therapies, and provocation of panic attacks through the administration of I.V. sodium lactate is reviewed. Focus is placed on a current hypothesis regarding the mechanism of action of lactate infusion.


Pectobacterium punjabense sp. nov., isolated from blackleg symptoms of potato plants in Pakistan.
Pectobacterium isolates SS95T, SS54 and SS56 were collected from a potato field in the Chiniot district in the plains of the Punjab province, Pakistan. Sequencing of the gapA barcode revealed that these strains belong to a novel phylogenetic group separated from P.ectobacterium wasabiae and Pectobacterium parmentieri species. Furthermore, multilocus sequence analyses of 13 housekeeping genes (fusA, rpoD, acnA, purA, gyrB, recA, mdh, mtlD, groEL, secY, glyA, gapA and rplB) clearly distinguished the type strain, SS95T, from its closest relatives, i.e. P. parmentieri RNS 08-42-1AT and P. wasabiae CFBP3304T, as well as from all the other known Pectobacteriumspecies. In silico DNA-DNA hybridization (<44.1 %) and average nucleotide identity (<90.75 %) values of strain SS95T compared with other Pectobacterium type strains supported the delineation of a new species. Genomic and phenotypic comparisons permitted the identification of additional traits that distinguished the Pakistani isolates from all other known Pectobacterium type strains. The name Pectobacterium punjabense sp. nov. is proposed for this taxon with the type strain SS95T (=CFBP 8604T=LMG 30622T).


Effect of nutritional iron deficiency on acute and chronic inflammation.
Mild nutritional iron deficiency significantly reduced the severity of adjuvant induced joint inflammation assessed by histology, microfocal radiography, and subjective scoring. Other indices of adjuvant induced inflammation, such as increased levels of serum acute phase reactants, characteristic pathological changes in the inguinal lymph nodes, and granuloma formation at the site of adjuvant injection, were not different from those of control animals. The level of iron deficiency used did not affect the acute inflammatory response to a range of irritants and was not sufficient to suppress immune function. Both the hypersensitivity reaction to oxazalone and lymphocyte tritiated thymidine incorporation were normal. These observations support the view that iron has a selective influence on joint mediated inflammation.


Effects of emotional context on impulse control.
High risk behaviors such as narcotic use or physical fighting can be caused by impulsive decision making in emotionally-charged situations. Improved neuroscientific understanding of how emotional context interacts with the control of impulsive behaviors may lead to advances in public policy and/or treatment approaches for high risk groups, including some high-risk adolescents or adults with poor impulse control. Inferior frontal gyrus (IFG) is an important contributor to response inhibition (behavioral impulse control). IFG also has a role in processing emotional stimuli and regulating emotional responses. The mechanism(s) whereby response inhibition processes interact with emotion processing in IFG are poorly understood. We used 4.7 T fMRI in 20 healthy young adults performing a rapid event-related emotional Go/NoGo task. This task combined the Go/NoGo task, which is a classic means of recruiting response inhibition processes, with emotionally neutral and aversive distractor images. In IFG, both response inhibition in an emotionally neutral context (neutral NoGo trials) and aversive emotional picture processing (aversive Go trials) evoked activation greater than the simple response baseline (neutral Go trials). These results are consistent with the literature. Activation for response inhibition in aversive contexts (aversive NoGo-neutral Go trials) was approximately the sum of response inhibition activation (neutral NoGo-neutral Go) and aversive emotional distractor activation (aversive Go-neutral Go). We conclude that response inhibition and aversive emotional stimulus processing activities combine additively (linearly) in IFG, rather than interfering with each other (sub-linearly) or mutually-enhancing each other (super-linearly). We also found previously undocumented interaction effects between response inhibition (NoGo vs. Go) and emotional context (aversive vs. neutral distractor pictures) in bilateral posterior middle temporal gyrus and angular gyrus, right frontal eye field, and other brain regions. These results may reflect the interaction of attention processes driven by emotional stimuli with conflict resolution processes related to Go/NoGo performance.


Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan.
Our past work indicates that growth-inhibiting chondroitin sulfate proteoglycan (CSPG) is abundant in the peripheral nerve sheaths and interstitium. In this study we tested if degradation of CSPG by chondroitinase enhances axonal regeneration through the site of injury after (a) nerve crush and (b) nerve transection and coaptation. Adult rats received the same injury bilaterally to the sciatic nerves and then chondroitinase ABC was injected near the injury site on one side, and the contralateral nerve was injected with vehicle alone. Nerves were examined 2 days after injury in the nerve crush model and 4 days after injury in the nerve transection model. Chondroitinase-dependent neoepitope immunolabeling showed that CSPG was thoroughly degraded around the injury site in the chondroitinase-treated nerves. Axonal regeneration through the injury site and into the distal nerve was assessed by GAP-43 immunolabeling. Axonal regeneration after crush injury was similar in chondroitinase-treated and control nerves. In contrast, axonal regrowth through the coaptation of transected nerves was markedly accelerated and the ingress of axons into the distal segment was increased severalfold in nerves injected with chondroitinase. On the basis of these results we concluded that growth inhibition by CSPG contributes critically to the poor regenerative growth of axons in nerve transection repair. In addition, degradation of CSPG by injection of chondroitinase ABC at the site of nerve repair increased the ingress of axonal sprouts into basal laminae of the distal nerve segment, presumably by enabling more latitude in growth at the interface of coapted nerve. This suggests that chondroitinase application may be used clinically to improve the outcome of primary peripheral nerve repair.


Oxytocin stimulates cell proliferation in vaginal cell line Vk2E6E7.
Objective During and after menopause, the symptoms of vaginal atrophy cause great discomfort and necessitate effective treatment options. Currently, vaginally applied oxytocin is being investigated as a treatment for the symptoms of vaginal atrophy in postmenopausal women. To clarify the mechanisms behind oxytocins effects on vaginal atrophy, the present study investigated the effects of oxytocin on cell proliferation in the cells of the Vk2E6E7 line, a non-tumour vaginal cell line. The study also compared the effects of oxytocin with those of estradiol (E2). Study design The effects of both oxytocin and E2 on the proliferation of Vk2E6E7 cells were investigated using Cell Proliferation ELISA BrdU Colorimetric Assay. The expression of both oxytocin and oxytocin receptor was studied in Vk2E6E7 cells using quantitative real-time polymerase chain reaction and immunofluorescent staining. Main outcome measures Cell proliferation and gene expression. Results Oxytocin increased cell proliferation both time dependently and dose dependently. This differed from the effect pattern observed in cells treated with E2. In addition, in oxytocin-treated cells, the oxytocin receptor was found to be co-localized with caveolin-1, indicating pro-proliferative signalling within the cell. Conclusions Oxytocin stimulates cell proliferation and the co-localization of oxytocin receptor with caveolin-1 in oxytocin-treated cells, supporting the role of oxytocin signalling in cell proliferation. In addition, these findings suggest that increased cell proliferation is one mechanism by which local vaginal oxytocin treatment increases vaginal thickness and relieves vaginal symptoms in postmenopausal women with vaginal atrophy.


Is Intraoperative Fluoroscopy Necessary for Central Venous Port System Placement in Children?
Central venous port (CVP) placement is traditionally performed under fluoroscopy guidance. However, efforts for radiation dose reduction in children have allowed the introduction of ultrasound guidance (USG) and anatomic landmarks as an alternative technique for CVP placement. The aim of this study is to determine whether intraoperative fluoroscopy (IF) is required to confirm the correct position of the catheter tip in children. A prospective, single-center study was performed between July and December 2017. Standard venous access site was the right internal jugular vein under USG. Estimated catheter length (ECL) was measured using anatomic landmarks. Ideal catheter length (ICL) was measured after placement under fluoroscopy guidance in the same patient. Age, sex, radiation dose, and complications were also analyzed. A t-test for paired samples and intraclass correlation coefficient were performed to analyze results. A total of 30 consecutive patients aged 7 ± 2 years underwent CVP placement. The mean ECL was 17.1 ± 1.8 cm, while the mean ICL was 17.7 ± 1.8 cm. The mean difference between measurements was 0.28 cm (95% confidence interval [CI], -0.29 to 0.86; p = 0.324). Intraclass correlation coefficient analysis showed an agreement of 0.95 (95% CI, 0.91-0.98) between measurements. Mean radiation exposure during the procedure was 1.060.78 mGym2 during 0.34 ± 0.6 minutes. There were no complications registered during CVP placement. The correlation between IF and USG and anatomically guided catheter tip placement is optimal. These results suggest that fluoroscopy and the radiation exposure it entails can be safely avoided in selected children.


