Sun-Smart Practices Amongst School Students (Grades 5, 7, and 9) in Alberta, Canada.
The aim of this study was to assess the current knowledge children possess on melanoma and sun-protective behaviour. A one-page survey was administered to students in grades 5, 7, and 9. Three hundred ninety-two students from 11 schools in Edmonton were surveyed. Seventy-one percent of students knew that sun exposure can cause skin cancers. Sixty-nine percent were taught by their parents about sun protection, but only 44% of students received similar instructions from teachers. Twenty percent of students indicated that they never or rarely wore sunscreen. Twenty-five percent of students had experienced painful sunburns, and only 46% were willing to use sunscreen if it were available at school. More Caucasian students reported painful or peeling sunburns in each grade level than their non-Caucasian peers (for grade 5, P = .003; for grade 7, P < .0001; for grade 9, P = .001). For all grade levels, the percentage of Caucasian students who indicated that they would not wear sunscreen when going out in the sun was greater than among their non-Caucasian peers (for grade 5, P < .001; for grade 7, P = .003; for grade 9, P = .015). A comprehensive and focused approach to sun-smart education is recommended for students.


Keratinocyte expression of the type 2 interleukin 1 receptor mediates local and specific inhibition of interleukin 1-mediated inflammation.
Epidermal keratinocytes can express two types of interleukin 1 (IL-1) receptors: IL-1R1, which is active in signal transduction, and the less well characterized IL-1R2, which is incapable of transducing a signal and can be shed from cells. The binding of IL-1 in solution by IL-1R2 has been demonstrated, and it has been proposed to inhibit IL-1-mediated responses through this mechanism. We and others have reported that keratinocytes can be induced to express IL-1R2 both in vitro and in vivo, often under conditions that also favor IL-1 gene expression. We hypothesized that production of IL-1R2 by keratinocytes would be an efficient means to achieve local inhibition of IL-1-mediated responses without systemic consequences. To test this hypothesis, we have generated transgenic mice that constitutively express IL-1R2 on basal keratinocytes. Keratinocytes cultured from these animals shed the soluble form of the receptor into culture supernatants, and IL-1-inducible production of granulocyte/macrophage colony-stimulating factor was markedly inhibited. In vivo, acute cutaneous vascular leakage, as well as chronic inflammation induced by a well characterized IL-1-dependent stimulus, was significantly inhibited in IL-1R2 transgenic animals. In contrast, contact hypersensitivity was unaffected, suggesting that overexpression of IL-1R2 did not inhibit all types of inflammation globally. Finally, systemic injection of IL-1 induced equivalent levels of plasma IL-6 in IL-1R2 transgenic and nontransgenic mice, suggesting that the activity of the transgenic IL-1R2 remained predominantly local and did not influence systemic IL-1 responses. We conclude that tissue-specific production of IL-1R2 can mediate IL-1 antagonism in tissue microenvironments without systemic consequences. Our transgenic mice may be a useful tool for determining the degree to which different types of cutaneous inflammation depend on the IL-1 system.


Chikungunya infection in travelers.
The largest described outbreak of chikungunya virus has been occurring on the islands of the southwest Indian Ocean since March 2005. We describe the manifestations of chikungunya virus infection in travelers returning from these islands, with focus on skin manifestations.


Proficiency testing in clinical cytogenetics. A 6-year experience with photographs, fixed cells, and fresh blood.
The College of American Pathologists and the American Society of Human Genetics offer a proficiency testing program in clinical cytogenetics. Two hundred twenty-five laboratories now provide data for this survey, which was begun in 1986. Challenges have consisted of photographed metaphases, fixed lymphoblastoid cell suspensions, fresh peripheral blood, and disarranged karyotypes. The "correct" response was based on 80% or greater consensus among either the referees or the participants. Referee laboratories performed better than participants. More laboratories were able to report accurate recognition of abnormalities by using a coded list than could write the interpretation in standardized nomenclature. Deletions, unbalanced translocations, and inversions were more difficult challenges than balanced translocations or trisomies. Prenatal and lymphocyte challenges were more likely to result in consensus than were bone marrow challenges. Participants performed best on whole-blood challenges. Fixed cell suspensions were less satisfactory. Excellent quality case material is essential for a successful challenge. A grading system has been devised to separate artifacts of the survey process from proficiency variables.


Comparative transcriptome analysis of Poncirus trifoliata identifies a core set of genes involved in arbuscular mycorrhizal symbiosis.
The perennial woody plants of citrus are one of the most important fruit crops in the world and largely depends on arbuscular mycorrhizal symbiosis (AMS) to obtain essential nutrients from soil. However, the molecular aspects of AMS in citrus and perennial woody plants in general have largely been understudied. We used RNA-sequencing to identify differentially expressed genes in roots of Poncirus trifoliata upon mycorrhization by the AM fungus Glomus versiforme and evaluated their conservation by comparative transcriptome analyses with four herbaceous model plants. We identified 282 differentially expressed genes in P. trifoliata, including orthologs of 21 genes with characterized roles in AMS and 83 genes that are considered to be conserved in AM-host plants. Comparative transcriptome analysis revealed a 'core set' of 156 genes from P. trifoliata whose orthologous genes from at least three of the five species also exhibited similar transcriptional changes during AMS. Functional analysis of one of these conserved AM-induced genes, a 3-keto-acyl-ACP reductase (FatG) involved in fatty acid biosynthesis, confirmed its involvement in AMS in Medicago truncatula. Our results identify a core transcriptional program for AMS that is largely conserved between P. trifoliata and other plants. The comparative transcriptomics approach adds to previous phylogenomics studies to identify conserved genes required for AMS.


Biosynthesis of guanidine in isolated rat hepatocytes, perfused rat liver and intact animals.
Plasma levels of guanidine (G) are reported to be increased in uremic patients and are synthesized from various guanidino compounds via a chemical reaction involving the hydroxyl radical in vitro. To identify both the metabolic precursor and the synthesizing organ of G, we investigated the concentrations of G in various organs of rats administered several guanidino compounds and we attempted to synthesize G biologically using isolated rat hepatocytes or perfused rat liver. In addition, we investigated the effect of the peroxidative state on the G synthesis in isolated hepatocytes using various reagents which alter this condition. Results show that the concentration of G increased in the kidney, liver and muscle following the administration of L-canavanine. In addition, G increased in the kidney at 90 min after the administration of guanidinoacetic acid (GAA). Moreover, G is synthesized from L-canavanine in isolated rat hepatocytes and perfused rat liver, and G synthesis in hepatocytes is partially inhibited by the addition of superoxide dismutase, catalase, glutathione or ethylenediaminetetraacetic acid. These results suggest that L-canavanine is possibly a biological precursor and GAA is an endogenous precursor of G. Furthermore, it is suggested that these reactions are closely related to the peroxidative state.


Role of intraoperative neuromonitoring of the recurrent laryngeal nerves during thyroid reoperations of recurrent goiter.
Reoperations of the thyroid gland are challenging to any surgeon. Such procedures are technically difficult and involve higher risk of complications than primary procedures. Recurrent laryngeal nerve (RLN) palsy is one of such complications The aim of the study was to evaluate the effectiveness of intraoperative neuromonitoring (IONM) in preventing RLN palsy during recurrent goiter operations. We retrospectively analyzed the results of thyroid reoperation performed at the Department of Endocrine, General and Vascular Surgery of Medical University of Lodz in the period from January 2014 to June 2016. The study included 80 patients, who were divided into 2 groups: group A consisted of 27 patients, who had undergone surgery with the use of IONM, while group B included 53 patients, in whom RLN was identified visually. During statistical analysis we took into account the number of nerves at risk, not the number of patients. There were 47 nerves at risk In group A and 86 in group B. We analyzed whether application of IONM had any effect on the frequency of RLN palsy and procedure duration. The frequency of RLN palsy was 10.64% (5/47) in group A and 15.12% (13/86) in group B (no statistical significance, p=0,47). Mean operation time was shorter in group B 71.29 ± 17.125 minutes vs. 75.75 ± 17.94 minutes in group A (no statistical significance, p=0,377). Use of IONM did not significantly reduce the occurrence of RLN palsy and procedure duration.


Biomonitoring Study of Deoxynivalenol Exposure in Chinese Inhabitants.
Objective: To investigate the levels of a deoxynivalenol (DON) biomarker in the urine of subjects living in two China provinces with different geographic locations and dietary patterns, and estimate their dietary DON exposures and health risks. Methods: First morning urine samples were collected on three consecutive days from 599 healthy subjects-301 from Henan province and 298 from Sichuan province-to analyze the total DON concentrations (tDON) after β-glucuronidase hydrolysis using a high-performance liquid chromatography tandem mass spectrometry-based method. The consumption of cereal foods in the previous 24 h before each urine collection was recorded using a duplicate diet method. DON exposure levels were estimated based on the urinary tDON concentrations. Results: Total DON were detected in 100% and 92% of the urine samples from Henan and Sichuan, respectively. Mean urinary tDON concentrations were 52.83 ng/mL in Henan subjects and 12.99 ng/mL in Sichuan subjects, respectively. The tDON levels were significantly higher in the urine of Henan subjects than that of the Sichuan subjects (p < 0.001). Urinary tDON levels were significantly different among age groups in both areas (Henan: p < 0.001; Sichuan: p = 0.026) and were highest in adolescents aged 13-17 years, followed by children aged 7-12 years. Based on the DON biomarker and exposure conversion reported by the European Food Safety Authority (EFSA), the mean estimated dietary intakes of DON were 1.82 μg/kg bw/day in Henan subjects and 0.45 μg/kg bw/day in Sichuan subjects. A total of 56% of Henan subjects and 12% of Sichuan subjects were estimated to exceed the PMTDI of 1 μg/kg bw/day. Consistent with urinary tDON levels, the highest estimated dietary DON intakes were also in children and adolescents aged 7-17 years. For all kinds of wheat-based foods except dumplings, the consumptions were significantly higher in Henan than those in Sichuan. The mean consumption of steamed buns was 8.4-fold higher in Henan (70.67 g/d) than that in Sichuan (8.45 g/d). The mean consumption of noodles in Henan (273.91 g/d) was 3.6-fold higher than that in Sichuan (75.87 g/d). Conclusions: The levels of urinary DON biomarker and the estimated dietary DON intakes in Henan province were high and concerning, especially for children and adolescents. The overall exposure level of Sichuan inhabitants was low.


