Human coronaviruses and therapeutic drug discovery.
Coronaviruses (CoVs) are distributed worldwide and have various susceptible hosts; CoVs infecting humans are called human coronaviruses (HCoVs). Although HCoV-specific drugs are still lacking, many potent targets for drug discovery are being explored, and many vigorously designed clinical trials are being carried out in an orderly manner. The aim of this review was to gain a comprehensive understanding of the current status of drug development against HCoVs, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A scoping review was conducted by electronically searching research studies, reviews, and clinical trials in PubMed and the CNKI. Studies on HCoVs and therapeutic drug discovery published between January 2000 and October 2020 and in English or Chinese were included, and the information was summarized. Of the 3248 studies identified, 159 publication were finally included. Advances in drug development against HCoV, especially SARS-CoV-2, are summarized under three categories: antiviral drugs aimed at inhibiting the HCoV proliferation process, drugs acting on the host's immune system, and drugs derived from plants with potent activity. Furthermore, clinical trials of drugs targeting SARS-CoV-2 are summarized. During the spread of COVID-19 outbreak, great efforts have been made in therapeutic drug discovery against the virus, although the pharmacological effects and adverse reactions of some drugs under study are still unclear. However, well-designed high-quality studies are needed to further study the effectiveness and safety of these potential drugs so as to provide valid recommendations for better control of the COVID-19 pandemic.


Insulin-Like Growth Factor Binding Protein 6 in Rheumatoid Arthritis: A Possible Novel Chemotactic Factor?
Immune cell migration from the bloodstream to target tissues is a hallmark of rheumatoid arthritis (RA) pathogenesis. The role of chemoattractants, mainly chemokines, and their possible targeting for therapeutic purposes have been under intense investigation over the last few years but the results were not as satisfactory as expected. The insulin-like growth factor binding protein 6 (IGFBP6), a direct inhibitor of insulin-like growth factor (IGF)-II, also exerts IGF-independent effects including tumor cell migration in vitro. We aimed to assess the expression of this protein in serum, synovial fluid, and synovial tissue (ST) of RA patients and to identify its possible chemotactic role in this disorder. IGFBP6 was measured in RA patients and healthy donors (HD) sera by Luminex xMAP® technology and in ST of RA patients and osteoarthritis (OA) controls by immunofluorescence. The identification of circulating IGFBP6+ cells was evaluated by flow cytometry and an in vitro migration assay was arranged. We demonstrated that IGFBP6 is able to induce greater in vitro migration of RA as compared to HD and OA T lymphocytes and is overexpressed in serum and ST of RA patients. This in vitro chemotactic activity can be partially inhibited by dexamethasone. Our findings suggest a pathogenic role of IGFBP6 in RA and support its possible targeting for therapeutic purposes.


Unsuspected esophageal perforation in association with chronic peptic stricture.
A case of vomiting-induced perforation of the lower esophagus proximal to a chronic peptic stricture is described. The patient had a remarkably benign course and conservative management resulted in complete cure. Criteria for nonoperative management of esophageal perforation are outlined. Esophageal injury due to retained pills, we believe, contributed to occurrence of this syndrome.


The identification of patients at risk from acute retention.
Clinical and urodynamic features of patients at risk from acute retention were investigated in 2 retrospective studies. It is suggested that detrusor decompensation may be a cause of acute retention in some individuals. This factor was investigated in a series of patients with outflow obstruction by a method of repeat cystometry.


A SEARCH FOR QUANTITATIVE TRAIT LOCI AFFECTING ASYMMETRY OF MANDIBULAR CHARACTERS IN MICE.
An interval mapping procedure was used to search for and describe the effects of any quantitative trait loci (QTLs) for directional asymmetry (DA) and fluctuating asymmetry (FA) of 10 bilateral mandible characters in house mice. It was hypothesized that more QTLs would be found for DA than for FA, but that any discovered for FA should tend to exhibit dominance. All mandible characters were triply measured and 76 microsatellite markers were scored in an average of 471 mice from the F2 intercross of the Large (LG/J) and Small (SM/J) inbred strains. A total of 16 QTLs significantly affected DA in nine of the 10 mandible characters, and this was more than the 9.5 expected by chance alone. These QTLs were found on seven of the 19 chromosomes, often at or near locations of QTLs affecting the mean of the two sides for various dimensions on the mandible. It was concluded that there is genetical variability for DA in these characters, although its level was low (4.4% of the total variation in this particular F2 population). Eleven QTLs were detected for FA, suggesting that there is very little genetic variability for FA, at least as seen in the mandible characters in this particular F2 population. As hypothesized, however, these QTLs did tend to exhibit dominance.


Bulk and compound-specific isotopic characterisation of illicit heroin and cling film.
Comparative analysis involves various but complementary methods and can be used for forensic intelligence purposes to group seizures of heroin into batches. Much forensic analysis now combines expertise in the traditional area of drugs investigation with a detailed understanding of supply, packaging, distribution, and drugs intelligence. It was the intention of this research to determine whether illicit heroin seizures and packaging material can be grouped according to isotopic compositions, and to explore factors that affect the isotopic compositions. In order to achieve these aims, 14 samples of seized heroin, thirteen provided by Avon and Somerset Constabulary (UK), were analysed by elemental analysis/isotope ratio mass spectrometry (EA/IRMS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) for carbon and hydrogen isotopes. These tests elucidated that a combination of the delta13C, delta15N, delta18O and delta2H results from EA/IRMS is able to distinguish between most samples of bulk heroin. We speculate that the delta13C values of the alkaloids, obtained by GC/C/IRMS, give indications of different geographical or temporal origins of some of the heroin samples. GC/C/IRMS of the cutting agent, caffeine, provides a means to link dilution events. Fifteen retail cling film samples and seven cling film samples from heroin seizures were analysed by EA/IRMS. A multivariate comparison of the carbon, hydrogen and oxygen isotope ratios was able to distinguish between most of the samples. This technique enabled the cling films from the heroin to be grouped according to seizure. Three solvents were tested on two samples of cling film of known composition. Methanol and chloroform were both found to extract material from PVC and from non-PVC cling films. Water-treated PVC was indistinguishable from the untreated PVC and thus water was found to be the most suitable solvent when washing cling film prior to IRMS analysis.


Human alternative complement pathway-mediated lysis of rabbit erythrocytes is enhanced by natural anti-Galalpha1-3Gal antibodies.
Human serum is effective at lysing unsensitized rabbit erythrocytes due to activation of the alternative complement pathway. Hemolysis is known to be enhanced by the addition of human IgG. We demonstrate that the enhancement of alternative pathway-mediated rabbit E lysis by human Ig is due to natural Abs specific for galactosyl (Gal)alpha1-3Gal. Depletion of normal human serum (NHS) of anti-Galalpha1-3Gal Abs removes almost all hemolytic activity from NHS, and activity can be restored by repletion with anti-Galalpha1-3Gal affinity-purified Abs. Factor B-depleted serum (inactive alternative pathway) did not lyse rabbit erythrocytes. Although C2-depleted serum was fully hemolytic, activity was removed by depletion of anti-Galalpha1-3Gal Abs. Of the total anti-Galalpha1-3Gal Abs affinity isolated from NHS, about one-third were IgM and two-thirds were IgG. Both anti-Galalpha1-3Gal IgG and IgM enhanced alternative pathway-mediated erythrocyte lysis.


Hyaluronidase in ophthalmic evisceration surgery.
To research the effectiveness of hyaluronidase in evisceration surgery. A total of 34 patients were studied as three groups: conventional surgery group (n = 13); isotonic fluid group (n = 8); and hyaluronidase group (n = 13). Hyaluronidase and isotonic fluid were introduced into the uveo-scleral space. Intraocular content was removed, if possible by a one-scoop method, with the aid of a spoon. Removing all the intraocular content as a one-scoop method was achieved in 10 of 13 (77%) in the hyaluronidase group and four of eight (50%) in the isotonic fluid group. The one-scoop method was not possible in any case without the introduction of fluid. The mean durations for the evisceration procedure were 32, 36.6 and 40.5 min in the three groups, respectively (P < 0.05). Using hyaluronidase in evisceration surgery greatly facilitates and speeds up the removal of all the intraocular content in ophthalmic evisceration surgery.


Emergence of Wrinkles during the Curing of Coatings.
Wrinkles often emerge on a paint layer when a second coat of paint is applied on an already-coated substrate. Wrinkle formation occurs when the first layer absorbs organic solvent from the second layer. We set up experiments to mimic the double-coating process, focusing on the interaction between a paint layer and an organic solvent. In the experiments, we investigated the characteristic wavelengths of the wrinkles and the time of wrinkle emergence. We employed a simple model to explain the wrinkle emergence and performed numerical simulations. The linear stability analysis of the model provides a relation between the wavelengths and the characteristic timescale that agrees reasonably well with our experimental data as well as numerical results. Our results indicate that compression of the layer due to swelling and delamination are both important factors in the formation of wrinkles.


Membrane recruitment of scaffold proteins drives specific signaling.
Cells must give the right response to each stimulus they receive. Scaffolding, a signaling process mediated by scaffold proteins, participates in the decoding of the cues by specifically directing signal transduction. The aim of this paper is to describe the molecular mechanisms of scaffolding, i.e. the principles by which scaffold proteins drive a specific response of the cell. Since similar scaffold proteins are found in many species, they evolved according to the purpose of each organism. This means they require adaptability. In the usual description of the mechanisms of scaffolding, scaffold proteins are considered as reactors where molecules involved in a cascade of reactions are simultaneously bound with the right orientation to meet and interact. This description is not realistic: (i) it is not verified by experiments and (ii) timing and orientation constraints make it complex which seems to contradict the required adaptability. A scaffold protein, Ste5, is used in the MAPK pathway of Saccharomyces cerevisiae for the cell to provide a specific response to stimuli. The massive amount of data available for this pathway makes it ideal to investigate the actual mechanisms of scaffolding. Here, a complete treatment of the chemical reactions allows the computation of the distributions of all the proteins involved in the MAPK pathway when the cell receives various cues. These distributions are compared to several experimental results. It turns out that the molecular mechanisms of scaffolding are much simpler and more adaptable than previously thought in the reactor model. Scaffold proteins bind only one molecule at a time. Then, their membrane recruitment automatically drives specific, amplified and localized signal transductions. The mechanisms presented here, which explain how the membrane recruitment of a protein can produce a drastic change in the activity of cells, are generic and may be commonly used in many biological processes.


