The panorama of different faces of mesothelial cells.
All effusions in serous cavities represent a pathologic processes secondary to inflammatory, neoplastic, hemodynamic, or mechanical/traumatic etiologies. This elicits reactive changes in the extremely sensitive mesothelial cells lining the serosal surfaces. The result is hypertrophy and hyperplasia which lead to broad changes with a wide range of morphological appearances. These reversible alterations may resolve entirely after the recovery of underlying pathology. Under the tertiary care situations, neoplastic effusion specimens are encountered more frequently. Although some non-neoplastic pathologic process may demonstrate a few diagnostic features, cytologic evaluation of malignant effusions usually show diagnostic malignant cells. However, the most versatile mesothelial cells demonstrate a very wide cytomorphological spectrum secondary to reactive challenges. These mesothelial cells are usually referred to as 'reactive mesothelial cells'. In addition other terms such as reactive mesothelial proliferation, reactive mesothelial hyperplasia, irritated mesothelial cells, activated mesothelial cells, hyperplastic mesothelial cells, hypertrophic mesothelial cells, and proliferative mesothelial cells. Rarely atypical mesothelial cells, although not recommended, is used inadvertently. Although there is a lack of general agreement defining these terms, some of these including atypical mesothelial cells, should not be preferred. With reference to this CMAS series, usually favored term 'reactive mesothelial cells' is preferred. The size of reactive mesothelial cells range from 15 to 30 µm (but may be up to 50 µm). These polyhedral cells with variable amount of cytoplasm and enlarged nuclei may show variation in sizes and shapes with conspicuous nucleoli. Bi- and multi-nucleation is frequent. Cohesive groups of mesothelial cells as sheets and three dimensional groups may be present. Some floridly reactive mesothelial cells with hyperchromatic enlarged nuclei with prominent nucleoli and scant cytoplasm may resemble malignant cells. This astonishingly wide morphological spectrum of reactive mesothelial cells is a significant interpretation challenge in effusion fluid cytology. Methodical interpretation approach with appropriate knowledge about this wide spectrum is important aspect in diagnostic cytopathology of effusion fluids.


Polymorphisms of the receptor for advanced glycation end products and glyoxalase I and long-term outcome in patients with breast cancer.
Receptor for advanced glycation end products and glyoxalase I metabolizing advanced glycation end product precursors may play important role in the pathogenesis and progression of cancer. Potential relation between soluble forms of receptor for advanced glycation end products (sRAGE), receptor for advanced glycation end products, glyoxalase I polymorphisms, and long-term outcome (median follow-up of 10.3 years) was studied in 116 patients with breast cancer. Gly82Ser and 2184 A/G RAGE polymorphisms were related to the mortality due to the breast cancer and -419 A/C glyoxalase I polymorphism was related to the overall mortality of the patients suggesting their role not only in the risk of breast cancer but also in the outcome of patients with breast cancer.


HIV type 1 infection of human macrophages induces an upregulation of manganese superoxide dismutase gene that may protect cells from death.
It has been previously demonstrated that HIV-1 infection induces a downregulation of MnSOD transcription in CD4+ lymphocytes. Using clinical isolates of macrophage-tropic HIV-1 strains we report here that conversely, purified normal human monocyte-derived macrophages (MDMs) overexpress the manganese superoxide dismutase (MnSOD) gene in response to infection and viral replication. This upregulation of MnSOD gene expression is concomitant with tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production and treatment of HIV-1-infected MDMs with a specific transcriptional inhibitor of TNF-alpha synthesis counteracts the HIV-1-induced MnSOD gene activation. Moreover, TNF-alpha but not IL-6 addition mimicks the effects of HIV-1 infection on MnSOD gene regulation in normal MDM cultures. These observations strongly suggest that the MnSOD gene induction detected in HIV-1-infected MDMs is triggered by TNF-alpha produced in culture supernatants in parallel to HIV-1 particle release. In contrast to MnSOD, HIV-1 infection or replication in human MDMs has no effect on copper-zinc superoxide dismutase (Cu/ZnSOD) gene expression.


Test-Retest Reliability of Measures Commonly Used to Measure Striatal Dysfunction across Multiple Testing Sessions: A Longitudinal Study.
Cognitive impairment is common amongst many neurodegenerative movement disorders such as Huntington's disease (HD) and Parkinson's disease (PD) across multiple domains. There are many tasks available to assess different aspects of this dysfunction, however, it is imperative that these show high test-retest reliability if they are to be used to track disease progression or response to treatment in patient populations. Moreover, in order to ensure effects of practice across testing sessions are not misconstrued as clinical improvement in clinical trials, tasks which are particularly vulnerable to practice effects need to be highlighted. In this study we evaluated test-retest reliability in mean performance across three testing sessions of four tasks that are commonly used to measure cognitive dysfunction associated with striatal impairment: a combined Simon Stop-Signal Task; a modified emotion recognition task; a circle tracing task; and the trail making task. Practice effects were seen between sessions 1 and 2 across all tasks for the majority of dependent variables, particularly reaction time variables; some, but not all, diminished in the third session. Good test-retest reliability across all sessions was seen for the emotion recognition, circle tracing, and trail making test. The Simon interference effect and stop-signal reaction time (SSRT) from the combined-Simon-Stop-Signal task showed moderate test-retest reliability, however, the combined SSRT interference effect showed poor test-retest reliability. Our results emphasize the need to use control groups when tracking clinical progression or use pre-baseline training on tasks susceptible to practice effects.


Sound-pressure measurements in the cochlear vestibule of human-cadaver ears.
The middle-ear pressure gain for the 50-Hz to 12-kHz range was determined from the ratio of sound pressures measured in the vestibule and the ear canal of four human-cadaver ears. The magnitude of the middle-ear pressure gain is 20 dB for frequencies between 500 Hz and 2 kHz. Above 4 kHz, the gain changes as a function of frequency at a rate of approximately -8 dB/octave and below 400 Hz at 4 dB/octave. The standard error of the mean magnitude across the four ears is typically less than 3 dB. The phase angle of the pressure gain also changes with frequency. Interruption of the ossicular chain decreases the vestibule pressure by at least 20 dB. It is shown that air bubbles in the inner ear can diminish the vestibule pressure; procedures are used to remove bubbles. From these pressure measurements and previous measurements of stapes motion, the frequency dependence of behavioral thresholds for tones was tested to discover whether it corresponds to the constancy of a physiological variable at the cochlear input. Among pressure, power, or stapes-motion measures, the vestibule pressure is most nearly constant with frequency at the behavioral "minimum audible pressure."


Monooxime Bispyridinium Reactivators Bearing Xylene Linker Synthesis and In Vitro Evaluation on Model of Organophosphate-Inhibited Acetylcholinesterase.
Nine novel mono-oxime reactivators bearing xylene linker were synthesized in an effort to improve previously prepared xylene bisoximes and monocarbamoyl-monooximes. The novel compounds were tested in vitro on the model of tabun-, paraoxon-, methylparaoxon- and DFP-inhibited human erythrocyte AChE. Their reactivation ability was compared to pralidoxime, asoxime, obidoxime and two previously prepared xylene linked bisoximes (K107, K108). All compounds showed minimal reactivation of tabun-inhibited AChE at selected concentration scale. This finding was explained by molecular modelling study. Bisoximes obidoxime and K108 resulted as the best reactivators for paraoxon-, methylparaoxon- and DFP-inhibited AChE. The loss of nonoxime moiety lead to the loss of reactivation ability within the novel compounds. Though the novel reactivators did not exceed previously known compounds, they confirmed former SAR findings for xylene-linked AChE reactivators.


Diminished proliferation of B blast cell in response to cytokines in ethanol-consuming mice.
We and others have demonstrated that ethanol suppresses the antibody response in humans and animals. The purpose of this study was to determine whether ethanol affects cytokine-induced proliferative responses of splenic B blast cells, and whether the decreased response was due to an imbalance of the cytokine activity. Thus, the ability of spleen cells from individual ethanol-diet-fed C57BL/6 mice to proliferate and produce cytokines was determined. The ability of anti-IgM monoclonal antibodies (mAb)-activated splenic B blast cells in response to mouse recombinant IL-2 (rIL-2) or rIL-4 was also assessed. A thymidine incorporation assay was used to determine cell proliferation, and the conventional bioassays for cytokine-dependent cell proliferation were used for determining the bioactivity of cytokines. Data were analyzed with general linear model procedure. Our results showed that ethanol weakened the proliferative response of B cells in response to mitogen as well as to mouse rIL-2 and rIL-4. The decreased B cell responses may result from an increase in the production of IL-4 by helper T cells. Finally, in the presence of excessive dose of rIL-4, the proliferative responses of B blast cells from all three groups of mice were diminished (p<0.01). Thus, our data clearly indicated that the diminished B cell proliferation in ethanol-consuming mice was due in part to an excessive amount of IL-4 produced and an inability of the B cell to interact properly with IL-4 that was secreted by helper T cells. The results should extend our basic understanding of the mechanism by which chronic alcoholism impairs the interactions and interdependence of T- and B-cell immune functions.


Dynamic multidrug therapies for hiv: optimal and sti control approaches.
We formulate a dynamic mathematical model that describes the interaction of the immune system with the human immunodeficiency virus (HIV) and that permits drug "cocktail " therapies. We derive HIV therapeutic strategies by formulating and analyzing an optimal control problem using two types of dynamic treatments representing reverse transcriptase (RT) in hibitors and protease inhibitors (PIs). Continuous optimal therapies are found by solving the corresponding optimality systems. In addition, using ideas from dynamic programming, we formulate and derive suboptimal structured treatment interruptions (STI)in antiviral therapy that include drug-free periods of immune-mediated control of HIV. Our numerical results support a scenario in which STI therapies can lead to long-term control of HIV by the immune response system after discontinuation of therapy.


Laundering of theatre scrubs at home.
Infections, particularly those caused by antibiotic-resistant gram-positive bacteria, such as methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), are a growing concern, particularly in units in which patients are immunosuppressed either intentionally (as for transplantation) or as a result of trauma (severe burns) or disease (such as acquired immunodeficiency disease) (Steinstraesser et al 2009). As more bacteria become resistant to antibiotics, our ability to control the spread of these bacteria with antibiotic treatments decreases (Steinstraesser et al 2009).


