Professional nursing education in the future: changes and challenges.
Trends in health care suggest changes in nursing practice and implications for nursing education. Changing demographics, emphasis on health promotion, health care costs, movement toward community-based care, and expanding technology are factors that shape the health care system of the future and educational preparation of nurses. This article examines these trends and implications for nursing education. Faculty are faced with preparing students for future practice that will be more complex and specialized than it now is; will be provided in multiple settings; and will require extensive knowledge, critical thinking and other cognitive skills, technologic and psychomotor skills, and a value system for making ethical decisions. Other outcomes of nursing education program include learning to learn, handling ambiguity, thinking like a professional, and accepting responsibility for decisions made in practice. For nursing to assume a central role in the health care system of tomorrow, reform in nursing education is needed today.


Seeing Double: Exploring the Phenomenology of Self-Reported Absence of Rivalry in Bistable Pictures.
Ambiguous images such as Rubin's vase-face can be interpreted in at least two different ways. These interpretations are typically taken to be mutually exclusive, and ambiguous images have thus served as models of perceptual competition. Here, we present data that challenges this view. In an online survey, we found that a large proportion of people within the general population reported that the two percepts were not competing but could be perceived simultaneously. Of those who reported that they could see both percepts simultaneously, we invited 17 participants to take part in a functional magnetic resonance imaging (fMRI) experiment. In the scanner, participants saw images that could be interpreted as either a landscape or a face and reported at every point in time whether they perceived predominantly the face, the landscape, or both simultaneously. We explored behavioral and neurophysiological (with fMRI) correlates of the reported subjective experience of entertaining two percepts simultaneously by comparing them to those of the simple percepts (i.e., face or landscape). First, by comparing percept durations, we found that the simultaneous state was as stable as the two other percepts. Second, by measuring blood-oxygen-level-dependent (BOLD) signal levels within the fusiform face area (FFA), occipital face area (OFA) and parahippocampal place area (PPA), we found evidence from objective data that confirmed the subjective reports. While the results in FFA and OFA were not conclusive, in PPA, BOLD signal levels during subjective reports of perceiving both a landscape and a face were lower than the BOLD signal levels associated with reports of perceiving a landscape (and, in turn, reports of seeing a landscape were associated with greater BOLD signal levels than reports of seeing a face, thus suggesting that BOLD signal levels in PPA are a valid correlate of subjective experience in this task). In sum, the objective measures suggest that entertaining two percepts simultaneously in mind can be regarded as a distinct (mixed) perceptual state. We argue with these results that a more central role of subjective report in cognitive neuroscience is sometimes warranted.


Nasal high flow clears anatomical dead space in upper airway models.
Recent studies showed that nasal high flow (NHF) with or without supplemental oxygen can assist ventilation of patients with chronic respiratory and sleep disorders. The hypothesis of this study was to test whether NHF can clear dead space in two different models of the upper nasal airways. The first was a simple tube model consisting of a nozzle to simulate the nasal valve area, connected to a cylindrical tube to simulate the nasal cavity. The second was a more complex anatomically representative upper airway model, constructed from segmented CT-scan images of a healthy volunteer. After filling the models with tracer gases, NHF was delivered at rates of 15, 30, and 45 l/min. The tracer gas clearance was determined using dynamic infrared CO2 spectroscopy and 81mKr-gas radioactive gamma camera imaging. There was a similar tracer-gas clearance characteristic in the tube model and the upper airway model: clearance half-times were below 1.0 s and decreased with increasing NHF rates. For both models, the anterior compartments demonstrated faster clearance levels (half-times < 0.5 s) and the posterior sections showed slower clearance (half-times < 1.0 s). Both imaging methods showed similar flow-dependent tracer-gas clearance in the models. For the anatomically based model, there was complete tracer-gas removal from the nasal cavities within 1.0 s. The level of clearance in the nasal cavities increased by 1.8 ml/s for every 1.0 l/min increase in the rate of NHF. The study has demonstrated the fast-occurring clearance of nasal cavities by NHF therapy, which is capable of reducing of dead space rebreathing.


Exosome Limitations in the Treatment of Inflammatory Diseases.
Despite the great interest and numerous studies, there is currently no unified standard describing the sequential manipulation with cells to obtain exosomes for clinical use.The use of exosomes has become an attractive alternative to cell therapy, since the flexible nature of these biological vesicles allows scientists to manipulate their composition to produce the desired exosomes carrying specific drugs, RNA and proteins. This study aimed to analyse scientific literature on the changes in the functional characteristics of exosomes, depending on the method of manipulation, potentially contributing to the development of negative effects in the treatment of diseases of inflammatory genesis. The choice of isolation method affects the expressed sets of protein markers, nucleic acids and receptors on microparticles. Various surface receptors present on the exosome membrane can be engineered to target lesions. Exosomes from healthy patients help to reduce inflammation, normalize intercellular communication and have anti-fibrotic, antioxidant, and cytoprotective effects. Exosomes can change the microenvironment, but the microenvironment can also change the composition of exosomes. Exosomes obtained from sick patients carry markers characteristic of the corresponding disease. Such exosomes can have pro-inflammatory, pro-fibrotic, cytotoxic, and oncogenic properties, and disrupt cellular cooperation. Until now, questions regarding the dose, reactions to repeated administration, and dosage regimes have not been completely resolved.


A feasibility study of neo-adjuvant low-dose fractionated radiotherapy with two different concurrent anthracycline-docetaxel schedules in stage IIA/B-IIIA breast cancer.
The aim of the study was to evaluate the feasibility of neoadjuvant low-dose fractionated radiotherapy, in combination with two anthracycline-docetaxel regimens, in breast cancer treatment. Women with stage IIA/B-IIIA breast cancer were assigned to receive the treatment of low-dose fractionated radiotherapy (0.4 Gy/per fraction, 2 fractions per day, for 2 days, every 21 days for 8-6 cycles) with concomitant neoadjuvant chemotherapy with non-pegylated liposomal doxorubicin and docetaxel. Two chemotherapy schedules were planned to be combined with low-dose fractionated radiotherapy. The first schedule consisted of four cycles of non-pegylated liposomal doxorubicin sequentially followed by four cycles of docetaxel, and the second schedule consisted of six cycles of non-pegylated liposomal doxorubicin plus concomitant docetaxel. Acute toxicity was evaluated according to the Radiation Therapy Oncology Group score system. Pathological response was evaluated by the Mandard score and expressed as tumor regression grade. Between March 2008 and February 2009, 10 patients underwent low-dose fractionated radiotherapy and concomitant chemotherapy. No grade 3-4 breast toxicity was observed. Five patients had a clinical complete response. Seven patients underwent conservative surgery. Overall, tumor regression grade 1 (absence of residual cancer) was achieved in one patient (10%) and grade 2 (residual isolated cells scattered through the fibrosis) in 4 patients (40%). The pathologic major response rate (tumor regression grade 1 + 2) was 20% in patients receiving low-dose fractionated radiotherapy and sequential non-pegylated liposomal doxorubicin and docetaxel and 80% in the group receiving low-dose fractionated radiotherapy and concurrent non-pegylated liposomal doxorubicin and docetaxel treatment. Concomitant low-dose fractionated radiotherapy combined with anthracycline and docetaxel is feasible. The toxicity profile of radio-chemotherapy was similar to that of chemotherapy alone: there was no acute skin or cardiac toxicity. The concurrent application of liposomal doxorubicin and docetaxel with low-dose fractionated radiation led to higher histological response rates compared to the sequential application of the same two drugs.


Early alveolar bone grafting has a negative effect on maxillary dental arch dimensions of pre-school children with complete unilateral cleft lip and palate.
To evaluate maxillary dental arch dimensions in pre-school children with a complete unilateral cleft lip and palate (CUCLP) after early alveolar bone grafting. Intercanine and intermolar widths, length of dental arch and mesiopalatal inclination of both maxillary segments were measured directly on the dental casts of 42 children (27 boys and 15 girls; mean age = 5.2 years, SD 0.5; Early-grafted group), 30 children (18 boys and 12 girls; mean age = 5.8 years, SD 0.8; Non-grafted group), and 40 children (25 boys and 15 girls, mean age = 5.8, SD 0.4; non-cleft Control group). Children from Early-grafted and Non-grafted groups had a CUCLP repaired with a one-stage closure of the entire cleft. An alveolar bone grafting was performed in the Early-grafted group between 2 and 4 years (mean = 2.4, SD 0.6). A one-way anova model with post hoc Tukey's multiple comparison procedures were used to identify intergroup differences. The mesiopalatal inclination of the lesser segment in the Early-grafted group was decreased in comparison with the Non-grafted and Control groups. The intercanine width had a tendency to be reduced in the Early-grafted group relative to Non-grafted group. Early bone grafting results in a larger collapse of the lesser segment than bone grafting carried out between 9 and 12 years of age.


Patients' perceptions on losing access to FPs: qualitative study.
To examine the health care-related experiences of individuals who have lost their FPs. A qualitative design using phenomenology. Southwestern Ontario. Eighteen participants (9 women and 9 men, with a mean age of 48.9 years) from urban or rural areas who had lost their FPs. Semistructured interviews were conducted, which were audiotaped and transcribed verbatim. An iterative approach using immersion and crystallization was employed for analysis. Participants reported having lost their FPs because of reasons specific to their physicians (eg, illness, retirement, career change) or system issues (eg, poor remuneration for FPs, cutbacks in health care leading to physician emigration). Participants described feelings of loss, abandonment, frustration, and anger related to losing their physicians. They expressed concerns about the difficulty of getting prescription medications, lack of continuity of care related to medical records, and preventive care. They faced considerable hurdles in accessing primary health care, turning to walk-in clinics and emergency departments despite concerns about quality and fragmentation of care. Some of those with chronic medical conditions prevailed upon specialists to help meet primary health care needs. Losing access to FPs evoked a variety of strong feelings among these participants. They engaged in a number of strategies to meet their primary care needs but not without reservations. In a health care system appropriately built on primary health care, the lack of access to FPs is regarded as the loss of a basic right to care.