Protective role of autophagy in triptolide-induced apoptosis of TM3 Leydig cells.
Triptolide (TP) is known to impair testicular development and spermatogenesis in mammals, but the mechanism of the side effects still needs to be investigated. The aim of the research is to confirm whether TP can cause autophagy in TM3 Leydig cells and the potential molecular pathway in vitro. TM3 Leydig cells are used to investigate the molecular pathway through Western blot, detection of apoptosis, transmission electron microscopy for autophagosomes and so on. The data show that TP treatment resulted in the decreasing of the viability of TM3 cells due to the increased apoptosis. Treated with TP, the formation of autophagosomes, the decrease in P62, and the increase in the conversion of LC3-I to LC3-II suggested the induction of autophagy. The induction of autophagy has accompanied the activation of the mTOR/P70S6K signal pathway. The viability of the TM3 cells was further inhibited when they were co-treated with autophagy inhibitor, chloroquine (CQ). All these data suggest that autophagy plays a very important role in antagonizing TM3 cell apoptosis during the TP exposure.


Impact of state of emergency for coronavirus disease 2019 on hospital visits and disease exacerbation: the Japan COVID-19 and Society Internet Survey.
Studies on the impact of coronavirus disease 2019 (COVID-19) on people's routine medical care are limited, and understanding the factors associated with medical care avoidance can inform us about the ongoing pandemic. We aimed to assess the impact of Japan's state of emergency and stay-at-home policy for COVID-19 on hospital visits and disease exacerbation; we also identified related factors. This cross-sectional study used data from the Japan COVID-19 and Society Internet Survey (JACSIS), which included randomly sampled research agency panellists in Japan. Among the 28,000 participants, we included 7,747 respondents who reported having any disease. We described baseline characteristics and avoidance-related hospital visit outcomes. We used multivariable logistic regression analyses to assess the association between chronic diseases and outcomes of hospital visit avoidance. Among 7,747 participants, 17.7% of patients with chronic diseases avoided hospital visits, 2.1% of patients postponed hospitalization or surgery, 4.9% of patients ran out of drug, and 5.3% of patients experienced disease exacerbation during the COVID-19 pandemic in April and May 2020. Exacerbations occurred mostly in participants with mental diseases, chronic pain and headache, and diabetes (OR 3.33 [95% confidence interval (CI): 2.51-4.41], 2.83 [95% CI: 2.19-3.66], and 1.53 [95% CI: 1.10-2.13], respectively). Patients with cardiovascular disease or cancer did not experience exacerbation [OR 0.55 (95% CI: 0.31-0.97), 0.79 (95% CI: 0.43-1.45)]. The rates of hospital visit avoidance and exacerbation varied among patients with different diseases under the COVID-19 stay-at-home policy in April and May 2020, and disease-specific preparedness may be necessary for the pandemic.


Identification of modules in Aspergillus niger by gene co-expression network analysis.
The fungus Aspergillus niger has been studied in considerable detail with respect to various industrial applications. Although its central metabolic pathways are established relatively well, the mechanisms that control the adaptation of its metabolism are understood rather poorly. In this study, clustering of co-expressed genes has been performed on the basis of DNA microarray data sets from two experimental approaches. In one approach, low amounts of inducer caused a relatively mild perturbation, while in the other approach the imposed environmental conditions including carbon source starvation caused severe perturbed stress. A set of conserved genes was used to construct gene co-expression networks for both the individual and combined data sets. Comparative analysis revealed the existence of modules, some of which are present in all three networks. In addition, experimental condition-specific modules were identified. Module-derived consensus expression profiles enabled the integration of all protein-coding A. niger genes to the co-expression analysis, including hypothetical and poorly conserved genes. Conserved sequence motifs were detected in the upstream region of genes that cluster in some modules, e.g., the binding site for the amino acid metabolism-related transcription factor CpcA as well as for the fatty acid metabolism-related transcription factors, FarA and FarB. Moreover, not previously described putative transcription factor binding sites were discovered for two modules: the motif 5'-CGACAA is overrepresented in the module containing genes encoding cytosolic ribosomal proteins, while the motif 5'-GGCCGCG is overrepresented in genes related to 'gene expression', such as RNA helicases and translation initiation factors.


Increase of manganese superoxide dismutase, but not of Cu/Zn-SOD, in experimental optic neuritis.
To evaluate the role of manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu/Zn-SOD) in cellular protection of the optic nerve against the oxidative injury that contributes to demyelination in experimental allergic encephalomyelitis (EAE). Immunocytochemistry for Mn-SOD and Cu/Zn-SOD and ultracytochemical localization of hydrogen peroxide (H2O2) were performed on the optic nerves of guinea pigs with EAE and normal guinea pigs. Cell-specific enzyme expression of SOD was quantitated by computerized morphometric analysis. Light microscopy showed a perivascular distribution of Mn-SOD-positive cells in the optic nerves of animals with EAE. Electron microscopy showed that the Mn-SOD immunogold was confined exclusively to mitochondria, whereas Cu/Zn-SOD immunogold was found in the cytoplasmic matrix and nucleus of cells of the optic nerve in both animals with EAE and normal animals. Results of quantitative analysis of the optic nerves of animals with EAE showed an 8-fold increase in Mn-SOD immunogold in astroglial cells and a 13-fold increase in microglial/phagocytic cells in comparison with that of normal animals. Increases in Mn-SOD immunogold were contiguous to H2O2-derived reaction product. No increases in Cu/Zn-SOD immunogold were detected in EAE. Increases in Mn-SOD activity in astroglial cells and microglial/phagocytic cells may contribute to the relative sparing of these cells from injury in EAE, whereas the low level of Mn-SOD in oligodendroglial cells and axons may increase their vulnerability to the effects of superoxide-induced oxidative injury that results in demyelination.


Atrial proarrhythmia due to increased inward rectifier current (I(K1)) arising from KCNJ2 mutation--a simulation study.
Atrial fibrillation (AF) has been linked to increased inward rectifier potassium current, I(K1), either due to AF-induced electrical remodelling, or from functional changes due to the Kir2.1 V93I mutation. The aim of this simulation study was to identify at cell and tissue levels' mechanisms by which increased I(K1) facilitates and perpetuates AF. The Courtemanche et al. human atrial cell action potential (AP) model was modified to incorporate reported changes in I(K1) induced by the Kir2.1 V93I mutation in both heterozygous (Het) and homozygous (Hom) mutant forms. The modified models for wild type (WT), Het and Hom conditions were incorporated into homogeneous 1D, 2D and 3D tissue models. Restitution curves of AP duration (APD), effective refractory period (ERP) and conduction velocity (CV) were computed and both the temporal and the spatial vulnerability of atrial tissue to re-entry were measured. The lifespan and tip meandering pattern of re-entry were also characterised. For comparison, parallel simulations were performed by incorporating into the Courtmanche et al. model a linear increase in maximal I(K1) conductance. It was found that the gain-in-function of V93I 'mutant'I(K1) led to abbreviated atrial APs and flattened APD, ERP and CV restitution curves. It also hyperpolarised atrial resting membrane potential and slowed down intra-atrial conduction. V93I 'mutant'I(K1) reduced the tissue's temporal vulnerability but increased spatial vulnerability to initiate and sustain re-entry, resulting in an increased overall susceptibility of atrial tissue to arrhythmogenesis. In the 2D model, spiral waves self-terminated for WT (lifespan < 3.3 s) tissue, but persisted in Het and Hom tissues for the whole simulation period (lifespan > 10 s). The tip of the spiral wave meandered more in WT tissue than in Het and Hom tissues. Increased I(K1) due to augmented maximal conductance produced similar results to those of Het and Hom Kir2.1 V93I mutant conditions. In the 3D model the dynamic behaviour of scroll waves was stabilized by increased I(K1). In conclusion, increased I(K1) current, either by the Kir2.1 V93I mutation or by augmented maximal conductance, increases atrial susceptibility to arrhythmia by increasing the lifespan of re-entrant spiral waves and the stability of scroll waves in 3D tissue, thereby facilitating initiation and maintenance of re-entrant circuits.


Pulmonary arterial hypertension in congenital heart disease: translational opportunities to study the reversibility of pulmonary vascular disease.
Pulmonary arterial hypertension (PAH) is a progressive and lethal pulmonary vascular disease (PVD). Although in recent years outcome has improved by new treatments that delay disease progression, a cure has not yet been achieved. In PAH associated with congenital heart disease (CHD), remodeling of the pulmonary vasculature reaches an irreversible phenotype similar to all forms of end-stage PAH. In PAH-CHD, however, also an early stage is recognised, which can be completely reversible. This reversible phase has never been recognised in other forms of PAH, most likely because these patients are only diagnosed once advanced disease has developed. We propose that the clinical model of PAH-CHD, with an early reversible and advanced irreversible stage, offers unique opportunities to study pathophysiological and molecular mechanisms that orchestrate the transition from reversible medial hypertrophy into irreversible plexiform lesions. Comprehension of these mechanisms is not only pivotal in clinical assessment of disease progression and operability of patients with PAH-CHD; specific targeting of these mechanisms may also lead to pharmacological interventions that transform 'irreversible' plexiform lesions into a reversible PVD: one that is amenable for a cure. In recent years, significant steps have been made in the strive to 'reverse the irreversible'. This review provides an overview of current clinical and experimental knowledge on the reversibility of PAH, focussing on flow-associated mechanisms, and the near-future potential to advance this field.


Transcatheter Retrieval of Cardiovascular Foreign Bodies in Children: A 15-Year Single Centre Experience.
There has been a rapid increase in the practice of interventional catheter treatment of congenital heart disease. Catheter retrieval of embolized cardiac devices and other foreign bodies is essential, yet no large studies have been reported in the paediatric population. Retrospective 15-year review of all children who underwent transcatheter foreign body retrieval in a tertiary cardiac centre from January 1997 to September 2012. Transcatheter retrieval of foreign bodies from the cardiovascular system was attempted in 78 patients [median age 4 (0.02-16) years and median weight 15 (1.7-74) kg] including 46 embolized devices. Transcatheter retrieval was successful in 70/78 (90%), surgical retrieval was required in 6. In two patients, small embolized coils were left in situ. Gooseneck snare was the most commonly used retrieval device. Median procedure and screening times were 90 (15-316) and 31 (2-161) min, respectively. There were no procedural deaths. Transient loss of foot pulses occurred in 5 and 2 patients required blood transfusion. Transcatheter retrieval of cardiovascular foreign bodies can be performed safely in the majority of children thus obviating the need for surgery. It is essential to have a comprehensive inventory of retrieval equipment and interventional staff conversant with its use.


