Adolescent disclosure and concealment: longitudinal and concurrent associations with aggression.
This longitudinal study assessed the association between prior (preschool) and concurrent physical and relational aggression as they relate to Russian adolescents' disclosure and concealment patterns with their parents. In the initial preschool study, there were 106 boys and 106 girls (mean age = 60.24 months, SD = 7.81). Both peer nominations and teacher ratings of aggression were obtained for these children. Ten years later, the majority of these children (72.2%; n = 153) completed a longitudinal follow-up battery of assessments. Included in these measures was a self-reported measure of aggression as well as an assessment of the extent to which these adolescents disclosed to and concealed information from their parents. Separate models were estimated by gender of child for the 153 children who participated in both Time 1 and Time 2 data collections. Preschool physical aggression proved an important longitudinal predictor of adolescent disclosure and concealment for girls. Concurrently, self-rated relational aggression was also significantly associated with concealment for both boys and girls.


Swelling behaviours of compacted lime-softening sludge for application in landfill liners.
The objective of this study was to investigate the swelling potential of compacted lime-softening sludge for application in landfill liners. The study involved the assessment of the effect of compaction and moulding moisture content (30-40%), corresponding to the Proctor standard compaction test. One-dimensional oedometer swell tests were conducted using distilled water, tap water, and municipal landfill leachate, resulting in the determination of the expansion indices. Moreover, changes in the moisture content and dry density during the swelling process were investigated. The expansion index was significantly influenced by the initial moisture content and liquid chemistry. Subsequently, these factors also affected the sludge dry density decrease, and its moisture content increase, whereas the impact of the initial dry density on expansion was of low importance. An increase in the sludge moulding moisture content, limited swelling in all liquids used. The highest expansion, dry density, and moisture content changes due to swelling were identified for leachate at w < wopt. It should be underlined that the effect of liquid on the swelling potential faded away along with a further increase in the moisture content w > wopt. The novelty of the work lies in identifying a significant plunge of the expansion index at w ≈ wopt for the leachate swelling test. The lime-softening sludge non-swelling moisture content was defined as wnon ≈ (wopt + 4.0%) - (wopt + 4.5%). For practical engineering implications, the moisture content between (wopt + 2.0%) and (wopt + 4.0%) was provided for the most suitable sludge application in landfill liners.


Highly efficient and durable antimicrobial nanocomposite textiles.
Healthcare associated infections cause millions of hospitalizations and cost billions of dollars every year. A potential solution to address this problem is to develop antimicrobial textile for healthcare fabrics (hospital bedding, gowns, lab coats, etc.). Metal nanoparticle-coated textile has been proven to possess antimicrobial properties but have not been adopted by healthcare facilities due to risks of leaching and subsequent loss of function, toxicity, and environmental pollution. This work presents the development and testing of antimicrobial zinc nanocomposite textiles, fabricated using a novel Crescoating process. In this process, zinc nanoparticles are grown in situ within the bulk of different natural and synthetic fabrics to form safe and durable nanocomposites. The zinc nanocomposite textiles show unprecedented microbial reduction of 99.99% (4 log10) to 99.9999% (6 log10) within 24 h on the most common Gram-positive and Gram-negative bacteria, and fungal pathogens. Furthermore, the antimicrobial activity remains intact even after 100 laundry cycles, demonstrating the high longevity and durability of the textile. Independent dermatological evaluation confirmed that the novel textile is non-irritating and hypoallergenic.


Denervation of rabbit lacrimal gland increases levels of transferrin and unidentified tear proteins of 44 and 36 kDa.
The main lacrimal gland secretes proteins and fluid that make up the aqueous component of the tears. Previous reports indicate that the parasympathetic innervation of the gland influences the secretion of protein from the lacrimal gland. We investigated the effect of lacrimal nerve transection on the levels of individual proteins and overall protein concentration in the tear fluid. The main lacrimal gland was unilaterally denervated in adult rabbits at the site of nerve entry to the gland. The contralateral gland (sham-operated) had identical surgical manipulations, excluding nerve transection. Tears were collected daily from both eyes for up to 9 days, after which lacrimal glands were collected. SDS-PAGE, densitometric and image analysis, and Western blot were performed. Consistently measurable tear protein bands ranged from 6 kDa to 85 kDa, using densitometric analysis. Lacrimal gland denervation produced a sustained increase in proteins of 85, 44, and 36 kDa in tears and lacrimal gland tissue from the denervated side, compared with the sham-operated side (0.025 > p > 0.001). The band at 85 kDa was identified as transferrin by Western blot. Tears from the denervated glands also showed transient decreases in low molecular weight tear proteins (18, 12/10, and 6 kDa), as well as a decrease in overall protein concentration, compared with tears from sham-operated glands and non-operated glands (p < 0.001). These results demonstrate that, in rabbit tears, the quantities of transferrin and two unidentified tear proteins, as well as overall protein concentration, are influenced by the sensory and/or autonomic innervation to the lacrimal gland. The decrease in overall tear protein concentration after lacrimal gland denervation may be related to a loss of nerve-regulated secretagogue-induced protein secretion.


Malignant mesothelioma in construction workers: the Apulia regional mesothelioma register, Southern Italy.
Asbestos was widely used in construction in both a friable and a compact form until the 1990s, before its use was banned. Today, many of these materials are still in situ and represent a source of risk for construction workers. The objective of the study was to analyse the cases of mesothelioma arising among construction workers registered in the Apulia regional register of mesothelioma. For the period 1993-2018, there were 178 male cases, and 10.2% of the cases were present in the regional register. The average age at diagnosis was 64.7 years. The site was pleural in 96.06% of cases, with a diagnosis of certainty in 86.5% of the total cases and 61.8% of cases with epithelial histology. The average latency is 43.9 years. In 75.2% of cases, the exposure began between 1941 and 1970, with an average duration of 24.3 years. The age at the start of exposure in 68.5% of cases is between 8 and 20 years. The ORs were 2.5 (C.I. 95% 1.01-6.17) for the epithelioid histotype and the high duration of exposure. The data underline the need for prevention and information on all activities involving construction workers in which asbestos-containing materials are still used.


Population structure of the Yersinia pseudotuberculosis complex according to multilocus sequence typing.
Multilocus sequence analysis of 417 strains of Yersinia pseudotuberculosis revealed that it is a complex of four populations, three of which have been previously assigned species status [Y. pseudotuberculosis sensu stricto (s.s.), Yersinia pestis and Yersinia similis] and a fourth population, which we refer to as the Korean group, which may be in the process of speciation. We detected clear signs of recombination within Y. pseudotuberculosis s.s. as well as imports from Y. similis and the Korean group. The sources of genetic diversification within Y. pseudotuberculosis s.s. were approximately equally divided between recombination and mutation, whereas recombination has not yet been demonstrated in Y. pestis, which is also much more genetically monomorphic than is Y. pseudotuberculosis s.s. Most Y. pseudotuberculosis s.s. belong to a diffuse group of sequence types lacking clear population structure, although this species contains a melibiose-negative clade that is present globally in domesticated animals. Yersinia similis corresponds to the previously identified Y. pseudotuberculosis genetic type G4, which is probably not pathogenic because it lacks the virulence factors that are typical for Y. pseudotuberculosis s.s. In contrast, Y. pseudotuberculosis s.s., the Korean group and Y. pestis can all cause disease in humans.