New Races and Novel Strains of the Spinach Downy Mildew Pathogen Peronospora effusa.
Downy mildew disease, caused by Peronospora effusa (=P. farinosa f. sp. spinaciae [Pfs]), is the most economically important disease of spinach. Current high-density fresh-market spinach production provides conducive conditions for disease development, and downy mildew frequently forces growers to harvest early owing to disease development, to cull symptomatic leaves prior to harvest, or to abandon the field if the disease is too severe. The use of resistant cultivars to manage downy mildew, particularly on increasing acreages of organic spinach production, applies strong selection pressure on the pathogen, and many new races of Pfs have been identified in recent years in spinach production areas worldwide. To monitor the virulence diversity in the Pfs population, downy mildew samples were collected from spinach production areas and tested for race identification based on the disease reactions of a standard set of international spinach differentials. Two new races (designated races 15 and 16) and eight novel strains were identified between 2013 and 2017. The disease reaction of Pfs 15 was similar to race 4, except race 4 could not overcome the resistance imparted by the RPF9 locus. Several resistance loci (RPF1, 2, 4, and 6) were effective in preventing disease caused by Pfs 15. The race Pfs 16 could overcome several resistance loci (RPF2, 4, 5, 9, and 10) but not others (RPF1, 3, 6, and 7). One novel strain (UA1014) could overcome the resistance of spinach resistant loci RPF1 to RPF7 but only infected the cotyledons and not the true leaves of certain cultivars. A new set of near-isogenic lines has been developed and evaluated for disease reactions to the new races and novel strains as differentials. None of the 360 U.S. Department of Agriculture spinach germplasm accessions tested were resistant to Pfs 16 or UA1014. A survey of isolates over several years highlighted the dynamic nature of the virulence diversity of the Pfs population. Identification of virulence diversity and evaluation of the genetics of resistance to Pfs will continue to allow for a more effective disease management strategy through resistance gene deployment.


Domestic violence, maternal parenting, maternal mental health, and infant externalizing behavior.
This study examined whether maternal functioning mediated the relationship between domestic violence (DV) and infant externalizing behavior. Participants were 203 mother-infant dyads. Support was found for a partially mediated model in which maternal functioning mediated the relationship between current DV and infant externalizing behaviors. Past DV was directly associated with infants' externalizing behavior. Results suggest the need for early intervention and prevention efforts for families living with DV.


Retinal vein occlusion.
Retinal vein occlusion can provoke a sudden loss of visual acuity. It is generally unilateral. Risk factors include ageing, arterial hypertension, diabetes and elevated intraocular pressure. Neovascularisation of the retina or iris can occur in patients with macular ischaemia, creating a risk of glaucoma. If macular oedema develops, recovery of visual acuity occurs spontaneously but slowly. Patients must be monitored in order to detect and treat neovascularisation as early as possible. Treatments for macular oedema are disappointing.


[Eco-ethological significance of the allometric development of the two visual systems in chiroptera].
Volumes of the rostral colliculus and the nuclei of the geniculate body were examined in 19 species of Chiroptera belonging to 8 families characterized by different eco-ethological adaptations. These volumes were compared to those of Basal Insectivores using the allometry formula. The data were expressed in terms of progression indices which estimate how many times a given brain center is greater than that of a Basal Insectivore of the same body weight. According to the progression indices of the rostral colliculus, Chiroptera separate into two groups: the Megachiroptera which have a mean index of 331 and the Microchiroptera with a mean index of 188. On the other hand, mean indices of the lateral geniculate body distinguish between three groups : the Megachiroptera (mean 869); the frugivorous and nectarivorous Microchiroptera (mean 293); the insect-eating, blood sucking, and fish eating Microchiroptera (mean 135). The results indicate that the two anatomically and structurally distinct elements belong to two functionally different visual systems which have evolved somewhat independently. The relation between allometric development of these visual centers and the eco-ethological adaptations of the species examined reveals, to a certain extent, the relative importance of the different functional aspects of vision.


Performance Assessment of Anti-Xa Assay-Based Heparin Dosing Protocol in Pediatric Patients on Extracorporeal Membrane Oxygenation.
The use of extracorporeal membrane oxygenation (ECMO) in the postoperative cardiac critical care setting is evolving. Anticoagulation monitoring is among the most challenging aspects of pediatrics. However, there is no consensus on the optimal dosing and monitoring of unfractionated heparin in this setting. To address this, we developed an anti-Xa assay-based protocol derived from the best available clinical and anecdotal evidence of ECMO use and assessed its effectiveness in achieving the anti-Xa assay therapeutic target. This prospective single-arm study was conducted in the pediatric carcardiac-surgery intensive care unit of a large tertiary hospital. We used two different anti-Xa assay intensity levels based on the patients' bleeding status. The median patient age was 7 (interquartile range [IQR]: 5-11.25) months, and the median weight was 5.7 (IQR: 3.8-13.82) kg. The median ECMO duration was 6 (IQR: 4.5-7.5) days. The bleeding protocol was used for most patients. Seventy percent achieved the anti-Xa assay therapeutic target during the study period (median: 75.5 h, IQR: 60.5-117.5 h). Hemorrhagic complications were reported in 40% of the patients, and thrombotic complications were reported in 25%. The median length of stay was 37 (IQR: 22-43) days, with a survival-to-discharge rate of 75%. Despite a failure to achieve the anti-Xa assay target within the first ECMO days, most patients achieved the target by the median ECMO duration. Moreover, using two different anti-Xa assay levels reduced thrombotic complications.


The perspective on cholesterol-lowering mechanisms of probiotics.
The use of probiotics as food components combats not only cardiovascular diseases but also many gastrointestinal tract disorders. Their health benefits along with their increased global market have interested scientists for better formulation and appropriate administration to the consumers. However, the lack of clear elucidation of their cholesterol-lowering mechanisms has complicated their proper dosage and administration to the beneficiaries. In this review, proposed mechanisms of cholesterol reduction such as deconjugation of bile via bile salt hydrolase activity, binding of cholesterol to probiotic cellular surface and incorporation into their cell membrane, production of SCFAs from oligosaccharides, coprecipitation of cholesterol with deconjugated bile, and cholesterol conversion to coprostanol have been discussed. Also, hypocholesterolemic effects on human- and animal-trial results, commonly used probiotics and synbiotics with effect on serum cholesterol regulation, types of bile salt hydrolase genes, and substrate specificities have been discussed.


[The prevalence of cognitive and emotional disturbances in epilepsy and its consequences for therapy].
In the course of epilepsy psychic disturbances appear. They concern cognitive as well as emotional dysfunctions. Cognitive and emotional dysfunctions are defined as poliaetiological - "organic" connected with brain pathology and "environmental". Cognitive dysfunctions concern global intelligence and chosen cognitive dysfunctions as well. There are about 30% people with cognitive dysfunctions connected to epilepsy. Primary and secondary emotional dysfunctions are distinguished in traditional approach. Primary emotional and cognitive dysfunctions might be caused by the same factor which cause epilepsy or develop due to the damage of the central nervous system in the course of epilepsy or are related to the pharmacological treatment. Secondary emotional deficits are connected with negative social actions and negative social attitudes toward ill persons with epilepsy. It concerns overprotective attitudes or social isolation. The prevalence of emotional disturbances is estimated at 5-50% in population of patients with epilepsy. The study shows the necessity of conducting psychotherapy and neuropsychological rehabilitation in the course of epilepsy as a part of schema of treatment. The aim of these activities is the improvement of the quality of life and the avoidance of progressive intellectual impairment as well.


Cardiovascular mortality in overweight subjects: the key role of associated risk factors.
The role of obesity and overweight as independent risk factors for cardiovascular disease is still debated. The aim of this study was to evaluate the impact of overweight on cardiovascular mortality according to the presence or absence of associated risk factors. This study included 139,562 men and 104,236 women, aged 18 to 95 years, who had a standard health checkup at the IPC Center between 1972 and 1988. The follow-up period for mortality ended in December 1997. In both genders, the prevalence of hypertension, diabetes, and hypercholesterolemia increased with body mass index (P<0.001). When compared with subjects with a body mass index <25 kg/m2 without associated risk factors, overweight subjects without associated risk factors did not have an increased risk of cardiovascular mortality. Risk of cardiovascular death increased significantly when overweight was associated with hypertension alone [hazard ratio: 2.05 (1.71 to 2.46) in men; 2.15 (1.48 to 3.11) in women]. In both genders, the association of overweight with diabetes alone or hypercholesterolemia alone did not increase the risk. By contrast, in the presence of hypertension, cardiovascular mortality dramatically increased in overweight subjects with hypercholesterolemia [hazard ratio: 2.65 (2.20 to 3.19) in men, 2.57 (1.80 to 3.68) in women] or diabetes [hazard ratio: 3.01 (2.29 to 3.95) in men; 4.50 (2.67 to 7.58) in women]. The data suggest that the presence of high blood pressure in overweight subjects is the key factor leading to a significant increase in cardiovascular mortality. Because overweight significantly increases the prevalence of associated risk factors, especially hypertension, it should be considered as a major cardiovascular risk determinant.


Bioavailability of Carbon Nanomaterial-Adsorbed Polycyclic Aromatic Hydrocarbons to Pimphales promelas: Influence of Adsorbate Molecular Size and Configuration.
Despite carbon nanomaterials' (CNMs) potential to alter the bioavailability of adsorbed contaminants, information characterizing the relationship between adsorption behavior and bioavailability of CNM-adsorbed contaminants is still limited. To investigate the influence of CNM morphology and organic contaminant (OC) physicochemical properties on this relationship, adsorption isotherms were generated for a suite of polycyclic aromatic hydrocarbons (PAHs) on multiwalled carbon nanotubes (MWCNTs) and exfoliated graphene (GN) in conjunction with determining the bioavailability of the adsorbed PAHs to Pimphales promelas using bile analysis via fluorescence spectroscopy. Although it appeared that GN adsorbed PAHs indiscriminately compared to MWCNTs, the subsequent bioavailability of GN-adsorbed PAHs was more sensitive to PAH morphology than MWCNTs. GN was effective at reducing bioavailability of linear PAHs by ∼70%, but had little impact on angular PAHs. MWCNTs were sensitive to molecular size, where bioavailability of two-ringed naphthalene was reduced by ∼80%, while bioavailability of the larger PAHs was reduced by less than 50%. Furthermore, the reduction in bioavailability of CNM-adsorbed PAHs was negatively correlated with the amount of CNM surface area covered by the adsorbed-PAHs. This study shows that the variability in bioavailability of CNM-adsorbed PAHs is largely driven by PAH size, configuration and surface area coverage.