Consanguinity and dysmorphology in Arabs.
Incidence rates of congenital disorders among the 350 million inhabitants of Arab countries could be influenced via the people's demographic and cultural characteristics. Arabs usually marry at a young age and have large families. They share certain core cultural values and beliefs, with the family accepted as the central structure of society. Consanguineous marriage is favored and respected in most if not all Arab communities, and intrafamilial unions currently account for 20-50% of all marriages. First-cousin unions are especially popular and constitute almost one quarter of all marriages in many Arab countries. Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a considerable proportion of all birth defects among Arabs. Arab geneticists, with their persistent commitment to advancing research, have contributed to the description of a number of rare and new AR syndromes with the identification of novel genes. The collaboration with research teams in high-income countries resulted in a plethora of data on pathogenic variants and their function in causing dysmorphic syndromes. There could still be a considerable number of rare dysmorphic syndromes that prevail among Arabs which are not hitherto described and whose underlying molecular pathologies are not yet defined. Arab countries should thus strive to deploy DNA diagnostics and to build research capability around local priorities. Furthermore, a characterization of the prevailing genetic disorders in each geographic location, together with their mutations, is needed to plan for appropriate screening and testing protocols. An overview of consanguinity in Arab countries and examples of dysmorphology syndromes associated with consanguinity with their available molecular bases will be discussed.


Adrenocorticotropin stimulates natural killer cell activity.
Central release of CRH has recently been implicated in modulating natural killer cell (NK) activity independent of its role in activation of the hypothalamic-pituitary-adrenal axis. In the present study, NK- and interleukin-2 (IL-2)-activated NK cytotoxicity against K-562 target cells was examined in porcine lymphocytes cultured in vitro with ACTH or pig lymphocytes after iv or im ACTH administration. Physiological concentrations of porcine ACTH (10(-8)-10(-11) M) added to the culture medium had no direct influence on NK- or IL-2-stimulated NK cytotoxicity. In a second experiment four unrestrained pigs with indwelling catheters given an iv bolus of vehicle or ACTH (1 IU/kg BW) at 0800 h showed significantly elevated cortisol levels for 3 h after ACTH. Although serum cortisol had returned to baseline by 4 h after ACTH treatment, NK- and IL-2-stimulated NK cytotoxicity was dramatically elevated (P less than 0.01) compared to that in saline-injected controls. NK cytotoxicity in control pigs followed a diurnal pattern, with low morning and high evening cytotoxicity. Exogenous ACTH, given by bolus in the morning, prevented the normal morning decline in NK cytotoxicity. Because of this unexpected dramatic increase in NK- and IL-2-stimulated NK cytotoxicity in animals given ACTH, the experiment was replicated in two subsequent studies using 16 pigs (8 controls and 8 experimental) in each. Pigs were injected im with either ACTH (1 IU/kg BW) or an equivalent volume of saline at 0600 h. Two hours later, blood was collected by venipuncture to determine NK cytotoxicity and measure the cortisol response. As was observed in the previous study, NK- and IL-2-stimulated NK cytotoxicity was significantly greater (P less than 0.01) than that in saline-injected controls. In the final experiment pigs were given either ACTH (1 IU/kg BW) or an equivalent volume of saline at 1800 h. Two hours later, blood was collected by venipuncture to determine NK cytotoxicity and cortisol response. ACTH administered in the evening increased NK cytotoxicity, but the effect was only marginally significant and far less dramatic than in previous studies. Because ACTH had little effect on NK- and IL-2-stimulated NK activity in vitro, we hypothesize that the stimulatory effect of exogenous ACTH is mediated through an indirect mechanism, possibly through the suppression of central CRH as a result of elevated cortisol. This effect is more pronounced when the stimulatory dose of ACTH is given at a time in the circadian cycle when NK cytotoxicity is normally low.


Report from the European Society of Thoracic Surgeons prospective thymic database 2017: a powerful resource for a collaborative global effort to manage thymic tumours.
We queried the European Society of Thoracic Surgeons (ESTS) prospective thymic database for descriptive analysis and for comparison with the ESTS retrospective thymic database (1990-2010). Data were retrieved (January 2007-November 2017) for 1122 patients from 75 ESTS institutions. There were 484 (65%) thymomas, 207 (28%) thymic carcinomas and 49 (7%) neuroendocrine thymic tumours. Staging (Masaoka) included 483 (67%) stage I and II, 100 (14%) stage III and 70 (10%) stage IV tumours. The new International Association for the Study of Lung Cancer/International Thymic Malignancies Interest Group tumour, node and metastasis (TNM) classification was available for 224 patients and including 177 (85%) stage I-II, 37 (16%) stage IIIA and 10 (4%) stage IIIB tumours. Chemotherapy as induction and adjuvant treatment was used in 14% and 15% of the patients. Radiotherapy was almost exclusively used postoperatively (24%). A minimally invasive surgical approach (video-assisted thoracic surgery/robotic-assisted thoracic surgery) was used in 276 (33%) patients. The overall recurrence rate was 10.8% (N = 38). Compared to the ESTS retrospective database, the increased prevalence of thymic carcinomas (from 9% to 28%) and neuroendocrine thymic tumours (from 2% to 7%), an increase in the use of minimally invasive techniques (from 6% to 34%) and a wider use of chemotherapy as induction (from 9% to 15%) and adjuvant (from 2% to 16%) treatment were observed in the prospective database. The introduction of a set of variables considered essential for the data use ('minimum dataset') resulted in an increased average completeness rate. The reported data from the ESTS prospective thymic database confirm the recent trends in the management of thymic tumours. The ESTS prospective thymic database represents a powerful resource open to all ESTS members for the global effort to manage these rare tumours.