Phytochelatin Synthesis Promotes Leaf Zn Accumulation of Arabidopsis thaliana Plants Grown in Soil with Adequate Zn Supply and is Essential for Survival on Zn-Contaminated Soil.
Phytochelatin (PC) synthesis is essential for the detoxification of non-essential metals such as cadmium (Cd). In vitro experiments with Arabidopsis thaliana seedlings had indicated a contribution to zinc (Zn) tolerance as well. We addressed the physiological role of PC synthesis in Zn homeostasis of plants under more natural conditions. Growth responses, PC accumulation and leaf ionomes of wild-type and AtPCS1 mutant plants cultivated in different soils representing adequate Zn supply, Zn deficiency and Zn excess were analyzed. Growth on Zn-contaminated soil triggers PC synthesis and is strongly impaired in PC-deficient mutants. In fact, the contribution of AtPCS1 to tolerating Zn excess is comparable with that of the major Zn tolerance factor MTP1. For plants supplied with a normal level of Zn, a significant reduction in leaf Zn accumulation of AtPCS1 mutants was detected. In contrast, AtPCS1 mutants grown under Zn-limited conditions showed wild-type levels of Zn accumulation, suggesting the operation of distinct Zn translocation pathways. Contrasting phenotypes of the tested AtPCS1 mutant alleles upon growth in Zn- or Cd-contaminated soil indicated differential activation of PC synthesis by these metals. Experiments with truncated versions identified a part of the AtPCS1 protein required for the activation by Zn but not by Cd.


Heptachlor degradation characteristics of a novel strain and its application.
With heptachlor as the sole carbon source, an effective heptachlor-degrading microorganism (named strain H) was isolated from the sludge of heptachlor-polluted sewage of a chemical plant, via enrichment, screening and purification. Strain H was identified as a facultative anaerobic Gram-negative bacterial strain belonging to genus Shigella based on the physiological-biochemical characteristics and the similarity analysis of its 16S rDNA gene sequence with the sequences logged in the Ribosomal Database Project and GenBank databases. When the optimal inoculation volume and the pH were 20% and 7.1-7.6, respectively, strain H was able to degrade heptachlor by more than 88.2% after130 h, with initial concentration of heptachlor being 300 μg/L at 30 ± 0.5 °C. It was also shown that strain H can grow on the degradation products of heptachlor such as 1-hydroxychlordene or heptachlor epoxide. Furthermore, additional carbon sources can accelerate the degradation rate of heptachlor because of co-metabolism. The degradation dynamics could be described by a first-order reaction model. A real-world field experiment demonstrated that strain H was effective in practical applications of heptachlor biodegradation in contaminated soil.


New xanthones and cytotoxic constituents from Garcinia mangostana fruit hulls against human hepatocellular, breast, and colorectal cancer cell lines.
Cancer has proceeded to surpass one of the most chronic illnesses to be the major cause of mortality in both the developing and developed world. Garcinia mangostana L. (mangosteen, family Guttiferae) known as the queen of fruits, is one of the most popular tropical fruits. It is cultivated in Southeast Asian countries: Malaysia, Indonesia, Sri Lanka, Burma, Thailand, and Philippines. Traditionally, numerous parts of G. mangostana have been utilized to treat various ailments such as abdominal pain, haemorrhoids, food allergies, arthritis, leucorrhoea, gonorrhea, diarrhea, dysentery, wound infection, suppuration, and chronic ulcer. Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated. The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry. The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50's ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50's ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additionally, by using annexin V-FITC/PI differential staining, 5 induced cells killing effect via the induction of apoptosis and necrosis in both HepG2 and HCT116 cells. Compound 3 produce necrosis and apoptosis only in HCT116 cells. On contrary, 6 induced apoptosis and necrosis in HepG2 cells and moderate necrosis in HCT116 cells. Fourteen compounds were isolated from chloroform fraction of G. mangostana fruit hulls. Cytotoxic properties exhibited by the isolated xanthones from G. mangostana reinforce the avail of it as a natural cytotoxic agent against various cancers. These evidences could provide relevant bases for the scientific rationale of using G. mangostana in anti-cancer treatment.


Drought exacerbates negative consequences of high-intensity cattle grazing in a semiarid grassland.
Grasslands managed for grazing are the largest land-use category globally, with a significant proportion of these grasslands occurring in semiarid and arid regions. In such dryland systems, the effect of grazing on native plant diversity has been equivocal, some studies suggesting that grazing reduces native plant diversity, others that grazing increases or has little impact on diversity. One impediment toward generalizing grazing effects on diversity in this region is that high levels of interannual variation in precipitation may obfuscate vegetative response patterns. By analyzing a long-term data set collected over a 20-yr period in a semiarid grassland, we explicitly evaluated the role of climate in regulating the effect of cattle grazing on plant communities, finding that climate interacted with grazing intensity to shape grassland communities. Community composition of plots that were intensively grazed varied considerably in response to climatic variation and native species richness was low relative to ungrazed and moderately grazed plots. Following a severe drought in 2002, exotic species richness rapidly increased in the high-intensity grazing plots. While this pattern was mirrored in the other treatments, exotic species richness increased to a greater extent and was slower to return to pre-drought levels in the high-intensity grazing plots. Overall, moderate grazing, even compared to grazing cessation, stabilized grassland communities through time, increased resilience to drought, and maintained the highest levels of native plant diversity and lowest levels of exotic diversity. These findings suggest that grazing, at moderate levels, may support grassland resilience to climate change in semiarid regions. However, grazing that exceeds tolerances, particularly in combination with extreme climatic events, like drought, can alter plant composition over relatively long timescales and possibly increase invasibility by nonnative species.


Hypomorphic FANCA mutations correlate with mild mitochondrial and clinical phenotype in Fanconi anemia.
Fanconi anemia is a rare disease characterized by congenital malformations, aplastic anemia, and predisposition to cancer. Despite the consolidated role of the Fanconi anemia proteins in DNA repair, their involvement in mitochondrial function is emerging. The purpose of this work was to assess whether the mitochondrial phenotype, independent of genomic integrity, could correlate with patient phenotype. We evaluated mitochondrial and clinical features of 11 affected individuals homozygous or compound heterozygous for p.His913Pro and p.Arg951Gln/Trp, the two residues of FANCA that are more frequently affected in our cohort of patients. Although p.His913Pro and p.Arg951Gln proteins are stably expressed in cytoplasm, they are unable to migrate in the nucleus, preventing cells from repairing DNA. In these cells, the electron transfer between respiring complex I-III is reduced and the ATP/AMP ratio is impaired with defective ATP production and AMP accumulation. These activities are intermediate between those observed in wild-type and FANCA-/- cells, suggesting that the variants at residues His913 and Arg951 are hypomorphic mutations. Consistent with these findings, the clinical phenotype of most of the patients carrying these mutations is mild. These data further support the recent finding that the Fanconi anemia proteins play a role in mitochondria, and open up possibilities for genotype/phenotype studies based on novel mitochondrial criteria.


Reproductive Traits of the Duckbill Sleeper Butis butis (Hamilton, 1822).
Butis butis is a commercially important goby that is widely distributed in Indo-Pacific regions; however, its reproductive biology is poorly characterized. We condcted the present study in estuarine and coastline areas in the Mekong Delta from June 2015 to May 2016 to generate reproductive parameters for this species. The results of data analysis based on a collection of 173 individuals (74 females and 99 males) indicate that the sex ratio of this species is close to 1:1. Mature (stage IV) and ripe (stage V) gonads were found monthly during the study period, suggesting that Butis butis is an iteroparous fish that spawns in a year-round cycle. Male B. butis matures first at 8.97 cm total length (TL), which is longer than females (6.82 cm TL). Butis butis is well adapted to tropical monsoon regions due to its high batch fecundity (46,017 ± 6941 SE), ranging from 15,000 (8.6 cm TL and 5.71 g W) to 78,500 (15.8 cm TL and 42.24 g W) eggs. Batch fecundity increases with fish size due to a strong positive relationship between batch fecundity and fish size (TL and W). These results help fill the knowledge gap on the reproductive biology of Butis butis, and contribute crucial information relevant to sustainable management of fish populations in the study region.