Co-administration of dextromethorphan with morphine attenuates morphine rewarding effect and related dopamine releases at the nucleus accumbens.
Morphine is one of the most effective analgesics in clinic to treat postoperative pain or cancer pain. A major drawback of its continuous use is the development of tolerance and dependence. In our previous study we found that a widely used antitussive agent in clinics, dextromethorphan [(DM); also known as a non-competitive N-methyl- d-aspartate (NMDA) antagonist], could prevent the development of morphine tolerance. In the present study, we further investigated its effect on morphine addiction. Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate the drug-seeking related behaviors, which were in correlation with psychological dependence. Our results showed that co-administered DM was able to abolish completely the CPP effect induced by morphine, but had no effect on morphine-induced behavioral sensitization. By employing the microdialysis technique in free-moving animals, we also determined the extracellular level of dopamine and serotonin metabolites in the shell region of the nucleus accumbens (NAc) in its response to morphine with/without DM. A significant increase in dopamine metabolites following morphine administration was demonstrated in the NAc. This increase by morphine could be attenuated by co-administered DM, whereas DM itself did not show any effect. Based on our results, it is speculated that DM may effectively attenuate morphine-induced psychological dependence. Neurochemical analysis revealed that the effect of DM could be through its action on the dopaminergic mesolimbic pathway, which could be activated by morphine and attributed to the cause of rewarding.


Invited and uninvited applause in political speeches.
According to Atkinson (e.g. 1983, 1984a, 1984b), a limited range of rhetorical devices are consistently used by political speakers to invite audience applause. A detailed review is presented of the research literature relevant to Atkinson's analysis, including a series of evaluative studies conducted by the author. From this review, it is argued that Atkinson overestimated the role of rhetorical devices in inviting applause and underestimated the significance of other features, such as asynchronous applause, speech delivery, speech content and uninvited applause. To integrate these features, a re-conceptualisation is presented of how audience applause occurs in political speeches, based on a fundamental distinction between invited and uninvited applause.


A new spectrometer design for the x-ray spectroscopy of laser-produced plasmas with high (sub-ns) time resolution.
This paper describes a new type of x-ray crystal spectrometer, which can be used in combination with gated x-ray detectors to obtain spectra from laser-produced plasmas with a high (sub-ns) time resolution. The spectrometer consists of a convex, spherically bent crystal, which images individual spectral lines as perfectly straight lines across multiple, sequentially gated, strip detectors. Since the Bragg-reflected rays are divergent, the distance between detector and crystal is arbitrary, so that this distance can be appropriately chosen to optimize the experimental arrangement with respect to the detector parameters. The spectrometer concept was verified in proof-of-principle experiments by imaging the Lβ1- and Lβ2-lines of tungsten, at 9.6735 and 9.96150 keV, from a micro-focus x-ray tube with a tungsten target onto a two-dimensional pixilated Pilatus detector, using a convex, spherically bent Si-422 crystal with a radius of curvature of 500 mm.


Peptide emulsions in incomplete Freund's adjuvant create effective nurseries promoting egress of systemic CD4+ and CD8+ T cells for immunotherapy of cancer.
Water-in-oil emulsion incomplete Freund's adjuvant (IFA) has been used as an adjuvant in preventive and therapeutic vaccines since its development. New generation, highly purified modulations of the adjuvant, Montanide incomplete seppic adjuvant (ISA)-51 and Montanide ISA-720, were developed to reduce toxicity. Montanide adjuvants are generally considered to be safe, with adverse events largely consisting of antigen and adjuvant dose-dependent injection site reactions (ISRs). Peptide vaccines in Montanide ISA-51 or ISA-720 are capable of inducing both high antibody titers and durable effector T cell responses. However, an efficient T cell response depends on the affinity of the peptide to the presenting major histocompatibility complex class I molecule, CD4+ T cell help and/or the level of co-stimulation. In fact, in the therapeutic cancer vaccine setting, presence of a CD4+ T cell epitope seems crucial to elicit a robust and durable systemic T cell response. Additional inclusion of a Toll-like receptor ligand can further increase the magnitude and durability of the response. Use of extended peptides that need a processing step only accomplished effectively by dendritic cells (DCs) can help to avoid antigen presentation by nucleated cells other than DC. Based on recent clinical trial results, therapeutic peptide-based cancer vaccines using emulsions in adjuvant Montanide ISA-51 can elicit robust antitumor immune responses, provided that sufficient tumor-specific CD4+ T cell help is given in addition to CD8+ T cell epitopes. Co-treatment with PD-1 T cell checkpoint inhibitor, chemotherapy or other immunomodulatory drugs may address local and systemic immunosuppressive mechanisms, and further enhance efficacy of therapeutic cancer peptide vaccines in IFA and its modern variants. Blinded randomized placebo-controlled trials are critical to definitively prove clinical efficacy. Mineral oil-based adjuvants for preventive vaccines, to tackle spread and severity of infectious disease, induce immune responses, but require more studies to reduce toxicity.


A step toward precision gerontology: Lifespan effects of calorie and protein restriction are consistent with predicted impacts on entropy generation.
Understanding aging is a key biological goal. Precision gerontology aims to predict how long individuals will live under different treatment scenarios. Calorie and protein restriction (CR and PR) extend lifespan in many species. Using data from C57BL/6 male mice under graded CR or PR, we introduce a computational thermodynamic model for entropy generation, which predicted the impact of the manipulations on lifespan. Daily entropy generation decreased significantly with increasing CR level, but not PR. Our predictions indicated the lifespan of CR mice should increase by 13 to 56% with 10 to 40% CR, relative to ad libitum-fed animals. This prediction was broadly consistent with the empirical observation of the lifespan impacts of CR in rodents. Modeling entropy fluxes may be a future strategy to identify antiaging interventions.


Brodie's Abscess: A Diagnostic Conundrum.
Atraumatic limb pain in a child raises concerns in a medical setting. That is how a typical case of Brodie's abscess presents, having pain without any other symptoms of systemic illness. Assessment and investigations might also not reveal anything significant unless adequate imaging is done. Although Brodie's abscess has a very low rate of complications and morbidity/disability, it is important that such a presentation is assessed clinically with a diagnosis of Brodie's abscess in mind to ensure an uneventful and good outcome. We illustrate in this case report a similar presentation of an 11-year-old girl who had multiple visits to primary care. She was then assessed through radiological imaging. By the time of her diagnosis, her abscess had protruded through the skin. Thankfully management was done swiftly after identification and the final outcome was good with complete recovery.


Does Sex Bias Play a Role for Dissatisfied Patients With Hypothyroidism?
The current state of the diagnosis and management of thyroid disease cannot be separated from the larger context of women's health for the following reasons: (1) the disproportionate incidence and prevalence of functional and structural thyroid diseases among women vs men; (2) the role of thyroid health on fertility, pregnancy, and postpartum; and (3) the challenge posed in managing the nonspecific symptoms of functional thyroid disease in the context of menopause. Here, we explore the hypothesis that sex bias has played a role in the management of thyroid diseases historically and has extended into the modern medical era. Once knowledge gaps that may have resulted from sex bias are recognized, we can strive to overcome this bias and develop better treatments to improve patient outcomes universally.


[Clinical characteristics of 96 patients with advanced schistosomiasis in Yingcheng City].
To understand the clinical characteristics of patients with advanced schistosomiasis in Yingcheng City, so as to provide evidences for the assistance work of advanced schistosomiasis. The clinical data of all the advanced schistosomiasis patients in Yingcheng City were collected and analyzed. Up to December 30, 2014, there were 96 advanced schistosomiasis patients in Yingcheng City, among which, 68 cases (70.8%) were male, 28 cases (29.2%) were female, and their average age was 64.2 years. Most of the patients (90.6%) were ascitic type, followed by splenomegaly type (5.2%), colon proliferation type (2.1%), and dwarf type (2.1%). Totally 48 cases (50.0%) were positive in immunological detections, among which 8 cases (8.3%) were positive in ELISA and 12 cases (12.5%) were positive in IHA. For all the 4 indexes of hepatic fibrosis (HA, LN, CIV and PCⅢ), only 15 cases (15.6%) were normal. Though Yingcheng City has reached the criteria of transmission control, the hepatic fibrosis of some patients continues to progress. Therefore, the intensity of the treatment and assistance could not be weakened, especially for those of the ascitic type patients.


Isolation of LEM domain-containing 1, a novel testis-specific gene expressed in colorectal cancers.
Through analysis of genome-wide expression profiles on a cDNA microarray consisting of 23,040 human genes, we have been attempting to isolate novel molecular targets for diagnosis, treatment and prevention of colorectal carcinoma (CRC). Among the genes that were frequently transactivated in colorectal tumors, we identified a novel gene termed LEMD1 (LEM domain-containing 1) whose expression was elevated in 17 of 18 CRCs compared with their corresponding non-cancerous mucosae. Northern blotting revealed that LEMD1 was expressed only in testis among the 16 normal adult tissues examined. Subsequent analysis identified six alternatively spliced forms of the transcript in normal testis, but only one of them (656 nucleotides) was expressed in CRCs. Since the LEMD1 protein appears to fall in the category of cancer-testis antigens (CTAs), it may represent a promising target antigen for immunotherapy of CRCs.


