Thoracic and lumbar vertebrae morphology in Lenke type 1 female adolescent idiopathic scoliosis patients.
Pedicle screws are widely used in adolescent idiopathic scoliosis (AIS) surgeries. Pedicle screw malposition may lead to serious vascular and neurologic complications. Knowledge of the morphometric anatomy of the thoracic and lumbar vertebrae is essential for the surgeon while implanting pedicle screws. It has been reported that there is a reduction of pedicle width at the concavity of the curve in AIS patients. However, it is unclear if gender plays a role in this pedicle width pattern. The goal of this study is to assess the vertebrae morphology in a more homogeneous group of AIS patients - female patients with Lenke type 1 curve. The thoracic and lumbar vertebra and pedicle morphometry of 17 consecutive Lenke type 1 female AIS patients was analyzed based on 1mm fine cut CT scans. Morphometric anatomy of 539 pedicles from T1 to L5 was studied. Measurements included pedicle length, chord length, transverse pedicle width, transverse pedicle angle and vertebral rotation angle. The mean age of the patients was 14 years old (range 12-18). The mean Cobb angle was 56° (range 43° -88°) and the mean angle of vertebral rotation varied between 4-13.8°. The apical vertebra was between T7 and T11. The transverse pedicle width was significantly smaller (p < 0.05) on the concave side in the apical region of the thoracic spine (T7 and T8), measuring between 2.1-2.2 mm on the concave side and 2.7-3.1 mm on the convex side. Meanwhile, in some upper thoracic vertebrae (T3, T4, T5), the width was significantly bigger (p < 0.05) on the concave side than on the convex side, measuring between 2.8-4 mm on the concave side and 1.8-2.4 mm on the convex side. In the lumbar spine, the width varied between 4.1-9.9 mm without significant differences between the concave and convex sides (p > 0.05). The pedicle length varied between 15.4-28.7 mm and was significantly smaller (p < 0.05) on the concave side at T4, T5 and L2. The chord length was shortest at T1, measuring 32.4 mm and increased gradually to 54.3 mm at L3 but no statistical difference was found between the concave and convex sides. The transverse pedicle angle varied between 11.8° and 35° and was significantly bigger on the concave side at T7 and on the convex side at L1 (p < 0.05). The vertebrae morphology in Lenke type 1 female AIS patients is substantially different from the vertebrae in normal spines especially at the apex and in the upper thoracic region. This is consistent with some previous reports which did not distinguish between male and female patients. Our findings suggest that gender does not play a major role in the vertebrae morphology pattern of AIS patients. Furthermore, recognizing this pattern is critical in order to optimize pedicle screw instrumentation and may allow for some leeway adjustments in the pedicle screw trajectory regardless of the methods of implantation.


Silver nanocube aggregation gradient materials in search for total internal reflection with high phase sensitivity.
We fabricated monolayer coatings of a silver nanocube aggregation to create a step-wise optical strip by applying different surface pressures during slow Langmuir-Blodgett deposition. The varying amount of randomly distributed nanocube aggregates with different surface coverages in gradient manner due to changes in surface pressure allows for continuous control of the polarization sensitive absorption of the incoming light over a broad optical spectrum. Optical characterization under total internal reflection conditions combined with electromagnetic simulations reveal that the broadband light absorption depends on the relative orientation of the nanoparticles to the polarization of the incoming light. By using computer simulations, we found that the electric field vector of the s-polarized light interacts with the different types of silver nanocube aggregations to excite different plasmonic resonances. The s-polarization shows dramatic changes of the plasmonic resonances at different angles of incidence (shift of 64 nm per 10° angle of incidence). With a low surface nanocube coverage (from 5% to 20%), we observed a polarization-selective high absorption of 80% (with an average 75%) of the incoming light over a broad optical range in the visible region from 400 nm to 700 nm. This large-area gradient material with location-dependent optical properties can be of particular interest for broadband light absorption, phase-sensitive sensors, and imaging.


When the word doesn't come out: A synthetic overview of dysarthria.
Motor speech disorders are common in a number of neurological conditions including diseases involving impairment of the pyramidal, extrapyramidal, and cerebellar pathways, cranial nerves, muscular apparatus, neuromuscular plaque, and of cognitive, symbolic and mnestic activities. The diagnosis of speech disorders, namely the dysarthrias, involves the assessment of characteristic structural cerebral, prosodic, phonetic and phonemic changes, often flanked by concomitant functional, clinical, neuroradiological, neurophysiological and behavioral impairment. This paper presents a brief outline of the most significant associations to facilitate prompt differential diagnosis and thereby reduce the number of instrumental examinations required for diagnostic testing.


A Few-Minute Synthesis of CsPbBr3 Nanolasers with a High Quality Factor by Spraying at Ambient Conditions.
Inorganic cesium lead halide perovskite nanowires, generating laser emission in the broad spectral range at room temperature and low threshold, have become powerful tools for the cutting-edge applications in the optoelectronics and nanophotonics. However, to achieve high-quality nanowires with the outstanding optical properties, it was necessary to employ long-lasting and costly methods of their synthesis, as well as postsynthetic separation and transfer procedures that are not convenient for large-scale production. Here we report a novel approach to fabricate high-quality CsPbBr3 nanolasers obtained by rapid precipitation from dimethyl sulfoxide solution sprayed onto hydrophobic substrates at ambient conditions. The synthesis technique allows producing the well-separated nanowires with a broad size distribution of 2-50 μm in 5-7 min, being the fastest method to the best of our knowledge. The formation of nanowires occurs via ligand-assisted reprecipitation triggered by intermolecular proton transfer from (CH3)2CHOH to H2O in the presence of a minor amount of water. The XRD patterns confirm an orthorhombic crystal structure of the as-grown CsPbBr3 single nanowires. Scanning electron microscopy images reveal their regular shape and truncated pyramidal end facets, while high-resolution transmission electron microscopy ones demonstrate their single-crystal structure. The lifetime of excitonic emission of the nanowires is found to be 7 ns, when the samples are excited with energy below the lasing threshold, manifesting the low concentration of defect states. The measured nanolasers of different lengths exhibit pronounced stimulated emission above 13 μJ cm-2 excitation threshold with quality factor Q = 1017-6166. Their high performance is assumed to be related to their monocrystalline structure, low concentration of defect states, and improved end facet reflectivity.


Estimation of physically realizable Mueller matrices from experiments using global constrained optimization.
One can explicitly retrieve physically realizable Mueller matrices from quantified intensity data even in the presence of noise. This is done by integrating the physical realizability criterion obtained by Givens and Kostinski, [J. Mod. Opt. 40, 471 (1993)], as an active constraint in a global optimization process. Among different global optimization techniques, two of them have been tested and their robustness analyzed: a deterministic approach based on sequential quadratic programming and a stochastic approach based on constrained simulated annealing algorithms are implemented for this purpose. We illustrate the validity of both methods on experimental data and on the inadmissible Mueller matrix given by Howell, [Appl. Opt. 18, No. 6, 808-812 (1979)]. In comparison, the constrained simulated annealing method produced higher accuracy with similar computing time.


The crystal structure of nitrophorin 2. A trifunctional antihemostatic protein from the saliva of Rhodnius prolixus.
Nitrophorin 2 (NP2) (also known as prolixin-S) is a salivary protein that transports nitric oxide, binds histamine, and acts as an anticoagulant during blood feeding by the insect Rhodnius prolixus. The 2.0-A crystal structure of NP2 reveals an eight-stranded antiparallel beta-barrel containing a ferric heme coordinated through His(57), similar to the structures of NP1 and NP4. All four Rhodnius nitrophorins transport NO and sequester histamine through heme binding, but only NP2 acts as an anticoagulant. Here, we demonstrate that recombinant NP2, but not recombinant NP1 or NP4, is a potent anticoagulant; recombinant NP3 also displays minor activity. Comparison of the nitrophorin structures suggests that a surface region near the C terminus and the loops between beta strands B-C and E-F is responsible for the anticoagulant activity. NP2 also displays larger NO association rates and smaller dissociation rates than NP1 and NP4, which may result from a more open and more hydrophobic distal pocket, allowing more rapid solvent reorganization on ligand binding. The NP2 protein core differs from NP1 and NP4 in that buried Glu(53), which allows for larger NO release rates when deprotonated, hydrogen bonds to invariant Tyr(81). Surprisingly, this tyrosine lies on the protein surface in NP1 and NP4.


Pooled Analysis of C-Reactive Protein Levels and Mortality in Prostate Cancer Patients.
Previous studies have reported that higher C-reactive protein (CRP) levels are significantly associated with worse outcome in prostate cancer patients. The size of each individual study was not large enough to allow sufficient statistical power to draw conclusions. We conducted a pooled analysis of individual data of published studies to evaluate the association between increased CRP level and risk of death in prostate cancer, and to find the best CRP cutoff that could predict mortality. Original research studies on prostate cancer survival and CRP levels were identified (n = 6). Corresponding authors were contacted and invited to share individual data. Two data sets were received (235 patients). The combined hazard ratio (HR) was calculated and adjusted for age, prostate-specific antigen, hemoglobin, and alkaline phosphatase. The best cutoff of CRP was explored using X-title software version 3.6.1. High CRP level was statistically significantly associated with mortality (meta-HR, 1.83 [95% confidence interval (CI), 1.51-2.21]), without evidence of heterogeneity among studies. At pooled analysis, adjusted pooled HR for CRP < 5 versus ≥ 5 mg/L was 1.44 (95% CI, 1.02-20.4). The best CRP cutoff was 12 mg/L: the adjusted HRpooled for CRP < 12 versus ≥ 12 mg/L was 1.53 (95% CI, 1.01-2.32). Increased CRP levels are associated with overall survival in prostate cancer patients. Because CRP is an affordable and readily available assay, it might hold promise in improving prognostication and potentially to predict the activity of specific therapeutic agents.