Electroacupuncture in the treatment of obesity.
Obesity is becoming one of the most common health problems in the world. Many other disorders, such as hypertension and diabetes are considered as the consequences of obesity. Since effective remedies are rare (only two drugs, Orlistat and Sibutramine, were officially approved by the US Food and Drug Administration for long-term obesity treatment so far), researchers are trying to discover new therapies for obesity, and acupuncture is among the most popular alternative approaches. To facilitate weight reduction, one can use manual acupuncture, electroacupuncture (EA) or transcutaneous electrical acupoint stimulation (TEAS). As the parameters of the EA or TEAS can be precisely characterized and the results are more or less reproducible, this review will focus on EA as a treatment modality for obesity. Results obtained in this laboratory in recent five years will be summarized in some detail.


Fosthiazate Controls Meloidogyne arenaria and M. incognita in Flue-Cured Tobacco.
The nematicide fosthiazate was evaluated over a 3-year period for management of Meloidogyne incognita race 3 (site 1) and M. arenaria race 2 (site 2) in flue-cured tobacco. Fosthiazate was applied broadcast and incorporated at rates ranging from 22 to 88 g a.i./100 m(2), and compared with the nematicides fenamiphos (67 g a.i./100 m(2)), 1,3-D (56.1 L/ha, 670 ml/100-m row), and an untreated control. Root-gall indices and leaf yields were averaged over the 3-year period. Root galling was negatively correlated in a linear relationship with fosthiazate application rate at sites 1 and 2. Leaf yields were positively correlated with fosthiazate application rate at site 1 and could be described by a quadratic equation. Leaf yields were greater at 33 and 88 g a.i./100 m(2) application rates (site 2) than the untreated control. Leaf yields in fosthiazate (88 g a.i./100 m(2))-treated plots infested with M. incognita or M. arenaria were not different from plots fumigated with 1,3-D. Plants in plots with fosthiazate applied in a row band (1993) had a lower root-gall index than those in plots with the same rate of fosthiazate applied broadcast. Fosthiazate may provide an alternative to fumigation for control of M. incognita and M. arenaria.


Changes in need satisfaction and motivation orientation as predictors of psychological and behavioural outcomes in exercise referral.
Employing Self-Determination Theory (Deci & Ryan, 1985) as a theoretical framework, this study examined psychological need satisfaction and motivational regulations as predictors of psychological and behavioural outcomes in exercise referral (ER). ER patients (N = 293; mean age 54.49) completed the measures of motivational regulations, psychological need satisfaction, health-related quality of life, life satisfaction, anxiety, depression and physical activity at entry, exit and 6 months following the end of a supervised exercise programme. Change in (Δ) intrinsic motivation during the scheme significantly predicted adherence and Δ habitual physical activity. Δ psychological need satisfaction from entry to exit significantly predicted Δ habitual physical activity from exit to 6-month follow-up. Δ psychological need satisfaction significantly predicted Δ motivational regulation and Δ psychological outcomes. Contrary to expectations, Δ self-determined regulation did not significantly predict Δ psychological outcomes during the structured part of the scheme, however, it did significantly predict Δ in psychological outcomes from exit to 6-month follow-up. These findings expand on cross-sectional research to demonstrate that psychological need satisfaction during supervised ER longitudinally predicts motivational regulation and psychological outcomes up to 6 months after a structured programme.


Bifidobacterium animalis AHC7 protects against pathogen-induced NF-κB activation in vivo.
Bifidobacteria and lactobacilli are among the early and important colonizers of the gastrointestinal tract and are generally considered to be part of a normal, healthy microbiota. It is believed that specific strains within the microbiota can influence host immune-reactivity and may play a role in protection from infection and aberrant inflammatory activity. One such strain, Bifidobacterium animalis AHC7, has been previously shown to protect against Salmonella typhimurium infection in mice and helps resolve acute idiopathic diarrhea in dogs. The aim of this study was to investigate the potential molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7 protective effect. Following 4 hours of infection with Salmonella typhimurium, NF-κB activation was significantly elevated in vivo in placebo and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7 consumption significantly attenuated the NF-κB response. In vitro anti-CD3/CD28 stimulated Peyer's patch cells secreted significantly less TNF-α and IFN-γ following Bifidobacterium animalis AHC7 consumption. Stimulated cells released more IL-12p70 but this difference did not reach statistical significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed. No statistically significant change in the cytokine profile of mesenteric lymph node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co-culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic cells resulted in a significant increase in CD25+Foxp3+ T cell numbers. Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via the attenuation of pro-inflammatory transcription factor activation in response to an infectious insult associated with modulation of pro-inflammatory cytokine production within the mucosa. The cellular mechanism underpinning Bifidobacterium animalis AHC7 mediated attenuation of NF-κB activation may include recognition of the bacterium by dendritic cells and induction of CD25+Foxp3+ T cells.


Chronic lymphocytic leukemia in young adults.
The occurrence of chronic lymphocytic leukemia (CLL), B-cell type, is thought to be distinctly uncommon in patients younger than 40 years of age. Previous case reports of CLL in young adults and children were published before the widespread use of immunologic surface markers in the diagnosis of lymphoproliferative disorders. The authors report four patients with B-cell CLL, all diagnosed with the aid of immunologic markers. The patients were 30 years of age or younger at the time of diagnosis. Their subsequent course has been similar to B-cell CLL in the older age group: one is alive without progression of disease 30 months after diagnosis; one has shown progression of the disease but is alive, after chemotherapy, 36 months after diagnosis; while the other two had continued progression of disease and died, one at six and a half years and the other at 14 months, after diagnosis. The occurrence of B-cell CLL in young adults and its potential implications are discussed.


The immunological milieu of the liver.
From the immunology standpoint, the liver is a peculiar organ for several reasons that range from its anatomical location to its cytoarchitecture and its variety of specific functions. Receiving blood directly from the digestive system, the liver is the crossroad at which the majority of antigens enter the organism. Hence, the milieu of the liver must provide a finely tuned balance between generating tolerance to self as well as to nonpathogenic molecules and microorganisms and producing an appropriate immune response to pathogens. Knowledge of the mechanisms that effectively maintain this balance is critical to the understanding of the pathogenesis of chronic inflammatory liver diseases, infectious, autoimmune, and others. Several theories have been proposed to explain what causes one or another response to take precedence. Although no definitive answer is yet available, the critical elements include, for tolerance, the particular cytoarchitectural features and the intrahepatic existence of antigen-presenting cells and, for immunity, inflammatory expressions including type 1 cytokines and chemokines, notably CCR5. Herein we review the available data on immune responses in the liver with particular emphasis on the unique structural and functional features of this "lymphoid" organ.