The prognostic value of post-exercise blood pressure reduction in patients with hypertensive response during exercise stress test.
Hypertensive response at peak-exercise and during the recovery phase of exercise stress test (ET) is associated with poor cardiovascular prognosis. We investigated whether decrease in blood pressure (BP) from peak to post-exercise would identify a subgroup at higher cardiovascular risk. Eighty-six non-hypertensive patients (0-4 cardiovascular risk factors) with hypertensive reaction at peak-ET (systolic>180 mm Hg and/or diastolic>100 mm Hg) were divided based on BP 5 min after exercise termination into two groups: Normal response (NrmR) (<160/90 mm Hg), Hypertensive response (HypR) (>/=160/90 mm Hg). Five years later the prevalence of cardiovascular risk factors and cardiovascular morbidity and mortality was assessed for each group. Both groups had similar pre- and peak-exercise BP. However the HypR group had higher post-exercise BP (systolic: 163+/-13 vs. 125+/-14 mm Hg, respectively, p<0.01, and diastolic: 74+/-6 vs. 75+/-4 mm Hg, respectively, p<0.01), smaller decrease in BP after exercise (Delta systolic: 46.9+/-3.1 vs. 73.9+/-3.6 mm Hg, respectively, p<0.01, Delta diastolic: 12.4+/-1.5 vs. 26.5+/-2.2 mm Hg, respectively, p<0.01), and higher post- than pre-exercise BP (Delta systolic: 24.5+/-3.5 vs. -6+/-4.1 mm Hg, respectively, p<0.01, A diastolic: 19+/-2.1 vs. -13+/-2.3 mm Hg, respectively, p<0.01). Five years later, HypR group had higher prevalence of abnormal cholesterol serum level (p<0.01), hypertension (p<0.01) and combined ischemic heart disease and cerebrovascular disease (RR 1.32, 95% CI=1.13-1.54, p<0.01). During ET evaluation, it is important to evaluate the BP at 5 min after exercise because reduced BP drop, at this routinely measured point, identifies a subgroup with higher cardiovascular risk.


Using a homology model of cytochrome P450 2D6 to predict substrate site of metabolism.
CYP2D6 is an important enzyme that is involved in first pass metabolism and is responsible for metabolizing ~25% of currently marketed drugs. A homology model of CYP2D6 was built using X-ray structures of ligand-bound CYP2C5 complexes as templates. This homology model was used in docking studies to rationalize and predict the site of metabolism of known CYP2D6 substrates. While the homology model was generally found to be in good agreement with the recently solved apo (ligand-free) X-ray structure of CYP2D6, significant differences between the structures were observed in the B' and F-G helical region. These structural differences are similar to those observed between ligand-free and ligand-bound structures of other CYPs and suggest that these conformational changes result from induced-fit adaptations upon ligand binding. By docking to the homology model using Glide, it was possible to identify the correct site of metabolism for a set of 16 CYP2D6 substrates 85% of the time when the 5 top scoring poses were examined. On the other hand, docking to the apo CYP2D6 X-ray structure led to a loss in accuracy in predicting the sites of metabolism for many of the CYP2D6 substrates considered in this study. These results demonstrate the importance of describing substrate-induced conformational changes that occur upon binding. The best results were obtained using Glide SP with van der Waals scaling set to 0.8 for both the receptor and ligand atoms. A discussion of putative binding modes that explain the distribution of metabolic sites for substrates, as well as a relationship between the number of metabolic sites and substrate size, are also presented. In addition, analysis of these binding modes enabled us to rationalize the typical hydroxylation and O-demethylation reactions catalyzed by CYP2D6 as well as the less common N-dealkylation.


Composites Formed from Thermoresponsive Polymers and Conductive Nanowires for Transient Electronic Systems.
The disintegration of transient electronic systems after a preprogrammed time or a particular stimulus (e.g., water, light, or temperature) is fundamentally linked to the properties and behavior of the materials used for their construction. Herein, we demonstrate that polymers exhibiting lower critical solution temperature (LCST) behavior can work as thermoresponsive substrates for circuitry and that these materials can be coupled with conductive nanowires to form a transient electronics platform with unique, irreversible temperature-responsive behavior. The transient systems formed from composites of LCST polymers and conductive nanowires exhibit stable electrical performance in solution (Tsolution > LCST) for over 24 h until a cooling stimulus triggers a rapid (within 5 min) and gigantic (3-4 orders of magnitude) transition in electrical conductance due to polymer dissolution. Using a parylene mask, we are able to fabricate thermoresponsive electrical components, such as conductive traces and parallel-plate capacitors, demonstrating the versatility of this material and patterning technique. With this unique stimulus-responsive transient system and polymers with LCSTs above room temperature (e.g., poly(N-isopropylacrylamide), methyl cellulose), we have developed a platform in which a circuit requires a source of heat to remain viable and is destroyed and vanishes once this heat source is lost.


Robust Parking Path Planning with Error-Adaptive Sampling under Perception Uncertainty.
In automated parking systems, a path planner generates a path to reach the vacant parking space detected by a perception system. To generate a safe parking path, accurate detection performance is required. However, the perception system always includes perception uncertainty, such as detection errors due to sensor noise and imperfect algorithms. If the parking path planner generates the parking path under uncertainty, problems may arise that cause the vehicle to collide due to the automated parking system. To avoid these problems, it is a challenging problem to generate the parking path from the erroneous parking space. To solve this conundrum, it is important to estimate the perception uncertainty and adapt the detection error in the planning process. This paper proposes a robust parking path planning that combines an error-adaptive sampling of generating possible path candidates with a utility-based method of making an optimal decision under uncertainty.By integrating the sampling-based method and the utility-based method, the proposed algorithm continuously generates an adaptable path considering the detection errors. As a result, the proposed algorithm ensures that the vehicle is safely located in the true position and orientation of the parking space under perception uncertainty.


Efficacy of Plasma Rich in Growth Factors (PRGF) in Stage 1 Neurotrophic Keratitis.
Neurotrophic keratitis (NK) is a neurodegenerative disease that can lead to corneal hypoesthesia, decreased tear production, and epitheliopathy. Based on the severity of ocular surface damage, NK is classified into 3 stages. Stage 1 NK is characterized by superficial punctate keratopathy, tear film instability, and reduced corneal sensation. The therapeutic efficacy of PRGF eye drops for NK stages 2 and 3 has been previously reported. In this study, we evaluated the efficacy and safety of autologous PRGF eye drops in improving corneal sensitivity and other ocular surface clinical signs in patients with stage 1 NK. Retrospective chart review. 26 eyes of 15 stage 1 NK patients (seven males, eight females), aged 76.3 ± 12.1 years, were included in the study. The mean treatment duration was 2 ± 1.8 months. With PRGF treatment, corneal sensitivity increased from 2.8 to 4.5 cm in 53.8% (14/26) (p < 0.01), TBUT increased from 3.6 to 5.0 s in 69.2% (18/26) (p < 0.01), and Schirmer score increased from 13.7 to 16.8 mm in 80.7% (21/26) of treated eyes (p < 0.01). Similarly, an improvement in corneal staining (punctate epithelial erosions) and MMP-9 levels was seen in 80.7% (n = 21) and 65.4% (n = 17) of treated eyes, respectively. BCVA improvement was seen in 26.9% of treated eyes (n = 7). This study demonstrates the effective role of PRGF therapy in recovering corneal sensation and tear film function and in the healing of corneal erosions in stage 1 NK patients.


Ternary Ni-Co-F Nanocrystal-Based Supercapacitors.
Ternary nickel cobalt fluoride (Ni-Co-F) nanocrystals are constructed solvothermally for use as the positive electrode materials in supercapacitors. The optimal Ni-Co-F (Ni/Co=2:1) shows slight chemical shifts in X-ray diffraction (XRD) data and X-ray photoelectron spectra (XPS) compared with bare Ni-F and Co-F. The Ni-Co-F (Ni/Co=2:1) exhibits typical square nanocrystal morphology together with a mesoporous surface structure, as observed through TEM observations and nitrogen sorption measurements. Owing to the stronger synergistic effect of Ni and Co redox species originated from the richer Ni and Co surface electroactive sites, Ni-Co-F (Ni/Co=2:1) shows superior performances of specific capacitance, rate capability, and charge-transfer kinetics (564 F g-1 at 1 Ag-1 , 418 F g-1 at 16 Ag-1 , 449 Ω) compared with all the other Ni-Co-F candidates. Moreover, the activated carbon (AC)//Ni-Co-F (Ni/Co=2:1) asymmetric capacitor designed based on charge balance delivers superior energy and power densities (18.4 Wh kg-1 , 6.64 kW kg-1 ) together with longer cycle life (77 % retention after 10 000 cycles at 4 A g-1 ).


[The effect of lead acetate on qualitative and quantitative characteristics of mammary mastocytes in primigravid rats].
The mammary mast cells number, structure and distribution was studied at 7, 14 and 21 days post-plug data in Wistar rats receiving lead acetate via drinking water or deionized water during first pregnancy. Toluidine blue or alcian blue and safranine-staining of the material from left abdominal mammary glands were used for histological, histochemical and morphometry evaluation. Thirty random oil immersion fields of three distant tissue section in the stromal compartment of each gland's areas were counted. The parallel progress of mast cells number with gestational progression of mammary gland, dominance alcian blue-stained positive, granulated and with epithelial unassociated mammary mast cells was estimated in normal pregnant animals. Significant increased mammary cells number, dominance of safranine-stained positive, with epithelium unassociated and degranulating mast cells was estimated in lead acetate treated pregnant animals. We concluded that lead acetate exerts on qualitative and quantitative characteristics of mammary mast cells during pregnancy in Wistar rats. We propose some protective role of mammary mast cells in pregnant animals treated by lead acetate.


Transcription factor organic cation transporter 1 (OCT-1) affects the expression of porcine Klotho (KL) gene.
Klotho (KL), originally discovered as an aging suppressor, is a membrane protein that shares sequence similarity with the β-glucosidase enzymes. Recent reports showed Klotho might play a role in adipocyte maturation and systemic glucose metabolism. However, little is known about the transcription factors involved in regulating the expression of porcine KL gene. Deletion fragment analysis identified KL-D2 (-418 bp to -3 bp) as the porcine KL core promoter. MARC0022311SNP (A or G) in KL intron 1 was detected in Landrace × DIV pigs using the Porcine SNP60 BeadChip. The pGL-D2-A and pGL-D2-G were constructed with KL-D2 and the intron fragment of different alleles and relative luciferase activity of pGL3-D2-G was significantly higher than that of pGL3-D2-A in the PK cells and ST cells. This was possibly the result of a change in KL binding ability with transcription factor organic cation transporter 1 (OCT-1), which was confirmed using electrophoretic mobility shift assays (EMSA) and chromatin immune-precipitation (ChIP). Moreover, OCT-1 regulated endogenous KL expression by RNA interference experiments. Our study indicates SNP MARC0022311 affects porcine KL expression by regulating its promoter activity via OCT-1.


