Offering an Off-Label Therapeutic Algorithm for Lichen Planus.
Lichen planus (LP) is a poorly characterized, chronic inflammatory dermatosis notable for violaceous to brown/ black polygonal pruritic papules and plaques, often with lacey scale, and reticular white erosions involving mucosal sites.


Effects of Isolated and Combined Exposure of the Brain and Lungs to a Laser-Induced Shock Wave(s) on Physiological and Neurological Responses in Rats.
Blast-induced traumatic brain injury (bTBI) has been suggested to be caused by direct head exposure and by torso exposure to a shock wave (thoracic hypotheses). It is unclear, however, how torso exposure affects the brain in real time. This study applied a mild-impulse laser-induced shock wave(s) (LISW[s]) only to the brain (Group 1), lungs (Group 2), or to the brain and lungs (Group 3) in rats. Because LISWs are unaccompanied by a dynamic pressure in principle, the effects of acceleration can be excluded, allowing analysis of the pure primary mechanism (the effects of a shock wave). For all rat groups, real-time monitoring of the brain and systemic responses were conducted for up to 1 h post-exposure and motor function assessments for up to seven days post-exposure. As reported previously, brain exposure alone caused cortical spreading depolarization (CSD), followed by long-lasting hypoxemia and oligemia in the cortices (Group 1). It was found that even LISW application only to the lungs caused prolonged hypoxemia and mitochondrial dysfunction in the cortices (Group 2). Importantly, features of CSD and mitochondrial dysfunction were significantly exacerbated by combined exposure (Group 3) compared with those caused by brain exposure alone (Group 1). Motor dysfunction was observed in all exposure groups, but their time courses differed depending on the groups. Rats with brain exposure alone exhibited the most evident motor dysfunction at one day post-exposure, and after that, it did not change much for up to seven days post-exposure. Alternatively, two groups of rats with lung exposure (Group 2 and Group 3) exhibited continuously aggravated motor functions for up to seven days post-exposure, suggesting different mechanisms for motor dysfunction caused by brain exposure and that caused by lung exposure. As for the reported thoracic hypotheses, our observations seem to support the volumetric blood surge and vagovagal reflex. Overall, the results of this study indicate the importance of the torso guard to protect the brain and its function.


Aerosol composition and properties variation at the ground and over the column under different air masses advection in South Italy.
Aerosol composition and properties variation under the advection of different air masses were investigated, as case studies, by contemporary measurements over the atmospheric column and at the ground in a semi-rural site in South Italy. The absence of local strong sources in this area allowed to characterize background aerosol and to compare particle mixing effects under various atmospheric circulation conditions. Aerosol optical depth (AOD) and Ǻngström parameters from radiometric measurements allowed the detection and identification of polluted, dust, and volcanic atmospheric conditions. AODs were the input for a suitable model to evaluate the columnar aerosol composition, according to six main atmospheric components (water-soluble, soot, sea salt accumulation, sea salt coarse, mineral dus,t and biological). Scanning electron microscope (SEM) analysis of particulate sampled with a 13-stage impactor at the ground showed not only fingerprints typical of the different air masses but also the effects of transport and aging on atmospheric particles, suggesting processes that changed their chemical and optical properties. Background columnar aerosol was characterized by 72% of water-soluble and soot, in agreement with ground-based findings that highlighted 60% of contribution from anthropogenic carbonate particles and soot. In general, a good agreement between ground-based and columnar results was observed. Under the advection of trans-boundary air masses, water-soluble and soot were always present in columnar aerosol, whereas, in variable percentages, sea salt and mineral particles characterized both dust and volcanic conditions. At the ground, sulfates characterized the amorphous matrix produced in finer stages by the evaporation of solutions of organic and inorganic aerosols. Sulfates were also one of the key players involved in heterogeneous chemical reactions, producing complex secondary aerosol, as such clay-sulfate internally mixed particle externally mixed with soot chains.


Future patterns of dental care--manpower implications for industrialised countries.
After a century of increasing dental caries levels there have been dramatic reductions in dental caries and periodontal disease in the past 15 years in most industrialised countries.


Formaldehyde scavengers function as novel antigen retrieval agents.
Antigen retrieval agents improve the detection of formaldehyde-fixed proteins, but how they work is not well understood. We demonstrate that formaldehyde scavenging represents a key characteristic associated with effective antigen retrieval; under controlled temperature and pH conditions, scavenging improves the typical antigen retrieval process through reversal of formaldehyde-protein adduct formation. This approach provides a rational framework for the identification and development of more effective antigen retrieval agents.


Improvement of abnormal vaginal flora in Ugandan women by self-testing and short use of intravaginal antimicrobials.
The vaginal composition of African women is more often lactobacillus-deficient compared to that of women from other areas around the world. Lactobacillus-deficient microflora is a known risk factor for serious health problems, such as preterm birth, cervix cancer, and entrapment of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). The aim of this study was to assess the effect of local vaginal antibiotic or antiseptic treatment on abnormal vaginal flora (AVF), aerobic vaginitis (AV), and bacterial vaginosis (BV) among women in rural, semi-urban, and urban areas in Uganda, as compared to placebo. In a double-blind, placebo-controlled, randomized trial, 300 women presenting for outpatient routine, follow-up, or medical care at Mulago Hospital in Kampala, Uganda, were enrolled to receive 6 days of treatment with vaginal rifaximin (RFX), dequalinium chloride (DQC), or placebo if they had an increased vaginal pH of >4.5 as determined by self-testing. At initial visit and at control visit after 4 weeks, a smear was taken for blinded wet mount microscopy to determine AVF, BV, AV, and Candida severity scores. As compared to placebo, both RFX or DQC treatments dramatically diminished BV prevalence and severity from the initial to follow-up visit: the BV score declined from 2.5 to 1.6 (p < 0.0001) and from 2.5 to 1.9 (p < 0.0001), respectively. Similarly, strong improvements in the AV score were seen in both treatment regimens: moderate and severe AV declined from AV scores of 6.3 to 3.6 (p = 0.003) and from 6.6 to 4.1 (p < 0.004), respectively. Also, women with AVF (deceased or absent lactobacilli) showed similar improvements when compared with placebo. Women with normal flora and Candida at the initial visit showed less Candida after 4 weeks in the group treated with DQC (p = 0.014). Even after a short duration of intravaginal treatment with local non-absorbable antiseptics or antibiotics produced significant, lasting improvements in the vaginal microbiome composition of women with disturbed vaginal microflora. As African women have high prevalences of BV, AV, and AVF, this approach could improve their odds to prevent health-compromising complications. Further studies assessing direct health outcomes are needed to substantiate this.


VYC-12 Injectable Gel Is Safe And Effective For Improvement Of Facial Skin Topography: A Prospective Study.
Evaluate safety and effectiveness of VYC-12 (Juvéderm Volite; an injectable crosslinked hyaluronic acid gel designed to improve skin quality attributes such as surface smoothness and hydration) for facial intradermal injection. In a prospective, single-arm study, subjects with moderate/severe cheek skin roughness per Allergan Skin Roughness Scale (ASRS) received VYC-12 in the cheeks and forehead, and/or neck, with touch-up treatment to correct asymmetry 30 days later and optional repeat treatment 9 months after last treatment. The primary effectiveness measure was ASRS responder rate (percentage of cheeks with ≥1-point improvement from baseline) at month 1. Skin hydration was instrument-assessed. Of 131 subjects treated, 31 (23.7%) received touch-up treatment. ASRS responder rate was 96.2% at month 1, 76.3% at month 4, 34.9% at month 6, and 87.1% after repeat treatment. Responder rate in cheeks with severe baseline roughness was 93.8%, 83.1%, and 52.3% at months 1, 4, and 6, respectively. Skin hydration improved significantly (P<0.01) from baseline at all timepoints through month 9. Injection site responses were as expected. All treatment-related adverse events were mild/moderate. VYC-12 safely and effectively improved skin smoothness up to 6 months and hydration lasting 9 months.


Full-length structural model of RET3 and SEC21 in COPI: identification of binding sites on the appendage for accessory protein recruitment motifs.
COPI, a 600 kD heptameric complex (consisting of subunits α, β, γ, δ, ε, ζ, and β') "coatomer," assembles non-clathrin-coated vesicles and is responsible for intra-Golgi and Golgi-to-ER protein trafficking. Here, we report the three-dimensional structures of the entire sequences of yeast Sec21 (γ-COPI mammalian ortholog), yeast Ret3 (ζ-COPI mammalian ortholog), and the results of successive molecular dynamics investigations of the subunits and assembly based on a protein-protein docking experiment. The three-dimensional structures of the subunits in their complexes indicate the residues of the two subunits that impact on assembly, the conformations of Ret3 and Sec21, and their binding orientations in the complexed state. The structure of the appendage domain of Sec21, with its two subdomains--the platform and the β-sandwich, was investigated to explore its capacity to bind to accessory protein recruitment motifs. Our study shows that a binding site on the platform is capable of binding the Eps15 DPF and epsin DPW2 peptides, whereas the second site on the platform and the site on the β-sandwich subdomain were found to selectively bind to the amphiphysin FXDXF and epsin DPW1 peptides, respectively. Identifying the regions of both the platform and sandwich subdomains involved in binding each peptide motif clarifies the mechanism through which the appendage domain of Sec21 engages with the accessory proteins during the trafficking process of non-clathrin-coated vesicles.


A recurrent longitudinally extensive transverse myelitis with Aquaporin-4(AQP4) antibody after herpes zoster.
Longitudinally extensive transverse myelitis (LETM) is a syndrome that involves three or more vertebral segments in the spinal cord lesion, and it is one of the characteristic features of neuromyelitis optica (NMO) differentiating it from multiple sclerosis. Many studies proved the importance of aquaporin-4 (AQP4) antibody, which plays a vital role in the pathogenesis of NMO. Recent reports suggest that recurrent LETM patients with positive anti-AQP4 antibody titers have a higher chance of converting to NMO, and they are now termed as NMO spectrum disorders (NMOSD). The specific role of AQP4 antibody in NMO is yet to be elucidated but there are reports to bring up the pathogenesis in relation with infectious events. Interestingly, parainfectious NMOSD tends to spare the optic nerve unlike classic NMOSD. Here we report a young woman who was once diagnosed as herpes zoster-related LETM, but later developed as recurrent LETM with positive AQP4 antibody titers, which renders the diagnosis of parainfectious LETM without optic neuritis.