Concerted Flexibility of Chromatin Structure, Methylome, and Histone Modifications along with Plant Stress Responses.
The spatial organization of chromosome structure within the interphase nucleus, as well as the patterns of methylome and histone modifications, represent intersecting layers that influence genome accessibility and function. This review is focused on the plastic nature of chromatin structure and epigenetic marks in association to stress situations. The use of chemical compounds (epigenetic drugs) or T-DNA-mediated mutagenesis affecting epigenetic regulators (epi-mutants) are discussed as being important tools for studying the impact of deregulated epigenetic backgrounds on gene function and phenotype. The inheritability of epigenetic marks and chromatin configurations along successive generations are interpreted as a way for plants to "communicate" past experiences of stress sensing. A mechanistic understanding of chromatin and epigenetics plasticity in plant response to stress, including tissue- and genotype-specific epigenetic patterns, may help to reveal the epigenetics contributions for genome and phenotype regulation.


Thermoresponsive N-alkoxyalkylacrylamide polymers as a sieving matrix for high-resolution DNA separations on a microfluidic chip.
In recent years, there has been an increasing demand for a wide range of DNA separations that require the development of materials to meet the needs of high resolution and high throughput. Here, we demonstrate the use of thermoresponsive N-alkoxyalkylacrylamide polymers as a sieving matrix for DNA separations on a microfluidic chip. The viscosities of the N-alkoxyalkylacrylamide polymers are more than an order of magnitude lower than that of a linear polyacrylamide (LPA) of corresponding molecular weight, allowing rapid loading of the microchip. At 25 degrees C, N-alkoxyalkylacrylamide polymers can provide improved DNA separations compared with LPA in terms of reduced separation time and increased separation efficiency, particularly for the larger DNA fragments. The improved separation efficiency in N-alkoxyalkylacrylamide polymers is attributed to the peak widths increasing only slightly with DNA fragment size, while the peak widths increase appreciably above 150 bp using an LPA matrix. Upon elevating the temperature to 50 degrees C, the increase in viscosity of the N-alkoxyalkylacrylamide solutions is dependent upon their overall degree of hydrophobicity. The most hydrophobic polymers exhibit a lower critical solution temperature below 50 degrees C, undergoing a coil-to-globule transition followed by chain aggregation. DNA separation efficiency at 50 degrees C therefore decreases significantly with increasing hydrophobic character of the polymers, and no separations were possible with solutions with a lower critical solution temperature below 50 degrees C. The work reported here demonstrates the potential for this class of polymers to be used for applications such as PCR product and RFLP sizing, and provides insight into the effect of polymer hydrophobicity on DNA separations.


Structure and properties of metal-organic frameworks modulated by sulfate ions.
Anions play a significant role in the construction of metal-organic frameworks (MOFs). Anions can affect coordination between metal ions and organic ligands, and the formation of crystal structures, thereby affecting the structure and properties of MOFs. Two novel 3D porous MOFs ({[Cd3(TIPE)2(SO4)1.6(H2O)2.4]·2.8OH·6.2H2O}n (MOF-1) and {[Cd3(TIPE)2(SO4)3(H2O)2]·10H2O}n (MOF-2)) were successfully synthesized, by introducing SO42- to design and adjust their structure and properties, in which the sulfate ions not only participated in coordination but also played a bridging role. Both MOF-1 and MOF-2 exhibited high stability and strong fluorescence properties, and their fluorescence properties also changed compared to those of previously reported 2D nonporous MOF-3 ({[Cd2(TIPE)2Cl3(ACN)]·CdCl3·3H2O}n) with an identical ligand. They could also be used in combination with MOF-3 to distinguish between Fe3+ and Cr2O72- ions, due to a change in their fluorescence properties. In this work, the structure was reshaped by introducing sulfate ions, and the role and function of the sulfate ions in the structure were studied, providing a feasible idea for the design and precise regulation of MOFs.


Wear studies on plasma-sprayed Al2O3 and 8mole% of Yttrium-stabilized ZrO2 composite coating on biomedical Ti-6Al-4V alloy for orthopedic joint application.
This paper presents the wear characteristics of the composite ceramic coating made with Al2O3-40wt%8YSZ on the biomedical grade Ti-6Al-4V alloy (grade 5) used for total joint prosthetic components, with the aim of improving their tribological behavior. The coatings were deposited using a plasma spraying technique, and optimization of plasma parameters was performed using response surface methodology to obtain dense coating. The tribological behaviors of the coated and uncoated substrates were evaluated using a ball-on-plate sliding wear tester at 37°C in simulated body-fluid conditions. The microstructure of both the titanium alloy and coated specimen were examined using an optical microscope and scanning electron microscope. The hardness of the plasma-sprayed alumina-zirconia composite coatings was 2.5 times higher than that of the Ti-6Al-4V alloy, while the wear rate of Ti-6Al-4V alloy was 253 times higher than that of the composite-coated Ti-6Al-4V alloy. The superior wear resistance of the alumina-zirconia coated alloy is attributed to its enhanced hardness and intersplat bonding strength. Wear-track examination showed that the predominant wear mechanism of Ti-6Al-4V alloy was abrasive and adhesive wear, whereas, in the case of alumina-zirconia composite coated alloy, the wear was dominated by microchipping and microcracking.


Efficacy of sodium chlorite in inactivating Vibrio parahaemolyticus attached to polyethylene terephthalate surfaces.
The inactivation of Vibrio parahaemolyticus cells attached to a polyethylene terephthalate (PET) disc in a sodium chlorite (NaClO2) solution was kinetically studied in a weakly acidic pH range of 4.0 - 6.5. The logarithmic reduction in the survival ratio depended on the concentration-time product. All inactivation curves showed a linear reduction phase, and the reduction in viable cells was greater than 4-log. No significant desorption of attached cells was observed during the inactivation treatment. The first-order inactivation rate constant (k) increased by approximately 4.5-fold for every 1.0 unit fall in pH. At all pH values, the k values calculated for the attached cells were approximately half of those for the unattached cells. These findings indicate that a weakly acidic NaClO2 solution is effective in inactivating bacteria attached to hard surfaces.


New therapeutic strategy for hepatocellular carcinoma by molecular targeting agents via inhibition of cellular stress defense mechanisms.
The prognosis of advanced hepatocellular carcinoma (HCC) has remained very poor.It has recently been reported that the molecular targeting agent sorafenib can improve the prognosis of patients with advanced HCC. However, the detailed mechanisms of sorafenib, especially its direct effects on hepatoma and hepatocyte cells, are poorly understood, making a more detailed investigation about the molecular mechanism of sorafenib necessary. Endoplasmic reticulum (ER) stress is related to the pathophysiology of various liver diseases, including chronic viral hepatitis, alcoholic and nonalcoholic steatohepatitis and HCC. In this regard, our recent data examining the molecular effects of sorafenib focused on the cellular defense mechanisms from ER stress, the unfolded protein response (UPR) and keratin phosphorylation, demonstrated that sorafenib inhibited both important cytoprotective mechanisms, UPR and keratin phosphorylation, and enhances the anti-tumor effect in combination with proteasome inhibitors. This review summarizes the cytoprotective mechanisms from ER stress and our results about the direct effect of sorafenib on the cytoprotective mechanisms.


[Effectiveness of zotepine in therapy-refractory psychoses. An open, multicenter study in eight psychiatric clinics].
Zotepine was administered to 45 patients suffering from therapy-resistant psychoses hospitalized in eight psychiatric institutes (University Hospital Okayama and affiliated institutions). The psychoses of these patients were characterised by positive symptoms--predominantly hallucinations and delusions--and could not be influenced by a large variety of conventional antipsychotics, such as haloperidol. Previous medications were discontinued or administered together with zotepine. To assess changes in the pattern of symptoms, the Brief Psychiatric Rating Scale (BPRS) was employed over a period of up to 12 weeks at 2-week intervals. Ten patients dropped out of the study because of undesirable effects or for other reasons. 35 patients completed the 12-week study according to schedule. There was a relation between general improvement and certain patient characteristics. Zotepine proved to be effective especially in the catatonic type of schizophrenia, in chronic schizophrenias with acute exacerbation (DSM-III) and in relatively young patients in whom the disease had existed for a short time only. In the 26 patients who were markedly, moderately or slightly improved, BPRS score had dropped significantly after only two weeks of treatment. This points to a rapid onset of the therapeutic action of zotepine.


Clinical, genetic and experimental studies of the Brooke-Spiegler (CYLD) skin tumor syndrome.
Brooke-Spiegler syndrome (BSS; a.k.a. tuban tumor syndrome) is an autosomal dominant inherited skin disorder caused by germline mutations in the CYLD tumor suppressor gene. BSS is characterized by multiple skin adnexal tumors, mainly cylindromas and spiradenomas on the head and neck. The tumors are often severely disfiguring and require repeated surgical interventions. Here, we describe a four-generation BSS-family with a novel germline c.1613_1614delGC CYLD mutation that introduces a premature STOP codon predicted to result in a truncated, inactivated CYLD protein. In addition, we present a pilot study describing establishment of the first patient-derived xenografts (PDXs) from cutaneous CYLD-defective cylindromas. Fresh tumor tissues from cylindromas were transplanted into immunocompromised mice to generate PDXs. One xenograft showed progressive tumor growth after 3 months whereas the others remained unchanged in size during the 6 months study period. Histopathological and immunohistochemical analyses of the PDXs revealed that they recapitulate the histological and molecular features of their respective primary tumors, including expression of NTRK3 and the oncogenic driver MYB. In summary, we present the first preclinical BSS-model that morphologically and genetically recapitulates human CYLD-defective cylindromas. This model will be useful for preclinical therapeutic drug testing and for further studies of the molecular pathogenesis of inherited cylindromas.