Fenugreek (Trigonella foenum graecum) seed protein isolate: extraction optimization, amino acid composition, thermo and functional properties.
With increasing demand for new protein sources, research on plant protein extraction and evaluation of the functional properties of protein isolates is necessary. In this study, pH and NaCl concentration, as two parameters affecting protein extraction of fenugreek seed, was investigated and the condition of fenugreek protein isolate (FPI) extraction was optimized using response surface methodology. FPI had significantly (P< 0.05) higher protein and essential amino acid content (891.00 and 387.41 g kg(-1) , respectively) compared with soy protein isolate (SPI). FPI was rich in Asp and Glu, confirming the presence of bands in the acidic region (30-39 kDa) of its electrophoretic pattern. Differential scanning calorimeter thermography of both FPI and SPI showed two peaks with high denaturation temperature, confirming the presence of high protein content and hydrophobic amino acids. Protein solubility, foaming capacity, foam stability and emulsion stability of FPI were higher than SPI; moreover, both FPI and SPI showed pH-dependent protein functionalities. Fenugreek seed protein extraction was optimized by control of pH and NaCl concentration. FPI could be used as a protein source with remarkable functional properties.


The Scintigraphic Findings of Gastroesophageal Reflux in Children is Related to Body Weight?
Gastroesophageal reflux disease (GERD) is the most common cause of children admissions to pediatric gastroenterology unit and affects about 30% of pediatric population. Body weight and height percentiles of children with GERD and their relationship between presence and the severity of reflux on scintigraphic images were studied. Patients who underwent reflux scintigraphy between 2005 - 2012 were retrospectively reviewed. Among 200 patients, 49 patients were involved that their ages were ranging from 0 to 18 years old and body weight and height percentiles were recorded. Accurately 37 MBq (1 mCi) 99mTc-MAA in 100 - 150 mL of milk was ingested by the patient. Presence, number, duration and level of reflux were evaluated on the dynamic images. Presences of reflux within last ten minute were also recorded. Region-of-interests were drawn on esophagus and stomach and reflux ratio (RR) was calculated. The ratio of the presence of reflux which occurred within the last ten minutes was significantly higher in children with low body weight percentile. High-level reflux frequency was higher in these children than in normal's. Presence of reflux which occurred within the last ten minutes was related with low body weight percentile. If reflux is shown within the last ten minutes and there is high level of reflux, the clinician should be warned about possible low body weight percentile in the future and scintigraphic study should be a guide or a reference for the assessment of more effective treatment methods.


Advances, challenges, and prospects in microalgal-bacterial symbiosis system treating heavy metal wastewater.
Heavy metal (HM) pollution, particularly in its ionic form in water bodies, is a chronic issue threatening environmental security and human health. The microalgal-bacterial symbiosis (MABS) system, as the basis of water ecosystems, has the potential to treat HM wastewater in a sustainable manner, with the advantages of environmental friendliness and carbon sequestration. However, the differences between laboratory studies and engineering practices, including the complexity of pollutant compositions and extreme environmental conditions, limit the applications of the MABS system. Additionally, the biomass from the MABS system containing HMs requires further disposal or recycling. This review summarized the recent advances of the MABS system treating HM wastewater, including key mechanisms, influence factors related to HM removal, and the tolerance threshold values of the MABS system to HM toxicity. Furthermore, the challenges and prospects of the MABS system in treating actual HM wastewater are analyzed and discussed, and suggestions for biochar preparation from the MABS biomass containing HMs are provided. This review provides a reference point for the MABS system treating HM wastewater and the corresponding challenges faced by future engineering practices.


Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?
To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009). One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.


Enhancer of zeste homolog 2 induces pulmonary artery smooth muscle cell proliferation.
Pulmonary Arterial Hypertension (PAH) is a progressively devastating disease characterized by excessive proliferation of the Pulmonary Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share an apoptosis-resistant state featuring excessive cell proliferation. The proliferation of cancer cells is mediated by increased expression of Enhancer of Zeste Homolog 2 (EZH2), a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes. However, the role of EZH2 in PAH has not been studied. In this study, it is hypothesized that EZH2 could play a role in the proliferation of PASMCs. In the present study, the expression patterns of EZH2 were investigated in normal and hypertensive mouse PASMCs. The effects of EZH2 overexpression on the proliferation of human PASMCs were tested. PASMCs were transfected with EZH2 or GFP using nucleofector system. After transfection, the cells were incubated for 48 hours at 37°C. Proliferation and cell cycle analysis were performed using flow cytometry. Apoptosis of PASMCs was determined using annexin V staining and cell migration was tested by wound healing assay. EZH2 protein expression in mouse PASMCs were correlated with an increase in right ventricular systolic pressure and Right Ventricular Hypertrophy (RVH). The overexpression of EZH2 in human PASMCs enhances proliferation, migration, and decrease in the rate of apoptosis when compared to GFP-transfected cells. In the G2/M phase of the EZH2 transfected cells, there was a 3.5 fold increase in proliferation, while there was a significant decrease in the rate of apoptosis of PASMCs, when compared to control. These findings suggest that EZH2 plays a role in the migration and proliferation of PASMCs, which is a major hallmark in PAH. It also suggests that EZH2 could play a role in the development of PAH and can serve as a potential target for new therapies for PAH.


Disseminated cancer in pregnancy: krukenberg tumour.
Disseminated cancer presenting in pregnancy is extremely rare and its presentation can easily be obscured by pregnancy and physiological changes that occur with it. This case describes a patient who was diagnosed incidentally following investigations for preeclampsia. Despite initially being thought to be of low risk, the final diagnosis was that of metastasis from a primary cancer of an unknown origin, most likely a gastric adenocarcinoma. Although patients are under thorough observation throughout their pregnancy, this case highlights the potential need for additional investigations or adjustment of current practices. It also draws attention to the lack of sufficient reporting of cancer in pregnancy, which, considering its rarity, greatly influences how patients are managed.


Deoxyribonucleic acid polymerase activities in normal and leukovirus-infected chicken embryo cells.
Chicken embryo cells normally contain, in addition to deoxyribonucleic acid (DNA)-dependent DNA (D-DNA) polymerases, a novel "R-DNA-polymerase" which specifically copies polyriboadenylic acid strands. This R-DNA polymerase cannot copy natural ribonucleic acid or polyribocytidylic acid strands to a significant extent. Infection of cells with the leukovirus RAV-2 leads to the intracellular formation of large amounts of the viral RNA-dependent DNA polymerase whose properties differ from the cell R-DNA polymerase. Chicken cells transformed by a Rous sarcoma virus mutant which produce noninfectious alpha-type Rous sarcoma virus (f), a leukovirus known to be deficient in the viral RNA-dependent DNA polymerase, do not contain detectable viral RNA-dependent DNA polymerase, whereas the cellular R-DNA polymerase is found in normal amounts. There seems to be no relationship between the cellular R-DNA polymerase and the RNA-dependent DNA polymerase of the avian leukoviruses.


Factors affecting the therapeutic effect of botulinum toxin A on trigeminal neuralgia: A follow-up retrospective study of 152 patients.
Botulinum toxin A (BTX-A) is a promising therapeutic modality against trigeminal neuralgia (TN) with certain controversies pertaining to its application. To provide further information on factors influencing the treatment outcomes of BTX-A, a retrospective study with 152 patients with TN treated with BTX-A was performed. The starting time and duration of the therapeutic effect, as well as side effects, of BTX-A in the treatment of TN were analyzed by sex, age, course of disease, number of branches and injected dose. A total of 136 patients exhibited symptom improvement within 2 weeks following BTX-A treatment as evaluated using a visual analog scale (VAS). The effect of BTX-A was sustained throughout the initial 6 months of the follow-up and was demonstrated to persist for as long as 28 months. Female sex, short disease course and high injection dose (>70 units) were associated with lower long-term VAS scores. Patients receiving short-term medium-(50-70 units) or high-dose injections were more likely to be completely cured. Patients with a median disease course (1-10 years) or multiple branches were more likely to exhibit facial asymmetry. Based on the stratified analysis, female patients with a median disease course (1-10 years) exhibited a higher incidence of side effects and male patients achieved better treatment outcomes with high BTX-A doses. BTX-A effectively alleviated patients with TN in both short or long term, although the treatment efficacy may depend on patient characteristics.


Correlation of platelets count with endoscopic findings in a cohort of Egyptian patients with liver cirrhosis.
Screening endoscopy is recommended for early detection of esophageal varices (EVs) in cirrhotic patients with portal hypertension. However, this approach is limited by its invasiveness and cost. The aim of the study was to determine if platelet count can predict the presence of EVs, especially large (grade III, IV) EVs in need of prophylactic therapy, in a cohort of Egyptian patients with liver cirrhosis. In all, 110 patients with cirrhosis were prospectively analyzed. The presence of medium or large EVs was correlated with patients' platelet count and FIB-4. Esophageal varices were present in 87 (79.09%) patients. Among those with thrombocytopenia (platelet level below 150,000), 25.97% (20 patients) and 27.27% (21 patients) had EV grade II and EV grade III or IV, respectively. Whereas in patients in whom the platelet count was above 150,000, only 21.21% (7 patients) and 9.09% (3 patients) of patients had grade II EV and EV grade III or IV, respectively. A platelet count cut-off value of 149,000 was found to have specificity of 82% and sensitivity 39% for detection of presence of varices. A FIB-4 cut-off value of 3.175 was found to have an 83.3% sensitivity and 39.5% specificity in detecting large (grade III, IV) EVs. Platelet count is a noninvasive parameter with high accuracy for prediction of EVs. Cirrhotic patients with normal platelet counts (above 150,000), especially in financially deprived developing countries, can avoid screening endoscopy as they are at a low risk for variceal bleeding, and presence of large EVs in these patients is much less common than in those with thrombocytopenia. A 3.175 cut-off value of FIB-4 could be useful as a noninvasive predictor of large varices requiring prophylactic banding in cirrhotic patients.


The incentive salience of alcohol: translating the effects of genetic variant in CNR1.
The gene that codes for cannabinoid receptor 1 (CNR1) represents an important target for investigations designed to elucidate individual differences in the etiology of alcohol dependence. To achieve a better understanding of the role of the CNR1 gene in the etiology and treatment of alcohol dependence. The present investigation spans multiple levels of analysis, including receptor binding in postmortem brain tissue, neuroimaging, human laboratory models, and analyses of treatment outcome data. Findings indicate that the C allele of rs2023239 is associated with greater CB1 binding in the prefrontal cortex, greater alcohol cue-elicited brain activation in the midbrain and prefrontal cortex, greater subjective reward when consuming alcohol, and more positive outcomes after treatment with a medication that targets the mesocorticolimbic neurocircuitry. In addition, there were strong correlations between cue-elicited brain activation and alcohol consumption measures in individuals with the C allele. Individuals with the C allele may be more susceptible to changes in the mesocorticolimbic neurocircuitry that is involved in the attribution of incentive salience after repeated exposure to alcohol.


