Is a small-caliber or large-caliber endoscope more suitable for colonic self-expandable metallic stent placement? A randomized controlled study.
The colonic self-expandable metallic stent (C-SEMS) with a 9-French (Fr) delivery system allows for a small-caliber endoscope (SCE) to be used to treat malignant colonic obstruction. Despite the lack of evidence, the SCE has become popular because it is considered easier to insert than the large-caliber endoscope (LCE). We aimed to determine whether the SCE is more suitable than the LCE for C-SEMS placement. Between July 2018 and November 2019, 50 consecutive patients who were scheduled to undergo C-SEMS for colon obstruction were recruited in this study. Patients were randomized to the SCE or LCE group. The SCE and LCE were used with 9-Fr and 10-Fr delivery systems, respectively. The primary outcome was the total procedure time. Secondary outcomes were the technical success rate, complication rate, clinical success rate, insertion time, guidewire-passage time, stent-deployment time, and colonic obstruction-scoring-system score. Forty-five patients (SCE group, n = 22; LCE group, n = 23) were analyzed. The procedure time in the LCE group (median, 20.5 min) was significantly (p = 0.024) shorter than that in the SCE group (median, 25.1 min). The insertion time in the LCE group (median, 2.0 min) was significantly (p = 0.0049) shorter than that in the SCE group (median, 6.0 min). A sub-analysis of the procedure difficulties showed that the insertion time in the LCE group (median, 5.0 min) was significantly shorter than that in the SCE group (median, 8.5 min). Both LCE and SCE can be used for C-SEMS; however, LCE is more suitable than SCE as it achieved a faster and equally efficacious C-SEMS placement as that of SCE. University Hospital Medical Information Network Clinical Trials Registry (UMIN 32748).


Detail investigation of toxicity, bioaccumulation, and translocation of Cd-based quantum dots and Cd salt in white mustard.
In this study, a model crop plant white mustard (Sinapis alba L.) was treated with an aqueous dispersion of silica-coated CdTe quantum dots (CdTe/SiO2 QDs) in a 72-h short-term toxicity test. The toxicity was established via measurements of (i) the root length and (ii) the chlorophyll fluorescence. These results were compared to two other sources of cadmium, free Cd ions (CdCl2) and prime un-shell nanoparticles CdTe QDs. Tested compounds were applied in concentrations representing 20 and 200 μM Cd. The uptake and translocation of Cd were investigated using inductively coupled plasma optical emission spectrometry (ICP-OES) and the spatial Cd distribution was investigated in detail applying laser induced breakdown spectroscopy (LIBS). The LIBS maps with a lateral resolution of 100 μm were constructed for the whole plants, and maps with a lateral resolution of 25 μm (micro-LIBS arrangement) were used to analyse only the most interesting parts of plants with Cd presence (e.g. root tips or a part crossing the root into the above-ground part). Our results show that the bioaccumulation patterns and spatial distribution of Cd in CdTe/SiO2 QDs-treated plants differ from the plants of positive control and CdTe QDs. Fluorescence microscopy photographs revealed that CdTe/SiO2 became adsorbed onto the plant surface in comparison to CdTe QDs. Further, a physico-chemical characterization of QDs before and after the test exposure showed only minor changes in the nanoparticle diameters and no tendencies of QDs for agglomeration or aggregation during the exposure.


Learning the Physics of Pattern Formation from Images.
Using a framework of partial differential equation-constrained optimization, we demonstrate that multiple constitutive relations can be extracted simultaneously from a small set of images of pattern formation. Examples include state-dependent properties in phase-field models, such as the diffusivity, kinetic prefactor, free energy, and direct correlation function, given only the general form of the Cahn-Hilliard equation, Allen-Cahn equation, or dynamical density functional theory (phase-field crystal model). Constraints can be added based on physical arguments to accelerate convergence and avoid spurious results. Reconstruction of the free energy functional, which contains nonlinear dependence on the state variable and differential or convolutional operators, opens the possibility of learning nonequilibrium thermodynamics from only a few snapshots of the dynamics.


Maggot development during morgue storage and its effect on estimating the post-mortem interval.
When insect evidence is obtained during autopsy, forensic entomologists make decisions regarding the effects of low-temperature (-1 degrees C to 4 degrees C) storage of the body and associated insects when estimating the post-mortem interval (PMI). To determine the effects of storage in a morgue cooler on the temperature of maggot masses, temperatures inside and outside of body bags containing a human cadaver and porcine cadavers (seven replicates) were measured during storage. Temperatures remained significantly higher (p<0.05) inside of the body bags relative to the cooler, and remained at levels sufficient for maggot feeding and development. If the assumption that no insect development takes place during preautopsy refrigeration is made, potential error rates in PMI estimation of 8.6-12.8% occur. The potential for blow fly larvae to undergo significant development while being stored in the morgue is a possibility that forensic entomologists should consider during an investigation involving samples collected from autopsy. Case and experimental evidence also demonstrate that substantial tissue loss can occur from maggot feeding during morgue storage.


A test of the nature of cosmic acceleration using galaxy redshift distortions.
Observations of distant supernovae indicate that the Universe is now in a phase of accelerated expansion the physical cause of which is a mystery. Formally, this requires the inclusion of a term acting as a negative pressure in the equations of cosmic expansion, accounting for about 75 per cent of the total energy density in the Universe. The simplest option for this 'dark energy' corresponds to a 'cosmological constant', perhaps related to the quantum vacuum energy. Physically viable alternatives invoke either the presence of a scalar field with an evolving equation of state, or extensions of general relativity involving higher-order curvature terms or extra dimensions. Although they produce similar expansion rates, different models predict measurable differences in the growth rate of large-scale structure with cosmic time. A fingerprint of this growth is provided by coherent galaxy motions, which introduce a radial anisotropy in the clustering pattern reconstructed by galaxy redshift surveys. Here we report a measurement of this effect at a redshift of 0.8. Using a new survey of more than 10,000 faint galaxies, we measure the anisotropy parameter beta = 0.70 +/- 0.26, which corresponds to a growth rate of structure at that time of f = 0.91 +/- 0.36. This is consistent with the standard cosmological-constant model with low matter density and flat geometry, although the error bars are still too large to distinguish among alternative origins for the accelerated expansion. The correct origin could be determined with a further factor-of-ten increase in the sampled volume at similar redshift.


Building addiction recovery capital through online participation in a recovery community.
This study examines how online participation in a community of recovery contributes to personal journeys of recovery. It investigates whether recovery capital building - as indicated by increased levels and quality of online social interactions - and markers of positive identity development predict retention in a recovery program designed around fostering community involvement for early stage recovery addicts. It was predicted that online participation on the group's Facebook page and positive identity development are associated to retention in the program. To map how participants interact online, social network analysis (SNA) based on naturally occurring online data (N = 609) on the Facebook page of a recovery community was conducted. Computerised linguistic analyses evaluated sentiment of the textual data (capturing social identity markers). Linear regression analyses evaluated whether indicators of recovery capital predict program retention. To illustrate the findings in the context of the specific recovery community, presented are two case studies of key participants who moved from the periphery to the centre of the social network. By conducting in-depth interviews with these participants, personal experiences of engagement in the online community of group members who have undergone the most significant changes since joining the community are explored. Retention in the program was determined by a) the number of comment 'likes' and all 'likes' received on the Facebook page; b) position in the social network (degree of centrality); and c) linguistic content around group identity and achievement. Positive online interactions between members of recovery communities support the recovery process through helping participants to develop recovery capital that binds them to groups supportive of positive change.


Correction of phase offset errors and quantification of background noise, signal-to-noise ratio, and encoded-displacement uncertainty on DENSE MRI for kinematics of the descending thoracic and abdominal aorta.
Displacement encoding with stimulated echoes (DENSE) MRI is a phase contrast technique that allows the encoding of tissue displacement into the phase of the magnetic resonance signal. Recent developments in this technique allow the imaging of relatively thin structures such as the aortic wall. Quantifying background noise associated to DENSE MRI is required to assess the uncertainty of derived displacement measurements and for the design and implementation of adequate noise-reduction techniques. Although noise and error management of cardiac DENSE MRI has been previously studied, developments for aortic applications are scarce. Herein, we evaluate the noise and uncertainty of DENSE MRI scans at three different locations along the descending aorta: the distal aortic arch (DAA), the descending thoracic aorta (DTA), and infrarenal abdominal aorta (IAA). Additionally, we analyze three datasets from in vitro validation experiments with polyvinyl alcohol phantoms. We implement and evaluate the effectiveness of an offset-error correction algorithm and noise filtering techniques on DENSE MRI for aortic motion applications. Our results show that the phase signal of pixels composing the static background was normally distributed, centered on average at 0.003 ± 0.02 rad and - 0.02 ± 0.024 rad for each phase directions, suggesting that background noise is random, isotropic, and DENSE MRI has little offset errors. However, background signal noise significantly increased with elapsed time of the cardiac cycle; and was spatially heterogeneous consistently increased towards the anterior space. Background noise showed no significant differences between the 3 aortic locations and the in vitro experiments. However, SNR depended on the displacement of the region of interest, in consequence it was found significantly larger at DAA (16.7 ± 8.5, p = 0.003) and DTA (15.4 ± 7.6, p = 0.008) than at the IAA (8.0 ± 4.1), but not significantly different than the SNR of in vitro experiments (8.0 ± 3.7), and had an overall average of 13 ± 7. The applied methods significantly reduced the offset error and effect of noise on the estimation of encoded displacements. Finally, this analysis suggests that the implemented DENSE MRI protocol is adequate to assess the motion of healthy human aortas. However, the relative effect of noise increased considerably on the analysis of an ageing or diseased aortas with impaired mobility, calling for further analyses on pathologically stiffened aortas.