Release of carcinoembryonic antigen from human colon cancer cells by phosphatidylinositol-specific phospholipase C.
Carcinoembryonic antigen (CEA) is released from colon cancer cells into the circulation where it is monitored clinically as an indicator of the recurrence or progression of cancer. We have studied the mechanism of CEA membrane attachment and release using the human colonic adenocarcinoma cell line LS-174T, specimens of human colon cancers, and serum from colon cancer patients. CEA release by cells in vitro and in vivo is associated with the conversion of CEA from a membrane-bound, hydrophobic molecule to a soluble, hydrophilic form with no apparent decrease in molecular mass. When LS-174T cell membranes were incubated with various buffers, proteases, and phospholipases, the only agents that released CEA and converted it to the hydrophilic form were preparations of phosphatidylinositol-specific phospholipase C (PI-PLC). Both [3H]ethanolamine and [3H]palmitate could be incorporated metabolically into CEA but only palmitate was released by treatment with PI-PLC, consistent with the presence of a glycosyl-phosphatidylinositol linkage. PI-PLC treatment also release significant quantities of CEA from living monolayers and from seven human colon cancer specimens. These experiments suggest that cellular CEA is anchored to membranes by a covalent linkage to a membrane phosphatidylinositol molecule, and that an endogenous phospholipase may be important for releasing CEA in vitro and in vivo.


Bonding between resin luting cement and glass infiltrated alumina-reinforced ceramics with silane coupling agent.
The purpose of this study was to evaluate the shear bond strengths of three dual-cured resin luting cements (Linkmax HV, Panavia Fluoro Cement, and RelyX ARC) to glass-infiltrated alumina-reinforced ceramic material and the effect of four silane coupling agents (Clearfil Porcelain Bond, GC Ceramic Primer, Porcelain LinerM, and Tokuso Ceramic Primer) on the bond strength. The two type-shaped of In-Ceram alumina ceramic glass-infiltrated specimens were untreated or treated with one of the four ceramic primers and then cemented together with one of the three dual-cured resin luting cements. Half of the specimens were stored in water at 37 degrees C for 24 h and the other half thermocycled 20,000 times before shear bond strength testing. Surface treatment by all silane coupling agents improved the shear bond strength compared with non-treatment. The specimens treated with Clearfil Porcelain Bond showed significantly greater shear bond strength than any of the other three silane coupling agents regardless of resin luting cements and thermocycling except for the use of Panavia Fluoro Cement at 20,000 thermocycles. When the alumina-reinforced ceramic material was treated with any silane coupling agent except GC Ceramic Primer and cemented with Linkmax HV, no significant differences in bond strength were noted between after water storage and after 20,000 thermocycles. After 20,000 thermocycles, all specimens except for the combined use of Clearfil Porcelain Bond or GC Ceramic Primer and Linkmax HV and GC Ceramic Primer and Panavia Fluoro Cement showed adhesive failures at the ceramic-resin luting cement interface.


ISAR Imaging of High-Speed Maneuvering Target Using Gapped Stepped-Frequency Waveform and Compressive Sensing.
In the case of a stepped-frequency waveform (SFW) inverse synthetic aperture radar (ISAR) system, the translational motion (TM) of a target can be usually divided into two parts: 1) target motion within a pulse repetition interval, called the inter-pulse translational motion (IPTM) and 2) target motion between bursts, called the inter-burst translational motion (IBTM). The former induces severe blurring in the ISAR images as well as range-compressed data (i.e., range profile), and the latter also causes dramatic degradation of the ISAR image quality. In this paper, a novel framework for high-resolution gapped SFW (GSFW) ISAR imaging of high-speed maneuvering target is proposed. The main novelty of the proposed method is twofold: 1) accurate TM parameter estimation in conjunction with a compressive sensing theory using a newly devised cost function and particle swarm optimization and 2) compensation for both the IPTM and IBTM phase errors simultaneously even with the GSFW data set. Simulation results using ideal point scatterers show that the proposed method is capable of precise reconstruction of ISAR image and accurate TM parameter estimation. Experimental results using real measured data verify the robustness and the effectiveness of the proposed method.


[Prophylactic effect of methylprednisolone on cisplatin-induced nephrotoxicity in rats].
Cis-diamminedichloroplatinum (II) (cisplatin) is a very effective antitumor drug, but It has an adverse effect of nephrotoxicity. There are many reports concerning protective agents against cisplatin nephrotoxicity, but clinically useful modalities are very few. In the present study, prophylactic effects of methylprednisolone (MP) on cisplatin-induced nephrotoxicity were examined. Male Sprague-Dawley rats were injected iv with 6.5 mg/kg of cisplatin combined with a subcutaneous MP given sc in various doses at various timing. Rats were killed 5 days after cisplatin injection to determine BUN and serum creatinine levels. BUN and serum creatinine levels in rats pretreated with MP 4 or 2 hr before cisplatin injection were significantly lower than those in rats received cisplatin alone. Our preliminary results suggest that pretreatment with MP is an effective means of protection against cisplatin-induced nephrotoxicity.


Red fluorescent cAMP indicator with increased affinity and expanded dynamic range.
cAMP is one of the most important second messengers in biological processes. Cellular dynamics of cAMP have been investigated using a series of fluorescent indicators; however, their sensitivity was sub-optimal for detecting cAMP dynamics at a low concentration range, due to a low ligand affinity and/or poor dynamic range. Seeking an indicator with improved detection sensitivity, we performed insertion screening of circularly permuted mApple, a red fluorescent protein, into the cAMP-binding motif of PKA regulatory subunit Iα and developed an improved cAMP indicator named R-FlincA (Red Fluorescent indicator for cAMP). Its increased affinity (Kd = 0.3 μM) and expanded dynamic range (860% at pH 7.2) allowed the detection of subtle changes in the cellular cAMP dynamics at sub-μM concentrations, which could not be easily observed with existing indicators. Increased detection sensitivity also strengthened the advantages of using R-FlincA as a red fluorescent indicator, as it permits a series of applications, including multi-channel/function imaging of multiple second messengers and combinatorial imaging with photo-manipulation. These results strongly suggest that R-FlincA is a promising tool that accelerates cAMP research by revealing unobserved cAMP dynamics at a low concentration range.


The common infectious diseases in Australia. A report from the australian general practitioner morbidity and prescribing survey.
A study of the common infectious diseases occurring in Australia during 1969 to 1973 showing the total patient-doctor contact for these diseases, the contact rate per episode and the estimated annual new cases seen is presented. In addition, the frequency by age-group and comments made on annual variations, sex differences (where applicable) and the treatment ordered by a large panel of general practitioners are shown.


Differentiation of chicken gonad as an endocrine organ: expression of LH receptor, FSH receptor, cytochrome P450c17 and aromatase genes.
The gonad is an endocrine organ secreting sex hormones and also a target of pituitary gonadotrophins. The expression of mRNAs encoding LH receptor (LHR), FSH receptor (FSHR), P450c17 and P450aromatase in the developing gonads of embryos between day 4 and day 6 of incubation was determined using a RT-PCR to elucidate the chicken gonad as a target organ of gonadotrophins. Although expression of mRNAs encoding LHR, FSHR and P450c17 was detected at day 4 of incubation in both sexes, mRNA encoding P450aromatase appeared at day 6 in female embryos only, indicating that mRNAs encoding gonadotrophin receptors can be identified before sexual differentiation. Quantitative PCR analysis revealed that expression of mRNA encoding LHR and FSHR remained low in male gonads from day 4 to day 6 of incubation, whereas they increased on day 6 in female gonads. The sexual dimorphism in the expression of mRNAs encoding LHR and FSHR was confirmed in the sexually differentiated gonads of embryos at day 12 of incubation (LHR in ovary ratio LHR in testis = 7 ratio 1; FSHR in ovary ratio FSHR in testis = 9 ratio 1).


Rapid development of entity-based data models for bioinformatics with persistence object-oriented design and structured interfaces.
Databases are imperative for research in bioinformatics and computational biology. Current challenges in database design include data heterogeneity and context-dependent interconnections between data entities. These challenges drove the development of unified data interfaces and specialized databases. The curation of specialized databases is an ever-growing challenge due to the introduction of new data sources and the emergence of new relational connections between established datasets. Here, an open-source framework for the curation of specialized databases is proposed. The framework supports user-designed models of data encapsulation, objects persistency and structured interfaces to local and external data sources such as MalaCards, Biomodels and the National Centre for Biotechnology Information (NCBI) databases. The proposed framework was implemented using Java as the development environment, EclipseLink as the data persistency agent and Apache Derby as the database manager. Syntactic analysis was based on J3D, jsoup, Apache Commons and w3c.dom open libraries. Finally, a construction of a specialized database for aneurysms associated vascular diseases is demonstrated. This database contains 3-dimensional geometries of aneurysms, patient's clinical information, articles, biological models, related diseases and our recently published model of aneurysms' risk of rapture. Framework is available in: http://nbel-lab.com.


The versatile synapse.
'Typically' chemical synaptic transmission takes place when an influx of calcium ions during a presynaptic nerve impulse triggers exocytosis of neurotransmitter substance from synaptic vesicles. The neurotransmitter diffuses across the synaptic cleft and occupies receptors embedded in the subsynaptic membrane. This interaction (directly or via a second messenger) operates characteristic ion channels and produces an increase in the postsynaptic membrane permeability to particular ions. Depending on the ionic species to which the postsynaptic membrane becomes more permeable, the physiological response will be an excitatory or an inhibitory postsynaptic potential. The action of neurotransmitters may be terminated either by enzymic inactivation or by cellular uptake mechanisms. Over the last decade it has become clear that a neurotransmitter substance may exert a number of different actions on a single postsynaptic neurone. These may involve opening or closure of either voltage-independent or voltage-dependent ion channels. It is also possible that in some instances transmitters may act on neuronal biochemical systems to modify the physiology of postsynaptic cells without directly altering their electrical characteristics. Analysis of the postsynaptic actions of neurotransmitter substances has become further complicated by the increasing body of evidence which indicates that more than one transmitter substance (one of which may be a peptide) can be released from a single presynaptic neurone. The significance of such dual transmitter systems has yet to be fully elucidated. The efficacy of transmission across many synapses may be modified by either presynaptic or postsynaptic mechanisms; both transmitter release and postsynaptic responsiveness may depend on the recent history of a single synapse, on synaptic inputs from other neurones or on circulating neuroactive substances.