Schizophrenia and comorbid human immunodeficiency virus or hepatitis C virus.
Patients with schizophrenia are at significantly increased risk for infection with human immunodeficiency virus (HIV), hepatitis C virus, or both. Several factors underlie this increased risk, including substance abuse and high-risk sexual behavior. Although being sexually active tends to be less common among patients with schizophrenia than among nonpsychotic individuals, patients with schizophrenia who are sexually active are more likely than nonpsychotic individuals to engage in high-risk behavior. Many patients with schizophrenia have inadequate knowledge about the risks of HIV, but delivering factual information is not likely, by itself, to bring about behavioral changes that reduce the risk of exposure and transmission. Comorbidity of schizophrenia and life-threatening viral illnesses incurs a worse prognosis for both conditions. Nevertheless, effective pharmacotherapy exists, and antipsychotics and highly active antiretroviral treatments for HIV can be used together successfully. The clinical challenge is to encourage adherence to treatment and to coordinate the clinical services needed to address the diverse psychiatric and medical problems that coexist in this population.


Generalized separable parameter space techniques for fitting 1K-5K serial compartment models.
Kinetic modeling is widely used to analyze dynamic imaging data, estimating kinetic parameters that quantify functional or physiologic processes in vivo. Typical kinetic models give rise to nonlinear solution equations in multiple dimensions, presenting a complex fitting environment. This work generalizes previously described separable nonlinear least-squares techniques for fitting serial compartment models with up to three tissue compartments and five rate parameters. The approach maximally separates the linear and nonlinear aspects of the modeling equations, using a formulation modified from previous basis function methods to avoid a potential mathematical degeneracy. A fast and robust algorithm for solving the linear subproblem with full user-defined constraints is also presented. The generalized separable parameter space technique effectively reduces the dimensionality of the nonlinear fitting problem to one dimension for 2K-3K compartment models, and to two dimensions for 4K-5K models. Exhaustive search fits, which guarantee identification of the true global minimum fit, required approximately 10 ms for 2K-3K and 1.1 s for 4K-5K models, respectively. The technique is also amenable to fast gradient-descent iterative fitting algorithms, where the reduced dimensionality offers improved convergence properties. The objective function for the separable parameter space nonlinear subproblem was characterized and found to be generally well-behaved with a well-defined global minimum. Separable parameter space fits with the Levenberg-Marquardt algorithm required fewer iterations than comparable fits for conventional model formulations, averaging 1 and 7 ms for 2K-3K and 4K-5K models, respectively. Sensitivity to initial conditions was likewise reduced. The separable parameter space techniques described herein generalize previously described techniques to encompass 1K-5K compartment models, enable robust solution of the linear subproblem with full user-defined constraints, and are amenable to rapid and robust fitting using iterative gradient-descent type algorithms.


Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The randomized, controlled ROSE trial.
To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up. A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients. These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.


Immunogold labelling to localize polyphenol oxidase (PPO) during wilting of red clover leaf tissue and the effect of removing cellular matrices on PPO protection of glycerol-based lipid in the rumen.
The enzyme polyphenol oxidase (PPO) reduces the extent of proteolysis and lipolysis within red clover fed to ruminants. PPO catalyses the conversion of phenols to quinones, which can react with nucleophilic cellular constituents (e.g. proteins) forming protein-phenol complexes that may reduce protein solubility, bioavailability to rumen microbes and deactivate plant enzymes. In this study, we localized PPO in red clover leaf tissue by immunogold labelling and investigated whether red clover lipid was protected in the absence of PPO-induced protein-phenol complexes and plant enzymes (lipases). PPO protein was detected to a greater extent (P < 0.001) within the chloroplasts of mesophyll cells in stressed (cut/crushed and wilted for 1 h) than freshly cut leaves for both palisade (61.6 and 25.6 Au label per chloroplast, respectively) and spongy mesophyll cells (94.5 and 40.6 Au label per chloroplast, respectively). Hydrolysis of lipid and C18 polyunsaturated fatty acid biohydrogenation during in vitro batch culture was lower (P < 0.05) for wild-type red clover than for red clover with PPO expression reduced to undetectable levels but only when cellular matrices containing protein-phenol complexes were present. Damaging of the leaves resulted in over a doubling of PPO detected within mesophyll cells, potentially as a consequence of conversion of the enzyme from latent to active form. PPO reduction of microbial lipolysis was apparent in macerated red clover tissue but not in the absence of the proteinaceous cellular matrix, suggesting that the PPO mechanism for reducing lipolysis may be primarily through the entrapment of lipid within protein-phenol complexes.


A rapid and reversible colorimetric assay for the characterization of aminated solid surfaces.
The covalent immobilization of synthetic or natural macromolecular compounds containing amino groups onto polystyrene (PS) solid surfaces is of great interest in diagnostic applications. A sensitive assay allowing the determination of reactive end groups is therefore a powerful tool for predicting the performance of the active surface. Recently, we reported the use of the Coomassie brilliant blue (CBB) colorimetric reagent to quantify protonated groups (N(+)) in linear and dendritic structures in solution (Coussot et al., Polym Int 58(5):511-518, 2009). In this work, a simple method using CBB dye for the characterization of PS aminated solid surfaces is developed. The proposed amino density estimation by colorimetric assay (ADECA) method is based on the reversible complexation of the dye with the N(+) groups on solid surfaces. The assay measures the released dye thanks to the use of a unique sodium carbonate-methanol buffer. Thereby, for the first time, the same surface can be used for characterization and for further coupling applications. A surface density of four N(+) groups per square nanometer can be measured in PS microwell format, the whole characterization being done within 30 min. Performances of this new colorimetric-based method are detailed. The ADECA method is further demonstrated to be useful for the characterization of aminated polypropylene and glass materials with various sizes and shapes.


Mid-Pregnancy Insomnia and its Association with Perinatal Depressive Symptoms: A Prospective Cohort Study.
Objective/Background: Insomnia and depression are disorders that affect many perinatal women and that often are interrelated. The present study aimed to examine concurrent and prospective associations between mid-pregnancy insomnia and depression during mid-pregnancy and 8 weeks postpartum. Furthermore, differences in depression and in the sleep-related characteristics insomnia, chronotype, and sleep efficiency were explored between the two time points (mid-pregnancy versus 8 weeks postpartum), and between primiparous and multiparous participants.Participants/Methods: The study was part of the Norwegian population-based Depression and Anxiety in the Perinatal Period (DAPP) prospective cohort study. Among 539 women that were recruited for participation when receiving a routine ultrasound examination, we analyzed data from hospital birth records and questionnaire responses from pregnancy week 17 and postpartum week 8. We used the Edinburgh Postnatal Depression Scale to measure depression. The Bergen Insomnia Scale, the reduced Horne-Östberg Morningness-Eveningness Questionnaire, and three questions from the Pittsburgh Sleep Quality Index were used to measure the sleep-related characteristics.Results: Mid-pregnancy insomnia was significantly associated with concurrent depression (p < .001), but not with postpartum depression (p = .288), in a linear mixed model with adjustment for several reproductive and psychosocial variables. Sleep efficiency was reduced from mid-pregnancy to postpartum (from 88% to 77%), and primiparous women reported less efficient sleep than multiparous women after childbirth.Conclusions: The results indicate that mid-pregnancy insomnia may be a marker for concurrent depression but not a predictor of postpartum depression. Future research should examine the extent to which treatment of insomnia from mid-pregnancy on reduces both perinatal insomnia and depression.


A critical question for HIV vaccine development: which antibodies to induce?
A vaccine against HIV-1 must prevent infection against genetically diverse virus strains. Two approaches are currently being pursued to elicit antibody-mediated protection: vaccines that induce potent and broadly reactive neutralizing antibodies (bnAbs) or vaccines that induce "conventional antibodies," which are less potent and broadly neutralizing in comparison. Although bnAbs may provide the greatest level of protection, their structural and genetic characteristics make their elicitation through vaccination a major challenge. In contrast, conventional HIV-1 antibodies have been induced by vaccination and correlated with reduced HIV-1 infection in a phase III vaccine trial. Here, I present evidence that both approaches should be pursued with equal vigor.