Genistein abrogates G2 arrest induced by curcumin in p53 deficient T47D cells.
The high cost and low level of cancer survival urge the finding of new drugs having better mechanisms. There is a high trend of patients to be "back to nature" and use natural products as an alternative way to cure cancer. The fact is that some of available anticancer drugs are originated from plants, such as taxane, vincristine, vinblastine, pacitaxel. Curcumin (diferuloylmethane), a dietary pigment present in Curcuma longa rizhome is reported to induce cell cycle arrest in some cell lines. Other study reported that genistein isolated from Glycine max seed inhibited phosphorylation of cdk1, gene involved during G2/M transition and thus could function as G2 checkpoint abrogator. The inhibition of cdk1 phosphorylation is one of alternative strategy which could selectively kill cancer cells and potentially be combined with DNA damaging agent such as curcumin. T47D cell line was treated with different concentrations of curcumin and genistein, alone or in combination; added together or with interval time. Flow Cytometry and MTT assay were used to evaluate cell cycle distribution and viability, respectively. The presence of apoptotic cells was determined using acridine orange-ethidium bromide staining. In this study curcumin induced G2 arrest on p53 deficient T47D cells at the concentration of 10 μM. Increasing concentration up to 30 μM increased the number of cell death. Whilst genistein alone at low concentration (≤10 μM) induced cell proliferation, addition of genistein (20 μM) 16 h after curcumin resulted in more cell death (89%), 34% higher than that administered at the same time (56%). The combination treatment resulted in apoptotic cell death. Combining curcumin with high dose of genistein (50 μM) induced necrotic cells. Genistein increased the death of curcumin treated T47D cells. Appropriate timing of administration and concentration of genistein determine the outcome of treatment and this method could potentially be developed as an alternative strategy for treatment of p53 defective cancer cells.


Scanning laser ophthalmoscopy and angiography with a wide-field contact lens system.
To perform fluorescein and indocyanine green angiography for large or peripheral chorioretinal structures using a contact lens system that provides a 5-fold increase in the field of view of a confocal scanning laser ophthalmoscope (SLO). Separate handheld contact and noncontact ophthalmoscopic lenses were manually aligned with the optical axis of a confocal SLO to demonstrate the feasibility of wide-field SLO angiography. An integrated, wide-field contact lens system was then designed and constructed to increase the SLO's 10 degrees , 20 degrees , and 30 degrees imaging fields to 50 degrees , 100 degrees , and 150 degrees , respectively. Simultaneous fluorescein and indocyanine green angiography was performed with the integrated, wide-field contact lens system for more than 50 patients with disorders that affect their peripheral retina and choroid. Retinal and choroidal abnormalities, including neovascularization and capillary nonperfusion, are easily detected and documented well beyond the range of conventional fundus cameras and SLOs. Peripheral retinal and choroidal hemodynamics can be readily observed and recorded. A confocal SLO has adequate resolution for clinically useful reflectance and angiographic imaging even when its field size is increased 5-fold by a wide-field contact lens system. Dynamic and static wide-field angiography can be performed without the limitations of manual or computer-automated photomontages. Peripheral retinal conditions can be studied and recorded to confirm observations from indirect ophthalmoscopy and to facilitate retinal photocoagulation and vitreoretinal surgery.


Genetic unmasking of an epigenetically silenced microRNA in human cancer cells.
The mechanisms underlying microRNA (miRNA) disruption in human disease are poorly understood. In cancer cells, the transcriptional silencing of tumor suppressor genes by CpG island promoter hypermethylation has emerged as a common hallmark. We wondered if the same epigenetic disruption can "hit" miRNAs in transformed cells. To address this issue, we have used cancer cells genetically deficient for the DNA methyltransferase enzymes in combination with a miRNA expression profiling. We have observed that DNA hypomethylation induces a release of miRNA silencing in cancer cells. One of the main targets is miRNA-124a, which undergoes transcriptional inactivation by CpG island hypermethylation in human tumors from different cell types. Interestingly, we functionally link the epigenetic loss of miRNA-124a with the activation of cyclin D kinase 6, a bona fide oncogenic factor, and the phosphorylation of the retinoblastoma, a tumor suppressor gene.