Changes in amplitude and phase of distortion-product otoacoustic emission fine-structure and separated components during efferent activation.
Medial olivocochlear (MOC) efferent fibers synapse directly on the outer hair cells (OHCs). Efferent activation evoked by contralateral acoustic stimulation (CAS) will affect OHC amplification and subsequent measures of distortion-product otoacoustic emissions (DPOAEs). The aim of this study was to investigate measures of total and separated DPOAEs during efferent activation. Efferent activation produces both suppression and enhancement of the total DPOAE level. Level enhancements occurred near fine-structure minima and were associated with consistent MOC evoked upward shifts in DPOAE fine-structure frequency. Examination of the phase of the separated components revealed that frequency shifts stemmed from increasing phase leads of the reflection component during CAS, while the generator component phase was nearly invariant. Separation of the two DPOAE components responsible for the fine-structure revealed more consistent reduction of the levels of both components. Using vector subtraction (which takes into account both level and phase) to estimate the changes in the unseparated DPOAE provided consistent evidence of DPOAE suppression. Including phase information provided a more sensitive, valid and consistent estimate of CAS function even if one does not know the position of the DPOAE in the fine-structure.


Primary and secondary sexual characters in alternative reproductive tactics of Chinook salmon: Associations with androgens and the maturation-inducing steroid.
The proximate mechanisms that underlie the evolution of within-sex variation in mating behavior, sexual characters and reproductive investment patterns are still poorly understood. Species exhibiting alternative reproductive tactics (ARTs) are ideal model systems to examine these mechanisms. Chinook salmon (Oncorhynchus tshawytscha) exhibits two distinct ARTs: hooknoses, which are large males that establish spawning dominance hierarchies via intense male-male competition and jacks, which are smaller precocious sneaking males that steal fertilizations via sperm competition. In this study, we examine plasma testosterone (T), 11-ketotestosterone (11-KT) and maturation-inducing steroid (MIS; 17α,20β-dihydroxy-4-pregnen-3-one) profiles of spawning hooknoses and jacks. Furthermore, we examine relationships between androgens and primary (gonad mass, gonadosomatic index and sperm traits) and secondary (total mass, body size, hump depth and kype length) sexual characters. Relationships between MIS and sperm traits are also examined. We found that hooknoses and jacks did not significantly differ in terms of plasma T, 11-KT or MIS concentrations. Moreover, we found significant positive relationships between levels of both androgens within each ART. There were no significant relationships between androgens, MIS and sperm traits. T and 11-KT concentrations co-varied positively with gonad investment and kype length in jacks. In hooknoses, 11-KT concentration was positively related to total mass, hump depth and condition factor. Overall, these findings suggest that there are differential androgen effects for each of the ARTs in Chinook salmon.


The diagnostic utility of midcarpal anesthetic injection in the evaluation of chronic wrist pain.
The evaluation of chronic wrist pain can be a diagnostic dilemma. Lidocaine injections combined with corticosteroids are often used for both diagnosis and therapy. The purpose of this study was to determine if a midcarpal injection of lidocaine could serve as a diagnostic tool in patients with chronic wrist pain. Specifically, the relationship of pain relief from the injection and improvement of grip strength were compared to the presence of intracarpal pathology as confirmed by wrist arthroscopy. Forty-five patients with chronic wrist pain underwent a midcarpal injection of lidocaine with or without corticosteroids. Forty of the 45 underwent comcomitant steroid injections; a majority of the 40 patients reported relief of pain for two or more weeks. Improvement of pain and improvement of grip strength were determined. Each of these patients subsequently underwent a radiocarpal and midcarpal arthroscopy, and the pathologic findings of arthroscopy were compared to the improvement of pain and grip strength. These data were compared to a cohort of six volunteers without history of wrist pain or trauma that underwent midcarpal injection of lidocaine. Statistical analysis was performed using Receiver-Operator-Characteristic analysis. The average age of patients with chronic pain was 30.3 years, with an average of 9.8 months of wrist pain. The ultimate diagnoses included 35 patients with carpal instability dissociative, two with nondissociative instability, seven with complex instability of the carpus, three with extensor carpi ulnaris tendonitis and one with deQuervain's tenosynovitis. After lidocaine injection, the normal cohort had a mean loss of 2 kg (-5.3%) (p = 0.02) in grip strength, whereas the experimental cohort had a mean improvement in grip strength of 5.73 kg (34.4%). Improvement of pain after injection did not correlate with pathologic arthroscopic findings (p = 0.92). Improvement in grip strength after midcarpal lidocaine injection of 6 kg or 28% had a 73% sensitivity and a 70% specificity (p = 0.02) of having intracarpal pathology at the time of arthroscopy. Of the chronic wrist pain patients, only four had a normal arthroscopy, and the remainder had at least one area of significant pathology attributing to their pain. We conclude that a midcarpal injection of lidocaine can serve as an effective diagnostic tool in the evaluation of the patient with chronic wrist pain. Improvement of grip of 28% with or without relief of pain is highly correlated with intracarpal pathology.


Predictive Models for Human Organ Toxicity Based on In Vitro Bioactivity Data and Chemical Structure.
Traditional toxicity testing reliant on animal models is costly and low throughput, posing a significant challenge with the increasing numbers of chemicals that humans are exposed to in the environment. The purpose of this investigation was to build optimal prediction models for various human in vivo/organ-level toxicity end points (extracted from ChemIDPlus) using chemical structure and Tox21 in vitro quantitative high-throughput screening (qHTS) bioactivity assay data. Several supervised machine learning algorithms were applied to model 14 human toxicity end points pertaining to vascular, kidney, ureter and bladder, and liver organ systems. Three metrics were used to evaluate model performance: area under the receiver operating characteristic curve (AUC-ROC), balanced accuracy (BA), and Matthews correlation coefficient (MCC). The top four models, with AUC-ROC values >0.8, were derived for endocrine (0.90 ± 0.00), musculoskeletal (0.88 ± 0.02), peripheral nerve and sensation (0.85 ± 0.01), and brain and coverings (0.83 ± 0.02) toxicities, whereas the best model AUC-ROC values were >0.7 for the remaining 10 toxicities. Model performance was found to be dependent on the specific data set, model type, and feature selection method used. In addition, chemical structure and assay data showed different levels of contribution to the prediction of different toxicity end points. Although in vitro assay data, when combined with chemical structure, slightly improved the predictive accuracy for most end points (11 out of 14), a noteworthy finding was the near equal success of the structure-only models, which do not require Tox21 qHTS screening data, and the relatively poor performance of assay-only models. Thus, the top-performing structure-only models from this study could be applied for hazard screening of large sets of chemicals for potential human toxicity, whereas the largest assay contributions to models (i.e., cellular targets) could be used, along with the top-contributing structural features, to provide insight into toxicity mechanisms.


Management of peripheral neuropathy caused by microtubule inhibitors.
Any patient receiving an agent that targets microtubules (e.g., taxanes, vinca alkaloids, epothilones) is at some risk for encountering peripheral neuropathy. This article provides tools and discussion to aid nurses in managing peripheral neuropathy in their patients through early identification and education. Some patients are at higher risk than others based on their chemotherapeutic regimen, pretreatment history, and comorbidities. When interacting with at-risk patients, nurses should be alert for primarily sensory neuropathy that presents as loss of sensation, numbness, or tingling, beginning at the distal ends of the extremities and moving proximally with a stocking or glove distribution. Clinical assessments for neuropathy generally employ grading scales, questionnaires, quantitative sensory testing, and psychometric assessments; each has benefits and limitations. Patients who experience moderate or severe neuropathy may require a dose reduction or delay until symptoms resolve; these patients may need a lower dose for the next treatment cycle. No known agents have proven to prevent or treat severe neuropathy more effectively than regular neurologic examinations, early intervention, and patient education. In this respect, nurses can make a substantial difference in the impact of neuropathy on treatment efficacy and patients' quality of life.


The antioxidant and chemical properties of Berberis vulgaris and its cytotoxic effect on human breast carcinoma cells.
In this study we evaluated the biological activity of alcoholic and aqueous extracts from the fruit of Berberis vulgaris. The total antioxidant capacity of Berberis was characterized by FRAP, DPPH, Folin-Ciocalteu while the anthocyanins content was measured by pH differential method. Cell viability and apoptotic property were determined by MTT and DNA fragmentation assays, respectively. Alcoholic extract of Berberis was richer in antioxidants and anthocyanins compared to aqueous extract. Although both extracts significantly inhibited proliferation of breast cancer cells (MCF-7); these changes were not observed in normal human breast epithelial cells (MCF10-A). The alcoholic extract was more effective in inducing apoptosis as detected by DNA fragmentation in treated cancer cells. Our results suggest that Berberis has potent antioxidant properties and cytotoxic effects that can induce apoptosis. Therefore, Berberis can potentially be exploited for the development of therapeutics to fight against human breast cancer.


Compositional patterning in systems driven by competing dynamics Of different length scale
We study an alloy system where short-ranged, thermally driven diffusion competes with externally imposed, finite-ranged, athermal atomic exchanges, as is the case in alloys under irradiation. Using a Cahn-Hilliard-type approach, we show that when the range of these exchanges exceeds a critical value labyrinthine concentration patterns at a mesoscopic scale can be stabilized. Furthermore, these steady-state patterns appear only for a window of the frequency of forced exchanges. Our results suggest that ion beams may provide a novel route to stabilize and tune the size of nanoscale structural features in materials.


Studies on the mechanism of ristocetin-induced platelet aggregation.
Adenine nucleotide metabolism and the release reaction were studied during ristocetin-induced platelet aggregation. Decreasing platelet ATP by incubation with metabolic poisons did not decrease ristocetin-induced aggregation. ADP and ATP were released from platelets during ristocetin-induced aggregation, and ATP was converted to hypoxanthine. However, these occurred after aggregation was almost complete. Aggregation was inhibited by p-choromercuribenzoic acid. By studying platelet suspensions, we were able to determine that this effect was on platelets and not on the plasma cofactor needed for aggregation. We postulate that ristocetin and its cofactor aggregate platelets by binding platelet membranes and that the platelet plays a passive role in this reaction.