Measuring the Autistic Women's Experience (AWE).
We developed a Dutch questionnaire called the Autistic Women's Experience (AWE) and compared its psychometric properties to the Autism Spectrum Quotient (AQ). Whilst attenuated gender differences on the AQ have been widely replicated, this instrument may not fully capture the unique experience of autistic women. The AWE was co-developed with autistic women to include items that reflect autistic women's experience. We investigated the AWE (49 items) and compared it with the AQ (50 items) in Dutch autistic individuals (N = 153, n = 85 women) and in the general population (N = 489, n = 246 women) aged 16+. Both the AQ and AWE had excellent internal consistency and were highly and equally predictive of autism in both women and men. Whilst there was a gender difference on the AQ among non-autistic people (men > women), there was no gender difference among autistic people, confirming all earlier studies. No gender differences were detected on the AWE overall scale, yet subtle gender differences were observed on the subscales. We conclude that the AQ is valid for both genders, but the AWE provides an additional useful perspective on the characteristics of autistic women. The AWE needs further validation in independent samples using techniques that allow for testing gender biases, as well as a confirmatory factor analysis in a larger sample.


[Experience with long-term preservation of international-standard cultures of Actinomycetes].
The results of the study on long-term maintenance (1-12 years) of 453 reference cultures of actinomycetes are presented. The cultures were maintained with the following methods: lyophilization, soil cultures and periodical passages on agarized nutrient media. Lyophilization was most efficient for storage of the majority of the cultures: 346 strains (77.4 per cent) preserved high viability over the observation period of 11-12 years. Lyophilization appeared less favourable for the cultures with low sporulation. The efficacy of the method of soil cultures on long-term storage of the whorl actinomycetes was low: 88 per cent of Streptoverticillium lost their viability within 1-2 years. However, this method was valuable for stabilization of the taxonomic features of streptomycetes. The maintenance of the actinomycetes by regular passages on agarized media every 6 months resulted in the changing of the cultural and morphological features in a number of the strains.


Acoustophoresis of monodisperse oil droplets in water: Effect of symmetry breaking and non-resonance operation on oil trapping behavior.
Acoustic manipulation of particles in microchannels has recently gained much attention. Ultrasonic standing wave (USW) separation of oil droplets or particles is an established technology for microscale applications. Acoustofluidic devices are normally operated at optimized conditions, namely, resonant frequency, to minimize power consumption. It has been recently shown that symmetry breaking is needed to obtain efficient conditions for acoustic particle trapping. In this work, we study the acoustophoretic behavior of monodisperse oil droplets (silicone oil and hexadecane) in water in the microfluidic chip operating at a non-resonant frequency and an off-center placement of the transducer. Finite element-based computer simulations are further performed to investigate the influence of these conditions on the acoustic pressure distribution and oil trapping behavior. Via investigating the Gor'kov potential, we obtained an overlap between the trapping patterns obtained in experiments and simulations. We demonstrate that an off-center placement of the transducer and driving the transducer at a non-resonant frequency can still lead to predictable behavior of particles in acoustofluidics. This is relevant to applications in which the theoretical resonant frequency cannot be achieved, e.g., manipulation of biological matter within living tissues.


Comparative molecular characterization of typical and exceptional responders in glioblastoma.
Glioblastoma (GBM) is the most common and the deadliest type of primary brain tumor, with a median survival time of only 15 months despite aggressive treatment. Although most patients have an extremely poor prognosis, a relatively small number of patients survive far beyond the median survival time. Investigation of these exceptional responders has sparked a great deal of interest and is becoming an important focus in the field of cancer research. To investigate the molecular differences between typical and exceptional responders in GBM, comparative analyses of somatic mutations, copy number, methylation, and gene expression datasets from The Cancer Genome Atlas were performed, and the results of these analyses were integrated via gene ontology and pathway analyses to assess the functional significance of the differential aberrations. Less severe copy number loss of CDKN2A, lower expression of CXCL8, and FLG mutations are all associated with an exceptional response. Typical responders are characterized by upregulation of NF-κB signaling and of pro-inflammatory cytokines, while exceptional responders are characterized by upregulation of Alzheimer's and Parkinson's disease pathways as well as of genes involved in synaptic transmission. The upregulated pathways and processes in typical responders are consistently associated with more aggressive tumor phenotypes, while those in the exceptional responders suggest a retained ability in tumor cells to undergo cell death in response to treatment. With the upcoming launch of the National Cancer Institute's Exceptional Responders Initiative, similar studies with much larger sample sizes will likely become possible, hopefully providing even more insight into the molecular differences between typical and exceptional responders.


Knockdown of Serum- and Glucocorticoid-Regulated Kinase 1 Enhances Cisplatin Sensitivity of Gastric Cancer Through Suppressing the Nuclear Factor Kappa-B Signaling Pathway.
Previous studies have published the promoting effect of serum and glucocorticoid-regulated kinase 1 (SGK1) in various malignant tumors. However, whether SGK1 promotes gastric cancer remains a mystery. To clarify the function of SGK1 in gastric cancer and its potential regulatory mechanism. Cell culture study. The SGK1-silenced model was generated in two gastric cancer cell lines and further evaluated their malignant behavior and susceptibility to cisplatin. The interaction between miR-15a-5p and SGK1 was evaluated by the luciferase reporter assay. The knockdown efficiency of SGK1 was confirmed by RT- qPCR and Western blot assays. Cell proliferation rate was assessed with CCK-8 assay, and flow cytometry was used to determine cell cycle progression and apoptosis. Western blot data displayed an elevated level of SGK1 in gastric cancer cell lines. Functionally, SGK1 deficiency suppressed gastric cancer cell proliferation (P < .01) by acting on cell-cycle progression. Moreover, SGK1 deficiency suppressed cell invasion and migration of gastric cancer cells (P < .01). Further, the silencing of SGK1 obviously suppressed cell proliferation and induced apoptosis of the cells after cisplatin treatment (P < .01), indicating that SGK1 deficiency facilitated the chemosensitivity of these 2 gastric cancer cell lines to cisplatin. Mechanically, downregulation of SGK1 repressed the cytoplasm- to-nucleus translocation of NF-κB p65. Interestingly, we found that miR-15a-5p binds to the 3'UTR of SGK1, which was confirmed using luciferase activity assay (P < .05). Moreover, the data suggested that SGK1 reversed the suppression effect of miR-15a-5p on gastric cancer cell migration (P < .01). Loss of SGK1 suppresses the malignant behavior of gastric cancer cells and increases cisplatin sensitivity by restraining the NF-κB signaling pathway. Moreover, SGK1 may exert an inhibitory effect in gastric cancer by being targeted by miR-15a-5p. Therefore, SGK1 may be a prospective target for future gastric cancer therapy.


Acute toxicity and induced weight changes in laboratory tests with Mn and Cu against Tilapia guineensis (Dumeril) and Tympanotonus fuscatus (Linne).
The acute toxicity of Mn and Cu against Tilapia guineensis and Tympanotonus fuscatus and the sub-lethal effects of the metals on weight changes were investigated in laboratory experiments employing standard bioassay techniques. Based on 96 hr LC50 values, copper was more toxic than manganese to either test animal by several orders of magnitude. Against either test metal, T. guineensis was remarkably more susceptible than T. fuscatus. At sub-lethal concentrations, particularly the two highest concentrations tested (0.016 and 0.03 mg Cu L(-1), 23.0 and 46.0 mg Mn I(-1)), both metals adversely affected the test species by bringing about reduced weight gains or weight loss in exposed animals compared to untreated controls at the end of the test periods. The implications of these findings for ecosystem viability and management are discussed.


Disease patterns among Saudi children undergoing colonoscopy for lower gastrointestinal bleeding: Single tertiary care center experience.
: The yield of colonoscopy in cases presenting with lower gastrointestinal bleeding (LGIB) in previously published studies varies according to several factors, including endoscopic skills, histopathological experience, and pattern of colonic pathology in different countries. The local literature is limited to a single small 20-year-old study. Our objective was to provide updated data on the diagnostic yield of colonoscopy in Saudi children with LGIB in Saudi Arabia. : This was a retrospective analysis of pediatric patients (0-14 years of age) who underwent colonoscopy for LGIB at the King Fahad Medical City (KFMC), from 2008 to 2018. LGIB was defined as fresh or dark blood per rectum. : During the study period, 175 children underwent colonoscopy for LGIB (99 males, mean age 7.05 ± 3.81 years), which constituted 53.5% of indications for colonoscopy procedures (n = 327) in our center. The terminal ileum was intubated in 81% of the procedures. Overall, inflammatory bowel disease (IBD) was the most commonly identified cause of LGIB (32% ) followed by colonic lymphonodular hyperplasia (CLNH) in 17% and juvenile polyp and rectal mucosal prolapse syndrome (RMPS), 11% each. On sub-analysis, cow's milk protein allergy (CMPA) and CLNH were the most common causes in infants and toddlers, 35% each; IBD (26.5%) and polyps (22.4%) in young children (2-6 years), and IBD (36%), CLNH (14.9%) and RMPS (14%) in older children (6-14 years). In comparing the IBD to the non-IBD group, IBD patients were older (mean 8.37 vs. 6.46 years, P = 0.002) and more likely to have diarrhea, weight loss, high erythrocyte sedimentation rate, anemia, and hypoalbuminemia (odds ratio 24, 11, 10.7, 6.5, and 4, respectively). Colonoscopy had a sensitivity of 97%, specificity of 100%, positive predictive value of 100%, negative predictive value of 81.4%, and accuracy of 97% in diagnosing LGIB. : Colonoscopy is an effective diagnostic tool in children with LGIB with a high diagnostic yield. Besides IBD, CLNH and RMPS are two other important pathologic entities that need to be considered in a child with LGIB.