Genotoxic and reproductive effects of an industrially contaminated soil on the earthworm Eisenia fetida.
Polluted soil sampled from a former coking plant in Lorraine (France) was studied for its genotoxicity and reproductive effects on the Eisenia fetida earthworm. Genotoxicity was investigated by means of the single-cell gel electrophoresis (comet) assay on the coelomocytes of earthworms after 4 and 10 days of exposure to the soil. DNA damage and a decline in the number of coelomocytes extruded from earthworms were observed at coking plant soil concentrations of 20 and 40% (w/w) in ISO soil. These soil concentrations had previously been shown to significantly reduce cocoon and juvenile productions after 28 and 56 days of earthworm exposure, respectively. The results showed that genotoxic pollutants in the tested soil were still bioavailable despite the age of the contaminated soil. Similar values of the no-observed-effect concentration (NOEC) corresponding to 10% of the contaminated soil and of the lowest soil concentration tested inducing effects (LOEC) corresponding to 20% of the contaminated soil were obtained from reproductive and genotoxicity endpoints. Among the soil pollutants measured, polycyclic aromatic hydrocarbons (PAHs) appeared to be the most likely source of the genotoxicity recorded, although effects of metals could not be excluded. Measurement of genotoxicity in earthworms could complement the existing standardized tests used in the ecotoxicological assessment of the risk associated with contaminated soils.


Highly sensitive capacitance-based nitrite sensing using polydopamine/AuNPs-modified screen-printed carbon electrode.
Regulatory bodies play a crucial role in establishing limits for food additives to ensure food quality and safety of food products, as excessive usage poses risks to consumers. In the context of processed animal-based foodstuffs, nitrite is commonly utilized as a means to slow down bacterial degradation. In this study, we have successfully leveraged the redox activity of an electrochemically deposited polydopamine (pDA) film onto gold nanoparticle (AuNP)-modified screen-printed electrodes (SPCE) to develop a sensitive and versatile methodology for the detection of nitrite using redox capacitance spectroscopy. By exploiting the interaction of the AuNPs/pDA electroactive interface with the target nitrite ions, we observed distinct changes in the redox distribution, subsequently leading to modifications in the associated redox capacitance. This alteration enables the successful detection of nitrite, exhibiting a linear response within the concentration range of 10 to 500 μM, with a limit of detection of 1.98 μM (S/N = 3). Furthermore, we applied the developed sensor to analyze nitrite levels in processed meats, yielding good recoveries. These results demonstrate the potential of our approach as a promising method for routine detection of ions.


Brain Amyloid Deposition Is Associated With Lower Instrumental Activities of Daily Living Abilities in Older Adults. Results From the MAPT Study.
Brain amyloid deposition is one of the key pathological hallmarks underlying the cognitive changes associated with Alzheimer's disease. Growing interest has been given to the earliest clinical manifestations of amyloid plaques. However, the relationship between amyloid status and activities of everyday function remains largely unknown. In the present study, we examined the relationship between instrumental activities of daily living performance (using the ADL-PI score) and amyloid status in older adults. Cross-sectional analyses of data from the Multidomain Alzheimer Preventive Trial (MAPT) were performed. Volunteers underwent a brain 18F-AV45 positron emission tomography examination. Bivariate analysis and regression models were conducted to study the relationships between brain amyloid deposition and the total ADL-PI score. We included 271 participants (women = 60%; age = 76±4 years). Amyloid positron emission tomography was positive (standard uptake value ≥1.17) for 103 participants (38%). The ADL-PI score was lower in amyloid positive participants than in their amyloid negative counterparts (38.8 vs 40.3, p = .007). This association was also confirmed in regression models adjusted for age, gender, and familial history of Alzheimer's disease (odds ratio = 0.94; 95% confidence interval 0.89-0.99; p = .02). This finding was consistent in cognitively normal individuals and in those with mild cognitive impairment, using the clinical dementia rating scale. This study highlighted an association between early functional limitations and brain amyloid deposition in elderly subjects. These symptoms could be the clinical manifestations of amyloid plaques even in the absence of overt dementia. Further prospective studies are warranted for examining the evolution of ADL-PI score over the course of Alzheimer's disease.


Metal-on-metal dysplasia cup total hip arthroplasty for hip osteoarthritis secondary to developmental dysplasia of the hip.
This study aims to evaluate the clinical and radiological results of metal-on-metal dysplasia cup total hip arthroplasty (THA) for hip osteoarthritis secondary to developmental dysplasia of the hip (DDH). Between May 2009 and October 2011, THA was performed on 27 hips (7 Crowe type II, 9 Crowe type III, 11 Crowe type IV) of 22 patients (2 males, 20 females; mean age 43 years; range 25 to 63 years) with hip osteoarthritis secondary to DDH. All patients were evaluated clinically and radiographically. Average follow-up period was 34.2 months (range 24-53 months). While mean Harris hip score (HHS) was 43 (range 30 to 72 points) preoperatively, it was 92 (range 87 to 98 points) at final follow-up. Two patients developed sciatic nerve palsy postoperatively. Recurrent dislocation occurred in one patient one year after the operation. Mean cup inclination was 45.6° (range 42°-51°). Heterotopic ossification developed in eight patients. No patient's acetabular and femoral component migrated or subsided significantly. None of the implants was revised. Early clinical and radiological results of metal-on-metal dysplasia cup THA in DDH are satisfactory.


Pig blastocyst-uterine interactions.
The litter-bearing pig is an invaluable model for research in reproductive biology. Spherical pig blastocysts on Day 10 of pregnancy undergo rapid morphological changes to tubular and then filamentous forms by Day 12 and a filamentous conceptus of almost 1m in length by Day 16 of pregnancy. Thus, trophectoderm of each conceptus achieves intimate contact with luminal uterine epithelium (LE) for exchange of nutrients, gases, hormones, growth factors and other key molecules for survival and development. Estrogens secreted between Days 11 and 13 of pregnancy signals pregnancy recognition to ensure that nutrients and prostaglandin F2-alpha (PGF) are secreted into the uterine lumen (exocrine secretion) rather than into the uterine vein (endocrine secretion) which would lead to regression of the corpora lutea (CL) and failure to maintain pregnancy. Pigs have a true epitheliochorial placenta. The fluid filled amnion bouys the embryo so that it develops symmetrically. The allantois fills with allantoic fluid to expand contact of the chorioallantois with uterine LE, and the allanotois supports the vascular system of the placenta. The chorion/trophectoderm in direct contact with uterine LE exchanges gases and nutrients and forms unique structures call areolae that absorb nutrient-rich secretions from uterine glands and transports them directly into fetal blood. The period from Days 20 to 70 of pregnancy is for placental growth in preparation for rapid fetal growth between Days 70 and 114 (term) of gestation. Maturation of the fetal hypothalamic-pituitary-adrenal axis leads to increases in secretion of cortisol from the fetal adrenal glands. Cortisol sets in motion secretion of estrogens, oxytocin, relaxin and prolactin, as well as increases in their receptors, which are required for delivery of piglets and for initiation of lactation and expression of maternal behavior. This review provides details of gestation in the pig with respect to uterine biology, implantation, placentation, fetal development and parturition.


Identification of Distinct Latent Classes Related to Sleep, PTSD, Depression, and Anxiety in Individuals Diagnosed With Severe Alcohol Use Disorder.
Objective/Background: Alcohol use disorders (AUDs) are often accompanied by comorbid physiologic and psychosocial conditions, including sleep disturbances. Sleep disturbances in these individuals may be associated with increased risk of relapse to drinking following detoxification and rehabilitation. Participants: The sample of inpatient treatment-seeking individuals with AUDs (N = 164) was 70.1% male and 47.6% African American with a mean age of 45.6 years (±9.5 years). Methods: Latent class analysis (LCA) was used to identify unmeasured class membership based on seven indicators: maximum Clinical Institute Withdrawal Assessment (CIWA) scores; sleep efficiency (actigraphy); sleep disturbances (Pittsburgh Sleep Quality Index-PSQI); anxiety or depression (Comprehensive Psychopathological Rating Scale [CPRS]); and current and lifetime posttraumatic stress disorder (PTSD). Results: The average number of drinking days in the 90 days preceding admission was 72.0 (±22.0 days), with an average of 13.16 drinks per day (±5.70 drinks). Nearly one quarter (24.4%) of respondents reported lifetime PTSD. Three latent classes were identified: Sleep Disturbance (SD); Sleep Disturbance, Anxiety and Depression (SD/AD); and Sleep Disturbance, Anxiety and Depression, and PTSD (SD/AD/PTSD). Members of the SD/AD/PTSD group were more likely to be female and had the highest withdrawal and sleep disturbance scores of all three groups. Conclusion: Findings support the use of LCA to identify subgroups of individuals with AUDs and accompanying sleep disturbances. Class identification may provide clinicians with insight into the integrative tailoring of interventions that meet the varied needs of individuals with AUDs, accompanying comorbidities, and sleep disturbances.


Expanding population edges: theories, traits, and trade-offs.
Recent patterns of global change have highlighted the importance of understanding the dynamics and mechanisms of species range shifts and expansions. Unique demographic features, spatial processes, and selective pressures can result in the accumulation and evolution of distinctive phenotypic traits at the leading edges of expansions. We review the characteristics of expanding range margins and highlight possible mechanisms for the appearance of phenotypic differences between individuals at the leading edge and core of the range. The development of life history traits that increase dispersal or reproductive ability is predicted by theory and supported with extensive empirical evidence. Many examples of rapid phenotypic change are associated with trade-offs that may influence the persistence of the trait once expansion ends. Accounting for the effects of edge phenotypes and related trade-offs could be critical for predicting the spread of invasive species and population responses to climate change.


Expression of intercellular adhesion molecule-1 (ICAM-1) in benign naevi and malignant melanomas.
Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound glycoprotein that is a ligand for lymphocyte function-associated antigen-1 (LFA-1) and is important for a number of cell adhesions in immune reactions. The molecule is expressed by several cell types (e.g. macrophages, endothelial cells, keratinocytes, melanoma cells and cell lines) and there are some indications that expression of this molecule in melanocytic lesions is confined to malignant tumours and is more pronounced in metastatic and advanced tumours than in earlier lesions. In an attempt to elucidate this issue, we have studied biopsy samples from benign naevi (n = 7) and malignant melanomas (n = 33) regarding reactivity with monoclonal anti-ICAM-1 (CD54). The results indicate that the great majority of malignant melanomas are ICAM-1-positive. The most abundant staining is seen in metastatic melanomas. In primary melanomas, staining is more variable and generally weaker. However, no correlation was found between the degree of ICAM-1 labelling and the degree of tumour invasion. Furthermore, ICAM-1 expression was not confined to malignant lesions, but was also seen in benign naevi. These data contrast with earlier reports and indicate that ICAM-1 expression is unlikely to be of major prognostic or diagnostic value in melanocytic tumours.