The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis.
In the present study, we performed a meta-analysis to assess the ability of leucine supplementation to increase the muscle protein fraction synthetic rate and to augment lean body mass or leg lean mass in elderly patients. A literature search was conducted on Medline, Cochrane, EMBASE and Google Scholar databases up to 31 December 2013 for clinical trials that investigated the administration of leucine as a nutrient that affects muscle protein metabolism and muscle mass in elderly subjects. The included studies were randomised controlled trials. The primary outcome for the meta-analysis was the protein fractional synthetic rate. Secondary outcomes included lean body mass and leg lean mass. A total of nine studies were included in the meta-analysis. The results showed that the muscle protein fractional synthetic rate after intervention significantly increased in the leucine group compared with the control group (pooled standardised difference in mean changes 1·08, 95% CI 0·50, 1·67; P< 0·001). No difference was found between the groups in relation to lean body mass (pooled standardised difference in mean changes 0·18, 95% CI - 0·18, 0·54; P= 0·318) or leg lean mass (pooled standardised difference in mean changes 0·006, 95% CI - 0·32, 0·44; P= 0·756). These findings suggest that leucine supplementation is useful to address the age-related decline in muscle mass in elderly individuals, as it increases the muscle protein fractional synthetic rate.


Prevalence of occult hepatitis B and hepatitis C virus infections in Turkish hemodialysis patients.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes of morbidity and mortality in maintenance hemodialysis patients. Although their exact prevalence is not known, HBV and HCV viral infections and occult viral hepatitis are frequent in these patients. This study aimed to determine the prevalence of occult HBV and HCV infections in maintenance hemodialysis patients. One hundred and eighty-eight end-stage renal disease patients on maintenance hemodialysis (100 male, mean age 49+/-29 [16-80] years, and mean duration of hemodialysis 98+/-66 [12-228] months) were enrolled in this study. Serological markers for HBV and HCV were determined with immunoenzymatic assay (ELISA) by using commercial diagnostic kits (Access and BioRad, Beckman-Coulter). HCV-RNA (Cobas Amplicor HCV kit) and HBV-DNA (Artus GmbH HBV kit) were determined quantitatively by polymerase chain reaction. Among the patients screened, 25 (13.3%) had HBV infection alone and 38 (20.2%) had HCV infection alone, while seven (3.7%) had dual infection of both viruses. Serological markers for occult hepatitis B and occult hepatitis C were positive in five (2.7%) and nine (4.8%) of the patients, respectively. Isolated anti-HBc was positive in 12 (6.4%) of all patients, three (7.9%) of the patients with anti-HCV and two (40%) of the patients with occult hepatitis B. Isolated anti-HBc positivity was more frequent in patients with occult hepatitis B than in those without (40% [2/5] vs. 5.5% [10/183], p=0.002). None of the patients with HCV had occult hepatitis B. Both occult and non-occult forms of HCV infection are more prevalent than HBV infection in hemodialysis patients. Especially the patients with isolated anti-HBc positivity should be tested for probable occult hepatitis B infection.


Hemodynamics and tissue oxygenation effects after increased in positive end-expiratory pressure in coronary artery bypass surgery.
Cardiac surgery is widely used in the treatment of cardiovascular diseases. However, several complications can be observed during the postoperative period. Positive end expiratory pressure (PEEP) improves gas exchange, but it might be related to decreased cardiac output and possible impairment of tissue oxygenation. The aim of this study was to investigate the hemodynamic effects and oxygen saturation of central venous blood (ScvO2) after increasing PEEP in hypoxemic patients after coronary artery bypass (CAB) surgery. Seventy post-cardiac surgery patients (CAB), 61 ± 7 years, without ventricular dysfunction (left ventricular ejection fraction 57 ± 2%), with hypoxemia (PaO2/FiO2 ratio <200) were enrolled. Heart rate, mean arterial pressure, arterial and venous blood samples were measured at intensive care unit and PEEP was increased to 12 cmH2O for 30 min. As expected, PEEP12 improved arterial oxygenation and PaO2/FiO2 ratio (p < 0.0001). Reduction in ScvO2 was observed between PEEP5 (63 ± 2%) and PEEP12 (57 ± 1%; p = 0.01) with higher values of blood lactate in PEEP12 (p < 0.01). No hemodynamic effects (heart rate, mean arterial pressure, SpO2; p > 0.05) were related. Increased PEEP after cardiac surgery decreased ScvO2 and increased blood lactate, even with higher O2 delivery. PEEP did not interfere in hemodynamics status in CAB patients, suggesting that peripheral parameters must be controlled and measured during procedures involving increased PEEP in post-cardiac surgery patients in the intensive care unit.


Poor stimulus discriminability as a common neuropsychological deficit between ADHD and reading ability in young children: a moderated mediation model.
Attention deficit hyperactivity disorder (ADHD) is frequently associated with poorer reading ability; however, the specific neuropsychological domains linking this co-occurrence remain unclear. This study evaluates information-processing characteristics as possible neuropsychological links between ADHD symptoms and RA in a community-based sample of children and early adolescents with normal IQ (⩾70). The participants (n = 1857, aged 6-15 years, 47% female) were evaluated for reading ability (reading single words aloud) and information processing [stimulus discriminability in the two-choice reaction-time task estimated using diffusion models]. ADHD symptoms were ascertained through informant (parent) report using the Development and Well-Being Assessment (DAWBA). Verbal working memory (VWM; digit span backwards), visuospatial working memory (VSWM, Corsi Blocks backwards), sex, socioeconomic status, and IQ were included as covariates. In a moderated mediation model, stimulus discriminability mediated the effect of ADHD on reading ability. This indirect effect was moderated by age such that a larger effect was seen among younger children. The findings support the hypothesis that ADHD and reading ability are linked among young children via a neuropsychological deficit related to stimulus discriminability. Early interventions targeting stimulus discriminability might improve symptoms of inattention/hyperactivity and reading ability.


Seasonal influenza surveillance (2009-2017) for pandemic preparedness in the WHO South-East Asia Region.
Influenza causes seasonal outbreaks each year and periodically causes a pandemic. The World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS) has contributed to global understanding of influenza patterns, but limited regional analysis has occurred. This study describes the virological patterns and influenza surveillance systems in the 11 countries of the WHO South-East Asia Region. Virological data were extracted in January 2018 from FluNet, GISRS's web-based reporting tool, for 10 of the 11 countries that had data available for the years 2009 to 2017. Descriptive data for 2017 on influenza surveillance systems, including the number of sentinel sites, case definitions and reporting frequency, were collected through an annual questionnaire. Data on surveillance systems were available for all 11 Member States, and 10 countries reported virological data to FluNet between 2009 and 2017. Influenza surveillance in the region and national participation increased over the 8 years. Seasons varied between countries, with some experiencing two peak seasons and others having one main predominant season. Bangladesh, Indonesia and Myanmar have only one season: Bangladesh and Myanmar have a mid-year pattern and Indonesia an end-year pattern. Influenza A was the predominant circulating type for all years except 2012 and 2016, when A and B co-circulated. Influenza A(H1N1)pdm09 was dominant in 2009 and 2010 (77% and 76%, respectively), 2015 (72%) and 2017 (54%); influenza A(H3) accounted for approximately half of the positive specimens in 2011 (46%), 2013 (51%) and 2014 (47%); and influenza B (lineage not determined) made up over 49% of positive specimens in 2012. Although the timings of peaks varied from country to country, the viruses circulating within the region were similar. Influenza surveillance remains a challenge in the region. However, timely reporting and regional sharing of information about influenza may help countries that have later peaks to allow them to prepare for the potential severity and burden associated with prevailing strains.


