Haematological effects among silk screening workers exposed to 2-ethoxy ethyl acetate.
2-Ethoxy ethyl acetate (2-EEA) is a solvent with broad industrial and commercial applications. It has been reported to cause hematological toxicity, infertility, and teratogenesis. To investigate the haematological effects in 2-EEA exposed workers. Workers from one silk screening shop (n = 29), using 2-EEA as the major cleaning and printing solvent, were recruited as a high exposure group. Workers with indirect and non-exposure to 2-EEA (n = 56) were recruited as the comparison group. Venous blood was collected for blood routine examination. Air concentration of 2-EEA in this plant was measured by eight hour personal sampling. The geometric mean (GM) of air concentration of 2-EEA in the high exposure group was 7.41 ppm (range 1.35-16.5 pppm). The mean exposure of female workers (GM = 9.34 ppm) was significantly higher than that of male workers (GM = 4.87 ppm). The GM of air 2-EEA concentration in the comparison group was 0.07 ppm (range: non-detectable to 3.62 ppm, n = 26). The haemoglobin and haematocrit in the female high 2-EEA exposure workers were significantly lower than those of female workers in the comparison group. No difference was found between male 2-EEA high exposure and comparison group workers. The haemoglobin, haematocrit, and RBC count in the study population had a significant dose-response relation with air 2-EEA levels. Results suggest that 2-EEA is a haematological toxicant, which leads to anaemic status in high exposure female workers.


Location dependent coordination chemistry and MRI relaxivity, in de novo designed lanthanide coiled coils.
Herein, we establish for the first time the design principles for lanthanide coordination within coiled coils, and the important consequences of binding site translation. By interrogating design requirements and by systematically translating binding site residues, one can influence coiled coil stability and more importantly, the lanthanide coordination chemistry. A 10 Å binding site translation along a coiled coil, transforms a coordinatively saturated Tb(Asp)3(Asn)3 site into one in which three exogenous water molecules are coordinated, and in which the Asn layer is no longer essential for binding, Tb(Asp)3(H2O)3. This has a profound impact on the relaxivity of the analogous Gd(iii) coiled coil, with more than a four-fold increase in the transverse relaxivity (21 to 89 mM-1 s-1), by bringing into play, in addition to the outer sphere mechanism present for all Gd(iii) coiled coils, an inner sphere mechanism. Not only do these findings warrant further investigation for possible exploitation as MRI contrast agents, but understanding the impact of binding site translation on coordination chemistry has important repercussions for metal binding site design, taking us an important step closer to the predictable and truly de novo design of metal binding sites, for new functional applications.


Cognitive screening for elderly people in long-term care institutions in the Miranda do Corvo municipality, Portugal.
This study aimed to screen the cognitive profile elderly people living in long-term care institutions in the municipality of Miranda do Corvo by evaluating 174 participants with the Mini Mental State Examination (MMSE) (n=96) and the clinical dementia diagnosis (n=78). According to the MMSE, 41.7% of respondents had scores suggestive of cognitive impairment. The percentage rose to 67.8% (n=118) by adding the diagnosis of dementia reported in individual medical records to this result. The comparison of our results with those obtained nationwide showed that this proportion was significantly higher (p<0.001). The educational level was a predictive factor for MMSE scores (p=0.001). We can conclude that the high prevalence of suspected cognitive impairment and dementia revealed in our study should lead us to reflect on the quality of care provided and on the lack/scarcity of cognitive stimulation programs in long-term care institutions for seniors. Thus, it is imperative to implement regular cognitive assessment and to apply intervention programs for the preservation and improvement of the cognitive functioning of institutionalized elderly of deprived areas.


Beta thalassemia IVS-I-5(G-->C) heterozygosity masked by the presence of HbJ-Meerut in a Dutch-Indian patient.
We describe the genotype/phenotype correlation in a 35 year old anemic female referred to our laboratory because a fast eluting minor fraction on HPLC, mild hemolysis and hematological parameters suggesting a Thalassemia trait, eventually in combination with iron depletion. Direct sequencing of the alpha globin genes revealed heterozygosity for HbJ-Meerut, a Glu-->Ala substitution at residue 120 not justifying the hematological parameters. No other point mutations were found on the alpha genes and Gap-PCR excluded the 6 common deletion defects. Direct sequencing of the beta-globin genes revealed the IVS-I-5 (G-->C) transversion in absence of the elevated HbA2 levels usually measured in carriers of this beta-Thalassemia mutation. The HbA2 tetramer in the presence of HbJ-Meerut divides in two parts. One alphaN2/delta2 migrating on the right spot on HPLC. The other alphaJ2/delta2 migrating under the HbA fraction. Classic alkaline electrophoresis and the modern capillary electrophoresis CE showed these two tetramers and the reduction of the elevated HbA2 level of the beta-Thalassemia trait by at least 20% due to HbA2 Meerut.


Association of depression with disease severity in patients with chronic obstructive pulmonary disease.
Patients with chronic obstructive pulmonary disease (COPD), which is predicted to be the third most common cause of death worldwide by 2020, often suffer from depression, one of the most common and modifiable comorbidities of COPD. This study assessed the prevalence of depression in patients with COPD and the association of depression with disease severity. This was a multicenter, prospective cross-sectional study of 245 patients with stable COPD. Disease severity was assessed using two scales: the global initiative for chronic obstructive lung disease (GOLD) stage and BODE index. Depression was measured using the Centers for Epidemiologic Studies Depression (CES-D) scales. Data were analyzed using descriptive statistics, Spearman correlation, and multivariate logistic regression. Depression defined as a CES-D score of 24 and higher was observed in 17.6 % of patients with COPD. The prevalence of depression increased with disease severity based on the BODE quartile (r = 0.16; P = 0.014). By contrast, no difference was observed in the prevalence of depression among the severity groups using the GOLD staging system (r = - 0.01; P = 0.898). Elementary school graduates were more likely to experience depression than graduates of high school and above [odds ratio (OR) = 3.67; 95 % confidence interval (CI) 1.37-9.85] and patients in BODE quartile II were more likely to experience depression than those with BODE quartile I (OR = 2.5; 95 % CI 1.04-6.06). Depression was associated with disease severity according to the BODE quartile in patients with COPD. BODE quartile II was a significant predictor of depression. Screening patients with a high risk of depression and proactive intervention for those patients are needed.


Prostate-specific antigen, digital rectal examination and transrectal ultrasonography: a meta-analysis for this diagnostic triad of prostate cancer in symptomatic korean men.
We conducted a meta-analysis using results from the Korean literature to determine whether prostate-specific antigen (PSA) or digital rectal examination (DRE) or transrectal ultrasonography (TRUS) provides a better diagnostic outcome for possible prostate cancer patients. An extensive literature search of MedRIC database et al. (1980 to 2003) was performed using the medical subject headings "PSA", "DRE", "TRUS" and "prostate cancer". Of the 108 articles that we retrieved, 13 studies (2,029 subjects) were selected for this meta-analysis. The criteria for quality evaluation were as follows: the study subjects must have been compared clinically for suspected prostate cancer, and the articles must have included individual data about sensitivity and specificity for this diagnostic triad based on the biopsy results as a reference standard. For the quantitative meta-analysis process the Hasselblad method was utilized. The pooled sensitivity and specificity for a PSA level greater than 4ng/mL were 91.3 % and 35.9 %, respectively; and those for a PSA level greater than 10ng/mL were 77.3 % and 67.5 %, respectively; and those for DRE were 68.4 % and 71.5 %, respectively; and those for TRUS were 73.6 % and 61.3 %, respectively. According to the results in a fixed effect model for PSA criteria, the estimates of d for PSA4 and PSA10 were 0.8517 [95 % confidence interval (CI): 0.6694, 1.0340] and 1.0996 (95 % CI: 0.9459, 1.2534), respectively. Also, according to the results using a random effect model for both DRE and TRUS criteria, the estimates of d for DRE and TRUS were 0.8398 (95 % CI: 0.7169, 0.9627) and 0.8002 (95 % CI: 0.6714, 0.9289), respectively. The detection rate for combination testing of PSA, DRE and TRUS for the diagnosis of prostate cancer jumped further to 68.3 % or to 76.8 %. In conclusion, this study suggests that this diagnostic triad for prostate cancer was noneffective when they were used separately. Therefore, we recommend that the urologists should use PSA together with DRE and TRUS for the primary diagnosis of prostate cancer in men with lower urological symptoms.


Vacuum-assisted closure: a new method for wound control and treatment: clinical experience.
Despite numerous advances, chronic and other difficult-to-manage wounds continue to be a treatment challenge. Presented is a new subatmospheric pressure technique: vacuum-assisted closure (The V.A.C.). The V.A.C. technique entails placing an open-cell foam dressing into the wound cavity and applying a controlled subatmospheric pressure (125 mmHg below ambient pressure). Three hundred wounds were treated: 175 chronic wounds, 94 subacute wounds, and 31 acute wounds. Two hundred ninety-six wounds responded favorably to subatmospheric pressure treatment, with an increased rate of granulation tissue formation. Wounds were treated until completely closed, were covered with a split-thickness skin graft, or a flap was rotated into the health, granulating would bed. The technique removes chronic edema, leading to increased localized blood flow, and the applied forces result in the enhanced formation of granulation tissue. Vacuum-assisted closure is an extremely efficacious modality for treating chronic and difficult wounds.


Wet Cough and Nasal Symptoms in Children: Can We Do Better?
The causes of chronic cough in children are mainly dependent on the setting and age of the child. Protracted bacterial bronchitis is a frequent cause of morbidity in childhood, and antibiotic treatment is beneficial. Prompt recognition and early treatment is important both to prevent inappropriate use of asthma medications and also progression to bronchiectasis, but the diagnosis should not be made uncritically, because chronic wet cough is not necessarily due to lower airway disease. Upper Airway Cough Syndrome (UACS) is considered by some to cause chronic cough in childhood. Underlying UACS are many common conditions, including allergic rhinitis, adenoiditis and rhinosinusitis. Diagnosis relies on a combination of clinical criteria that are relatively sensitive but non-specific. The role of nasal endoscopy in children with chronic cough and signs suggesting UACS is unclear. Nasal saline solution irrigation is commonly used in UACS, but most studies have methodological biases, and efficacy data are scanty. Randomized controlled trials are urgently required. However, if saline washes, rather than oral antibiotics, can effectively treat some children with wet cough associated with upper airway conditions, antibiotic resistance could potentially be reduced. There is a need to further study wet cough and not to assume it to be equivalent to lower airway infection in all children.