Rapid growth of metastatic brain tumor from gastric undifferentiated pleomorphic sarcoma: A case report.
Brain metastasis from undifferentiated pleomorphic sarcoma (UPS) is a rare occurrence, and its clinical course is little known. In this report, we investigate a case of a rapidly growing brain metastasis from gastric UPS. An 82-year-old man with a known gastric tumor, pathologically compatible with UPS, underwent partial gastrectomy at an outside facility. 3 months later, a 4-cm brain tumor was detected, which was completely resected. The patient was diagnosed with metastatic tumor from previously treated gastric UPS. Within 2 months of the initial resection, a large recurrent mass was detected in the same location, which was again removed. Although the patient underwent radiotherapy and chemotherapy for other metastatic tumors, he died 5 months after the second craniotomy. Brain metastasis from gastric UPS is rare and difficult to treat. Although aggressive treatment, such as surgical intervention, may improve patient survival in some cases, the timing of treatment is challenging because cerebral metastasis rapidly grows and and patients frequently suffer from synchronous systematic metastasis. Therefore, early detection and close follow-up of rapidly progressing brain metastasis are important to improve treatment outcomes.


Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation.
Mutations frequently have outcomes that differ across individuals, even when these individuals are genetically identical and share a common environment. Moreover, individual microbial and mammalian cells can vary substantially in their proliferation rates, stress tolerance, and drug resistance, with important implications for the treatment of infections and cancer. To investigate the causes of cell-to-cell variation in proliferation, we used a high-throughput automated microscopy assay to quantify the impact of deleting >1500 genes in yeast. Mutations affecting mitochondria were particularly variable in their outcome. In both mutant and wild-type cells mitochondrial membrane potential - but not amount - varied substantially across individual cells and predicted cell-to-cell variation in proliferation, mutation outcome, stress tolerance, and resistance to a clinically used anti-fungal drug. These results suggest an important role for cell-to-cell variation in the state of an organelle in single cell phenotypic variation.


Trophic resources and mercury exposure of two silvertip shark populations in the Northeast Pacific Ocean.
Worldwide shark populations have experienced rapid declines over the last decades, mainly due to overfishing. Marine protected areas (MPAs) have thus become an indispensable tool for the protection of these marine predators. Two recently-created MPAs in the Northeast Pacific Ocean, the Revillagigedo National Park and Clipperton Atoll, are characterized by different trophic structures potentially influencing the trophic niche and contaminant exposure of resident sharks in these two sites. In this context, we used carbon (δ13C) and nitrogen (δ15N) stable isotope analyzes as well as total mercury concentrations ([THg]) to assess the effect of foraging site on the trophic niche and Hg levels of juvenile silvertip (ST) sharks Carcharhinus albimarginatus. Analyzing fin clip samples from Revillagigedo and Clipperton, we found that shark δ15N varied spatially in relation to δ15N baselines, suggesting similar trophic position in both MPAs. Moreover, δ13C values indicated that ST sharks from Revillagigedo would feed on different food webs (i.e. both benthic and pelagic) while individuals from Clipperton would only rely on benthic food webs. These differences between MPAs led to a weak overlap of isotopic niches between the two populations, highlighting the site residency of juvenile ST sharks. Within each population, [THg] was not correlated with trophic tracers (δ15N and δ13C) and was also similar between populations. This study revealed no influence of site or food web in [THg] and raises the question of the origin of Hg exposure for reef shark populations in the Northeast Pacific Ocean.


Correlates of smoking among adolescents with asthma.
This study examined the correlates of smoking among asthmatic adolescents to gain a better understanding of who is at particular risk. Smoking is especially harmful to individuals with asthma. However, smoking is surprisingly prevalent among asthmatic individuals, with prevalence rates similar to or higher than those of the general adult or adolescent populations. Despite this notable finding, there has been little research about factors (i.e. biophysical, psychosocial and behavioural) influencing asthmatic adolescents' tobacco use patterns. A Canadian provincial cross-sectional survey. The study about adolescents' tobacco use and health status was conducted in secondary schools in 2004, 608 asthmatic adolescents participated. Demographic factors, biophysical (body mass index and physical health), psychosocial factors (parents' and peers' smoking, environmental tobacco smoke exposure and depression) and behavioural factors (marijuana use, alcohol use and exercise frequency) were explored. Multinomial logistic regression analyses were conducted to identify risk factors associated with tobacco use. Of the 608 asthmatic adolescents, 17.4% currently smoked and 12.0% formerly smoked. Girls, compared with boys, were more likely to smoke (OR: 3.34, 95% CI: 1.62-6.96) after adjusting for differences in the other demographic, biophysical, psychosocial and behavioural factors. Asthmatic girls who had relatively higher body mass index, were in the higher school grades, used marijuana or alcohol, had minor to severe depressive symptoms, had environmental tobacco smoke exposure in their homes and had friends who smoked or were currently more likely to smoke. The former smokers had similar risk factors including higher body mass index, environmental tobacco smoke exposure at home, friends who smoked and marijuana use. Despite their health condition, asthmatic adolescents continue currently or formerly to smoke. Gender appropriate prevention and cessation interventions for asthmatic adolescents may need to address important psychosocial and environmental factors that increase the risk of these adolescents initiating and maintaining tobacco use.