Organogels from trehalose difatty ester amphiphiles.
Saccharide diesters have been recently shown to be excellent gelators of vegetable oils. In this paper, different fatty acid trehalose diesters were synthesized by a selective enzymatic transesterification performed only on the primary hydroxyl group of the trehalose. The resulting trehalose diesters demonstrated their ability to self-assemble in a large variety of edible vegetable oils with a minimum gelation concentration of 0.25 wt%/v. Microscopic analysis and X-ray scattering studies indicate that the gels are obtained by the self-assembly of trehalose diesters in crystalline fibers constituting the tridimensional network. The rheological study revealed that the properties of the gels depend on the kind of fatty acid grafted on the trehalose but are also influenced by the vegetable oil composition.


Effectiveness of Mechanical Treatment for Plantar Fasciitis: A Systematic Review.
Plantar fasciitis is one of the most common foot injuries. Several mechanical treatment options, including shoe inserts, ankle-foot orthoses, tape, and shoes are used to relieve the symptoms of plantar fasciitis. To investigate the effectiveness of mechanical treatment in the management of plantar fasciitis. The review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. A systematic search was performed in PubMed, CINAHL, Embase, and Cochrane up to March 8, 2018. Two independent reviewers screened eligible articles and assessed risk of bias using the Cochrane Collaboration's risk of bias tool. A total of 43 articles were included in the study, evaluating 2837 patients. Comparisons were made between no treatment and treatment with insoles, tape, ankle-foot orthoses including night splints and shoes. Tape, ankle-foot orthoses, and shoes were also compared with insoles. Follow-up ranged from 3 to 5 days to 12 months. Cointerventions were present in 26 studies. Mechanical treatment can be beneficial in relieving symptoms related to plantar fasciitis. Contoured full-length insoles are more effective in relieving symptoms related to plantar fasciitis than heel cups. Combining night splints or rocker shoes with insoles enhances improvement in pain relief and function compared with rocker shoes, night splints, or insoles alone. Taping is an effective short-term treatment. Future studies should aim to improve methodological quality using blinding, allocation concealment, avoid cointerventions, and use biomechanical measures of treatment effects.


Predicting individual variation in language from infant speech perception measures.
There are increasing reports that individual variation in behavioral and neurophysiological measures of infant speech processing predicts later language outcomes, and specifically concurrent or subsequent vocabulary size. If such findings are held up under scrutiny, they could both illuminate theoretical models of language development and contribute to the prediction of communicative disorders. A qualitative, systematic review of this emergent literature illustrated the variety of approaches that have been used and highlighted some conceptual problems regarding the measurements. A quantitative analysis of the same data established that the bivariate relation was significant, with correlations of similar strength to those found for well-established nonlinguistic predictors of language. Further exploration of infant speech perception predictors, particularly from a methodological perspective, is recommended.


Investigating preference-performance relationships in aboveground-belowground life cycles: a laboratory and field study with the vine weevil (Otiorhynchus sulcatus).
The preference-performance hypothesis has principally considered insect herbivores with aboveground lifecycles, although the hypothesis could be equally relevant to insects with life stages occurring both aboveground and belowground. Moreover, most studies have focussed on either laboratory or field experiments, with little attempt to relate the two. In this study, the preference-performance hypothesis was examined in an aboveground-belowground context in the laboratory using the vine weevil (Otiorhynchus sulcatus (F.)) (Coleoptera: Curculionidae) and two cultivars of red raspberry (Rubus idaeus), Glen Rosa and Glen Ample. A two-year field study (2008-2009) was also undertaken to characterise the population dynamics of adult weevils on the two raspberry cultivars. Larval performance (abundance and mass) differed significantly between Glen Rosa and Glen Ample, with Glen Rosa resulting in 26% larger but 56% fewer larvae compared to Glen Ample. Larval abundances were significantly and positively correlated with root nitrogen and magnesium concentrations, but negatively correlated with root iron. However, concentrations of these minerals were not significantly different in the two cultivars. Adult weevils did not preferentially select either of the two cultivars for egg laying (laying 3.08 and 2.80 eggs per day on Glen Ample and Glen Rosa, respectively), suggesting that there was no strong preference-performance relationship between adult vine weevils and their belowground offspring. Field populations of adult vine weevils were significantly higher on Glen Ample than Glen Rosa, which may reflect the higher larval survival on Glen Ample observed in laboratory experiments.


[Secondary reconstruction, after maxillectomy, using an osteocutaneous flap from the fibula. Report of a case].
Surgical functional reconstruction after partial maxillectomy with fibula free flap. A bilateral upper alveolar bone, gingival and palatal defect after tumor resection, has various problems originating from reconstruction with prosthesis or temporalis muscle flap. We report a secondary reconstructive procedure using the fibula osteocutaneous free flap. The combined bone segments created the upper alveolar arch, and the skin paddle closed the palatal defect. This procedure restored the patient to masticatory function of the upper jaw, intelligible speech and natural facial appearance. As a result quality of life of patient was extremely improved.


Schizophrenia-related neuregulin-1 single-nucleotide polymorphisms lead to deficient smooth eye pursuit in a large sample of young men.
Neuregulin-1 (NRG1) variations have been shown to modulate schizophrenia candidate endophenotypes related to brain structure and function. The aim of this study was to determine the effect of NRG1 on several oculomotor schizophrenia endophenotypes. The effects of 5 core single-nucleotide polymorphisms (SNPs) within the NRG1 gene to oculomotor parameters in a battery of oculomotor tasks (saccade, antisaccade, smooth eye pursuit, fixation) were investigated in a sample of 2243 young male military conscripts. Additive regression models, bootstrap and permutation techniques, were used as well as structural equation modeling and haplotype analysis. A deficit in global smooth eye pursuit performance measured using the root-mean-square error (RMSE) was related to the risk allele of SNP8NRG243177, and a deficit in global smooth eye pursuit performance measured using the saccade frequency was related with the risk allele of SNP8NRG433E1006. Structural equation modeling confirmed a global effect of NRG1 genotype on smooth eye pursuit performance using the RMSE, while the effect on saccade frequency was not confirmed. Haplotype analysis further confirmed the prediction from the structural equation modeling that a combination of alleles corresponding to the Icelandic high-risk haplotype was related to a deficit in global pursuit performance. NRG1 genotype variations were related to smooth eye pursuit variations both at the SNP level and at the haplotype level adding to the validation of this gene as a candidate gene for the disorder.


Intermanual Transfer Effects on Performance Gain Following Dominant Hand Training in Community-Dwelling Healthy Adults: A Preliminary Study.
This study aimed to evaluate the intermanual transfer effects of dominant hand training on the functional task of the untrained hand. Fifty community-dwelling healthy adults (mean age, 23.4 ± 2.5 Y; females, 60%) were participated. Participants in the experimental group received 15 minutes of right-hand training on a pegboard apparatus twice a week for four weeks. The control group received no training. The Jebsen Taylor test (JTT) and a 16-hole pegboard test were used for the assessment of hand function and dexterity. Most of the JTT subtests except the writing and simulated feeding subtests and the performance of pegboard task by untrained hand were significantly improved in the experimental group after 4 weeks of training. However, no changes in the untrained hand function after 4 weeks in the control group. There were no significant differences in the pegboard task and JTT subtests found at baseline between the two groups. There were significant differences in the pegboard task between the two groups after dominant hand training. The experimental group took 4.3- and 2.5-second lesser time to complete the pegboard task using the dominant and non-dominant hand, respectively. Similarly, most of the JTT subtests except the writing and simulated feeding subtests were significantly better in the training group than the control group. This study indicates that the function of the untrained non-dominant hand may be improved after functional training of the dominant hand. Since this study included only healthy young adults, results of this study cannot be generalized to other groups of people such as the elderly. While this study suggests that intermanual transfer could have a therapeutic value in many clinical situations, more longitudinal studies are warranted to examine the intermanual transfer effects of functional gain in different clinical conditions, such as stroke, parkinsonism, rheumatoid arthritis, and so on.


Scale-free amplitude modulation of low-frequency fluctuations in episodic migraine.
Arrhythmic fluctuations in neural activity occur at many levels of the nervous system. Such activity does not have a characteristic temporal periodicity but can exhibit statistical similarities, most commonly power-law scaling behavior, which is indicative of scale-free dynamics. The recurrence of scaling laws across many different systems and its manifestation in behavior has prompted a search for unifying principles in human brain function. With this in mind, a focused search for abnormities in scale-free dynamics is of considerable clinical relevance to migraine and other clinical pain disorders. Here, we examined the scale-free properties of the resting-state functional magnetic resonance imaging (fMRI) signal in the broadband frequency range known to be related to spontaneous neural activity (0.01-0.1 Hz). In a large cohort of episodic migraine patients (N = 40), we observed that the strength of long-range temporal correlations in the fMRI signal (captured by the scaling exponent α) was significantly higher in the sensorimotor network compared with healthy controls. Increases in the scaling exponent were positively correlated with fMRI signal variance and negatively correlated with the patient's self-reported headache intensity. These changes in the fMRI signal suggest that the temporal structure of amplitude fluctuations carries valuable information about the dynamic state of the underlying neuronal networks and ensuing sensory impairments in migraine. The demonstrated scaling laws pose a novel quantitative approach for examining clinically relevant interindividual variability in migraine and other pain disorders.


Craniosynostosis in vitamin D-resistant rickets. A mouse model.
Craniosynostosis and associated craniofacial deformities, such as frontal bossing, often occur as symptoms of vitamin D-resistant rickets in children. Similar skull deformities develop in mice with X-linked dominant hypophosphatemia, the most common form of vitamin D-resistant rickets. These mice have a short, wide, high neurocranium, which suggested an inhibition of coronal suture growth. To study this question, we compared histologically the postnatal development of the coronal sutures in normal and hypophosphatemic mice between 1 and 13 weeks of age. Premature fusion of the coronal suture occurred in hypophosphatemic mice by 4 weeks of age. The proportion of the suture obliterated by bone varied among individual animals, but craniosynostosis was present in all animals studied at 4 weeks and older. Fusion of the coronal suture did not occur through 13 weeks of age in any of the normal mice studied. The x-linked hypophosphatemic mouse is an animal model that can be used to study the role of vitamin D-resistant rickets in the development of craniosynostosis, to relate craniosynostosis to the development of associated skull deformities, and to test new treatment procedures.