Electrically vs. imaging-guided left ventricular lead placement in cardiac resynchronization therapy: a randomized controlled trial.
To test in a double-blinded, randomized trial whether the combination of electrically guided left ventricular (LV) lead placement and post-implant interventricular pacing delay (VVd) optimization results in superior increase in LV ejection fraction (LVEF) in cardiac resynchronization therapy (CRT) recipients. Stratified according to presence of ischaemic heart disease, 122 patients were randomized 1:1 to LV lead placement targeted towards the latest electrically activated segment identified by systematic mapping of the coronary sinus tributaries during CRT implantation combined with post-implant VVd optimization (intervention group) or imaging-guided LV lead implantation by cardiac computed tomography venography, 82Rubidium myocardial perfusion imaging and speckle tracking echocardiography targeting the LV lead towards the latest mechanically activated non-scarred myocardial segment (control group). Follow-up was 6 months. Primary endpoint was absolute increase in LVEF. Additional outcome measures were changes in New York Heart Association class, 6-minute walk test, and quality of life, LV reverse remodelling, and device related complications. Analysis was intention-to-treat. A larger increase in LVEF was observed in the intervention group (11 ± 10 vs. 7 ± 11%; 95% confidence interval 0.4-7.9%, P = 0.03); when adjusting for pre-specified baseline covariates this difference did not maintain statistical significance (P = 0.09). Clinical response, LV reverse remodelling, and complication rates did not differ between treatment groups. Electrically guided CRT implantation appeared non-inferior to an imaging-guided strategy considering the outcomes of change in LVEF, LV reverse remodelling and clinical response. Larger long-term studies are warranted to investigate the effect of an electrically guided CRT strategy.


Variation in the visual habitat may mediate the maintenance of color polymorphism in a poeciliid fish.
The conspicuousness of animal signals is influenced by their contrast against the background. As such, signal conspicuousness will tend to vary in nature because habitats are composed of a mosaic of backgrounds. Variation in attractiveness could result in variation in conspecific mate choice and risk of predation, which, in turn, may create opportunities for balancing selection to maintain distinct polymorphisms. We quantified male coloration, the absorbance spectrum of visual pigments and the photic environment of Poecilia parae, a fish species with five distinct male color morphs: a drab (i.e., grey), a striped, and three colorful (i.e., blue, red and yellow) morphs. Then, using physiological models, we assessed how male color patterns can be perceived in their natural visual habitats by conspecific females and a common cichlid predator, Aequidens tetramerus. Our estimates of chromatic and luminance contrasts suggest that the three most colorful morphs were consistently the most conspicuous across all habitats. However, variation in the visual background resulted in variation in which morph was the most conspicuous to females at each locality. Likewise, the most colorful morphs were the most conspicuous morphs to cichlid predators. If females are able to discriminate between conspicuous prospective mates and those preferred males are also more vulnerable to predation, variable visual habitats could influence the direction and strength of natural and sexual selection, thereby allowing for the persistence of color polymorphisms in natural environments.


GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer's disease: association hypothesis for an uncommon genetic variant.
Glutathione S-transferases are multifunctional enzymes involved in cellular detoxification. A genetic linkage was found between Alzheimer's Disease (AD) and the chromosome 10q, where the GSTO1 and GSTO2 genes are located, leading to the hypothesis that GST Omega class (GSTO) genes may be an AD risk factor. Since it is still controversial, we decided to explore GSTO polymorphisms in Italian cohorts. We analyzed 119 AD patients and 114 healthy controls for the GSTO gene polymorphisms. In particular we investigated two common polymorphisms (GSTO1*A140D, GSTO2*N142D) and two uncommon variants (GSTO1*E155del, GSTO1*E208K) to find loci associated with AD risk. Detection of GSTO1*A140D and GSTO2*N142D was performed by PCR-RFLP, while GSTO1*E155del and GSTO1*E208K were detected using confronting two-pair primer and allele specific PCR, respectively. While GSTO1*A140D, GSTO1*E208K and GSTO2*N142D polymorphisms did not show significant outcomes, the GSTO1*E155del polymorphism is associated with AD [P=0.003; adjusted OR=3.70 (1.57-8.75)]. Our results suggest that GSTO1-1 plays a role in AD since the GSTO1*del155 variant is involved in changes in GSTO1-1 activities decreasing in enzyme stability. Specifically, three hypotheses may explain the role of GSTO1-1 in the pathophysiology of AD: the antioxidant activity of GSTO1-1 may protect brain tissue against oxidative stress; GSTO1-1 activity regulate interleukin-1β activation and its genetic variation may act to modulate inflammation in AD; GSTO1-1 is involved in the arsenic biotransformation pathway and gene polymorphisms may be implicated in the modulation of arsenic neurotoxicity. In conclusion, we hypothesized that GSTO1*E155del is an uncommon genetic variant associated with AD risk.


Screening wish theories: dream psychologies and early cinema.
The analogy between dream and film represents a central thread in the psychoanalytic discussion of cinema. Using examples taken from films created between 1900 and 1906, this paper develops a typology of dream scenes in early film. The basis for the proposed typology is provided by the dream knowledge in circulation toward the end of the nineteenth century. This knowledge was fed by a great variety of sources, some of them in the proximity of scientific research and some of them far from it, including wish-fulfilling prognostic models and those based on the reservoir of memory or on bodily stimuli. By setting cinema in a context of contemporary dream psychologies, it is possible to trace the specific conditions under which the analogy between dream and cinema could become effective.


Pathogenesis of mucosal disease: a cytopathogenic pestivirus generated by an internal deletion.
Cytopathogenic bovine viral diarrhea virus (BVDV) arises by RNA recombination in animals persistently infected with noncytopathogenic BVDV. Such animals develop fatal mucosal disease. In this report, the genome of a cytopathogenic BVDV isolate, termed CP9, is characterized. CP9-infected cells contained not only viral genomic RNA of 12.3 kb but also a BVDV-specific RNA of 8 kb. cDNA cloning and sequencing revealed that the 8-kb RNA is a BVDV genome with an internal deletion of 4.3 kb. The 8-kb RNA represents the genome of a typical defective interfering particle (DI), since its replication was strictly dependent on the presence of a helper virus and strongly interfered with the replication of the helper. Cell culture experiments demonstrated that the CP9 virus stock contains two viruses, namely, a helper virus and DI9. While the helper virus alone was noncytopathogenic, the presence of the DI conferred cytopathogenicity. Expression experiments demonstrated that p80, the marker protein of cytopathogenic BVDV, is translated from the defective genome. The occurrence of this cytopathogenic DI is linked to a fatal disease in cattle.


Effects of clonidine and sumatriptan on postprandial gastric volume response, antral contraction waves and emptying: an MRI study.
Gastric emptying (GE) may be driven by tonic contraction of the stomach ('pressure pump') or antral contraction waves (ACW) ('peristaltic pump'). The mechanism underlying GE was studied by contrasting the effects of clonidine (alpha(2)-adrenergic agonist) and sumatriptan (5-HT(1) agonist) on gastric function. Magnetic resonance imaging provided non-invasive assessment of gastric volume responses, ACW and GE in nine healthy volunteers. Investigations were performed in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) under placebo [0.9% NaCl intravenous (IV) and subcutaneous (SC)], clonidine [0.01 mg min(-1) IV, max 0.1 mg (placebo SC)] or sumatriptan [6 mg SC (placebo IV)]. Total gastric volume (TGV) and gastric content volume (GCV) were assessed every 5 min for 90 min, interspersed with dynamic scan sequences to measure ACW activity. During gastric filling, TGV increased with GCV indicating that meal volume dictates initial relaxation. Gastric contents volume continued to increase over the early postprandial period due to gastric secretion surpassing initial gastric emptying. Clonidine diminished this early increase in GCV, reduced gastric relaxation, decreased ACW frequency compared with placebo. Gastric emptying (GE) rate increased. Sumatriptan had no effect on initial GCV, but prolonged gastric relaxation and disrupted ACW activity. Gastric emptying was delayed. There was a negative correlation between gastric relaxation and GE rate (r(2 )=49%, P < 0.001), whereas the association between ACW frequency and GE rate was inconsistent and weak (r2=15%, P = 0.05). These findings support the hypothesis that nutrient liquid emptying is primarily driven by the 'pressure pump' mechanism.


The quantitative assessment of risk factors to overstress at adjacent segments after lumbar fusion: removal of posterior ligaments and pedicle screws.
Finite element method. To investigate the changes in the disc stress and range of motion (ROM) at adjacent segments after lumbar fusion based on whether or not pedicle screws are removed and whether or not the continuity of the proximal posterior ligament complex (PLC) is preserved. The ablation of proximal PLC continuity and the presence of pedicle screws have been reported to affect the biomechanics at adjacent segments after lumbar fusion. However, there have been few studies regarding the quantitative assessment of their contribution to overstress at adjacent segments after lumbar fusion. In the validated intact lumbar finite element model (L2-L5), four types of L3-L4 fusion models were simulated. These models included the preservation of the PLC continuity with pedicle screws (Pp WiP), the preservation of PLC continuity without pedicle screws (Pp WoP), the sacrifice of PLC with pedicle screws (Sp WiP), and the sacrifice of PLC without pedicle screws (Sp WoP). In each scenario, the ROM, maximal von Mises stress of discs, and the facet joint contract force at adjacent segments were analyzed. RESULTS.: Among the four models, the Sp WiP yielded the greatest increase in the ROM and the maximal von Mises stress of the disc at adjacent segments under four moments. Following the SP WiP, the order of increase of the ROM and the disc stress was Pp WiP, Sp WoP, and Pp WoP. Furthermore, the increase of ROM and disc stress at the proximal adjacent segment was more than at the distal adjacent segment under all four moments in each model. The facet joint contact was also most increased in the Sp WiP under extension and torsion moment. The current study suggests that the preservation of the PLC continuity or the removal of pedicle screws after complete fusion could decrease the stress at adjacent segments, and their combination could act synergistically.