Troubleshooting FoCUS Image Acquisition: Patient Positioning, Transducer Manipulation, and Image Optimization.
Focused cardiac ultrasound (FoCUS) is a limited, clinician-performed application of echocardiography to add real-time information to patient care. These bedside exams are problem oriented, rapidly and repeatedly performed, and largely qualitative in nature. Competency in FoCUS includes mastery of the stereotactic and psychomotor skills required for transducer manipulation and image acquisition. Competency also requires the ability to optimize the setup, troubleshoot image acquisition, and understand the sonographic limitations because of complex clinical environments and patient pathology. This article presents concepts for successful, high-quality two-dimensional (B-mode) image acquisition in FoCUS. Concepts of high-quality image acquisition can be applied to all established sonographic windows of the FoCUS exam: the parasternal long-axis (PLAX), parasternal short-axis (PSAX), apical four chamber (A4C), subcostal fourchamber (SC4C), and the inferior vena cava (IVC). The apical five-chamber (A5C) and subcostal short-axis (SCSA) views are mentioned, but are not discussed in-depth. A pragmatic figure illustrating the movements of the phased array transducer is also provided to serve as a cognitive aid during FoCUS image acquisition.


Thoracoscopic intrapericardial lingular segmentectomy for advanced lung cancer following immunotherapy.
Very little data exists on salvage surgery in previously unresectable or metastatic disease treated with initial immunotherapy. Only a handful of case reports/series regarding surgery for advanced lung cancer after immunotherapy mention the technical challenges involved. We report the case of a 67-year-old female with a left lung squamous cell lung cancer revealed by computed tomography-guided biopsy. Treatment started with chemotherapy followed by immunotherapy in which a partial response was recorded. Subsequent salvage lingulectomy with the thoracoscopic approach was performed. The patient fully recovered and shows no sign of recurrence at follow-up 16 months on. Our case discusses the surgical tactics involved in the procedure, highlights similar findings encountered in the literature, and contributes to the few reports therein.


The development of a retroperitoneal dissection model.
Knowledge of ureteric anatomy is essential for ureteric injury prevention in laparoscopic gynecologic surgery. Rates of injury increase with limited surgical experience and reduced surgical volume. Currently, there are no low-fidelity or high-fidelity simulation models for teaching and practicing ureteric dissection. Our goal was to design a laparoscopic simulation model for retroperitoneal anatomy with high face validity that is low-cost and easily reproducible. A low-fidelity 3-dimensional simulation model was developed that represents key anatomic structures encountered during retroperitoneal dissection and ureteric identification. Materials, construction steps, and costs were determined. The models were trialed by expert laparoscopic surgeons. Demographic information that included age, gender, surgical experience, and complex laparoscopic case volumes was collected. Face validity was assessed with a 5-item Likert-scale. The total cost of 1 model ranged from $65 to $75. The majority of the materials that were used were reusable, except for 2 components that cost <$1 per use. Seven expert surgeons participated in the study, all of whom were fellowship-trained minimally invasive gynecologic surgeons or currently enrolled in this type of fellowship program. Participants agreed or strongly agreed that the model resembled the texture of the ureter, vessels, and peritoneal layer (n=6; 86%), approximated the correct anatomic course of the ureter (n=7; 100%), and closely approximated live surgery (n=5; 71%). They also agreed or strongly agreed that the model would be useful for teaching laparoscopic retroperitoneal dissection (n=7; 100%), for assessing a learner's ability before performing in the operating room (n=6; 86%), was low-cost (n=7; 100%), and was easily reproducible (n=6; 86%). This unique model fills a gap in laparoscopic simulation training. No other low- or high-fidelity models for laparoscopic retroperitoneal ureteric dissection have been identified in the literature. This simulation model is low-cost, easily reproducible, closely resembles retroperitoneal dissection during laparoscopic gynecologic surgery, and can be used for education and assessment.


Acyclic Retinoid Combined With Tenascin-C-derived Peptide Reduces the Malignant Phenotype of Neuroblastoma Cells Through N-Myc Degradation.
Despite intensive chemotherapy, the survival rates for high-risk neuroblastoma, most of which have MYCN amplification, remain low. Overexpression of N-myc oncoprotein promotes expression of cancer-associated properties. We recently found that combination of all-trans retinoic acid (ATRA) with the β1-integrin-activating peptide TNIIIA2 attenuated cancer-associated properties of neuroblastoma cells through N-Myc degradation. However, ATRA has serious side-effects and there are concerns about late adverse effects. The aim of this study was to examine the effects of the combination of acyclic retinoid (ACR) with TNIIIA2 on neuroblastoma. The effects of ACR and TNIIIA2 were examined by neuroblastoma cell proliferation and survival assays as well as by using a neuroblastoma xenograft model. The levels of N-Myc and cancer-associated malignant properties were assayed by western blot and colony formation assay, respectively. Combining ACR, which is clinically safe, with TNIIIA2 induced proteasomal degradation of N-Myc and reduction of neuroblastoma cell malignant properties. An in vivo experiment showed therapeutic potential. ACR-TNIIIA2 combination treatment may be efficacious and clinical safe chemotherapy for high-risk neuroblastoma.


The role of monokines in granuloma formation in mice: the ability of interleukin 1 and tumor necrosis factor-alpha to induce lung granulomas.
Granulomatous inflammation is associated with many significant human diseases, including tuberculosis, leprosy, sarcoidosis, parasite infection, and berylliosis. Very little is known about the basic mechanism of this type of inflammation. In the present study, we showed that pulmonary granulomas were induced in mice by the intratracheal injection of agarose beads coupled to recombinant interleukin 1 (IL-1) or tumor necrosis factor-alpha (TNF-alpha). Histologically, the bulk of granulomas was composed of macrophages and their derivatives. In contrast, the inflammatory reactions induced by beads coupled to either recombinant IL-2 or murine interferon-gamma were considerably smaller than those induced by beads coupled to monokines. These results suggest that macrophages and monokines such as IL-1 and TNF-alpha, but not T cell-derived lymphokines, play an essential role in granuloma formation.


Field study on swine influenza virus (SIV) infection in weaner pigs and sows.
The aim of this field study was to explore the occurrence of and factors associated with the detection of swine influenza virus (SIV) by RTqPCR in weaner pigs and sows from herds with a history of respiratory or reproductive disorders. The sample set was based on nasal swabs from 823 sows (123 submissions) and 562 weaner pigs (80 submissions). Nasal swab samples were taken and submitted by 51 veterinary practices from all over Germany. Corresponding to the pig density most of the submissions originated from the north-western part of Germany. The nasal swabs were used to detect SIV RNA by real-time RT-PCR (RTqPCR). Subtyping of SIV RNA by conventional RT-PCR and sequencing was attempted directly from clinical samples or from isolates when available. The herd characteristics, management and housing conditions of the pig herd as well as the course of the disease were collected by a telephone questionnaire with the herd attending veterinarian. SIV was detected by RTqPCR in 53.8% of the submissions from weaner pigs with a history of respiratory disease. Moreover SIV was detected in 10.6% of the submissions from sows. The predominant endemic subtype found in nasal swabs from sows and weaner pigs was H1N1 (60.5%) whereas subtypes H1N2 (14.0%) and H3N2 (14.0%) were detected less frequently. In addition, human pandemic H1N1 virus or reassortants thereof were found in 11.5%. The results underline the significance of a SIV infection in young pigs. A significant lower detection of SIV in wea- ner pigs was associated with the vaccination of piglets against por- cine circovirus type 2 (PCV2), possibly indicating an interaction of SIV and PCV2. Most of the positive samples from sows originated from gilts, whereas only two originated from sows. An association between reproductive disorders and the detection of SIV could not be confirmed.


The end-stage renal disease industry and exit strategies for nephrologists.
The purpose of this presentation is to identify exit strategies for nephrologists under changing conditions in the dialysis market. The end-stage renal disease service provider market continues to be highly receptive to consolidation. Taking advantage of large economies of scale, large for-profit dialysis chains have surpassed independent operators in both number of clinics and total patients. With relatively low barriers to entry, new smaller clinics continue to open, serving a niche outside the larger chains. Additional competition comes in the form of medium players funded by venture capitalists with the added pressure of rapid growth and financial return. To ensure market power in both dialysis products and managed care negotiation leverage, medium and large service providers will continue to seek out attractive acquisition targets. For nephrologists to capitalize on investment, clinic and business preparation will continue to be the driving force for these divestitures.


[Progress on the studies of cyclic lipopeptides].
Cyclic lipopeptide, also named as acylpeptide, which was characteristic with novel structures, was paid more attention in the recent years. Cyclic lipopeptide showed various bioactivities including antibacterial, anti-tumor, anti-inflammatory, etc. Cyclic lipopeptide originated mainly from the second metabolites of microorganism, such as Cyanobacterium, Bacterium, Actinomyces, etc. The bacteria included the genus of Bacillus and Pseudomonas. In this account, the review has been made on the development of cyclic lipopeptide.


[Variations in hyperbilirrubinemia in low birth weight newborns under phototherapy and continous or discontinous agar oral administration (author's transl)].
Therapeutic attitude in hyperbilirrubinemia is always worth because other infrequent complications but not for this, less important. Phototherapy innocuousness, largely demonstrated, fosters its profilactic use at beginning and not only for those babies with serum bilirrubin over 10 mg % in the first day of life. Previously we have reported positive results with agar oral administration without collateral effects. On this grounds we have planned the following experience in a homogenous group of L.B.W.: one group was fed with agar previously to each formula administration; other group received the same amount of agar but divided in only three administrations in 24 hours; the last group received continuous phototherapy for 96 hours with a white cold fluorescent light from a source of 8-Vita-lite lamp of 40 watts with a intensity of 500 foot candle and 30 lumens. All of these babies weighed less than 2.500 g. and were between 10 and 90 percentil of Lubschenko diagram. They were fed with the same formula and same time table with no infusions, rejecting all that presented any type of pathology. Obstetric conditions were basically identical. This population was randomly divided in four groups. 1) Control group with no profilaxis, but with identical bilirrubin andhematocrit determinations. 2) Group with continuous agar oral administration, 125 mg. before each of the seven formula feeding. 3) Group with discontinuous agar administration, 250 mg. before three of the seven formula feeding. 4) Group with continuous phototherapy for 96 hours. These is initial identification of the groups with statistic signification, and after that a quantitative and sequential evolution of bilirrubin is analized in each group.