Slow axonal transport in acrylamide neuropathy: different abnormalities produced by single-dose and continuous administration.
Alterations in axonal caliber and neurofilament content have been associated with altered neurofilament transport in several models of neurofibrillary degeneration. Acrylamide intoxication provides a prototype of distal axonal degeneration, the most frequent pattern of axonal pathology in human and experimental neurotoxic injury. Neurofibrillary changes are a variable and often minor aspect of the early pathological changes observed in acrylamide intoxication, and previous studies of slow axonal transport have produced conflicting results. In this study, we have correlated slow axonal transport, specifically neurofilament transport, with structural changes in the sciatic nerve complex of rats exposed to acrylamide. To study direct toxic effects of acrylamide, young rats were given a single dose of acrylamide (75 mg/kg, i.p.). A second group received daily injections of acrylamide at a lower dose (30 mg/kg, i.p.) in order to study animals with established acrylamide neuropathy. The slow component of axonal transport was labeled by intraspinal injections of [35S] methionine. Transport of individual slow component polypeptides was compared to profiles obtained from age-matched controls. Similarly intoxicated rats were perfused for morphometric and morphological studies. Results demonstrate that two different abnormalities of the slow component of axonal transport arise at different stages during the development of experimental acrylamide neuropathy. Both patterns of altered transport have structural correlates which reflect the changes in neurofilament transport. Following a single high dose, there was a modest retardation of the leading edge of the slow component. At this time, neurofilaments accumulated in proximal axons with formation of axonal swellings. During chronic administration, when distal axonal degeneration was present, the proportion of neurofilaments in the slow component was markedly reduced, and there was prominent loss of caliber in proximal axons. We suggest that these early changes represent a direct toxic effect of acrylamide on slow transport, whereas the later changes reflect reordering of slow transport as a neuronal response to toxin-induced axonal injury. This latter effect is of sufficient magnitude to obscure the acrylamide-induced retardation of slow transport.


Submicron fibers as a morphological improvement of amorphous zirconium oxide particles and their utilization in antimonate (Sb(v)) removal.
Mesoporous and large surface area zirconium oxide aggregate granules with good adsorption properties were synthesized using a simple precipitation method. Since utilization of these small and fragile particles is considered rather difficult in larger scale column operation, the product was formed into a fibrous form to improve its usability. The submicron fibers were obtained from an optimized electroblowing synthesis that resulted in elastic and uniform fibers with a tetragonal structure and high length-to-diameter ratio. In antimonate (Sb(v)) adsorption experiments, the higher calcination temperature (350 °C) of the fibers did not seem to decrease the Sb(v) adsorption capacity excessively since the high theoretical adsorption capacities were 113 mg g-1 and 58 mg g-1 for the aggregate and fibers, respectively. Both materials had fast kinetics, fibers being faster in the beginning of the reaction. Moreover, both materials offered efficient Sb(v) removal in the studied pH range from 1 to 11 by reaching over 99.9% adsorption in the optimal pH range. X-ray absorption near edge spectroscopy (XANES) revealed that Sb(v) stays as pentavalent antimony after being adsorbed by these materials and based on the isoelectric point shifts in the zeta potential measurement, adsorption occurs mainly by an inner-sphere complexation reaction. Finally, our study showed that pressure buildup in a flow-through column packed with zirconium oxide fibers was significantly lower than in a column packed with aggregates. Thus, zirconium oxide aggregates can be formed into submicron fibers with enhanced column operation properties without a too large compromise in the adsorption properties.


Reliability of patient-reported functional outcome in a joint replacement registry. A comparison of primary responders and non-responders in the Danish Shoulder Arthroplasty Registry.
Patient-reported outcome measures (PROMs) are used by some arthroplasty registries to evaluate results after surgery, but non-response may bias the results. The aim was to identify a potential bias in the outcome scores of subgroups in a cohort of patients from the Danish Shoulder Arthroplasty Registry (DSR) and to characterize non-responders. Patient-reported outcome of 787 patients operated in 2008 was assessed 12 months postoperatively using the Western Ontario Osteoarthritis of the Shoulder (WOOS) index. In January 2012, non-responders and incomplete responders were sent a postal reminder. Non-responders to the postal reminder were contacted by telephone. Total WOOS score and WOOS subscales were compared for initial responders (n = 509), responders to the postal reminder (n = 156), and responders after telephone contact (n = 27). The predefined variables age, sex, diagnosis, geographical region, and reoperation rate were compared for responding and non-responding cohorts. A postal reminder increased the response rate from 65% (6% incomplete) to 80% (3% incomplete) and telephone contact resulted in a further increase to 82% (2% incomplete). We did not find any statistically significant differences in total WOOS score or in any of the WOOS subscales between responders to the original questionnaire, responders to the postal reminder, and responders after telephone contact. However, a trend of worse outcome for non-responders was found. The response rate was lower in younger patients. Non-responders did not appear to bias the overall results after shoulder replacement despite a trend of worse outcome for a subgroup of non-responders. As response rates rose markedly by the use of postal reminders, we recommend the use of reminders in arthroplasty registries using PROMs.


Witnessing suicide-related behavior in prison: a qualitative study of young male prisoners in England.
Rates of suicide and suicide-related behavior (SRB) are high in prison. Those witnessing such behavior may develop psychological morbidity. Most previous studies have been quantitative. Little has been written about the witnesses' qualitative experience. The aim of the study was to explore, through interview and then thematic analysis, the core concerns of those witnessing another's SRB in prison. We interviewed 70 detained young men about their experience of another's SRB in prison. Three main themes were identified: their experience of another's SRB; their thoughts of why the victim died by/attempted suicide; and the physical, emotional, and cognitive effects of another's SRB on them. Responses to questions about the witnesses' experience of support from others, unmet needs, and peers' responses are also described. Two categories within the theme "thoughts of why the victim died by/attempted suicide" were associated with being in prison, all others could be experienced in the community. Over half of the sample reported negative reactions to witnessing another's SRB. Most themes were unrelated to prison. Though many reported negative reactions to their experience, suggesting a need for support, many denied that need. The implication of this study is that prison discipline and health-care staff need to consider how to provide needed support and care in an acceptable form to young men in prison.


The effectiveness of compulsory drug treatment: A systematic review.
Despite widespread implementation of compulsory treatment modalities for drug dependence, there has been no systematic evaluation of the scientific evidence on the effectiveness of compulsory drug treatment. We conducted a systematic review of studies assessing the outcomes of compulsory treatment. We conducted a search in duplicate of all relevant peer-reviewed scientific literature evaluating compulsory treatment modalities. The following academic databases were searched: PubMed, PAIS International, Proquest, PsycINFO, Web of Science, Soc Abstracts, JSTOR, EBSCO/Academic Search Complete, REDALYC, SciELO Brazil. We also searched the Internet, and article reference lists, from database inception to July 15th, 2015. Eligibility criteria are as follows: peer-reviewed scientific studies presenting original data. Primary outcome of interest was post-treatment drug use. Secondary outcome of interest was post-treatment criminal recidivism. Of an initial 430 potential studies identified, nine quantitative studies met the inclusion criteria. Studies evaluated compulsory treatment options including drug detention facilities, short (i.e., 21-day) and long-term (i.e., 6 months) inpatient treatment, community-based treatment, group-based outpatient treatment, and prison-based treatment. Three studies (33%) reported no significant impacts of compulsory treatment compared with control interventions. Two studies (22%) found equivocal results but did not compare against a control condition. Two studies (22%) observed negative impacts of compulsory treatment on criminal recidivism. Two studies (22%) observed positive impacts of compulsory inpatient treatment on criminal recidivism and drug use. There is limited scientific literature evaluating compulsory drug treatment. Evidence does not, on the whole, suggest improved outcomes related to compulsory treatment approaches, with some studies suggesting potential harms. Given the potential for human rights abuses within compulsory treatment settings, non-compulsory treatment modalities should be prioritized by policymakers seeking to reduce drug-related harms.