Reliability and prognostic value of radiomic features are highly dependent on choice of feature extraction platform.
To investigate the effects of Image Biomarker Standardisation Initiative (IBSI) compliance, harmonisation of calculation settings and platform version on the statistical reliability of radiomic features and their corresponding ability to predict clinical outcome. The statistical reliability of radiomic features was assessed retrospectively in three clinical datasets (patient numbers: 108 head and neck cancer, 37 small-cell lung cancer, 47 non-small-cell lung cancer). Features were calculated using four platforms (PyRadiomics, LIFEx, CERR and IBEX). PyRadiomics, LIFEx and CERR are IBSI-compliant, whereas IBEX is not. The effects of IBSI compliance, user-defined calculation settings and platform version were assessed by calculating intraclass correlation coefficients and confidence intervals. The influence of platform choice on the relationship between radiomic biomarkers and survival was evaluated using univariable cox regression in the largest dataset. The reliability of radiomic features calculated by the different software platforms was only excellent (ICC > 0.9) for 4/17 radiomic features when comparing all four platforms. Reliability improved to ICC > 0.9 for 15/17 radiomic features when analysis was restricted to the three IBSI-compliant platforms. Failure to harmonise calculation settings resulted in poor reliability, even across the IBSI-compliant platforms. Software platform version also had a marked effect on feature reliability in CERR and LIFEx. Features identified as having significant relationship to survival varied between platforms, as did the direction of hazard ratios. IBSI compliance, user-defined calculation settings and choice of platform version all influence the statistical reliability and corresponding performance of prognostic models in radiomics. • Reliability of radiomic features varies between feature calculation platforms and with choice of software version. • Image Biomarker Standardisation Initiative (IBSI) compliance improves reliability of radiomic features across platforms, but only when calculation settings are harmonised. • IBSI compliance, user-defined calculation settings and choice of platform version collectively affect the prognostic value of features.


Determination of the Optimal Shell Thickness for Self-Catalyzed GaAs/AlGaAs Core-Shell Nanowires on Silicon.
We present a set of experimental results showing a combination of various effects, that is, surface recombination velocity, surface charge traps, strain, and structural defects, that govern the carrier dynamics of self-catalyzed GaAs/AlGaAs core-shell nanowires (NWs) grown on a Si(111) substrate by molecular beam epitaxy. Time-resolved photoluminescence of NW ensemble and spatially resolved cathodoluminescence of single NWs reveal that emission intensity, decay time, and carrier diffusion length of the GaAs NW core strongly depend on the AlGaAs shell thickness but in a nonmonotonic fashion. Although 7 nm AlGaAs shell can efficiently suppress the surface recombination velocity of the GaAs NW core, the influence of the surface charge traps and the strain between the core and the shell that redshift the luminescence of the GaAs NW core remain observable in the whole range of the shell thickness. In addition, the band bending effect induced by the surface charge traps can alter the scattering of the excess carriers inside the GaAs NW core at the core/shell interface. If the AlGaAs shell thickness is larger than 50 nm, the luminescence efficiency of the GaAs NW cores deteriorates, ascribed to defect formation inside the AlGaAs shell evidenced by transmission electron microscopy.


Lectins identify glycan biomarkers on glioblastoma-derived cancer stem cells.
Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. Despite aggressive therapy with surgery, radiotherapy, and chemotherapy, nearly all patients succumb to disease within 2 years. Several studies have supported the presence of stem-like cells in brain tumor cultures that are CD133-positive, are capable of self-renewal, and give rise to all cell types found within the tumor, potentially perpetuating growth. CD133 is a widely accepted marker for glioma-derived cancer stem cells; however, its reliability has been questioned, creating a need for other identifiers of this biologically important subpopulation. We used a panel of 20 lectins to identify differences in glycan expression found in the glycocalyx of undifferentiated glioma-derived stem cells and differentiated cells that arise from them. Fluorescently labeled lectins that specifically recognize α-N-acetylgalactosamine (GalNAc) and α-N-acetylglucosamine (GlcNAc) differentially bound to the cell surface based on the state of cellular differentiation. GalNAc and GlcNAc were highly expressed on the surface of undifferentiated cells and showed markedly reduced expression over a 12-day duration of differentiation. Additionally, the GalNAc-recognizing lectin Dolichos biflorus agglutinin was capable of specifically selecting and sorting glioma-derived stem cell populations from an unsorted tumor stock and this subpopulation had proliferative properties similar to CD133(+) cells in vitro and also had tumor-forming capability in vivo. Our preliminary results on a single cerebellar GBM suggest that GalNAc and GlcNAc are novel biomarkers for identifying glioma-derived stem cells and can be used to isolate cancer stem cells from unsorted cell populations, thereby creating new cell lines for research or clinical testing.


Perception of mistuned harmonics in complex sounds by the bullfrog (Rana catesbeiana).
The ability of 73 male bullfrogs (Rana catesbeiana) to detect single mistuned harmonics in an otherwise periodic signal was studied. Bullfrogs in their natural environment were presented with playbacks of synthetic signals, resembling their species advertisement calls, that differed in the frequency of 1 harmonic component (out of 22). There were significant differences in the number and latency of the males' evoked vocal responses to these stimuli, suggesting that males were sensitive to the differences between the sounds. Differences in envelope shape (rate and depth of amplitude modulation) produced by the harmonic mistunings may underlie the differences in response. Frogs, like birds and humans, can discriminate sounds on the basis of harmonic structure, indicating that this is a general perceptual trait shared among vertebrates.


Community health centre evaluation. Paper 1: Working patterns of allied health professionals.
Community health centres are a new development on the Australian health scene and current indications are that they may play a greater role in the delivery of primary health care of the future. Therefore, information about these centres, what they are doing and who they are affecting, must be forthcoming if more public funds are to be channelled their way. The study reported here and in subsequent papers attempts an in-depth examination of the Southern Memorial Hospital--Community Care Centre for the purpose of establishing a base line from which this centre can measure its progress and with which other centres providing health care can compare. This paper reports the methodology of the evaluation study and the results of a survey of the working patterns of allied health professionals.


Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity. This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135), HRV (n = 30), and influenza (n = 16) LRTI, and healthy age- and sex-matched controls (n = 39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%-98%]) and specificity (98% [95% CI 88%-99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo). We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2. Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets, and demonstrates that large microarray datasets can be translated into a biologically meaningful context and applied to the clinical setting. Please see later in the article for the Editors' Summary.


Forced vibrations of a bubble in a liquid-filled elastic vessel.
There is increasing demand for accurate characterization of the in vivo behavior of microbubble agents used for ultrasound imaging and therapy. This study examines bubble-vessel interaction, in particular the propagation of disturbances along the vessel wall. Finite element simulations of a 3 μm radius microbubble suspended in a viscous liquid and enclosed in a 4 μm radius elastic vessel were performed, and the results compared with existing analytical results for wave propagation in elastic liquid-filled tubes. The vessel wall was shown to have a significant effect upon the amplitude of bubble oscillation and hence acoustic radiation from it, as well as distension of the vessel wall. It was found that the most important factor was the ratio of the excitation frequency to the natural "ring" frequency of the vessel which in turn depends upon its dimensions and mechanical properties. As this ratio increases, the motion of the vessel wall becomes increasingly localized to the site of the bubble. It was also shown that the validity of the results obtained using the applied model of vessel elasticity is limited to frequencies below the ring frequency, and this should be taken into account in the development of protocols for ultrasound safety and/or therapeutic procedures.


Prevalence of ketosis, ketonuria, and ketoacidosis during liberal glycemic control in critically ill patients with diabetes: an observational study.
It is uncertain whether liberal glucose control in critically ill diabetic patients leads to increased ketone production and ketoacidosis. Therefore, we aimed to assess the prevalence of ketosis, ketonuria and ketoacidosis in critically ill diabetic patients treated in accordance with a liberal glycemic control protocol. We performed a prospective observational cohort study of 60 critically ill diabetic patients with blood and/or urine ketone bodies tested in ICU. All patients were treated according to a liberal glucose protocol targeting a blood glucose level (BGL) between 10 and 14 mmol/l in a single tertiary intensive care unit in Australia. We measured quantitative bedside blood 3-beta-hydroxybutyrate (β-OHB) and semi-quantitative urine ketones on ICU admission and daily during ICU stay, for a maximum of 10 consecutive days. Median blood β-OHB level on admission was 0.3 (0.1, 0.8) mmol/l. Ketoacidosis was rare (3 %), but some level of ketosis (β-OHB ≥0.6 mmol/l) was found in 38 patients (63 %) early during their ICU stay. However, there was no significant difference in prevalence or severity of ketonemia and ketonuria among patients with BGL above (permissive hyperglycemia) or below 10 mmol/l. On multivariable linear regression analysis there was no association between blood ketone levels and BGL, HbA1c, lactate levels, hematocrit, catecholamine infusion or APACHE III score. In contrast, blood ketone levels tended to be higher after cardiopulmonary bypass surgery (P = 0.06). Liberal glycemic control in critically ill diabetic patients does not appear to be associated with a high prevalence of ketoacidosis or ketonemia. Moreover, ketosis is typically present on admission and resolves rapidly. Finally, cardiopulmonary bypass surgery may be an important trigger of ketone body production. Australian New Zealand Clinical Trials Registry ( ACTRN12615000216516 ; trial registration date 5 March 2015).


Oncolytic viruses improve cancer immunotherapy by reprogramming solid tumor microenvironment.
Immunotherapies using immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell therapy have achieved successful results against several types of human tumors, particularly hematological malignancies. However, their clinical results for the treatment of solid tumors remain poor and unsatisfactory. The immunosuppressive tumor microenvironment (TME) plays an important role by interfering with intratumoral T-cell infiltration, promoting effector T-cell exhaustion, upregulating inhibitory molecules, inducing hypoxia, and so on. Oncolytic viruses are an encouraging biocarrier that could be used in both natural and genetically engineered platforms to induce oncolysis in a targeted manner. Oncolytic virotherapy (OV) contributes to the reprogramming of the TME, thus synergizing the functional effects of current ICIs and CAR T-cell therapy to overcome resistant barriers in solid tumors. Here, we summarize the TME-related inhibitory factors affecting the therapeutic outcomes of ICIs and CAR T cells and discuss the potential of OV-based approaches to alleviate these barriers and improve future therapies for advanced solid tumors.