[The medical curriculum need not take the religious beliefs and cultural background of the students into consideration].
Newly graduated doctors must be able to solve a limited number of patient-specific problems in an adequate manner. The patient is at the centre of attention here, not the doctor. Accepting religious beliefs and cultural differences as an excuse for not learning something would mean that other excuses would also be accepted more readily, thus changing the primary goals of the medical curriculum.


Converting a Natural Protein Compartment into a Nanofactory for the Size-Constrained Synthesis of Antimicrobial Silver Nanoparticles.
Engineered biological systems are used extensively for the production of high value and commodity organics. On the other hand, most inorganic nanomaterials are still synthesized via chemical routes. By engineering cellular compartments, functional nanoarchitectures can be produced under environmentally sustainable conditions. Encapsulins are a new class of microbial nanocompartments with promising applications in nanobiotechnology. Here, we engineer the Thermotoga maritima encapsulin EncTm to yield a designed compartment for the size-constrained synthesis of silver nanoparticles (Ag NPs). These Ag NPs exhibit uniform shape and size distributions as well as long-term stability. Ambient aqueous conditions can be used for Ag NP synthesis, while no reducing agents or solvents need to be added. The antimicrobial activity of the synthesized protein-coated or shell-free Ag NPs is superior to that of silver nitrate and citrate-capped Ag NPs. This study establishes encapsulins as an engineerable platform for the synthesis of biogenic functional nanomaterials.


Prevalence and intensity of urinary schistosomiasis among school children in the district of Niakhar, region of Fatick, Senegal.
Urinary schistosomiasis is a parasitic disease that exists in all regions of Senegal. It is a major public health issue in this country. This study was carried out to determine the prevalence and intensity of this parasitosis in 12 villages of Niakhar (Fatick, Senegal). A total of 210 schoolchildren, aged 7 to 15 years, were enrolled in this study, and urine samples were examined for Schistosoma haematobium eggs using a standard urine filtration technique. Of these children, 121 (57.6%) were found to be infected with a mean geometric count of 185 eggs per 10 ml of urine. The disease was present in all surveyed villages, and the prevalence ranged from 14.3% to 92.8%. The prevalence of infection was significantly correlated with increasing age and was higher in boys. Infection intensity was significantly higher in boys but did not significantly differ with age. Significant relationships between i) water contact or access to running water and ii) the prevalence or intensity of urinary schistosomiasis were also noted. The district of Niakhar is endemic for urinary schistosomiasis, with a high intensity of infection. A control program to decrease the prevalence and intensity should be implemented in this area to improve community health.


Proton Transfer in Mixed Clusters of Methanesulfonic Acid, Methylamine, and Oxalic Acid: Implications for Atmospheric Particle Formation.
Understanding the properties of atmospheric particles made of several components is a very challenging problem. In this paper, we perform quantum chemical calculations for small multicomponent clusters of atmospheric relevance that incorporate methanesulfonic acid (MSA), methylamine (MA), oxalic acid (OxA), and water (H2O). Potential correlations between theoretical predictions of proton transfer in the small clusters and findings of recent experiments on formation of particles of detectable sizes (>2 nm) from the same components are studied. It is proposed that proton transfer from the acid to the amine in the 1:1 clusters correlates with experiments on particle formation in systems, such as MSA-MA and MSA-MA-OxA. In the case of OxA + MA, which has been observed to give few particles, proton transfer does not occur for the 1:1 cluster but does for the 2:2 cluster. Adding H2O to OxA-MA promotes the occurrence of proton transfer, and corresponding particles are slightly enhanced. The partial charge on the MA component increases by adding OxA or H2O to MSA-MA, which is correlated with enhanced particle formation compared to MSA-MA alone. Ab initio molecular dynamics simulations show that proton transfer at room temperature (T = 298 K) and high temperature (T = 500 K) is little affected compared with the equilibrium structure (T = 0 K). These results suggest that small cluster calculations may be useful in predicting the formation of multicomponent particles in the atmosphere.


Can microbial-based insecticides replace chemical pesticides in agricultural production?
Extensive use of chemical insecticides to control insect pests in agriculture has improved yields and production of high-quality food products. However, chemical insecticides have been shown to be harmful also to beneficial insects and many other organisms like vertebrates. Thus, there is a need to replace those chemical insecticides by other control methods in order to protect the environment. Insect pest pathogens, like bacteria, viruses or fungi, are interesting alternatives for production of microbial-based insecticides to replace the use of chemical products in agriculture. Organic farming, which does not use chemical pesticides for pest control, relies on integrated pest management techniques and in the use of microbial-based insecticides for pest control. Microbial-based insecticides require precise formulation and extensive monitoring of insect pests, since they are highly specific for certain insect pests and in general are more effective for larval young instars. Here, we analyse the possibility of using microbial-based insecticides to replace chemical pesticides in agricultural production.


A comparison of antioxidant status and free radical peroxidation of plasma lipoproteins in healthy young persons from Naples and Bristol.
Ischaemic heart disease mortality is much lower in Southern Italy than in the U.K. and this is not entirely explained by differences in classical risk factors. Differences in antioxidant intake, affecting free radical peroxidation of plasma lipoproteins, may be relevant. Therefore, dietary intake, antioxidant status and plasma lipid peroxidation were compared in healthy young persons eating typical regional diets from Naples (22) and Bristol (26). The Naples group consumed more fresh tomatoes, more fat as monounsaturates (from olive oil) and had higher plasma levels of the lipid antioxidants vitamin E (mean (SD; 95% CI) 29.1 (4.5; 26.8 to 31.3) vs 25.1 (3.86; 23.4 to 26.8) mumol.l-1, P = 0.005) and beta-carotene (4.74 (1.2; 4.14 to 5.34) vs 2.85 (0.8; 2.5 to 3.2) mumol.l-1, P < 0.001). Intakes of vitamin C, total uncooked fruit and vegetables, plasma vitamin A, serum selenium and copper levels were similar. All indices of plasma lipid peroxidation were significantly lower in the Naples group: conjugated dienes (median (interquartile range; non-parametric 95% CI)) 29 (21.5-39.9; 24 to 36.7) vs 41.5 (37-48.5; 38 to 44.5) mumol.l-1, P < 0.001; diene conjugation index 1.38 (1.02-1.55; 1.06 to 1.49) x 10(-2) vs 1.57 (1.43-1.74; 1.44 to 1.71) x 10(-2), P = 0.019; lipid peroxides (geometric mean (95% CI) 1.24 (1.12 to 1.37) vs 4.58 (3.84 to 5.46) mumol.l-1, P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)


The amino acid sequence, immunofluorescence and microinjection studies on the 15 kDa calcium-binding protein from sea urchin egg.
The 15 kDa protein is the most abundant low molecular weight Ca2+-binding protein, different from calmodulin, in eggs of sea urchin, Hemicentrotus pulcherrimus. The data from the amino acid sequence demonstrated that the 15 kDa protein belonged to the troponin C superfamily. Based on immunofluorescent and immunomicroscopic observations, we showed that the 15 kDa protein localized in the nuclei of fertilized eggs and mitotic apparatus of dividing eggs. Microinjection of the antibody against 15 kDa protein into sea urchin blastomeres resulted in the arresting of cell division. These results suggest that the 15 kDa protein plays an important role in mitosis of sea urchin egg.


Chronic hepatitis C complicated by Coombs-negative hemolytic anemia during interferon treatment.
Autoimmune hemolytic anemia is an autoimmune diseases which is reported to be caused by interferon treatment. A 33-year-old male with chronic hepatitis C developed Coombs-negative hemolytic anemia, probably due to administration of interferon-alpha 2b. This is, to our knowledge, the first report of chronic hepatitis C complicated by Coombs-negative hemolytic anemia during interferon treatment.


Improving the prehospital management of ST elevation myocardial infarction: a national quality improvement initiative.
ST elevation myocardial infarction (STEMI) is a time-dependent clinical emergency. Early recognition and intervention in the clinical course of STEMI are key to reducing mortality and morbidity. As a result, the benefits of the prehospital management of patients presenting with STEMI are well supported by the literature. Given these benefits, much of the focus on the development of quality and performance measures for Emergency Medical Services has focused on STEMI care. Historically, within Qatar, however, no measures of prehospital STEMI care have previously existed and as such, little is understood regarding the quality of prehospital care delivered to patients with STEMI. The overall aim of this national initiative was to improve the effectiveness of the prehospital care of patients with STEMI, to a minimum compliance of 75%, as measured by four process measures and one bundle measure, over a 12-month period. Initial efforts were aimed at the development of relevant indicators to guide assessment and identifying an appropriate patient cohort to test improvement efforts. Using these measures and criteria, the project team highlighted several areas for potential improvement centred on three key domains within the service: clinical practice, training and clinical equipment/medication. There was significant and sustained improvement across all measures recorded. For the bundle measure, the median proportional compliance increased from 39% pre-improvement activities to 76% post-improvement activities and remained sustained at 12 months post-implementation. The initiative was successful in meeting all of its aims and furthermore showed sustained compliance at 12 months post-implementation, thanks in part to what were designed to be changes that were simple, yet pragmatic, and readily producible at scale. While a formal cost analysis was not conducted, the improvement activities capitalised on existing organisational structures and processes with the resultant cost perceived to be negligible.


Creating High-Number Defect Sites through a Bimetal Approach in Metal-Organic Frameworks for Boosting Trace SO2 Removal.
Herein, we represent a bimetallic approach to enhance the defect number, leading to eight defect sites per node in a metal-organic framework, showing both a higher SO2 adsorption capacity and higher SO2/CO2 selectivity. The results can be further strongly supported by density functional theory calculations.