Expression of the melatonin receptor (MT) 1 in benign and malignant human bone tumors.
The beneficial effects of melatonin on bone homeostasis have been shown in various diseases. As this indoleamine causes dose-dependent modulation of bone-forming osteoblast and bone-resorbing osteoclast activities by receptor-independent and -dependent pathways, we investigated the expression of G-protein-coupled melatonin receptors (MTs) in malignant and non-malignant human bone lesions. By TaqMan polymerase chain reaction (PCR), we analyzed 30 specimens from osteosarcoma and 11 from benign bone tumors for MT1-mRNA expression. Furthermore, we determined mRNA expression levels of the osteoclast activity-stimulating receptor activator of nuclear factor-kappa B ligand (RANKL) and its counterpart osteoprotegerin (OPG). Although mean MT1-mRNA levels were similar (P = 0.596) in malignant (4.39 +/- 4.98-fold) and benign samples (4.64 +/- 6.81-fold), the highest MT1-mRNA levels (up to 27-fold) were observed in individual osteosarcomas, particularly, in two specimens of patients with local recurrence of the tumor. Moreover, mean RANKL- and OPG-mRNA levels were similar in malignant and benign specimens (RANKL: 7.38 +/- 9.61-fold versus 3.57 +/- 3.11-fold, P = 0.207; OPG: 23.45 +/- 32.76 versus 8.07 +/- 7.23-fold, P = 0.133). Again, highest RANKL- and OPG-mRNA levels (up to 41- and 160-fold, respectively) were observed in individual osteosarcomas. Expression of MT1-mRNA was confirmed in two human osteosarcoma cell lines (HOS, MG63). High expression levels of MT1-mRNA together with low OPG-mRNA were found in both osteosarcoma cell lines, while in normal human osteoblasts and bone marrow stromal cells, high OPG-mRNA levels were associated with low MT1-mRNA levels. These data on the abundant expression of MT1-mRNA in human bone tumors and osteosarcoma cells lines suggest an important role for MT1 in bone pathology.


Mechanical and Thermal Performance of Macro-Encapsulated Phase Change Materials for Pavement Application.
Macro-encapsulated phase change material (PCM) lightweight aggregates (ME-LWA) were produced and evaluated for their mechanical and thermal properties in road engineering applications. The ME-LWAs were first characterised in terms of their physical and geometrical properties. Then, the ME-LWAs were investigated in detail by applying the European Standards of testing for the Bulk Crushing Test and the Polished Stone Value (PSV) coefficient as well as Micro-Deval and laboratory profilometry. In addition, the thermal performance for possible construction of smart pavements with the inclusion of ME-LWAs for anti-ice purposes was determined. The crushing resistance of the ME-LWAs was improved, while their resistance to polishing was reduced. Thermal analysis of the encapsulated PCM determined it to possess excellent thermal stability and a heat storage capacity of 30.43 J/g. Based on the research findings, the inclusion of ME-LWAs in surface pavement layers could be considered a viable solution for the control of surface temperatures in cold climates. Road safety and maintenance could benefit in terms of reduced ice periods and reduced treatments with salts and other anti-ice solutions.


Relationship between levels of the heavy metals lead, cadmium and mercury, and metallothionein in the gills and stomach of Crassostrea iredalei and Crassostrea glomerata.
Background: The objective of this study was to compare the levels of heavy metals (Pb, Hg, and Cd) and metallothionein (MT) in the gills and stomach of two species of mussels ( Crassostrea iredalei and Crassostrea glomerata), and to observe the ability of the mussels to absorb the heavy metals Pb, Hg and Cd present in the water. Methods: The mussels were obtained from Mayangan, Kenjeran and Gresik ports, East Java, Indonesia. MT levels were determined using ELISA. Heavy metal levels of Pb, Hg and Cd were assayed using atomic absorption spectrophotometry. Results: The levels of Pb and Cd in water were below the maximum permissible levels for local water quality standards. By contrast, the level of Hg in the water was above the maximum permissible levels for water quality standards. At Mayangan Port (Station 1), the level of Pb was higher than Hg and Cd. Levels of MT and heavy metals varied greatly among of C. iredalei and C. glomerata individuals, but were always higher in the gills than in the stomach. The highest MT level (160,250 ng/g) was observed at Kenjeran Port (Station 2). MT levels were shown to be significantly associated with heavy metal level ( P<0.0001). Conclusions: This result indicates that MT may be responsible for the sequestration of these heavy metals, as has already been observed in terrestrial animals.


[The secular trend in growth].
The secular changes in growth of the Spanish male population throughout the current century are presented. Data are adult mean height: 163.4 cm in 1910 and 174.5 cm in 1995. The increase was produced after 1950 and specially after 1965. From this last date, the increase by decade was between 2 and 2.9 cm. Lately the increase is gone on but more slowly. It was possible establish a direct relationship between height and culture and income of population. Maturation of female was studied using the menarcheal age. In 1998 it was 12.5 years. The menarcheal ag is now 0.3 years before than 15 years ago.


Changes in total, CD4+, and CD8+ lymphocytes during pregnancy and 1 year postpartum in human immunodeficiency virus-infected women. The Women and Infants Transmission Study.
To assess changes in lymphocyte subsets during pregnancy and 1 year postpartum in human immunodeficiency virus (HIV)-infected women. Changes in CD4+ and CD8+ cell counts, CD4 and CD8 percent, CD4/CD8 ratio, and total lymphocyte count and percent were assessed in each of 226 HIV-infected women followed during pregnancy and 1 year postpartum, and for each of 100 nonpregnant HIV-infected woman during 1 year. Trends over time were compared between pregnant women with and without several covariates. Postpartum changes over a 1-year period were compared to a 1-year period in the nonpregnant cohort. There was a mean increase of 2.76 per week in the CD4+ cell count during pregnancy (P = .04). No other characteristics changed significantly during pregnancy. The mean CD4+ and CD8+ cell counts, the CD8 percent, and the total lymphocyte count and percent increased immediately postdelivery. During the first postpartum year, there were statistically significant declines in the absolute CD4+ and CD8+ cell counts, the relative CD4 and CD8 percentages, and the total lymphocyte count and percentage. The rate of change for CD4+ and CD8+ counts, but not for CD4 percent, was less during 1 year in the nonpregnant cohort than in the first postpartum year, and the CD8 percent increased in the nonpregnant women. A wide variability in trends of all measurements during pregnancy was seen. During pregnancy, CD4 and CD8 percentages remain stable. There are no clinically significant changes during pregnancy or postpartum in any lymphocyte parameter we assessed. Postpartum changes in lymphocytes and lymphocyte subsets most likely represent a return to baseline from the physiologic changes of pregnancy and the immediate postpartum period.


Metagenomic Insights Into the Taxonomic and Functional Features of Kinema, a Traditional Fermented Soybean Product of Sikkim Himalaya.
Kinema is an ethnic, naturally fermented soybean product consumed in the Sikkim Himalayan region of India. In the present study, the whole metagenome sequencing approach was adopted to examine the microbial diversity and related functional potential of Kinema, consumed in different seasons. Firmicutes was the abundant phylum in Kinema, ranging from 82.31 to 93.99% in different seasons, followed by Actinobacteria and Proteobacteria. At the species level, the prevalent microorganisms were Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus licheniformis, Corynebacterium glutamicum, Bacillus pumilus, and Lactococcus lactis. The abundance of microbial species varied significantly in different seasons. Further, the genomic presence of some undesirable microbes like Bacillus cereus, Proteus mirabilis, Staphylococcus aureus, Proteus penneri, Enterococcus faecalis, and Staphylococcus saprophyticus, were also detected in the specific season. The metagenomic analysis also revealed the existence of bacteriophages belonging to the family Siphoviridae, Myoviridae, and Podoviridae. Examination of the metabolic potential of the Kinema metagenome depicted information about the biocatalysts, presumably involved in the transformation of protein and carbohydrate polymers into bioactive molecules of health-beneficial effects. The genomic resource of several desirable enzymes was identified, such as β-galactosidase, β-glucosidase, β-xylosidase, and glutamate decarboxylase, etc. The catalytic function of a novel glutamate decarboxylase gene was validated for the biosynthesis of γ-aminobutyric acid (GABA). The results of the present study highlight the microbial and genomic resources associated with Kinema, and its importance in functional food industry.


Regulation of plant arginase by wounding, jasmonate, and the phytotoxin coronatine.
In mammalian cells, induced expression of arginase in response to wound trauma and pathogen infection plays an important role in regulating the metabolism of L-arginine to either polyamines or nitric oxide (NO). In higher plants, which also utilize arginine for the production of polyamines and NO, the potential role of arginase as a control point for arginine homeostasis has not been investigated. Here, we report the characterization of two genes (LeARG1 and LeARG2) from Lycopersicon esculentum (tomato) that encode arginase. Phylogenic analysis showed that LeARG1 and -2, like all other plant arginases, are more similar to agmatinase than to arginases from vertebrates, fungi, and bacteria. Nevertheless, recombinant LeARG1 and -2 exhibited specificity for L-arginine over agmatine and related guanidino substrates. The plant enzymes, like mammalian arginases, were inhibited (K(i) approximately 14 microM) by the NO precursor N(G)-hydroxy-L-arginine. These results indicate that plant arginases define a distinct group of ureohydrolases that function as authentic L-arginases. LeARG1 and LeARG2 transcripts accumulated to their highest levels in reproductive tissues. In leaves, LeARG2 expression and arginase activity were induced in response to wounding and treatment with jasmonic acid (JA), a potent signal for plant defense responses. Wound- and JA-induced expression of LeARG2 was not observed in the tomato jasmonic acid-insensitive1 mutant, indicating that this response is strictly dependent on an intact JA signal transduction pathway. Infection of wild-type plants with a virulent strain of Pseudomonas syringae pv. tomato also up-regulated LeARG2 expression and arginase activity. This response was mediated by the bacterial phytotoxin coronatine, which exerts its virulence effects by co-opting the host JA signaling pathway. These results highlight striking similarities in the regulation of arginase in plants and animals and suggest that stress-induced arginase may perform similar roles in diverse biological systems.


Poor social integration and suicide: fact or artifact? A case-control study.
Sociological studies have shown that poor social integration confers suicide risk. It is not known whether poor integration amplifies risk after adjusting statistically for the effects of mental disorders and employment status. A case-control design was used to compare 86 suicides and 86 living controls 50 years of age and older, matched on age, gender, race, and county of residence. Structured interviews were conducted with proxy respondents for suicides and controls. Social integration was defined in reference to two broad levels of analysis: family (e.g. sibship status, childrearing status) and social/ community (e.g. social interaction, religious participation, community involvement). Bivariate analyses showed that suicides were less likely to be married, have children, or live with family. They were less likely to engage in religious practice or community activities and they had lower levels of social interaction. A trimmed logistic regression model showed that marital status, social interaction and religious involvement were all associated with suicide even after statistical adjusting for the effects of affective disorder and employment status. Adding substance abuse to the model eliminated the effects of religious involvement. The association between family and social/community indicators of poor social integration and suicide is robust and largely independent of the presence of mental disorders. Findings could be used to enhance screening instruments and identify problem behaviors, such as low levels of social interaction, which could be targeted for intervention.