Activity-dependent gating of lateral inhibition in the mouse olfactory bulb.
Lateral inhibition is a circuit motif found throughout the nervous system that often generates contrast enhancement and center-surround receptive fields. We investigated the functional properties of the circuits mediating lateral inhibition between olfactory bulb principal neurons (mitral cells) in vitro. We found that the lateral inhibition received by mitral cells is gated by postsynaptic firing, such that a minimum threshold of postsynaptic activity is required before effective lateral inhibition is recruited. This dynamic regulation allows the strength of lateral inhibition to be enhanced between cells with correlated activity. Simulations show that this regulation of lateral inhibition causes decorrelation of mitral cell activity that is evoked by similar stimuli, even when stimuli have no clear spatial structure. These results show that this previously unknown mechanism for specifying lateral inhibitory connections allows functional inhibitory connectivity to be dynamically remapped to relevant populations of neurons.


c-myc antisense oligonucleotides inhibit the colony-forming capacity of Colo 320 colonic carcinoma cells.
Colo 320 cells are colonic carcinoma cells known to express abundant c-myc mRNA. Based on the response of several hematopoietic cell lines to chemical inducers of differentiation, we reasoned that such agents might have similar inductive activity in Colo 320 cells. Accordingly, we exposed Colo 320 cells to 5 mM sodium butyrate (NaBT) for 7 d. C-myc expression decreased threefold and self-replicative potential decreased (defined as a greater than 60% decrease in colony-forming capacity in soft agar that did not contain inducer). In an effort to demonstrate a direct cause and effect between myc expression and the colony-forming capacity of Colo 320 cells, we exposed these cells to a 15-base antisense c-myc oligonucleotide (complementary to the translation initiation region of exon II). Cells were also exposed to equimolar (20 microM) amounts of sense and missense oligonucleotides. Subsequently, cells were incubated at 10, 20, 30, and 40 microM antisense DNA for 16 h, then washed and plated in oligonucleotide-free agar medium. We demonstrated that: (a) the oligomers were stable in the extracellular medium and in the cell cytoplasm; (b) the uptake of the oligonucleotides was 0.7%; (c) sense and missense oligonucleotides had no effect on colony-forming capacity; and (d) the antisense c-myc oligonucleotide resulted in a 40-75% concentration-dependent decrease in colony-forming capacity. The specific inhibition of colony-forming capacity by antisense DNA suggests that the role of myc expression in Colo 320 cells is similar to its role in hematopoiesis, and that the failure to inhibit myc expression maintains colony-forming capacity. This system provides a new strategy for inducing differentiation and may provide further insight into the genetic factors that govern the process of colonic carcinogenesis.


Spatio-temporal expression dynamics differ between homologues of flowering time genes in the allopolyploid Brassica napus.
Polyploidy is a recurrent feature of eukaryotic evolution and has been linked to increases in complexity, adaptive radiation and speciation. Within angiosperms such events have occurred repeatedly in many plant lineages. Here we investigate the retention and spatio-temporal expression dynamics of duplicated genes predicted to regulate the floral transition in Brassica napus (oilseed rape, OSR). We show that flowering time genes are preferentially retained relative to other genes in the OSR genome. Using a transcriptome time series in two tissues (leaf and shoot apex) across development we show that 67% of these retained flowering time genes are expressed. Furthermore, between 64% (leaf) and 74% (shoot apex) of the retained gene homologues show diverged expression patterns relative to each other across development, suggesting neo- or subfunctionalization. A case study of homologues of the shoot meristem identity gene TFL1 reveals differences in cis-regulatory elements that could explain this divergence. Such differences in the expression dynamics of duplicated genes highlight the challenges involved in translating gene regulatory networks from diploid model systems to more complex polyploid crop species.


3-D target-based distributed smart camera network localization.
For distributed smart camera networks to perform vision-based tasks such as subject recognition and tracking, every camera's position and orientation relative to a single 3-D coordinate frame must be accurately determined. In this paper, we present a new camera network localization solution that requires successively showing a 3-D feature point-rich target to all cameras, then using the known geometry of a 3-D target, cameras estimate and decompose projection matrices to compute their position and orientation relative to the coordinatization of the 3-D target's feature points. As each 3-D target position establishes a distinct coordinate frame, cameras that view more than one 3-D target position compute translations and rotations relating different positions' coordinate frames and share the transform data with neighbors to facilitate realignment of all cameras to a single coordinate frame. Compared to other localization solutions that use opportunistically found visual data, our solution is more suitable to battery-powered, processing-constrained camera networks because it requires communication only to determine simultaneous target viewings and for passing transform data. Additionally, our solution requires only pairwise view overlaps of sufficient size to see the 3-D target and detect its feature points, while also giving camera positions in meaningful units. We evaluate our algorithm in both real and simulated smart camera networks. In the real network, position error is less than 1 ('') when the 3-D target's feature points fill only 2.9% of the frame area.


Modelling the Inactivation and Possible Regrowth of Salmonella enterica Treated with Chlorophyllin-Chitosan Complex and Visible Light.
The study focuses on predictive modelling of inactivation of Salmonella enterica after treatment with chlorophyllin-chitosan complex and visible light. Salmonella cells were incubated with chlorophyllin-chitosan complex (0.001% chlorophyllin and 0.1% chitosan) for different times (5-60 min) and then illuminated with visible light (λ=405 nm, H e=38 J/cm2). Inactivation curves and post-treatment regrowth curves were built based on microbiological viability tests and data were fitted to ten inactivation and two regrowth models. The photoactivated complex reduced Salmonella population, which were unable to regrow. Weibull and Baranyi models were the best to describe the inactivation and regrowth kinetics respectively. In conclusion, data from the kinetic analysis and predictive modelling confirmed that photoactivated chlorophyllin-chitosan complex is a promising non-thermal approach for inactivation of Gram-negative pathogens, since no bacterial regrowth after treatment has been predicted.


Molecular biology of the hepatitis B virus and role of the X gene.
The hepatitis B virus (HBV) is a widespread human pathogen and a major health problem in many countries. Molecular cloning and sequencing of the viral DNA genome has demonstrated a small and compact structure organized into four overlapping reading frames that encode the viral proteins. Besides structural proteins of the core and the envelope, HBV encodes a DNA polymerase with reverse transcriptase activity, a secreted antigen of unknown function, and a transcriptional activator that is essential for viral replication. Major steps of the viral life cycle have been unraveled, including transcription of all viral RNAs from nuclear covalently closed circular DNA (cccDNA), followed by encapsidation of pregenomic RNA, a more-than-genome length transcript, and reverse transcription of pregenomic RNA leading to asymmetric synthesis of the DNA strands. Although HBV has been recognized as a human tumor virus, no direct transforming activity could be evidenced in different cellular and animal models. However, the transcriptional regulatory protein HBx encoded by the X gene is endowed with weak oncogenic activity. HBx harbors pleiotropic activities and plays a major role in HBV pathogenesis and in liver carcinogenesis.