Erp72 expression activated by transient cerebral ischemia or disturbance of neuronal endoplasmic reticulum calcium stores.
Stress-induced activation of the expression of the endoplasmic reticulum (ER)-resident chaperon and member of the protein disulfide isomerase family erp72 was studied after transient cerebral ischemia in vivo using the four-vessel occlusion method and experimental depletion of ER calcium stores in primary neuronal cell cultures. After 8 days in vitro, neurons were exposed to thapsigargin (Tg), an irreversible inhibitor of ER Ca2+-ATPase, or the Tg solvent DMSO. In separate experiments neurons were pre-loaded with the cell-permeant calcium chelator BAPTA-AM before Tg exposure. Stress-induced changes in erp72 expression were analysed by quantitative PCR. Transient cerebral ischemia produced a significant increase in erp72 mRNA levels which rose to about 200% of control (hippocampus) or 300% of control (cortex). After depletion of ER calcium stores neuronal erp72 mRNA levels rose markedly, peaking at 12 h of recovery. Counteracting the Tg-induced rise in cytoplasmic calcium activity by preloading cells with the chelator BAPTA-AM did not influence erp72 expression significantly, suggesting that the activation of erp72 expression resulted from the depletion of ER calcium stores and not from the corresponding increase in cytoplasmic calcium activity. An activation of erp72 expression is indicative of a disturbance of ER function. The results of the present study therefore provide evidence to support the notion that transient cerebral ischemia induces disturbances of neuronal ER function, probably through a depletion of ER calcium stores.


Method for transforming alkynes into (E)-dibromoalkenes.
The highly stereoselective bromination of alkynes has been realized by using copper(II) bromide as both the reacting partner and the catalyst, offering a generally efficient synthesis of (E)-dibromoalkenes. The reaction conditions are exceptionally mild, and a wide range of functional groups are well tolerated.


Scale-Up of Academic Mesenchymal Stromal Cell Production.
Many clinical trials have reported the use of mesenchymal stromal cells (MSCs) following the indication of severe SARS-CoV-2 infection. However, in the COVID19 pandemic context, academic laboratories had to adapt a production process to obtain MSCs in a very short time. Production processes, especially freezing/thawing cycles, or culture medium have impacts on MSC properties. We evaluated the impact of an intermediate cryopreservation state during MSC culture to increase production yields. Seven Wharton's jelly (WJ)-MSC batches generated from seven different umbilical cords with only one cryopreservation step and 13 WJ-MSC batches produced with intermediate freezing were formed according to good manufacturing practices. The identity (phenotype and clonogenic capacities), safety (karyotype, telomerase activity, sterility, and donor qualification), and functionality (viability, mixed lymphocyte reaction) were analyzed. No significant differences between MSC production processes were observed, except for the clonogenic capacity, which was decreased, although it always remained above our specifications. Intermediate cryopreservation allows an increase in the production yield and has little impact on the basic characteristics of MSCs.


Fluorescence of tryptophan in designed hairpin and Trp-cage miniproteins: measurements of fluorescence yields and calculations by quantum mechanical molecular dynamics simulations.
The quantum yield of tryptophan (Trp) fluorescence was measured in 30 designed miniproteins (17 β-hairpins and 13 Trp-cage peptides), each containing a single Trp residue. Measurements were made in D(2)O and H(2)O to distinguish between fluorescence quenching mechanisms involving electron and proton transfer in the hairpin peptides, and at two temperatures to check for effects of partial unfolding of the Trp-cage peptides. The extent of folding of all the peptides also was measured by NMR. The fluorescence yields ranged from 0.01 in some of the Trp-cage peptides to 0.27 in some hairpins. Fluorescence quenching was found to occur by electron transfer from the excited indole ring of the Trp to a backbone amide group or the protonated side chain of a nearby histidine, glutamate, aspartate, tyrosine, or cysteine residue. Ionized tyrosine side chains quenched strongly by resonance energy transfer or electron transfer to the excited indole ring. Hybrid classical/quantum mechanical molecular dynamics simulations were performed by a method that optimized induced electric dipoles separately for the ground and excited states in multiple π-π* and charge-transfer (CT) excitations. Twenty 0.5 ns trajectories in the tryptophan's lowest excited singlet π-π* state were run for each peptide, beginning by projections from trajectories in the ground state. Fluorescence quenching was correlated with the availability of a CT or exciton state that was strongly coupled to the π-π* state and that matched or fell below the π-π* state in energy. The fluorescence yields predicted by summing the calculated rates of charge and energy transfer are in good accord with the measured yields.


Anesthesia in an Aging Infant: Neonatal Progeroid Syndrome.
Neonatal progeroid syndrome is a unique condition wherein features of aging are apparent in a newborn at birth. It is a very rare genetic disorder. The first case in India was reported in December 2011. The anesthetic management of any infant with this condition could not be found in the medical literature. Independently described by Rautenstrauch and Wiedemann, neonatal progeroid syndrome poses significant challenges to the anesthesiologist for a variety of anatomic and physiologic reasons. Coronary and cerebrovascular atherosclerosis pose significant concerns in such children. Here, we present the successful anesthetic management of a 6-month-old male infant with neonatal progeroid syndrome operated on for bilateral inguinoscrotal swellings.


(-)-7'-Isothiocyanato-11-hydroxy-1',1'-dimethylheptylhexahydrocannabinol (AM841), a high-affinity electrophilic ligand, interacts covalently with a cysteine in helix six and activates the CB1 cannabinoid receptor.
The CB1 cannabinoid receptor has been shown to play important physiological roles in the central nervous system, as well as peripherally, and is a target for development of therapeutic medications. To gain insight on the ligand binding site(s) and structural features of activation, we designed and synthesized (-)-7'-isothiocyanato-11-hydroxy-1',1'-dimethylheptylhexahydrocannabinol (AM841), a classical cannabinoid affinity label that incorporates an isothiocyanate substituent as an electrophilic reactive group capable of interacting irreversibly with a suitably located and properly oriented nucleophilic amino acid residue at or near the binding site. To obtain evidence for the site of covalent attachment of AM841, C6.47, identified in part by interactive ligand docking, was mutated to serine, alanine, and leucine to reduce or eliminate the nucleophilic character. Wild-type (WT) and mutant CB1 receptors were evaluated for their abilities to recognize a series of cannabinergic ligands. Each bound comparably to WT, excluding C6.47L, which displayed a reduced affinity for 3H-labeled (1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol (CP55940), AM841, 11-hydroxy-1',1'-dimethylheptylhexahydrocannabinol (AM4056), and (-)-7'-bromo-11-hydroxy-1',1'-dimethylheptylhexahydrocannabinol (AM4043) and an improvement in affinity for (-)-trans-delta9-tetrahydrocannabinol (delta9-THC). The affinity of 3H-labeled [2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](naphthyl)methanone (WIN55212-2) was unchanged across all mutants. It is noteworthy that AM841 was shown to bind irreversibly to WT CB1 but exhibited no covalent attachment with the mutants and behaved as an agonist suggesting irreversible attachment to C6.47 maintains CB1 in its active state. The evidence presented identifies C6.47 as the site of covalent bond formation with AM841 and combined with the binding data fully supports the molecular modeling. These studies present the first report of tandem applications of affinity labeling, site-directed mutagenesis, and interactive ligand docking for CB1.


Global mobility for psychologists: the role of psychology organizations in the United States, Canada, Europe, and other regions.
Global mobility for psychologists is rapidly improving because of an emerging consensus on recognition standards, the demand for cross-border mobility both internal and external to the profession, and the efforts of membership, credentialing, and regional organizations to promote mobility. In the United States, multiple credentialing organizations promote mobility, primarily through individual endorsement of credentials. The Canadian regulatory boards signed a mutual recognition agreement implementing fast-track mechanisms for licensed psychologists seeking mobility and a competency-based assessment for initial registration. Europe plans to reduce barriers to mobility through mutual recognition of qualifications via a EuroPsy diploma that provides a benchmark for professional psychology education and training. Other regions have not made as much progress with regard to promoting mobility, as many do not yet even regulate the practice of psychology. The authors examine who seeks mobility, which geographic regions promote mobility, and by which mechanisms.


CT findings in duodenal diverticulitis.
Duodenal diverticulitis is a rare complication of duodenal diverticulosis. It is often clinically misdiagnosed because it has no pathognomonic signs or symptoms and its CT findings may mimic other intraabdominal processes. We describe two patients with duodenal diverticulitis who presented with abdominal pain, nausea, and leukocytosis. At the time of initial presentation, only one of the two patients was diagnosed correctly. In the first case, which was initially misdiagnosed as acute pancreatitis, the correct diagnosis was evident only after the disease process had become more quiescent and a follow-up CT scan using orally and i.v.-administered contrast agents was performed. In the second case, the coronal reformatted images confirmed the diagnosis suggested by the axial images. Duodenal diverticulitis can be a difficult CT diagnosis to make; however, maintaining it in the differential diagnosis of duodenal and pancreatic inflammatory processes and masses as well as defining the anatomy with nonaxial imaging including coronal images may be helpful in confirming the diagnosis.


Donor-acquired fat embolism syndrome after lung transplantation.
Fat embolism is a known complication of severe trauma and closed chest cardiac resuscitation both of which are more common in the lung transplant donor population and can lead to donor-acquired fat embolism syndrome (DAFES). The objective was to review the diagnosis and management of DAFES in the lung transplantation literature and at our centre. We performed a literature review on DAFES using the Medline database. We then reviewed the transplant record of Brigham and Women's Hospital, a large academic hospital with an active lung transplant programme, for cases of DAFES. We identified 2 cases of DAFES in our centre, one of which required extracorporeal membrane oxygenation (ECMO) for successful management. In contrast to the broader literature on DAFES, which emphasizes unsuccessfully treated cases, both patients survived. DAFES is a rare but likely underappreciated early complication of lung transplant as it can mimic primary graft dysfunction. Aggressive interventions, including ECMO, may be necessary to achieve a good clinical outcome following DAFES.


[Delay in the diagnosis of tuberculosis].
In five patients, a 46-year-old Surinamese man, a 45-year-old Dutch barkeeper, a 41-year-old woman from Eritrea, and an 18-year-old Afghan woman and her 43-year-old mother, tuberculosis was diagnosed and treated after a considerable delay. Such a late diagnosis and subsequent treatment is not uncommon for tuberculosis as the symptoms, physical examination, laboratory tests, imaging techniques and bacteriological results are often not very specific. However under certain circumstances, tuberculosis (including the extrapulmonary manifestations) should be considered at an earlier stage, especially among certain risk groups such as the homeless, drug addicts, immigrants and asylum seekers. In the five patients discussed the causes of delay were identified as: delay caused by the asymptomatic phase of the disease, the patient's delay in presenting, a delay on the part of the physician, a delay in diagnostic confirmation and a delay in the treatment.