[Action mechanisms of plant growth-promoting rhizobacteria (PGPR): a review].
Plants during their growth may suffer from many biotic and abiotic stresses, resulting in a decrease of biological production. They may also establish some mechanisms to resist or tolerate the stresses under the stimulation or induction by a variety of factors, among which, plant growth-promoting rhizobacteria (PGPR) is an important one. In this paper, the recently published papers related to this subject were reviewed, and two categories of the action mechanisms of PGPR, namely, induced systemic resistance (ISR) and induced systemic tolerance (IST), were elaborated. The diversity of the action mechanisms of PGPR implied that PGPR could be applied in more agro-ecosystems.


Impairment of lymphocyte-suppressive system in recent-onset insulin-dependent diabetes mellitus. Correlation with metabolic control.
Impairment of suppressor-cell activity may be important in the pathogenesis and maintenance of insulin-dependent diabetes mellitus (IDDM). In 23 recent-onset IDDM patients, lymphocyte sensitivity in vitro to theophylline was tested both in basal conditions and after improvement of metabolic control. This pharmacologic agent is mainly effective on a lymphocytic subpopulation with phenotypic and functional suppressive features. Peripheral blood lymphocytes from IDDM patients showed a loss of theophylline sensitivity, identified as inhibition of both E-rosette formation and blastogenic response to polyclonal mitogens concanavalin A (ConA) and phytohemagglutinin (PHA). An inverse relationship was demonstrated between the theophylline-induced suppression of ConA blastogenic response and blood glucose and glycosylated hemoglobin levels (P less than .01). Metabolic control seemed to be important even in relation to lymphocyte subpopulation distribution. In IDDM patients we found a significant (P less than .05) reduction of OKT4+ lymphocytes that is correlated with blood glucose and glycosylated hemoglobin levels (P less than .01). The improvement of metabolic control led to recovery of theophylline sensitivity. We suggest a deficiency in a suppressive system that could be involved in IDDM onset and the possible role of metabolic control in the impairment of some immunologic functions reported with this pathologic condition.


Pea Ferritin Stability under Gastric pH Conditions Determines the Mechanism of Iron Uptake in Caco-2 Cells.
Iron deficiency is an enduring global health problem that requires new remedial approaches. Iron absorption from soybean-derived ferritin, an ∼550-kDa iron storage protein, is comparable to bioavailable ferrous sulfate (FeSO4). However, the absorption of ferritin is reported to involve an endocytic mechanism, independent of divalent metal ion transporter 1 (DMT-1), the transporter for nonheme iron. Our overall aim was to examine the potential of purified ferritin from peas (Pisum sativum) as a food supplement by measuring its stability under gastric pH treatment and the mechanisms of iron uptake into Caco-2 cells. Caco-2 cells were treated with native or gastric pH-treated pea ferritin in combination with dietary modulators of nonheme iron uptake, small interfering RNA targeting DMT-1, or chemical inhibitors of endocytosis. Cellular ferritin formation, a surrogate measure of iron uptake, and internalization of pea ferritin with the use of specific antibodies were measured. The production of reactive oxygen species (ROS) in response to equimolar concentrations of native pea ferritin and FeSO4 was also compared. Pea ferritin exposed to gastric pH treatment was degraded, and the released iron was transported into Caco-2 cells by DMT-1. Inhibitors of DMT-1 and nonheme iron absorption reduced iron uptake by 26-40%. Conversely, in the absence of gastric pH treatment, the iron uptake of native pea ferritin was unaffected by inhibitors of nonheme iron absorption, and the protein was observed to be internalized in Caco-2 cells. Chlorpromazine (clathrin-mediated endocytosis inhibitor) reduced the native pea ferritin content within cells by ∼30%, which confirmed that the native pea ferritin was transported into cells via a clathrin-mediated endocytic pathway. In addition, 60% less ROS production resulted from native pea ferritin in comparison to FeSO4. With consideration that nonheme dietary inhibitors display no effect on iron uptake and the low oxidative potential relative to FeSO4, intact pea ferritin appears to be a promising iron supplement.