Differential calcium regulation of proinflammatory activities in human neutrophils exposed to the neuropeptide pituitary adenylate cyclase-activating protein.
The neuropeptide pituitary adenylate cyclase-activating protein (PACAP) acts via the G protein-coupled receptor vasoactive intestinal peptide/PACAP receptor-1 to induce phospholipase C/calcium and MAPK-dependent proinflammatory activities in human polymorphonuclear neutrophils (PMNs). In this study, we evaluate other mechanisms that regulate PACAP-evoked calcium transients, the nature of the calcium sources, and the role of calcium in proinflammatory activities. Reduction in the activity of PMNs to respond to PACAP was observed after cell exposure to inhibitors of the cAMP/protein kinase A, protein kinase C, and PI3K pathways, to pertussis toxin, genistein, and after chelation of intracellular calcium or after extracellular calcium depletion. Mobilization of intracellular calcium stores was based on the fact that PACAP-associated calcium transient was decreased after exposure to 1) thapsigargin, 2) Xestospongin C, and 3) the protonophore carbonyl cyanide 4-(trifluoromethoxy) phenyl hydrazone; inhibition of calcium increase by calcium channel blockers, by nifedipine and verapamil, indicated that PACAP was also acting on calcium influx. Such mobilization was not dependent on a functional actin cytoskeleton. Homologous desensitization with nanomoles of PACAP concentration and heterologous receptors desensibilization by G protein-coupled receptor agonists were observed. Intracellular calcium depletion modulated PACAP-associated ERK but not p38 phosphorylation; in contrast, extracellular calcium depletion modulated PACAP-associated p38 but not ERK phosphorylation. In PACAP-treated PMNs, reactive oxygen species production and CD11b membrane up-regulation in contrast to lactoferrin release were dependent on both intra- and extracellular calcium, whereas matrix metalloproteinase-9 release was unaffected by extracellular calcium depletion. These data indicate that both extracellular and intracellular calcium play key roles in PACAP proinflammatory activities.


Footstep Energy Harvesting with the Magnetostrictive Fiber Integrated Shoes.
Wearable energy harvesting devices attract attention as the devices provide electrical power without inhibiting user mobility and independence. While the piezoelectric materials integrated shoes have been considered as wearable energy harvesting devices for a long time, they can lose their energy harvesting performance after being used several times due to their brittleness. In this study, we focused on Fe-Co magnetostrictive materials and fabricated Fe-Co magnetostrictive fiber integrated shoes. We revealed that Fe-Co magnetostrictive fiber integrated shoes are capable of generating 1.2 µJ from 1000 steps of usual walking by the Villari (inverse magnetostrictive) effect. It seems that the output energy is dependent on user habit on ambulation, not on their weight. From both a mechanical and functional point of view, Fe-Co magnetostrictive fiber integrated shoes demonstrated stable energy harvesting performance after being used many times. It is likely that Fe-Co magnetostrictive fiber integrated shoes are available as sustainable and wearable energy harvesting devices.


Oxidation of a P-C Bond under Mild Conditions.
The reactivity of phosphenium dication [(Ph3P)2C-P-NiPr2](2+), 1(2+), towards pyridine N-oxide (O-py) has been investigated. The resulting oxophosphonium dication [(Ph3P)2C(NiPr2)P(O)(O-py)](2+), 2(2+), was surprisingly stabilized by a less nucleophilic O-py ligand instead of pyridine (py). This compound was then identified as an analogue of the elusive Criegee intermediate as it underwent oxygen insertion into the P-C bond through a mechanism usually observed for Baeyer-Villiger oxidations. This oxygen insertion appears to be the first example of a Baeyer-Villiger oxidation involving O-py.


Experiences, Attitudes, and Perceptions of Female Adjunct Clinical Instructors in Teaching Male Prelicensure Nursing Students.
Male students often report experiencing barriers during nursing education, resulting in decreased retention and success. Clinical instructors are one influence that potentially deters men in nursing. This qualitative study interviewed female clinical instructors about their experiences, attitudes, and perceptions of teaching males. The results reveal a general acceptance of males, with hesitation and ambivalence from some clinical instructors. Further training for clinical instructors, education of the public, and recruitment of more males into education are suggested to improve male student outcomes.


Clinical metagenomics-challenges and future prospects.
Infections lacking precise diagnosis are often caused by a rare or uncharacterized pathogen, a combination of pathogens, or a known pathogen carrying undocumented or newly acquired genes. Despite medical advances in infectious disease diagnostics, many patients still experience mortality or long-term consequences due to undiagnosed or misdiagnosed infections. Thus, there is a need for an exhaustive and universal diagnostic strategy to reduce the fraction of undocumented infections. Compared to conventional diagnostics, metagenomic next-generation sequencing (mNGS) is a promising, culture-independent sequencing technology that is sensitive to detecting rare, novel, and unexpected pathogens with no preconception. Despite the fact that several studies and case reports have identified the effectiveness of mNGS in improving clinical diagnosis, there are obvious shortcomings in terms of sensitivity, specificity, costs, standardization of bioinformatic pipelines, and interpretation of findings that limit the integration of mNGS into clinical practice. Therefore, physicians must understand the potential benefits and drawbacks of mNGS when applying it to clinical practice. In this review, we will examine the current accomplishments, efficacy, and restrictions of mNGS in relation to conventional diagnostic methods. Furthermore, we will suggest potential approaches to enhance mNGS to its maximum capacity as a clinical diagnostic tool for identifying severe infections.


Jumping higher: is it still possible? The ALTTO trial challenge.
Trastuzumab, a humanized monoclonal antibody directed against HER2, used alone or in combination with chemotherapy, has shown significant clinical benefit in improving survival in the metastatic setting, as well as halving the recurrence rate and improving survival in HER2-positive early breast cancer. Lapatinib is an orally active, reversible, small-molecule tyrosine kinase inhibitor that potently inhibits both HER1 and HER2 tyrosine kinase activity. This agent is the most advanced in terms of clinical trials and has been shown to have a favorable safety profile. Owing to the promising activity seen in advanced breast cancer, lapatinib is the ideal candidate for testing in the adjuvant setting. Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) is a four-arm randomized trial designed to compare trastuzumab and lapatinib in women with early-stage HER2-positive breast cancer. Specifically, ALTTO will examine which anti-HER2 agent is more effective and which is their best schedule of administration, namely, what benefit will be derived by taking the drugs separately, in tandem order or in combination. Overall, 8000 patients will be enrolled worldwide.


Enhancement of wound healing efficiency mediated by artificial dermis functionalized with EGF or NRG1.
The use of artificial dermis as a skin substitute is a field of active study, as acellular dermal matrices from cadavers are susceptible to infection owing to their human origin. One such alternative dermal replacement scaffold, INSUREGRAF®, is derived primarily from extracellular matrix proteins such as collagen and elastin and has been clinically used to treat severe skin wounds such as burns. This scaffold has proven to be useful to minimize wound contraction and scar formation owing to its biocompatibility, interconnected pore structure, sufficient biodegradability, and suitable mechanical properties. However, INSUREGRAF® does not provide scar-free wound healing in cases of severe skin damage such as full-thickness (FT) excision. Considering that the efficient recruitment of fibroblasts and keratinocytes into a wound site represents a critical step in the regeneration of damaged skin, we attempted to enhance the efficiency for wound healing by fabricating growth factor-functionalized INSUREGRAF®. In particular, we utilized epidermal growth factor (EGF) and an EGF family member, neuregulin-1 (NRG1), not previously studied in the context of wound healing, whose cellular role is to promote proliferation and migration in fibroblasts and keratinocytes. Both artificial dermis-growth factor combinations led to efficient recruitment of fibroblasts and keratinocytes into a wound site during the early steps of skin regeneration. Notably, EGF- or NRG1-functionalized INSUREGRAF® induced rapid proliferation of skin cells in an ERK pathway-dependent manner and exhibited efficient wound healing in a Sprague-Dawley rat FT excision and grafting model. These results provide the foundation for expanding the use of growth factor-functionalized INSUREGRAF® to clinical application in cases of severe skin injury.


Update on the surgical management of Paget's disease.
Mammary Paget's disease is a rare form of breast neoplasm that often presents with a pruritic eczema-like rash involving the nipple-areolar complex, and is refractory to common remedies. It is often associated with underlying breast cancer, and is sometimes difficult to diagnose. In this review, we present an update of the approach to Paget's disease and its surgical treatment.


Studies of the interaction of the viral suppressor of RNA silencing protein p19 with small RNAs using fluorescence polarization.
Tombusviruses use a 19 kDa protein (p19) as a suppressor of the RNA silencing pathway during infection. The p19 protein binds to short-interfering RNA (siRNA) as a dimer and shows a high selectivity for short duplex RNAs over other RNA species. Since p19 can bind to synthetic and RNA silencing generated small RNAs with little sequence dependence and with size selectivity, this protein has utility as a tool for studying RNA silencing pathways in eukaryotes. However, the ability of p19 to serve as a tool for studying RNA silencing pathways may be complicated by the presence of other endogenous small RNAs such as micro-RNAs (miRNAs). To understand the importance of endogenous small RNA components with respect to p19's ability to bind to siRNAs, we examined the interactions of p19 with human miR-122, a 23-nucleotide duplex miRNA containing several mismatched base pairs that is highly abundant in the liver. The binding characteristics were compared with those of an siRNA optimized against the human kinase CSK. The binding studies were performed using fluorescence polarization experiments on duplex oligonucleotides containing Cy3 dye labels at the 5'-end of one of the strands of RNA as well as electrophoretic gel mobility shift assays. Both methods indicate that the synthetic siRNA with no mismatches in base pairing bound with >3-fold selectivity over that of miR-122. Our results suggest that p19 can distinguish between siRNAs and miRNA species, although the difference in binding constants is not so large that interactions with endogenous miRNAs can be totally ignored.


A near fatal case of high dose peppermint oil ingestion- Lessons learnt.
Peppermint oil is easily available as a constituent of medicines. A near fatal case due to ingestion of toxic dose of oral peppermint oil is being reported. The patient came in a comatosed state and was in shock. She was managed with mechanical ventilation and ionotropes. Her vital parameters reached normal within 8 hours and became conscious by 24 hours. The side effects of peppermint oil are considered to be mild but this case report warns that ingestion of oral toxic doses of peppermint oil could be dangerous.


Comparison of video analysis and simulations of a drum coating process.
Tablet coating is a common unit operation in the pharmaceutical industry. To improve currently established processes, it is important to understand the influence of the process parameters on the coating quality. One of the critical parameters is the tablet velocity. In this work, numerical results are compared to results obtained experimentally. Tablet movement in the drums was simulated using the Discrete Element Method (DEM). The simulation parameters were adapted to fit the simulation to the experimental data. A comparison of the experimental and simulation results showed that the simulation correctly represents the real tablet velocity. A change in the velocity over time and its dependence on the rotation rates and the baffle position in the simulation were similar to the experimental results. In summary, simulations can improve the understanding of tablet coating processes and will thus provide insights into the underlying process mechanics, which cannot be obtained via ordinary experiments.