Modeling the fate of particulate components in aerobic sludge stabilization--performance limitations.
The study investigated the effect of sludge composition on the limitations of aerobic stabilization. It was designed with the foresight that the stabilization mechanism could only be elucidated if the observed volatile suspended solids reduction were correlated with the fate of particulate components in sludge. Biomass sustained at sludge ages of 2 and 10 days were used in the stabilization reactors. Particulate components were determined by model evaluation of corresponding oxygen uptake rate profiles. Interpretation of the experimental data by modeling, based on death-regeneration mechanism without external substrate, could simulate the fate and evolution of major components in sludge during stabilization. It showed that both microbial decay and hydrolysis of non viable cellular material proceeded at much slower rates as compared with biological systems sustained with substrate feeding. Modeling also indicated that particulate metabolic products generated by sludge acclimated to high sludge age undergo slow biodegradation under prolonged stabilization.


Brain corticosteroid receptor balance in health and disease.
In this review, we have described the function of MR and GR in hippocampal neurons. The balance in actions mediated by the two corticosteroid receptor types in these neurons appears critical for neuronal excitability, stress responsiveness, and behavioral adaptation. Dysregulation of this MR/GR balance brings neurons in a vulnerable state with consequences for regulation of the stress response and enhanced vulnerability to disease in genetically predisposed individuals. The following specific inferences can be made on the basis of the currently available facts. 1. Corticosterone binds with high affinity to MRs predominantly localized in limbic brain (hippocampus) and with a 10-fold lower affinity to GRs that are widely distributed in brain. MRs are close to saturated with low basal concentrations of corticosterone, while high corticosterone concentrations during stress occupy both MRs and GRs. 2. The neuronal effects of corticosterone, mediated by MRs and GRs, are long-lasting, site-specific, and conditional. The action depends on cellular context, which is in part determined by other signals that can activate their own transcription factors interacting with MR and GR. These interactions provide an impressive diversity and complexity to corticosteroid modulation of gene expression. 3. Conditions of predominant MR activation, i.e., at the circadian trough at rest, are associated with the maintenance of excitability so that steady excitatory inputs to the hippocampal CA1 area result in considerable excitatory hippocampal output. By contrast, additional GR activation, e.g., after acute stress, generally depresses the CA1 hippocampal output. A similar effect is seen after adrenalectomy, indicating a U-shaped dose-response dependency of these cellular responses after the exposure to corticosterone. 4. Corticosterone through GR blocks the stress-induced HPA activation in hypothalamic CRH neurons and modulates the activity of the excitatory and inhibitory neural inputs to these neurons. Limbic (e.g., hippocampal) MRs mediate the effect of corticosterone on the maintenance of basal HPA activity and are of relevance for the sensitivity or threshold of the central stress response system. How this control occurs is not known, but it probably involves a steady excitatory hippocampal output, which regulates a GABA-ergic inhibitory tone on PVN neurons. Colocalized hippocampal GRs mediate a counteracting (i.e., disinhibitory) influence. Through GRs in ascending aminergic pathways, corticosterone potentiates the effect of stressors and arousal on HPA activation. The functional interaction between these corticosteroid-responsive inputs at the level of the PVN is probably the key to understanding HPA dysregulation associated with stress-related brain disorders. 5. Fine-tuning of HPA regulation occurs through MR- and GR-mediated effects on the processing of information in higher brain structures. Under healthy conditions, hippocampal MRs are involved in processes underlying integration of sensory information, interpretation of environmental information, and execution of appropriate behavioral reactions. Activation of hippocampal GRs facilitates storage of information and promotes elimination of inadequate behavioral responses. These behavioral effects mediated by MR and GR are linked, but how they influence endocrine regulation is not well understood. 6. Dexamethasone preferentially targets the pituitary in the blockade of stress-induced HPA activation. The brain penetration of this synthetic glucocorticoid is hampered by the mdr1a P-glycoprotein in the blood-brain barrier. Administration of moderate amounts of dexamethasone partially depletes the brain of corticosterone, and this has destabilizing consequences for excitability and information processing. 7. The set points of HPA regulation and MR/GR balance are genetically programmed, but can be reset by early life experiences involving mother-infant interaction. 8. (ABSTRACT TRUNCATED)


Multimodal Evaluation of Neurovascular Functionality in Early Parkinson's Disease.
Parkinson's disease (PD) is a multisystem neurological condition affecting different neurotransmitter pathways characterized by aberrant functional connectivity (FC) and perfusion alteration. Since the FC, measuring neuronal activity, and cerebral blood flow (CBF) are closely related through the neurovascular coupling (NVC) mechanism, we aim to assess whether FC changes found in PD mirror perfusion ones. A multimodal MRI study was implemented by acquiring resting state functional MRI (rsfMRI) and arterial spin labeling (ASL) datasets on a group of 26 early PD (66.8 ± 8 years, 22 males, median [interquartile range] Hoehn and Yahr = 1.5 [1]) and 18 age- and sex-matched healthy controls (HCs). In addition, a T1-weighted MPRAGE was also acquired in the same scan session. After a standard preprocessing, resting state networks (RSNs) and CBF maps were extracted from rsfMRI and ASL dataset, respectively. Then, by means of a dual regression algorithm performed on RSNs, a cluster of FC differences between groups was obtained and used to mask CBF maps in the subsequent voxel-wise group comparison. Furthermore, a gray matter (GM) volumetric assessment was performed within the FC cluster in order to exclude tissue atrophy as a source of functional changes. Reduced FC for a PD patient with respect to HC group was found within a sensory-motor network (SMN, pFWE = 0.01) and visual networks (VNs, primary pFWE = 0.022 and lateral pFWE = 0.01). The latter was accompanied by a decreased CBF (primary pFWE = 0.037, lateral pFWE = 0.014 VNs), while no GM atrophy was detected instead. The FC alteration found in the SMN of PD might be likely due to a dopaminergic denervation of the striatal pathways causing a functional disconnection. On the other hand, the changes in connectivity depicted in VNs might be related to an altered non-dopaminergic system, since perfusion was also reduced, revealing a compromised NVC. Finally, the absence of GM volume loss might imply that functional changes may potentially anticipate neurodegeneration. In this framework, FC and CBF might be proposed as early functional biomarkers providing meaningful insights in evaluating both disease progression and therapeutic/rehabilitation treatment outcome.


Acylcarnitines in plasma and blood spots of patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase defiency.
The acylcarnitines in plasma and blood spots of 23 patients with proven deficiency of long-chain 3-hydroxyacylcoenzyme A dehydrogenase were reviewed. Long-chain 3-hydroxyacylcarnitines of C14:1, C14, C16 and C18:1 chain length, and long-chain acylcarnitines of C12, C14:1, C14, C16, C18:2 and C18:1 chain length were elevated. Acetylcarnitine was decreased. In plasma, elevation of hydroxy-C18:1 acylcarnitine over the 95th centile of controls, in combination with an elevation of two of the three acylcarnitines C14, C14:1 and hydroxy-C16, identified over 85% of patients with high specificity (less than 0.1% false positive rate). High endogenous levels of long-chain acylcarnitines in normal erythrocytes reduced the diagnostic specificity in blood spots compared with plasma samples. The results were also diagnostic in asymptomatic patients, and were not influenced by genotype. Treatment with diet low in fat and high in medium-chain triglyceride decreased all disease-specific acylcarnitines, often to normal, suggesting that this assay is useful in treatment monitoring.


Comparison of clinical effectiveness and subsequent fertility between hysteroscopic resection and vaginal repair in patients with cesarean scar defect: a prospective observational study.
To evaluate the clinical effectiveness and pregnancy rate after hysteroscopic resection (HR) and/or vaginal repair (VR) in patients with cesarean scar defect (CSD). This prospective observational study enrolled 191 patients who received CSD surgery in the First affiliated hospital of Sun Yat-sen University between September 2019 to February 2022 (96 in HR and 95 in VR, respectively). Patient follow-up were performed three months after surgery in both groups by transvaginal ultrasound to confirm the presence of fluid in the niche, along with the resolution of prolonged menses at the same time. The primary outcome was the clinical effectiveness between HR and VR, identified by the resolution of prolonged menses. The rates of niche-fluid disappearance (70.1% vs 60.2%, P = 0.176) and prolonged menses resolution (74.8% vs 80.0%, P = 0.341) were comparable for HR and VR. A subgroup analysis for niche size revealed that HR provides patients with small niche a more favorable rate of menstrual resolution compared to VR (size of niche ≤ 15 mm2, aOR = 3.423, 95% confidence interval [CI] 1.073-10.918), but patients with large niche experience a lower rate of resolution compared to VR (size of niche > 25 mm2, aOR = 0.286, 95% CI 0.087- 0.938). During follow-up, 41 patients who wanted to conceive became pregnant. Kaplan-Meier estimates of the cumulative probability of pregnancy at 12 months and 24 months were 47.1% (95% CI: 34.5%, 58.8%) and 63.8% (95% CI: 52.5%, 72.9%), respectively. The median pregnancy time was 22 months (95% CI: 14.2, 29.8) after VR and 12 months (95% CI: 8.3, 15.7, Gehan-Breslow-Wilcoxon P = 0.021) after HR. Among patients with subsequent infertility, 31.6% achieved pregnancy by unassisted mode and 29.8% by IVF/ICSI. Moreover, among patients with previously failed IVF/ICSI treatment, 60% (12/20) obtained pregnancy, including 71.4% (10/14) after HR and 33.3% (2/6) after VR. Hysteroscopic resection is as effective as vaginal repair at relieving symptoms of CSD-associated prolonged menses. Hysteroscopic resection is the modality of choice with an improvement in prolonged menses for small niche, while vaginal might be considered for a large niche. Furthermore, surgical intervention could improve the clinical pregnancy rate of CSD patients. All of these provide evidence for the individualized management of CSD.


