A firearm bullet lodged into the thoracic spinal canal without vertebral bone destruction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Firearm injuries account for 13% to 17% of all spinal cord injuries, and are generally caused during warfare or assault with intent to kill. Spinal cord injuries caused by firearms are usually observed in patients aged 15 to 34 years old, and are especially common among men.</p> <p>Case presentation</p> <p>We report the case of a 28-year-old Iraqi man who was referred to our radiology department with lower limb paraplegia secondary to a gunshot wound. We performed 64-slice computerized tomography with two-dimensional and three-dimensional reconstruction of the thoracolumbar spine. On the two-dimensional and three-dimensional reconstructed axial images of the thoracolumbar spine, an intra-canalicular bullet nucleus was found at the mid-spinal cord at the T8 level, with no evidence of vertebral bone destruction.</p> <p>Conclusions</p> <p>To the best of our knowledge, there is only one previous report in the literature describing a case of a bullet nucleus lodged into the inferior epidural spinal canal without destruction of the vertebral bone. With the rise of violence worldwide the incidence of gunshot injuries continues to increase, and, thus, it is essential for radiologists to have a clear understanding of gunshot injuries and the findings on radiographic images.</p

Anterograde trafficking of KCa3.1 in polarized epithelia is Rab1- And Rab8-Dependent and recycling endosome-independent

The intermediate conductance, Ca2+-activated K+ channel (KCa3.1) targets to the basolateral (BL) membrane in polarized epithelia where it plays a key role in transepithelial ion transport. However, there are no studies defining the anterograde and retrograde trafficking of KCa3.1 in polarized epithelia. Herein, we utilize Biotin Ligase Acceptor Peptide (BLAP)-tagged KCa3.1 to address these trafficking steps in polarized epithelia, using MDCK, Caco-2 and FRT cells. We demonstrate that KCa3.1 is exclusively targeted to the BL membrane in these cells when grown on filter supports. Following endocytosis, KCa3.1 degradation is prevented by inhibition of lysosomal/proteosomal pathways. Further, the ubiquitylation of KCa3.1 is increased following endocytosis from the BL membrane and PR-619, a deubiquitylase inhibitor, prevents degradation, indicating KCa3.1 is targeted for degradation by ubiquitylation. We demonstrate that KCa3.1 is targeted to the BL membrane in polarized LLC-PK1 cells which lack the m1B subunit of the AP-1 complex, indicating BL targeting of KCa3.1 is independent of μ1B. As Rabs 1, 2, 6 and 8 play roles in ER/Golgi exit and trafficking of proteins to the BL membrane, we evaluated the role of these Rabs in the trafficking of KCa3.1. In the presence of dominant negative Rab1 or Rab8, KCa3.1 cell surface expression was significantly reduced, whereas Rabs 2 and 6 had no effect. We also co-immunoprecipitated KCa3.1 with both Rab1 and Rab8. These results suggest these Rabs are necessary for the anterograde trafficking of KCa3.1. Finally, we determined whether KCa3.1 traffics directly to the BL membrane or through recycling endosomes in MDCK cells. For these studies, we used either recycling endosome ablation or dominant negative RME-1 constructs and determined that KCa3.1 is trafficked directly to the BL membrane rather than via recycling endosomes. These results are the first to describe the anterograde and retrograde trafficking of KCa3.1 in polarized epithelia cells. © 2014 Bertuccio et al

Chronic adaptations of lung function in breath-hold diving fishermen

Objectives: The aim of this study was to verify and analyze the existence of chronic adaptations of lung function in freediving fishermen whose occupation is artisanal fishing. Material and Methods: This was a cross-sectional study involving 11 breath-hold diving fishermen and 10 non-breath-hold diving fishermen (control) from the village of Bitupitá in the municipality of Barroquinha (Ceará - Brazil). Anthropometric measurements, chest and abdominal circumferences as well as spirometric and respiratory muscle strength tests were conducted according to the specifications of the American Thoracic Society/European Respiratory Society (ATS/ERS). In order to compare the measured values versus the predicted values, Student t test was used in the case of parametric test and Wilcoxon test in the case of nonparametric test. To compare the inter-group means Student t test was used for parametric test and Mann-Whitney test for the nonparametric one. The level of significance was set at α = 5%. Results: The forced vital capacity (FVC) (4.9±0.6 l vs. 4.3±0.4 l) and forced expiratory volume in 1 s (FEV1) (4.0±0.5 l vs. 3.6±0.3 l) were, respectively, higher in the group of divers compared to the control group (p ≤ 0.05). Furthermore, in the group of free divers, the measured FVC, FEV1 and FEV1/FVC ratios were significantly greater than the predicted ones. No differences were found between the measured respiratory pressures. Conclusions: These results indicate that breath-hold diving seems to produce chronic adaptations of the respiratory system, resulting in elevated lung volumes with no airway obstruction