Progression of coronary artery calcification at the crossroads: sign of progression or stabilization of coronary atherosclerosis?
Coronary artery calcification (CAC) has been strongly established as an independent predictor of adverse events, with a significant incremental prognostic value over traditional risk stratification algorithms. CAC progression has been associated with a higher rate of events. In parallel, several randomized studies and meta-analysis have shown the effectiveness of statins to slow progression and even promote plaque regression. However, evidence regarding the effect of routine medical therapy on CAC has yielded conflicting results, with initial studies showing significant CAC regression, and contemporaneous data showing rather the opposite. Accordingly, there is currently a great controversy on whether progression of CAC is a sign of progression or stabilization of coronary artery disease (CAD). The finding of inexorable CAC progression despite the implementation of intensive contemporaneous medical therapy suggests that further understanding of this phenomenon should be undertaken before the implementation of CAC as a surrogate endpoint for longitudinal studies, or for prospective follow-up of patients under routine medical treatment.


Pain-coping strategies in chronic pain patients: psychometric characteristics of the pain-coping inventory (PCI).
This article presents a series of studies aimed at validating a comprehensive pain-coping inventory (PCI) that is applicable to various types of patients with chronic pain. Item and scale analyses were performed for patients with rheumatoid arthritis (RA), patients with chronic headache, and pain clinic outpatients. The following 6 scales were derived from a simultaneous component analysis: Pain Transformation, Distraction, Reducing Demands, Retreating, Worrying, and Resting, all of which were internally reliable. A higher order factor analysis grouped the PCI scales into active (transformation, distraction, reducing demands) and passive (retreating, worrying, resting) pain-coping dimensions. Differences in use of strategy found between RA patients and headache patients indicated that the PCI scales were sufficiently sensitive to measure differences between groups. Concurrent validity was assessed for patients with RA and patients with fibromyalgia and predictive validity was assessed for patients with recently diagnosed RA after 1 and 3 years. In both analyses the validity of the scales was supported, in particular the predictive validity of passive coping scales for future outcomes.


Structural diversity in pyridine and polypyridine adducts of ring slipped manganocene: correlating ligand steric bulk with quantified deviation from ideal hapticity.
We have synthesized several new manganocene-adduct ([Cp2Mn(L)] = 1-L) complexes using pyridine and polypyridine ligands and report their molecular structures and characterization data. Consistent with other molecules in this class [(ηx-Cp)2MnLn] or [(ηx-Cp)2Mn(L-L)] (n = 1, 2; x = 1, 3, or 5), the manganese-cyclopentadienide interaction deviates from the classical ηx interactions (x = 3 or 5). Such deviations have been ascribed to steric factors and often called non-ideal hapticity. However, there is no quantification of this non-ideal hapticity and thus it is difficult to evaluate the extent of ring slippage or assign hapticity. Furthermore, the hypothesis that non-ideal hapticity in high-spin MnII complexes is induced by steric interactions has not been systematically evaluated. Therefore, we report herein a quantified scale for deviation from ideal hapticity between zero (ideal η5 interaction) and one ("η1" interaction). This quantified deviation from ideal hapticity has an empirical relationship with the ligand's steric properties, which strongly supports the premise that steric interactions cause the deviations in ionic M-Cp interactions.


A dose-dependent relationship between mercury exposure from dental amalgams and urinary mercury levels: a further assessment of the Casa Pia Children's Dental Amalgam Trial.
Dental amalgams are a commonly used dental restorative material, and amalgams are about 50% mercury (Hg). In our study, urinary Hg levels was examined in children of age 8-18 years, with and without dental amalgam fillings, from a completed clinical trial (parent study) that was designed to evaluate the potential health consequences of prolonged exposure to Hg from dental amalgam fillings. Our study was designed to determine whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and urinary Hg levels. Hg exposure depends on the size and number of teeth with dental amalgams. Overall, consistent with the results observed in the parent study, there was a statistically significant dose-dependent correlation between cumulative exposure to Hg from dental amalgams and urinary Hg levels, after covariate adjustment. Further, it was observed that urinary Hg levels increased by 18% to 52% among 8 to 18 year old individuals, respectively, with an average exposure to amalgams, in comparison to study subjects with no exposure to amalgams. The results of our study suggest that dental amalgams contribute to ongoing Hg exposure in a dose-dependent fashion.


A practical guide to successful breast-feeding management.
It is often difficult for new mothers to know whom to approach for the necessary guidance and practical problem solving required for successful long-term lactation. Although obstetricians are familiar with the care of the breast, they may not maintain the degree of postpartum follow-up necessary to ensure its proper function nor is it their responsibility to ensure that the infant receives proper nourishment. Pediatricians are expected to offer advice and information regarding not only the advantages and disadvantages of breastfeeding but also practical management of this art. We provide a guide for practitioners who wish to assist breast-feeding mothers and their infants.


Effect of repeated suboptimal chlorate treatment on ruminal and fecal bacterial diversity.
The minimal effective dose of sodium chlorate as an intervention to reduce the carriage of pathogenic bacteria in food-producing animals has not been clearly established. The effect of low-level oral chlorate administration to ewes was assessed by comparing the diversity of prominent bacterial populations in their gastrointestinal tract. Twelve lactating crossed Pelibuey and Blackbelly-Dorper ewes (average body weight, 65 kg) were randomly assigned (four per treatment) to receive a control treatment (TC; consisting of 3 g of NaCl per animal per day) or one of two chlorate treatments (T3 or T9; consisting of 1.8 or 5.4 g of NaClO3 per animal per day, respectively). Treatments were administered twice daily via oral gavage for 5 days. Ruminal and fecal samples were collected daily, starting 3 days before and ending 6 days after treatment, and were subjected to denaturing gradient gel electrophoresis of the 16S rRNA gene sequence amplified from total population DNA. For ruminal microbes, percent similarity coefficients (SCs) between groups varied from 23.0 to 67.5% and from 39.4 to 43.3% during pretreatment and treatment periods, respectively. During the treatment period, SCs within groups ranged from 39.4 to 90.3%, 43.3 to 86.7%, and 67.5 to 92.4% for TC, T3, and T9, respectively. For fecal microbes, SCs between groups varied from 38.0 to 85.2% and 38.0 to 94.2% during pretreatment and treatment periods, respectively. SCs for fecal populations during treatment were most varied for TC (38.0 to 67.9%), intermediate for T9 (75.6 to 92.0%), and least varied for T3 (80.6 to 90.6%). Heterogeneity within and between groups provided no evidence of an effect of chlorate treatment on ruminal or fecal microbial populations.


Autoantibodies against muscarinic type 3 receptor in Sjögren's syndrome inhibit aquaporin 5 trafficking.
Sjögren's syndrome (SjS) is a chronic autoimmune disease that mainly targets the salivary and lacrimal glands. It has been controversial whether anti-muscarinic type 3 receptor (α-M3R) autoantibodies in patients with SjS inhibit intracellular trafficking of aquaporin-5 (AQP5), water transport protein, leading to secretory dysfunction. To address this issue, GFP-tagged human AQP5 was overexpressed in human salivary gland cells (HSG-hAQP5) and monitored AQP5 trafficking to the plasma membrane following carbachol (CCh, M3R agonist) stimulation. AQP5 trafficking was indeed mediated by M3R stimulation, shown in partial blockage of trafficking by M3R-antagonist 4-DAMP. HSG-hAQP5 pre-incubated with SjS plasma for 24 hours significantly reduced AQP5 trafficking with CCh, compared with HSG-hAQP5 pre-incubated with healthy control (HC) plasma. This inhibition was confirmed by monoclonal α-M3R antibody and pre-absorbed plasma. Interestingly, HSG-hAQP5 pre-incubated with SjS plasma showed no change in cell volume, compared to the cells incubated with HC plasma showing shrinkage by twenty percent after CCh-stimulation. Our findings clearly indicate that binding of anti-M3R autoantibodies to the receptor, which was verified by immunoprecipitation, suppresses AQP5 trafficking to the membrane and contribute to impaired fluid secretion in SjS. Our current study urges further investigations of clinical associations between SjS symptoms, such as degree of secretory dysfunction, cognitive impairment, and/or bladder irritation, and different profiles (titers, isotypes, and/or specificity) of anti-M3R autoantibodies in individuals with SjS.


Metabolomics for improving pregnancy outcomes in women undergoing assisted reproductive technologies.
In order to overcome the low effectiveness of assisted reproductive technologies (ART) and the high incidence of multiple births, metabolomics is proposed as a non-invasive method to assess oocyte quality, embryo viability, and endometrial receptivity, and facilitate a targeted subfertility treatment. To evaluate the effectiveness and safety of metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity for improving live birth or ongoing pregnancy rates in women undergoing ART, compared to conventional methods of assessment. We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL and two trial registers (Feburary 2018). We also examined the reference lists of primary studies and review articles, citation lists of relevant publications, and abstracts of major scientific meetings. Randomised controlled trials (RCTs) on metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity in women undergoing ART. Pairs of review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary outcomes were rates of live birth or ongoing pregnancy (composite outcome) and miscarriage. Secondary outcomes were clinical pregnancy, multiple and ectopic pregnancy, cycle cancellation, and foetal abnormalities. We combined data to calculate odds ratios (ORs) for dichotomous data and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. We included four trials with a total of 924 women, with a mean age of 33 years. All assessed the role of metabolomic investigation of embryo viability. We found no RCTs that addressed the metabolomic assessment of oocyte quality or endometrial receptivity.We found low-quality evidence of little or no difference between metabolomic and non-metabolomic assessment of embryos for rates of live birth or ongoing pregnancy (OR 1.02, 95% CI 0.77 to 1.35, I² = 0%; four RCTs; N = 924), live birth alone (OR 0.99, 95% CI 0.69 to 1.44, I² = 0%; three RCTs; N = 597), or miscarriage (OR 1.18, 95% CI 0.77 to 1.82; I² = 0%; three RCTs; N = 869). A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for live birth or ongoing pregnancy (OR 0.90, 95% CI 0.66 to 1.25, I² = 0%; two RCTs; N = 744). Our findings suggested that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics.We found low-quality evidence of little or no difference between groups in rates of clinical pregnancy (OR 1.11, 95% CI 0.85 to 1.45; I²= 44%; four trials; N = 924) or multiple pregnancy (OR 1.50, 95% CI 0.70 to 3.19; I² = 0%; two RCTs, N = 180). Rates of cycle cancellation were higher in the metabolomics group (OR 1.78, 95% CI 1.18 to 2.69; I² = 51%; two RCTs; N = 744, low quality evidence). There was very low-quality evidence of little or no difference between groups in rates of ectopic pregnancy rates (OR 3.00, 95% CI 0.12 to 74.07; one RCT; N = 417), and foetal abnormality (no events; one RCT; N = 125). Data were lacking on other adverse effects. A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for clinical pregnancy (OR 1.03, 95% CI 0.76 to 1.38; I² = 40%; two RCTs; N = 744).The overall quality of the evidence ranged from very low to low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting, and other biases), imprecision, and inconsistency across trials. According to current trials in women undergoing ART, there is no evidence to show that metabolomic assessment of embryos before implantation has any meaningful effect on rates of live birth, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy or foetal abnormalities. The existing evidence varied from very low to low-quality. Data on other adverse events were sparse, so we could not reach conclusions on these. At the moment, there is no evidence to support or refute the use of this technique for subfertile women undergoing ART. Robust evidence is needed from further RCTs, which study the effects on live birth and miscarriage rates for the metabolomic assessment of embryo viability. Well designed and executed trials are also needed to study the effects on oocyte quality and endometrial receptivity, since none are currently available.