A Marathon session: a town's MDs develop a philosophy to call their own.
Last June CMAJ described how Marathon--a remote town in Northern Ontario--had gone from medical rags to riches in just over a year (CMAJ 1997;156:1593-6). Once chronically underserviced in terms of physician services, this community of 5500 people went from a single overworked doctor to a group practice of 7 physicians. The change involved far more than numbers, however. The Marathon solution was built on a philosophy of physician sustainability and long-term retention, not just recruitment. The change was designed to ensure that the town could finally get off the roller-coaster ride that saw more than 75 doctors come--and go--during the previous 10 years. A year after its initial report, CMAJ returned to see if the Marathon experiment was still working.


Cdk5-dependent Mst3 phosphorylation and activity regulate neuronal migration through RhoA inhibition.
The radial migration of newborn neurons is critical for the lamination of the cerebral cortex. Proper neuronal migration requires precise and rapid reorganization of the actin and microtubule cytoskeleton. However, the underlying signaling mechanisms controlling cytoskeletal reorganization are not well understood. Here, we show that Mst3, a serine/threonine kinase highly expressed in the developing mouse brain, is essential for radial neuronal migration and final neuronal positioning in the developing mouse neocortex. Mst3 silencing by in utero electroporation perturbed the multipolar-to-bipolar transition of migrating neurons and significantly retards radial migration. Although the kinase activity of Mst3 is essential for its functions in neuronal morphogenesis and migration, it is regulated via its phosphorylation at Ser79 by a serine/threonine kinase, cyclin-dependent kinase 5 (Cdk5). Our results show that Mst3 regulates neuronal migration through modulating the activity of RhoA, a Rho-GTPase critical for actin cytoskeletal reorganization. Mst3 phosphorylates RhoA at Ser26, thereby negatively regulating the GTPase activity of RhoA. Importantly, RhoA knockdown successfully rescues neuronal migration defect in Mst3-knockdown cortices. Our findings collectively suggest that Cdk5-Mst3 signaling regulates neuronal migration via RhoA-dependent actin dynamics.


Albumin regulates the Na+/H+ exchanger 3 in OKP cells.
Albumin filtered by the glomerulus is reabsorbed in the proximal tubule. We have shown previously that proteinuria stimulates the proximal tubular Na(+)/H(+) exchanger 3 (NHE3) in rats. Activation of NHE3 may be a pathophysiologically important factor in the development of renal salt and water retention observed in the nephrotic syndrome. For examining whether albumin is a specific inducer of proximal tubular Na(+)/H(+) exchange and to determine the molecular mechanisms by which it regulates Na(+)/H(+) exchange, the effect of albumin on NHE3 in opossum kidney cells was studied. Albumin activated Na(+)/H(+) exchange in a time- and dose-dependent manner up to 100% in 48 h. In the early phase of stimulation (2 to 12 h), NHE3 activity was increased without changes in NHE3 protein and mRNA. At 24 h, increased NHE3 activity was accompanied by increase in cell surface NHE3 protein. The increase in surface NHE3 was associated with increased bidirectional trafficking of NHE3 protein between intracellular compartments and the cell surface. At 48 h, total cell NHE3 protein abundance and mRNA were increased as well. Whereas NHE3 translation was increased, NHE3 protein half-life remained unchanged. The effects of albumin on NHE3 protein abundance were modified by hydrocortisone in a complicated pattern. These results indicate that albumin directly regulates proximal tubular NHE3 at multiple levels.


Bezoar in upper gastrointestinal endoscopy: A single center experience.
We aimed to investigate the association of bezoar with endoscopic findings, risk factors for bezoar occurrence, and the success of endoscopic treatment in a tertiary center. This retrospective study was conducted between January 2012 and December 2015. Overall, 8200 endoscopy records were examined and 66 patients with bezoar were included in the study. We enrolled 29 (44%) female and 37 (56%) male patients in this study. The mean age of the patients was 63±9.4 years. The most frequent risk factors were history of gastrointestinal surgery (23%), diabetes mellitus (17%), trichophagia (9%), and anxiety disorder (6%). Gastric ulcer, duodenal ulcer, erosive gastritis, and reflux esophagitis were present in 27%, 11%, 20%, and 23% of the patients, respectively. While bezoars were most commonly observed in the stomach (70%), the majority of them were phytobezoars (91%). The mean number of interventions for each patient was 1.5 (range, 1-6). Endoscopy was successful in removing bezoars in 86.5% of the patients. Among those referred to surgery, seven patients underwent gastrostomy (10.5%); one (1.5%) patient underwent gastroenterostomy because of concomitant pyloric stenosis; and one (1.5%) patient underwent fistula repair surgery due to the development of duodenal fistula caused by bezoar. The findings of this study indicated that bezoars are more common among subjects with history of gastrointestinal surgery, diabetes mellitus, or psychiatric disorders; bezoars are closely related to peptic ulcer and reflux esophagitis; and they can be successfully treated with endoscopy.


The distribution of functional impairment across the lateral border of acutely ischemic myocardium.
To evaluate the degree and lateral extent of dysfunction in nonischemic myocardium adjacent to ischemic muscle, we measured systolic wall thickening with sonomicrometers during circumflex coronary occlusion in 12 anesthetized, open-chest dogs. The locations of the wall thickness measurements relative to the perfusion boundary were determined with myocardial blood flow (microspheres) maps constructed from multiple, small tissue samples. Five minutes after circumflex occlusion, systolic wall thickening in the central ischemic zone decreased from 3.00 +/- 0.61 (mean +/- SD) mm to -0.61 +/- 0.36 mm (P less than 0.01). In nonischemic myocardium greater than 10 mm from the perfusion boundary, systolic wall thickening increased from 2.56 +/- 0.57 to 3.24 +/- 0.72 mm (P less than 0.01). In nonischemic myocardium within 10 mm of the perfusion boundary, systolic wall thickening was slightly but significantly reduced compared with control (2.72 +/- 0.80 to 2.44 +/- 0.79 mm, P less than 0.05), supporting the concept of regional dysfunction in nonischemic myocardium at the lateral borders of an ischemic area. Sigmoid curves were fitted to the data to model changes in wall thickening as a continuous function of distance from the perfusion boundary. This allowed estimation of the extent of dysfunction into nonischemic myocardium which averaged less than 8 mm (approximately 30 degrees of endocardial circumference) at one border. The level of functional impairment in this zone was relatively modest, and systolic wall thickening in the immediate border area was reduced more than 50% from control only in tissue characterized by a blood supply of mixed ischemic and nonischemic origin. We conclude that a functional border zone exists lateral to an acutely ischemic area, but measurement of regional function produces relatively small exaggeration of the size of the acutely ischemic zone if severe reduction in mechanical performance is used to define the extent of the ischemic area.


[Epidermoid splenic cysts and partial splenectomy].
We communicate two cases of epidermoid splenic cyst of great size in four and six years old children, with pain in right hypochondrium in one of them, having been casual the discovery of the other one in ultrasound study of the abdomen. In both cases the abdominal ultrasound study was the most useful exploration for its diagnosis. The surgical treatment by means of partial splenectomy and conservation of more than a third of the organ it has been feasible in both patients, with a favorable evolution and without complications. The histopathologic study confirmed the discovery of epidermoid spleen cysts. Later on a clinical, analytic pursuit has been made and of these patients image with a very satisfactory evolution.


A brief review of the management of platinum-resistant-platinum-refractory ovarian cancer.
Ovarian cancer, which ranks fifth in cancer deaths among women, is the most lethal gynecologic malignancy. Epithelial ovarian cancer (EOC) is the most common histologic type, with the 5-year survival for all stages estimated at 45.6%. This rate increases to more than 70% in the minority of patients who are diagnosed at an early stage, but declines to 35% in the vast majority of patients diagnosed at advanced stage. Recurrent EOC is incurable. Platinum sensitivity (or lack thereof) is a major determinant of prognosis. The current standard treatment is primary surgery followed by platinum-based chemotherapy. In recurrent platinum-resistant/platinum-refractory EOC, sequential single-agent salvage chemotherapy is superior to multiagent chemotherapy. Multiagent regimens increase toxicity without clear benefit; however, no preferred sequence of single agents is recommended. The impact of targeted therapies and immunotherapies on progression-free survival and overall survival, which remains dismal, is under active investigation. Currently, clinical trials offer the best hope for the development of a new treatment paradigm in this recalcitrant disease.


Comparison of maternal and perinatal outcomes in women with super obesity based on planned mode of delivery.
Currently, little evidence exists to guide mode of delivery in pregnant women with super obesity. There is a trend toward elective caesarean delivery in this population with little evidence of improved maternal or neonatal outcomes. Our study compares maternal and neonatal outcomes based on planned mode of delivery and aimed to identify predictors for a successful vaginal delivery. This retrospective observational study explored maternal and neonatal outcomes of women with a body mass index ≥50 who birthed following a singleton pregnancy at ≥36 weeks gestation over a 10 year period at a single centre in Melbourne, Australia. Outcomes between women having a planned vaginal or planned caesarean birth were compared on an intention-to-treat basis, with logistic regression used to determine factors predictive of a vaginal birth. A total of 275 women with super obesity were identified. One hundred and ninety-nine (72%) planned a vaginal birth, which was successful for 70%. Planned vaginal birth was associated with lower rates of postpartum complications requiring readmission (5% vs 16%; P = 0.003). Neonatal resuscitation requirements and Apgar scores at five minutes were similar between groups. Multiparity was the strongest predictor of a successful vaginal birth while medical intervention in labour was associated with a reduced rate of success in primiparous women. Contrary to current trends in practice, a trial of labour for women with super obesity, when facilities and skills permit, appears a safe option for mother and baby.