KEGG2Net: Deducing gene interaction networks and acyclic graphs from KEGG pathways.
The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database provides a manual curation of biological pathways that involve genes (or gene products), metabolites, chemical compounds, maps, and other entries. However, most applications and datasets involved in omics are gene or protein-centric requiring pathway representations that include direct and indirect interactions only between genes. Furthermore, special methodologies, such as Bayesian networks require acyclic representations of graphs. We developed KEGG2Net, a web resource that generates a network involving only the genes represented on a KEGG pathway with all of the direct and indirect gene-gene interactions deduced from the pathway. KEGG2Net offers four different methods to remove cycles from the resulting gene interaction network, converting them into directed acyclic graphs (DAGs). We generated synthetic gene expression data using the gene interaction networks deduced from the KEGG pathways and performed a comparative analysis of different cycle removal methods by testing the fitness of their DAGs to the data and by the number of edges they eliminate. Our results indicate that an ensemble method for cycle removal performs as the best approach to convert the gene interaction networks into DAGs. Resulting gene interaction networks and DAGs are represented in multiple user-friendly formats that can be used in other applications, and as images for quick and easy visualisation. The KEGG2Net web portal converts KEGG maps for any organism into gene-gene interaction networks and corresponding DAGS representing all of the direct and indirect interactions among the genes.


Immunohistochemistry of deparaffinised sections using antigen retrieval with microwave combined pressure cooking versus immunofluorescence in the assessment of human renal biopsies.
Immunofluorescence of frozen tissue sections (IF-F) is a traditional technique used in renal biopsy. However, IF-F has certain disadvantages, such as a few or even no glomeruli in the section, and limited long-term preservation of the fluorescently labelled samples. We compared two-step immunohistochemistry (IHC) staining of deparaffinised sections for antigen retrieval with microwave combined high-pressure cooking to IF-F used to detect antigens of IgG, IgA, IgM, C3, C1q, κ and λ in patient renal biopsy samples. The number of glomeruli detected, sensitivity and specificity of positive staining, tissue structure, and location staining of the antigens were determined using the two methods in 285 patients diagnosed with different renal diseases. Concordant observations between IF-F and IHC were 99% for all antigen staining (1969 of 1995 observations) and 100% for IgG, IgA and IgM (all 285 observations). The number of glomeruli in IHC sections was significantly greater compared with IF-F sections (p<0.001). IHC provided clearer images of tissue structure, more precise localisation of positive-staining antigens, and IHC staining allowed simultaneous evaluation of tissue by light microscopy. Correlation between tissue structure and immune deposits are not readily attained by IF-F. IHC is superior to IF-F for immunopathological diagnosis of renal biopsy tissue and is a reliable replacement for the more traditional IF-F method.


Three-dimensional tomosynthesis and cone-beam computed tomography: an experimental study for fast, low-dose intraoperative imaging technology for guidance of sinus and skull base surgery.
To describe three-dimension (3-D) tomosynthesis and cone beam computed tomography (CBCT) as an intraoperative imaging system to guide both sinus and skull-base surgery in a cadaveric model. Five cadaveric heads underwent baseline CBCT imaging. Surgical targets were resected from each head (uncinectomy, ethmoidectomy, medial maxillectomy, pituitary gland resection, and clivus ablation). Intraoperative imaging was provided so that for a given task, the acquisition arc (theta(tot) = 20 degrees , 45 degrees , 60 degrees , 90 degrees , 178 degrees ) of the tomosynthesis scan was fixed. Different heads and tasks were allocated different acquisition angles. There was no limit to the number of scans that could be requested. Residual target was highlighted with 3-D visualization software. The larger the image acquisition angle, the better the image. Only CBCT (theta(tot) approximately 178 degrees ) provided nearly isotropic 3-D spatial resolution and soft-tissue visibility in all three views. The volume of residual tissue remaining and the volume of adjacent-normal tissue that was resected were calculated as a function of tomosynthesis angle. For the easier surgical tasks (uncinectomy, ethmoidectomy) the residual tissue was not related to the tomosynthesis angle. However, for the difficult ablative tasks, the image quality became more important and tomosynthesis angle was related to the residual tissue. We describe an intraoperative imaging platform that can deliver near-real-time images of the target and related structures with low radiation dose. Tomosynthesis scanning angles higher than 60 degrees provided quantifiable benefits to the surgeon and facilitated total target ablation while helping to spare surrounding structures.


Describing complex cells in primary visual cortex: a comparison of context and multifilter LN models.
Receptive field (RF) models are an important tool for deciphering neural responses to sensory stimuli. The two currently popular RF models are multifilter linear-nonlinear (LN) models and context models. Models are, however, never correct, and they rely on assumptions to keep them simple enough to be interpretable. As a consequence, different models describe different stimulus-response mappings, which may or may not be good approximations of real neural behavior. In the current study, we take up two tasks: 1) we introduce new ways to estimate context models with realistic nonlinearities, that is, with logistic and exponential functions, and 2) we evaluate context models and multifilter LN models in terms of how well they describe recorded data from complex cells in cat primary visual cortex. Our results, based on single-spike information and correlation coefficients, indicate that context models outperform corresponding multifilter LN models of equal complexity (measured in terms of number of parameters), with the best increase in performance being achieved by the novel context models. Consequently, our results suggest that the multifilter LN-model framework is suboptimal for describing the behavior of complex cells: the context-model framework is clearly superior while still providing interpretable quantizations of neural behavior. NEW & NOTEWORTHY We used data from complex cells in primary visual cortex to estimate a wide variety of receptive field models from two frameworks that have previously not been compared with each other. The models included traditionally used multifilter linear-nonlinear models and novel variants of context models. Using mutual information and correlation coefficients as performance measures, we showed that context models are superior for describing complex cells and that the novel context models performed the best.


Lipase activity of Basidiobolus and Conidiobolus species.
Two isolates of Basidiobolus namely, B. haptosporus (ATCC 36600) and B. ranarum (MHB1), and one isolate of Conidiobolus coronatus (C1) were grown in modified Sierra medium for twelve days. Periodic measurements of their lipase activity showed significant activity of the enzyme from the fourth day with a steady increase up to the twelfth day of incubation. The lipases produced by the three isolates were stable over a wide range of pH (4-8) and temperature (30-60 degrees C). Maximum lipase activity for B. haptosporus and C. coronatus was at pH 5.0 and that for B. ranarum was at pH 6.0. The three fungi exhibited a peak of activity at the same temperature, i.e. 35 degrees C.


EULAR points to consider for the development, evaluation and implementation of mobile health applications aiding self-management in people living with rheumatic and musculoskeletal diseases.
Mobile health applications (apps) are available to enable people with rheumatic and musculoskeletal diseases (RMDs) to better self-manage their health. However, guidance on the development and evaluation of such apps is lacking. The objective of this EULAR task force was to establish points to consider (PtC) for the development, evaluation and implementation of apps for self-management of RMDs. A systematic literature review of app content and development strategies was conducted, followed by patient focus group and an online survey. Based on this information and along with task force expert opinion, PtC were formulated in a face-to-face meeting by a multidisciplinary task force panel of experts, including two patient research partners. The level of agreement among the panel in regard to each PtC was established by anonymous online voting. Three overarching principles and 10 PtC were formulated. Three PtC are related to patient safety, considered as a critical issue by the panel. Three are related to relevance of the content and functionalities. The requirement for transparency around app development and funding sources, along with involvement of relevant health professionals, were also raised. Ease of app access across ages and abilities was highlighted, in addition to considering the cost benefit of apps from the outset. The level of agreement was from 8.8 to 9.9 out of 10. These EULAR PtC provide guidance on important aspects that should be considered for the development, evaluation and implementation of existing and new apps.


Modelling crystal aggregation and deposition in the catheterised lower urinary tract.
Urethral catheters often become encrusted with crystals of magnesium struvite and calcium phosphate. The encrustation can block the catheter, which can cause urine retention in the bladder and reflux into the kidneys. We develop a mathematical model to investigate crystal deposition on the catheter surface, modelling the bladder as a reservoir of fluid and the urethral catheter as a rigid channel. At a constant rate, fluid containing crystal particles of unit size enters the reservoir, and flows from the reservoir through the channel and out of the system. The crystal particles aggregate, which we model using Becker-Döring coagulation theory, and are advected through the channel, where they continue to aggregate and are deposited on the channel's walls. Inhibitor particles also enter the reservoir, and can bind to the crystals, preventing further aggregation and deposition. The crystal concentrations are spatially homogeneous in the reservoir, whereas the channel concentrations vary spatially as a result of advection, diffusion and deposition. We investigate the effect of inhibitor particles on the amount of deposition. For all parameter values, we find that crystals deposit along the full length of the channel, with maximum deposition close to the channel's entrance.


Serum prostate-specific antigen as a predictor of radiographic staging studies in newly diagnosed prostate cancer.
The standard staging evaluation of prostate cancer includes digital rectal examination, measurement of serum tumor markers, radionuclide bone scan, and abdominal pelvic computed tomography (CT) or nuclear magnetic resonance imaging (MRI). We retrospectively reviewed 300 cases of newly diagnosed, untreated adenocarcinoma of the prostate to evaluate the ability of serum prostate-specific antigen (PSA) to predict results of staging radiographic studies (bone scan, CT/MRI). The medical records of 300 newly diagnosed, untreated prostate cancer patients were reviewed. The following information was collected on a standard data form: age, clinical stage based on digital rectal examination, method of diagnosis, histological grade, serum PSA level, results of radionuclide bone scan and additional radiographic studies to confirm bone scan results, results of abdominal pelvic CT/MRI, and presence or absence of bone pain. The results of this review were tabulated and analyzed with regard to the ability of serum PSA level to predict positive results of radiographic staging studies. The mean PSA level of the study group was 24.6 ng/ml. Ten patients (3.6%) presented with positive bone scan results with 5 of these having serum PSA levels greater than 20 ng/ml (range 27.6 ng/ml-144 ng/ml, mean 66.3 ng/ml). The 5 remaining patients all had elevated PSA levels ranging between 4.1 and 20.0 ng/ml. No patient with a positive staging bone scan presented with a normal serum PSA. Ten patients (4.0%) presented with a positive abdominal/pelvic CT/MRI (adenopathy only; no patients had radiographic evidence of abnormalities of the upper urinary tract). Eight had serum PSA levels greater than 20 ng/ml, ranging from 30.0 to 234 ng/ml. No patient with a positive study presented with a normal serum PSA level. No patient with either positive bone scan or abdominal pelvic CT/MRI presented with bone pain. We conclude that in asymptomatic patients with newly diagnosed, untreated prostate cancer and serum PSA levels of less than 10 ng/ml, a staging radionuclide bone scan may not be necessary. Likewise, in patients with serum PSA levels of less than 20 ng/ml the likelihood of positive findings on abdominal/pelvic CT/MRI is extremely low. Abdominal/pelvic CT/MRI does not appear necessary in this setting. With over 130,000 cases of newly diagnosed prostate cancer each year in the United States, elimination of staging radiographic studies in the patients outlined above could result in economic savings on the order of 30-80 million dollars per year.