Type X collagen synthesis during in vitro development of chick embryo tibial chondrocytes.
In the developing chick embryo tibia type X collagen is synthesized by chondrocytes from regions of hypertrophy and not by chondrocytes from other regions (Capasso, O., G. Tajana, and R. Cancedda, 1984, Mol. Cell. Biol. 4:1163-1168; Schmid, T. M., and T. F. Linsenmayer, 1985, Dev. Biol. 107:375-381). To investigate further the relationship between differentiation of endochondral chondrocytes and type X collagen synthesis we have developed a novel culture system for chondrocytes from 29-31-stage chick embryo tibiae. At the beginning of the culture these chondrocytes are small and synthesize type II and not type X collagen, but when grown on agarose-coated dishes they further differentiate into hypertrophic chondrocytes that synthesize type X collagen. The synthesis of type X collagen has been monitored in cultured cells by analysis of labeled collagens and in vitro translation of mRNAs. When the freshly dissociated chondrocytes are plated in anchorage-permissive dishes, most of the cells attach and dedifferentiate, as revealed by their fibroblastic morphology. Dedifferentiated chondrocytes, after several passages, can still reexpress the differentiated phenotype and continue their development to hypertrophic, type X collagen-synthesizing chondrocytes. Hypertrophic chondrocytes, when plated in anchorage permissive dishes, attach, maintaining the differentiated phenotype, and continue the synthesis of type X collagen.


Comparison of three arterial pulse waveform classification techniques.
Peripheral pulse waveforms can become stretched and damped with increasing severity of peripheral vascular disease (PVD) and hence could provide valuable diagnostic information. This study compares the diagnostic performance of 3 established classification techniques (a linear discriminant classifier, a k-nearest neighbour classifier, and an artificial neural network) for the detection of lower limb arterial disease from pulse waveforms obtained using photoelectric plethysmography (PPG). Pulse waveforms and pre- and post-exercise Doppler ultrasound ankle to brachial pressure indices (ABPI) were obtained from patients attending a vascular measurement laboratory. A single PPG pulse from each big toe was recorded direct to computer, pre-processed, and then used as classifier input data. The correct classifier outputs were the corresponding ABPI diagnostic classification. Pulse and ABPI measurements from 100 legs were used as training data for each classifier, and the computed classifications for pulses from a further 266 legs were then compared with their ABPI diagnoses. The diagnostic accuracy of the artificial neural network (80%; was higher than for the optimized k-nearest neighbour classifier (k = 27, accuracy 76% and the linear discriminant classifier (71%). The Kappa measure of agreement which excludes chance was highest for the artificial neural network (57%) and significantly higher than that of the linear discriminant classifier (Kappa 40%, p < 0.05). The value of Kappa for the optimized k-nearest neighbour classifier (k = 27) was intermediate at 47%. This study has shown that classifiers can be taught to discriminate between small, and perhaps subtle, differences in features. We have demonstrated that artificial neural networks can be used to classify arterial pulse waveforms, and can perform better overall than k-nearest neighbour or linear discriminant classifiers for this application.


On the equivalence of superordinate concepts.
Psychological studies of superordinates have generally treated them as equivalent. However, many languages distinguish mass superordinates (e.g., clothing) from count superordinates (e.g., vehicle). In the present paper, experimental evidence is presented which suggests that the two types of superordinates are conceptually distinct as well. One study showed that the members of mass superordinates more often co-occur. A second study showed that people more often interact with the members of mass superordinates in temporal proximity whereas people primarily interact with single members of count superordinates on a specific occasion. Also, properties that characterize an individual are a more salient aspect of count superordinates. These findings imply that mass superordinates refer to unindividuated groups of objects, united by spatial and functional contiguity. Two other studies supported this hypothesis by showing that the class inclusion relation between a single object and a category is stronger for count superordinates. Taken together, the findings suggest that mass superordinates are not true taxonomic categories. We relate the findings to previous views of superordinates and to the count/mass distinction in general.


Overexpression of OSM and IL-6 impacts the polarization of pro-fibrotic macrophages and the development of bleomycin-induced lung fibrosis.
Although recent evidence indicates that gp130 cytokines, Oncostatin M (OSM) and IL-6 are involved in alternative programming of macrophages, their role in lung fibrogenesis is poorly understood. Here, we investigated the effect of transient adenoviral overexpression of OSM or IL-6 in mice during bleomycin-induced lung fibrosis. Lung fibrosis and M2-like macrophage accumulation were assessed by immunohistochemistry, western blotting, gene expression and flow cytometry. Ex-vivo isolated alveolar and bone marrow-derived macrophages were examined for M2-like programming and signalling. Airway physiology measurements at day 21 demonstrated that overexpression of OSM or IL-6 exacerbated bleomycin-induced lung elastance, consistent with histopathological assessment of extracellular matrix and myofibroblast accumulation. Flow cytometry analysis at day 7 showed increased numbers of M2-like macrophages in lungs of mice exposed to bleomycin and OSM or IL-6. These macrophages expressed the IL-6Rα, but were deficient for OSMRβ, suggesting that IL-6, but not OSM, may directly induce alternative macrophage activation. In conclusion, the gp130 cytokines IL-6 and OSM contribute to the accumulation of profibrotic macrophages and enhancement of bleomycin-induced lung fibrosis. This study suggests that therapeutic strategies targeting these cytokines or their receptors may be beneficial to prevent the accumulation of M2-like macrophages and the progression of fibrotic lung disease.


Global health strategies versus local primary health care priorities--a case study of national immunisation days in Southern Africa.
Building on the successful eradication of smallpox, the World Health Organisation, together with other agencies, is now moving quickly to the eradication of poliomyelitis, originally aimed for the year 2000. Plans for the subsequent global eradication of measles are in an advanced stage. Eradication of both polio and measles incorporate as a fundamental strategy high routine coverage, surveillance and special national immunisation days (NIDs), which are supplementary to routine vaccination services. There has been a lively debate on whether poor countries, with many health problems that could be controlled, should divert their limited resources for a global goal of eradication that may have low priority for their children. From a cost-effectiveness perspective, NIDs are fully justifiable. However, field observations in sub-saharan Africa show that NIDs divert resources and, to a certain extent, attention from the development of comprehensive primary health care (PHC). The routine immunisation coverage rates dropped on average since the introduction of NIDs in 1996, which is contrary to what was observed in the western Pacific and other regions. The additional investment to be made when moving from disease control to eradication may exceed the financial capacity of an individual country. Since the industrialised countries benefit most from eradication, they should take responsibility for covering the needs of those countries that cannot afford the investment. The WHO's frequent argument that NIDs are promotive to PHC is not confirmed in the southern African region. The authors think that the WHO should, therefore, focus its attention on diminishing the negative side-effects of NIDs and on getting the positive side-effects incorporated in the integrated health services in a sustainable way.


A study protocol for a randomised controlled trial evaluating the effects of intraoperative computed tomography on the outcomes of zygomatic fractures.
Zygomaticomaxillary complex (ZMC) and zygomatic arch (ZA) fractures are common injuries resulting from facial trauma and frequently require surgical management (Huang et al., Craniomaxillofac Trauma Reconstr 8(4):271-6, 2015). A substantial number of post-operative functional and cosmetic complications can arise from the surgical management of these fractures. These include scarring, inadequate facial profile restoration, facial asymmetries and diplopia (Ellis et al. J Oral Maxillofac Surg 54(4):386-400, 1996; Yang et al. Oral Maxillofac Surg Clin North Am 23(1):31-45, 2011; Kloss et al. Int J Oral Maxillofac Surg 40(1):33-7, 2011). Intuitively, most of these aforementioned complications arise as a result of inadequate fracture reduction; however, current standard practice is to assess reduction post-operatively through plain radiographs or computed tomography (CT) scans. The role of intra-operative CT scanning to assess the reduction of ZMC/ZA fractures and the potential impact on complications, has thus far not been established. This is a prospective randomised controlled trial currently being undertaken at the Royal Brisbane and Women's Hospital. All patients who require operative management of their ZMC or ZA fractures are offered enrollment in the trial. The patients are randomised into two groups: interventional (intra-operative CT) and control (no intra-operative CT). All patients in each group will have post-operative radiographs taken. From these radiographs, the reduction of the ZMC and/or ZA fracture is graded by a blinded assessor. Patients will be reviewed in clinic at 1 week and 6 weeks post-surgery. During these consultations, all patients will be assessed for scarring, diplopia, facial profile restoration and need for revision surgery. Many complications associated with surgical management of ZMC and ZA fractures involve poor aesthetic results as a direct consequence of inadequate fracture reduction. Inadequate fracture reduction is predictable given that small incisions are used and only limited visualisation of the fractures is possible during the procedure. This is due to a desire to limit scarring and reduce the risk of damage to vital structures in an aesthetically sensitive region of the body. It follows that an intraoperative adjunctive tool such as a CT scan, which can assist in visualisation of the fractures and the subsequent reduction, could potentially improve reduction and reduce complications. Australian New Zealand Clinical Trials Registry, ACTRN12616000693426 . Registered on 26 May 2016.


Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial.
Traumatic brain injury (TBI) caused by a high-speed transportation accident results in a mechanism of injury commonly described as diffuse axonal injury (DAI), which is associated with a reduction in dopamine turnover in the brain. Because of its affect on both dopamine and N-methyl-D-aspartate (NMDA) channels, amantadine has been the subject of considerable interest and clinical use in acute TBI. In this study, 35 subjects, who had a TBI in a transportation accident and were initially seen with a Glasgow Coma Scale score of 10 or less within the first 24 hours after admission, were randomly assigned to a double-blind, placebo-controlled, crossover design trial. Amantadine, 200 mg, or placebo was each administered for 6 weeks (12 weeks total) to patients who were recruited consecutively. There was an improvement in the Mini-Mental Status (MMSE) scores of 14.3 points (P =.0185), Disability Rating Scale (DRS) score of 9.8 points (P =.0022), Glasgow Outcome Scale (GOS) score of 0.8 points (P =.0077), and in the FIM Cognitive score (FIM-cog) of 15.1 points (P =.0033) in the group that received amantadine during the first 6 weeks (group 1), but there was no improvement in the second 6 weeks on placebo (P >.05). In group 2 (active drug second 6 weeks), there was an improvement in the MMSE of 10.5 points, in the DRS of 9.4 points (P =.0006), in the GOS of 0.5 points (P =.0231), and in the FIM-cog of 11.3 points (P =.0030, Wilcoxon signed rank) spontaneously in the first 6 weeks on placebo (P =.0015). However, group 2 gained a statistically significant additional 6.3 points of recovery in the MMSE (P =.0409), 3.8 points in the DRS (P =.0099), 0.5 points in the GOS (P =.4008), and 5.2 points in the FIM-cog (P =.0173, Wilcoxon signed rank) between the sixth week and the twelfth week of treatment on the active drug. There was a consistent trend toward a more rapid functional improvement regardless of when a patient with DAI-associated TBI was started on amantadine in the first 3 months after injury.


Challenges in conducting trials for pediatric tuberculous meningitis: lessons from the field.
SETTING: TBM-KIDS is a phase I/II trial enrolling children with tuberculous meningitis (TBM) in three tertiary referral centers in India and Malawi.OBJECTIVE: To describe the challenges encountered in conducting the first randomized clinical trial of antimicrobial agents in pediatric TBM.DESIGN: The sources of the data were primarily monthly trial reports, non-enrollment case report forms, study diaries and registers maintained for recruitment, experiences shared by key team members during regular study calls and comments from site review visits. We reviewed, broadly categorized, and describe in detail the challenges encountered by study teams in trial implementation.RESULTS: Over 17 months, 3371 children with clinical presentations consistent with meningoencephalitis or undergoing lumbar puncture were assessed for eligibility; 21 (<1%) met enrollment criteria. We encountered challenges related to diagnosis, management of sick children, large catchment areas, adverse event attribution, concomitant medications, infrastructure requirements, expensive pediatric formulations with short expiry, and detection of treatment response in a highly variable disease across the age continuum. Training and adaptation of tools for neurocognitive and neurologic function assessment were necessary. Special care was undertaken to explain study participation to distraught caregivers and manage children longitudinally.CONCLUSION: Interventional trials in pediatric TBM are challenging but are critically important for improving the treatment of a disease that disables children physically, cognitively and emotionally. Sharing these challenges may help to address them more effectively as a TB research community and to advance treatments for this at-risk population.


Proton and Heavy Particle Intracranial Radiosurgery.
Stereotactic radiosurgery (SRS) involves the delivery of a highly conformal ablative dose of radiation to both benign and malignant targets. This has traditionally been accomplished in a single fraction; however, fractionated approaches involving five or fewer treatments have been delivered for larger lesions, as well as lesions in close proximity to radiosensitive structures. The clinical utilization of SRS has overwhelmingly involved photon-based sources via dedicated radiosurgery platforms (e.g., Gamma Knife® and Cyberknife®) or specialized linear accelerators. While photon-based methods have been shown to be highly effective, advancements are sought for improved dose precision, treatment duration, and radiobiologic effect, among others, particularly in the setting of repeat irradiation. Particle-based techniques (e.g., protons and carbon ions) may improve many of these shortcomings. Specifically, the presence of a Bragg Peak with particle therapy at target depth allows for marked minimization of distal dose delivery, thus mitigating the risk of toxicity to organs at risk. Carbon ions also exhibit a higher linear energy transfer than photons and protons, allowing for greater relative biological effectiveness. While the data are limited, utilization of proton radiosurgery in the setting of brain metastases has been shown to demonstrate 1-year local control rates >90%, which are comparable to that of photon-based radiosurgery. Prospective studies are needed to further validate the safety and efficacy of this treatment modality. We aim to provide a comprehensive overview of clinical evidence in the use of particle therapy-based radiosurgery.


Genome-wide screening for DNA variants associated with reading and language traits.
Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome-wide association scan (GWAS) meta-analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading- and language-related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P ≈ 10(-7) for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on-going international efforts to identify genes contributing to reading and language skills.


First evidence for a Vibrio strain pathogenic to Mytilus edulis altering hemocyte immune capacities.
Bacterial isolates were obtained from mortality events affecting Mytilus edulis and reported by professionals in 2010-2013 or from mussel microflora. Experimental infections allowed the selection of two isolates affiliated to Vibrio splendidus/Vibrio hemicentroti type strains: a virulent 10/068 1T1 (76.6% and 90% mortalities in 24 h and 96 h) and an innocuous 12/056 M24T1 (0% and 23.3% in 24 h and 96 h). These two strains were GFP-tagged and validated for their growth characteristics and virulence as genuine models for exposure. Then, host cellular immune responses to the microbial invaders were assessed. In the presence of the virulent strain, hemocyte motility was instantaneously enhanced but markedly slowed down after 2 h exposure. By contrast, hemocyte velocity increased in the presence of the innocuous 12/056 M24T1. At the same time interval, 10/068 1T1 invaded hemocytes and was more rapidly internalized than the innocuous strain. Extracellular products (ECPs) prepared from 10/068 1T1 cultures significantly inhibited phagocytic activity while 12/056 M24T1 ECPs had no effect. Furthermore, the pathogenic strain and its ECPs inhibited oxidative burst unlike 12/056 M24T1 strain/ECPs which enhanced ROS production. Taken together, our results suggest that the mussel pathogen 10/068 1T1 may escape immune response by altering hemocytes functions.


Chromosome loading of cohesin depends on conserved residues in Scc3.
Cohesin is essential for sister chromatid cohesion, which ensures equal segregation of the chromatids to daughter cells. However, the molecular mechanism by which cohesin mediates this function is elusive. Scc3, one of the four core subunits of cohesin, is vital to cohesin activity. However, the mechanism by which Scc3 contributes to the activity and identity of its functional domains is not fully understood. Here, we describe an in-frame five-amino acid insertion mutation after glutamic acid 704 (scc3-E704ins) in yeast Scc3, located in the middle of the second armadillo repeat. Mutated cohesin-scc3-E704ins complexes are unable to establish cohesion. Detailed molecular and genetic analyses revealed that the mutated cohesin has reduced affinity to the Scc2 loader. This inhibits its enrichment at centromeres and chromosomal arms. Mutant complexes show a slow diffusion rate in live cells suggesting that they induce a major conformational change in the complex. The analysis of systematic mutations in the insertion region of Scc3 revealed two conserved aspartic acid residues that are essential for the activity. The study offers a better understanding of the contribution of Scc3 to cohesin activity and the mechanism by which cohesin tethers the sister chromatids during the cell cycle.


A genome-wide analysis of MADS-box genes in peach [Prunus persica (L.) Batsch].
MADS-box genes encode a family of eukaryotic transcription factors distinguished by the presence of a highly-conserved ~58 amino acid DNA-binding and dimerization domain (the MADS-box). The central role played by MADS-box genes in peach endodormancy regulation led us to examine this large gene family in more detail. We identified the locations and sequences of 79 MADS-box genes in peach, separated them into established subfamilies, and broadly surveyed their tissue-specific and dormancy-induced expression patterns using next-generation sequencing. We then focused on the dormancy-related SVP/AGL24 and FLC subfamilies, comparing their numbers and phylogenetic relationships with those of other sequenced woody perennial genomes. We identified 79 MADS-box genes distributed across all eight peach chromosomes and frequently located in clusters of two or more genes. They encode proteins with a mean length of 248 ± 72 amino acids and include representatives from most of the thirteen Type II (MIKC) subfamilies, as well as members of the Type I Mα, Mβ, and Mγ subfamilies. Most Type I genes were present in species-specific monophyletic lineages, and their expression in the peach sporophyte was low or absent. Most Type II genes had Arabidopsis orthologs and were expressed at much higher levels throughout vegetative and fruit tissues. During short-day-induced growth cessation, seven Type II genes from the SVP/AGL24, AGL17, and SEP subfamilies showed significant changes in expression. Phylogenetic analyses indicated that multiple, independent expansions have taken place within the SVP/AGL24 and FLC lineages in woody perennial species. Most Type I genes appear to have arisen through tandem duplications after the divergence of the Arabidopsis and peach lineages, whereas Type II genes appear to have increased following whole genome duplication events. An exception to the latter rule occurs in the FLC and SVP/AGL24 Type II subfamilies, in which species-specific tandem duplicates have been retained in a number of perennial species. These subfamilies comprise part of a genetic toolkit that regulates endodormancy transitions, but phylogenetic and expression data suggest that individual orthologs may not function identically across all species.


The Myeloid Cell Compartment-Cell by Cell.
Myeloid cells are a major cellular compartment of the immune system comprising monocytes, dendritic cells, tissue macrophages, and granulocytes. Models of cellular ontogeny, activation, differentiation, and tissue-specific functions of myeloid cells have been revisited during the last years with surprising results; for example, most tissue macrophages are yolk sac derived, monocytes and macrophages follow a multidimensional model of activation, and tissue signals have a significant impact on the functionality of all these cells. While these exciting results have brought these cells back to center stage, their enormous plasticity and heterogeneity, during both homeostasis and disease, are far from understood. At the same time, the ongoing revolution in single-cell genomics, with single-cell RNA sequencing (scRNA-seq) leading the way, promises to change this. Prevailing models of hematopoiesis with distinct intermediates are challenged by scRNA-seq data suggesting more continuous developmental trajectories in the myeloid cell compartment. Cell subset structures previously defined by protein marker expression need to be revised based on unbiased analyses of scRNA-seq data. Particularly in inflammatory conditions, myeloid cells exhibit substantially vaster heterogeneity than previously anticipated, and work performed within large international projects, such as the Human Cell Atlas, has already revealed novel tissue macrophage subsets. Based on these exciting developments, we propose the next steps to a full understanding of the myeloid cell compartment in health and diseases.