A simple and efficient method to quantify the cell parameters of the seed coat, embryo and silique wall in rapeseed.
Researchers interested in the seed size of rapeseed need to quantify the cell size and number of cells in the seed coat, embryo and silique wall. Scanning electron microscope-based methods have been demonstrated to be feasible but laborious and costly. After image preparation, the cell parameters are generally evaluated manually, which is time consuming and a major bottleneck for large-scale analysis. Recently, two machine learning-based algorithms, Trainable Weka Segmentation (TWS) and Cellpose, were released to overcome this long-standing problem. Moreover, the MorphoLibJ and LabelsToROIs plugins in Fiji provide user-friendly tools to deal with cell segmentation files. We attempted to verify the practicability and efficiency of these advanced tools for various types of cells in rapeseed. We simplified the current image preparation procedure by skipping the fixation step and demonstrated the feasibility of the simplified procedure. We developed three methods to automatically process multicellular images of various tissues in rapeseed. The TWS-Fiji (TF) method combines cell detection with TWS and cell measurement with Fiji, enabling the accurate quantification of seed coat cells. The Cellpose-Fiji (CF) method, based on cell segmentation with Cellpose and quantification with Fiji, achieves good performance but exhibits systematic error. By removing border labels with MorphoLibJ and detecting regions of interest (ROIs) with LabelsToROIs, the Cellpose-MorphoLibJ-LabelsToROIs (CML) method achieves human-level performance on bright-field images of seed coat cells. Intriguingly, the CML method needs very little manual calibration, a property that makes it suitable for massive-scale image processing. Through a large-scale quantitative evaluation of seed coat cells, we demonstrated the robustness and high efficiency of the CML method at both the single-cell level and the sample level. Furthermore, we extended the application of the CML method to developing seed coat, embryo and silique wall cells and acquired highly precise and reliable results, indicating the versatility of this method for use in multiple scenarios. The CML method is highly accurate and free of the need for manual correction. Hence, it can be applied for the low-cost, high-throughput quantification of diverse cell types in rapeseed with high efficiency. We envision that this method will facilitate the functional genomics and microphenomics studies of rapeseed and other crops.


The non-gastric H,K-ATPase is oligomycin-sensitive and can function as an H+,NH4(+)-ATPase.
We used the baculovirus/Sf9 expression system to gain new information on the mechanistic properties of the rat non-gastric H,K-ATPase, an enzyme that is implicated in potassium homeostasis. The alpha2-subunit of this enzyme (HKalpha2) required a beta-subunit for ATPase activity thereby showing a clear preference for NaKbeta1 over NaKbeta3 and gastric HKbeta. NH4(+), K+, and Na+ maximally increased the activity of HKalpha2-NaKbeta1 to 24.0, 14.2, and 5.0 micromol P(i) x mg(-1) protein x h(-1), respectively. The enzyme was inhibited by relatively high concentrations of ouabain and SCH 28080, whereas it was potently inhibited by oligomycin. From the phosphorylation level in the presence of oligomycin and the maximal NH4(+)-stimulated ATPase activity, a turnover number of 20,000 min(-1) was determined. All three cations decreased the steady-state phosphorylation level and enhanced the dephosphorylation rate, disfavoring the hypothesis that Na+ can replace H+ as the activating cation. The potency with which vanadate inhibited the cation-activated enzyme decreased in the order K+ > NH4(+) > Na+, indicating that K+ is a stronger E2 promoter than NH4(+), whereas in the presence of Na+ the enzyme is in the E1 form. For K+ and NH4(+), the E2 to E1 conformational equilibrium correlated with their efficacy in the ATPase reaction, indicating that here the transition from E2 to E1 is rate-limiting. Conversely, the low maximal ATPase activity with Na+ is explained by a poor stimulatory effect on the dephosphorylation rate. These data show that NH4(+) can replace K+ with similar affinity but higher efficacy as an extracellular activating cation in rat nongastric H,K-ATPase.


Continuous Monitoring of Blood Pressure and Vascular Hemodynamic Properties With Miniature Extravascular Hall-Based Magnetic Sensor.
Continuous measurement of vascular and hemodynamic parameters could improve monitoring of disease progression and enable timely clinical decision making and therapy surveillance in patients suffering from cardiovascular diseases. However, no reliable extravascular implantable sensor technology is currently available. Here, we report the design, characterization, and validation of an extravascular, magnetic flux sensing device capable of capturing the waveforms of the arterial wall diameter, arterial circumferential strain, and arterial pressure without restricting the arterial wall. The implantable sensing device, comprising a magnet and a magnetic flux sensing assembly, both encapsulated in biocompatible structures, has shown to be robust, with temperature and cyclic-loading stability. Continuous and accurate monitoring of arterial blood pressure and vascular properties was demonstrated with the proposed sensor in vitro with a silicone artery model and validated in vivo in a porcine model mimicking physiologic and pathologic hemodynamic conditions. The captured waveforms were further used to deduce the respiration frequency, the duration of the cardiac systolic phase, and the pulse wave velocity. The findings of this study not only suggest that the proposed sensing technology is a promising platform for accurate monitoring of arterial blood pressure and vascular properties, but also highlight the necessary changes in the technology and the implantation procedure to allow the translation of the sensing device in the clinical setting.


Effect of NGF on in vitro preformed microtubules. Evidence for a protective action against vinblastine.
The nerve growth factor protein (NGF) induces organization of in vitro preformed microtubules (MTs) to form multiple arrays. These complexes, in cross-section, appear to be formed by clusters of single tubules in parallel in close contact with center distance similar to the diameter of a microtubule. In the absence of NGF, on the contrary, microtubules are far apart from each other. Addition of vinblastine to NGF-MT complexes does not result in the usual reorganization of microtubules into paracrystalline arrays, noticeable when the growth factor is not present. The vinblastine treated NGF-MT complexes have several round-shaped elements along the tubules and at their endings which, at higher magnification, appear to be formed by closely packed, ring-like structures. These 'boutons' are postulated to represent the point of resistance to the depolymerizing action of the vinca alkaloid. These findings are discussed in relation to a similar antagonistic effect observed in vivo between NGF and vinblastine and to the possible involvement of microtubules in the mechanism of action of the growth factor.


Pitfalls related to the use of endostaplers during video-assisted thoracic surgery.
The use of staplers during thoracoscopic pulmonary resections has entailed several incidents. This study aimed to evaluate the rate of adverse events related to the use of an endostapler during video-assisted thoracic surgery (VATS). All thoracoscopic procedures involving the use of an endostapler were prospectively studied. The study was based on the analysis of data prospectively entered into a database and the review of videotapes recorded during the procedure. The video clip of each incident was included into the database. The following events were recorded: oozing or hemorrhage on the staple line, partial or total disruption of the staple line, and any other technical issue. A total of 434 firings were made during 130 thoracoscopic operations. The operations involved 77 wedge resections of lung nodules, 11 pulmonary biopsies, 34 bullectomies, and 8 thoracoscopic lobectomies. Although firing was uneventful for most patients, a minor or major problem was encountered during 34 firings (7.6%). Two technical malfunctions of the device occurred, both of them noticed by the scrub nurse before introduction of the stapler into the trocar. The other pitfalls were oozing (13 cases) and active hemorrhages (5 cases) on the staple line and disruption of the staple line, either partial (13 cases) or total (1 case). Conversion to thoracotomy was never necessary. Whereas no specific action was imposed by the pitfall in 12 cases, the incident led to a repair in 22 cases. None of the incidents had a clinical consequence in the postoperative course. The video tapes were reviewed to check whether the accident was unpredictable or due the surgeon's misuse or misjudgment. In 14 cases, no cause was found. In 5 cases, the lung parenchyma probably was too thick for the staples chosen, whereas no technical error was found in the remaining 15 cases. Although some adverse events are attributable to surgical errors, many are linked to the device. This underscores the need for improving staplers and evaluating new technologies.


Spatial variations of dimethylsulfide and dimethylsulfoniopropionate in the surface microlayer and in the subsurface waters of the South China Sea during springtime.
Spatial variations in dimethylsulfide (DMS) and dimethylsulfoniopropionate (DMSP) were surveyed in the surface microlayer and in the subsurface waters of the low productivity South China Sea in May 2005. Overall, average subsurface water concentrations of DMS and DMSP of dissolved (DMSPd) and particulate (DMSPp) fractions were 1.74 (1.00-2.50), 3.92 (2.21-6.54) and 6.06 (3.40-8.68) nM, respectively. No enrichment in DMS and DMSPp was observed in the microlayer. In contrast, the microlayer showed a DMSPd enrichment, with an average enrichment factor (EF, defined as the ratio of the microlayer concentration to subsurface water concentration) of 1.40. In the study area, none of the sulfur components were correlated with chlorophyll a. An important finding in this study was that DMS, DMSP and chlorophyll a concentrations in the surface microlayer were respectively correlated with those in the subsurface water, suggesting a close linkage between these two water bodies. The ratios of DMS:Chl-a and DMSPp:Chl-a showed a gradually increasing trend from North to South. This might be due to changes in the proportion of DMSP producers in the phytoplankton community with the increased surface seawater temperature. A clear diurnal variation in the DMS and DMSP concentrations was observed at an anchor station with the highest concentrations appearing during the day and the lowest concentrations during the night. The higher DMS and DMSP concentrations during daytime might be attributed to the light-induced increase in both algal synthesis and exudation of DMSP and biological production of DMS. The mean flux of DMS from the investigated area to the atmosphere was estimated to be 2.06 micromo lm(-2)d(-1). This low DMS emission flux, together with the low DMS surface concentrations was attributed to the low productivity in this sea.