A Multiwell Microfluidic Device for Analyzing and Screening Nonhormonal Contraceptive Agents.
Birth control and family planning play pivotal roles in the economic growth and reduction of maternal, infant, and child mortality. Current contraceptives, such as hormonal agents and intrauterine devices, target only a small subset of reproductive processes and can have serious side effects on the health of women. To develop novel contraceptive agents, a scalable microfluidic device is established for analyzing and screening the effects of potential contraceptive agents on the maturation of the cumulus-oocyte complex. The microfluidic device performs on-chip incubation for studying oocyte maturation and cumulus expansion and isolates the microwells by oil-water interfaces to avoid crosstalk between the wells. A filter membrane is incorporated in the device to simplify incubation, medium exchange, washing, and fluorescence staining of oocytes. Cumulus expansion can be monitored directly in the device and oocyte maturation can be examined after enzymatic removal of cumulus cells and on-chip fluorescence staining. The performance of the device is evaluated by studying the influence of three drugs known to block oocyte maturation and/or cumulus expansion.


SoccerStories: a kick-off for visual soccer analysis.
This article presents SoccerStories, a visualization interface to support analysts in exploring soccer data and communicating interesting insights. Currently, most analyses on such data relate to statistics on individual players or teams. However, soccer analysts we collaborated with consider that quantitative analysis alone does not convey the right picture of the game, as context, player positions and phases of player actions are the most relevant aspects. We designed SoccerStories to support the current practice of soccer analysts and to enrich it, both in the analysis and communication stages. Our system provides an overview+detail interface of game phases, and their aggregation into a series of connected visualizations, each visualization being tailored for actions such as a series of passes or a goal attempt. To evaluate our tool, we ran two qualitative user studies on recent games using SoccerStories with data from one of the world's leading live sports data providers. The first study resulted in a series of four articles on soccer tactics, by a tactics analyst, who said he would not have been able to write these otherwise. The second study consisted in an exploratory follow-up to investigate design alternatives for embedding soccer phases into word-sized graphics. For both experiments, we received a very enthusiastic feedback and participants consider further use of SoccerStories to enhance their current workflow.


New Insights from Studies of Clonal Hematopoiesis.
Clonal hematopoiesis (CH) describes an asymptomatic expansion of blood cells descended from a single hematopoietic stem cell. Recent studies have shown that CH increases in frequency with aging and is often driven by somatic mutations in genes that are recurrently mutated in hematologic malignancies. When CH is associated with a mutation in a leukemia-associated gene at a variant allele frequency of 0.02 or greater, it is termed "clonal hematopoiesis of indeterminate potential" (CHIP). CHIP has a 0.5% to 1% risk per year of progression to hematologic neoplasia, and increases both all-cause mortality and the risk of myocardial infarction and ischemic stroke due to a proinflammatory interaction between clonally derived leukocytes and vascular endothelium. CH frequently emerges in the context of immune-mediated marrow failure syndromes such as aplastic anemia, whereas CH emerging after cytotoxic cancer therapy is strongly associated with subsequent development of a therapy-related myeloid neoplasm, especially if a TP53 mutation is present. However, risk factors for developing CH other than aging, marrow failure, and cytotoxic radiotherapy or chemotherapy are poorly defined. In this review, we discuss the epidemiology, molecular mechanisms, and clinical consequences of this common and clinically important biological state. Clin Cancer Res; 24(19); 4633-42. ©2018 AACR.


Promoting residents' professional development and academic productivity using a structured faculty mentoring program.
The importance of effective mentoring in career success is universally accepted but has not been well studied in academic medicine. The purpose was to describe a formal mentoring program of residents by faculty in obstetrics and gynecology and assess professional and educational outcomes. In 2006, a formal mentoring program was developed. Faculty and residents were provided instruction. Residents selected their mentors and met regularly. Resident-mentor contracts were signed. Mentors developed corrective plans and monitored residents with problems. Outcomes were measured prospectively. Twenty-five residents and 18 faculty participated. After 2 years, 7 residents (28%) had scientific publications as compared to 10% in the year preceding the mentoring program. Eleven (44%) presented oral or poster presentations, and 17 (68%) were conducting scientific research. Mentors' effectiveness was rated between 4.3 and 4.7 (Likert scale of 1-5). Three of 4 residents in remediation fulfilled their educational requirements. Four residents noted insufficient meeting time. A simple but well-organized mentoring system can be an effective means of improving resident learning and enhancing their academic portfolio. Mentoring should be strongly encouraged for residents, especially those with specific deficiencies.


Sampled Bragg gratings in chalcogenide (As(2)S(3)) rib-waveguides.
We have written a sampled Bragg grating into a highly photosensitive chalcogenide (As(2)S(3)) rib-waveguide using a scanning Sagnac interferometer. The grating exhibits evenly spaced rejection peaks over a 40 nm bandwidth. We estimate the induced refractive index change of the waveguide to be over 0.03 by matching the measured spectrum to numerical solutions of the coupled mode equations while accounting for an induced chirp. The sampled Bragg grating presented is comparable in strength and bandwidth to the best sampled Bragg gratings obtained to date in silica optical fibre.


Asymmetric split ring resonators for optical sensing of organic materials.
Asymmetric Split Ring Resonators are known to exhibit resonant modes where the optical electric field is strongest near the ends of the arms, thereby increasing the sensitivity of spectral techniques such as surface enhanced Raman scattering (SERS). By producing asymmetry in the structures, the two arms of the ring produce distinct plasmonic resonances related to their lengths - but are also affected by the presence of the other arm. This combination leads to a steepening of the slope of the reflection spectrum between the resonances that increases the sensitivity of the resonant behavior to the addition of different molecular species. We describe experimental results, supported by simulation, on the resonances of a series of circular split ring resonators with different gap and section lengths--at wavelengths in the mid-infra red regions of the spectrum--and their utilization for highly sensitive detection of organic compounds. We have used thin films of PMMA with different thicknesses, resulting in characteristic shifts from the original resonance. We also demonstrate matching of asymmetric split ring resonators to a molecular resonance of PMMA.


Voluntary self-touch increases body ownership.
Experimental manipulations of body ownership have indicated that multisensory integration is central to forming bodily self-representation. Voluntary self-touch is a unique multisensory situation involving corresponding motor, tactile and proprioceptive signals. Yet, even though self-touch is frequent in everyday life, its contribution to the formation of body ownership is not well understood. Here we investigated the role of voluntary self-touch in body ownership using a novel adaptation of the rubber hand illusion (RHI), in which a robotic system and virtual reality allowed participants self-touch of real and virtual hands. In the first experiment, active and passive self-touch were applied in the absence of visual feedback. In the second experiment, we tested the role of visual feedback in this bodily illusion. Finally, in the third experiment, we compared active and passive self-touch to the classical RHI in which the touch is administered by the experimenter. We hypothesized that active self-touch would increase ownership over the virtual hand through the addition of motor signals strengthening the bodily illusion. The results indicated that active self-touch elicited stronger illusory ownership compared to passive self-touch and sensory only stimulation, and show an important role for active self-touch in the formation of bodily self.


Pathways of evolution of influenza A (H1N1) viruses from 1977 to 1986 as determined by oligonucleotide mapping and sequencing studies.
The evolutionary relationships of epidemic influenza A (H1N1) viruses isolated between 1982 and 1986 have been examined by oligonucleotide mapping and partial DNA sequencing. The T1 mapping studies confirmed our previous report that the evolution of the influenza virus genome generally results in an average of four to six oligonucleotide changes per year. Between 1982 and 1986, however, two apparent exceptions to this finding occurred. H1N1 antigenic variants (including the A/Chile/83 and A/Victoria/83 reference strains) that caused influenza outbreaks and epidemics from 1983 to 1984 differed by 20 to 30 oligonucleotides from viruses isolated during the previous influenza season. T1 mapping of individual RNA segments and sequencing revealed that all six internal genes of a representative 1983 A/Chile-like virus were more closely related to genes of non-reassortant H1N1 viruses that circulated from 1977 to 1982 than to genes of H3N2 viruses. Therefore, the 1983 variant viruses were not H1N1-H3N2 reassortants. The A/Taiwan/86-like H1N1 antigenic variants that emerged in south-east Asia in the spring of 1986 and caused epidemic activity the following winter also exhibited changes of 20 to 30 oligonucleotides from the A/Chile/83-like or A/Victoria/83-like H1N1 viruses that circulated during the previous influenza season. Fewer oligonucleotide changes were observed between the 1986 A/Taiwan/86-like and H1N1 viruses isolated before 1983, however, suggesting that the former evolved from viruses that circulated before the 1983 antigenic variants became the predominant H1N1 epidemic virus strains. This was confirmed by sequencing the HA1 domain of the haemagglutinin genes of three A/Taiwan/86-like viruses. These studies provide evidence that other genes of influenza A viruses, in addition to the haemagglutinin gene, may evolve concurrently along two or more separate pathways.