A new approach to the management of malignant ascites; a permanently implanted abdominal drain.
A new approach to the problem of intractable malignant ascites in preterminal abdominal carcinoma is presented. Seventeen patients treated with a new implantable silastic drain are described. Symptomatic relief was excellent in all patients for as long as the drain was patent. Complications included abdominal wall cellulitis in two instances and one case of peritonitis, but did not preclude continued drain function in 15 of the 17 cases. In eight of the 17 cases organisms were cultured from the ascitic fluid while the catheter was in situ. Drainage of ascitic fluid in this way appears to be a practical management for intractable malignant ascites.


Global Post-Translational Modification Discovery.
A new global post-translational modification (PTM) discovery strategy, G-PTM-D, is described. A proteomics database containing UniProt-curated PTM information is supplemented with potential new modification types and sites discovered from a first-round search of mass spectrometry data with ultrawide precursor mass tolerance. A second-round search employing the supplemented database conducted with standard narrow mass tolerances yields deep coverage and a rich variety of peptide modifications with high confidence in complex unenriched samples. The G-PTM-D strategy represents a major advance to the previously reported G-PTM strategy and provides a powerful new capability to the proteomics research community.


A Preliminary Study on the Equivalence between Standing Back-Extension and Superman Training in Lumbar Multifidus Exercise.
To explore the equivalence of an easier and more convenient lumbar multifidus (LM) muscle exercise pattern among standing back-extension, static standing, and superman training. A total of 26 healthy young volunteers were enrolled, including 14 males and 12 females, aged from 22 to 44 years with an average of 31.77 ± 7.06 years. Ultrasonography was used to measure the thickness of the left LM of the transverse process of the L5 vertebra during static standing, static prone decubitus, standing back-extension, and prone superman training. In this study, measurement data were expressed as Mean ± SD and compared using the t-test. The left LM thickness of the L5 vertebra was 2.92 ± 0.46 cm during static standing and 2.78 ± 0.39 cm during static prone decubitus, showing no statistical difference between the two groups (P > 0.05). The left LM thickness of the L5 vertebra was 3.16 ± 0.51 cm during standing back-extension and 3.33 ± 0.41 cm during the prone superman training, indicating no statistical difference between the two groups (P > 0.05). There is no significant statistical difference in the LM thickness between static standing and static prone decubitus and between standing back-extension and prone superman training, indicating the equivalence of the two methods in LM exercise, providing a simpler and easier way for clinical exercise of lumbodorsal muscles.


Rituximab-induced Acute Thrombocytopenia in High Tumor Burden Follicular Lymphoma.
Rituximab-induced acute thrombocytopenia (RIAT), a rare complication of rituximab administration, has not yet been described in follicular lymphoma (FL). A 65-year-old man received rituximab for the treatment of high tumor burden follicular lymphoma in the leukemic phase. The next day, his platelet count abruptly dropped from 85,000 to 5,000/μL, which spontaneously recovered in a few days without specific treatment. We speculate that the occurrence of infusion-related cytokine release syndrome in rituximab-sensitive high tumor burden FL contributed to the development of RIAT. Frequent monitoring of the platelet count is advisable for select patients considered to be at a high risk for RIAT.


Detection of sputum eicosanoids in cystic fibrosis and in normal saliva by bioassay and radioimmunoassay.
We have measured arachidonic acid (AA) metabolites, leukotrienes (LTs) and prostanoids (Ps), in sputum of patients with cystic fibrosis (CF) and in normal saliva using bioassay and radioimmunoassay (RIA). Almost three times as much LTB4 is present in CF extracts compared with slow reacting substances (SRSs). Leukotrienes were not detected in normal saliva. In CF sputum there is a three-fold increase in the level of the vasodilator prostanoid prostaglandin E2 (PGE2) and the stable metabolite of prostacyclin, 6-oxo PGF1 alpha compared with the vasoconstrictor prostaglandin F2 alpha (PGF2 alpha) and thromboxane B2 (TxB2), a hydrolysis product of thromboxane A2. Experiments with BW755c (25 micrograms ml-1, n = 3) indicated that the majority of this activity was not produced during the extraction procedure. The detection of LTs and Ps in sputum of CF patients shows that these substances are present at biologically active concentrations and may contribute to the pathophysiology of this disease.


Antibiotic-Eluting Envelopes to Prevent Cardiac-Implantable Electronic Device Infection: Past, Present, and Future.
Cardiac-implantable electronic device (CIED) infections are associated with significant morbidity and mortality. In this review, we describe the risk factors and pathogenesis of CIED infections and review the rationale and the evidence for the use of antibiotic-eluting envelopes (ABEs) in patients at increased risk for CIED infections. The majority of CIED infections are caused by staphylococci that involve generator pocket and occur due to contamination of the device or the pocket tissues at the time of implantation. Clinical trials have shown that extending the duration of post-operative systemic antibacterial therapy is not beneficial in reducing CIED infection rate. However, ABEs that reduce device migration after implantation and provide sustained local delivery of prophylactic antibiotics at the pocket site, may provide benefit in reducing infection. Currently, there are two types of commercially available CIED envelope devices in the United States. The first ABE device (TYRX™, Medtronic Inc., Monmouth Junction, NJ) is composed of a synthetic absorbable mesh envelope that elutes minocycline and rifampin and has been shown to reduce CIED pocket infections in a large multi-center randomized clinical trial. The second ABE device (CanGaroo-G™, Aziyo Biologics, Silver Spring, MD) is composed of decellularized extracellular matrix (ECM) and was originally designed to stabilize the device within the pocket, limiting risk for migration or erosion, and providing a substrate for tissue ingrowth in a preclinical study. This device has shown promising results in a preclinical study with local delivery of gentamicin. Compared with artificial materials, such as synthetic surgical mesh, biologic ECM has been shown to foster greater tissue integration and vascular ingrowth, a reduced inflammatory response, and more rapid clearance of bacteria. ABE devices provide sustained local delivery of antibiotics at the generator pocket site and appear beneficial in reducing CIED pocket infections. Given the continued increase in the use of CIED therapy and resultant infectious complications, innovative approaches to infection prevention are critical.


Aetiological factors involved in the low response to gonadotrophins in infertile women with normal basal serum follicle stimulating hormone levels.
This study was designed to investigate possible aetiological factors involved in the low response to gonadotrophins in women with normal basal serum follicle stimulating hormone (FSH) concentrations, stimulated for assisted reproduction. Nine of these patients with normal basal serum FSH and 22 normal controls (five of whom had had a normal response to previous gonadotrophin stimulation) were prospectively subjected to: (i) transvaginal pulsed colour Doppler ultrasound evaluation of the vessels surrounding the dominant follicle for blood flow impedance analysis, (ii) the clonidine test to explore the ability of the pituitary to release growth hormone, and (iii) detection of anti-granulosa cell auto-antibodies in blood using an enzyme-linked immunosorbent assay (ELISA). The pulsatility and resistance indices (PI, RI) were significantly (P < 0.01) higher in the women with low responses as compared to the controls on days -1 and 0 (day 0 = ovulation). Seven out of the nine low responders were out of the range calculated for normal values after evaluation of the controls. A significant (P < 0.05) decrease in the secretion of growth hormone 60-90 min after clonidine ingestion was observed in the low responders as compared to five controls with previous normal response to ovarian stimulation. Six out of the nine low responders showed a negative clonidine test. No increase in anti-granulosa cell auto-antibodies was observed in the low responders as compared to the controls, including normal responders. In conclusion, an abnormal follicular blood flow impedance in the natural cycle may be related to low responses to gonadotrophins in patients with normal serum FSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)


[Survey on risk factors for type 2 diabetes mellitus at a higher education institution].
The increase in the population's life expectancy, the decrease in people's physical activity and the increase in calorie intake play an important role in the onset of diabetes. Therefore, this study aims at identifying risks factors for type-2 diabetes mellitus in 99 subjects from a teaching institution in a city in the interior of São Paulo State, Brazil. The results enabled the conclusion that 51.5% of the subjects were overweight; 51.5% had hereditary antecedents, 70% did not do physical exercises regularly, 68% felt stressed at work and 6% had altered pressure levels. The results showed the need for an education program within the institution aiming at awaking in the subjects the need to look for healthy life styles in order to prevent risks factors for type-2 diabetes.


Metabolism and macromolecular binding of the carcinogen Michler's ketone in rats.
1. Studies on the metabolism of 14C-Michler's ketone (4,4'-bis-(dimethylamino)[carbonyl- 14C]benzophenone) in rats have revealed that this carcinogen is subject to demethylation, ring-hydroxylation and N-acetylation after adjacent methyl groups have been removed. 2 As identified by mass spectral analysis, microsomal metabolites are the mono-, di-, tri- and tetra-demethylated derivatives. 3. The major metabolites appearing in the bile are the di- and tri-demethylated derivatives and the N-acetylated tetra-demethylated compound; minor metabolites, tentatively identified, are the ring-hydroxylated derivatives of di- and tri-demethylated Michler's ketone and of N-acetylated tri- and tetra-demethylated Michler's ketone. 4. The major urinary metabolite is tentatively identified as a ring-hydroxylated derivative of N-acetylated, di-demethylated Michler's ketone; a minor urinary metabolite lacks the hydroxyl group. 5. Injection of 14C-Michler's ketone into rats resulted in the irreversible binding of radioactivity to liver proteins. 6. When the rats were pretreated with phenobarbital, this binding was increased and extended to proteins of some other tissues and to DNA and RNA of liver and DNA of kidney.