Model-based design space determination of peptide chromatographic purification processes.
Operating a chemical process at fixed operating conditions often leads to suboptimal process performances. It is important in fact to be able to vary the process operating conditions depending upon possible changes in feed composition, products requirements or economics. This flexibility in the manufacturing process was facilitated by the publication of the PAT initiative from the U.S. FDA [1]. In this work, the implementation of Quality-by-design in the development of a chromatographic purification process is discussed. A procedure to determine the design space of the process using chromatographic modeling is presented. Moreover, the risk of batch failure and the critical process parameters (CPP) are assessed by modeling. The ideal cut strategy is adopted and therefore only yield and productivity are considered as critical quality attributes (CQA). The general trends in CQA variations within the design space are discussed. The effect of process disturbances is also considered. It is shown that process disturbances significantly decrease the design space and that only simultaneous and specific changes in multiple process parameters (i.e. critical process parameters (CPP) lead to batch failure. The reliability of the obtained results is proven by comparing the model predictions to suitable experimental data. The case study presented in this work proves the reliability of process development using a model-based approach.


Fighting the infodemic: the 4 i Framework for Advancing Communication and Trust.
The proliferation of false and misleading health claims poses a major threat to public health. This ongoing "infodemic" has prompted numerous organizations to develop tools and approaches to manage the spread of falsehoods and communicate more effectively in an environment of mistrust and misleading information. However, these tools and approaches have not been systematically characterized, limiting their utility. This analysis provides a characterization of the current ecosystem of infodemic management strategies, allowing public health practitioners, communicators, researchers, and policy makers to gain an understanding of the tools at their disposal. A multi-pronged search strategy was used to identify tools and approaches for combatting health-related misinformation and disinformation. The search strategy included a scoping review of academic literature; a review of gray literature from organizations involved in public health communications and misinformation/disinformation management; and a review of policies and infodemic management approaches from all U.S. state health departments and select local health departments. A team of annotators labelled the main feature(s) of each tool or approach using an iteratively developed list of tags. We identified over 350 infodemic management tools and approaches. We introduce the 4 i Framework for Advancing Communication and Trust (4 i FACT), a modified social-ecological model, to characterize different levels of infodemic intervention: informational, individual, interpersonal, and institutional. Information-level strategies included those designed to amplify factual information, fill information voids, debunk false information, track circulating information, and verify, detect, or rate the credibility of information. Individual-level strategies included those designed to enhance information literacy and prebunking/inoculation tools. Strategies at the interpersonal/community level included resources for public health communicators and community engagement approaches. Institutional and structural approaches included resources for journalists and fact checkers, tools for managing academic/scientific literature, resources for infodemic researchers/research, resources for infodemic managers, social media regulation, and policy/legislation. The 4 i FACT provides a useful way to characterize the current ecosystem of infodemic management strategies. Recognizing the complex and multifaceted nature of the ongoing infodemic, efforts should be taken to utilize and integrate strategies across all four levels of the modified social-ecological model.


TEMPS-I: delineating the most discriminant traits of the cyclothymic, depressive, hyperthymic and irritable temperaments in a nonpatient population.
Although most personality constructs have been standardized in population studies, cyclothymic, depressive, irritable and hyperthymic temperaments putatively linked to mood disorders have been classically derived from clinical observations. We therefore administered the semi-structured affective temperament schedule of Memphis, Pisa, Paris and San Diego, Interview version (TEMPS-I) -- in its original University of Tennessee operationalization -- to 1010 Italian students aged between 14 and 26. The interview, administered in a randomized format, took 20 min per subject. The semi-structured interview was easy to administer and well accepted by subjects, with no refusals. Principal component analysis with varimax rotation confirmed the hypothesized four-dimensional factor structure of the interview, with good to excellent internal consistency. Furthermore, discriminant analysis and multiple regression provided suggestions for identifying the traits that are most useful in defining a weighted cut-off for each of the temperaments (and which, with minor exceptions, are in agreement with those previously proposed on clinical grounds). In an additional exploratory factorial analysis, a depressive type which loads negatively on hyperthymia was distinguished from cyclothymia; the irritable temperament did not appear to have significant loading on either factor. All the present analyses were internal to the scale itself, but ongoing studies are comparing them with other systems of temperament as well as testing their clinical cogency for affectively ill populations. While more work needs to be done on better operationalization of the irritable temperament, our findings overall support the existence -- in a relatively young nonpatient population -- of cyclothymic, depressive and hyperthymic types according to the classic descriptions of Kraepelin, Kretschmer and Schneider, in their TEMPS-I operationalization. Coupled with a previous report identifying 10% of the same 14-26-year-old nonpatient population meeting an empirically defined statistical cut-off for these temperaments, the present data define the putative 'fundamental states' that Kraepelin considered to be the personal predisposing anlagé of major affective disorders.


Targeting integrin αvβ3 with indomethacin inhibits patient-derived xenograft tumour growth and recurrence in oesophageal squamous cell carcinoma.
A high risk of post-operative recurrence contributes to the poor prognosis and low survival rate of oesophageal squamous cell carcinoma (ESCC) patients. Increasing experimental evidence suggests that integrin adhesion receptors, in particular integrin αv (ITGAV), are important for cancer cell survival, proliferation and migration. Therefore, targeting ITGAV may be a rational approach for preventing ESCC recurrence. Protein levels of ITGAV were determined in human ESCC tumour tissues using immunohistochemistry. MTT, propidium iodide staining, and annexin V staining were utilized to investigate cell viability, cell cycle progression, and induction of apoptosis, respectively. Computational docking was performed with the Schrödinger Suite software to visualize the interaction between indomethacin and ITGAV. Cell-derived xenograft mouse models, patient-derived xenograft (PDX) mouse models, and a humanized mouse model were employed for in vivo studies. ITGAV was upregulated in human ESCC tumour tissues and increased ITGAV protein levels were associated with poor prognosis. ITGAV silencing or knockout suppressed ESCC cell growth and metastatic potential. Interestingly, we identified that indomethacin can bind to ITGAV and enhance synovial apoptosis inhibitor 1 (SYVN1)-mediated degradation of ITGAV. Integrin β3, one of the β subunits of ITGAV, was also decreased at the protein level in the indomethacin treatment group. Importantly, indomethacin treatment suppressed ESCC tumour growth and prevented recurrence in a PDX mouse model. Moreover, indomethacin inhibited the activation of cytokine TGFβ, reduced SMAD2/3 phosphorylation, and increased anti-tumour immune responses in a humanized mouse model. ITGAV is a promising therapeutic target for ESCC. Indomethacin can attenuate ESCC growth through binding to ITGAV, promoting SYVN1-mediated ubiquitination of ITGAV, and potentiating cytotoxic CD8+ T cell responses.


[Cloverleaf skull. Presentation of three cases].
Three patients who presented cloverleaf skull are described. The first one associated with tanatophoric dwarfism, the second case was an isolate anomaly and the third one was associated with facial fissures. The three patients showed the outstanding diversity of the clinic manifestations encountered in this entity. The findings at central nervous system level, by computarized tomographic and ultrasonographic studies, are described. The relevance of genetic counselling is emphasized.


Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product.
The dbl oncogene product contains a 238-amino acid domain, which is shared by an expanding family of growth regulatory proteins. These include the Saccharomyces cerevisiae cell division cycle protein, CDC24, the breakpoint cluster region protein, the ect2 and vav oncogene products, and the brain GDP-releasing factor for Ras. Previous studies have provided evidence that oncogenic Dbl or an associated protein stimulates GDP dissociation from the human species (Hs) homolog of CDC42. We show here that Dbl specifically complexes with the GDP-bound forms of CDC42Hs and RhoA, but not Rac1 or TC10, and that this specificity correlates with the ability of Dbl to act as a GDP-releasing factor. Small deletions throughout the Dbl domain, which inactivate transformation, eliminated the ability of Dbl to stimulate GDP dissociation, whereas deletions outside of this domain did not impair either function. Finally, the Dbl domain itself, when expressed and purified as a recombinant protein, was shown to stimulate GDP dissociation from purified, recombinant CDC42Hs. These findings establish that a minimal unit on Dbl that is critical to its transforming function directly regulates GDP-GTP exchange activity.


Efficiency improvement in proton dose calculations with an equivalent restricted stopping power formalism.
The equivalent restricted stopping power formalism is introduced for proton mean energy loss calculations under the continuous slowing down approximation. The objective is the acceleration of Monte Carlo dose calculations by allowing larger steps while preserving accuracy. The fractional energy loss per step length ϵ was obtained with a secant method and a Gauss-Kronrod quadrature estimation of the integral equation relating the mean energy loss to the step length. The midpoint rule of the Newton-Cotes formulae was then used to solve this equation, allowing the creation of a lookup table linking ϵ to the equivalent restricted stopping power L eq, used here as a key physical quantity. The mean energy loss for any step length was simply defined as the product of the step length with L eq. Proton inelastic collisions with electrons were added to GPUMCD, a GPU-based Monte Carlo dose calculation code. The proton continuous slowing-down was modelled with the L eq formalism. GPUMCD was compared to Geant4 in a validation study where ionization processes alone were activated and a voxelized geometry was used. The energy straggling was first switched off to validate the L eq formalism alone. Dose differences between Geant4 and GPUMCD were smaller than 0.31% for the L eq formalism. The mean error and the standard deviation were below 0.035% and 0.038% respectively. 99.4 to 100% of GPUMCD dose points were consistent with a 0.3% dose tolerance. GPUMCD 80% falloff positions ([Formula: see text]) matched Geant's [Formula: see text] within 1 μm. With the energy straggling, dose differences were below 2.7% in the Bragg peak falloff and smaller than 0.83% elsewhere. The [Formula: see text] positions matched within 100 μm. The overall computation times to transport one million protons with GPUMCD were 31-173 ms. Under similar conditions, Geant4 computation times were 1.4-20 h. The L eq formalism led to an intrinsic efficiency gain factor ranging between 30-630, increasing with the prescribed accuracy of simulations. The L eq formalism allows larger steps leading to a [Formula: see text] algorithmic time complexity. It significantly accelerates Monte Carlo proton transport while preserving accuracy. It therefore constitutes a promising variance reduction technique for computing proton dose distributions in a clinical context.


Mitochondrial DNA genetic diversity of black muntjac (Muntiacus crinifrons), an endangered species endemic to China.
Genetic diversities based on the mtDNA control region were measured for both a wild population (n = 26) and a captive population (n = 18) of the black muntjac. In total, nine haplotypes were obtained from 44 samples. The wild population exhibited a low nucleotide diversity (pi = 0.00562), which suggests that the black muntjac had a small effective population size historically. In contrast to its low nucleotide diversity, haplotype diversity (h = 0.862) of the wild population was relatively high. Haplotype distribution among local samples shows a distinct difference. As anticipated because of the paucity of available founders, nucleotide diversity (pi = 0.00214) of the captive population was very low. Additionally, a high degree of haplotype identity and an obvious haplotype frequency bias was revealed in the captive population, which implies that the current breeding program should be readjusted to balance distributions of haplotypes, and some new founders should be introduced to the captive population to alleviate potential inbreeding depression.