Development of a low cost high precision three-layer 3D artificial compound eye.
Artificial compound eyes are typically designed on planar substrates due to the limits of current imaging devices and available manufacturing processes. In this study, a high precision, low cost, three-layer 3D artificial compound eye consisting of a 3D microlens array, a freeform lens array, and a field lens array was constructed to mimic an apposition compound eye on a curved substrate. The freeform microlens array was manufactured on a curved substrate to alter incident light beams and steer their respective images onto a flat image plane. The optical design was performed using ZEMAX. The optical simulation shows that the artificial compound eye can form multiple images with aberrations below 11 μm; adequate for many imaging applications. Both the freeform lens array and the field lens array were manufactured using microinjection molding process to reduce cost. Aluminum mold inserts were diamond machined by the slow tool servo method. The performance of the compound eye was tested using a home-built optical setup. The images captured demonstrate that the proposed structures can successfully steer images from a curved surface onto a planar photoreceptor. Experimental results show that the compound eye in this research has a field of view of 87°. In addition, images formed by multiple channels were found to be evenly distributed on the flat photoreceptor. Additionally, overlapping views of the adjacent channels allow higher resolution images to be re-constructed from multiple 3D images taken simultaneously.


Central modulation of pain.
It has long been appreciated that the experience of pain is highly variable between individuals. Pain results from activation of sensory receptors specialized to detect actual or impending tissue damage (i.e., nociceptors). However, a direct correlation between activation of nociceptors and the sensory experience of pain is not always apparent. Even in cases in which the severity of injury appears similar, individual pain experiences may vary dramatically. Emotional state, degree of anxiety, attention and distraction, past experiences, memories, and many other factors can either enhance or diminish the pain experience. Here, we review evidence for "top-down" modulatory circuits that profoundly change the sensory experience of pain.


Sensitivity enhancement of grating interferometer based two-dimensional sensor arrays using two-wavelength readout.
Diffraction gratings integrated with microelectromechanical systems (MEMS) sensors offer displacement measurements with subnanometer sensitivity. However, the sensitivity of the interferometric readout may drop significantly based on the gap between the grating and the reference surface. A two-wavelength (2-λ) readout method was previously tested using a single MEMS sensor for illustrating increased displacement measurement capability. This work demonstrates sensitivity enhancement on a sensor array with large scale parallelization (~20,000 sensors). The statistical representation, which is developed to model sensitivity enhancement within a grating based sensor array, is supported by experimental results using a thermal sensor array. In the experiments, two lasers at different wavelengths (633 and 650 nm) illuminate the thermal sensor array from the backside, time-sequentially. The diffracted first order light from the array is imaged onto a single CCD camera. The target scene is reconstructed by observing the change in the first diffracted order diffraction intensity for both wavelengths. Merging of the data from two measurements with two lasers was performed by taking the larger of the two CCD measurements with respect to the reference image for each sensor. ~30% increase in the average sensitivity was demonstrated for a 160×120 pixel IR sensor array. Proposed architecture is also applicable to a variety of sensing applications, such as parallel biosensing and atomic force microscopy, for improved displacement measurements and enhanced sensitivity.


Dynamic Trees for unsupervised segmentation and matching of image regions.
We present a probabilistic framework--namely, multiscale generative models known as Dynamic Trees (DT)--for unsupervised image segmentation and subsequent matching of segmented regions in a given set of images. Beyond these novel applications of DTs, we propose important additions for this modeling paradigm. First, we introduce a novel DT architecture, where multilayered observable data are incorporated at all scales of the model. Second, we derive a novel probabilistic inference algorithm for DTs--Structured Variational Approximation (SVA)--which explicitly accounts for the statistical dependence of node positions and model structure in the approximate posterior distribution, thereby relaxing poorly justified independence assumptions in previous work. Finally, we propose a similarity measure for matching dynamic-tree models, representing segmented image regions, across images. Our results for several data sets show that DTs are capable of capturing important component-subcomponent relationships among objects and their parts, and that DTs perform well in segmenting images into plausible pixel clusters. We demonstrate the significantly improved properties of the SVA algorithm--both in terms of substantially faster convergence rates and larger approximate posteriors for the inferred models--when compared with competing inference algorithms. Furthermore, results on unsupervised object recognition demonstrate the viability of the proposed similarity measure for matching dynamic-structure statistical models.


Spatio-temporal correlation between human and bovine schistosomiasis in China: insight from three national sampling surveys.
Insight into the spatial and temporal contamination of the environment by bovine faeces in China can provide important information on the significance of bovines in the transmission of human schistosomiasis. This insight will be useful for the new evidence-based strategy of the Chinese national schistosomiasis control programme. To enhance our understanding of the spatio-temporal relationship between the prevalence of human and bovine schistosomiasis, we performed correlation and regression analyses using data from three national sampling surveys on schistosomiasis, carried out in 1989, 1995 and 2004. In addition, we established a geographical information system and performed spatial analyses to identify the high-risk areas of the disease. We found that schistosomiasis is mainly concentrated in the marshlands along the Yangtze River. It was also noted that, although the human prevalence and force of transmission in highly endemic areas has been reduced since 1989, the relative importance of bovine schistosomiasis has increased. This is seen in a declining Spearman correlation coefficient between the infection prevalence in humans and in bovines over time (0.812 in 1989, 0.754 in 1995 and 0.376 in 2004). In parallel, the slope of the linear regression decreased from 0.395 in 1989 to 0.215 in 2004. Our data therefore suggest that future schistosomiasis control efforts in China should more vigorously address the important role of bovines in the transmission of human schistosomiasis, and to reduce the environmental contamination of Schistosoma japonicum eggs by bovines.


Prevalence of human papillomavirus in anal and oral sites among patients with genital warts.
Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal cancers has been demonstrated. The frequency of oral HPV infection in patients with genital warts and the association between concomitant genital, anal and oral infection is unclear. A total of 201 men and women with genital wart-like lesions were recruited. Swab samples were obtained from the genital warts and the anal canal and an oral rinse was collected. Anal HPV was found in 46.2% and oral HPV in 10.4% of the participants. Concordance between anal and genital wart HPV types was 78.1%, while concordance between oral and genital wart types was 60.9%. A lower concordance of 21.7% was observed between anal and oral HPV types. Significantly more women than men had multiple HPV types and anal HPV. In conclusion, extra genital HPV is common in patients with genital warts. A gender inequality seems to exist.


Improving Adherence to Care Recommendations Using a Community Health Worker (CHW) Intervention with the Pediatric Medical Home.
While CHW interventions improve health outcomes, evidence identifying specific domains of CHW-delivered support resulting in positive outcomes is limited. Our goals were to identify domains of CHW-delivered support that assist families with adhering to recommended pediatric care; and, to identify predictors of successful completion of an enriched medical home intervention (EMHI) using trained CHWs making home visits to provide health education and support positive health behaviors. We performed a prospective descriptive study of 88 families participating in a protocol-based EMHI. Completers (N = 46) finished the program with mutual agreement that the family can independently adhere to recommended clinical care. Non-completers (N = 42) were lost to follow-up or dropped out of the program before reaching this milestone. Using Grounded Theory, two trained coders evaluated CHW tasks recorded in an electronic database and classified these tasks across 17 domains. We assessed predictors of EMHI completion using logistic regression. The 88 EMHI participants were primarily <24 months of age (80 %), Hispanic (56 %), and Medicaid enrollees (67 %). Hispanic families (OR = 2.76, p = 0.04) and those with self-reported program goals to 'facilitate family's creation of a system to keep track of child's medical information' (OR = 3.11, p = 0.02) or a 'newborn-specific goal' (OR = 3.21, p = 0.04), such as feeding and safety tips, were more likely to complete the EMHI compared to their counterparts. The most consistent CHW tasks were supporting medical appointments, medication maintenance, and providing health education. CHW interventions designed to improve health behavior outcomes of 'at-risk' families, including Medicaid enrollees, may benefit from support in goal-setting and strategies to systematically manage their child's medical care.


Influence of open vegetation fires on black carbon and ozone variability in the southern Himalayas (NCO-P, 5079 m a.s.l.).
We analysed the variability of equivalent black carbon (BC) and ozone (O3) at the global WMO/GAW station Nepal Climate Observatory-Pyramid (NCO-P, 5079 m a.s.l.) in the southern Himalayas, for evaluating the possible contribution of open vegetation fires to the variability of these short-lived climate forcers/pollutants (SLCF/SLCP) in the Himalayan region. We found that 162 days (9% of the data-set) were characterised by acute pollution events with enhanced BC and O3 in respect to the climatological values. By using satellite observations (MODIS fire products and the USGS Land Use Cover Characterization) and air mass back-trajectories, we deduced that 56% of these events were likely to be affected by emissions from open fires along the Himalayas foothills, the Indian Subcontinent and the Northern Indo-Gangetic Plain. These results suggest that open fire emissions are likely to play an important role in modulating seasonal and inter-annual BC and O3 variability over south Himalayas.


Exceptionally strong hydrogels through self-assembly of an indole-capped dipeptide.
The synthesis of a new hydrogelator with an indole capping group, 1, is reported. 1 forms exceptionally strong hydrogels in a variety of environments, with values for the storage modulus G' amongst the highest reported for supramolecular hydrogels. These gels exhibit strong bundling characteristics, which gives the high values for G' observed. Cell viability studies show that at low concentrations, 1 is biocompatible, however upon self-assembly at higher concentrations, cytotoxic effects are observed.