The forkhead transcription factor Hcm1 promotes mitochondrial biogenesis and stress resistance in yeast.
In Saccharomyces cerevisiae, the forkhead transcription factor Hcm1 is involved in chromosome segregation, spindle pole dynamics, and budding. We found that Hcm1 interacts with the histone deacetylase Sir2 and shifts from cytoplasm to the nucleus in the G(1)/S phase or in response to oxidative stress stimuli. The nuclear localization of Hcm1 depends on the activity of Sir2 as revealed by activators and inhibitors of the sirtuins and the Δsir2 mutant. Hcm1-overexpressing cells display more mitochondria that can be attributed to increased amounts of Abf2, a protein involved in mitochondrial biogenesis. These cells also show higher rates of oxygen consumption and improved resistance to oxidative stress that would be explained by increased catalase and Sod2 activities and molecular chaperones such as Hsp26, Hsp30, and members of Hsp70 family. Microarray analyses also reveal increased expression of genes involved in mitochondrial energy pathways and those allowing the transition from the exponential to the stationary phase. Taken together, these results describe a new and relevant role of Hcm1 for mitochondrial functions, suggesting that this transcription factor would participate in the adaptation of cells from fermentative to respiratory metabolism.


Extended high-frequency pure tone hearing thresholds and core executive functions.
To examine the relationship between extended high-frequency pure tone hearing thresholds (frequencies 10 to 14 kHz) and working memory capacity (WMC), inhibitory control, and cognitive flexibility. Experimental study measuring correlations between different high-frequency hearing threshold measures and cognitive measures. Pure tone audiometry was assessed in the extended high-frequency (frequencies 10, 12.5 and 14 kHz). Subjects were also tested regarding WMC, inhibitory control (response inhibition), and cognitive flexibility (information updating and shifting ability). Forty-three subjects between 20 and 29 years old with normal hearing (≤ 20 dB HL) in the frequency range between 0.125 to 8 kHz. No significant correlations were seen between high-frequency hearing thresholds defined as average best and worst ear high-frequency hearing thresholds and the cognitive measures. Differences between the best and the worst ear showed significant negative correlations with inhibitory control and global executive function (combination score for WMC, inhibitory control and cognitive flexibility). The present study suggests that global executive functions, more specifically response inhibition, and hearing threshold asymmetry in the extended high-frequency range are interrelated.


CO exposure, puff topography, and subjective effects in waterpipe tobacco smokers.
Waterpipe tobacco smoking is increasing in popularity though the toxicant exposure and effects associated with this tobacco use method are not well understood. Sixty-one waterpipe tobacco smokers (56 males; mean age +/- SD, 30.9 +/- 9.5 years; mean number of weekly waterpipe smoking episodes, 7.8 +/- 5.7; mean duration of waterpipe smoking 8.5 +/- 6.1 years) abstained from smoking for at least 24 hr and then smoked tobacco from a waterpipe ad libitum in a laboratory. Before and after smoking, expired-air carbon monoxide (CO) and subjective effects were assessed; puff topography was measured during smoking. The mean waterpipe use episode duration was 33.1 +/- 13.1 min. Expired-air CO increased significantly from a mean of 4.0 +/- 1.7 before to 35.5 +/- 32.7 after smoking. On average, participants took 169 +/- 100 puffs, with a mean puff volume of 511 +/- 333 ml. Urge to smoke, restlessness, craving, and other tobacco abstinence symptoms were reduced significantly after smoking, while ratings of dizzy, lightheaded, and other direct effects of nicotine increased. Expired-air CO and puff topography data indicate that, relative to a single cigarette, a single waterpipe tobacco smoking episode is associated with greater smoke exposure. Abstinent waterpipe tobacco smokers report symptoms similar to those reported by abstinent cigarette smokers, and these symptoms are reduced by subsequent waterpipe tobacco smoking. Taken together, these data are consistent with the notion that waterpipe tobacco smoking is likely associated with the risk of tobacco/nicotine dependence.


Galactography acquired with digital mammography in patients with nipple discharge: a retrospective analysis.
To evaluate the galactographic findings taken with digital mammography and to compare the findings between benign and malignant breast diseases. Galactographic findings were retrospectively analyzed and compared with histopathological results for 42 patients who showed abnormal findings on galactography and had histologically proven diagnoses between January 2005 and March 2008. A galactography was acquired using full-field digital mammography (Hologic Lorad Selenia; Danbury, USA). The difference in galactographic findings between malignant and benign breast diseases was analyzed using chi(2) test. A value of P < 0.05 was considered statistically significant. Of the total 42 cases, 11 cases were malignant breast diseases and 31 were benign diseases. Common galactographic findings of benign diseases include ductal obstruction (48.3%) and single filling defect (51.6%), and common findings for malignant tumor include ductal dilatation (72.7%) and stenosis (63.6%). Ductal stenosis, microcalcifications or mass adjacent to abnormal duct, multiple filling defects, ductal wall irregularity, ductal distortion and irregular filling defects were more prevalently seen in malignant cases. A single filling defect and lobular filling defect was more prevalently seen in benign cases (P < 0.05). Ductal dilatation was a common finding in both malignant and benign cases with no significant difference. Ductal lesions were well visualized on galactography acquired with a digital mammography. A preoperative diagnostic galactography is useful in making a differential diagnosis between benign diseases and malignant tumors in patients with pathologic nipple discharge.


Affinity of the gastric pathogen Helicobacter pylori for the N-sulphated glycosaminoglycan heparan sulphate.
Binding of 125I-heparan sulphate was a common property of Helicobacter pylori strains isolated from patients with gastroduodenal ulcer diseases. Binding was (i) saturable; (ii) reversible by the addition of unlabelled heparan sulphate and heparin; (iii) inhibited by unlabelled heparan sulphate, heparin, and heparin oligosaccharides but not by other glycosaminoglycans of comparable size (chondroitin sulphate and dermatan sulphate) or by highly glycosylated glycoproteins (hog gastric mucin and fetuin); (iv) reduced by heat treatment (80 degrees C, 10 min) and exposure of the bacteria to pronase E, proteinase K, trypsin and chymotrypsin, but unaffected by treatment with pepsin and neuraminidase; and (v) time-, pH-, and ionic strength-dependent. Scatchard plot analysis of the binding data indicated the presence of one class of high-affinity receptor (Kd = 9 x 10(-9) M) for heparan sulphate.


The three stages of building and testing mid-level theories in a realist RCT: a theoretical and methodological case-example.
Randomised controlled trials (RCTs) of social interventions are often criticised as failing to open the 'black box' whereby they only address questions about 'what works' without explaining the underlying processes of implementation and mechanisms of action, and how these vary by contextual characteristics of person and place. Realist RCTs are proposed as an approach to evaluation science that addresses these gaps while preserving the strengths of RCTs in providing evidence with strong internal validity in estimating effects. In the context of growing interest in designing and conducting realist trials, there is an urgent need to offer a worked example to provide guidance on how such an approach might be practically taken forward. The aim of this paper is to outline a three-staged theoretical and methodological process of undertaking a realist RCT using the example of the evaluation of a whole-school restorative intervention aiming to reduce aggression and bullying in English secondary schools. First, informed by the findings of our initial pilot trial and sociological theory, we elaborate our theory of change and specific a priori hypotheses about how intervention mechanisms interact with context to produce outcomes. Second, we describe how we will use emerging findings from the integral process evaluation within the RCT to refine, and add to, these a priori hypotheses before the collection of quantitative, follow-up data. Third, we will test our hypotheses using a combination of process and outcome data via quantitative analyses of effect mediation (examining mechanisms) and moderation (examining contextual contingencies). The results are then used to refine and further develop the theory of change. The aim of the realist RCT approach is thus not merely to assess whether the intervention is effective or not, but to develop empirically informed mid-range theory through a three-stage process. There are important implications for those involved with reporting and reviewing RCTs, including the use of new, iterative protocols. Current Controlled Trials ISRCTN10751359 (Registered 11 March 2014).


Role of ATG3 in the parasite Toxoplasma gondii: autophagy in an early branching eukaryote.
Toxoplasma gondii belongs to the phylum Apicomplexa, a diverse group of early branching unicellular eukaryotes related to dinoflagellates and ciliates. Like several other Apicomplexa such as Plasmodium (the causative agent of malaria), T. gondii is a human pathogen responsible for a potentially lethal disease called toxoplasmosis. Most Apicomplexa have complex life cycles, involving intermediate hosts and vectors, which include obligatory intracellular developmental stages. In the case of malaria and toxoplasmosis, it is that replicative process, leading to the ultimate lysis of the host cell, which is causing the symptoms of the disease. For Toxoplasma, the invasive and fast-replicating form of the parasite is called the tachyzoite. While autophagy has been a fast-growing field of research in recent years, not much was known about the relevance of this catabolic process in medically important apicomplexan parasites. Vesicles resembling autophagosomes had been described in drug-treated Plasmodium parasites in the early 1970s and a potential role for autophagy in organelle recycling during differentiation between Plasmodium life stages has also been recently described. Interestingly, recent database searches have identified putative orthologs of the core machinery responsible for the formation of autophagosomes in several protists, including Toxoplasma. In spite of an apparently reduced machinery (only about one-third of the yeast ATG genes appear to be conserved), T. gondii seemed thus able to perform macroautophagy, but the cellular functions of the pathway for this parasite remained to be demonstrated.