Stable isotope ratios and mercury levels in red meat products from baleen whales sold in Japanese markets.
We analyzed the δ(13)C, δ(15)N and δ(18)O values and Hg concentration in red meat products originating from the predominant types sold in Japan for human consumption: two populations of common minke (J- and O-types), Bryde's and sei whales in the western North Pacific Ocean, and fin and Antarctic minke whales in the Southern Ocean. The order of the trophic positions, evaluated by δ(15)N values and Hg concentrations, coincided with their known feeding habits: common minke (J-type)=common minke (O-type)> Bryde's ≥ sei ≥ Antarctic minke ≥ fin. The Hg concentrations in the combined samples from the six samples were significantly correlated with their δ(15)N values (γ=0.455, n=66, p<0.05), reflecting overall differences in the trophic level. This correlation was not significant for within-species comparison for the common minke (J- and O-types) or the Bryde's whale, probably reflecting the higher δ(15)N value and lower Hg concentration in the North Pacific Ocean around Japan. Determination of δ(13)C, δ(15)N and δ(18)O could be used to discriminate between the red meat products originating from the whale species in the North Pacific and Southern Oceans. However, the four whale species or populations in the Pacific Ocean could not be discriminated on basis of these values, nor could the two species in the Southern Ocean. Positive correlations between the δ(13)C and δ(15)N values and negative correlations between the δ(15)N and δ(18)O values and the δ(13)C and δ(18)O values, probably reflecting migration patterns, were found in some whale species in the North Pacific and Southern Oceans.


Composition of proteoglycans from human atherosclerotic lesions.
Proteoglycans from human atherosclerotic lesions and from uninvolved aortic intima were isolated and their composition was studied. The tissues were sequentially extracted by guanidine hydrochloride followed by hydrolysis of the tissue by elastase. Chondroitin sulfate/dermatan sulfate proteoglycans were predominant in guanidine hydrochloride extracts of the tissue. Most of the heparan sulfate proteoglycans were released from the tissue by hydrolysis with elastase. The content of proteoglycan material, measured as uronate per unit weight of wet tissue, was lower in fatty streaks and fibrous plaques than in uninvolved tissue (0.58 and 0.48 mg vs. 0.7 mg/g wet tissue). The distribution of different glycosaminoglycans in guanidine hydrochloride-extracted proteoglycans was similar among the lesions and uninvolved tissue, but varied in the elastase-hydrolyzed extracts. Gel filtration studies suggested that the major proteoglycan material, chondroitin sulfate proteoglycans, from lesions had greater molecular weight than proteoglycans from uninvolved tissue. The studies indicate that alteration in intrinsic composition and molecular size of proteoglycans occurs in atherosclerotic lesions.


Good responsiveness with EuroQol 5-Dimension questionnaire and Short Form (36) Health Survey in 20-69 years old patients with a femoral neck fracture: A 2-year prospective follow-up study in 182 patients.
EQ-5D and SF-36 are two questionnaires used to measure health related quality of life (HRQoL). The responsiveness of these instruments has previously been evaluated in elderly populations with hip fracture but not in a younger population. The purpose was to evaluate the responsiveness of SF-36 and EQ-5D in a younger population with femoral neck fracture. 182 patients aged 20-69 were consecutively included. HRQoL was measured by EQ-5D and SF-36 at 4, 12 and 24 months. Pain and function were measured by Harris Hip Score (HHS) on the same occasions. The responsiveness of EQ-5D and SF-36 was evaluated by calculation of two effect sizes; standardized effect size (SES) and standardized response mean (SRM), and by analysing how changes in score correlated to changes in function and subjective state of health. External responsiveness was also evaluated by calculating receiver operating characteristic curve and area under the curve. SES was large at four months for both EQ-5D and SF-36 (1.09 and 0.83 respectively) and moderate at the 12- and 24-month follow-ups. The correlation between changes (4-24 months) in HHS and changes in HRQoL were 0.44 for EQ-5D and 0.37 for SF-36. EQ-5D and SF-36 were both more sensitive than HHS in their ability to predict subjective improvements after a hip fracture. The effect sizes and the ability to follow and predict the external standard indicates that both EQ-5D and SF-36 have good internal and external responsiveness in this younger population with femoral neck fracture. The generic HRQoL questionnaires were superior to a hip-specific instrument in predicting the patients' subjective feelings of an improved state of health. EQ-5D is simple to administer and shows similar responsiveness as SF-36 and may be sufficient to use as an outcome measure in clinical trials.


Giant adrenal myelolipoma: report of a case.
Adrenal myelolipomas are rare benign tumors composed of mature adipose tissue and hematopoietic elements that resemble bone marrow. They are usually asymptomatic, and most cases are incidentally found at radiological examination or autopsy. Symptoms such as abdominal pain and increasing girth occur only when the tumor grows large. We report the case of a giant adrenal myelolipoma in a 51-year old man who presented with a huge abdominal mass and abdominal pain. The resected tumor weighed 6,000 g and could represent the largest such tumor ever documented in the literature. We discuss the diagnosis and treatment of this unusual tumor.


Horner's syndrome secondary to T1-T2 intervertebral disc prolapse.
T1-T2 intervertebral disc prolapse (IVDP) is a rare clinical condition. Horner's syndrome is an extremely rare clinical finding in these patients. A 56-year-old man presented with the left C8 T1 radiculopathy, left hand grip weakness, and ipsilateral Horner's syndrome. Magnetic resonance imaging of the spine showed a contrast-enhancing lesion in the left T1 foramen compressing the left T1 nerve root. He underwent left T1 hemilaminectomy, upper half of left T2 hemilaminectomy and removal of the left foraminal lesion. A biopsy of the lesion was sent for histopathological diagnosis which revealed tissue consistent with disc material. Postoperatively, he had near-complete recovery with residual minimal Horner's syndrome. T1-T2 IVDP should be considered in the differential diagnosis when a patient presents with C8 T1 radiculopathy and Horner's syndrome.


Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction.
Endoscopic sphincterotomy is not without risks, and is also ineffective in about half of patients with type III sphincter of Oddi dysfunction (SOD), i.e. those without clinical evidence of biliary obstruction (normal liver tests, normal bile duct diameter, and regular drainage time at endoscopic retrograde cholangiography). The present study therefore investigated the efficacy and safety of endoscopic botulinum toxin (BTX) injection into the papilla of Vater, and analyzed whether the symptomatic response to BTX injection might be a predictor of outcome for endoscopic sphincterotomy. Twenty-two patients who had undergone cholecystectomy and had manometrically confirmed type III SOD were enrolled during a three-year study period. All patients received treatment with an endoscopic single-shot injection of 100 mouse units of BTX into the papilla of Vater. Initial symptomatic responses were analyzed six weeks later. If the BTX injection had been ineffective, or if biliary symptoms recurred after initial benefit during the follow-up period, endoscopic manometry and endoscopic sphincterotomy were performed. All patients then received further prospective clinical follow-up examinations. With the exception of one patient with mild pancreatitis (4.5%), no side effects were observed after endoscopic BTX injection. Six weeks after BTX injection, 12 SOD patients (55%) were symptom-free, but ten patients (45%) were not. However five of these ten SOD patients who did not experience symptomatic benefit from BTX injection had normal basal sphincter of Oddi pressures (< 40 mmHg) at this time, and none of these five patients was free of complaints after subsequent endoscopic sphincterotomy. Two of the remaining five patients with sustained sphincter hypertension after BTX injection benefitted from endoscopic sphincterotomy. Eleven of the 12 SOD patients who had initially responded to BTX injection developed recurrent symptoms after a median period of six months. Manometry revealed sphincter hypertension in all 11 cases, and all patients became free of complaints again after endoscopic sphincterotomy during a median follow-up of a further 15 months. Overall, 11 of the 12 patients who responded to BTX injection, versus two of the ten patients who did not gain pain relief after BTX injection, later benefitted from endoscopic sphincterotomy (p < 0.01). Endoscopic injection of botulinum toxin into the papilla of Vater is a safe procedure and provides short-term relief of symptoms in half of patients with type III SOD. Our results also indicate that the clinical response to BTX injection can predict whether SOD patients will gain long-term benefit from endoscopic sphincterotomy.


A reappraisal of antigenic determinants for nitrogenase from Azotobacter and nitrate reductase from Escherichia coli.
Previous work based on double immunodiffusion assays had shown that there are common antigenic determinants for nitrate reductase from Escherichia coli and component I of nitrogenase from Azotobacter vinelandii. Further work reported herein using a variety of immunoelectrophoretic techniques indicates that the cross-reaction between nitrate reductase and antiserum to component I of nitrogenase results from a contaminant antigen co-purified with nitrate reductase.


Gastrointestinal stromal tumor (GIST) presenting in a Meckel's diverticulum.
A meckel's diverticulum is a congenital abnormality of the GI tract seen in approximately 3% of the population. Tumor arising within this entity is a rare, although know complication. We report a gastrointestinal tumor arising within a Meckel's diverticulum in a 28-year-old male.


2-Morpholinoisoflav-3-enes as flexible intermediates in the synthesis of phenoxodiol, isophenoxodiol, equol and analogues: vasorelaxant properties, estrogen receptor binding and Rho/RhoA kinase pathway inhibition.
Isoflavone consumption correlates with reduced rates of cardiovascular disease. Epidemiological studies and clinical data provide evidence that isoflavone metabolites, such as the isoflavan equol, contribute to these beneficial effects. In this study we developed a new route to isoflavans and isoflavenes via 2-morpholinoisoflavenes derived from a condensation reaction of phenylacetaldehydes, salicylaldehydes and morpholine. We report the synthesis of the isoflavans equol and deoxygenated analogues, and the isoflavenes 7,4'-dihydroxyisoflav-3-ene (phenoxodiol, haganin E) and 7,4'-dihydroxyisoflav-2-ene (isophenoxodiol). Vascular pharmacology studies reveal that all oxygenated isoflavans and isoflavenes can attenuate phenylephrine-induced vasoconstriction, which was unaffected by the estrogen receptor antagonist ICI 182,780. Furthermore, the compounds inhibited U46619 (a thromboxane A(2) analogue) induced vasoconstriction in endothelium-denuded rat aortae, and reduced the formation of GTP RhoA, with the effects being greatest for equol and phenoxodiol. Ligand displacement studies of rat uterine cytosol estrogen receptor revealed the compounds to be generally weak binders. These data are consistent with the vasorelaxation activity of equol and phenoxodiol deriving at least in part by inhibition of the RhoA/Rho-kinase pathway, and along with the limited estrogen receptor affinity supports a role for equol and phenoxodiol as useful agents for maintaining cardiovascular function with limited estrogenic effects.