Role of endogenous angiotensin II and prostaglandins in the antihypertensive mechanism of angiotensin converting enzyme inhibitor in hypertension.
The role of endogenous angiotensin II and prostaglandins (PGs) in the antihypertensive effect of converting enzyme inhibitor, captopril, was studied in essential hypertension by the separate and the combined administration of captopril and indomethacin. Although plasma angiotensin II was similarly suppressed by the separate and the combined administration of captopril and indomethacin, captopril lowered and indomethacin increased the mean blood pressure. There were negative correlations between the changes in mean blood pressure and in urinary sodium excretion as well as in urinary PGE excretion. These results suggest that endogenous PGs may be implicated in the antihypertensive effect of captopril through the alteration of sodium balance.


Purification and structural characterization of lectins from the cnidarian Bunodeopsis antilliensis [corrected].
Purification and characterization of two different lectins from the Mexican anemone Bunodeopsis antilliensis are reported. These two lectins named Bunodeopsis antilliensis agglutinin-A (BAA-A) and -B (BAA-B) presented the following characteristics: BAA-A was resolved as a component, with haemagglutinating activity for human blood type A (N-acetylgalactosamine-galactose-fucose), with a molecular weight of 28,900 obtained by means of mass spectrometry, showed an isoelectric point of 5.04 with a higher carbohydrate specificity for N-acetylgalactosamine (GalNAc). The analysis of the N-terminal revealed it is related to phosphoesterase and GTP binding protein. BAA-B mainly active with human blood type B (galactose-galactose-fucose) was resolved into three fractions (BAA-B1-3). Their molecular weight were: BAA-B(1) 39,350, BAA-B(2) 28,300 and BAA-B(3) 17,550. The estimated isoelectric points were 8.05, 4.66 and 6.60, respectively. Only fraction 3 exhibited haemagglutinating activity with a higher carbohydrate specificity for galactose and mannose. The analysis of the N-terminal pointed out it is related with phospholipase A(2). We suggest these lectins could be related to a feeding strategy[corrected].


The application of BMRT-HPV viral load to secondary screening strategies for cervical cancer.
Evaluate the significance of BMRT HPV assay viral load and its performance for secondary screening. BMRT-HPV reports type-specific viral loads/10,000 cells. We tested 1,495 physician collected, stored specimens from Chinese Multiple-center Screening Trial (CHIMUST), that were positive by Cobas, SeqHPV, and/or Cytology (≥LSIL); and 2,990 age matched, negatives in a nested case control study. We explored the relationship between BMRT HR-HPV viral load and cervical lesions, determined alternative CIN2+ cut-points by ROC curve, and evaluated BMRT HR-HPV for primary / secondary cervical cancer screening. The viral loads of HPV16/18, 12 other subtypes HR-HPV and 14 HR-HPV were statistically different in all grades of cervical lesions (P<0.05, among which HPV16, 33 and 58 showed the strongest relationship (P<0.01). The viral load of HR-HPV also increased with the grade of cervical lesions (P<0.05). The sensitivity for CIN2+ and CIN3+ of BMRT was comparable to Cobas (92.6% vs 94.3%, 100% vs 100%, P>0.05), specificity was higher than Cobas (84.8% vs 83.3%, 83.5% vs 82.0%, P<0.001). When using HPV16/18 viral load(log cut-point ≥3.2929), plus the viral-load of 12 other subtypes (log cut-point ≥3.9625) as secondary triage, compared with Cobas HPV16/18+ plus cytology ≥ASC-US as triage, the sensitivities for CIN2+ and CIN3+ were similar (P>0.05). However, the BMRT HR-HPV viral load combined with subtypes did not require cytology. BMRT is as sensitive as Cobas4800 for primary cervical cancer screening. BMRT HR-HPV viral load combined with subtypes can be used as a secondary strategy for cervical cancer screening, especially for areas with insufficient cytological resources.


Psychological characteristics of long-term female temporomandibular joint pain patients.
Analysis from the Taylor Manifest Anxiety Scale (TMAS) scores of 44 long-term temporomandibular joint (TMJ) pain patients and 10 facial pain patients of a non-TMJ variety shows no significant differences. Both groups were significantly higher than a normative group. After treatment TMJ patients are not significantly different on the TMAS than the normative group. Etiological implications are discussed.


Preparation of a Superhydrophobic and Peroxidase-like Activity Array Chip for H2O2 Sensing by Surface-Enhanced Raman Scattering.
In this paper, we propose a novel and simple method for preparing a dual-biomimetic functional array possessing both superhydrophobic and peroxidase-like activity that can be used for hydrogen peroxide (H2O2) sensing. The proposed method is an integration innovation that combines the above two properties and surface-enhanced Raman scattering (SERS). We integrated a series of well-ordered arrays of Au points (d = 1 mm) onto a superhydrophobic copper (Cu)/silver (Ag) surface by replicating an arrayed molybdenum template. Instead of using photoresists and the traditional lithography method, we utilized a chemical etching method (a substitution reaction between Cu and HAuCl4) with a Cu/Ag superhydrophobic surface as the barrier layer, which has the benefit of water repellency. The as-prepared Au points were observed to possess peroxidase-like activity, allowing for catalytic oxidation of the chromogenic molecule o-phenylenediamine dihydrochloride (OPD). Oxidation was evidenced by a color change in the presence of H2O2, which allows the array chip to act as an H2O2 sensor. In this study, the water repellency of the superhydrophobic surface was used to fabricate the array chip and increase the local reactant concentration during the catalytic reaction. As a result, the catalytic reaction occurred when only 2 μL of an aqueous sample (OPD/H2O2) was placed onto the Au point, and the enzymatic product, 2,3-diaminophenazine, showed a SERS signal distinguishable from that of OPD after mixing with 2 μL of colloidal Au. Using the dual-biomimetic functional array chip, quantitative analysis of H2O2 was performed by observing the change in the SERS spectra, which showed a concentration-dependent behavior for H2O2. This method allows for the detection of H2O2 at concentrations as low as 3 pmol per 2 μL of sample, which is a considerable advantage in H2O2 analysis. The as-prepared substrate was convenient for H2O2 detection because only a small amount of sample was required in each analysis. Highly sensitive detection was realized using SERS. Therefore, this chip was shown to exhibit significant potential for applications in bioanalysis.


Control of Liquid Crystal Microarray Optical Signals Using a Microspectral Mode Based on Photonic Crystal Structures.
Herein, a novel liquid crystal microarray (LCM) film with optical regulation ability is first constructed by combining liquid crystals (LC) and the highly ordered microporous structure of inverse opal photonic crystals (IOPhCs). The LCM films are fabricated by infiltrating LC molecules into the LC polymer with the structure of IOPhCs, and their properties are very different from those without the LC. Interestingly, the optical property of LCM films can be controlled by changing the orientation of LC molecules, which varies with the interfacial force. In combination with polarization images, spectral reflection peak, circular dichroism spectra, potential difference, and fluorescence images of LCM films, the mechanism of this change is investigated. It is found that the exposed basic group of single-stranded DNA is the key to the change of the optical property of LC microarrays. Meanwhile, the optical signals of LC microarrays based on the PhCs provide a novel LC signal mode for an LC sensing system (microspectral signal mode), and it can be recorded by a fiber-optic spectrometer, which is a great improvement on LC sensing signals. Therefore, the LC microarray sensing signal can be used for accurate analysis of targets by the change of the reflection peak intensity of PhCs. When the LC molecules are induced by different aptamers, the LC microarray sensing interface can be further used for the determination of different targets, such as cocaine and Hg2+. The research on LCM films is of significant value for the development of LC sensing technology and also shows great application prospects in biochemical sensing fields.


Probabilistic networks of blood metabolites in healthy subjects as indicators of latent cardiovascular risk.
The complex nature of the mechanisms behind cardiovascular diseases prevents the detection of latent early risk conditions. Network representations are ideally suited to investigate the complex interconnections between the individual components of a biological system that underlies complex diseases. Here, we investigate the patterns of correlations of an array of 29 metabolites identified and quantified in the plasma of 864 healthy blood donors and use a systems biology approach to define metabolite probabilistic networks specific for low and high latent cardiovascular risk. We adapted methods based on the likelihood of correlation and methods from information theory and combined them with resampling techniques. Our results show that plasma metabolite networks can be defined that associate with latent cardiovascular disease risk. The analysis of the networks supports our previous finding of a possible association between cardiovascular risk and impaired mitochondrial activity and highlights post-translational modifications (glycosilation and oxidation) of lipoproteins as a possible target-mechanism for early detection of latent cardiovascular risk.


Childhood choledochal cyst with intrahepatic enlarged cyst-like bile ducts.
A five-year-old boy was investigated for intermittent, crampy abdominal pain over several months. His abdomen was distended. Hepatomegaly and cystic masses were demonstrated in both lobes of the liver on ultrasound and computed tomographic examinations. An operative cholangiogram revealed a choledochal cyst of the cystic duct with massive dilatation of intrahepatic and extrahepatic bile ducts. After resection of the choledochal cyst and anastomosis of the jejunum to the common bile duct, the hepatic ducts have become near normal.


El Niño 1997-1998 impact on the plankton dynamics in the Gulf of Nicoya, Pacific coast of Costa Rica.
The impact of the El Niño 1997-1998 phenomenom on plankton dynamics was studied during 1997 at the Punta Morales estuary, Gulf of Nicoya, Pacific coast of Costa Rica. The study covered dry season/transition and the rainy season. Phytoplankton (microphytoplankton > 30 microm and nanophytoplankton) were collected at two depths (50 and 10% light incidence) using a 5 L Niskin bottle, and samples taken to determine chlorophyll a. Temperature, salinity, oxygen, and Secchi depth were measured. Horizontal sub-surface zooplankton hauls were conducted with a conic zooplankton net of 0.49 m diameter and 280 microm mesh width, supplied with a flowmeter. Surface sea water temperature average was 29.9 +/- 0.9 degrees C, with a maximum of 31.5 degrees C in April and a minimun of 28 degrees C in March and October. Chlorophyll a concentration (phytoplankton net) averaged 3.1 +/- 1.7 mg/m3, with higher values during the rainy season and lower values during the transition. Nanophytoplankton chlorophyll a concentration averaged 2.5 +/- 1.2 mg/m3, with a maximum during the transition season. For both fractions there were significant differences between transition and rainy seasons, and for nanophytoplankton between dry and transition seasons (p < 0.05). In the last case, differences were explained by temperature. Herbivorous copepods dominated the abundance and biomass of zooplankton, with a biomass maximun of 167.3 in October and a minimun of 7.1 mg DW/m3 in December. These values are higher than those found some years ago in the same zone and those reported for some places in the Caribbean. The El Niño 1997-1998 phenomenon in the plankton dynamics appears to have produced a change in the phytoplankton structure. This is the first attempt to evaluate the possible impact of El Niño on the plankton dynamics of the Pacific coast of Central America.