Failure of artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria in southern Cambodia

<p>Abstract</p> <p>Background</p> <p>Resistance to anti-malarial drugs hampers control efforts and increases the risk of morbidity and mortality from malaria. The efficacy of standard therapies for uncomplicated <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>malaria was assessed in Chumkiri, Kampot Province, Cambodia.</p> <p>Methods</p> <p>One hundred fifty-one subjects with uncomplicated falciparum malaria received directly observed therapy with 12 mg/kg artesunate (over three days) and 25 mg/kg mefloquine, up to a maximum dose of 600 mg artesunate/1,000 mg mefloquine. One hundred nine subjects with uncomplicated vivax malaria received a total of 25 mg/kg chloroquine, up to a maximum dose of 1,500 mg, over three days. Subjects were followed for 42 days or until recurrent parasitaemia was observed. For <it>P. falciparum </it>infected subjects, PCR genotyping of <it>msp1</it>, <it>msp2</it>, and <it>glurp </it>was used to distinguish treatment failures from new infections. Treatment failure rates at days 28 and 42 were analyzed using both per protocol and Kaplan-Meier survival analysis. Real Time PCR was used to measure the copy number of the <it>pfmdr1 </it>gene and standard 48-hour isotopic hypoxanthine incorporation assays were used to measure IC₅₀for anti-malarial drugs.</p> <p>Results</p> <p>Among <it>P. falciparum </it>infected subjects, 47.0% were still parasitemic on day 2 and 11.3% on day 3. The PCR corrected treatment failure rates determined by survival analysis at 28 and 42 days were 13.1% and 18.8%, respectively. Treatment failure was associated with increased <it>pfmdr1 </it>copy number, higher initial parasitaemia, higher mefloquine IC₅₀, and longer time to parasite clearance. One <it>P. falciparum </it>isolate, from a treatment failure, had markedly elevated IC₅₀for both mefloquine (130 nM) and artesunate (6.7 nM). Among <it>P. vivax </it>infected subjects, 42.1% suffered recurrent <it>P. vivax </it>parasitaemia. None acquired new <it>P. falciparum </it>infection.</p> <p>Conclusion</p> <p>The results suggest that artesunate-mefloquine combination therapy is beginning to fail in southern Cambodia and that resistance is not confined to the provinces at the Thai-Cambodian border. It is unclear whether the treatment failures are due solely to mefloquine resistance or to artesunate resistance as well. The findings of delayed clearance times and elevated artesunate IC₅₀suggest that artesunate resistance may be emerging on a background of mefloquine resistance.</p

Crown Plasticity and Competition for Canopy Space: A New Spatially Implicit Model Parameterized for 250 North American Tree Species

BACKGROUND: Canopy structure, which can be defined as the sum of the sizes, shapes and relative placements of the tree crowns in a forest stand, is central to all aspects of forest ecology. But there is no accepted method for deriving canopy structure from the sizes, species and biomechanical properties of the individual trees in a stand. Any such method must capture the fact that trees are highly plastic in their growth, forming tessellating crown shapes that fill all or most of the canopy space. METHODOLOGY/PRINCIPAL FINDINGS: We introduce a new, simple and rapidly-implemented model--the Ideal Tree Distribution, ITD--with tree form (height allometry and crown shape), growth plasticity, and space-filling, at its core. The ITD predicts the canopy status (in or out of canopy), crown depth, and total and exposed crown area of the trees in a stand, given their species, sizes and potential crown shapes. We use maximum likelihood methods, in conjunction with data from over 100,000 trees taken from forests across the coterminous US, to estimate ITD model parameters for 250 North American tree species. With only two free parameters per species--one aggregate parameter to describe crown shape, and one parameter to set the so-called depth bias--the model captures between-species patterns in average canopy status, crown radius, and crown depth, and within-species means of these metrics vs stem diameter. The model also predicts much of the variation in these metrics for a tree of a given species and size, resulting solely from deterministic responses to variation in stand structure. CONCLUSIONS/SIGNIFICANCE: This new model, with parameters for US tree species, opens up new possibilities for understanding and modeling forest dynamics at local and regional scales, and may provide a new way to interpret remote sensing data of forest canopies, including LIDAR and aerial photography