Heavy metal removal from waste waters by ion flotation.
Flotation studies were carried out to investigate the removal of heavy metals such as copper (II), zinc (II), chromium (III) and silver (I) from waste waters. Various parameters such as pH, collector and frother concentrations and airflow rate were tested to determine the optimum flotation conditions. Sodium dodecyl sulfate and hexadecyltrimethyl ammonium bromide were used as collectors. Ethanol and methyl isobutyl carbinol (MIBC) were used as frothers. Metal removal reached about 74% under optimum conditions at low pH. At basic pH it became as high as 90%, probably due to the contribution from the flotation of metal precipitates.


Effects of (56)Fe radiation on hippocampal function in mice deficient in chemokine receptor 2 (CCR2).
(56)Fe irradiation affects hippocampus-dependent cognition. The underlying mechanisms may involve alterations in neurogenesis, expression of the plasticity-related immediate early gene Arc, and inflammation. Chemokine receptor-2 (CCR2), which mediates the recruitment of infiltrating and resident microglia to sites of CNS inflammation, is upregulated by (56)Fe irradiation. CCR2 KO and wild-type mice were used to compare effects of (56)Fe radiation (600MeV, 0.25Gy) on hippocampal function using contextual fear conditioning involving tone shock pairing during training (+/+) and exposure to the same environment without tone shock pairings (-/-). In the -/- condition, irradiation enhanced habituation in WT mice, but not CCR2 KO mice, suggesting that a lack of CCR2 was associated with reduced cognitive performance. In the +/+ condition, irradiation reduced freezing but there was no genotype differences. There were no significant correlations between the number of Arc-positive cells in the dentate gyrus and freezing in either genotype. While measures of neurogenesis and gliogenesis appeared to be modulated by CCR2, there were no effects of genotype on the total numbers of newly born activated microglia before or after irradiation, indicating that other mechanisms are involved in the genotype-dependent radiation response.


Implementing a Produce Prescription Program in Partnership With a Community Coalition.
Healthy eating reduces risk for chronic disease, but can be out of reach for many Americans experiencing food insecurity. Produce Prescription Programs (PPPs) have emerged as an intervention to address barriers related to fruit and vegetable consumption. Using a social prescribing model, PPPs connect patients with referrals to community resources to reduce barriers to healthy eating. There is evidence of success of PPPs at improving dietary intake, yet little discussion within the literature of practical aspects of implementation. As interest grows around establishing PPPs within communities, increased attention to strategic planning and implementation remains necessary to develop robust and effective programming. We describe implementing the Pontiac Prescription for Health pilot program, highlighting the participatory planning process with partners. Development and implementation included a program model, recruitment methods and materials, a voucher contract and tracking system with produce vendors, physical activity opportunities, culturally competent health education sessions, and evaluation tools. We offer insight into lessons learned and practical implications for future "on-the-ground" planning and implementation. Engaging in a rigorous participatory planning process with all community partners, allowing adequate time to establish service agreements and a voucher system with vendors, and engaging program participants in different ways and spaces throughout the community can enhance program success.


Prophylactic antibiotics for head and neck surgery with flap reconstruction.
The leading cause of postoperative morbidity in patients undergoing major head and neck surgical procedures is postoperative infection. This prospective randomized multi-institutional clinical trial was designed to compare the effectiveness of clindamycin phosphate and high-dose cefazolin sodium therapy in preventing postoperative wound sepsis in patients undergoing contaminated head and neck surgical procedures in which flap reconstruction was required. Either clindamycin phosphate (900 mg) or cefazolin sodium (2 g) therapy was instituted intravenously prior to surgery and continued every 8 hours, for a total of 24 hours. The patients received postoperative follow-up, and the wounds were graded according to the worst condition observed. One hundred cases were evaluated. Fifty-one patients received clindamycin and 49 patients received high doses of cefazolin; wound infection developed in 10 patients (19.6%) and 11 patients (21.6%), respectively. This difference was not statistically significant. The average duration of surgery was approximately 8 hours for both the infected and the noninfected groups of patients. High-dose cefazolin and clindamycin have similar efficacy when administered prophylactically under these circumstances. Reconstruction with free vascularized tissue may aid in reducing postoperative wound infection.


HaploRec: efficient and accurate large-scale reconstruction of haplotypes.
Haplotypes extracted from human DNA can be used for gene mapping and other analysis of genetic patterns within and across populations. A fundamental problem is, however, that current practical laboratory methods do not give haplotype information. Estimation of phased haplotypes of unrelated individuals given their unphased genotypes is known as the haplotype reconstruction or phasing problem. We define three novel statistical models and give an efficient algorithm for haplotype reconstruction, jointly called HaploRec. HaploRec is based on exploiting local regularities conserved in haplotypes: it reconstructs haplotypes so that they have maximal local coherence. This approach--not assuming statistical dependence for remotely located markers--has two useful properties: it is well-suited for sparse marker maps, such as those used in gene mapping, and it can actually take advantage of long maps. Our experimental results with simulated and real data show that HaploRec is a powerful method for the large scale haplotyping needed in association studies. With sample sizes large enough for gene mapping it appeared to be the best compared to all other tested methods (Phase, fastPhase, PL-EM, Snphap, Gerbil; simulated data), with small samples it was competitive with the best available methods (real data). HaploRec is several orders of magnitude faster than Phase and comparable to the other methods; the running times are roughly linear in the number of subjects and the number of markers. HaploRec is publicly available at http://www.cs.helsinki.fi/group/genetics/haplotyping.html.


Tissue engineering scaffolds based on photocured dimethacrylate polymers for in vitro optical imaging.
Model tissue engineering scaffolds based on photocurable resin mixtures with sodium chloride have been prepared for optical imaging studies of cell attachment. A photoactivated ethoxylated bisphenol A dimethacrylate was mixed with sieved sodium chloride (NaCl) crystals and photocured to form a cross-linked composite. Upon soaking in water, the NaCl dissolved to leave a porous scaffold with desirable optical properties, mechanical integrity, and controlled porosity. Scaffolds were prepared with salt crystals that had been sieved to average diameters of 390, 300, 200, and 100 microm, yielding porosities of approximately 75 vol %. Scanning electron microscopy and X-ray microcomputed tomography confirmed that the pore size distribution of the scaffolds could be controlled using this photocuring technique. Compression tests showed that for scaffolds with 84% (by mass fraction) salt, the larger pore size scaffolds were more rigid, while the smaller pore size scaffolds were softer and more readily compressible. The prepared scaffolds were seeded with osteoblasts, cultured between 3 and 18 d, and examined using confocal microscopy. Because the cross-linked polymer in the scaffolds is an amorphous glass, it was possible to optically image cells that were over 400 microm beneath the surface of the sample.


Pitfalls in EEG Analysis in Patients With Nonconvulsive Status Epilepticus: A Preliminary Study.
Objective: Electroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis were still not reliable for the diagnosis of nonconvulsive status epilepticus (NCSE). This study aimed to identify typical pitfalls in the EEG analysis and make suggestions as to how those pitfalls might be avoided. Methods: We analyzed the EEG recordings of individuals who had clinically confirmed or suspected NCSE. Epileptiform EEG activity during seizures (ictal discharges) was visually analyzed by 2 independent raters. We investigated whether unreliable EEG visual interpretations quantified by low interrater agreement can be predicted by the characteristics of ictal discharges and individuals' clinical data. In addition, the EEG recordings were automatically analyzed by in-house algorithms. To further explore the causes of unreliable EEG interpretations, 2 epileptologists analyzed EEG patterns most likely misinterpreted as ictal discharges based on the differences between the EEG interpretations through the visual and automated analysis. Results: Short ictal discharges with a gradual onset (developing over 3 s in length) were liable to be misinterpreted. An extra 2 min of ictal discharges contributed to an increase in the kappa statistics of >0.1. Other problems were the misinterpretation of abnormal background activity (slow-wave activities, other abnormal brain activity, and the ictal-like movement artifacts), continuous interictal discharges, and continuous short ictal discharges. Conclusion: A longer duration criterion for NCSE-EEGs than 10 s that is commonly used in NCSE working criteria is recommended. Using knowledge of historical EEGs, individualized algorithms, and context-dependent alarm thresholds may also avoid the pitfalls.


Comparing the accuracy of ES-BC, EIS-GS, and ES Oxi on body composition, autonomic nervous system activity, and cardiac output to standardized assessments.
THE ELECTRO SENSOR COMPLEX (ESC) IS SOFTWARE THAT COMBINES THREE DEVICES USING BIOELECTRICAL IMPEDANCE, GALVANIC SKIN RESPONSE, AND SPECTROPHOTOMETRY: (1) ES-BC (Electro Sensor-Body Composition; LD Technology, Miami, FL) to assess body composition, (2) EIS-GS (Electro Interstitial Scan-Galvanic Skin; LD Technology) to predict autonomic nervous system activity, and (3) ES Oxi (Electro Sensor Oxi; LD Technology) to assess cardiac output. The objective of this study was to compare each to a standardized assessment: ES-BC to dual-energy X-ray absorptiometry (DXA), EIS-GS to heart rate variability, and ES Oxi to BioZ Dx Diagnostic System (BioZ Dx; SonoSite Inc, Bothell, WA). The study was conducted in two waves. Fifty subjects were assessed for body composition and autonomic nervous system activity. Fifty-one subjects were assessed for cardiac output. We found adequate relative and absolute agreement between ES-BC and DXA for fat mass (r = 0.97, P < 0.001) with ES-BC overestimating fat mass by 0.1 kg and for body fat percentage (r = 0.92, P < 0.001) with overestimation of fat percentage by 0.4%. For autonomic nervous system activity, we found marginal relative agreement between EIS-GS and heart rate variability by using EIS-GS as the predictor in a linear regression equation (adjusted R(2) = 0.56, P = 0.03). For cardiac output, adequate relative and absolute agreement was found between ES Oxi and BioZ Dx at baseline (r = 0.60, P < 0.001), after the first exercise stage (r = 0.79, P < 0.001), and after the second exercise stage (r = 0.86, P < 0.001). Absolute agreement was found at baseline and after both bouts of exercise; ES Oxi overestimated baseline and stage 1 exercise cardiac output by 0.3 L/minute and 0.1 L/minute, respectively, but exactly estimated stage 2 exercise cardiac output. ES-BC and ES Oxi accurately assessed body composition and cardiac output compared to standardized instruments, whereas EIS-GS showed marginal predictive ability for autonomic nervous system activity. The ESC software managing the three devices would be useful to help detect complications related to metabolic syndrome, diabetes, and cardiovascular disease and to noninvasively and rapidly manage treatment follow-up.