Expression and purification of recombinant G protein-coupled receptors: A review.
Given their extensive role in cell signalling, GPCRs are significant drug targets; despite this, many of these receptors have limited or no available prophylaxis. Novel drug design and discovery significantly rely on structure determination, of which GPCRs are typically elusive. Progress has been made thus far to produce sufficient quantity and quality of protein for downstream analysis. As such, this review highlights the systems available for recombinant GPCR expression, with consideration of their advantages and disadvantages, as well as examples of receptors successfully expressed in these systems. Additionally, an overview is given on the use of detergents and the styrene maleic acid (SMA) co-polymer for membrane solubilisation, as well as purification techniques.


Effect of PCL/nHAEA nanocomposite to osteo/odontogenic differentiation of dental pulp stem cells.
The green synthesis of nanoparticles has recently opened up a new route in material production. The aim of this study was to evaluate the effect of nanohydroxyapatite (nHA) synthesized from Elaeagnus angustifolia (EA) extract in polycaprolactone (PCL) nanofibers (PCL/nHAEA) to odontogenic differentiation of dental pulp stem cells (DPSCs) and their potential applications for dentin tissue engineering. Green synthesis of nHA via EA extract (nHAEA) was done by the sol-gel technique. Then electrospun nanocomposites containing of PCL blended with nHA (P/nHA) and nHAEA (P/nHAEA) were fabricated, and the characterization was evaluated via X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and the contact angle. The morphology of nanofibers and the cell adhesion capacity of DPSCs on nanofibers were evaluated using SEM. Cytocompatibility was assessed by MTT. Osteo/odontogenic differentiation ability of the nanocomposites were assessed using alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and quantitative real-time polymerase chain reaction (qPCR) technique. Viability and adhesion capacity of DPSCs were higher on P/nHAEA nanofibers than PCL and P/nHA nanofibers. ARS assay, ALP activity, and qPCR analysis findings confirmed that the nHAEA blended nanofibrous scaffolds substantially increased osteo/odontogenic differentiation of DPSCs. PCL/nHAEA nanocomposites had a noticeable effect on the odontogenic differentiation of DPSCs and may help to improve cell-based dentin regeneration therapies in the future.


The kinetic effects of in vitro phosphorylation of rabbit muscle enolase by protein kinase C. A possible new kind of enzyme regulation.
Rabbit muscle enolase was found to be phosphorylated in vitro by calcium-activated phospholipid-dependent protein kinase. The extent of incorporation (about 0.6 mol/mol subunit) and the apparent Km for the reaction (3.0 microM subunit) were determined. Kinetic studies on the unphosphorylated and phosphorylated enzymes displayed an unexpected effect of phosphorylation resulting in activation of the forward reaction and inhibition of the backward one.


Quality and Safety in Health Care, Part VI: More on Crossing the Quality Chasm.
One of the most important aspects of the Institute of Medicine (IOM) Crossing the Quality Chasm. A New Health System for the 21st Century report (Chasm report) was that 6 major aims for US health care were set forth. In addition, the report indicated that health care in the United States care should be redesigned in accordance with 10 enumerated rules. There were other recommendations as well, to try to bridge the huge gap between the health care many people in the United States receive and what they should receive.


Maxillary first molar with aberrant canal configuration: a report of 3 cases.
The prognosis for endodontic treatment in teeth exhibiting morphological aberrations is unfavorable if the clinician fails to recognize extra root canals. This report demonstrates 3 clinical cases of maxillary first molars that presented 2 canals in the palatal root merging at the apical third (Vertucci's type II canal morphology), a pattern that is rare and seldom encountered.


Fostering interprofessional communication through case discussions and simulated ward rounds in nursing and medical education: A pilot project.
Poor communication between physicians and nursing staff could result in inadequate interprofessional collaboration with negative effects on patient health. In order to ensure optimal health care for patients, it is important to strengthen interprofessional communication and collaboration between physicians and nurses during their education. The aim of this project is to foster communication for medical and nursing students through interprofessional case discussions and simulated ward rounds as a form of training. In 2013-15 a total of 39 nursing students and 22 medical students participated in eight seminars, each covering case discussions and simulated ward rounds. The seminar was evaluated based on student assessment of the educational objectives. Students who voluntarily signed up for the seminar profited from the interprofessional interaction and gathered positive experiences working in a team. Through practicing case discussions and ward rounds as a group, interprofessional communication could be fostered between medical and nursing students. Students took advantage of the opportunity to ask those from other profession questions and realized that interprofessional interaction can lead to improved health care.


An autopsy case of protracted necrotic encephalitis with marked atrophy of unilateral temporal lobe.
Clinical and neuropathological findings in a case of an unusually protracted encephalitis have been described. The patient was a 44-year-old man who experienced mental deterioration, right abducens and facial paresis, right and, subsequently, left hemiparesis, and consciousness disturbance with an intermittent low grade fever and occasional headache during one year and three months. Electroenphalograms showed periodic lateralized epileptiform discharges. Virus titers including herpes simplex virus were all normal. Neuropathological examinations revealed marked atrophic changes in the right temporal lobe, insular lobe and hippocampus with minimal inflammatory signs. The distribution of the lesions was almost identical with that of acute necrotic encephalitis or herpes simplex encephalitis despite its unusually protracted course.


Laue crystal structure of Shewanella oneidensis cytochrome c nitrite reductase from a high-yield expression system.
The high-yield expression and purification of Shewanella oneidensis cytochrome c nitrite reductase (ccNiR) and its characterization by a variety of methods, notably Laue crystallography, are reported. A key component of the expression system is an artificial ccNiR gene in which the N-terminal signal peptide from the highly expressed S. oneidensis protein "small tetraheme c" replaces the wild-type signal peptide. This gene, inserted into the plasmid pHSG298 and expressed in S. oneidensis TSP-1 strain, generated approximately 20 mg crude ccNiR per liter of culture, compared with 0.5-1 mg/L for untransformed cells. Purified ccNiR has nitrite and hydroxylamine reductase activities comparable to those previously reported for Escherichia coli ccNiR, and is stable for over 2 weeks in pH 7 solution at 4 °C. UV/vis spectropotentiometric titrations and protein film voltammetry identified five independent one-electron reduction processes. Global analysis of the spectropotentiometric data also allowed determination of the extinction coefficient spectra for the five reduced ccNiR species. The characteristics of the individual extinction coefficient spectra suggest that, within each reduced species, the electrons are distributed among the various hemes, rather than being localized on specific heme centers. The purified ccNiR yielded good-quality crystals, with which the 2.59-Å-resolution structure was solved at room temperature using the Laue diffraction method. The structure is similar to that of E. coli ccNiR, except in the region where the enzyme interacts with its physiological electron donor (CymA in the case of S. oneidensis ccNiR, NrfB in the case of the E. coli protein).


Approximate analytical model for transient transport and oxygen-limited biodegradation of vapor-phase petroleum hydrocarbon compound in soil.
Volatile organic compounds (VOCs) contamination may occur in subsurface soil due to various reasons and pose great threat to people. Petroleum hydrocarbon compound (PHC) is a typical kind of VOC, which can readily biodegrade in an aerobic environment. The biodegradation of vapor-phase PHC in the vadose zone consumes oxygen in the soil, which leads to the change in aerobic and anaerobic zones but has not been studied by the existing analytical models. In this study, a one-dimensional analytical model is developed to simulate the transient diffusion and oxygen-limited biodegradation of PHC vapor in homogeneous soil. Laplace transformation and Laplace inversion of the Talbot method are adopted to derive the solution. At any given time, the thickness of aerobic zone is determined by the dichotomy method. The analytical model is verified against numerical simulation and experimental results first and parametric study is then conducted. The transient migration of PHC vapor can be divided into three stages including the pure aerobic zone stage (Stage I), aerobic-anaerobic zones co-existence stage (Stage II), and steady-state stage (Stage III). The proposed analytical model should be adopted to accommodate scenarios where the transient effect is significant (Stage II), including high source concentration, deep contaminant source, high biodegradation capacity, and high water saturation. The applicability of this model to determine the breakthrough time for better vapor intrusion assessment is also evaluated. Lower first-order biodegradation rate, higher source concentration, and shallower source depth all lead to smaller breakthrough time.


A scenario for the origin of life: Volume regulation by bacteriorhodopsin required extremely voltage sensitive Na-channels and very selective K-channels.
The osmotic activity produced by internal, non-permeable, anionic nucleic acids and metabolites causes a persistent and life-threatening cell swelling, or cellular edema, produced by the Gibbs-Donnan effect. This evolutionary-critical osmotic challenge must have been resolved by LUCA or its ancestors, but we lack a cell-physiology look into the biophysical constraints to the solutions. Like mycoplasma, early cells conceivably preserved their volume with Cl- , Na+ , and K+ -channels, Na+ /H+ -exchangers, and a light-dependent bacteriorhodopsin-like H+ -pump. Here, I simulated protocells having these ionic-permeabilities and inhabiting an oceanic pond before the Great-Oxygenation-Event. Protocells showed better volume control and stable resting potentials at lower external pH and higher temperatures, favoring a certain type of extremophile life. Prevention of Na+ -influx at night, with low bacteriorhodopsin activity, required deep shutdown of highly voltage-sensitive Na+ -channels and extremely selective K+ -channels, two conserved features essential for modern neuronal encoding. The Gibbs-Donnan effect universality implies that extraterrestrial cells, if they exist, may reveal similar volume-controlling mechanisms.


Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability.
Liver cancer is the second leading cause of global cancer mortality. The major risk factors for hepatocellular carcinoma (HCC) are being addressed with success by prevention efforts. Vaccination against hepatitis B virus has reduced incidence of HCC in Taiwan and is partly responsible for lower rates in China. New infections with hepatitis C virus are low in developed countries because of prevention of posttransfusion infections and reduced exposure to HCV by drug users. Aflatoxin exposure has been reduced by better grain storage and dietary changes. Obesity, metabolic syndrome, and diabetes are increasing in developed and developing countries and will lead to more cases of HCC.


Occurrence and characterization of a tetrahedral nucleopolyhedrovirus from Spilarctia obliqua (Walker).
Spilarctia obliqua Walker (Lepidoptera: Arctiidae) is a polyphagous insect pest damaging pulses, oil seeds, cereals, vegetables and medicinal and aromatic plants in India. The pest also infests turmeric and ginger sporadically in Kerala. We observed an epizootic caused by a nucleopolyhedrovirus (NPV) in field populations of the insects in December 2013. The NPV was purified and characterized. The isolate was tetrahedral in shape and belonged to multicapsid NPV. The REN profile of the SpobNPV genome with Pst I, Xho I and HindIII enzymes showed a genome size of 99.1±3.9 kbp. Partialpolh, lef-8 and lef-9 gene sequences of the isolate showed a close relationship with HycuNPV and SpphNPV. Phylogram and K-2-P distances between similar isolates suggested inclusion of the present SpobNPV isolate to group I NPV. The biological activity of the isolate was tested under laboratory conditions against third instar larvae of S. obliqua and the LC50 was 4.37×10(3)OBs/ml occlusion bodies (OBs) per ml. The median survival time (ST50) was 181 h at a dose of 1×10(6)OBs/ml and 167 h at a dose of 1×10(8)OBs/ml. SpobNPV merits further field evaluation as a potential biological control agent of S. obliqua, a serious pest of many agriculturally important crops in the Oriental region.


An additional variant of the persistent primitive trigeminal artery: accessory meningeal artery--antero-superior cerebellar artery anastomosis associated with moyamoya disease.
Persistent embryological carotid-basilar anastomoses are rare. There has been no report on persistent anastomosis between the accessory meningeal artery and the antero-superior cerebellar artery. We describe a 3-year-old boy with moyamoya disease manifesting such a congenital vascular anomaly, namely, a large anastomosis between the accessory meningeal artery and the antero-superior cerebellar artery associated with marked hypoplasia of the basilar artery. This persistent vascular anomaly is considered embryologically as an additional variant of the persistent primitive trigeminal artery, i.e., a "stapedo-trigemino-cerebellar" variant.


Effect of 4-hydroxypyrazolo (3,4-d) pyrimidine (allopurinol) on postirradiation cerebral blood flow: implications of free radical involvement.
In an attempt to elucidate mechanisms underlying the irradiation-induced decrease in regional cerebral blood flow (rCBF) in primates, hippocampal and hypothalamic blood flows of rhesus monkeys were measured by hydrogen clearance, before and after exposure to 100 Gy, whole body, gamma irradiation. Systemic blood pressures were monitored simultaneously. Compared to control animals, the irradiated monkeys exhibited an abrupt decline in systemic blood pressure to 35% of the preirradiation level within 10 min postirradiation, falling to 12% by 60 min. A decrease in hippocampal blood flow to 32% of the preirradiation level was noted at 10 min postirradiation, followed by a slight recovery to 43% at 30 min and a decline to 23% by 60 min. The hypothalamic blood flow of the same animals showed a steady decrease to 43% of the preirradiation levels by 60 min postirradiation. The postradiation systemic blood pressure of the allopurinol treated monkeys was not statistically different from the untreated, irradiated monkeys and was statistically different from the control monkeys. However, the treated, irradiated monkeys displayed rCBF values that were not significantly different from the nonirradiated controls. These findings suggest the involvement of free radicals in the postirradiation decrease in regional cerebral blood flow but not necessarily in the postirradiation hypotension seen in the primate.


Inhibition of cell proliferation in black-capped chickadees suggests a role for neurogenesis in spatial learning.
Following development, the avian brain continues to produce neurons throughout adulthood, which functionally integrate throughout the telencephalon, including the hippocampus. In food-storing birds like the black-capped chickadee (Poecile atricapillus), new neurons incorporated into the hippocampus are hypothesized to play a role in spatial learning. Previous results on the relation between hippocampal neurogenesis and spatial learning, however, are correlational. In this study, we experimentally suppressed hippocampal neuronal recruitment and tested for subsequent effects on spatial learning in adult chickadees. After chickadees exhibited significant learning, we treated birds with daily injections of either saline or methylazoxymethanol (MAM), a toxin that suppresses cell proliferation in the brain and monitored subsequent spatial learning. MAM treatment significantly reduced cell proliferation around the lateral ventricles and neuronal recruitment in the hippocampus, measured using the cell birth marker bromodeoxyuridine. MAM-treated birds performed significantly worse than controls on the spatial learning task 12 days following the initiation of MAM treatment, a time when new neurons would begin functionally integrating into the hippocampus. This difference in learning, however, was limited to a single trial. MAM treatment did not affect any measure of body condition, suggesting learning impairments were not a product of non-specific adverse effects of MAM. This is the first evidence of a potential causal link between hippocampal neurogenesis and spatial learning in birds.


Peonidin-3-O-glucoside and cyanidin increase osteoblast differentiation and reduce RANKL-induced bone resorption in transgenic medaka.
Experimental and clinical studies suggest a positive impact of anthocyanins on bone health; however, the mechanisms of anthocyanins altering the differentiation and function of osteoblasts and osteoclasts are not fully understood. This work demonstrates that dietary anthocyanins and resveratrol increased proliferation of cultured human hFOB 1.19 osteoblasts. In addition, treatment of serum starvation of hFOB osteoblasts with anthocyanins and resveratrol at 1.0 μg/ml reduced apoptosis, the Bax/Bcl-2 ratio, p53, and HDAC1 expression, but increased SIRT1/3 and PGC1α mRNA expression, suggesting mitochondrial and epigenetic regulation. In Sp7/osterix:mCherry transgenic medaka, peonidin-3-O-glucoside and resveratrol increased osteoblast differentiation and increased the expression of Sp7/osterix. Cyanidin, peonidin-3-O-glucoside, and resveratrol also reduced RANKL-induced ectopic osteoclast formation and bone resorption in col10α1:nlGFP/rankl:HSE:CFP medaka in doses of 1-4 μg/ml. The results indicate that both cyanidin and peonidin-3-O-glucoside have anabolic effects on bone, increasing osteoblast proliferation and differentiation, mitochondrial biogenesis, and by altering the osteoblast epigenome. Cyanidin and peonidin-3-O-glucoside also reduced RANKL-induced bone resorption in a transgenic medaka model of bone resorption. Thus, peonidin-3-O-glucoside and cyanidin appear to both increase bone formation and reduce bone loss, suggesting that they be further investigated as potential treatments for osteoporosis and osteomalacia.


Rational nanostructured FeSe2 wrapped in nitrogen-doped carbon shell for high-rate capability and long cycling sodium-ion storage.
Transition metal selenides (TMSs) have drawn substantial attention as promising anode materials for sodium-ion batteries (SIBs) on account oftheir rapid reaction kinetics and high reversible capacity. However, the undesirable capacity decay and inferior rate performance still hamper their large-scale application. Herein, an anode material comprising combination of olivary nanostructure FeSe2 core and nitrogen-doped carbon shell (designated as FeSe2@NC) is well designed by in-situ polymerization and selenization method. The well-designed nitrogen-doped carbon shell can not only alleviate the volume variation during the electrode cycling but also provide an optimized ion/electron transport pathway. The resulting FeSe2@NC electrodes exhibit a superior rate capability of 228.4 mA h g-1 at 10 A g-1 and a long cycling performance of 246.5 mA h g-1 at 5 A g-1 after 1000 cycles, which can be assigned to the enhanced structural integrity and improved electrical conductivity. The strategy would present a promising thought for structure design of TMSs as anode materials, which could enhance high-rate and long-lasting cycle performances for SIBs.


Outcome of older adults at risk of frailty.
The integral part of the definition of frailty is the outcome associated with it. Older adults at risk of frailty are in the process of becoming frail. This study looked at the clinical characteristics and outcomes of older adults at risk of frailty. The study population was selected from outpatient department of the geriatric medicine department in a tertiary care hospital. Older adults identified as at risk of frailty were assessed at baseline and then followed up after 1 year for the composite primary outcome of death, falls, hospitalization, and self-rated poor quality of life in the follow-up period. The study included 324 older adults who had completed 1-year follow up. Mean (SD) age was 74.49 (4.58) years, and males were 241 (74.15%). Frail and pre-frail at baseline among the study population were 31.17% and 61.11%, respectively. The primary outcome occurred in 43 (13.27%) patients. Poor baseline IADL was significantly associated with primary outcome at the end of 1 year. An unfavorable outcome in older adults at risk of frailty was significantly higher and independent of their baseline frailty status. Poor baseline IADL value may be considered as a predictor for primary outcome at 1 year of follow up.


The effects of far-red light on plant growth and flavonoid accumulation in Brassica napus in the presence of ultraviolet B radiation.
Flavonoid induction is regulated by complex signal transduction pathways involving cryptochrome, phytochrome and UVB photoreceptors. Previously, we identified the UVB-inducible flavonoids in Brassica napus cv. Topas leaves and showed that UVA affected accumulation of the quercetin (Q) and kaempferol (K) glycosides (Wilson et al. [2000] Photochem. Photobiol. 73, 678-684). In this study, we examined the effects of far-red light (FR, 700-780 nm) on UVB-mediated flavonoid accumulation in B. napus. Plants were grown under photosynthetically active radiation (PAR, 400-700 nm, 150 micromol m(-2) s(-1)) plus a moderate level of FR (35 micromol m(-2) s(-1)) for 14 days, and then transferred to five different irradiation regimes (PAR +/- [UVA + UVB] + moderate, intermediate or low fluence FR) for 4 days. Kinetics of flavonoid accumulation were assessed via HPLC. Accumulation of flavonoids, in general, was suppressed by increasing the amount of FR in the spectrum. Furthermore, addition of UVB (290-320 nm) to the spectrum altered the flavonoid composition by causing significant changes in the quantities of individual flavonoids. The relative levels of acylated K glycosides were diminished whereas the relative levels of nonacylated Q glycosides increased dramatically. With UVB exposure there was a five-fold increase in the Q:K ratio. In contrast, increasing the level of FR in the presence of UVB decreased the Q:K ratio by half.