Pathogenic Microorganisms Associated with Fresh Produce.
The presence of numerous genera of spoilage bacteria, yeasts and molds, and an occasional pathogen on fresh produce has been recognized for many years. Several outbreaks of human gastroenteritis have been linked to the consumption of contaminated fresh vegetables and, to a lesser extent, fruits. Salads containing raw vegetables have been identified as vehicles of traveler's diarrhea, an illness sometimes experienced by visitors to developing countries. Enterotoxigenic Escherichia coli is the most common cause of this illness. Enterohemorrhagic E. coli , specifically serotype O157:H7, has been implicated as the causative agent in an outbreak of gastroenteritis resulting from the consumption of cantaloupes. Outbreaks of salmonellosis in humans have been attributed to consumption of contaminated tomatoes, mustard cress, bean sprouts, cantaloupe, and watermelon. An onion-associated outbreak of Shigella flexneri gastroenteritis has recently been reported in the United States. Outbreaks of human listeriosis have been epidemiologically linked to the consumption of fresh cabbage and lettuce. Gastrointestinal illness caused by the consumption of raw vegetable seed sprouts contaminated by Bacillus cereus has been documented. The ability of Aeromonas hydrophila and Aeromonas sobria to produce several virulence factors has been documented and their fairly common occurrence in water raises concern over public health risks that may be associated with the consumption of salad vegetables, although their role as agents in foodborne illness has not been fully confirmed. Viruses are not likely to grow on contaminated vegetables and fruits but can survive long enough to cause life-threatening illness in humans. An increased per capita consumption of fresh and lightly processed produce in the United States and other countries, coupled with an increase in importation of produce to these countries from regions where standards for growing and handling produce may be compromised, has resulted in heightened interest in outbreaks of human gastroenteritis that may be attributed to contaminated fresh produce, particularly salad vegetables. Likewise methods of handling, processing, packaging, and distribution of fresh produce on a regional or local scale within countries are receiving attention in terms of identifying and controlling microbiological hazards. Hazard analysis critical control point (HACCP) programs are being developed in an effort to minimize the risk of illness associated with consumption of fresh produce. Examples of pathogenic microorganisms associated with fresh produce as well as procedures that can be used to reduce their incidence at the point of consumption are discussed.


Sample size and precision in NIH peer review.
The Working Group on Peer Review of the Advisory Committee to the Director of NIH has recommended that at least 4 reviewers should be used to assess each grant application. A sample size analysis of the number of reviewers needed to evaluate grant applications reveals that a substantially larger number of evaluators are required to provide the level of precision that is currently mandated. NIH should adjust their peer review system to account for the number of reviewers needed to provide adequate precision in their evaluations.


[Proximal displacement of the femoral head after Chiari pelvic osteotomy for coxarthrosis with dysplastic acetabulum].
Proximal displacement of the femoral head can been seen sometimes after Chiari pelvic osteotomy. In order to clarify the causes of the displacement, a quantification analysis was performed to evaluate the factors of this osteotomy. The statistical analysis showed that 54% of the causes could be explained as being due to the angle of osteotomy, obesity ratio, the variation of the acetabular trochanteric distance, and other three factors. Paying attention to get good results: 1) making the angle of osteotomy from 11 degrees to 20 degrees, 2) keeping the variation of the acetabular trochanteric distance within 20mm, 3) the improvement of the lever arm ratio within 15%, and 4) the approximate acetabular index above 30%. In a case with the greater trochanter pulled down, a computer simulation showed that the centripetal force of the femoral head was decreased, and the displacement was increased.


Feeding habits and trophic ecology of Dasyatis longa (Elasmobranchii: Myliobatiformes): sexual, temporal and ontogenetic effects.
Sexual, ontogenic and temporal effects in the diet of Dasyatis longa were evaluated to determine feeding habits and trophic ecology. Numeric indices and the index of relative importance were applied to establish the feeding strategy of the species. Independence of the diet with respect to sex, dry or rainy season and size was evaluated with contingency tables, correspondence analysis and multivariate analysis (MANOVA). The trophic relationships of D. longa (by sex and size intervals) were determined using Levin's niche breadth index and the Pianka's diet overlap index and their significance was determined by null models. The trophic level for each size interval and the species was also calculated. Dasyatis longa showed a narrow niche breadth feeding mainly on shrimps and fishes and its diet was dependent on size, but not on sex or season. Juvenile individuals (class I) fed on shrimps, sub-adults (class II) on fishes and adults (class III) on stomatopods. Significant overlaps between size classes I and II and classes II and III were found. The trophic level shows D. longa to be a secondary or tertiary consumer. Due to considerable fishing pressures on shrimps, the principal prey of D. longa, it will be important to determine their ability to adapt to changes in prey populations.


Cellular specificity of the blood-CSF barrier for albumin transfer across the choroid plexus epithelium.
To maintain the precise internal milieu of the mammalian central nervous system, well-controlled transfer of molecules from periphery into brain is required. Recently the soluble and cell-surface albumin-binding glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been implicated in albumin transport into developing brain, however the exact mechanism remains unknown. We postulate that SPARC is a docking site for albumin, mediating its uptake and transfer by choroid plexus epithelial cells from blood into cerebrospinal fluid (CSF). We used in vivo physiological measurements of transfer of endogenous (mouse) and exogenous (human) albumins, in situ Proximity Ligation Assay (in situ PLA), and qRT-PCR experiments to examine the cellular mechanism mediating protein transfer across the blood-CSF interface. We report that at all developmental stages mouse albumin and SPARC gave positive signals with in situ PLAs in plasma, CSF and within individual plexus cells suggesting a possible molecular interaction. In contrast, in situ PLA experiments in brain sections from mice injected with human albumin showed positive signals for human albumin in the vascular compartment that were only rarely identifiable within choroid plexus cells and only at older ages. Concentrations of both endogenous mouse albumin and exogenous (intraperitoneally injected) human albumin were estimated in plasma and CSF and expressed as CSF/plasma concentration ratios. Human albumin was not transferred through the mouse blood-CSF barrier to the same extent as endogenous mouse albumin, confirming results from in situ PLA. During postnatal development Sparc gene expression was higher in early postnatal ages than in the adult and changed in response to altered levels of albumin in blood plasma in a differential and developmentally regulated manner. Here we propose a possible cellular route and mechanism by which albumin is transferred from blood into CSF across a sub-population of specialised choroid plexus epithelial cells.


Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal.
The designation, DYT4, was assigned to an Australian family with whispering dysphonia. The role of known causes of dystonia has not been comprehensively investigated in this family, nor has the possible relationship with Wilson disease (WND) in 2 siblings. Eighteen family members were neurologically examined, and DNA samples were obtained. Linkage analysis was performed to DYT1, DYT6, DYT7, DYT11, DYT13, DYT15, and ATP7B with microsatellite markers and the THAP1 (DYT6), PRKRA (DYT16), and ATP7B (WND) genes were sequenced. Reevaluation of the family identified 9 living affected family members, 6 of whom are newly affected. Phenotypic expression was variable, ranging from isolated spasmodic dysphonia (often with mild craniocervical dystonia) to severe generalized dystonia. Two newly described features included an extrusional tongue dystonia and a unique "hobby horse gait." Genetic analyses excluded all tested loci. Haplotype analysis of the ATP7B region resulted in three different combinations of the two parental alleles in the 8 investigated siblings of the 2 deceased WND patients, indicating that the fourth combination (of two mutated alleles) had occurred only in the deceased WND patients. On these two alleles, we identified a missense (c.2297C>G; p.T766R) and a splice-site mutation (IVS5+1G>T). The c.2297C>G mutation was detected in 3 affected and 4 unaffected family members, whereas the IVS5+1G>T mutation was detected in 1 affected and unaffected family member. Five DYT4 patients carried neither mutation. DYT4 is a familial form of dystonia unrelated to known dystonia genes and loci. ATP7B mutations do not segregate with the dystonia phenotype, indicating two independent genetic diseases in this family.


Chemical ionization mass spectrometry using carbon nanotube field emission electron sources.
A novel chemical ionization (CI) source has been developed based on a carbon nanotube (CNT) field emission electron source. The CNT-based electron source was evaluated and compared with a standard filament thermionic electron source in a commercial explosives trace detection desktop mass spectrometer. This work demonstrates the first reported use of a CNT-based ion source capable of collecting CI mass spectra. Both positive and negative modes were investigated. Spectra were collected for a standard mass spectrometer calibration compound, perfluorotributylamine (PFTBA), as well as trace explosives including trinitrotoluene (TNT), Research Department explosive (RDX), and pentaerythritol tetranitrate (PETN). The electrical characteristics, lifetime at operating pressure, and power requirements of the CNT-based electron source are reported. The CNT field emission electron sources demonstrated an average lifetime of 320 h when operated in constant emission mode under elevated CI pressures. The ability of the CNT field emission source to cycle on and off can provide enhanced lifetime and reduced power consumption without sacrificing performance and detection capabilities. Graphical Abstract .


Persistence of Neighborhood Demographic Influences over Long Phylogenetic Distances May Help Drive Post-Speciation Adaptation in Tropical Forests.
Studies of forest dynamics plots (FDPs) have revealed a variety of negative density-dependent (NDD) demographic interactions, especially among conspecific trees. These interactions can affect growth rate, recruitment and mortality, and they play a central role in the maintenance of species diversity in these complex ecosystems. Here we use an equal area annulus (EAA) point-pattern method to comprehensively analyze data from two tropical FDPs, Barro Colorado Island in Panama and Sinharaja in Sri Lanka. We show that these NDD interactions also influence the continued evolutionary diversification of even distantly related tree species in these FDPs. We examine the details of a wide range of these interactions between individual trees and the trees that surround them. All these interactions, and their cumulative effects, are strongest among conspecific focal and surrounding tree species in both FDPs. They diminish in magnitude with increasing phylogenetic distance between heterospecific focal and surrounding trees, but do not disappear or change the pattern of their dependence on size, density, frequency or physical distance even among the most distantly related trees. The phylogenetic persistence of all these effects provides evidence that interactions between tree species that share an ecosystem may continue to promote adaptive divergence even after the species' gene pools have become separated. Adaptive divergence among taxa would operate in stark contrast to an alternative possibility that has previously been suggested, that distantly related species with dispersal-limited distributions and confronted with unpredictable neighbors will tend to converge on common strategies of resource use. In addition, we have also uncovered a positive density-dependent effect: growth rates of large trees are boosted in the presence of a smaller basal area of surrounding trees. We also show that many of the NDD interactions switch sign rapidly as focal trees grow in size, and that their cumulative effect can strongly influence the distributions and species composition of the trees that surround the focal trees during the focal trees' lifetimes.