Calcium . calmodulin-dependent protein kinase II and calcium . phospholipid-dependent protein kinase activities in rat tissues assayed with a synthetic peptide.
Rat tissue levels of Ca2+ . calmodulin-dependent protein kinase II (protein kinase II) and Ca2+ . phospholipid-dependent protein kinase (protein kinase C) were selectively assayed using the synthetic peptide syntide-2 as substrate. The sequence of syntide-2 (pro-leu-ala-arg-thr-leu-ser-val-ala-gly-leu-pro-gly-lys-lys) is homologous to phosphorylation site 2 in glycogen synthase. The relative Vmax/Km ratios of the known Ca2+-dependent protein kinases for syntide-2 were determined to be as follows: protein kinase II, 100; protein kinase C, 22; phosphorylase kinase, 2; myosin light chain kinase, 0.005. Levels of protein kinase II were highest in cerebrum (3.36 units/g tissue) and spleen (0.85 units/g) and lowest in testis (0.05 units/g) and kidney (0.04 units/g). Protein kinase II activity was localized predominantly in the 100,000g particulate fraction of cerebrum and testis, in the supernatant fraction of heart, liver, adrenal, and kidney, and about equally distributed between particulate and supernatant in spleen and lung. Likewise, protein kinase C activity was highest in cerebrum (0.56 units/g) and spleen (0.47 units/g), and the majority of activity was present in the cytosolic fraction for all tissues measured except for cerebrum and testis in which the kinase activity was equal in both fractions. Finally, the ratios of protein kinase II to protein kinase C were different in various rat tissues and between particulate and supernatant fractions. These results suggest somewhat different functions for these two Ca2+-regulated, multifunctional protein kinases.


Barriers to HIV testing in Europe: a systematic review.
In the European Union (EU) and neighbouring countries, HIV/AIDS, of all infectious diseases, has one of the highest morbidity and mortality rates. An estimated 30% of people living with HIV are unaware of their infection, and may therefore not benefit from timely treatment or may transmit HIV to others, unknowingly. Evidence shows that opportunities are being missed to diagnose HIV infections in EU Member States, particularly in regular health care settings. There is a need to better understand the barriers to HIV testing and counselling with the aim to contribute to the decrease of the number of undiagnosed people. A systematic review of literature on HIV testing barriers in Europe was conducted, applying a free text strategy with a set of search terms. A total of 24 studies published in international peer-reviewed journals and meeting the review's eligibility criteria were identified. Fourteen studies report on barriers at the level of the patient; six on barriers at health care provider level and seven on institutional barriers referring to the policy level. The barriers described are centralized around low-risk perception; fear and worries; accessibility of health services, reluctance to address HIV and to offer the test; and scarcity of financial and well trained human resources. Some barriers to HIV testing and counselling have been illustrated in the literature. Nevertheless, there is lack of structured information on barriers considering (i) legal, administrative and financial factors, (ii) attitudes and practices of health care providers and (iii) perception of patients. Such data is critical to improve effectiveness of HIV testing and counselling.


Cretaceous gnetalean yields first preserved plant gum.
Some liquid plant exudates (e.g. resin) can be found preserved in the fossil record. However, due to their high solubility, gums have been assumed to dissolve before fossilisation. The visual appearance of gums (water-soluble polysaccharides) is so similar to other plant exudates, particularly resin, that chemical testing is essential to differentiate them. Remarkably, Welwitschiophyllum leaves from Early Cretaceous, Brazil provide the first chemical confirmation of a preserved gum. This is despite the leaves being exposed to water twice during formation and subsequent weathering of the Crato Formation. The Welwitschiophyllum plant shares the presence of gum ducts inside leaves with its presumed extant relative the gnetalean Welwitschia. This fossil gum presents a chemical signature remarkably similar to the gum in extant Welwitschia and is distinct from those of fossil resins. We show for the first time that a water-soluble plant exudate has been preserved in the fossil record, potentially allowing us to recognise further biomolecules thought to be lost during the fossilisation process.