Molecular Docking and Drug Discovery in β-Adrenergic Receptors.
Evolution in computer engineering, availability of increasing amounts of data and the development of new and fast docking algorithms and software have led to improved molecular simulations with crucial applications in virtual high-throughput screening and drug discovery. Moreover, analysis of protein-ligand recognition through molecular docking has become a valuable tool in drug design. In this review, we focus on the applicability of molecular docking on a particular class of G protein-coupled receptors: the β-adrenergic receptors, which are relevant targets in clinic for the treatment of asthma and cardiovascular diseases. We describe the binding site in β-adrenergic receptors to understand key factors in ligand recognition along with the proteins activation process. Moreover, we focus on the discovery of new lead compounds that bind the receptors, on the evaluation of virtual screening using the active/ inactive binding site states, and on the structural optimization of known families of binders to improve β-adrenergic affinity. We also discussed strengths and challenges related to the applicability of molecular docking in β-adrenergic receptors. Molecular docking is a valuable technique in computational chemistry to deeply analyze ligand recognition and has led to important breakthroughs in drug discovery and design in the field of β-adrenergic receptors.


Disparities in Neuro-Oncology.
Health disparities are preventable differences in the diagnosis, treatment, and outcomes of many diseases, including central nervous system (CNS) tumors. This review will summarize and compile the existing literature on health disparities in neuro-oncology and provide directions for future research and interventions. Patients from historically marginalized groups are more likely to receive inadequate treatment, develop complications, and experience a shorter life expectancy. Financial toxicity can be particularly severe for patients with CNS tumors due to the high costs of treatment. Additionally, CNS clinical trials and research lack diverse representation.


Genetic regulation of canine skeletal traits: trade-offs between the hind limbs and forelimbs in the fox and dog.
Genetic variation in functionally integrated skeletal traits can be maintained over 10 million years despite bottlenecks and stringent selection. Here, we describe an analysis of the genetic architecture of the canid axial skeleton using populations of the Portuguese Water Dog Canis familiaris) and silver fox (Vulpes vulpes). Twenty-one skeletal metrics taken from radiographs of the forelimbs and hind limbs of the fox and dog were used to construct separate anatomical principal component (PC) matrices of the two species. In both species, 15 of the 21 PCs exhibited significant heritability, ranging from 25% to 70%. The second PC, in both species, represents a trade-off in which limb-bone width is inversely correlated with limb-bone length. PC2 accounts for approximately 15% of the observed skeletal variation, approximately 30% of the variation in shape. Many of the other significant PCs affect very small amounts of variation (e.g., 0.2-2%) along trade-off axes that partition function between the forelimbs and hind limbs. These PCs represent shape axes in which an increase in size of an element of the forelimb is associated with a decrease in size of an element of the hind limb and vice versa. In most cases, these trade-offs are heritable in both species and genetic loci have been identified in the Portuguese Water Dog for many of these. These PCs, present in both the dog and the fox, include ones that affect lengths of the forelimb versus the hind limb, length of the forefoot versus that of the hind foot, muscle moment (i.e., lever) arms of the forelimb versus hind limb, and cortical thickness of the bones of the forelimb versus hind limb. These inverse relationships suggest that genetic regulation of the axial skeleton results, in part, from the action of genes that influence suites of functionally integrated traits. Their presence in both dogs and foxes suggests that the genes controlling the regulation of these PCs of the forelimb versus hind limb may be found in other tetrapod taxa.


A GATA-1-regulated microRNA locus essential for erythropoiesis.
MicroRNAs (miRNAs) control tissue development, but their mechanism of regulation is not well understood. We used a gene complementation strategy combined with microarray screening to identify miRNAs involved in the formation of erythroid (red blood) cells. Two conserved miRNAs, miR 144 and miR 451, emerged as direct targets of the critical hematopoietic transcription factor GATA-1. In vivo, GATA-1 binds a distal upstream regulatory element to activate RNA polymerase II-mediated transcription of a single common precursor RNA (pri-miRNA) encoding both mature miRNAs. Zebrafish embryos depleted of miR 451 by using antisense morpholinos form erythroid precursors, but their development into mature circulating red blood cells is strongly and specifically impaired. These results reveal a miRNA locus that is required for erythropoiesis and uncover a new regulatory axis through which GATA-1 controls this process.


First report of canine morbillivirus infection of adipose tissue-derived stem cells from dogs with distemper.
Ribonucleic acid viruses remain latent in different cell types, including mesenchymal stem cells; however, the distemper virus remains undetected in these cells. This study aimed to determine whether adipose stem cells (ASCs) from dogs with distemper disease are infected with the canine morbillivirus (CM). Twelve dogs with the neurological phase of the disease and who were positive for CM by reverse transcription polymerase chain reaction (RT-PCR), were studied. ASCs from adipose tissue of the lesser omentum of these infected dogs were isolated and characterized. Direct fluorescence was used to detect the viral antigen in cell cultures. Flow cytometry and RT-PCR identified detectable quantities of the virus in two cultures, while electron microscopy confirmed the CM particles within ASCs. This study revealed that ASCs of the omentum of dogs with distemper disease can be infected with CM, indicating their possible involvement in this virus latency and persistence. This suggests that its detection should be considered within the quality control process of stem cells intended for regenerative medicine. To the best of our knowledge, this is the first study that demonstrates that omentum ASCs from dogs with distemper disease can be infected with CM and may be involved in viral latency or persistence. Our study also suggests that the detection of CM should be considered within the quality control process of stem cells intended for regenerative medicine.


Echinococcosis in Libya. III. Further studies on the prevalence of Echinococcus granulosus in dogs.
Of 92 dogs examined for Echinococcus granulosus at five sites in Libya from April 1985 to September 1988 33 (35.9%) were infected, the prevalences ranging from 60% (Zawiyah) and 52.0% (Tripoli) in the north-west, to 28.6% (Benghazi) and 28.5% (Darna) in the north-east. None of eight dogs at Al-Kufra, in the south-eastern desert, were infected. Twenty dogs each had two to 200 worms, nine had 201-1000 worms and four each had over 1000 worms (one dog in Tripoli had 17,120 worms). Most infections were seen in dogs aged three to four years; 45.4% of bitches and 35.4% of males were infected.


Early acute kidney injury in military casualties.
While acute kidney injury (AKI) has been well studied in a variety of patient settings, there is a paucity of data in patients injured in the course of the recent wars in Iraq and Afghanistan. We sought to establish the rate of early AKI in this population and to define risk factors for its development. We combined the results of two studies performed at combat support hospitals in Afghanistan. Only US service members who required care in the intensive care unit were included for analysis. Data on age, race, sex, Injury Severity Score (ISS), first available lactate, and requirement for massive transfusion were collected. Univariate analyses were performed to identify factors associated with the subsequent development of early AKI. Multivariable Cox regression was used to adjust for potential confounders. The two observational cohorts yielded 134 subjects for analysis. The studies had broadly similar populations but differed in terms of age and need for massive transfusion. The rate of early AKI in the combined cohort was 34.3%, with the majority (80.5%) occurring within the first two hospital days. Patients with AKI had higher unadjusted mortality rates than those without AKI (21.7% vs. 2.3%, p < 0.001). After adjustment, ISS (hazard ratio, 1.02; 95% confidence interval, 1.00-1.03; p = 0.046) and initial lactate (hazard ratio, 1.16; 95% confidence interval, 1.03-1.31; p = 0.015) were independently associated with the development of AKI. AKI is common in combat casualties enrolled in two prospective intensive care unit studies, occurring in 34.3%, and is associated with crude mortality. ISS and initial lactate are independently associated with the subsequent development of early AKI. Prognostic and epidemiologic study, level III.


One Digital Health: A Unified Framework for Future Health Ecosystems.
One Digital Health is a proposed unified structure. The conceptual framework of the One Digital Health Steering Wheel is built around two keys (ie, One Health and digital health), three perspectives (ie, individual health and well-being, population and society, and ecosystem), and five dimensions (ie, citizens' engagement, education, environment, human and veterinary health care, and Healthcare Industry 4.0). One Digital Health aims to digitally transform future health ecosystems, by implementing a systemic health and life sciences approach that takes into account broad digital technology perspectives on human health, animal health, and the management of the surrounding environment. This approach allows for the examination of how future generations of health informaticians can address the intrinsic complexity of novel health and care scenarios in digitally transformed health ecosystems. In the emerging hybrid landscape, citizens and their health data have been called to play a central role in the management of individual-level and population-level perspective data. The main challenges of One Digital Health include facilitating and improving interactions between One Health and digital health communities, to allow for efficient interactions and the delivery of near-real-time, data-driven contributions in systems medicine and systems ecology. However, digital health literacy; the capacity to understand and engage in health prevention activities; self-management; and collaboration in the prevention, control, and alleviation of potential problems are necessary in systemic, ecosystem-driven public health and data science research. Therefore, people in a healthy One Digital Health ecosystem must use an active and forceful approach to prevent and manage health crises and disasters, such as the COVID-19 pandemic.


Non-surgical therapy of lung cancer--a critical review by a respiratory physician.
The state of the art of radiotherapy and chemotherapy in inoperable lung cancer is described. The possible role of radical and palliative radiotherapy is also discussed. There is an extreme contrast between small cell lung cancer and non small cell lung cancer with regard to prognosis (with and without therapy) and to their sensitivity to chemotherapy. Radiotherapy with curative intent (radical dosage) is disappointing in both cell types, however as a palliative measure it is most useful in the majority of situations in all lung cancer cell types. Small cell cancer is in general extremely sensitive to chemotherapy but the responses are usually of limited duration, probably due to the development of drug resistance. Non small cell lung cancer is insensitive to chemotherapy. New trends in radiotherapy and chemotherapy are described.


[Effect of blockaders of biogenic amine receptors on experimental ulcer development].
The effects of serotonin antagonist peritol, cholinolytic atropine, H2-receptor blocker cimetidine and dopaminergic receptor blocker metoclopramide on stress- and exogenous serotonin-induced gastric ulcerogenesis in rats were studied. Peritol was shown to inhibit significantly serotonin- an stress-induced hemorrhagic effect. Similar but less pronounced inhibit produced by metoclopramide and cimetidine. Atropine decreased gastric hemorrhages induced by serotonin but failed to affect stress-induced hemorrhagic lesions. All antagonists tested decreased stress-induced erosions. Erosive lesions stimulated by exogenous serotonin were significantly decreased by atropine only. Metoclopramide known for its cholinomimetic action increased serotonin-induced erosions. It was concluded that serotonin plays an essential role in the pathogenesis of gastric lesions, and its effects suggest the involvement of acetylcholine, histamine and dopamine.