Effects of AMF inoculation on the growth, photosynthesis, and root physiological morphology of root-pruned Robinia pseudoacacia seedlings.
Root pruning hinders the absorption and utilization of nutrients and water by seedlings in the short term. Arbuscular mycorrhizal fungi (AMF) are an important source of nutrient and water for seedlings except for the root system. However, the mechanism by which AMF affect the physiological growth of seedlings after root pruning has rarely been studied. In this study, a pot experiment was conducted through a three-compartment partition system to clarify the effects of Funneliformis mosseae (F. mosseae) strain BGC XJ07A on the physiological growth of root-pruned Robinia pseudoacacia (R. pseudoacacia) seedlings. Five root pruning treatments (0, 1/5, 1/4, 1/3, and 1/2 of the taproot length was removed) were applied to noninoculated seedlings and those inoculated with F. mosseae. The results showed that the presence of F. mosseae significantly increased the shoot and root biomasses, leaf photosynthetic rate, stomatal conductance, and transpiration rate. The root projected area, root surface area, average root diameter, root density, root volume, and number of root tips of the inoculated seedlings were higher than those without inoculation in all root pruning treatments. The root cytokinin (CTK), gibberellins (GA) and indole-3-acetic acid (IAA) concentrations but root abscisic acid (ABA) concentration were higher than those measured in the absence of inoculation in all root pruning treatments. Moreover, the changes in the root endogenous hormone concentrations of the seedlings were closely related to the root morphological development and seedling biomass. AMF increased the soil available nitrogen, soil available phosphorus, soil available potassium and soil organic matter concentrations compared with the noninoculated treatment. These results indicate that AMF can alleviate the adverse effects of root pruning on the physiological growth of R. pseudoacacia and soil properties and provide a basis for AMF application to forest cultivation and the sustainable development of forest ecosystems.


Accurate Vehicle Location System Using RFID, an Internet of Things Approach.
Modern infrastructure, such as dense urban areas and underground tunnels, can effectively block all GPS signals, which implies that effective position triangulation will not be achieved. The main problem that is addressed in this project is the design and implementation of an accurate vehicle location system using radio-frequency identification (RFID) technology in combination with GPS and the Global system for Mobile communication (GSM) technology, in order to provide a solution to the limitation discussed above. In essence, autonomous vehicle tracking will be facilitated with the use of RFID technology where GPS signals are non-existent. The design of the system and the results are reflected in this paper. An extensive literature study was done on the field known as the Internet of Things, as well as various topics that covered the integration of independent technology in order to address a specific challenge. The proposed system is then designed and implemented. An RFID transponder was successfully designed and a read range of approximately 31 cm was obtained in the low frequency communication range (125 kHz to 134 kHz). The proposed system was designed, implemented, and field tested and it was found that a vehicle could be accurately located and tracked. It is also found that the antenna size of both the RFID reader unit and RFID transponder plays a critical role in the maximum communication range that can be achieved.


Quercetagetin and Patuletin: Antiproliferative, Necrotic and Apoptotic Activity in Tumor Cell Lines.
Quercetagetin and patuletin were extracted by the same method from two different Tagetes species that have multiple uses in folk medicine in Mexico and around the globe, one of which is as an anticancer agent. Their biological activity (IC50 and necrotic, apoptotic and selective activities of these flavonols) was evaluated and compared to that of quercetin, examining specifically the effects of C6 substitution among quercetin, quercetagetin and patuletin. We find that the presence of a methoxyl group in C6 enhances their potency.


Interplay between antiretroviral therapy and oxidative stress in HIV seropositive patients.
HIV infection results in a decline of CD4+ T-cells count and ultimately results in qualitative impairments of CD4+ T-cell function. Antiretroviral therapy results in an increase in the number of CD4+ cells and the functional reconstitution of the immune system. However, patients on therapy commonly experience adverse effects; management of HIV infection thus becomes a balancing act between the benefits of HIV suppression and the risks of drug toxicity with Highly Active Antiretroviral Therapy (HAART). Purpose and Findings: This review intended to look into the relationship between adverse effects with HAART in relation to its induction of oxidative stress in the host. From literature,. HAART has been shown to induce oxidative stress by several biochemical mechanisms. However, the induction of oxidative stress by HAART is minimal compared to HIV induction of oxidative stress-in the host. The use of HAART in the management of HIV-AIDS thus remains inevitable and the combination with exogenous antioxidants is advocated. Exogenous antioxidants mop up infection induced reactive oxygen species (ROS), and may also be beneficial in ameliorating some of the adverse effects induced by HAART. Further review on individual adverse effects of ART is recommended and our ongoing research on the teratogenic potentials of HAART will also be very relevant on this subject.


Polyglycolic acid-polylactic acid scaffold response to different progenitor cell in vitro cultures: a demonstrative and comparative X-ray synchrotron radiation phase-contrast microtomography study.
Spatiotemporal interactions play important roles in tissue development and function, especially in stem cell-seeded bioscaffolds. Cells interact with the surface of bioscaffold polymers and influence material-driven control of cell differentiation. In vitro cultures of different human progenitor cells, that is, endothelial colony-forming cells (ECFCs) from a healthy control and a patient with Kaposi sarcoma (an angioproliferative disease) and human CD133+ muscle-derived stem cells (MSH 133+ cells), were seeded onto polyglycolic acid-polylactic acid scaffolds. Three-dimensional (3D) images were obtained by X-ray phase-contrast microtomography (micro-CT) and processed with the Modified Bronnikov Algorithm. The method enabled high spatial resolution detection of the 3D structural organization of cells on the bioscaffold and evaluation of the way and rate at which cells modified the construct at different time points from seeding. The different cell types displayed significant differences in the proliferation rate. In conclusion, X-ray synchrotron radiation phase-contrast micro-CT analysis proved to be a useful and sensitive tool to investigate the spatiotemporal pattern of progenitor cell organization on a bioscaffold.


Association between sensory function and medio-lateral knee position during functional tasks in patients with anterior cruciate ligament injury.
Patients with anterior cruciate ligament (ACL) injury often exhibit reduced movement quality during functional tasks in the form of a knee-medial-to-foot position (KMFP). This movement pattern is suggested to be more common in women than in men, but the possible contributing sensorimotor factors for this altered knee position are poorly studied in these patients. The aim of this study was to evaluate the association between sensory function and medio-lateral knee position during functional tasks in men and women with ACL injury. Fifty-one patients (23 women) aged 18-40 years with ACL injury were included in this cross-sectional study. Measures of sensory function were assessed by the threshold to detection of passive motion (TDPM) for knee kinesthesia and by the vibration perception threshold (VPT) for vibration sense. Movement quality was assessed by visual observation of the position of the knee relative to the foot during the following four functional tasks with different degrees of difficulty: the single-limb mini-squat, stair descending, the forward lunge, and the drop-jump. Spearman's rank correlation coefficient was used to determine the relationship between the sensory measures and the medio-lateral knee position during the functional tasks. Differences in TDPM and/or VPT between subjects with good and poor movement quality were evaluated using the independent t-test. Separate gender analyses were performed. Worse TDPM was associated with a KMFP during the drop jump in men. Worse VPT at the toe and ankle was associated with a KMFP during stair descending and the forward lunge in women, but no associations were found in men. Worse kinesthesia, measured by TDPM, might be associated with KMFP during the drop jump in men with ACL injury while worse vibration sense, measured by the VPT, at the foot and ankle might be related to KMFP in women. Further studies are needed to confirm these results.


Using the Alzheimer's Association web site to improve knowledge of Alzheimer's disease in health care providers.
The purpose of the current study was to investigate whether an informative Web site is effective at producing higher scores for an individual's knowledge of Alzheimer's disease (AD) relative to those who do not visit a Web site. A total of 552 participants completed the study on Amazon's Mechanical Turk; half were randomly assigned to visit alz.org, while a control group did not. Both groups were given the AD Knowledge Scale (ADKS) to assess their knowledge of AD. Participants who visited alz.org scored significantly higher on the ADKS than those in the control group. Participants who were health care workers demonstrated higher scores than others in the experimental condition. Findings indicate that the Alzheimer's Association Web site is effective at producing higher scores for AD knowledge relative to no Web site at all and that it is especially helpful for health care workers compared to those who are not health care workers.


[Male genital lesions caused by papillomaviruses. Importance of colposcopy].
Ten years after the description of cervical flat condyloma, it is now admitted that Human Papillomaviruses (HPVs) type 6 and 11 are responsible for condylomata acuminata and typical flat condyloma of the uterine cervix. HPV DNA type 16 and, less frequently, 18, 33 and other as yet uncharacterized HPV types (G. Orth, personal communication), are found in the majority of Cervical Intraepithelial Neoplasia (CIN), Vulvar Intraepithelial Neoplasia (VIN) and cervical and vulvar invasive cancers. Since HPVs are sexually transmissible, recent interest has focused on the "male factor". Clinically detectable lesions of male genitalia are condylomata acuminata, bowenoid papulosis and flat condyloma-like papules. The aim of our study was the colposcopical screening, recently suggested, of different groups of male patients in order to detect HPV-related lesions and the description of the colposcopical features of subclinical HPV-related lesions, since most of them have never been reported, to our knowledge, in the literature. A total of 114 men were examined. Among them, 18 presented clinically detected recalcitrant condylomata acuminata, 28 had been treated for the same pathology 1 to 5 days earlier and were clinically free of lesions, 46 were sexual partners of women with cervical atypia (flat condyloma and/or CIN) and 22 had a clinical diagnosis of genital infection without HPV-related lesions. A careful examination of external genitalia was performed. Then all patients underwent penile colposcopy before and after application of 5 p. 100 acetic acid. Selected biopsies were performed in all lesions which were clinically and colposcopically different from classic warts. Colpophotographs were taken in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of microtubules and dynein rescues human immunodeficiency virus type 1 from owl monkey TRIMCyp-mediated restriction in a cellular context-specific fashion.
IFN-induced restriction factors can significantly affect the replicative capacity of retroviruses in mammals. TRIM5α (tripartite motif protein 5, isoform α) is a restriction factor that acts at early stages of the virus life cycle by intercepting and destabilizing incoming retroviral cores. Sensitivity to TRIM5α maps to the N-terminal domain of the retroviral capsid proteins. In several New World and Old World monkey species, independent events of retrotransposon-mediated insertion of the cyclophilin A (CypA)-coding sequence in the trim5 gene have given rise to TRIMCyp (also called TRIM5-CypA), a hybrid protein that is active against some lentiviruses in a species-specific fashion. In particular, TRIMCyp from the owl monkey (omkTRIMCyp) very efficiently inhibits human immunodeficiency virus type 1 (HIV-1). Previously, we showed that disrupting the integrity of microtubules (MTs) and of cytoplasmic dynein complexes partially rescued replication of retroviruses, including HIV-1, from restriction mediated by TRIM5α. Here, we showed that efficient restriction of HIV-1 by omkTRIMCyp was similarly dependent on the MT network and on dynein complexes, but in a context-dependent fashion. When omkTRIMCyp was expressed in human HeLa cells, restriction was partially counteracted by pharmacological agents targeting MTs or by small interfering RNA-mediated inhibition of dynein. The same drugs (nocodazole and paclitaxel) also rescued HIV-1 from restriction in cat CRFK cells, although to a lesser extent. Strikingly, neither nocodazole, paclitaxel nor depletion of the dynein heavy chain had a significant effect on the restriction of HIV-1 in an owl monkey cell line. These results suggested the existence of cell-specific functional interactions between MTs/dynein and TRIMCyp.