Sexual dimorphic parameters of femur: a clinical guide in orthopedics and forensic studies.
Sexual dimorphic studies of various parameters of the femur play an important role in forensic studies. Various femur morphometric parameters help estimate an individual's age, sex, and stature from unknown skeletal remains. This research was done to analyze maximum length, trochanteric oblique length, and diameter of the femur head for sexual dimorphism. The study was done on 200 (128 male & 72 female) Indian adult human femora, which were fully ossified, dry, and free from deformity. The maximum length of the femur (L), trochanteric oblique length (TOL), and vertical diameter of the head (VDH) were measured using an osteometric board and digital Vernier calipers. The mean length of the femur was 436.88 mm in males and 402.38 mm in females, respectively. The mean trochanteric oblique length of the femur was 423.78 mm in males and 387.18 mm in females, respectively. The mean vertical diameter of the femur head was 43 mm in males and 38.19 mm in females, respectively. Depending upon the results of this study, it was concluded that the mean values of maximum length, trochanteric oblique length, and vertical diameter of the femur head are significantly higher in males than females. These parameters are useful and reliable for sexual dimorphism in anthropometric and forensic studies, especially in identifying skeletal remains. These differences can also be considered in selecting or designing the exact ranges of the gender-specific prosthesis for Orthopedic surgeries.


EuroFIR guidelines for assessment of methods of analysis: GAMA.
Analytical methodology is a key factor in food composition databases and specific criteria, at the component level, is needed for comparison of analytical data from different sources. The aim of this work is to describe how EuroFIR guidelines for assessment of methods of analysis are created and made available to users. Comprehensive information for macronutrients, vitamins, minerals and trace elements addressing all aspects of analytical procedures was obtained from international standards, and scientific literature. Documentation was compiled in a confluence wiki format provided for each component: background information, description of reference methods of analysis and critical steps, available reference materials, proficiency testing schemes, other analytical methods and relevant references. The information for each nutrient was collated, edited and presented with hypertext links to additional pages where more detailed information can be accessed using full text searches. The wiki format is a useful tool for preparing information and disseminating to users.


[Endoscopic pancreatic stenting in pancreatic fistulas management].
To present 18-year experience of endoscopic transpapillary stenting in patients with pancreatic fistula. The study included 48 patients with pancreatic fistula resistant to conservative management. Pancreatic stenting was successful in 32 (66.7%) patients. In 30 (93.8%) of them stenting appeared as the final stage of pancreatic fistula treatment. Inclidence of complications after endoscopic treatment was 4.2%. We evaluated long-term results in 23 cases within 8-184 months. There were good results in 21 (91.3%) cases and satisfactory - in 2 (8.7%) cases. We had not unsatisfactory results in our experience.


Alemtuzumab (Campath 1-H).
Alemtuzumab is an exciting targeted therapy for patients with CD52-sensitive malignancies. The drug is being used in a variety of hematologic malignancies in different dosing schedules and different routes of administration. The Cancer and Leukemia Group B is conducting a study using alemtuzumab as consolidation treatment for patients with B-CLL. The group also is conducting a phase I and II dose-escalation study using alemtuzumab during intensification therapy in adults with untreated acute lymphoblastic leukemia. A national pharmaceutical protocol is actively accruing participants for a trial in which alemtuzumab is used in combination with fludarabine for relapsed and refractory B-CLL. The SQ route of administration is gaining popularity because it is highly effective with fewer side effects than IV infusions. Nurses administering alemtuzumab are in a unique position to ensure patient safety and tolerance of the therapy. By understanding the mechanism of action and the potential complications associated with alemtuzumab, nurses will be better able to provide optimal care to patients as the use of targeted monoclonal therapy continues to progress.


Six-membered ring phosphates and phosphonates as model compounds for cyclic phosphate prodrugs: is the anomeric effect involved in the selective and spontaneous cleavage of cyclic phosphate prodrugs?
In recent years, several six-membered ring phosph(on)ates and phosphonamides have been reported as potent prodrugs against liver diseases such as hepatitis B and C and also as antitumor agents. Apparently, the success for their biological activity depends on the selective cleavage of the C4-O3 bond within the respective P-heterocyclic ring. Empirical observations have suggested that the group attached to the C4 position (aryl or pyridyl group) is responsible for the selective cleavage. In this regard, we show in the present work that the configuration at the P-atom, the conformation of the P-heterocyclic ring, and particularly, the anomeric effect are involved in the spontaneous and selective cleavage of the C4-O3 bond in cyclic phosph(on)ates. We arrived at this assumption based on the conformational and configurational study of simple model phosphates and phosphonates, where it was observed that the spontaneous conversion of unstable six-membered ring phosphates to their most stable six-membered ring phosphate (4d, 6d and 7d to 5d), by a selective C4-O3 bond cleavage, depends on both: the stereochemistry of the aryl group at C4 and the electronic nature of the substituent attached to the P-atom. Thus, we postulated that the anomeric effect weakens the C4-O3 bond within the 1,3,2-dioxaphosphorinane ring, favoring thus their selective cleavage and spontaneous conversion, similarly to the proposed mechanistic mode of action of six-membered ring P-heterocyclic prodrugs.


Cross-cultural adaptation of the pain understanding and confidence questionnaire into Japanese.
[Purpose] This study aimed to develop a culturally adapted Japanese version of the Pain Understanding and Confidence Questionnaire (PUnCQ). The first-factor structure describes management from 12 perspectives for a case vignette of chronic pain and determines whether the management is based on a biomedical or biopsychosocial perspective. The second-factor structure evaluates the confidence level in management skills for the same case from 21 perspectives. [Participants and Methods] We conducted a cross-cultural adaptation based on five stages according to Beaton's guidelines (two forward translations, creation of an integrated forward translation version, two backward translations, creation of a provisional Japanese version, and a pilot test). In the pilot test, we asked 40 Japanese physical therapists to rate their understanding of the PUnCQ descriptions on a five-point Likert scale (1, not at all understandable; 5, completely understandable) and provide comments when they rated 1 to 3. We repeated revisions and pilot tests until less than 10% of the respondents rated 1 for all descriptions. [Results] By conducting two rounds of the pilot test, all items of descriptions satisfied the preestablished criteria. [Conclusion] A Japanese version of the PUnCQ was developed.


Effect of recombinant hematopoietic growth factors on proliferation of human marrow progenitor cells in serum-deprived liquid culture.
We investigated the effects of recombinant interleukin-3 (IL-3), granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF and G-CSF), and erythropoietin (Ep) on the number of human hematopoietic progenitors after two to ten days of incubation in liquid cultures deprived of fetal bovine serum (FBS). The source of progenitor cells was normal human marrow depleted of T lymphocytes and/or adherent cells. When adherent cell-depleted marrow was cultured without growth factors, the number of progenitor cells was relatively constant for periods up to eight days. In contrast, a progressive decline in the number of progenitor cells was detected in cultures of nonadherent, T-cell-depleted marrow cells. In both cases, the addition of IL-3 increased by two- to fourfold over input the number of erythroid burst-forming cells (BFU-E) per culture. The number of BFU-E peaked either at day 4 or 8. G-CSF had no effect on the number of progenitor cells per culture. GM-CSF and Ep had no effect in cultures of nonadherent marrow cells but maintained the number of BFU-E in cultures of nonadherent, T-cell-depleted marrow cells. The addition of a neutralizing anti-GM-CSF monoclonal antibody, but not anti-IL-3 neutralizing antiserum, decreased the number of BFU-E in cultures of nonadherent marrow cells. None of the growth factors investigated enhanced the number of GM progenitors to the same degree as the number of BFU-E. However, in cultures of nonadherent, T-cell-depleted marrow cells, IL-3 and GM-CSF maintained the number of GM progenitors up to eight days. These results indicate that IL-3 alone is capable of increasing the number of BFU-E and of maintaining the number of GM progenitors in liquid culture, whereas GM-CSF and Ep are capable of maintaining, but not increasing, BFU-E in this system.


The Evolving Role of Diverse Gaseous Transmitters Mediating Heterocellular Communication Within the Vasculature.
Heterocellular communication between different cell types of the vasculature, both within the blood vessel wall and cells interacting with the blood vessel wall, is absolutely vital and must be tightly regulated. In this Forum, the role of four different gaseous transmitters [nitric oxide [NO], carbon monoxide (CO), hydrogen sulfide (H2S), and superoxide (O2•-)] is examined by four different research groups in detail, with two original articles and two reviews of the literature. In this editorial, we discuss how each of them may contribute their own component to heterocellular signaling in the vasculature. Antioxid. Redox Signal. 26, 881-885.


Extension of breast cancer: comparison of CT and MRI.
To compare three-dimensional (3D) helical CT with 3D MRI in the evaluation of intraductal spread of breast cancer. Fifty patients with breast cancer were examined. Tumor size ranged from Tis to T2. The whole breast was scanned by both breath-holding helical CT and MRI with contrast media. Linear or segmental enhancement, and spotty enhancement around the main tumor were considered to indicate ductal carcinoma in situ (DCIS) or ductal spread. These findings were compared with thin section histopathologic data. Seventeen of 35 patients had intraductal spread with invasive cancer and 15 patients had DCIS. The sensitivity, specificity, and accuracy of 3D CT in detecting intraductal spread or DCIS were 71.9%, 83.3%, and 76.0%, respectively, and those of 3D MRI were 87.5%, 61.1%, and 78.0%. Overestimations numbered three (6.0%) on CT and seven (14.0%) on MRI, and underestimations numbered nine (18.0%) on CT and four (8.0%) on MRI. 3D helical CT can provide good information about the spread of breast cancer and could be an alternative to 3D MRI for preoperative examination of breast cancer.


Rheumatoid discitis with cord compression at the thoracic level.
A 63-year-old man presented with spinal cord compression caused by rheumatoid discitis at a high thoracic level. Nuclear magnetic resonance imaging proved to be very useful in evaluating the extent of the inflammatory process. Early decompression and internal fixation resulted in cure with only some residual functional impairment.