The Reflection Room®: Moving from Death-Avoiding to Death-Discussing.
We developed, implemented, and evaluated a participatory arts-based storytelling initiative called the Reflection Room project. Our aim was to investigate if visiting a Reflection Room, (1) creates opportunities for disclosing emotions and processing thoughts, (2) increases comfort discussing dying and death, and (3) supports advance care planning (ACP), conversations. In the pilot phase of the Reflection Room project, a Reflection Room was installed in 25 sites across Canada from 2016-2017. Data collection included reflection cards (n = 463), and surveys completed by visitors upon exiting a room (n = 271) and 3 months later (n = 50). Analysis involved theoretically driven coding, inductive content analysis, and descriptive statistics. We found reflections contained both emotional disclosures and reflective processing. Survey data indicated visiting a Reflection Room increased comfort in thinking and talking about dying and death as well as the likelihood of engaging in ACP. In the future, we will explore the extent to which the project fosters social connections and well-being.


Presenilin-1 differentially facilitates endoproteolysis of the beta-amyloid precursor protein and Notch.
Mutations in the presenilin-1 (PS1) gene are associated with Alzheimer's disease and cause increased secretion of the neurotoxic amyloid-beta peptide (Abeta). Critical intramembraneous aspartates at residues 257 and 385 are required for the function of PS1 protein. Here we investigate the biological function of a naturally occurring PS1 splice variant (PS1 Deltaexon 8), which lacks the critical aspartate 257. Cell lines that stably express PS1 Deltaexon 8 or a PS1 protein in which aspartate residue 257 is mutated secrete significant levels of Abeta, whereas Abeta generation is severely reduced in cells transfected with PS1 containing a mutation of aspartate 385. In contrast, endoproteolytic processing of Notch is almost completely inhibited in cell lines expressing any of the PS1 variants that lack one of the critical aspartates. These data indicate that PS1 may differentially facilitate gamma-secretase-mediated generation of Abeta and endoproteolysis of Notch.


Association of exposure to violence and potential traumatic events with self-reported physical and mental health status in the Central African Republic.
For decades, the Central African Republic (CAR) has experienced violence, economic stagnation, and institutional failure. The latest wave of violence erupted in 2001 and continues to this day in some areas. Yet there has been little attention to the conflict and even less research to document and quantify the conflict's human cost. To study levels of violence in CAR, including mortality levels, and the association between exposure to violence and traumatic events with self-reported physical and mental health status. Multistage stratified cluster random survey of 1879 adults 18 years or older in selected households conducted in 5 administrative units of CAR (3 in the south, which has been free from recent violence, and 2 in the north, in which violence continues) between October and December 2009. Mortality, morbidity, exposure to potential traumatic events, sense of insecurity, and meeting of symptom criteria for depression and anxiety using the Hopkins Symptom Checklist-25 with a cut-off score of 1.75. The crude mortality rate (CMR) was 4.9 deaths (95% confidence interval [CI], 4.6-5.1) per 1000 population per month and self-reported CMR due to violence was 0.8 deaths (95% CI, 0.6-1.0) per 1000 population per month. Thirty-five percent reported their physical health status as being good or very good while 29% described it as bad or very bad. Respondents in northern prefectures reported higher rates of mortality, exposure to trauma, and insecurity and lower levels of physical health and access to health services compared with those in the south. The estimated prevalences of symptoms of depression and anxiety were 55.3% (95% CI, 51.6%-59.0%) and 52.5% (95% CI, 48.1%-56.8%), respectively. Exposure to violence and self-reported physical health were statistically associated with mental health outcomes (P < .001). Anxiety symptom scores were higher for respondents in the northern prefectures than those in the south (t = 2.54, P = .01). A high proportion of adult respondents in CAR reported witnessing or having personally experienced traumatic events over the course of the conflicts, and more than half met symptom criteria for depression and anxiety.


Lunar anorthosites: rare-Earth and other elemental abundances.
Elemental abundances of major (Ti, Al, Fe, and Ca), minor (Na, Mn, and Cr), and trace elements [14 rare-earth elements (REE), Y, In, Cd, Rb, Cs, Ba, Co, and Sc] in lunar anorthosites separated from Apollo 11 sample 10085 coarse fines have been determined by means of instrumental and radiochemical neutron activation analysis. The REE distribution pattern of lunar anorthosites, relative to ordinary chondrites, has a positive Eu anomaly. On the assumption that (i) the lunar composition is similar to that of ordinary chondritic meteorites low in total Fe ( approximately 13 percent); (ii) lunar anorthosites are derived from highland cratering events and are representative of the highlands; and (iii) the moon differentiated into olivine, hypersthene, and basaltic and anorthositic phases, and plagioclase crysstallization began after approximately 93 percent solidification, then mass balance calculations yield approximately 30-kilometer and approximately 10-kilometer thicknesses for the lunar highlands for the melting and chemical differentiation of the entire moon and of the upper 200 kilometers, respectively. Corresponding thicknesses of the basaltic basement rocks were approximately 5 kilometers and approximately 2 kilometers, respectively. Alternatively, if the anorthosites of this study are representative of the highlands and the onset of plagioclase crystallization occurred after approximately 50 percent solidification of the initially melted moon, calculations with REE and Ba partition coefficients suggest that the REE and Ba abundances in the primeval moon were similar to those observed in basaltic achondrites.


Using Historical Atlas Data to Develop High-Resolution Distribution Models of Freshwater Fishes.
Understanding the spatial pattern of species distributions is fundamental in biogeography, and conservation and resource management applications. Most species distribution models (SDMs) require or prefer species presence and absence data for adequate estimation of model parameters. However, observations with unreliable or unreported species absences dominate and limit the implementation of SDMs. Presence-only models generally yield less accurate predictions of species distribution, and make it difficult to incorporate spatial autocorrelation. The availability of large amounts of historical presence records for freshwater fishes of the United States provides an opportunity for deriving reliable absences from data reported as presence-only, when sampling was predominantly community-based. In this study, we used boosted regression trees (BRT), logistic regression, and MaxEnt models to assess the performance of a historical metacommunity database with inferred absences, for modeling fish distributions, investigating the effect of model choice and data properties thereby. With models of the distribution of 76 native, non-game fish species of varied traits and rarity attributes in four river basins across the United States, we show that model accuracy depends on data quality (e.g., sample size, location precision), species' rarity, statistical modeling technique, and consideration of spatial autocorrelation. The cross-validation area under the receiver-operating-characteristic curve (AUC) tended to be high in the spatial presence-absence models at the highest level of resolution for species with large geographic ranges and small local populations. Prevalence affected training but not validation AUC. The key habitat predictors identified and the fish-habitat relationships evaluated through partial dependence plots corroborated most previous studies. The community-based SDM framework broadens our capability to model species distributions by innovatively removing the constraint of lack of species absence data, thus providing a robust prediction of distribution for stream fishes in other regions where historical data exist, and for other taxa (e.g., benthic macroinvertebrates, birds) usually observed by community-based sampling designs.


Prevalence and correlates of smoking on the roof of the world.
To determine the prevalence and correlates of cigarette smoking among adults in high mountain rural areas of northern Pakistan. Cross sectional survey. A sample of 4203 adults (aged 18 years and over) were selected by stratified random sampling from 16 villages. Self reported smoking prevalence; age of smoking initiation; daily cigarette consumption and association between current smoking and sociodemographic variables, use of snuff, wine, body mass index, blood pressure, family history of stroke, and hypertension. 614/1406 men (43.7%) and 154/2797 (5.5%) women reported smoking cigarettes. The age standardised prevalence of smoking was 40.5% for men and 6.3% for women. Men were more likely (odds ratio (OR) 6.5, 95% confidence interval (CI) 4.75 to 8.79) to be smokers. Smokers were more likely to use snuff (OR 1.39, 95% CI 1.12 to 1.73), drink wine (OR 3.47, 95% CI 2.81 to 4.29), and were more likely to work as farmers (OR 1.55, 95% CI 1.05 to 2.29) or shopkeepers (OR 2.63, 95% CI 1.67 to 4.14). Individuals with college level education and with desirable body mass index were less likely to smoke (OR 0.55, 95% CI 0.35 to 0.87; OR 0.74, 95% CI 0.57 to 0.96). Cigarette smoking is a major public health problem in this high mountain community of Pakistan, particularly among the male population, the majority of whom begin to smoke quite early in life. A comprehensive tobacco control effort incorporated into the existing community based health infrastructure is needed.


Lack of correlation between P-glycoprotein and chemotherapy resistance in nasal NK/T-cell lymphomas.
Thirty patients with nasal natural killer (NK)/T-cell lymphoma, who underwent systemic chemotherapy with or without involved-field radiotherapy between 1993 and 1998, were retrospectively reviewed to determine the clinical significance of P-glycoprotein immunohistochemically identified in tumor specimens. Eighty percent of previously untreated patients expressed P-glycoprotein. According to P-glycoprotein immunoreactivity, all patients with nasal NK/T-cell lymphoma were divided into 2 groups; (a) P-glycoprotein-negative group (N = 6) and (b) P-glycoprotein-positive group (N = 24). There was no significant difference in clinical profiles between both groups. Regardless of the P-glycoprotein expressions, Epstein-Barr virus genomes were almost identically detected in patients of the 2 groups. Contrary to our expectations, however, P-glycoprotein expressions were not found to be a strong predictor of chemotherapy resistance. Although 2 (33%) of 6 P-glycoprotein-negative patients and 10 (42%) of the 24 P-glycoprotein-positive patients showed a favorable response to systemic chemotherapy, 4 (67%) of 6 P-glycoprotein-negative patients did not achieve complete response (CR) to chemotherapy, which led to an early death, whereas 4 (17%) of the 24 P-glycoprotein-positive patients achieved CR to chemotherapy despite positive P-glycoprotein immunoreactivity. Overall, there were no significant differences in either CR rate or the response rate of patients in the two groups. Overall 5-year actuarial survival and disease-free survival for all patients were 44% and 47%, respectively, but no differences in survival rates were observed between 2 groups. (5-year actuarial survival rate: 33% for the P-glycoprotein-negative, 50% for the P-glycoprotein-positive) (P = 0.7093, log-rank). On univariate and multivariate analyses, P-glycoprotein expressions by immunohistochemical study were not found to be an important prognostic factor. Given these observations, we conclude that the molecular mechanisms of resistance to chemotherapy in nasal NK/T-cell lymphoma patients are not entirely dependent on P-glycoprotein, and that other complex mechanisms of drug action and resistance may be likely to be involved.