Understanding and managing metabolic dysfunction in Amyotrophic Lateral Sclerosis.
Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease that leads to death after a median survival of 36 months. The development of an effective treatment has proven to be extremely difficult due to the inadequate understanding of the pathogenesis of ALS. Energy metabolism is thoroughly involved in the disease based on the discoveries of hypermetabolism, lipid/glucose metabolism, the tricarboxylic acid (TCA) cycle, and mitochondrial impairment. Many perturbed metabolites within these processes have been identified as promising therapeutic targets. However, the therapeutic strategies targeting these pathways have failed to produce clinically significant results. The authors present in this review the metabolic disturbances observed in ALS and the derived-therapeutics. The authors suggest that this is due to the insufficient knowledge of the relationship between the metabolic targets and the type of ALS of the patient, depending on genetic and environmental factors. We must improve our understanding of the pathological mechanisms and pay attention to the subtle hidden effects of changing diet, for example, and to use this strategy in addition to other drugs or to use metabolism status to determine subgroups of patients.


Detection of mild factor VIII Deficiency by thrombokinetics.
The maximal rate of change in optical density (Vmax-deltaOD)of plasma clots forming in the activated partial thromboplastin time test (APTT) may be significantly influenced by reductions in factor VIII activity insufficient to also cause a distinctly abnormal timed clotting endpoint. Analysis of relationships between Vmax-deltaOD of clotting plasma in the APTT, prothrombin time, and thrombin time tests provides a basis for increasing the screening value of the APTT in suggesting intrinsic system abnormalities. Three illustrative case reports support the added benefit of thrombokinetics in the detection of mild factor VIII deficiency in hemophilia A and in von Willebrand's disease.


Effects of the interaction between PTSD and ADHD symptoms on the level of reporting psychotic-like experiences: findings from a non-clinical population.
Psychotic-like experiences (PLEs) are increasingly being recognized as subclinical phenomena that might predict the development of various mental disorders that are not limited to the psychosis spectrum. Accumulating evidence suggests that attention-deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) are highly comorbid mental disorders. However, their interactive effect on the occurrence of PLEs has not been investigated so far. Therefore, in the present study we aimed to investigate the effect of interaction between ADHD and PTSD symptoms on the level of psychotic-like experiences (PLEs) in the non-clinical sample. The study included 3,000 individuals aged 18-35 years with a negative history of psychiatric treatment. The symptoms of ADHD and PTSD were assessed using self-reports. There was a significant association of the interaction between ADHD and PTSD with the level of reporting PLEs. This association remained significant after adjustment for age, gender, the level of education, the current vocational situation, lifetime history of problematic substance use, and depressive symptoms. Post-hoc tests demonstrated significantly higher levels of reporting PLEs in participants with positive screening for both ADHD and PTSD compared to other subgroups of participants. Also, individuals with positive screening for one vulnerability (either ADHD or PTSD) reported significantly higher levels of reporting PLEs compared to those with a negative screening for ADHD and PTSD. In turn, no significant differences between individuals reporting one vulnerability, i.e., between those with positive screening for ADHD and those with positive screening for PTSD, were observed. Findings from the present study imply that both PTSD and ADHD symptoms the interaction effect on the level of reporting PLEs that might be of importance for early intervention strategies. However, observed associations require replication in clinical samples.


The evolution of genomic stability to a mechanism in reproduction and psychiatry.
There are two forms of immune defense, the specific or adaptive immune defense and the unspecific innate immune defense. Vaccination is utilized against specific bacteria via the adaptive immune system. The innate immunity DNA stress defense is a non-toxic mechanism developed in yeasts and conserved in mammals and in plants. Although the steroidal hormone cascade has overtaken the stress response and allows superfast response via non-genomic receptors, the old innate immunity response is still mediated via the steroidal hormones cascade. The classical drug/receptor model has provided for many solutions, however, in antibiotics, cancer, and in severe mental diseases this model reaches to certain limits. The NIH/Department of Mental Health has developed a new model that shows severe mental diseases may be immune diseases that can be treated by replacing old diseased nerve cells by new healthy nerve cells, where the old innate immunity may be exploited. This means that severe mental diseases are physical diseases. A newly developed model, where modifications of the steroidal hormone cascade help to understand bipolarity, schizophrenia, and PTSD in men and women can be transferred to gynecological hormone modifications in women, where innate immunity is mediated via the same steroidal hormone cascade. Treatment via immune response via the DNA cascade should be developed in cancer, infections and severe mental disease, because foreign cells or diseased cells may be removed by the unspecific innate immunity.


The auto segmentation for cardiac structures using a dual-input deep learning network based on vision saliency and transformer.
Accurate segmentation of cardiac structures on coronary CT angiography (CCTA) images is crucial for the morphological analysis, measurement, and functional evaluation. In this study, we achieve accurate automatic segmentation of cardiac structures on CCTA image by adopting an innovative deep learning method based on visual attention mechanism and transformer network, and its practical application value is discussed. We developed a dual-input deep learning network based on visual saliency and transformer (VST), which consists of self-attention mechanism for cardiac structures segmentation. Sixty patients' CCTA subjects were randomly selected as a development set, which were manual marked by an experienced technician. The proposed vision attention and transformer mode was trained on the patients CCTA images, with a manual contour-derived binary mask used as the learning-based target. We also used the deep supervision strategy by adding auxiliary losses. The loss function of our model was the sum of the Dice loss and cross-entropy loss. To quantitatively evaluate the segmentation results, we calculated the Dice similarity coefficient (DSC) and Hausdorff distance (HD). Meanwhile, we compare the volume of automatic segmentation and manual segmentation to analyze whether there is statistical difference. Fivefold cross-validation was used to benchmark the segmentation method. The results showed the left ventricular myocardium (LVM, DSC = 0.87), the left ventricular (LV, DSC = 0.94), the left atrial (LA, DSC = 0.90), the right ventricular (RV, DSC = 0.92), the right atrial (RA, DSC = 0.91), and the aortic (AO, DSC = 0.96). The average DSC was 0.92, and HD was 7.2 ± 2.1 mm. In volume comparison, except LVM and LA (p < 0.05), there was no significant statistical difference in other structures. Proposed method for structural segmentation fit well with the true profile of the cardiac substructure, and the model prediction results closed to the manual annotation. The adoption of the dual-input and transformer architecture based on visual saliency has high sensitivity and specificity to cardiac structures segmentation, which can obviously improve the accuracy of automatic substructure segmentation. This is of gr.


The effect of mobile text messages on knowledge and perception towards cancer and behavioral risks among college students, Northeast Ethiopia: A randomized controlled trial protocol.
Cancer is an emerging public health problem in Ethiopia. A significant proportion of premature cancer deaths are preventable. The socioeconomic impact of cancer can be considerably reduced provided that effective interventions are put in place to control risk factors. Text-messaging has been currently targeted as a simple and efficient tool for providing people with health information. To evaluate the effectiveness of mobile text messages in improving knowledge and perception on cancer and behavioral risks among college students. Design: a single-blind, 2-arm randomized controlled trial will be used. Setting: the study will be conducted among public colleges in Dessie town, Northeast Ethiopia. Study population: students who are studying in all public colleges. Intervention: a text message related to cancer risk factors once a day for two months. Control groups will receive general health messages daily for two months. Data: Socioeconomic characteristics, health belief variables, and behavioral risk factors of cancer will be collected before and after the intervention. Text messages will be provided based on the health belief model (HBM). Primary outcomes: cancer risk knowledge score and risk perception will be measured at baseline and 6 months post-randomization. Secondary outcomes: a change in mean healthy diet score, physical activity level, alcohol intake, and tobacco use will be measured at baseline-, 3, and 6 months post-randomization. Analysis: We will compute descriptive statistics for each outcome pre and post-intervention. To test the change in knowledge and perception, paired t-test will be used. Analysis of Covariance will be used to test over group comparison. ClinicalTrials.gov (https://register.clinicaltrials.gov) NCT04269018.


Going into town or staying home: Rural patient experience and preference with home-based versus clinic-based telehealth.
Telehealth is a model of care with potential to improve access, and in turn outcomes, for people living in rural areas. Since 2013, our endocrine clinic-based telehealth program has provided care at rural community hospitals in Nebraska and Iowa. At the start of the COVID-19 pandemic, when regulations around telehealth were adjusted, patients previously seen via clinic-based telehealth had the option to continue clinic-based visits or have a home-based telehealth visit. There is no literature comparing patient experiences between home-based and clinic-based telehealth. The purpose of this study was to understand rural patient preferences regarding endocrinology home-based versus clinic-based telehealth visits. This was a survey study of adult, rural patients who experienced both a clinic-based and home-based telehealth visit with their established endocrinology provider. Respondents were asked about demographics, their reason for visit, preference for home versus clinic-based telehealth, and how they would have received care if telehealth were not an option. Forty-two patients (40.8%) responded to the survey, with 27 patients (64.3%) preferring home-based telehealth. There were no significant differences between the groups. However, 47.5% of patients would not have sought specialty care if telehealth were not an option. This survey of endocrine patients experienced in both clinic-based and home-based telehealth indicates that, while most respondents preferred home-based telehealth, there are distinct advantages to each model and patients appreciate having options. We believe it is important to maintain both lines of service to provide patient-centered care and improve access to specialty care.


Responses to the Acupuncture Trialists' Collaboration individual patient data meta-analysis.
In September 2012 the Acupuncture Trialists' Collaboration published the results of an individual patient data meta-analysis of almost 18 000 patients in high quality randomised trials. The results favoured acupuncture. Although there was little argument about the findings in the scientific press, a controversy played out in blog posts and the lay press. This controversy was characterised by ad hominem remarks, anonymous criticism, phony expertise and the use of opinion to contradict data, predominantly by self-proclaimed sceptics. There was a near complete absence of substantive scientific critique. The lack of any reasoned debate about the main findings of the Acupuncture Trialists' Collaboration paper underlines the fact that mainstream science has moved on from the intellectual sterility and ad hominem attacks that characterise the sceptics' movement.