Overcoming complications of breast implants.
Having nice breasts is important to many women and their self-images. For those women who have had congenital deformities, were not blessed naturally with the shape they wanted, have had experiences that have adversely affected breast tissue, or have had a mastectomy as a result of breast cancer, breast implants can provide a boost in self-confidence. This article provides an overview of breast implant issues and treatments, and reviews breast implant complications, their potential causes and treatments.


The Role of Phospholipase D in Regulated Exocytosis.
There are a diversity of interpretations concerning the possible roles of phospholipase D and its biologically active product phosphatidic acid in the late, Ca(2+)-triggered steps of regulated exocytosis. To quantitatively address functional and molecular aspects of the involvement of phospholipase D-derived phosphatidic acid in regulated exocytosis, we used an array of phospholipase D inhibitors for ex vivo and in vitro treatments of sea urchin eggs and isolated cortices and cortical vesicles, respectively, to study late steps of exocytosis, including docking/priming and fusion. The experiments with fluorescent phosphatidylcholine reveal a low level of phospholipase D activity associated with cortical vesicles but a significantly higher activity on the plasma membrane. The effects of phospholipase D activity and its product phosphatidic acid on the Ca(2+) sensitivity and rate of fusion correlate with modulatory upstream roles in docking and priming rather than to direct effects on fusion per se.


mtDNA analysis reveals a major late Paleolithic population expansion from southwestern to northeastern Europe.
mtDNA sequence variation was studied in 419 individuals from nine Eurasian populations, by high-resolution RFLP analysis, and it was followed by sequencing of the control region of a subset of these mtDNAs and a detailed survey of previously published data from numerous other European populations. This analysis revealed that a major Paleolithic population expansion from the "Atlantic zone" (southwestern Europe) occurred 10,000-15,000 years ago, after the Last Glacial Maximum. As an mtDNA marker for this expansion we identified haplogroup V, an autochthonous European haplogroup, which most likely originated in the northern Iberian peninsula or southwestern France at about the time of the Younger Dryas. Its sister haplogroup, H, which is distributed throughout the entire range of Caucasoid populations and which originated in the Near East approximately 25,000-30,000 years ago, also took part in this expansion, thus rendering it by far the most frequent (40%-60%) haplogroup in western Europe. Subsequent migrations after the Younger Dryas eventually carried those "Atlantic" mtDNAs into central and northern Europe. This scenario, already implied by archaeological records, is given overwhelming support from both the distribution of the autochthonous European Y chromosome type 15, as detected by the probes 49a/f, and the synthetic maps of nuclear data.


Electron beam computed tomographic scanning in preventive medicine.
Undetected coronary atherosclerosis is present in the majority of patients suffering myocardial infarction or sudden death. Electron beam computed tomography affords noninvasive scanning of the heart to detect and measure coronary calcification. These data permit dramatically improved assessment of both short-term and future risk for cardiac and other events. Knowledge of this risk gives the physician an opportunity for timely and cost-effective interventions.


Characterization of a Williopsis saturnus var. mrakii high molecular weight secreted killer toxin with broad-spectrum antimicrobial activity.
Williopsis saturnus var. mrakii MUCL 41968 secretes a killer toxin (WmKT), which is active against a wide range of pathogens. From the W. saturnus var. mrakii MUCL 41968 culture supernatant a protein of 85 kDa with killer activity was purified to homogeneity. The purified protein was demonstrated to be a killer toxin since it displays the toxin activity and cross-reacts with mAbKT4, a monoclonal antibody that blocks WmKT activity. Its partial amino acid sequencing revealed that WmKT might be related to yeast SUN proteins, but not to other killer toxins described. Immunofluorescence studies using polyclonal antibodies raised against purified WmKT revealed that it acts by binding to the cell surface of sensitive strains. We showed that WmKT is inactive against mutant strains of Saccharomyces cerevisiae deficient in the synthesis of beta-glucans, indicating that these polysaccharides constitute the target of the toxin. WmKT was demonstrated to induce rapid lethal cell permeation, since strong propidium iodide labelling was shown for sensitive strains treated with the killer toxin. These findings indicate that WmKT is a novel killer toxin whose molecular characterization may lead to the development of new wide-spectrum antimicrobial compounds.


Glucose oxidase as an alternative to antibiotic growth promoters improves the immunity function, antioxidative status, and cecal microbiota environment in white-feathered broilers.
This study aimed to demonstrate the effects of glucose oxidase (GOD) on broilers as a potential antibiotic substitute. A total of four hundred twenty 1-day-old male Cobb500 broilers were randomly assigned into five dietary treatments, each with six replicates (12 chicks per replicate). The treatments included two control groups (a basal diet and a basal diet with 50 mg/kg aureomycin) and three GOD-additive groups involving three different concentrations of GOD. Analysis after the t-test showed that, on day 21, the feed:gain ratio significantly decreased in the 1,200 U/kg GOD-supplied group (GOD1200) compared to the antibiotic group (Ant). The same effect was also observed in GOD1200 during days 22-42 and in the 600 U/kg GOD-supplied group (GOD600) when compared to the control group (Ctr). The serum tests indicated that, on day 21, the TGF-β cytokine was significantly decreased in both GOD600 and GOD1200 when compared with Ctr. A decrease in malondialdehyde and an increase in superoxide dismutase in GOD1200 were observed, which is similar to the effects seen in Ant. On day 42, the D-lactate and glutathione peroxidase activity changed remarkably in GOD1200 and surpassed Ant. Furthermore, GOD upregulated the expression of the jejunal barrier genes (MUC-2 and ZO-1) in two phases relative to Ctr. In the aureomycin-supplied group, the secretory immunoglobulin A significantly decreased in the jejunum at 42 days. Changes in microbial genera were also discovered in the cecum by sequencing 16S rRNA genes at 42 days. The biomarkers for GOD supplementation were identified as Colidextribacter, Oscillibacter, Flavonifractor, Oscillospira, and Shuttleworthia. Except for Shuttleworthia, all the abovementioned genera were n-butyrate producers known for imparting their various benefits to broilers. The PICRUSt prediction of microbial communities revealed 11 pathways that were enriched in both the control and GOD-supplied groups. GOD1200 accounted for an increased number of metabolic pathways, demonstrating their potential in aiding nutrient absorption and digestion. In conclusion, a diet containing GOD can be beneficial to broiler health, particularly at a GOD concentration of 1,200 U/kg. The improved feed conversion ratio, immunity, antioxidative capacity, and intestinal condition demonstrated that GOD could be a valuable alternative to antibiotics in broiler breeding.


In vivo dual-modality photoacoustic and optical coherence tomography imaging of human dermatological pathologies.
Vascular abnormalities serve as a key indicator for many skin diseases. Currently available methods in dermatology such as histopathology and dermatoscopy analyze underlying vasculature in human skin but are either invasive, time-consuming, and laborious or incapable of providing 3D images. In this work, we applied for the first time dual-modality photoacoustic and optical coherence tomography that provides complementary information about tissue morphology and vasculature of patients with different types of dermatitis. Its noninvasiveness and relatively short imaging time and the wide range of diseases that it can detect prove the merits of the dual-modality imaging system and show the great potential of its clinical use in the future.


Overexpression of microRNA-133b is associated with the increased survival of patients with hepatocellular carcinoma after curative hepatectomy: Involvement of the EGFR/PI3K/Akt/mTOR signaling pathway.
The aim of the present study was carried out to investigate the association of microRNA-133b (miRNA-133b) expression with the prognosis of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. In the present study, the expression of miRNA-133b in HCC tissues was determined to be lower than that noted in the adjacent normal tissues. Overall and disease-free survival of the HCC patients with high miRNA-133b expression was observably extended, compared with the HCC patients with low miRNA‑133b expression. Moreover, the overexpression of miRNA-133b inhibited cell proliferation, increased lactate dehydrogenase (LDH) activity, induced apoptosis and promoted caspase‑3/-8 activities and Bax/Bcl-2 protein expression in HCC cells, whereas the protein expression of epidermal growth factor receptor (EGFR) was significantly decreased. The overexpression of miRNA-133b significantly suppressed PI3K, phosphorylated (p)-Akt and p-mTOR protein expression in HCC cells. GW2974, an EGFR inhibitor, suppressed the protein expression of EGFR, inhibited cell proliferation, increased LDH activity, induced apoptosis and promoted caspase-3/-8 activities and Bax/Bcl-2 protein expression, downregulated PI3K, p-Akt and p-mTOR protein expression in the transfected HCC cells overexpressing miRNA-133b. Taken together, our results indicate that the overexpression of miRNA-133b is associated with the increased survival of HCC patients after curative hepatectomy. The effects of miRNA-133b in HCC are mediated through the EGFR/PI3K/Akt/mTOR signaling pathway.


Nocturnal foot blood flow in patients with arterial insufficiency.
Twenty-four hour continuous recording of xenon (133Xe) wash-out from the forefoot was performed on patients with normal circulations (n = 10) and on patients with different degrees of arterial insufficiency (n = 36). During day hours the calculated subcutaneous blood flow in the forefoot was on average the same in patients with normal circulations and in patients with different degrees of arterial insufficiency (mean: 2.0 +/- 0.8 ml min-1 100 g-1). During sleep the blood flow nearly doubled in patients with normal circulations; no systematic change was seen in patients with intermittent claudication. In patients with severe ischaemia, i.e. having rest pain, the blood flow decreased by approximately 50%. The changes in local blood flow may be due to changes in local sympathetic tone and to changes in local perfusion pressure.


[A Case of Laparoscopic Surgery for Preoperatively Diagnosed Gastric Metastasis of Lung Cancer].
The patient was a 66-year-old male who had undergone an operation for lung cancer and solitary brain metastases. Follow- up PET-CT after 1 year detected FDG accumulation in the stomach. We performed esophagogastroscopy and found an approximately 20 mm-sized Type 2 tumor on the greater curvature of the upper stomach. A pathological diagnosis of lung adenocarcinoma metastasis in the stomach was made. Laparoscopic surgery was performed on the metastatic lesion to prevent bleeding and perforation, and resection was achieved with minimal invasion. The current development of chemotherapy, including immunotherapy, has contributed to the improved prognosis of cancer patients, including those with lung metastasis in the stomach. Considering these backgrounds, preventive surgical resection under laparoscopy may be an effective approach for improving prognosis and preventing acute life-threatening adverse events. We report this case along with a literature review.