Dimensions of health system reform.
During recent years there has been a growth of worldwide interest in health system reform. Countries at all levels of economic development are engaged in a creative search for better ways of organizing and financing health care, while promoting the goals of equity, effectiveness, and efficiency. Together with economic, political, and ideological reasons, this search has been fueled by the need to find answers to the complexities posed by the epidemiologic transition, whereby many nations are facing the simultaneous burdens of old, unresolved problems and new, emerging challenges. In order to better understand reform attempts, it is necessary to develop a clear conception of the object of reform: the health system. This paper presents the health system as a set of relationships among five major groups of actors: the health care providers, the population, the state as a collective mediator, the organizations that generate resources, and the other sectors that produce services with health effects. The relationships among providers, population, and the state form the basis for a typology of health care modalities. The type and number of modalities present in a country make it possible to characterize its health system. In the last part, the paper proposes that health system reform operates at four policy levels: systemic, which deals with the institutional arrangements for regulation, financing, and delivery of services; programmatic, which specifies the priorities of the system, by defining a universal package of health care interventions; organizational, which is concerned with the actual production of services by focusing on issues of quality assurance and technical efficiency; and instrumental, which generates the institutional intelligence for improving system performance through information, research, technological innovation, and human resource development. The dimensions of reform offer a repertoire of policy options, which need to be enriched by cross-national comparison of experiences and rigorous social experimentation. Maybe then reform will be a more systematic effort, and nations will be better able to learn from each other.


Modulation of human neutrophil function by monohydroxy-eicosatetraenoic acids.
The generation from arachidonic acid and purification of large quantities of a series of monohydroxy-eicosatetraenoic acids (HETEs) which differed only in the position of the hydroxyl group permitted an in vitro analysis of the relative effects of the HETEs on a variety of human neutrophil functions. All of the HETEs elicited maximal neutrophil chemotactic responses of comparable magnitude, but the chemotactic potencies exhibited a distinct rank order with 5-HETE greater than 8-HETE:9-HETE (85:15, w:w) greater than 11-HETE=12-L-HETE. Peak chemotactic responses were achieved at concentrations of 1 microgram/ml for 5-HETE, 5 microgram/ml for 8-HETE:9-HETE and 10 microgram/ml for 11-HETE and 12-L-HETE. In the absence of a concentration gradient, the HETEs were similar in potency with respect to the stimulation of neutrophil chemokinesis and the enhancement of the expression of neutrophil C3b receptors. At optimally chemotactic and chemokinetic concentrations, none of the HETEs stimulated the generation of superoxide by neutrophils, altered the expression of neutrophil IgG-Fc receptors, or evoked the release of lysosomal enzymes. Methyl esterification of 5-HETE and 12-L-HETE reduced the chemotactic activity to less than 12% of that of the parent compound. The HETE methyl esters competitively inhibited the chemotactic activity of the homologous free acids by approximately 50% at equimolar concentrations, without inhibiting the chemotactic activity of formyl-methionyl peptides or of chemotactic fragments of the fifth component of complement (C5fr). The stimulus specificity of the competitive inhibition of chemotaxis by HETE methyl esters and the functional selectivity of the HETEs as compared to the formyl-methionyl peptides and C5fr, which stimulate neutrophil oxidative metabolism and lysosomal enzyme release, suggest that HETEs activate human neutrophils by a unique mechanism.


Triclosan exposure induces immunotoxic impacts by disrupting the immunometabolism, detoxification, and cellular homeostasis in blood clam (Tegillarca granosa).
Omnipresent presence of triclosan (TCS) in aqueous environment puts a potential threat to organisms. However, it's poorly understood about its immunometabolic impacts of marine invertebrates. In present study, we use a representative bivalve blood clam (Tegillarca granosa) as a model, investigating the effects of TCS exposure at 20 and 200 μg/L for 28 days on immunometabolism, detoxification, and cellular homeostasis to explore feasible toxicity mechanisms. Results demonstrated that the clams exposed to TCS resulting in evident immunotoxic impacts on both cellular and humoral immune responses, through shifting metabolic pathways and substances, as well as suppressing the expressions of genes from the immune- and metabolism-related pathways. In addition, significant alterations in contents (or activity) of detoxification enzymes and the expression of key detoxification genes were detected in TCS-exposed clams. Moreover, exposure to TCS also disrupted cellular homeostasis of clams through increasing MDA contents and caspase activities, and promoting activation of the apoptosis-related genes. These findings suggested that TCS might induce immunotoxic impacts by disrupting the immunometabolism, detoxification, and cellular homeostasis.


[Clinico-pathogenetic aspects of peptic ulcer in children].
Overall 98 children with duodenal ulcer were examined. It is shown that the rise of the products of lipid peroxidation in gastric juice enhances the aggressive properties of gastric juice and stimulates defence reactions of the gastric mucosa and duodenum. Lipid oxidation and the antioxidant systems of gastric juice were discovered to be disordered. The changes thus revealed are of diagnostic importance for detecting the recurrent nature of the disease.


Ethyl Rosmarinate Protects High Glucose-Induced Injury in Human Endothelial Cells.
Ethyl rosmarinate (RAE) is one of the active constituents from Clinopodium chinense (Benth.) O. Kuntze, which is used for diabetic treatment in Chinese folk medicine. In this study, we investigated the protective effect of RAE on high glucose-induced injury in endothelial cells and explored its underlying mechanisms. Our results showed that both RAE and rosmarinic acid (RA) increased cell viability, decreased the production of reactive oxygen species (ROS), and attenuated high glucose-induced endothelial cells apoptosis in a dose-dependent manner, as evidenced by Hochest staining, Annexin V⁻FITC/PI double staining, and caspase-3 activity. RAE and RA both elevated Bcl-2 expression and reduced Bax expression, according to Western blot. We also found that LY294002 (phosphatidylinositol 3-kinase, or PI3K inhibitor) weakened the protective effect of RAE. In addition, PDTC (nuclear factor-κB, or NF-κB inhibitor) and SP600125 (c-Jun N-terminal kinase, or JNK inhibitor) could inhibit the apoptosis in endothelial cells caused by high glucose. Further, we demonstrated that RAE activated Akt, and the molecular docking analysis predicted that RAE showed more affinity with Akt than RA. Moreover, we found that RAE inhibited the activation of NF-κB and JNK. These results suggested that RAE protected endothelial cells from high glucose-induced apoptosis by alleviating reactive oxygen species (ROS) generation, and regulating the PI3K/Akt/Bcl-2 pathway, the NF-κB pathway, and the JNK pathway. In general, RAE showed greater potency than RA equivalent.


[Study of myoblast culture and myoblast transfer therapy in dystrophic mice].
In this report, we study the suitable conditions for myoblast cultures through analysis of myoblast growth and differentiation, and then try to develop a mouse model for myoblast transfer therapy (MTT). Recently, some research has indicated that Muscular Dystrophy Murine Mice (MDX) have an X-linked recessive dystrophin deficiency which is caused by dystrophin gene point mutation at the X chromosome. Therefore, MDX mice are usually used for MTT models of muscular dystrophy disease. Control mice, C57BL10/SCSN (B-10) were chosen as a source of normal myoblasts. Myoblasts isolated from the hindlimb muscle tissues of two- to three-day-old neonatal B-10 mice were cultured in vitro for one to seven days. Through our modifyied techniques of isolation and culturing conditions, a myoblast purity of 70% could be achieved, with fibroblast the only contaminating cell type. The proliferative capacity and the doubling time of myoblasts were counted from analysis of growth kinetics. While differentiative capacity was analyzed morphologically, we found the fusion of myoblasts was time-dependent. Immunostaining myoblasts of different stages with anti-dystrophin antibody showed that purified myoblasts with the capacity of fusion can express dystrophin and can be utilized as a donating source in MTT. In the MTT experiment, eight young MDX mice were injected with normal myoblasts at a concentration of 1 x 10(6) cells. All transplated mice received daily cyclosporine A injection for immunosuppression. Two to three months later, dystrophin was found in the myoblast-transferred muscles while staining immunocytochemically. The result suggests that we successfully transferred the normal dystrophin gene from the normal myoblasts into the MDX mice since their myoblast-injected muscle could express dystrophin.


Assessment of the umbilical cord outside of the delivery room. Part 2.
The umbilical cord is crucial to the growth and development of the fetus. Careful inspection in the delivery room and throughout the newborn period is essential. Part 1 of this 2-part series, entitled "Look Before You Clamp: Delivery Room Examination of the Umbilical Cord" (Advances in Neonatal Care, Vol. 2, No. 1, pp 19-26), reviewed umbilical problems that present in the delivery room. A number of subtle but significant umbilical cord abnormalities present outside the delivery room. These abnormalities will be the focus of Part 2 of this series. A review of the embryologic development of the umbilical cord enhances the clinician's understanding of umbilical abnormalities that present in the newborn period. The process of umbilical cord separation is outlined. Conditions associated with delayed cord separation are discussed. A systematic approach to the physical examination of the umbilicus is offered, with an emphasis on early detection of abnormalities. Common and uncommon physical findings, such as omphalitis, periumbilical necrotizing fascitis, vitelline duct remnants, and urachal anomalies are presented along with select photographs. A brief discussion of the clinical implications for newborn care is provided for the practicing clinician.