Interleukin 1 alpha (IL1A) polymorphisms and risk of endometriosis in Iranian population: a case-control study.
Endometriosis is one of the most common gynecological diseases and a major cause of pain and infertility. It is influenced by genetic, epigenetic, and environmental factors. Recently, genome-wide association studies have revealed a strong association between IL1A single nucleotide polymorphisms (SNPs) and increased risk of endometriosis in Japanese women. The aim of the present study was to evaluate the association of three IL1A SNPs, rs17561, rs1304037, and rs2856836 with the risk of endometriosis in Iranian population. Totally, 105 women with diagnosis of endometriosis and 102 healthy women as control group were included. Three SNPs of the IL1A, rs17561 G/T, rs1304037 A/G, and rs2856836 T/C, were genotyped by PCR and RFLP. The rs2856836 TC genotype was significantly higher (p = .002; OR = 3.1, 95% CI: 1.5-6.5) in the patients (28.1%) than the control group (12.7%). The rs2856836 CC genotype was significantly higher (p = .047; OR = 2.3, 95% CI: 1.0-5.3) in the patients (17.5%) than the control group (10.8%). The rs2856836 C allele was significantly higher (p = .001; OR = 2.2, 95% CI: 1.4-3.6) in the patients (31.6%) than the control group (17.2%). The IL1A rs2856836 T/C SNP was associated with susceptibility to endometriosis and the rs2856836 C allele may increase the risk of endometriosis in Iranian women.


Changes in the incorporation of free fatty acids upon the stimulation of human polymorphonuclear leukocytes.
We have investigated the incorporation of free fatty acids into the cellular lipids of human polymorphonuclear leukocytes (PMN). Resting PMN incorporated both saturated and unsaturated fatty acids into triacylglycerol with only small amounts incorporated into the phospholipids. In contrast, PMN stimulated with the calcium ionophore A23187 incorporated significantly higher amounts of fatty acids, predominantly those other than arachidonic acid, into phosphatidylcholine and phosphatidylinositol, with reduced incorporation into triacylglycerol. Stimulation of PMN with serum-treated zymosan or the chemotactic peptide f-met-leu-phe but not phorbol myristate acetate, also increased the incorporation of fatty acids into these phospholipids. This stimulation-induced incorporation of fatty acids into cellular phospholipids was directed exlusively into position 2 of the lipid and probably reflects the reacylation of lysophospholipids after the release of arachidonic acid by phospholipase A2.


Geniohyoid muscle properties and myosin heavy chain composition are altered after short-term intermittent hypoxic exposure.
Patients with obstructive sleep apnea (OSA) often exhibit fatigued or inefficient upper airway dilator and constrictor muscles; an upper airway dilator, the geniohyoid (GH) muscle, is a particular example. Intermittent hypoxia (IH) is a frequent concomitant of OSA, and it may trigger muscle fiber composition changes that are characteristic of a fatigable nature. We examined effects of short-term IH on diaphragmatic and GH muscle fiber composition and fatigue properties by exposing 24 rats to alternating 10.3% O(2)-balance N(2) and room air every 480 s (240 s duty cycle) for a total duration of 5, 10, 15, 20, or 30 h. Sternohyoid fiber composition was also examined. Control animals were exposed to room air on the same schedule. Single-fiber analyses showed that GH muscle fiber types changed completely from myosin heavy chain (MHC) type 2A to MHC type 2B after 10 h of exposure, and the conversion was maintained for at least 30 h. Sternohyoid muscle fibers showed a delayed transition from MHC type 2A/2B to MHC type 2B. In contrast, major fiber types of the diaphragm were not significantly altered. The GH muscles showed similar tension-frequency relationships in all groups, but an increased fatigability developed, proportional to the duration of IH treatment. We conclude that short-term IH exposure alters GH muscle composition and physical properties toward more fatigable, fast-twitch types and that it may account for the fatigable upper airway fiber types found in sleep-disturbed breathing.


Chicken genome editing for investigating poultry pathogens.
Major advances in pathogen identification, treatment, vaccine development, and avian immunology have enabled the enormous expansion in global poultry production over the last 50 years. Looking forward, climate change, reduced feed, reduced water access, new avian pathogens and restrictions on the use of antimicrobials threaten to hamper further gains in poultry productivity and health. The development of novel in vitro cell culture systems, coupled with new genetic tools to investigate gene function, will aid in developing novel interventions for existing and newly emerging poultry pathogens. Our growing capacity to cryopreserve and generate genome-edited chicken lines will also be useful for developing improved chicken breeds for poultry farmers and conserving chicken genetic resources.


[Percutaneous nephrolithotomy in patients with solitary kidney].
Percutaneous nephrolithotomy (PCNL) is the method of choice for large and staghorn renal stones, including those in patients with solitary kidney. The aim of the literature review was to analyze the results of PCNL in patients with large stones in the solitary kidney. The literature search was conducted in databases Embase, Medline, Google Scholar, Scopus for the period from 2010 to 2019. A total 94 articles were selected, of which 16 papers were included in the review after analyzing the abstracts. Data was pooled and analyzed using SPSS Statistics 22.0. The primary stone-free rate for PCNL in these patients was 68.3+/-14.2%, and the final stone-free rate increased by 86.5+/-4.9%. The average duration of the operation was 86+/-25 (43.7-138.3) min, the length of stay was 5 (2-6) days. The baseline creatinine level was 137 (110-200) mmol/L, compared to 142 (122-183) mmol/L postoperatively. The mean difference between the baseline and postoperative Hb level was 7.8 (1.3-17.5) g/l. The estimated glomerular filtration rate (GFR) before PCNL was 62.3+/-7.5 ml/min/1.73 m2, and it did not exceed 62.5+/-9.3 ml/min/1.73 m2 postoperatively. The overall complication rate ranged from 10.6 to 68.8%, averaging 29.9%. In most cases, there were grade I and II complications, according to Clavien-Dindo classification, which didnt require additional interventions. PCNL is a highly effective treatment method for patients with large stones in solitary kidney. Complications rate is relatively low, which is achieved by an individual approach, with a consideration of the condition and all risk factors.


Is there any evidence that one continent diversion is any better than any other or than ileal conduit?
There is an obvious discrepancy between the perceived advantages of the different forms of continent urinary diversion from an expert's point of view and the limited utilization of these techniques outside of academic and tertiary referral centers. The vast majority of studies are retrospective with numerous confounding factors and often poorly defined outcomes. The rates of postoperative morbidity and need for reoperation varies widely among studies, even for the same procedure. The utilization of continent diversion depends on demographic, socioeconomic, provider-based, and clinical variables, with low case volume and lack of experience probably being the most obvious reasons for avoidance of more complex techniques. In contrast to the prevailing notion that patients undergoing continent diversion have superior quality of life than those receiving a conduit, existing studies fail to show significant advantages of one technique over the other. The current body of published literature is insufficient to conclude that there is a superior form of urinary diversion in terms of evidence-based medicine. It is quite clear, however, that not all patients are candidates for one type of diversion. The best results are obtained when a comprehensive concept is tailored to the individual patient.


What is the effect of ghrelin on rat uterine contractility in vitro?
Ghrelin, a recently isolated gastric hormone, is an endogenous ligand for growth hormone secretagogue receptors. There is novel evidence that ghrelin might be expressed in rat ovaries, placental tissues, and the uterus. It has been reported to have modulatory effects on smooth muscle contractility. In this study, we investigated the effects of ghrelin on spontaneous and oxytocin-induced contractions in the rat uterus in vitro and tried to detect its signaling pathway. Myometrium strips were removed from virgin female albino Wister rats and placed in a jacketed tissue bath. After initiation of spontaneous contractions, ghrelin was added to the tissue bath alone or after administration of indomethacin or NG-nitro-L-arginine methyl ester (L-NAME) or propranolol HCl. Student's t-test was used for statistical analysis. Our results revealed an inhibitory effect of ghrelin on both spontaneous and oxytocin-induced myometrial contractions. This effect was not affected by the application of indomethacin or L-NAME but was blocked after propranolol HCl administration. Ghrelin has an inhibitory effect on basal and oxytocin-induced rat myometrial contractions in vitro, and this myometrial response to ghrelin might be mediated by β-receptor signaling pathway.


Dental anxiety among adolescents in St. Petersburg, Russia.
This small-size epidemiologic investigation examined the prevalence and etiology of dental fear and anxiety among 288 schoolchildren aged 13-18 years in St. Petersburg, Russia. The adolescent population was collected from a larger sociological investigation performed in Russia during the early period of reforms. The investigation revealed a comparatively elevated anxiety level with an average DAS score of 10.0 and a prevalence of high dental fear of 12.6%. The present study showed that the origin of dental anxiety as reported by adolescent, urban Russians parallels much of previous results from the US and Western Europe. Thus, the etiology of dental anxiety was related to negative dental experiences and this conditional learning seemed to be especially prevalent in the presence of previous oral pain experiences and an existing dental anxiety in the family.


[Laryngotracheal reconstruction in children with subglottic stenosis].
To study the effect of laryngotracheal reconstruction (LTR) in children with subglottic stenosis (SGS), and to discuss the indications and the risks of intraoperative and postoperative treatment of LTR. From September 2008 to February 2010, 5 children (4 girls and 1 boy, aged 4 to 6 years) were treated by LTR. Among the 5 children, there were 2 congenital SGS and 3 acquired SGS. One had mild grade III SGS, 3 had severe grade III SGS, and one had grade IV SGS. One child with mild III SGS was treated by single-stage LTR, and the rest four children were treated by double-stage LTR. The surgical technique consisted of cricoid lamina midline vertical incision, rib cartilage graft interposition and endotracheal tube (ETT) stenting for 2 to 3 weeks. Four children with grade III SGS were de-cannulated 3 months after operation, and the child with grade IV SGS got de-cannulated 6 months after operation. Of all children, rib cartilage graft grower well, and the size of subglottis were amplified by grade III SGS to grade I SGS, and grade IV SGS to grade II SGS. All children obtained stable airway. One child with grade IV SGS who had hoarseness got effective phonation during follow-up 2 years after operation. LTR is a safe and effective treatment for pediatric subglottic stenosis. The important factors of successful operation are correct assessment and evaluation of the severity and overall medical status and selection of suitable surgical techniques.