Non-intubated anaesthetic technique in open bilobectomy in a patient with severely impaired lung function.
General anaesthesia has been the most commonly used method for almost all types of thoracic surgery. Recently, there has been a growing interest in non-intubated anaesthetic techniques. The rationale being, to prevent complications related to general anaesthesia and positive pressure ventilation such as barotrauma or ventilation-perfusion mismatch. We present a case with severely impaired forced expiration volume (26%), carbon monoxide diffusing capacity (26%) and VO2max (13.9 mL/kg/min). According to current guidelines, this patient was suitable to undergo one-lung ventilation only with high risk of morbidity and mortality. Therefore, we chose the non-intubated technique for thoracotomy. Oxygenation was satisfactory throughout, the patient remained hemodynamically stable and the operation was uneventful. Oxygen supplementation was stopped from day 2 and he was discharged on day 7. To our knowledge, this is the first case report where a planned non-intubated method was applied for thoracotomy, and our results suggest that it might be a feasible and safe approach for open thoracotomy in difficult cases where severely impaired lung function indicates that one lung ventilation may carry significant risks.


Stretchable and tough conductive hydrogels for flexible pressure and strain sensors.
Flexible pressure and strain sensors have great potential for applications in wearable and implantable devices, soft robotics and artificial skin. Compared to flexible sensors based on filler/elastomer composites, conductive hydrogels are advantageous due to their biomimetic structures and properties, as well as biocompatibility. Numerous chemical and structural designs provide unlimited opportunities to tune the properties and performance of conductive hydrogels to match various demands for practical applications. Many electronically and ionically conductive hydrogels have been developed to fabricate pressure and strain sensors with different configurations, including resistance type and capacitance type. The sensitivity, reliability and stability of hydrogel sensors are dependent on their network structures and mechanical properties. This review focuses on tough conductive hydrogels for flexible sensors. Representative strategies to prepare stretchable, strong, tough and self-healing hydrogels are briefly reviewed since these strategies are illuminating for the development of tough conductive hydrogels. Then, a general account on various conductive hydrogels is presented and discussed. Recent advances in tough conductive hydrogels with well designed network structures and their sensory performance are discussed in detail. A series of conductive hydrogel sensors and their application in wearable devices are reviewed. Some perspectives on flexible conductive hydrogel sensors and their applications are presented at the end.


Inhibition of carbonic anhydrase using aspirin is a novel method to block schistosomiasis infection of the parasitic trematode, Schistosoma mansoni, in the intermediate snail host, Biomphalaria glabrata.
Schistosomiasis is a major public health concern worldwide. Although praziquantel is currently available as the only treatment option for schistosomiasis, the absence of reliable diagnostic and prognostic tools highlights the need for the identification and characterization of new drug targets. Recently, we identified the B. glabrata homolog (accession number XP_013075832.1) of human CAXIV, showing 37% amino acid sequence identity, from a BLAST search in NCBI (National Center for Biotechnology Information). Carbonic Anhydrases (CAs) are metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3. These enzymes are associated with many physiological processes, and their role in tumorigenesis has been widely implicated. CAs create an acidic extracellular environment that facilitates the survival, metastasis, and growth of cancer cells. In this study, we investigated the role of CA inhibition in B. glabrata snails exposed to S. mansoni miracidia. We analyzed the expression of the B. glabrata CA encoding transcript in juvenile susceptible and resistant snails, with and without exposure to S. mansoni. Our results showed that the expression of the CA mRNA encoding transcript was upregulated during early and prolonged infection in susceptible snails (BBO2), but not in the resistant BS-90 stock. Notably, sodium salicylate, a form of aspirin, inhibited the expression of CA, post-exposure, to the parasite. Increasing research between parasites and cancer has shown that schistosomes and cancer cells share similarities in their capacity to proliferate, survive, and evade host immune mechanisms. Here, we show that this model system is a potential new avenue for understanding the role of CA in the metastasis and proliferation of cancer cells. Further studies are needed to explore the potential of CA as a biomarker for infection in other schistosomiasis-causing parasites, including S. japonicum and S. haematobium.


Predicted correspondence between species abundances and dendrograms of niche similarities.
We examine a hypothesized relationship between two descriptions of community structure: the niche-overlap dendrogram that describes the ecological similarities of species and the pattern of relative abundances. Specifically, we examine the way in which this relationship follows from the niche hierarchy model, whose fundamental assumption is a direct connection between abundances and underlying hierarchical community organization. We test three important, although correlated, predictions of the niche hierarchy model and show that they are upheld in a set of 11 communities (encompassing fishes, amphibians, lizards, and birds) where both abundances and dendrograms were reported. First, species that are highly nested in the dendrogram are on average less abundant than species from branches less subdivided. Second, and more significantly, more equitable community abundances are associated with more evenly branched dendrogram structures, whereas less equitable abundances are associated with less even dendrograms. This relationship shows that abundance patterns can give insight into less visible aspects of community organization. Third, one can recover the distribution of proportional abundances seen in assemblages containing two species by treating each branch point in the dendrogram as a two-species case. This reconstruction cannot be achieved if abundances and the dendrogram are unrelated and suggests a method for hierarchically decomposing systems. To our knowledge, this is the first test of a species abundance model based on nontrivial predictions as to the origins and causes of abundance patterns, and not simply on the goodness-of-fit of distributions.


Solution structure and backbone dynamics of the TGFbeta type II receptor extracellular domain.
Isoforms of transforming growth factor beta (TGFbeta) are 25 kDa homodimeric polypeptides that signal by binding and bringing together two related, functionally distinct cell surface receptors designated as TbetaR1 and TbetaR2. Here, we report the solution structure of the 13.8 kDa extracellular domain of human TbetaR2 (ecTbetaR2) as calculated from N(N)-H(N), C(alpha)-H(alpha), and C(alpha)-C(O) residual dipolar coupling restraints in conjunction with NOE distance, dihedral angle, and scalar coupling restraints. Comparison of the free ecTbetaR2 solution structure with the TGFbeta3-bound ecTbetaR2 crystal structure reveals backbone conformations that superimpose with RMSDs of 1.0 A over the regions of regular secondary structure and 1.4 A overall. The differences in structure fall mainly in loop regions that are either poorly defined by the available NMR data or are involved in crystal contacts. The noted similarities between the NMR structure of the free form and the crystal structure of the TGFbeta-bound form are also consistent with the close correspondence, 0.16 A RMSD for regions of secondary structure and 0.51 A RMSD overall, for the crystal structure of free ecTbetaR2 as compared to the crystal structure of TGFbeta3-bound ecTbetaR2. Despite the apparent similarities between the free and the bound forms, there appears to be small but significant differences in structure involving the interfacial contact region of the receptor. Measurements of backbone (15)N relaxation times and interpretation of these by the model-free formalism with axial diffusional anisotropy further reveal significant ms to micros time scale motions centered about two of the conserved disulfide bonds and in several residues that comprise the TGFbeta binding surface. Together, these observations indicate that binding likely occurs through a mechanism with a small component of induced fit character, whereby flexibility within the receptor facilitates the transition to the TGFbeta-bound state.


Assessing mental well-being in family carers of people with dementia using the Warwick-Edinburgh Mental Well-Being Scale.
Understanding and measuring mental health and well-being among carers of people with dementia has become an important public health issue. In the present study we used the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) to identify predictors of positive mental health in a convenience sample of family carers of people with dementia using a cross-sectional design. WEMWBS showed a negative correlation with anxiety and depressive symptoms, and a positive correlation with physical health status. Regression analyses indicated that overall nearly 70% of the variance in mental well-being in carers could be attributed to caregiver's age, physical health, stress specific to caregiving, and social support. Preliminary data show that the WEMWBS demonstrates strong internal consistency. Confirmatory factor analysis demonstrated one underlying factor of positive mental well-being. WEMWBS is a psychometrically strong measure of mental well-being, and can be used to identify factors that promote positive mental health in family carers of people with dementia. Current results provide preliminary data supporting the usefulness of the scale as an overall indicator of population mental health and well-being for carers of people with dementia.


[Related factors to re-bleeding and mortality in cirrhotic patients with acute variceal bleeding at Hipolito Unanue Hospital, Lima, Peru].
To determine related factors to 5 days re-bleeding and 6 week-mortality of an episode of variceal bleeding in cirrhotic patients. Observational, descriptive, co relational, retrospective study. In this study were included the cirrhotic patients who entered to Hipolito Unanue Hospital, Lima, Peru, between January 2006 and February 2012 with suspicion of variceal bleeding. Were excluded patients who bled from nonvariceal origin, or that did not have the data in clinical history to calculate the Child Pugh score, the Model for terminal diseases of the liver (MELD), or the endoscopic report detailing the bleeding source and the presence of esophageal and/or gastric varices. We include 63 patients, 35 (55.6%) were men. The median of age was of 64 years. 26 of them (41.3%) were Child Pugh C, where as the median of MELD score was 9. The multivariate analysis found that the Child Pugh score was related to 6 weeks-mortality (p=0,003), where as the presence of active bleeding during endoscopy (p=0.012) and the value of creatinine (p=0.012) were related to 5 days re-bleeding. The Child Pugh score was related to 6 weeks-mortality in cirrhotic patients with variceal bleeding. Active bleeding during endoscopy and the value of creatinine were related to 5 days re-bleeding.


A Deep-Learning-Driven Light-Weight Phishing Detection Sensor.
This paper designs an accurate and low-cost phishing detection sensor by exploring deep learning techniques. Phishing is a very common social engineering technique. The attackers try to deceive online users by mimicking a uniform resource locator (URL) and a webpage. Traditionally, phishing detection is largely based on manual reports from users. Machine learning techniques have recently been introduced for phishing detection. With the recent rapid development of deep learning techniques, many deep-learning-based recognition methods have also been explored to improve classification performance. This paper proposes a light-weight deep learning algorithm to detect the malicious URLs and enable a real-time and energy-saving phishing detection sensor. Experimental tests and comparisons have been conducted to verify the efficacy of the proposed method. According to the experiments, the true detection rate has been improved. This paper has also verified that the proposed method can run in an energy-saving embedded single board computer in real-time.