[Clinical aspects of depression in the psychotic patient].
In order to study clinical aspects of depression in psychotic patients, it is necessary to first differentiate between the following states, as a function of the currently accepted international classification of mental disorders: 1) depressions correlated with psychotic symptomatology (delirium, hallucinations); 2) psychotic disorders with depressive symptomatology; 3) schizo-affective disorders. The greatest interest is currently in the assessment of the second category, in particular study of depression in schizophrenics. This is due to a number of factors, including the relatively great frequency of the disorder, its differential significance as a function of the time in the natural history of the disease, as well as prognostic and therapeutic implications. Proper clinical evaluation is thus important. Until the last few years, this evaluation was based primarily upon use of depression scales or factorial scores, either from general psychopathology scales or specific schizophrenia scales. A number of empirical studies have recently cast some doubt upon validity of these scales for evaluation of depression in psychotic patients, and more specific instruments such as the Calgary Depression Scale (CDS) and the Psychotic Depression Scale (PDS) have been developed. The first validation studies with these scales open up an interesting perspective, in particular for the evaluation of the effects of neuroleptics.


Densities and numbers of calbindin and parvalbumin positive neurons across the rat and mouse brain.
The calcium-binding proteins parvalbumin and calbindin are expressed in neuronal populations regulating brain networks involved in spatial navigation, memory processes, and social interactions. Information about the numbers of these neurons across brain regions is required to understand their functional roles but is scarcely available. Employing semi-automated image analysis, we performed brain-wide analysis of immunohistochemically stained parvalbumin and calbindin sections and show that these neurons distribute in complementary patterns across the mouse brain. Parvalbumin neurons dominate in areas related to sensorimotor processing and navigation, whereas calbindin neurons prevail in regions reflecting behavioral states. We also find that parvalbumin neurons distribute according to similar principles in the hippocampal region of the rat and mouse brain. We validated our results against manual counts and evaluated variability of results among researchers. Comparison of our results to previous reports showed that neuron numbers vary, whereas patterns of relative densities and numbers are consistent.


Does health information affect lifestyle behaviours? The impact of a diabetes diagnosis.
Despite an increasing interest in the effect of health information on health-behaviours, evidence on the causal impact of a diagnosis on lifestyle factors is still mixed and does not often account for long-term effects. We explore the role of health information in individual health-related decisions by identifying the causal impact of a type-2 diabetes diagnosis on body mass index (BMI) and lifestyle behaviours. We employ a fuzzy regression discontinuity design (RDD) exploiting the exogenous cut-off value in the diagnosis of type-2 diabetes provided by a biomarker (glycated haemoglobin) drawn from unique administrative longitudinal data from Spain. We find that following a type-2 diabetes diagnosis individuals appear to reduce their weight in the short-term. Differently from previous studies, we also provide evidence of statistically significant long-term impacts of a type-2 diabetes diagnosis on BMI up to three years from the diagnosis. We do not find perceivable effects of a type-2 diabetes diagnosis on quitting smoking or drinking. Overall, health information appears to have a sustained causal impact on weight reduction, a key lifestyle and risk factor among individuals with type-2 diabetes.


Genomic profiling of murine mammary tumors identifies potential personalized drug targets for p53-deficient mammary cancers.
Targeted therapies against basal-like breast tumors, which are typically 'triple-negative breast cancers (TNBCs)', remain an important unmet clinical need. Somatic TP53 mutations are the most common genetic event in basal-like breast tumors and TNBC. To identify additional drivers and possible drug targets of this subtype, a comparative study between human and murine tumors was performed by utilizing a murine Trp53-null mammary transplant tumor model. We show that two subsets of murine Trp53-null mammary transplant tumors resemble aspects of the human basal-like subtype. DNA-microarray, whole-genome and exome-based sequencing approaches were used to interrogate the secondary genetic aberrations of these tumors, which were then compared to human basal-like tumors to identify conserved somatic genetic features. DNA copy-number variation produced the largest number of conserved candidate personalized drug targets. These candidates were filtered using a DNA-RNA Pearson correlation cut-off and a requirement that the gene was deemed essential in at least 5% of human breast cancer cell lines from an RNA-mediated interference screen database. Five potential personalized drug target genes, which were spontaneously amplified loci in both murine and human basal-like tumors, were identified: Cul4a, Lamp1, Met, Pnpla6 and Tubgcp3 As a proof of concept, inhibition of Met using crizotinib caused Met-amplified murine tumors to initially undergo complete regression. This study identifies Met as a promising drug target in a subset of murine Trp53-null tumors, thus identifying a potential shared driver with a subset of human basal-like breast cancers. Our results also highlight the importance of comparative genomic studies for discovering personalized drug targets and for providing a preclinical model for further investigations of key tumor signaling pathways.


[Cerebral tuberculosis without meningitis in a immunocompetent child].
Cerebral tuberculosis TB (tuberculomas) without meningitis is an uncommon disease with a high morbidity and mortality. We report on a case that illustrates the complexity of this clinical presentation. An 11 month old, previously healthy male infant was brought to the clinic due to fever present during the last 1.5 months, associated with loss of neurodevelopmental goals and signs of endocranial hypertension. CT scan of the skull revealed dilatation of the ventricular system with transependimary edema; MRI showed multiple intra- and extra-axial micronodular images and hydrocephalus. Studies of CSF (cyto-chemical analysis, staining, culture for aerobes, fungi, mycobacteria, and molecular tests for TB were negative). Empirical management for subacute meningoencephalitis was prescribed complemented with tetraconjugated treatment for TB and steroids. As there was no microbiological isolation, biopsy of a cerebellar lesion was performed, which revealed chronic necrotizing granulomatous inflammation and acid-alcohol resistant bacilli. The diagnosis of cerebral TB without meningeal involvement was confirmed. The objective of the present report is to emphasize the importance of considering this presentation of TB in children, to remark the need of exhaustive search for the etiologic agent by obtaining samples of the different fluids and tissues even if it implies recurring to invasive methods.


New Horizons in the use of routine data for ageing research.
The past three decades have seen a steady increase in the availability of routinely collected health and social care data and the processing power to analyse it. These developments represent a major opportunity for ageing research, especially with the integration of different datasets across traditional boundaries of health and social care, for prognostic research and novel evaluations of interventions with representative populations of older people. However, there are considerable challenges in using routine data at the level of coding, data analysis and in the application of findings to everyday care. New Horizons in applying routine data to investigate novel questions in ageing research require a collaborative approach between clinicians, data scientists, biostatisticians, epidemiologists and trial methodologists. This requires building capacity for the next generation of research leaders in this important area. There is a need to develop consensus code lists and standardised, validated algorithms for common conditions and outcomes that are relevant for older people to maximise the potential of routine data research in this group. Lastly, we must help drive the application of routine data to improve the care of older people, through the development of novel methods for evaluation of interventions using routine data infrastructure. We believe that harnessing routine data can help address knowledge gaps for older people living with multiple conditions and frailty, and design interventions and pathways of care to address the complex health issues we face in caring for older people.


Comparative study of lens proteins of gray squirrel and human.
1. The four crystallins of the gray squirrel lens have been characterized using gel filtration chromatography, polyacrylamide gel electrophoresis, and immunoblotting. Alpha, beta-heavy, beta-light, and gamma crystallins of squirrel lenses have been identified immunologically, and they cross-react strongly with rabbit polyclonal antibodies. The gamma-24 crystallin of the squirrel lens also reacts strongly with monoclonal anti-human lens gamma-24, as shown by its inhibition of the ELISA reaction by 85%. 2. The water-insoluble urea soluble proteins represent non-covalently associated species of soluble crystallins and the lens cytoskeletal proteins. The membrane intrinsic protein in the urea insoluble pellet has a mol. wt of 27,000 but other lower and higher mol. wt components are also present, which were removed by washing with 0.1 NaOH. The N-terminal 30 amino acid of squirrel lens gamma crystallin was found to be identical to that of the bovine (and human) lens. 3. Measurements of the distribution and state of SH and SS compounds in the squirrel lens have shown greater similarities to those of primates than those of rodents. The findings show that on the basis of both protein and sulfur chemistry the squirrel lens is a representative model for studies of oxidative lens changes in diurnal animals, including man.


Radiologic technology educators and andragogy.
Radiologic technology educators are in constant contact with adult learners. However, the theoretical framework that radiologic educators use to guide their instruction may not be appropriate for adults. This article examines the assumptions of the standard instructional theory and the most modern approach to adult education-- andragogy . It also shows how these assumptions affect the adult learner in a radiologic education setting.


[The second opinion in oncology].
The medical second opinion (MSO) means the process through which it is possible to consult any available medical institution or a single physician, to compare, confirm and/or review a first diagnosis and/or a proposed treatment. The MSO is of the utmost importance when patients are suffering serious and disabling diseases or when risking their lives. Oncology is a really complex discipline in which, daily, doctors and patients have to deal with new clinical, managerial and sociological problems. Most patients are now better informed-often having gathered information from the Web, newspapers, magazines.This information is often very mixed and confusing and the number of MSO is increasing.