The 2022 monkeypox outbreak in nonendemic countries: a review for the emergency department clinician.
Since May 2022, monkeypox (MPX) cases have been reported from several European countries, and this outbreak rapidly spread globally. Although MPX is not a new disease, most clinicians in nonendemic countries are unfamiliar with it. In addition, this current outbreak, unlike previous outbreaks in Africa, shows unique features in terms of epidemiology, transmission routes, and clinical manifestation. Most cases were men who have sex with men, had no travel history to an MPX endemic area, and presented with anogenital lesions, suggesting human-to-human transmission via close contact during sexual activity. In the emergency department setting, rapid identification of suspected cases and implementation of effective infection control and preventive measures are critical for preventing further transmission to healthcare workers and other patients. Emergency department clinicians should be aware of the clinical presentations of MPX and be alert to patients presenting with fever and vesicular rash or sexually transmitted disease-associated rash, especially among those with travel history to countries reporting an MPX outbreak. This brief review provides current information of MPX to help emergency department clinicians understand the epidemiology, transmission, clinical manifestation, diagnosis, treatment, and infection prevention and control of MPX.


Transesophageal echocardiography for detection of a papillary fibroelastoma of the aortic valve.
Papillary fibroelastoma (PF) is a benign cardiac tumor, typically attached to the cardiac valves. It is usually found incidentally at autopsy or surgery. It is rarely symptomatic, but can cause myocardial infarction, cerebral infarction and systemic embolism, even in young patients, and sometimes results in sudden death. We report on a case of a PF attached to the nodulus arantii of the left coronary cusp in a 56-year-old woman. She was referred to our institution due to a non ST-elevation myocardial infarction diagnosed by troponin positive-test. No other embolic source was identified. Diagnosis was obtained by two-dimensional echocardiography and confirmed by transesophageal echocardiography. After complete surgical removal of the tumor, we reconstructed the left coronary cusp with autologous pericardium. The histology revealed the diagnosis of a PF. Intraoperative transesophageal echocardiography confirmed complete restoration of aortic valve cusp coaptation. The clinical course was uneventful.


Rh-coordinated histidyl bolaamphiphile assembly: a catalyst for the isomerization of cis-stilbene and cis-alkene.
In this study, we present a colloidal assembly of histidyl bolaamphiphiles whose imidazoles coordinate with rhodium ions (HisC7[Rh]) to exhibit catalytic isomerization activity for cis-stilbene and cis-alkene molecules. The histidyl bolaamphiphiles self-assemble to form a soft scaffold that functions analogously to an apoenzyme. This scaffold exposes multiple histidyl imidazoles and carboxylates on its surface, to which rhodium ions bind, generating catalytically active sites. The Rh coordination with the biochemical functional groups was verified through comprehensive vibrational spectroscopy and calorimetry. The colloidal HisC7[Rh] demonstrated a significant catalytic effect on the isomerization of cis- to trans-stilbene under mild H2 conditions, resulting in 69% yield of trans-stilbene. In contrast, when Rh(cod)2BF4 was employed as a control catalyst, only the hydrogenated products of bibenzyl were obtained. These findings underscore the crucial role of histidyl motifs in exhibiting unique catalytic isomerization activity through the coordination with Rh. The catalytic activity of HisC7[Rh] is governed by several factors, such as rhodium content, solvent composition, temperature, and H2 pressure. Moreover, HisC7[Rh] displayed moderate isomerization activity towards not only stilbene but also unsaturated fatty acid isomers, highlighting its expansive potential as an isomerization catalyst.


Repression of Human T-lymphotropic virus type 1 Long Terminal Repeat sense transcription by Sp1 recruitment to novel Sp1 binding sites.
Human T-lymphotropic Virus type 1 (HTLV-1) infection is characterized by viral latency in the majority of infected cells and by the absence of viremia. These features are thought to be due to the repression of viral sense transcription in vivo. Here, our in silico analysis of the HTLV-1 Long Terminal Repeat (LTR) promoter nucleotide sequence revealed, in addition to the four Sp1 binding sites previously identified, the presence of two additional potential Sp1 sites within the R region. We demonstrated that the Sp1 and Sp3 transcription factors bound in vitro to these two sites and compared the binding affinity for Sp1 of all six different HTLV-1 Sp1 sites. By chromatin immunoprecipitation experiments, we showed Sp1 recruitment in vivo to the newly identified Sp1 sites. We demonstrated in the nucleosomal context of an episomal reporter vector that the Sp1 sites interfered with both the sense and antisense LTR promoter activities. Interestingly, the Sp1 sites exhibited together a repressor effect on the LTR sense transcriptional activity but had no effect on the LTR antisense activity. Thus, our results demonstrate the presence of two new functional Sp1 binding sites in the HTLV-1 LTR, which act as negative cis-regulatory elements of sense viral transcription.


Gastrointestinal quality of life and bowel function in adults born with anorectal malformation and hirschsprung disease.
To assess the quality of life and disease-specific functioning of adults with anorectal malformations (ARM) or Hirschsprung disease (HD) compared to healthy reference scores. Patients with the diagnosis of ARM or HD from the Adult Colorectal Research Registry completed the Short Form 36 Health Survey (SF-36), the Gastrointestinal Quality of Life Index (GIQoLI), and the Bowel Function Score (BFS) between October 2019 and August 2022. One-sample Wilcoxon test compared the results to reported healthy references with a significance level of < 0.05. The response rate was 67%. All three surveys were completed by 133 adults with a slight preponderance of males (51%). Median age was 31 years, 117 were born with ARM and 16 with HD. All subgroups had significantly lower BFS than healthy references. ARM patients scored significantly lower than the healthy reference population when assessed for GIQoL. All showed significant impairment with the mental component summary (MCS) of SF-36. Patients with a successful bowel management had significantly higher scores on all three questionnaires than those with fecal accidents. Our results emphasize the importance of a successful bowel management and its impact on the quality of life and bowel function. Long-term follow-up is recommended with attention to mental health.


[Celiac disease: a fertile field for diagnostic errors].
There has been considerable interest in celiac disease both in specialized and lay audiences during the past two decades, after it was shown to be much more prevalent in general population than previously thought. This disease can have a wide variety of clinical presentations, ranging from a silent form to a full-blown, sometimes severe disease. The diagnosis of celiac disease requires a high degree of suspicion, is fraught with potential pitfalls, and is a very rigorous process, given the protean nature of the disease. Clinicians should perform appropriate serum testing and conclude with the diagnostic "gold standard": documenting the hallmark histological findings in a small bowel biopsy. This paper reviews potential causes of celiac disease misdiagnosis.


A laboratory evaluation of wipe testing based on lead oxide surface contamination.
Although wipe testing has been used extensively as a measure of surface contamination in industrial hygiene, few scientific studies have been reported to validate the procedure with respect to quantitative recovery, repeatability or methodology. Consequently, a laboratory evaluation of wipe testing with particular attention to the OSHA procedure was undertaken using lead oxide dust as the test contaminant. A dust dispersion system was devised using a Wright dust feeder to produce relatively uniform surface concentrations in an aerosol chamber. Wipe materials included moistened filter paper, commercial paper towels, adhesive paper labels and adhesive tape. The quantitative recovery and repeatability of the wipe procedures were related to surface concentrations and the operational and material variables. Significant improvements in recoveries of up to 90% can be obtained with good repeatability for removable lead oxide dust on non-porous surfaces using moist paper on a fixed test surface area. For porous surfaces, which show significantly lower recovery by all methods, adhesive sampling materials applied at maximum pressure provided an optimum recovery of 77%. The importance of reliable surface contamination measurements in assessing potential health hazards underscores the desirability of improving the demonstrated deficiencies of the OSHA and other wipe sampling procedures.


Increased radiosensitivity and radioresistant DNA synthesis in cultured fibroblasts from patients with coronary atherosclerosis.
Cultured skin fibroblasts from five patients with atherosclerosis who underwent coronary artery bypass graft surgery were compared with those from one ataxia telangiectasia (AT) homozygote, three AT heterozygotes, and five healthy subjects to determine their sensitivity to gamma radiation as determined by a colony survival assay. Fibroblasts from four of these patients were also compared with those from two AT homozygotes, two AT heterozygotes, and three healthy subjects to determine postirradiation [3H]thymidine incorporation, indicating the levels of radioresistant DNA synthesis (RDS). On the basis of colony survival assay, after long-term irradiation (at low dose rate, ie, 0.007 Gy/min), fibroblasts from all five patients with atherosclerosis exhibited radiosensitivity that was intermediate between that of the healthy subjects and that of patients with the known radiosensitive syndrome AT. However, there was a considerable interstrain difference in the radiosensitivity of fibroblasts from patients with atherosclerosis, with their mean D10 values (radiation dose resulting in 10% cell survival) varying between 2.3 and 6.2 Gy, whereas the mean D10 values for the cells from the AT homozygote, AT heterozygotes, and healthy subjects were 2.0, 3.8, and 9.0 Gy, respectively. One of the patients with atherosclerosis showed cellular radiosensitivity quite similar to that of the AT homozygote, up to 2% to 10% of survival levels after short- (at a dose rate of 8 Gy/min) and long-term irradiation, respectively. The results of [3H]thymidine incorporation showed an AT heterozygote-like RDS in fibroblasts from patients with atherosclerosis that appeared to be intermediate between that of AT homozygotes and that of healthy subjects, suggesting a partial deregulation of cell cycle in the patients with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Zebrafish Embryo as an In Vivo Model for Behavioral and Pharmacological Characterization of Methylxanthine Drugs.
Zebrafish embryo is emerging as an important tool for behavior analysis as well as toxicity testing. In this study, we compared the effect of nine different methylxanthine drugs using zebrafish embryo as a model. We performed behavioral analysis, biochemical assay and Fish Embryo Toxicity (FET) test in zebrafish embryos after treatment with methylxanthines. Each drug appeared to behave in different ways and showed a distinct pattern of results. Embryos treated with seven out of nine methylxanthines exhibited epileptic-like pattern of movements, the severity of which varied with drugs and doses used. Cyclic AMP measurement showed that, despite of a significant increase in cAMP with some compounds, it was unrelated to the observed movement behavior changes. FET test showed a different pattern of toxicity with different methylxanthines. Each drug could be distinguished from the other based on its effect on mortality, morphological defects and teratogenic effects. In addition, there was a strong positive correlation between the toxic doses (TC50) calculated in zebrafish embryos and lethal doses (LD50) in rodents obtained from TOXNET database. Taken together, all these findings elucidate the potentiality of zebrafish embryos as an in vivo model for behavioral and toxicity testing of methylxanthines and other related compounds.


Garre's osteomyelitis associated with a fistula: a case report.
A report of Garre's osteomyelitis of the mandible associated with a fistula is presented. Elimination of pulpal periapical infection through endodontic therapy was shown to be an effective treatment. The total bone healing was observed one year later.