Ultrasound-Guided High Intensity Focused Ultrasound Ablation for Symptomatic Uterine Fibroids: Preliminary Clinical Experience.
To evaluate the middle-term efficacy and complications of ultrasound-guided high intensity focused ultrasound (USgHIFU) for the treatment of symptomatic uterine fibroids in an NHS population. A prospective observational single-center study at a single university hospital in Oxford, UK. Patients with symptomatic uterine fibroids who declined standard surgical/radiological intervention and were referred to the HIFU unit were considered for USgHIFU treatment. Clinical evaluation, adverse event monitoring, uterine fibroid symptoms and health-related quality of life questionnaire (UFS-QOL) and contrast-enhanced pelvic magnetic resonance imaging (MRI) were performed before and at regular intervals after treatment to assess patient outcome. 12 of 22 referred patients underwent one session of USgHIFU ablation of 14 fibroids overall and received a two-year follow-up. No serious adverse events were reported, but a second-degree skin burn was observed in one patient who had a surgical scar from a previous caesarean section. Mean symptom severity scores (SSS-QOL) improved significantly from 56.5 ± 29.1 (SD) at baseline to 33.4 ± 23.3 (p < 0.01) at three months, 45.0 ± 35.4 (p < 0.05) at one year and 40.6 ± 32.7 (p < 0.01) at two years post-treatment. The mean non-perfused volume ratio was 67.7 ± 39.0 % (SD) in the treated fibroids (n = 14) within three months of treatment. The mean volume reduction rates of the treated fibroids were 23.3 ± 25.5 % (SD) at 3 months post-treatment (p < 0.01, n = 14), 49.3 ± 23.7 % at 12 months (p < 0.05, n = 8), and 51.9 ± 11.1 % at 24 months (p < 0.005, n = 8). This study demonstrates the clinical efficacy of USgHIFU ablation of uterine fibroids and the low risk of complications. We believe that this noninvasive approach may offer an alternative therapy for women with symptomatic uterine fibroids. While HIFU is fast becoming the standard of care for fibroid ablation in other countries, to our knowledge, this study is the first to present clinical experience of US-guided HIFU ablation of symptomatic uterine fibroids in an NHS population. High intensity focused ultrasound (HIFU) can be used for the noninvasive ablation of symptomatic uterine fibroids, and MR-guided treatment has already gained FDA approval. Ultrasound-guided HIFU has the advantage of offering practicalities in anesthesia and considerable cost-savings over MR-guided treatments. In this prospective study we have demonstrated the middle-term efficacy and favorable safety profile of ultrasound-guided HIFU for the treatment of symptomatic uterine fibroids for the first time in an NHS population.


Torque, power and muscle activation of eccentric and concentric isokinetic cycling.
This study aimed to establish the effect of cycling mode and cadence on torque, external power output, and lower limb muscle activation during maximal, recumbent, isokinetic cycling. After familiarisation, twelve healthy males completed 6 × 10 s of maximal eccentric (ECC) and concentric (CON) cycling at 20, 40, 60, 80, 100, and 120 rpm with five minutes recovery. Vastus lateralis, medial gastrocnemius, rectus femoris, and biceps femoris surface electromyography was recorded throughout. As cadence increased, peak torque linearly decreased during ECC (350-248 N·m) and CON (239-117 N·m) and peak power increased in a parabolic manner. Crank angle at peak torque increased with cadence in CON (+13°) and decreased in ECC (-9.0°). At all cadences, peak torque (mean +129 N·m, range 111-143 N·m), and power (mean +871 W, range 181-1406 W), were greater during ECC compared to CON. For all recorded muscles the crank angle at peak muscle activation was greater during ECC compared to CON. This difference increased with cadence in all muscles except the vastus lateralis. Additionally, peak vastus laterallis and biceps femoris activation was greater during CON compared to ECC. Eccentric cycling offers a greater mechanical stimulus compared to concentric cycling but the effect of cadence is similar between modalities. Markers of technique (muscle activation, crank angle at peak activation and torque) were different between eccentric and concentric cycling and respond differently to changes in cadence. Such data should be considered when comparing between, and selecting cadences for, recumbent, isokinetic, eccentric and concentric cycling.


Pharmacokinetics of doxycycline in dogs.
Six adult dogs were given doxycycline hyclate at a dosage of 5 mg/kg of body weight intravenously so that pharmacokinetic parameters could be evaluated. Serum doxycycline concentrations were determined over a 48 h period using a modified agar well bioassay. Compartmental pharmacokinetic evaluation of the serum concentration time data indicated that doxycycline has a half-life of 10.36 h, a body clearance of 1.68 +/- 0.44 mL/min/kg, and a volume of distribution at steady state of 1.468 +/- 0.237 L/kg. Doxycycline pharmacokinetics are favorable for therapeutic use in the dog.


Sound-Making Actions Lead to Immediate Plastic Changes of Neuromagnetic Evoked Responses and Induced β-Band Oscillations during Perception.
Auditory and sensorimotor brain areas interact during the action-perception cycle of sound making. Neurophysiological evidence of a feedforward model of the action and its outcome has been associated with attenuation of the N1 wave of auditory evoked responses elicited by self-generated sounds, such as talking and singing or playing a musical instrument. Moreover, neural oscillations at β-band frequencies have been related to predicting the sound outcome after action initiation. We hypothesized that a newly learned action-perception association would immediately modify interpretation of the sound during subsequent listening. Nineteen healthy young adults (7 female, 12 male) participated in three magnetoencephalographic recordings while first passively listening to recorded sounds of a bell ringing, then actively striking the bell with a mallet, and then again listening to recorded sounds. Auditory cortex activity showed characteristic P1-N1-P2 waves. The N1 was attenuated during sound making, while P2 responses were unchanged. In contrast, P2 became larger when listening after sound making compared with the initial naive listening. The P2 increase occurred immediately, while in previous learning-by-listening studies P2 increases occurred on a later day. Also, reactivity of β-band oscillations, as well as θ coherence between auditory and sensorimotor cortices, was stronger in the second listening block. These changes were significantly larger than those observed in control participants (eight female, five male), who triggered recorded sounds by a key press. We propose that P2 characterizes familiarity with sound objects, whereas β-band oscillation signifies involvement of the action-perception cycle, and both measures objectively indicate functional neuroplasticity in auditory perceptual learning.SIGNIFICANCE STATEMENT While suppression of auditory responses to self-generated sounds is well known, it is not clear whether the learned action-sound association modifies subsequent perception. Our study demonstrated the immediate effects of sound-making experience on perception using magnetoencephalographic recordings, as reflected in the increased auditory evoked P2 wave, increased responsiveness of β oscillations, and enhanced connectivity between auditory and sensorimotor cortices. The importance of motor learning was underscored as the changes were much smaller in a control group using a key press to generate the sounds instead of learning to play the musical instrument. The results support the rapid integration of a feedforward model during perception and provide a neurophysiological basis for the application of music making in motor rehabilitation training.


Large-scale protein level comparison of Deltaproteobacteria reveals cohesive metabolic groups.
Deltaproteobacteria, now proposed to be the phyla Desulfobacterota, Myxococcota, and SAR324, are ubiquitous in marine environments and play essential roles in global carbon, sulfur, and nutrient cycling. Despite their importance, our understanding of these bacteria is biased towards cultured organisms. Here we address this gap by compiling a genomic catalog of 1 792 genomes, including 402 newly reconstructed and characterized metagenome-assembled genomes (MAGs) from coastal and deep-sea sediments. Phylogenomic analyses reveal that many of these novel MAGs are uncultured representatives of Myxococcota and Desulfobacterota that are understudied. To better characterize Deltaproteobacteria diversity, metabolism, and ecology, we clustered ~1 500 genomes based on the presence/absence patterns of their protein families. Protein content analysis coupled with large-scale metabolic reconstructions separates eight genomic clusters of Deltaproteobacteria with unique metabolic profiles. While these eight clusters largely correspond to phylogeny, there are exceptions where more distantly related organisms appear to have similar ecological roles and closely related organisms have distinct protein content. Our analyses have identified previously unrecognized roles in the cycling of methylamines and denitrification among uncultured Deltaproteobacteria. This new view of Deltaproteobacteria diversity expands our understanding of these dominant bacteria and highlights metabolic abilities across diverse taxa.


Effect of Turkish Propolis on miRNA Expression, Cell Cycle, and Apoptosis in Human Breast Cancer (MCF-7) Cells.
Enriched in flavonoid compounds, phenol acids, and terpene derivatives, propolis has been shown to regulate apoptosis signaling pathways and alter the expression of microRNAs (miRNAs). In the present study, it has been aimed to examine the effects of Turkish propolis on miRNA levels of breast cancer (MCF-7) cells, and its relationship with cell proliferation and apoptosis. Cytotoxic activity of ethanolic propolis extract (EEP) was evaluated using MTT assay. Mechanisms involved in the cytotoxic action of Turkish propolis in MCF-7 cells were investigated with regard to apoptosis and cell cycle using flow cytometry and western blot. Mitochondrial membrane potential (MMP) were evaluated by spectrofluorometric method. miRNA levels were detected by qRT-PCR method. EEP exhibited selective toxicity against MCF-7 cells compared to normal fibroblast cells. EEP increased the cell cycle arrest at the G1 phase. EEP elevated the apoptotic cell death through increasing pro-apoptotic protein levels (p21, Bax, p53, p53-Ser46, and p53-Ser15), decreasing MMP and altering the expression levels of specific tumor suppressors (miR-34, miR-15a, and miR-16-5p) and oncogenic (miR-21) miRNAs. These data support that Turkish propolis may be evaluated as a potential natural agent for new anticancer drugs in future.


Diagnosis and epidemiology of osteoporosis.
Osteoporosis remains a major public health problem through its association with fragility fractures. Recent data suggest that the annual cost in Europe is 13 billion euros, mainly accounted for by hospitalisation after fracture. Understanding the epidemiology of osteoporosis is an essential step in developing strategies to reduce the burden of osteoporotic fracture in the population. This article will review recent advances surrounding the epidemiology of osteoporosis, the burden of fracture in children and adults in this country and abroad, morbidity associated with such fractures, associations of disease and medication with fragility fracture, and advances in diagnostic techniques and identification of at-risk groups. The papers studied highlight the wealth of high-quality research in this field, and they help in the visualisation of strategies to identify individuals at high risk of fragility fracture and to quantify fracture risk by measurement of bone density, bone quality, and risk factor algorithms.