Effects of embryo culture media do not persist after implantation: a histological study in mice.
Is post-implantation embryonic development after blastocyst transfer affected by exposure to different assisted reproduction technology (ART) culture media? Fetal development and placental histology of ART embryos cultured in vitro in different ART media was not impaired compared with embryos grown in vivo. The application of different in vitro culture (IVC) media for human ART has an effect on birthweight of newborns. In the mouse model, differences in blastocyst formation were reported after culture in different ART media. Moreover, abnormalities in the liver and heart have been detected as a result of suboptimal IVC conditions. Fertilized oocytes from inbred and outbred breeding schemes were retrieved and either immediately transferred to foster mothers or incubated in control or human ART culture media up to the blastocyst stage prior to transfer. Placental and fetal anatomy and particularly bone development were evaluated. B6C3F1 female mice were used as oocyte donors after ovulation induction. C57Bl/6 and CD1 males were used for mating and CD1 females as foster mothers for embryo transfer. Fertilized oocytes were recovered from mated females and incubated in sequential human ART media (ISM1/ISM2 and HTF/Multiblast), in control media [KSOM(aa) and Whitten's medium] or grown in utero without IVC (zygote control). As in vivo, control B6C3F1 females were superovulated and left untreated. Fetuses and placentae were isolated by Caesarean section and analysed at 18.5 days post-coitum (dpc) for placenta composition and at 15.5 dpc for body weight, crown-rump length (CRL), fetal organ development, morphological development, total bone length and extent of bone ossification. No major differences in the number of implantation sites or in histological appearance of the placentae were detected. CRL of KSOM(aa) fetuses was higher compared with zygote control and Whitten's medium. Histological analysis of tissue sections revealed no gross morphological differences compared with the in vitro groups or in vivo controls. Furthermore, no changes in skeletal development and degree of ossification were observed. However, fibula and tibia of ISM1/ISM2 fetuses were longer than the respective ones from in vivo fetuses. Findings in the mouse embryo and fetus may not be fully transferable to humans. In addition to skeletal development and placentation, there may be other parameters, e.g. on the molecular level which respond to IVC in ART media. Some comparisons have limited statistical power. Our data suggest that once implantation is achieved, subsequent post-implantation development unfolds normally, resulting in healthy fetuses. With mouse models, we gather information for the safety of human ART culture media. Our mouse study is reassuring for the safety of ART conditions on human embryonic development, given the lack of bold detrimental effects observed in the mouse model. This work was supported by the Deutsche Forschungsgemeinschaft (BO 2540/4-1 and SCHL 394/9-1) and by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (S.L.G.); Bilateral grant NWO-DFG 63-258. None of the authors has any conflict of interest to declare. Not applicable.


A Quadruple-Hydrogen-Bonded Supramolecular Binder for High-Performance Silicon Anodes in Lithium-Ion Batteries.
With extremely high specific capacity, silicon has attracted enormous interest as a promising anode material for next-generation lithium-ion batteries. However, silicon suffers from a large volume variation during charge/discharge cycles, which leads to the pulverization of the silicon and subsequent separation from the conductive additives, eventually resulting in rapid capacity fading and poor cycle life. Here, it is shown that the utilization of a self-healable supramolecular polymer, which is facilely synthesized by copolymerization of tert-butyl acrylate and an ureido-pyrimidinone monomer followed by hydrolysis, can greatly reduce the side effects caused by the volume variation of silicon particles. The obtained polymer is demonstrated to have an excellent self-healing ability due to its quadruple-hydrogen-bonding dynamic interaction. An electrode using this self-healing supramolecular polymer as binder exhibits an initial discharge capacity as high as 4194 mAh g-1 and a Coulombic efficiency of 86.4%, and maintains a high capacity of 2638 mAh g-1 after 110 cycles, revealing significant improvement of the electrochemical performance in comparison with that of Si anodes using conventional binders. The supramolecular binder can be further applicable for silicon/carbon anodes and therefore this supramolecular strategy may increase the choice of amendable binders to improve the cycle life and energy density of high-capacity Li-ion batteries.


Validation of a Mouse Model to Disrupt LINC Complexes in a Cell-specific Manner.
Nuclear migration and anchorage within developing and adult tissues relies heavily upon large macromolecular protein assemblies called LInkers of the Nucleoskeleton and Cytoskeleton (LINC complexes). These protein scaffolds span the nuclear envelope and connect the interior of the nucleus to components of the surrounding cytoplasmic cytoskeleton. LINC complexes consist of two evolutionary-conserved protein families, Sun proteins and Nesprins that harbor C-terminal molecular signature motifs called the SUN and KASH domains, respectively. Sun proteins are transmembrane proteins of the inner nuclear membrane whose N-terminal nucleoplasmic domain interacts with the nuclear lamina while their C-terminal SUN domains protrudes into the perinuclear space and interacts with the KASH domain of Nesprins. Canonical Nesprin isoforms have a variable sized N-terminus that projects into the cytoplasm and interacts with components of the cytoskeleton. This protocol describes the validation of a dominant-negative transgenic mouse strategy that disrupts endogenous SUN/KASH interactions in a cell-type specific manner. Our approach is based on the Cre/Lox system that bypasses many drawbacks such as perinatal lethality and cell nonautonomous phenotypes that are associated with germline models of LINC complex inactivation. For this reason, this model provides a useful tool to understand the role of LINC complexes during development and homeostasis in a wide array of tissues.


Intensive Care Unit Hyperglycemia After Cardiac Surgery: Risk Factors and Clinical Outcomes.
Patients with hyperglycemia after cardiac surgery face increased morbidity and mortality due to postoperative complications. The main purpose of this study was to evaluate the incidence of postoperative hyperglycemia, the hyperglycemia risk factors, and its association with clinical outcomes in patients admitted to the cardiac surgery intensive care unit after cardiac surgery. Prospective, observational study. Single-center hospital. Two hundred ten consecutive postoperative cardiac surgery patients admitted to the cardiac surgery intensive care unit. Patients' blood glucose levels were evaluated immediately after cardiac surgery and every 3 hours daily for 7 days or earlier upon discharge. Intravenous insulin was administered as per the institution's protocol. Perioperative predisposing risk factors for hyperglycemia and clinical outcomes were assessed. Postoperative hyperglycemia, defined as glucose level ≥180 mg/dL, occurred in 30% of cardiac surgery patients. Diabetes mellitus (odds ratio [OR] 6.73; 95% CI [3.2-14.3]; p < 0.001), white blood cell count (OR 1.28; 95% CI [1.1-1.4]; p < 0.001), and EuroSCORE II (OR 1.20; 95% CI [1.1-1.4]; p = 0.004) emerged as independent prognostic factors for hyperglycemia. Moreover, patients with glucose ≥180 mg/dL had higher rates of acute kidney injury (34.9% v 18.9%, p = 0.013), longer duration of mechanical ventilation (959 v 720 min, p = 0.019), and sedation (711 v 574 min, p = 0.034), and higher levels of intensive care unit (ICU)-acquired weakness (14% v 5.5%, p = 0.027) and rate of multiorgan failure (6.3% v 0.7%, p = 0.02) compared with patients with glucose levels <180 mg/dL. In the intensive care unit, hyperglycemia occurs frequently in patients immediately after cardiac surgery. Diabetes, high EuroSCORE II, and preoperative leukocytosis are independent risk factors for postoperative hyperglycemia. Hyperglycemia is associated with worse clinical outcomes, including a higher rate of acute kidney injury and ICU-acquired weakness, greater duration of mechanical ventilation, and a higher rate of multiorgan failure.


Bacterial flora of the hemolymph of the blue crab, Callinectes sapidus: most probable numbers.
The hemolymph of 290 freshly collected blue crabs from Chincoteague Bay, Va., was sampled over a 15-month period from August 1968 through November 1969 and most probable numbers of bacteria were determined by tube dilution. The hemolymph of 18% of all crabs sampled was found to be sterile, with 16% sterility in summer and 23% in winter samples. Despite individual variations, male crabs as a group had a higher bacterial hemolymph burden than females, and among both sexes summer counts were higher than winter. The hemolymph of crabs with missing appendages had significantly higher counts than uninjuried crabs. The annual mean hemolymph most probable numbers per ml was 2,756 for males, 1,300 for females, and 1,876 for both sexes. The higher bacterial levels found in the hemolymph of male crabs may, in part, be explained by the fact that males, which predominated in the summer samples, had a higher incidence of injury and missing appendages than did females.


[Determination of interacting segments of tRNA(Leu) from cow mammary glands with homologous aminoacyl-tRNA-synthetase by a chemical modification method].
The interaction of the cow mammary gland tRNA(IAGLeu), having a long variable loop, with the cognate aminoacyl-tRNA synthetase has been studied by the alkylation with ethylnitrosourea. It was shown that leucyl-tRNA synthetase protects from alkylation 3'-phosphates of the nucleotides 12-13 in D-loop, 23-24 in D-stem and 37-43 in the anticodon arm of tRNA(IAGLeu). All regions of interaction with the aminoacyl-tRNA synthetase are located in the same plane of tRNA whereas the long variable loop is in another plane.


Thermogenic and lipogenic activities in brown adipose tissue of I-strain mice.
The thermogenic capacity of brown adipose tissue has been investigated in I-strain mice to determine whether this tissue could play a role in the lower efficiency of food utilization reported in this strain of mice. (1) As compared with C57BL mice (a control strain), interscapular-brown-adipose-tissue weight and lipid percentage were decreased by 40% and 13% respectively in I-strain mice. (2) Mitochondrial protein content and cytochrome c oxidase activity were similar in the two strains, but the number of mitochondrial GDP-binding sites and uncoupling-protein content were increased by 2-fold in I-strain mice. (3) Fatty acid synthetase and citrate-cleavage enzyme (units/mg of protein) were 3-fold higher in the brown adipose tissue of I-strain mice. These results indicate that I-strain mice possess a very active brown adipose tissue. This enhanced capacity of energy dissipation in brown adipose tissue could contribute to the decreased capacity of I-strain mice to store adipose tissue.


Immigrant parents' perceptions of school environment and children's mental health and behavior.
Research has increasingly identified the perception of school environment as an influential factor in children's lives. There has been sparse research attention, however, on the potential importance of parents' perceptions of school environment on child adjustment. This study examined the relationship between parents' perceptions of school environment and children's emotional and behavioral problems. Data were derived from the New Canadian Children and Youth Study, a study of the children (aged 4-6 and 11-13) of immigrant parents. Analyses focused on a subsample of Mainland Chinese, Hong Kong Chinese, and Filipino immigrants in a large metropolitan area. Parental perception of school environment was negatively associated with physical aggression in children even after controlling for child age and gender, parental characteristics, family functioning, and aspects of acculturation. In contrast, parental perception was not significantly related to symptoms of emotional distress in children. There were some ethnic differences in perception of school environment. Parental perception of school environment is important to the well-being of the children of immigrant parents, and reinforces the relevance of initiatives to improve the dynamics between parents and schools.