[Psychiatric and psychological problems of the court expertise in military crimes].
The responsibility for committing the military crime by an active service soldier is not always depending on the level of the accountability by the offender. The basis of the psychiatric and psychological court expertise in giving an opinion on military crimes have to be the motivation process. It is known that the motivation is creating by individualistic, biological and situational factors. Among soldiers the situational factors are connected with the decompensation of the personal accountability or with the adaptive disorders. Therefore, it is necessery and obligatory to appoint the psychologist for making court expertise.


Ternary ionic liquid-water pretreatment systems of an agave bagasse and municipal solid waste blend.
Pretreatment is necessary to reduce biomass recalcitrance and enhance the efficiency of enzymatic saccharification for biofuel production. Ionic liquid (IL) pretreatment has gained a significant interest as a pretreatment process that can reduce cellulose crystallinity and remove lignin, key factors that govern enzyme accessibility. There are several challenges that need to be addressed for IL pretreatment to become viable for commercialization, including IL cost and recyclability. In addition, it is unclear whether ILs can maintain process performance when utilizing low-cost, low-quality biomass feedstocks such as the paper fraction of municipal solid waste (MSW), which are readily available in high quantities. One approach to potentially reduce IL cost is to use a blend of ILs at different concentrations in aqueous mixtures. Herein, we describe 14 IL-water systems with mixtures of 1-ethyl-3-ethylimidazolium acetate ([C2C1Im][OAc]), 1-butyl-3-ethylimidazolium acetate ([C4C1Im][OAc]), and water that were used to pretreat MSW blended with agave bagasse (AGB). The detailed analysis of IL recycling in terms of sugar yields of pretreated biomass and IL stability was examined. Both biomass types (AGB and MSW) were efficiently disrupted by IL pretreatment. The pretreatment efficiency of [C2C1Im][OAc] and [C4C1Im][OAc] decreased when mixed with water above 40%. The AGB/MSW (1:1) blend demonstrated a glucan conversion of 94.1 and 83.0% using IL systems with ~10 and ~40% water content, respectively. Chemical structures of fresh ILs and recycle ILs presented strong similarities observed by FTIR and 1H-NMR spectroscopy. The glucan and xylan hydrolysis yields obtained from recycled IL exhibited a slight decrease in pretreatment efficiency (less than 10% in terms of hydrolysis yields compared to that of fresh IL), and a decrease in cellulose crystallinity was observed. Our results demonstrated that mixing ILs such as [C2C1Im][OAc] and [C4C1Im][OAc] and blending the paper fraction of MSW with agricultural residues, such as AGB, may contribute to lower the production costs while maintaining high sugar yields. Recycled IL-water mixtures provided comparable results to that of fresh ILs. Both of these results offer the potential of reducing the production costs of sugars and biofuels at biorefineries as compared to more conventional IL conversion technologies.Graphical abstractSchematic of ionic liquid (IL) pretreatment of agave bagasse (AB) and paper-rich fraction of municipal solid waste (MSW).


Arabidopsis CNGC Family Members Contribute to Heavy Metal Ion Uptake in Plants.
Heavy metal ions, including toxic concentrations of essential ions, negatively affect diverse metabolic and cellular processes. Heavy metal ions are known to enter cells in a non-selective manner; however, few studies have examined the regulation of heavy metal ion transport. Plant cyclic nucleotide-gated channels (CNGCs), a type of Ca2+-permeable-channel, have been suggested to be involved in the uptake of both essential and toxic cations. To determine the candidates responsible for heavy metal ion transport, a series of Arabidopsis CNGC mutants were examined for their response to Pb2+ and Cd2+ ions. The primary focus was on root growth and the analysis of the concentration of heavy metals in plants. Results, based on the analysis of primary root length, indicated that AtCNGC1, AtCNGC10, AtCNGC13 and AtCNGC19 play roles in Pb2+ toxicity, while AtCNGC11, AtCNGC13, AtCNGC16 and AtCNGC20 function in Cd2+ toxicity in Arabidopsis. Ion content analysis verified that the mutations of AtCNGC1 and AtCNGC13 resulted in reduced Pb2+ accumulation, while the mutations of AtCNGC11, AtCNGC15 and AtCNGC19 resulted in less Pb2+ and Cd2+ accumulation in plants. These findings provide functional evidence which support the roles of these AtCNGCs in the uptake and transport of Pb2+ or Cd2+ ion in plants.


Sequential and Dynamic Variations of IL-6, CD18, ICAM, TNF-α, and Microstructure in the Early Stage of Diabetic Retinopathy.
The purpose of this project is to make sequential and indepth observation of the variations of retinal microvascular, microstructure, and inflammatory mediators at the early stage of diabetic retinopathy (DR) in streptozotocin-induced diabetes mellitus (DM) rats. DM was induced by a single intraperitoneal injection of 60 mg/kg body weight streptozotocin (STZ). The fluorescein fundus angiography, hematoxylin and eosin staining, periodic acid-Schiff staining, fluorescence imaging techniques, quantitative real-time PCR, and vascular endothelial growth factor- (VEGF-) A ELISA were performed on the 8th day, at the 4th week, 6th week, 8th week, and 10th week after DM induction, respectively. In this study, we observed not only the decrease of retinal ganglion cells (RGCs) and the increase of endotheliocytes to pericytes (E/P) ratio, acellular capillaries, and type IV collagen-positive strands began to occur on the 8th day after induction but the vascular permeability and new vessel buds began to appear in the diabetes group at the 8th week, while the expression of VEGF-A, VEGF mRNA, IL-6 mRNA, ICAM mRNA, and TNF-α mRNA were significantly higher in the diabetes group compared with the normal group(P < 0.01) on the 8th day after induction and maintained a high expression level throughout the 10-week observation period. However, the expression of CD18 mRNA began to increase significantly at the 4th week after induction and reached a peak at the 6th week. Our study indicated the abnormal alterations of microvessels, microstructure, and inflammatory mediators at the early stage of DR, which confirms and supplements the previous research, and also promotes an indepth understanding and exploration of the pathophysiology and underlying pathogenesis of DR.


When math operations have visuospatial meanings versus purely symbolic definitions: Which solving stages and brain regions are affected?
How does processing differ during purely symbolic problem solving versus when mathematical operations can be mentally associated with meaningful (here, visuospatial) referents? Learners were trained on novel math operations (↓, ↑), that were defined strictly symbolically or in terms of a visuospatial interpretation (operands mapped to dimensions of shaded areas, answer = total area). During testing (scanner session), no visuospatial representations were displayed. However, we expected visuospatially-trained learners to form mental visuospatial representations for problems, and exhibit distinct activations. Since some solution intervals were long (~10s) and visuospatial representations might only be instantiated in some stages during solving, group differences were difficult to detect when treating the solving interval as a whole. However, an HSMM-MVPA process (Anderson and Fincham, 2014a) to parse fMRI data identified four distinct problem-solving stages in each group, dubbed: 1) encode; 2) plan; 3) compute; and 4) respond. We assessed stage-specific differences across groups. During encoding, several regions implicated in general semantic processing and/or mental imagery were more active in visuospatially-trained learners, including: bilateral supramarginal, precuneus, cuneus, parahippocampus, and left middle temporal regions. Four of these regions again emerged in the computation stage: precuneus, right supramarginal/angular, left supramarginal/inferior parietal, and left parahippocampal gyrus. Thus, mental visuospatial representations may not just inform initial problem interpretation (followed by symbolic computation), but may scaffold on-going computation. In the second stage, higher activations were found among symbolically-trained solvers in frontal regions (R. medial and inferior and L. superior) and the right angular and middle temporal gyrus. Activations in contrasting regions may shed light on solvers' degree of use of symbolic versus mental visuospatial strategies, even in absence of behavioral differences.


Selection criteria for high risk and low risk groups of recurrence and metastasis in patients with primary colorectal cancer.
Among 371 patients with primary colorectal cancer, 54 patients suffered from recurrence/metastasis (recurrence group) and 317 survived without recurrence for at least 5 years (non-recurrence group). The clinicopathological characteristics of the 2 groups were compared and occult neoplastic cells (ONCs) in the lymph node sinuses were detected by cytokeratin immunohistochemistry. There were significant differences of the following factors: venous invasion (v-) vs. (v+) for Dukes' A patients (p=0.0315); harvested lymph nodes (LN) <or=14 vs. >or=15 for Dukes' B patients (p=0.0388); (v-) vs. (v+) (p=0.0059), lymphatic invasion (ly-) vs. (ly+) (p=0.0435) for Dukes' A and B patients combined; D>n vs. D=n (p=0.0033), depth of tumor invasion <or=ss/a1 vs. >or=se/a2 (p=0.0329) for Dukes' C patients. When the detection of >or=3 ONCs was defined as positive, the sensitivity, specificity, PPV, and NPV were respectively 77%, 100%, 100% and 71% in Dukes' B patients, as well as 75%, 72%, 73% and 74% in Dukes' C patients. The high-risk groups for recurrence/metastasis were identified by the following criteria: (v+) and (ly+), <or=14 LN, and ONCs (+) of those with all factors for Dukes' A and B patients (selection rate, approximately 23.5%), while the criteria were D=n, >or=se/a2, and ONCs (+) of those with >or=2 factors for Dukes' C patients (selection rate; approximately 21.2-37.5%). These factors seem to be appropriate for separating patients into high-risk and low-risk groups of colorectal cancer recurrence/metastasis.


Common Neonatal Skin Lesions: Melanocytic Nevi, Pigment Alterations, and Nonmelanocytic Nevi.
Birthmarks are common in the healthy population and are generally harmless. Certain presentations, however, raise concern for associated syndromes or potential complications. It is important for pediatricians to be familiar with both harmless and potentially concerning birthmarks. This article discusses congenital melanocytic nevi, café-au-lait macules, hypomelanotic macules, nevus depigmentosus, nevus anemicus, epidermal nevi, and nevus sebaceous, including potential syndromes and complications. [Pediatr Ann. 2019;48(1):e23-e29.].


Cytopathologic diagnosis of liver mass lesions.
The liver is a common site for metastatic malignancies, particularly from the gastrointestinal tract. It also may be involved by primary neoplasms, both benign and malignant. Cytopathologic examination of mass lesions of the liver with pertinent use of ancillary studies is a useful method of establishing a correct diagnosis for patient management. The authors reviewed the literature for articles pertaining to cytologic characteristics of specific tumor types, utility of immunohistochemical markers and pertinent molecular studies, differential diagnoses and pitfalls.