Different Factors Affecting Human ANP Amyloid Aggregation and Their Implications in Congestive Heart Failure

Atrial Natriuretic Peptide (ANP)-containing amyloid is frequently found in the elderly heart. No data exist regarding ANP aggregation process and its link to pathologies. Our aims were: i) to experimentally prove the presumptive association of Congestive Heart Failure (CHF) and Isolated Atrial Amyloidosis (IAA); ii) to characterize ANP aggregation, thereby elucidating IAA implication in the CHF pathogenesis.A significant prevalence (85\%) of IAA was immunohistochemically proven ex vivo in biopsies from CHF patients. We investigated in vitro (using Congo Red, Thioflavin T, SDS-PAGE, transmission electron microscopy, infrared spectroscopy) ANP fibrillogenesis, starting from α-ANP as well as the ability of dimeric β-ANP to promote amyloid formation. Different conditions were adopted, including those reproducing β-ANP prevalence in CHF. Our results defined the uncommon rapidity of α-ANP self-assembly at acidic pH supporting the hypothesis that such aggregates constitute the onset of a fibrillization process subsequently proceeding at physiological pH. Interestingly, CHF-like conditions induced the production of the most stable and time-resistant ANP fibrils suggesting that CHF affected people may be prone to develop IAA.We established a link between IAA and CHF by ex vivo examination and assessed that β-ANP is, in vitro, the seed of ANP fibrils. Our results indicate that β-ANP plays a crucial role in ANP amyloid deposition under physiopathological CHF conditions. Overall, our findings indicate that early IAA-related ANP deposition may occur in CHF and suggest that these latter patients should be monitored for the development of cardiac amyloidosis

Transcriptional Evidence for the Role of Chronic Venlafaxine Treatment in Neurotrophic Signaling and Neuroplasticity Including also Glutatmatergic- and Insulin-Mediated Neuronal Processes.

OBJECTIVES: Venlafaxine (VLX), a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD). Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration. METHODS: Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day) VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment. RESULTS: Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2). Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3), glutamatergic transmission (Gria3, Grin2b and Grin2a), neuroplasticity (Camk2g/b, Cd47), synaptogenesis (Epha5a, Gad2) and cognitive processes (Clstn2). Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1). Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1), a mechanism that has recently been linked to neuroprotection, learning and memory. CONCLUSIONS: Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in regulatory networks of motor cortical areas. These results are consonant with the synaptic (network) hypothesis of depression and antidepressant-induced motor recovery after stroke

TILLING - a shortcut in functional genomics

Recent advances in large-scale genome sequencing projects have opened up new possibilities for the application of conventional mutation techniques in not only forward but also reverse genetics strategies. TILLING (Targeting Induced Local Lesions IN Genomes) was developed a decade ago as an alternative to insertional mutagenesis. It takes advantage of classical mutagenesis, sequence availability and high-throughput screening for nucleotide polymorphisms in a targeted sequence. The main advantage of TILLING as a reverse genetics strategy is that it can be applied to any species, regardless of its genome size and ploidy level. The TILLING protocol provides a high frequency of point mutations distributed randomly in the genome. The great mutagenic potential of chemical agents to generate a high rate of nucleotide substitutions has been proven by the high density of mutations reported for TILLING populations in various plant species. For most of them, the analysis of several genes revealed 1 mutation/200–500 kb screened and much higher densities were observed for polyploid species, such as wheat. High-throughput TILLING permits the rapid and low-cost discovery of new alleles that are induced in plants. Several research centres have established a TILLING public service for various plant species. The recent trends in TILLING procedures rely on the diversification of bioinformatic tools, new methods of mutation detection, including mismatch-specific and sensitive endonucleases, but also various alternatives for LI-COR screening and single nucleotide polymorphism (SNP) discovery using next-generation sequencing technologies. The TILLING strategy has found numerous applications in functional genomics. Additionally, wide applications of this throughput method in basic and applied research have already been implemented through modifications of the original TILLING strategy, such as Ecotilling or Deletion TILLING

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research