The effect of MgO/TiO2 on structural and crystallization behavior of near invert phosphate-based glasses.
Varying formulations in the glass system of 40P2 O5 ─(24 - x)MgO─(16 + x)CaO─(20 - y)Na2 O─yTiO2 (where 0 ≤ x ≤ 22 and y = 0 or 1) were prepared via melt-quenching. The structure of the glasses was confirmed by X-ray diffraction (XRD), Fourier transform infrared (FTIR), micro Raman and solid-state nuclear magnetic resonance (NMR) spectroscopies. The thermal properties and the activation energy of crystallization (Ec ) were measured using thermal analysis and the Kissinger equation, respectively. The glass forming ability of the formulations investigated was seen to decrease with reducing MgO content down to 8 mol% and the glass stability region also decreased from 106 to 90°C with decreasing MgO content. The activation energy of crystallization (Ec ) values also decreased from 248 (for 24 mol% MgO glass) to 229 kJ/mol (for the 8 mol% MgO content) with the replacement of MgO by CaO for glasses with no TiO2 . The formulations containing less than 8 mol% MgO without TiO2 showed a strong tendency toward crystallization. However, the addition of 1 mol% TiO2 in place of Na2 O for these glasses with less than 8 mol% MgO content, inhibited their crystallization tendency. Glasses containing 8 mol% MgO with 1 mol% TiO2 revealed a 12°C higher glass transition temperature, a 14°C increase in glass stability against crystallization and a 38 kJ/mol increase in Ec in comparison to their non TiO2 containing counterpart. NMR spectroscopy revealed that all of the formulations contained almost equal percentages of Q1 and Q2 species. However, FTIR and Raman spectroscopies showed that the local structure of the glasses had been altered with addition of 1 mol% TiO2 , which acted as a network modifier, impeding crystallization by increasing the cross-linking between phosphate chains and consequently leading to increased Ec as well as their glass forming ability.


Simulation Study and Analysis of Diffusive Molecular Communications With an Apertured Plane.
Molecular communication via diffusion (MCvD) is a method of achieving nano- and micro-scale connectivity by utilizing the free diffusion mechanism of information molecules. The randomness in diffusive propagation is the main cause of inter-symbol interfe-rence (ISI) and the limiting factor of high data rate MCvD applications. In this paper, an apertured plane is considered between the transmitter and the receiver of an MCvD link. Either after being artificially placed or occurring naturally, surfaces or volumes that resemble an apertured plane only allow a fraction of the molecules to pass. Contrary to intuition, it is observed that such topology may improve communication performance, given the molecules that can pass through the aperture are the ones that take more directed paths towards the receiver. Furthermore, through both computer simulations and a theoretical signal evaluation metric named signal-to-interference and noise amplitude ratio (SINAR), it is found that the size of the aperture imposes a trade-off between the received signal power and the ISI combating capability of an MCvD system, hinting to an optimal aperture size that minimizes the bit error rate (BER). It is observed that the trend of BER is accurately mirrored by SINAR, suggesting the proposed metric's applicability to optimization tasks in MCvD systems, including finding the optimal aperture size of an apertured plane. In addition, computer simulations and SINAR show that said optimal aperture size is affected by the location of the aperture and the bit rate. Lastly, the paper analyzes the effects of radial and angular offsets in the placement of the apertured plane, and finds that a reduction in BER is still in effect up to certain offset values. Overall, our results imply that apertured plane-like surfaces may actually help communication efficiency, even though they reduce the received signal power.


Prevalence, correlates, and mortality impacts of ventricular arrhythmia among older men and women: a population-based cohort study in Moscow.
In Russia, cardiovascular disease (CVD) mortality is high and the mortality gap between men and women is large. Conventional risk factors cannot explain these phenomena. Ventricular arrhythmia (VA) is an important contributor to the death toll in community-based populations. The study examines the prevalence and the mortality impacts of VA in men and women and the role of VA in the male mortality excess at older ages. This is a secondary analysis of data from the Stress, Aging, and Health in Russia (SAHR) study that was fielded in 2007-9 in Moscow (1800 individuals, mean age 68.8 years), with mean mortality follow-up of 7.4 years (416 deaths, 248 CVD deaths). Indicators reflecting the frequency and the complexity of VA were derived from 24-h ambulatory ECG recordings. Other covariates were: socio-demographic characteristics, conventional risk factors, markers of inflammation, reported myocardial infarction, and stroke. The impacts of VA and other variables on CVD and all-cause mortality among men and women were estimated with the proportional hazard models. We assessed the contributions of VAs to the male-female mortality gap using hazard models that do and do not include groups of the predictors. Logistic models were used to assess the associations between VA and other biomarkers. VAs were about twice as prevalent among men as among women. In both sexes, they were significantly associated with CVD and all-cause mortality independently of conventional risk factors. The highest hazard ratios (HRs) for CVD death were found for the runs of ventricular premature complexes (VPCs) HR = 2.45, 95% CI 1.63-3.68 for men and 2.75, 95% CI 1.18-6.40 for women. The mortality impacts of the polymorphic VPCs were significant among men only (HR = 1.50, 95% CI 1.08-2.07). VA indicators can potentially explain 12.3% and 9.1% of the male-female gaps in mortality from CVD and all causes, respectively. VAs were associated with ECG-registered ischemic problems and reported MI, particularly among men. VA indicators predicted mortality in older Muscovites independently of other risk factors, and have the potential to explain a non-trivial share of the excess male mortality. The latter may be related to more severe coronary problems in men compared to women.