Co-Occurring Substance Use Disorders and Grief during Recovery.
Individuals with substance use disorders (SUDs) often experience loss and grief when recovering from addiction. With fatal overdoses and suicide rates increasing for individuals with SUDs and other mental health concerns, individuals in recovery are often faced with mourning the loss of a loved one while navigating their life in recovery. The loss of a loved one can be compounded by the effect of losing their relationship with their drug of choice. These co-occurring losses may prove overwhelming during recovery and precipitate a relapse. We wish to propose the use of two bereavement models to address the grief present for individuals with SUDs experiencing loss so that providers are better able meet the complex needs of this population. This article presents two separate bereavement models that may be used to shape treatment for individuals in recovery from addiction with co-occurring grief from the loss of a loved one: the dual-process model of coping with bereavement (DPM) and the two-track model of bereavement. We propose the application of these two grief models in treatment for individuals with SUDs who are experiencing co-occurring grief issues. We discuss therapeutic interventions that may be utilized to support clients with co-occurring losses.Conclusion/Importance: If an individual experiences the loss of a loved one while navigating their life in recovery from a SUD, they can experience complicated grief due to co-occurring losses. These models provide an opportunity for mental health providers to help those with SUDs work through this complex grief.


Relationship of body condition score and oxidant stress to tumor necrosis factor expression in dairy cattle.
The relationship between body condition score (BCS) with measures of oxidative status and TNF-alpha production was examined in 16 mid-lactation dairy cows. Cows were selected based on either a normal (2.5-2.7) or a high (> or =3.5) BCS using the standard five-point scaling system. The metabolic status of all cows was determined by plasma nonesterified fatty acid levels (NEFA). Plasma samples or white blood cell lysates also were analyzed for indices of oxidant stress and for the expression of TNF-alpha. Cows with a high BCS had significantly lower NEFA levels when compared to normal BCS cows and the over-conditioned animals were not in a state of negative energy balance. No significant changes in lipid hydroperoxide levels, glutathione peroxidase activity, or the ratio of reduced (GSH) to oxidized (GSSG) glutathione was detected with respect to BCS. However, high BCS cows did have a significantly lower overall antioxidant potential and reduced TrxR activities when compared with the normal BCS cows. Changes in the oxidative state of over-conditioned cows were accompanied by a significantly higher expression of TNF-alpha. Results from this study suggest that cows with a high BCS can experience oxidant stress in the absence of altered energy status. Increased TNF-alpha expression may be related to the pro-oxidant state of over-conditioned cows and possibly be a contributing factor to the enhanced susceptibility to disease in high BCS dairy cattle.


Energy metabolic regulation of oscillatory contraction activity in Physarum polycephalum.
The influence of inhibitors of respiration (KCN), glycolysis (2-deoxy-D-glucose alone or in combination with monoiodo-acetate) and anaerobic conditions (N2 or 95% N2 + 5% CO2), as well as the effect of application of appropriate substrates (D-glucose, sodium acetate, alpha-ketoglutarate and pyruvate) on contraction behavior (of plasmodia) of Physarum polycephalum was investigated under low intensity red-light illumination. Application of inhibitors of respiration or glycolysis leads to significantly different periods of the force oscillations (2.0 +/- 0.4 min and 4.1 +/- 0.5 min, in the presence of inhibitors of glycolysis and respiration, respectively). In both cases, the force amplitude of oscillations is diminished in comparison to undisturbed energy production. The persistence of oscillations in the presence of inhibitors of glycolysis seems to rule out an exclusively glycolytic origin of the force oscillations. A continuous production of ATP is necessary since a blockade of the energy production causes a cessation of the oscillations. Application of substrates for respiration in the presence of inhibitors of glycolysis leads to an increase in the force amplitude and a slight prolongation of the oscillation period. In contrast, an application of glucose in the presence of a respiration inhibitor has no effect on the force amplitude and period.


Distribution of ergot alkaloids and ricinoleic acid in different milling fractions.
The sclerotia of the fungus Claviceps sp. are still a challenge for the milling industry. Ergot sclerotia are a constant contamination of the rye crop and have to be removed by modern milling technologies. Changing sizes and coloration of the sclerotia make it difficult to separate them from the grain. Ergot sclerotia are a problem when cleaning is insufficient and non-separated specimens or sclerotia fragments get into the milling stream and thus ergot alkaloids are distributed into the different cereal fractions. In model milling experiments, the residues of ergot in rye flour and the distribution of ergot into different milling fractions were investigated. Rye grains were mixed with whole ergot sclerotia and in another experiment with ergot powder and cleaned afterwards before milling. The ergot alkaloids ergometrine, ergosine, ergotamine, ergocornine, ergocryptine, ergocristineand their related isomeric forms (-inine-forms), and additionally ricinoleic acid as a characteristic component of ergot, were quantified in the different milling fractions. From the first experiment, it can be shown that after harvesting even simple contact of sclerotia with bulk grains during ordinary handling or movement of bulk grain in the granary is sufficient to contaminate all the healthy or sound rye grains with ergot alkaloids. Thereby, the amount of ergot residue correlates with the amount of peripheral layers of rye grains in the flour. In an additional experiment without sclerotia specimens, bulk rye grains were loaded with powder of sclerotia. After subsequent cleaning, aconcentration of ergot alkaloids was detected, which was tenfold higher than the ergot alkaloidconcentration of the experiment with intact ergot sclerotia.


Epidemiology of silent myocardial ischemia in asymptomatic middle-aged men (the ECCIS Project).
To evaluate the prevalence of type I silent myocardial ischemia and silent myocardial infarction, 4,842 men aged 40 to 59 years, identified in occupational samples in Florence and Rome, and free from major heart disease, severe illnesses and chest pain, underwent a 3-stage diagnostic procedure. The first stage included resting electrocardiogram, hyperventilation test, exercise electrocardiogram and 24-hour Holter electrocardiogram. The subjects who were suspected of having type 1 silent myocardial ischemia or previous silent infarction at the first stage (n = 439; 9.1%) were entered into the second stage, which included echocardiogram, thallium 201 scintigraphy in conjunction with exercise testing or dipyridamole test, exercise radionuclide ventriculography and ergonovine test. Three hundred eighty-seven men participated in the second stage; after the diagnostic procedures were performed, 104 men (2.1%) were still suspected of having type 1 silent myocardial ischemia or infarction on the basis of predefined criteria. Sixty-two men continued on into the third diagnostic workup including coronary angiography. The final diagnosis of type 1 silent myocardial ischemia or infarction was reached in 25 patients (prevalence 0.52%; adjusted estimate 0.89%). Of these 25, 19 had coronary atherosclerotic disease, 1 had Kawasaki disease, 1 had coronary anomaly, 1 had induced focal coronary spasm, and 2 had normal coronary arteriograms despite the presence of unquestionable old myocardial infarction. Altogether, 6 patients with silent myocardial infarction were identified.(ABSTRACT TRUNCATED AT 250 WORDS)


Regulator of G-protein signalling 3 and its regulator microRNA-133a mediate cell proliferation in gastric cancer.
Regulator of G-protein signalling 3 (RGS3) plays a pivotal role in Wnt signalling and epithelial-mesenchymal transition. RGS3 overexpression in gastric cancer suggests that RGS3 and its regulators have the potential to serve as therapeutic targets for gastric cancer. Therefore, we aimed to investigate the roles of RGS3 and its regulator microRNA-133a in gastric cancer tumorigenesis. mRNA and protein expression levels of RGS3 in 107 paired human gastric cancer tissues and gastric cancer cells were examined using qRT-PCR and immunoblotting, respectively. The relationship between RGS3/microRNA-133a expression and clinicopathological characteristics was assessed using t-test. TargetScan, miRanda and MicroCosm Targets were employed to predict the binding site on the 3'-untranslated region of RGS3 that is targeted by microRNA-133a. Moreover, dual-luciferase reporter assay was performed to validate target prediction. microRNA-133a expression level in gastric cancer tissues and cell lines was determined by qRT-PCR. Finally, the proliferation activity of gastric cancer cells was evaluated using Cell Counting Kit-8 and bromodeoxyuridine incorporation assays. RGS3 expression level markedly increased in both gastric cancer tissues and cells compared with that in the corresponding normal tissues and cells. However, microRNA-133a expression level markedly decreased in gastric cancer tissues and cells and was negatively correlated with RGS3 expression. Higher RGS3 and lower microRNA-133a expression levels were associated with a larger tumour size, lymph node metastasis, local invasion and advanced tumour-node-metastasis stage in gastric cancer. Dual-luciferase reporter assay verified that microRNA-133a targeted RGS3 via mRNA 3'-untranslated region binding. Finally, microRNA-133a inhibited gastric cancer cell proliferation, whereas RGS3 overexpression attenuated this inhibitory effect. MicroRNA-133a is a regulator of RGS3 in gastric cancer and the microRNA-133a-RGS3 axis possibly participates in the malignant progression of gastric cancer.


Serum iron, ferritin, folic acid, and vitamin B12 levels in recurrent aphthous stomatitis.
The exact aetiology of recurrent aphthous stomatitis (RAS) is still unknown, but different predisposing factors, including iron, vitamin B12 and folic acid deficiencies, have been proposed. Serum iron, ferritin, folic acid and vitamin B12 levels were investigated in 35 patients with RAS and in 26 healthy controls. Vitamin B12 levels were found significantly lower in subjects with RAS than in controls. No significant differences were found in other parameters. We concluded that vitamin B 12 deficiency may be an aetiological factor in recurrent aphthous stomatitis.