Cathepsin D expression in normal, hyperplastic and malignant endometrial tissue: an immunohistochemical analysis.
Cathepsin D (CathD), a lysosomal aspartyl protease secreted by normal and malignant cells, is considered to be involved in breakdown of the extracellular matrix. Aim of the present study was to determine the frequency and tissue distribution of CathD in normal, hyperplastic and malignant endometrium. Paraffin-fixed endometrial tissue was obtained from premenopausal women in the proliferative phase (n = 5), early secretory phase (n = 4) and late secretory phase (n = 4) as well as glandular-cystic hyperplasia (n = 5), endometrial polyps (n = 5), endometrial polyps from the use of tamoxifen (n = 5), adenomatous hyperplasia (AH) grade I (n = 5), grade II (n = 4), grade III (n = 5) and endometroid adenocarcinoma (n = 5). CathD expression was evaluated with the IRS score and ANOVA analysis was used for statistical evaluation. CathD was primarily localised in luminal and glandular epihelium with little staining in stromal cells. The expression of CathD was significantly higher during the late secretory phase than in the proliferative phase. Highest expression of CathD was observed in the late secretory phase and in glandular-cystic hyperplasia, whereas endometroid carcinoma showed no expression. A continuous increase in CathD expression was observed in AH, with a significant difference between AH grade I and III. In conclusion, CathD was found to be expressed in normal and hyperplastic endometrial tissue. CathD immunostaining in normal endometrial glands varied on the basis of the phase of the menstrual cycle, suggesting physiological functions of CathD in endometrial maturation and degradation. Adenocarcinomas did express significant lower amounts of CathD. Therefore, the prognostic value of this parameter remains uncertain. A continuous increase in CathD immunostaining was observed in AH. Since AH grade III can be considered as a precursor of endometrial cancer, CathD could be a possible parameter for assessing malignant transformation.


Differences in malaria and haematocrit presentation in children living in different settings, North West Region, Cameroon.
Malaria continues to be a major cause of morbidity and mortality in Cameroon. With all efforts being made to eliminate malaria, it is imperative to describe the epidemiology of the disease in different parts of the country in order to inform control policies. This study aimed to present the differences in the prevalence and intensity of malaria and the anaemic status of children living in different areas of the North West region of Cameroon. This study was carried out from April 2016-July 2017. Blood samples were collected from children via finger pricking. Stained thick and thin blood films were examined through microscopy (x100) to detect the presence of parasites and to estimate the geometric mean parasite density (GMPD). Packed cell volume (PCV) values were determined by micro-centrifugation. Data was analysed using SPSS to determine proportions and test for significance levels between these. Overall prevalence of malaria was 45.3%. Awing and Obang recorded the highest prevalence while Mankon and Nkwen recorded the lowest (p=0.01). The GMPD of infection was highly heterogeneous between the different localities (p=0.03). Age significantly affected the prevalence of malaria (p=0.02). Sex did not affect the prevalence nor the GMPD of malaria infection (p>0.05). Overall mean PCV value was 32.9±3.9. Localities in urban settings recorded the highest mean PCV values compared to those in rural settings (p=0.68). Sex and age did not affect mean PCV values (p>0.05). Malaria still remains a major problem in the North West region of Cameroon. Malaria control interventions should therefore be based on evident spatial and temporal heterogeneity of Plasmodium species in a particular area so as not to waste resources that would only be of limited effectiveness and value to the populations at risk.


Brief Psychological Screening Questions Can be Useful for Ruling Out Psychological Conditions in Patients With Chronic Pain.
Psychological symptoms are highly prevalent in chronic pain patients. Timely and accurate identification may enable individualized treatment and improve outcomes. The aims of this study were to (1) investigate the concurrent validity of brief psychological screening questions assessing anxiety, fear of movement, stress, pain catastrophization, and depression in chronic pain patients, and (2) to determine screening question cut-points at which the likely probability of having these psychological states was <10%. Responses to 1-item or 2-item screening questions within each of these 5 psychological constructs were compared with those of validated full-length questionnaires in 894 patients with diverse chronic pain conditions. Compared with scores from full-length questionnaires, brief screening question scores had correlations between 0.54 and 0.66, and area under the curve between 0.79 and 0.83. At the dichotomized threshold scores that we chose, the posttest probability after a negative test result ranged from 6.5% to 8.6% for all these psychological constructs, except fear of movement. The pretest probability was so high (70%) for fear of movement that no threshold resulted in a posttest probability (negative test result) that was below 10%. Use of these screening tests and scoring thresholds would have correctly identified that between 38.5% and 60.5% of the sample were unlikely to have these psychological states (true negatives), with a false-negative rate between 3.4% and 5.3%. This would allow clinicians to focus on whether there are other patient attributes in those patients requiring more thorough investigation using comprehensive validated questionnaires or structured clinical interviews.


Ex vivo model with bovine heart: a proposal for training microscopic dissection and vascularmicroanastomoses.
Training is a process that requires patience and constant practice. The execution of microscopic procedures is present in the day-to-day of several surgical specialties, but unfortunately experimental models are not easy to access in our environment. We propose a bovine heart model used by residents and young surgeons in the training of microscopic dissection and microanastomoses. It is described the assembly of this model, which can be performed individually and with accessible material to the surgical departments. Our experience in the preparation of the pieces, as well as tips for the process, are described in the text. The bovine myocardial model can be reproduced in any center with benches and surgical instruments. Low cost, fast preparation, and wide availability of the used tissue are among the advantages of this model. We consider the project useful in the training of surgical residents and young surgeons.


Case of solitary pulmonary capillary hemangioma: pathological features based on frozen section analysis.
Solitary pulmonary capillary hemangioma (SPCH) is a rare benign lung tumor that must be distinguished from small and early lung cancers. Here, we report a case of SPCH for which we performed frozen section diagnosis. The patient was a 55-year-old Japanese woman. Five years before the operation, mixed ground-glass opacity was detected by computed tomography in the left posterior basal segment of the lower lobe (S10). Because the interior tumor density of the ground-glass opacity increased slightly, video-assisted thoracic surgery wedge resection was performed. Frozen section diagnosis revealed a benign tumor without proliferation of atypical epithelial cells. The tumor had narrow alveolar lumens, thickened alveolar septa and a clear boundary separating it from normal lung tissue. The proliferated lumens varied in size and were lined with single layers of flat cells. After the operation, immunohistochemical staining of a paraffin section revealed that the thickened alveolar septa resulted from the proliferation of capillary vessels, the flat cells of which were positive for CD31 and CD34 and negative for podoplanin; the tumor was diagnosed as SPCH. Here, we discuss the pathological features of SPCH on frozen sections with reference to this case and review previous related reports.


Patterns of Cone-Beam Computed Tomography (CBCT) Utilization by Various Dental Specialties: A 4-Year Retrospective Analysis from a Dental and Maxillofacial Specialty Center.
The study aimed to analyze the uses of cone-beam computed tomography (CBCT) in the diagnosis and treatment in various dental specialties. This 4-year cross-sectional study analyzed the records of 1409 individuals who underwent a CBCT at the Oral and Maxillofacial Center at Sheba Medical Center, Israel. The average age of the patients was 27.9 ± 11.5 (range: 9-86 years). Patients were referred for CBCT by the following departments: Oral and Maxillofacial Surgery (1063; 75.5%), Endodontics (182; 12.9%), Periodontology (122; 8.6%) and Orthodontics (42; 3.0%). Most CBCT radiographs evaluated the maxilla (774; 55.0%), followed by the mandible (481; 34.1%) and both (154; 10.9%). The target anatomical structures included: bone (694; 49.3%), teeth (307; 21.7%), and both jaws (408; 29.0%). The main indications for CBCT use were: assessment of anatomical structures and implant sites (787; 55.9%), determine root canals morphology (182; 12.9%), visualization of impacted teeth, tooth alignment, and localization (177; 12.6%), suspected cysts or tumors (148; 10.5%), evaluation of Temporomandibular joint disorders (106; 7.5%) and other reasons (9; 0.6%). In 279 (19.8%) of cases, the diagnosis changed following CBCT, mainly in Orthodontics tooth analysis (28 (66.7%); p < 0.001). Practitioners and health authorities should be aware of this baseline information regarding CBCT use in the diagnosis and assessment of various oral and maxillofacial pathologies, anomalies and tooth position relative to anatomic structures. Continuing research and publications of CBCT utilization and guidelines are recommended.


Idarucizumab for Dabigatran Reversal in the Management of Patients With Gastrointestinal Bleeding.
Although dabigatran has a favorable risk-benefit profile compared with vitamin K antagonist therapy for venous thromboembolism and nonvalvular atrial fibrillation, major bleeding events, including gastrointestinal (GI) bleeding, may occur. Therefore, our aim was to provide insights into the efficacy and safety of idarucizumab for urgent dabigatran reversal in patients with major GI bleeding. Patients with uncontrollable GI bleeding requiring reversal were enrolled from June 2014 through July 2016 in the RE-VERSE AD study (Reversal of Dabigatran Anticoagulant Effect With Idarucizumab), a prospective, multicenter, open-label study of idarucizumab, and were followed up for 90 days for primary and secondary outcomes. Patients were to receive a 5-g dose of intravenous idarucizumab, administered as 2 bolus infusions of 2.5 g no more than 15 minutes apart. The primary end point was the maximum reversal of dabigatran anticoagulation within 4 hours after administration of idarucizumab as measured by the dabigatran-specific assays diluted thrombin time and ecarin clotting time. Further end points included investigator-reported bleeding cessation within the first 24 hours and incidence of rebleeding, thromboembolic events, or mortality. GI bleeding occurred in 137 patients enrolled in RE-VERSE AD, of which 84% was adjudicated as major or life-threatening, 48 (35.0%) was upper GI tract in origin, 43 (31.4%) was lower GI in origin, and 46 (33.6%) was either both or unknown. Complete reversal of dabigatran was observed in 118 of 121 patients (97.5%) with an elevated diluted thrombin time at presentation and 95 of 131 patients (72.5%) with an elevated ecarin clotting time and was similar for upper and lower GI bleeding. Bleeding cessation within 24 hours was reported in 92 of 134 evaluable patients (68.7%) after a median duration of 2.4 hours (interquartile range, 2.0-3.9 hours). During the 90-day follow-up, 6 patients (4.4%) had a postreversal thromboembolic event, and 20 patients (14.6%) died. Idarucizumab showed a rapid and complete reversal of dabigatran activity in nearly all patients presenting with GI bleeding, facilitating emergency patient care without the additional presence of anticoagulation. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02104947.