Incorporating research evidence into decision-making processes: researcher and decision-maker perceptions from five low- and middle-income countries.
The 'Sponsoring National Processes for Evidence-Informed Policy Making in the Health Sector of Developing Countries' program was launched by the Alliance for Health Policy and Systems Research, WHO, in July 2008. The program aimed to catalyse the use of evidence generated through health policy and systems research in policymaking processes through (1) promoting researchers and policy advocates to present their evidence in a manner that is easy for policymakers to understand and use, (2) creating mechanisms to spur the demand for and application of research evidence in policymaking, and (3) increased interaction between researchers, policy advocates, and policymakers. Grants ran for three years and five projects were supported in Argentina, Bangladesh, Cameroon, Nigeria and Zambia. This paper seeks to understand why projects in some settings were perceived by the key stakeholders involved to have made progress towards their goals, whereas others were perceived to have not done so well. Additionally, by comparing experiences across five countries, we seek to illustrate general learnings to inform future evidence-to-policy efforts in low- and middle-income countries. We adopted the theory of knowledge translation developed by Jacobson et al. (J Health Serv Res Policy 8(2):94-9, 2003) as a framing device to reflect on project experiences across the five cases. Using data from the projects' external evaluation reports, which included information from semi-structured interviews and quantitative evaluation surveys of those involved in projects, and supplemented by information from the projects' individual technical reports, we applied the theoretical framework with a partially grounded approach to analyse each of the cases and make comparisons. There was wide variation across projects in the type of activities carried out as well as their intensity. Based on our findings, we can conclude that projects perceived as having made progress towards their goals were characterized by the coming together of a number of domains identified by the theory. The domains of Jacobson's theoretical framework, initially developed for high-income settings, are of relevance to the low- and middle-income country context, but may need modification to be fully applicable to these settings. Specifically, the relative fragility of institutions and the concomitantly more significant role of individual leaders point to the need to look at leadership as an additional domain influencing the evidence-to-policy process.


Experiences of Healthcare Worker Returnees in Their Home Countries: A Scoping Review.
International migration of healthcare workers is a global phenomenon driven by growing demand in developed countries and expectations of healthcare workers from developing countries to have improved employment and lives. This migration has been understood to impact both the individuals and countries involved, with positive and negative consequences. However, little is known about returnees' experiences that could be used to address challenges and optimize benefits. The aim of this review was to understand what is known about experiences of migrant health workers after returning to their home countries. A scoping review of primary research addressing experiences of migrant health workers upon their return to their homelands. A range of database were searched including Career and Technical Education Database via ProQuest, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Education database via ProQuest, Excerpta Medica Care (EMCare) via Ovid, Education Resources Information Center (ERIC), Excerpta Medica database (EMBASE) via Ovid, MEDLINE and Scopus. A systematic process was performed guided by the work of Arksey and O'Malley. Eight databases were searched and 226 articles were retrieved. After screening articles and abstracts, 15 full-texts were assessed for eligibility, and finally seven studies were further analyzed and synthesized. Five qualitative studies, one quantitative study and one mixed methods study met inclusion criteria. Five themes emerged: (1) reasons to return, (2) upskilling and deskilling, (3) impact on human, financial, and social capital, (4) challenges and opportunities in the home country, and (5) facilitation supports. Return migration is portrayed as a complex situation experienced by returnees. Structured policy and supports are required to help healthcare worker returnees prepare, and to adjust to life after their return. This study highlights the importance of comprehensive approach in return migration stage. Return migration policy should support healthcare worker returnees in their home country and facilitate utilization of their skills. Multi-stakeholder partnerships are vital to develop platforms for helping and facilitating returnees in the reintegration process at their home countries.


Imaging mRNA and protein interactions within neurons.
RNA-protein interactions are essential for proper gene expression regulation, particularly in neurons with unique spatial constraints. Currently, these interactions are defined biochemically, but a method is needed to evaluate them quantitatively within morphological context. Colocalization of two-color labels using wide-field microscopy is a method to infer these interactions. However, because of chromatic aberrations in the objective lens, this approach lacks the resolution to determine whether two molecules are physically in contact or simply nearby by chance. Here, we developed a robust super registration methodology that corrected the chromatic aberration across the entire image field to within 10 nm, which is capable of determining whether two molecules are physically interacting or simply in proximity by random chance. We applied this approach to image single-molecule FISH in combination with immunofluorescence (smFISH-IF) and determined whether the association between an mRNA and binding protein(s) within a neuron was significant or accidental. We evaluated several mRNA-binding proteins identified from RNA pulldown assays to determine which of these exhibit bona fide interactions. Surprisingly, many known mRNA-binding proteins did not bind the mRNA in situ, indicating that adventitious interactions are significant using existing technology. This method provides an ability to evaluate two-color registration compatible with the scale of molecular interactions.


Hepatic encephalopathy.
Hepatic encephalopathy is a serious and potentially fatal complication of both acute and chronic liver disease, arising as a result of hepatocellular failure, cirrhosis and/or portal-systemic shunting (Ferenci et al, 2002). It reflects a broad spectrum of neuropsychiatric abnormalities, encompassing a range of defects in psychomotor, locomotive, cognitive, emotional and behavioural functions (Prakash and Mullen, 2010). Hepatic encephalopathy is either overt or minimal. While overt hepatic encephalopathy can be diagnosed using bedside clinical tests, minimal hepatic encephalopathy is clinically invisible and requires psychometric testing to diagnose. The rising prevalence of end-stage viral hepatitis-related liver disease, coupled with the growing problem of alcoholic and non-alcoholic fatty liver disease, has significantly increased the burden of disease from cirrhosis (Mooney et al, 2007; Fleming et al, 2008), so recognition and appropriate management of the manifestations of decompensating cirrhosis (including hepatic encephalopathy) is essential. Hepatic encephalopathy has a substantial societal burden because of its impact on survival, quality of life and daily functioning, including an impaired ability to drive, leaving patients especially vulnerable to road traffic accidents (Ferenci et al, 2002; Prakash and Mullen, 2010).


ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements.
CIC rearrangements have been reported in two-thirds of EWSR1-negative small blue round cell tumors (SBRCTs). However, a number of SBRCTs remain unclassified despite exhaustive analysis. Fourteen SBRCTs lacking driver genetic events by RNA sequencing (RNAseq) analysis were collected. Unsupervised hierarchical clustering was performed using samples from our RNAseq database, including 13 SBRCTs with non-CIC genetic abnormalities and 2 CIC-rearranged angiosarcomas among others. Remarkably, all 14 study cases showed high mRNA levels of ETV1/4/5, and by unsupervised clustering most grouped into a distinct cluster, separate from other tumors. Based on these results indicating a close relationship with CIC-rearranged tumors, we manually inspected CIC reads in RNAseq data. FISH for CIC and DUX4 abnormalities and immunohistochemical stains for ETV4 were also performed. In the control group, only 2 CIC-rearranged angiosarcomas had high ETV1/4/5 expression. Upon manual inspection of CIC traces, 7 of 14 cases showed CIC-DUX4 fusion reads, 2 cases had DUX4-CIC reads, while the remaining 5 were negative. FISH showed CIC break-apart in 7 cases, including 5 cases lacking CIC-DUX4 or DUX4-CIC fusion reads on RNAseq manual inspection. However, no CIC abnormalities were detected by FISH in 6 cases with CIC-DUX4 or DUX4-CIC reads. ETV4 immunoreactivity was positive in 7 of 11 cases. Our results highlight the underperformance of FISH and RNAseq methods in diagnosing SBRCTs with CIC gene abnormalities. The downstream ETV1/4/5 transcriptional up-regulation appears highly sensitive and specific and can be used as a reliable molecular signature and diagnostic method for CIC fusion positive SBRCTs.


A decrease in bulk water and mannitol and accumulation of trehalose and trehalose-based oligosaccharides define a two-stage maturation process towards extreme stress resistance in ascospores of Neosartorya fischeri (Aspergillus fischeri).
Fungal propagules survive stresses better than vegetative cells. Neosartorya fischeri, an Aspergillus teleomorph, forms ascospores that survive high temperatures or drying followed by heat. Not much is known about maturation and development of extreme stress resistance in fungal cells. This study provides a novel two-step model for the acquisition of extreme stress resistance and entry into dormancy. Ascospores of 11- and 15-day-old cultures exhibited heat resistance, physiological activity, accumulation of compatible solutes and a steep increase in cytoplasmic viscosity. Electron spin resonance spectroscopy indicated that this stage is associated with the removal of bulk water and an increase of chemical stability. Older ascospores from 15- to 50-day-old cultures showed no changes in compatible solute content and cytoplasmic viscosity, but did exhibit a further increase of heat resistance and redox stability with age. This stage was also characterized by changes in the composition of the mixture of compatible solutes. Mannitol levels decreased and the relative quantities of trehalose and trehalose-based oligosaccharides increased. Dormant ascospores of N. fischeri survive in low-water habitats. After activation of the germination process, the stress resistance decreases, compatible solutes are degraded and the cellular viscosity drops. After 5 h, the hydrated cells enter the vegetative stage and redox stability has decreased notably.


The microtensile bond strength of self-etching adhesives to ground enamel.
It is uncertain whether single-phase self-etching adhesives form bonds to enamel as reliable as those of etch-and-rinse adhesives. This study compared the microtensile bond strengths to ground enamel of three self-etching adhesive systems, a self-etching primer system and an etchand-rinse adhesive system. Human enamel was ground flat with 320-grit silicone carbide paper. The self-etching adhesives iBond (Heraeus Kulzer), Prompt L-Pop (3M ESPE) and Xeno III (Caulk/Dentsply), the adhesive with a self-etching primer Clearfil SE Bond (Kuraray) and the etch-and-rinse adhesive Scotchbond Multipur-pose (3M/ESPE) were applied as directed, followed by a core of the same manufacturers' hybrid resin composite. A microtensile bond strength evaluation was performed after 48 hours of water storage, using untrimmed beams approximately 0.9 mm2 in cross-sectional area at a crosshead speed of 0.6 mm/minute. There were no pretest failures in any group, and failures were predominately adhesive or mixed. Adhesion to enamel of Clearfil SE was not significantly different from Scotchbond Multi-Purpose, while the three self-etching adhesive systems demonstrated significantly lower bond strengths (One-way ANOVA, Tukey-Kramer Multiple-Comparison Test, p < 0.00001).