Celiac Crisis Presenting with Refractory Hypokalemia and Bleeding Diathesis.
Celiac disease is an immune mediated disorder elicited by the ingestion of gluten in genetically susceptible person and associated with some HLA subtypes. It is characterized by chronic inflammation of small intestine associated with villous atrophy. Symptoms usually appear when weaning from breast milk is done and gluten is introduced in diet. Failures to thrive, chronic diarrhea, vomiting abdominal distension are usual symptoms. Celiac crisis is rare but well known complication of celiac disease presenting with various systemic and metabolic manifestations like hypokalemia, hyponatremia, shock and bleeding diathesis. Celiac crisis usually has some underlying precipitating factor and is more common in patient with noncompliance with gluten free diet. We report a case of 14 year and three months old female child, a known case of celiac disease having the poor compliance with gluten free diet, presenting in celiac crisis with shock, refractory hypokalemia and bleeding diathesis.


Reference values of conditioned pain modulation.
Background and aims Endogenous pain modulation can be studied in humans by conditioned pain modulation (CPM): pain induced by a test stimulus is attenuated by a distantly applied noxious conditioning stimulus. The detection of impaired CPM in individual patients is of potential importance to understand the pathophysiology and predict outcomes. However, it requires the availability of reference values. Methods We determined reference values of CPM in 146 pain-free subjects. Pressure and electrical stimulation were the test stimuli. For electrical stimuli, we recorded both pain threshold and threshold for the nociceptive withdrawal reflex. Cold pressor test was the conditioning stimulus. The 5th, 10th and 25th percentiles for the three tests were computed by quantile regression analyses. Results The average thresholds increased after the conditioning stimulus for all three tests. However, a subset of subjects displayed a decrease in thresholds during the conditioning stimulus. This produced negative values for most of the computed percentiles. Conclusions This study determined percentile reference values of CPM that can be used to better phenotype patients for clinical and research purposes. The negative value of percentiles suggests that a slightly negative CPM effect can be observed in pain-free volunteers. Implications Pain facilitation rather than inhibition during the conditioning stimulus occurs in some pain-free volunteers and may not necessarily represent an abnormal finding.


Cultivating tobacco-free farms.
A multi-agency initiative encouraging farmers to switch from tobacco cultivation to healthier and more ecologically sustainable crops is getting attention in Kenya. Gary Humphreys reports.


Evaluation of ¹⁸F-fluorodeoxyglucose uptake in enlarged mediastinal lymph nodes in patients with lung cancer.
Accurate lymph nodal staging of lung cancer is critical for determining the treatment options. With the help of (18)F-fluorodeoxyglucose positron emission tomography/computer tomography ((18)F-FDG-PET/CT), the clinician can rule out/in the regional lymph nodes positive for metastasis in the patients with lung cancer in a majority of cases. However, a small proportion of cases with false positivity of metastasis have been reported. Transbronchial needle aspirations and mediastinoscopic biopsies are still necessary to determine whether enlarged hypermetabolic mediastinal lymph nodes are positive for lung cancer metastasis. Here we report three intricate cases showing hypermetabolic activity in the mediastinal lymph nodes in the patients with pathologically diagnosed lung cancer on PET/CT. The first patient had squamous cell carcinoma in the left upper lobe of the lung with surrounding necrotizing granulomas and concurrent with silicosis and granulomatous inflammation in the lymph nodes; the second presented with symptoms of viral pneumonia, which was pathologically diagnosed as a lung adenocarcinoma, stage IA, concurrent with sarcoidosis involving the lymph nodes; the last case was diagnosed as squamous cell carcinoma in the right upper lobe of the lung, but lymph nodes showed reactive hyperplasia. These cases suggest that some cases are so complex that avid (18)F-FDG uptake in the mediastinal lymph nodes in the patients with pathologically diagnosed lung cancer should be carefully analyzed based on individual patients' clinical background.


Photodynamic-active smart biocompatible material for an antibacterial surface coating.
Here we present a new effective antibacterial material suitable for a coating, e.g., surface treatment of textiles, which is also time and financially undemanding. The most important role is played by hydrophobic carbon quantum dots, as a new type of photosensitizer, produced by carbonization of different carbon precursors, which are incorporated by swelling from solution into various polymer matrices in the form of thin films, in particular polyurethanes, which are currently commercially used for industrial surface treatment of textiles. The role of hydrophobic carbon quantum dots is to work as photosensitizers upon irradiation and produce reactive oxygen species, namely singlet oxygen, which is already known as the most effective radical for elimination different kinds of bacteria on the surface or in close proximity to such modified material. Therefore, we have mainly studied the effect of hydrophobic carbon quantum dots on Staphylococcus aureus and the cytotoxicity tests, which are essential for the safe handling of such material. Also, the production of singlet oxygen by several methods (electron paramagnetic spectroscopy, time-resolved near-infrared spectroscopy), surface structures (atomic force microscopy and contact angle measurement), and the effect of radiation on polymer matrices were studied. The prepared material is easily modulated by end-user requirements.


Clinical discussion and review of the management of brain metastases.
Brain metastases are common in patients with cancer and are associated with a poor prognosis. Optimal treatment requires an integrative multidisciplinary approach, and therapeutic options may include stereotactic radiosurgery, whole-brain radiation therapy, surgical resection, chemotherapy, and targeted agents. The goals of therapy are to prolong survival, preserve neurologic function, and palliate symptoms. This article outlines the various therapeutic modalities, factors that guide treatment decisions, and medical management of frequently encountered complications of brain metastases.


[The concept of "psychological risk" in the professional activity of employees of fly-in fly-out method of labor organization on the example of oil and gas companies in the Far North].
Professional work in shift team in the Far North contributes to the formation of unfavorable functional states and the development of destructive personality traits of employees, which lead to a decrease in the level of mental health, productivity and work efficiency With the aim to predict the professional efficiency of the rotational personnel it is necessary to determine the probability of negative psychological states, properties and qualities that will prevent its implementation, i.e, the psychological risks in professional activities. Psychological risk in the professional activity is the probability of occurrence of a professional personal destructions and the formation of unfavorable functional states of employees when performing job functions due to the prolonged negative impact of social-household and occupational factors in the lack of personal and environmental resource.


High frequency percussive ventilation (HFPV). Case reports.
Treatment of acute respiratory failure is still a hot issue in intensive care everyday practice: in the last few years high frequency ventilation techniques have been employed as a therapy for adult respiratory distress syndrome (ARDS) and acute respiratory failure (ARF). We applied high frequency percussive ventilation (HFPV) to 3 patients affected by ARDS or ARF, who did not improve after 24 hours of conventional mechanical ventilation (CMV). All our patient underwent 12 hours of HFPV, and showed an improvement of both respiratory exchange and radiological imaging. Even if the pathogenesis of ARF was quite different, in all patient we registered a good response and no complications.


ICTV Virus Taxonomy Profile: Metaviridae.
Metaviridae is a family of retrotransposons and reverse-transcribing viruses with long terminal repeats belonging to the order Ortervirales. Members of the genera Errantivirus and Metavirus include, respectively, Saccharomyces cerevisiae Ty3 virus and its Gypsy-like relatives in drosophilids. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Metaviridae, which is available at ictv.global/report/metaviridae.


Acute myeloid leukemia with t(6;9) (p23;q34): association with myelodysplasia, basophilia, and initial CD34 negative immunophenotype.
The translocation (6;9)(p23;q34) is a rare cytogenetic aberration found in patients with acute myeloid leukemia (AML). The clinical, morphologic, and immunophenotypic findings of eight t(6;9) acute leukemias are described. The patients included six men and two women with a mean age of 38.5 years. The leukemias were classified in the French-American-British (FAB) system as AML FAB M2 in four cases and as FAB M4 in four cases. Underlying myelodysplasia was evident in six cases. Bone marrow basophilia was found at presentation in six of the seven cases studied. In two cases with basophilia, darkly stained granules were also present in many eosinophils. In one case, initial basophilia was absent, but was present at relapse, as were eosinophils containing darkly stained granules. Iron stains were available in five cases; four showed increased incorporation and three had ringed sideroblasts. All cases studied by flow cytometry (six at presentation and three at relapse) expressed CD13, CD33, and human leukocyte antigen-DR. At presentation, five cases were CD34 negative. In one case at presentation, a subset of blasts (18%) weakly expressed CD34. Three cases studied at relapse were positive for CD34. Two of seven cases studied were terminal deoxynucleotidyl transferase positive. The t(6;9)(p23;q34) was the only cytogenetic abnormality in five cases. Trisomy 8 was found in two cases, and ring 12 was present in one case. Three patients are living with refractory leukemia 6 weeks to 6 months after initial diagnosis, and three patients died of complications of allogeneic bone marrow transplantation. Only one patient is alive without evidence of disease 3 years after bone marrow transplantation. t(6;9) leukemia is an unusual type of AML that is associated with poor prognosis, early age of onset, basophilia, myelodysplasia with frequent ringed sideroblasts, and a CD34-negative initial phenotype.


Continuous Blood Purification Ameliorates Multiple Organ Failure Through Inhibiting the Activation of the P38 MAPK Signaling Pathway in a Rat Model.
Multiple organ failure (MOF) is a primary threat to the survival of patients with systemic inflammation. Blood purification is employed in the treatment of MOF, as an artificial kidney or artificial liver. This study focuses on the effects of continuous blood purification (CBP) on ameliorating MOF through regulating the p38 mitogen-activated protein kinase (MAPK) signaling pathway in a rat model. A rat model of MOF was successfully established by endotoxin injection after hemorrhagic shock resuscitation. The mRNA expressions of inducible nitric oxide synthase (iNOS) and p38 MAPK of liver, kidney, and lung tissues in each group were measured by RT-qPCR at each measuring time point. To evaluate the activation of p38 MAPK signaling pathway, protein levels of phosphorylated p38 (p-p38) MAPK and p38 MAPK was measured by western blot analysis. The serum levels of nitric oxide and TNF-α were determined. After CBP treatment, the levels of SGPT, SGOT, Cr, and BUN were significantly declined, while the PaO2 value was increased. Expressions of p38 MAPK mRNA, iNOS mRNA, p-p38 MAPK protein and p38 MAPK protein, and nitric oxide and TNF-α levels were markedly elevated in MOF, an effect blunted by CPB. Meanwhile, pathological sections of liver, kidney, and lung tissues after CPB treatment ameliorated swelling and inflammation. Our study proved that CBP could downregulate the p38 MAPK signaling pathway, suppress iNOS expression, reduced the serum levels of nitric oxide and TNF-α, thus ameliorate symptom of MOF.


Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen.
Human polymorphonuclear leukocytes (PMN) have previously been shown to bind to aggregates of fibrin and to fibrinogen-coated surfaces. During their interactions with fibrinogen-coated surfaces, PMN make such close contact with the surface that a portion of the secreted elastase activity is protected from macromolecular protease inhibitors in the surrounding medium. Here we show that the receptor on PMN that mediates this interaction is complement receptor type 3 (CR3; CD11b/CD18), a molecule previously identified as a receptor for the complement protein fragment C3bi. Monoclonal antibodies against CR3 that block the binding of C3bi also block the binding of PMN to fibrinogen-coated surfaces and the formation of a protected compartment. The region of fibrinogen recognized by CR3 lies at the carboxyl terminus of the gamma chain, since peptides based on this sequence effectively inhibit the binding of PMN to fibrinogen-coated surfaces. These peptides also block the binding of C3bi-coated erythrocytes to CR3, thus indicating that a single binding site is used for binding both C3bi and fibrinogen. Sequence analysis shows strong structural similarity between this region of fibrinogen and other known ligands of CR3. These studies thus indicate that CR3 functions as a receptor not only for C3bi but also for fibrinogen.


ON BIOLOGICAL OXIDATIONS AS FUNCTION OF TEMPERATURE.
1. The critical thermal increments are calculated for respiratory processes (O(2) consumption, CO(2) production) in various plants and animals. They are characteristically found to be of two, possibly three, types: micro = 11,500, and 16,100 or 16,700. The first is commonly encountered above 15 degrees , the second below that temperature, but these relations may be reversed. (The value of micro may be significantly changed in inanition.) 2. For reduction of methylene blue by bacteria, through removal of H from succinic acid, micro = 16,700. This process (Quastel and Whetham, 1924) at constant temperature is a function of the hydroxyl ion concentration. The suggestive identity is pointed out of the critical increment for this reduction phenomenon with that deduced for biological respirations in which a dehydrogenation mechanism is supposed to be of widespread occurrence, and in connection with which Fe very likely has a catalytic rôle. The action of OH' is believed to be revealed in the value micro = 11,500, frequently obtained in connection with respiration. 3. A somewhat lower micro (16,140) is associated with the oxidation of Fe'', and may be compared with (1) that of respiration in sea urchin eggs, for which (Warburg) iron is catalyst, and (2) that for some simple reactions in which Fe is known to serve as catalyst; it is not found for oxidative reactions in which Fe is not involved. 4. The bearing of these findings is discussed in relation to the theory of functional analysis of concurrent catalyzed reactions in protoplasm. It is shown that for a number of activities in which the effects of respiration may safely be assumed, the values of the critical increments are consistent with those determined for processes of respiration. 5. The further development of these views may lead to an extremely important method of identifying controlling reactions in undisturbed living matter.


Sec3 exocyst component knockdown inhibits axonal formation and cortical neuronal migration during brain cortex development.
Neurons are the largest known cells, with complex and highly polarized morphologies and consist of a cell body (soma), several dendrites, and a single axon. The establishment of polarity necessitates initial axonal outgrowth in concomitance with the addition of new membrane to the axon's plasmalemma. Axolemmal expansion occurs by exocytosis of plasmalemmal precursor vesicles primarily at the neuronal growth cone membrane. The multiprotein exocyst complex drives spatial location and specificity of vesicle fusion at plasma membrane. However, the specific participation of its different proteins on neuronal differentiation has not been fully established. In the present work we analyzed the role of Sec3, a prominent exocyst complex protein on neuronal differentiation. Using mice hippocampal primary cultures, we determined that Sec3 is expressed in neurons at early stages prior to neuronal polarization. Furthermore, we determined that silencing of Sec3 in mice hippocampal neurons in culture precluded polarization. Moreover, using in utero electroporation experiments, we determined that Sec3 knockdown affected cortical neurons migration and morphology during neocortex formation. Our results demonstrate that the exocyst complex protein Sec3 plays an important role in axon formation in neuronal differentiation and the migration of neuronal progenitors during cortex development.


Studying synthetic lethal interactions in the zebrafish system: insight into disease genes and mechanisms.
The post-genomic era is marked by a pressing need to functionally characterize genes through understanding gene-gene interactions, as well as interactions between biological pathways. Exploiting a phenomenon known as synthetic lethality, in which simultaneous loss of two interacting genes leads to loss of viability, aids in the investigation of these interactions. Although synthetic lethal screening is a powerful technique that has been used with great success in many model organisms, including Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans, this approach has not yet been applied in the zebrafish, Danio rerio. Recently, the zebrafish has emerged as a valuable system to model many human disease conditions; thus, the ability to conduct synthetic lethal screening using zebrafish should help to uncover many unknown disease-gene interactions. In this article, we discuss the concept of synthetic lethality and provide examples of its use in other model systems. We further discuss experimental approaches by which the concept of synthetic lethality can be applied to the zebrafish to understand the functions of specific genes.


Pachymetry-guided intrastromal air injection ("pachy-bubble") for deep anterior lamellar keratoplasty.
To evaluate an innovative technique for intrastromal air injection to achieve deep anterior lamellar keratoplasty (DALK) with bare Descemet membrane (DM). Thirty-four eyes with anterior corneal pathology, including 27 with keratoconus, underwent DALK. After 400 μm trephination with a suction trephine, ultrasound pachymetry was performed 0.8 mm internally from the trephination groove in the 11 to 1 o'clock position. In this area, a 2-mm incision was created, parallel to the groove, with a micrometer diamond knife calibrated to 90% depth of the thinnest measurement. A cannula was inserted through the incision and 0.5 mL of air was injected to dissect the DM from the stroma. After peripheral paracentesis, anterior keratectomy was carried out to bare the DM. A 0.25-mm oversized graft was sutured in place. Overall, 94.1% of eyes achieved DALK. Bare DM was achieved in 30 eyes, and a pre-DM dissection was performed in 2 eyes. Air injection was successful in detaching the DM (achieving the big bubble) in 88.2% of the eyes. In keratoconus eyes, the rate was 88.9%. All cases but one required a single air injection to achieve DM detachment. Microperforations occurred in 5 cases: 3 during manual layer-by-layer dissection after air injection failed to detach the DM, 1 during removal of the residual stroma after big-bubble formation, and 1 during the diamond knife incision. Two cases (5.9%) were converted to penetrating keratoplasty because of macroperforations. The technique was reproducible, safe, and highly effective in promoting DALK with bare DM.


Epidemiology of prostate cancer in Asian countries.
The incidence of prostate cancer has been increasing worldwide in recent years. The GLOBOCAN project showed that prostate cancer was the second most frequently diagnosed cancer and the fifth leading cause of cancer mortality among men worldwide in 2012. This trend has been growing even in Asian countries, where the incidence had previously been low. However, the accuracy of data about incidence and mortality as a result of prostate cancer in some Asian countries is limited. The cause of this increasing trend is multifactorial. One possible explanation is changes in lifestyles due to more Westernized diets. The incidence is also statistically biased by the wide implementation of early detection systems and the accuracy of national cancer registration systems, which are still immature in most Asian countries. Mortality rate decreases in Australia, New Zealand and Japan since the 1990s are possibly due to the improvements in treatment and/or early detection efforts employed. However, this rate is increasing in the majority of other Asian countries. Studies of latent and incidental prostate cancer provide less biased information. The prevalence of latent and incidental prostate cancer in contemporary Japan and Korea is similar to those in Western countries, suggesting the influence of lifestyle changes on carcinogenesis. Many studies reported evidence of both congenital and acquired risk factors for carcinogenesis of prostate cancer. Recent changes in the acquired risk factors might be associated with the increasing occurrence of prostate cancer in Asian countries. This trend could continue, especially in developing Asian countries.


Viscoelastic properties of white and gray matter-derived microglia differentiate upon treatment with lipopolysaccharide but not upon treatment with myelin.
The biomechanical properties of the brain have increasingly been shown to relate to brain pathology in neurological diseases, including multiple sclerosis (MS). Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions. We hypothesize that the biomechanical, in addition to biochemical, properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions. Primary glial cultures from WM or GM of rat adult brains were treated with either lipopolysaccharide (LPS), myelin, or myelin+LPS for 24 h or left untreated as a control. After treatment, microglial cells were indented using dynamic indentation to determine the storage and loss moduli reflecting cell elasticity and cell viscosity, respectively, and subsequently fixed for immunocytochemical analysis. In parallel, gene expression of inflammatory-related genes were measured using semi-quantitative RT-PCR. Finally, phagocytosis of myelin was determined as well as F-actin visualized to study the cytoskeletal changes. WM-derived microglia were significantly more elastic and more viscous than microglia derived from GM. This heterogeneity in microglia biomechanical properties was also apparent when treated with LPS when WM-derived microglia decreased cell elasticity and viscosity, and GM-derived microglia increased elasticity and viscosity. The increase in elasticity and viscosity observed in GM-derived microglia was accompanied by an increase in Tnfα mRNA and reorganization of F-actin which was absent in WM-derived microglia. In contrast, when treated with myelin, both WM- and GM-derived microglia phagocytose myelin decrease their elasticity and viscosity. In demyelinating conditions, when myelin debris is phagocytized, as in MS lesions, it is likely that the observed differences in WM- versus GM-derived microglia biomechanics are mainly due to a difference in response to inflammation, rather than to the event of demyelination itself. Thus, the differential biomechanical properties of WM and GM microglia may add to their differential biochemical properties which depend on inflammation present in WM and GM lesions of MS patients.