Information and communication technology (ICT) and environmental sustainability: a panel data analysis.
This study investigates the impact of information and communication technology (ICT) on carbon dioxide emissions for a panel of 91 countries over the period 1990 to 2017. The study constructs an ICT index through principal component analysis and tests for the presence of cross-sectional dependence (CSD) in the data. The study employs pooled ordinary least squares, fixed-effects model, and system-generalized method of moments estimation techniques with panel-corrected standard errors (PCSE) to tackle the issues of CSD in the data. The findings of the study show that ICT reduces CO2 emissions for the full sample of countries. However, the comparative study of developed and developing countries depicts that ICT encourages environmental sustainability in developed countries whereas opposite results are found for developing countries. Moreover, presence of the environmental Kuznets curve is confirmed for the full sample as well as for developed and developing countries. It suggests that with higher levels of development of a country, it would be possible to contribute towards environmental sustainability along with ICT diffusion. Therefore, the outcome of this study may be helpful for policymaker and policies may be designed to encourage ICT investments in developing countries, as ICT will take care of environmental sustainability with higher levels of development.


The effect of the antiprogestin RU 486 on uterine contractility and sensitivity to prostaglandin and oxytocin.
The effect of RU 486, a steroid acting as an antiprogestin at the receptor level, on uterine contractility and sensitivity to the prostaglandin analogue, 16-phenoxy-PGE2 methyl sulfonylamide (16-phenoxy-PGE2) and to oxytocin was studied in 29 women in early pregnancy. Seven untreated women at the same stage of pregnancy served as controls. In the untreated women no spontaneous uterine contractility was recorded and the response to 0.25 mg 16-phenoxy-PGE2 was characterized by an increase in uterine tonus with superimposed irregular contractions of low amplitude. Treatment with 25 mg RU 486 twice daily resulted in the appearance of regular uterine contractions at 24 h in two out of five patients and in all patients at 36, 48 and 72 h after the start of RU 486 treatment. The withdrawal of progesterone influence changed the inactive early pregnant uterus into an active organ. Administration of 16-phenoxy-PGE2 caused an obvious stimulation of both frequency and amplitude of the contractions. In addition, the significantly increased sensitivity to the prostaglandin analogue, but not to oxytocin, was already apparent 24 h after the start of RU 486 treatment. We have previously shown that the addition of one intramuscular injection of 16-phenoxy-PGE2 on the fourth day of treatment with RU 486 (25 mg twice daily) significantly increased the abortifacient effect of the antiprogestin during early pregnancy. The present study suggests that a shorter treatment may be possible.


The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates.
The A site of the small ribosomal subunit participates in the fidelity of decoding by switching between two states, a resting 'off' state and an active decoding 'on' state. Eight crystal structures of RNA duplexes containing two minimal decoding A sites of the Homo sapiens mitochondrial wild-type, the A1555G mutant or bacteria have been solved. The resting 'off' state of the mitochondrial wild-type A site is surprisingly different from that of the bacterial A site. The mitochondrial A1555G mutant has two types of the 'off' states; one is similar to the mitochondrial wild-type 'off' state and the other is similar to the bacterial 'off' state. Our present results indicate that the dynamics of the A site in bacteria and mitochondria are different, a property probably related to the small number of tRNAs used for decoding in mitochondria. Based on these structures, we propose a hypothesis for the molecular mechanism of non-syndromic hearing loss due to the mitochondrial A1555G mutation.


A sandwich ELISA for properdin in clinical specimens.
We have developed a symmetrical sandwich ELISA for measuring human properdin (P) in serum by using the globulin fraction from a commercial antiserum as the capture antibody adsorbed on the plastic. The detecting reagent was a glutaraldehyde conjugate of this Ig fraction with alkaline phosphatase. Two types of inhibition were observed in this study. First, inhibition was observed when greater than 2.5 micrograms/ml of the globulin fraction was used to coat the plates. A second type of inhibition was observed for serum dilutions less than 1/400; it was independent of the concentration of capture Ab and did not occur when purified P was assayed. The data generated with this assay could be fitted in log-log mode by a quadratic equation. The coefficient of the linear term in this equation was found to be the same for serum and purified P, within the limits of experimental error. The results for different samples run on the same plate were expressed in terms of the relative concentration of each sample required to produce an OD405 = 0.2. A sample of pooled normal human serum was run on each plate as a reference; it was assigned a titer of 100 ELISA units/ml (EU/ml). The titers of the unknown samples were expressed in terms of EU/ml by reference to this standard. For purified P, the assay could readily detect 10 ng/ml. By comparing purified P with our reference serum pool, we found that 1 EU equals 0.57 microgram. Day-to-day variation for a group of nine normal sera showed a mean difference of -0.85 EU/ml, SD 5.85 EU/ml. The mean titer for these normal sera was 78.9 EU/ml, SD 15.7 EU/ml. In three recovery experiments in which purified P was mixed with pooled normal serum, the recoveries ranged from 96 to 117%. We conclude that the sandwich ELISA constitutes an adequate immunochemical assay for human P in serum specimens.


Time-dependent Gutzwiller theory for multiband Hubbard models.
Based on the variational Gutzwiller theory, we present a method for the computation of response functions for multiband Hubbard models with general local Coulomb interactions. The improvement over the conventional random-phase approximation is exemplified for an infinite-dimensional two-band Hubbard model where the incorporation of the local multiplet structure leads to a much larger sensitivity of ferromagnetism on the Hund coupling. Our method can be implemented into local-density approximation and Gutzwiller schemes and will therefore be an important tool for the computation of response functions for strongly correlated materials.


Feeling Not Wanted/Loved and Depression: Does Gender Matter?
Depression affects over 17 million American adults yearly and has been identified as the leading cause of disability in people between the ages of 15 and 44 years. There is evidence that feeling neglect or a lack of parental attachment during childhood is associated with depression. One construct that has been overlooked is love from a parent. The purpose of this study was to analyze the association between individuals who felt not wanted/loved during adolescence and lifetime depression and to examine this association by gender. We examined 5114 participants aged 24-32 years at Wave IV of the National Longitudinal Study of Adolescent Health (Add Health) public use dataset. We used logistic regression analysis to determine the association between an individual feeling not wanted/loved by their parent/caregiver prior to age 18, covariates, and lifetime depression. We then stratified by gender and ran logistic models for both men and women separately. Overall, 16.2% (n = 827) reported lifetime depression diagnosis, while 16.5% of the participants reported feeling not wanted/loved "often," while 29.8% reported it as "sometimes." Feeling not wanted/loved "often" was associated with higher odds of depression (AOR = 3.00; 95% CI, 2.45-3.66; p < .001) versus "sometimes" (AOR = 1.59; 95% CI, 1.31-1.90; p < .001). When stratified by gender, feeling not loved/wanted was associated with depression among both men (AOR = 3.70; 95% CI, 2.60-5.25; p < .001) and women (AOR = 2.73; 95% CI, 2.13-3.48; p < .001). Feeling not loved or wanted by a parent/caregiver during adolescence has serious implications, for both men and women. Future studies should further examine this construct and identify family-based interventions that focus on parent/caregiver and child relationships.


Washing and chilling as critical control points in pork slaughter hazard analysis and critical control point (HACCP) systems.
The aim of this research was to examine the effects of preslaughter washing, pre-evisceration washing, final carcass washing and chilling on final carcass quality and to evaluate these operations as possible critical control points (CCPs) within a pork slaughter hazard analysis and critical control point (HACCP) system. This study estimated bacterial numbers (total viable counts) and the incidence of Salmonella at three surface locations (ham, belly and neck) on 60 animals/carcasses processed through a small commercial pork abattoir (80 pigs d(-1)). Significant reductions (P < 0.05) in bacterial numbers were noted at some stages of the slaughter/dressing process, i.e. the process of hair removal (scalding-dehairing and singeing) resulted in an approx. 4.5 log10 cfu cm(-2) decrease in bacterial numbers. A significant increase (P < 0.05) in bacterial numbers was observed after pre-evisceration washing. Final washing increased the bacterial counts to between 3.6 and 3.8 log10 cfu cm(-2) while chilling effected a small but statistically significant (P < 0.05) increase to between 4.5 and 4.7 log10 cfu cm(-2). The incidence of Salmonella on pigs at the farm was 27%, decreasing to 10% after preslaughter washing. However, stunning and bleeding effected a considerable increase in Salmonella contamination and the incidence after these operations was 50%, which was reduced to 0% during the scalding-dehairing process. Washing the live animals and subsequent carcasses with cold water is not an effective control measure but chilling may be used as a CCP. Recent changes in European Union legislation legally mandate HACCP in pork slaughter plants. This research will provide a sound scientific basis on which to develop and implement effective HACCP in pork abattoirs.


3D ultrasound navigation system for screw insertion in posterior spine surgery: a phantom study.
Posterior spinal fusion surgery is required to correct severe idiopathic scoliosis. The surgery involves insertion of screws which requires high accuracy to prevent neurologic damage to the spinal cord. Although conventional CT navigation can reduce this risk, 3D-ultrasound-based navigation could achieve this without added ionizing radiation and usage of expensive and bulky equipment. This study aimed to evaluate the accuracy of a 3D ultrasound navigation system for posterior spine surgery. A custom 3D ultrasound (3DUS) with model-to-surface registration algorithm was developed and integrated into a 3D navigation environment. A CT scan of an adolescent spine (T3-T11) was segmented and 3D printed for experiments. A probe with reflective markers was placed in vertebral pedicles 684 times in varying levels, positions in the capture space and orientation of vertebra, and the entrypoint and trajectory accuracies were measured. Among 684 probe placements in vertebral levels T3 to T11 in the phantom spine, 95.5% were within 1 mm and 5° of accuracy, with an average accuracy of 0.4 ± 0.4 mm and 2.1 ± 0.9°, requiring 8.8 s to process. Accuracies were statistically significantly affected by vertebral orientation and position in the capture volume, though this was still within the targeted accuracies of 1 mm and 5°. This preliminary ultrasound-based navigation system is accurate and fast enough for guiding placement of pedicle screws into the spine in posterior fusion surgery. The current results are limited to phantom spines, and future study in animal or human cadavers is needed to investigate soft tissue effects on registration accuracy.


Brain maturation after preterm birth.
Two translational studies--one in humans and one in sheep--suggest that (i) premature birth is associated with delayed maturation of grey matter in the cerebral cortex and (ii) medical care that prohibits impairment of growth in premature neonates may enhance cortical development and reduce neurological disabilities associated with preterm birth.