Sex reversal following deletion of a single distal enhancer of Sox9.
Cell fate decisions require appropriate regulation of key genes. Sox9, a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Sox9 Although others are redundant, enhancer 13 (Enh13), a 557-base pair element located 565 kilobases 5' from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with Sox9 transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans.


Atm heterozygosity cooperates with loss of Brca1 to increase the severity of mammary gland cancer and reduce ductal branching.
The role of homozygous ataxia telangiectasia mutated (ATM) mutations in familial and sporadic forms of cancer is well established, but the contribution of ATM heterozygosity to mammary gland and other cancers has been controversial. To test the effect of Atm heterozygosity on mammary gland cancer, mice with complete loss of exon 11 of Brca1 specifically in mammary epithelium (Brca1-MG-Deltaex11) were studied in either Atm heterozygous or Atm wild-type backgrounds. Targeted deletion of Brca1 in mammary epithelium resulted in carcinomas and adenocarcinomas of varying histology with long (>9 months) latency. Latency to tumorigenesis was found to be unchanged in the Brca1-MG-Deltaex11;Atm heterozygous mice compared with Brca1-MG-Deltaex11;Atm wild-type mice. However, the mice displayed variable tumor severity and differences in mammary tissue development. Mammary tumors from Brca1-MG-Deltaex11;Atm heterozygous mice were anaplastic and undifferentiated in all 20 tumors tested, whereas tumors from mice that were Brca1-MG-Deltaex11 but wild-type for Atm displayed variable histologic profiles, with some anaplastic tumors and other differentiated and less invasive tumor types. Previously reported developmental defects for Brca1-deficient mice were also observed in our model with and without Atm heterozygosity, but Brca1-MG-Deltaex11;Atm heterozygous mice displayed decreased ductal branching during puberty, a phenotype that was not observed in Brca1-MG-Deltaex11;Atm wild-type mice. Our results provide evidence that Atm heterozygosity influences severity of mammary gland tumors in the Brca1-MG-Deltaex11 tumor-prone mouse and suggest that this mutation leads to a newly characterized developmental defect during glandular maturation.


Is Amphiorchis (Digenea: Spirorchiidae) an Exclusive Parasite of Sea Turtles?
The side-necked turtle Hydromedusa tectifera commonly inhabits the tributary streams of the Rio de La Plata and occasionally is found in brackish waters within the estuary of the Rio de La Plata. Few studies have been conducted on its parasitic fauna, especially in Argentina. In the present work Amphiorchis sp. is registered for the first time in a freshwater turtle, expanding the knowledge about the specifi city of the genus that until now was considered inhabiting only marine turtles.


Understanding head injury and intellectual recovery from brain damage: is IQ an adequate measure?
A person's intelligence (or IQ) has long been synonymous with cognitive and general abilities to function daily on an effective level. When traumatic brain injury occurs, there is a natural desire to find some measure that identifies the amount of damage that has occurred and whether it is permanent or temporary. Given the popularity of the IQ test, there is a tendency to use this measure as such a yardstick. It is argued that such a global measure is not appropriate. The predominant reason that it is not a wise choice is that IQ test does not tap into many of the critical areas of a person's functioning, such as personality regulation, shorter-term memory, various types of attentional capacity, and the ability to organize and plan effectively. Rather, to truly and accurately reflect a person's neuropsychological strengths and weaknesses requires the use of many different measures, not just a single one such as an IQ score.


Comparison of two ways of altering carpal tunnel pressure with ultrasound surface wave elastography.
Higher carpal tunnel pressure is related to the development of carpal tunnel syndrome. Currently, the measurement of carpal tunnel pressure is invasive and therefore, a noninvasive technique is needed. We previously demonstrated that speed of wave propagation through a tendon in the carpal tunnel measured by ultrasound elastography could be used as an indicator of carpal tunnel pressure in a cadaveric model, in which a balloon had to be inserted into the carpal tunnel to adjust the carpal tunnel pressure. However, the method for adjusting the carpal tunnel pressure in the cadaveric model is not applicable for the in vivo model. The objective of this study was to utilize a different technique to adjust carpal tunnel pressure via pressing the palm and to validate it with ultrasound surface wave elastography in a human cadaveric model. The outcome was also compared with a previous balloon insertion technique. Results showed that wave speed of intra-carpal tunnel tendon and the ratio of wave speed of intra-and outer-carpal tunnel tendons increased linearly with carpal tunnel pressure. Moreover, wave speed of intra carpal tunnel tendon via both ways of altering carpal tunnel pressure showed similar results with high correlation. Therefore, it was concluded that the technique of pressing the palm can be used to adjust carpal tunnel pressure, and pressure changes can be detected via ultrasound surface wave elastography in an ex vivo model. Future studies will utilize this technique in vivo to validate the usefulness of ultrasound surface wave elastography for measuring carpal tunnel pressure.


Dexamethasone alleviates motion sickness in rats in part by enhancing the endocannabinoid system.
Low-dose dexamethasone has been widely used for the prevention of nausea and vomiting after chemotherapy and surgical procedures and to treat motion sickness due to its minimal adverse effects, but the mechanisms underlying its anti-motion sickness effects are poorly understood. Previous studies have demonstrated that the endocannabinoid system is suppressed by motion sickness but stimulated by dexamethasone. The aim of the present study was to determine whether dexamethasone has an anti-motion sickness effect in rats and to elucidate the mechanism of this action. We used HPLC-MS/MS to measure the plasma concentrations of anandamide and 2-arachidonoylglycerol+1-arachidonoylglycerol, and we employed real-time quantitative PCR (qRT-PCR) and/or Western blot analysis to assay the expression of N-acylphosphatidyl-ethanolamine hydrolyzing phospholipase D, sn-1-selective diacylglycerol lipase, fatty acid hydrolase, monoacylglycerol lipase and endocannabinoid CB1 receptor in the dorsal vagal complex and stomach of rats exposed to a motion sickness protocol. The results showed that dexamethasone lowered the motion sickness index and restored the levels of endogenous cannabinoids and the expression of the endocannabinoid CB1 receptor, which declined after the induction of motion sickness, in the dorsal vagal complex and stomach.


Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance.
An increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.


Epidemiologic evidence on the relationship between formaldehyde exposure and cancer.
Over 30 epidemiologic studies have evaluated cancer risks associated with formaldehyde exposure. Excesses were reported for several sites, leukemia and cancers of the nasal cavities, nasopharynx, lung, and brain generating the greatest interest. The excesses of leukemia and brain and colon cancer found among professionals may not be related to formaldehyde exposure, since similar excesses were not observed among industrial workers. Inconsistencies among and within studies impede assigning formaldehyde a convincing causal role for the excesses of lung cancer found among industrial workers. A causal role for formaldehyde is the most probable for cancers of the nasopharynx and, to a less extent, the nasal cavities. Evidence of exposure-response relationships, the fact that direct contact with formaldehyde may occur at these upper respiratory sites, and the consistency of these findings with experimental studies make this assumption highly probable.


A motility function for the paraflagellar rod of Leishmania parasites revealed by PFR-2 gene knockouts.
We demonstrate a functional role for the paraflagellar rod (PFR) in motility of Leishmania mexicana. The PFR is a complex cytoskeletal structure running parallel to the axoneme in the flagella of kinetoplastid protozoa. The PFR is composed of a latticework of protein filaments whose major constituents are two related proteins (PFR-1 and PFR-2 in Leishmania). The molecular details of their assembly into PFR filaments are unknown as is the biological function of the PFR. As an approach to understanding the structure and function of the PFR in Leishmania, we made L. mexicana null mutants of PFR-2. PFR-2 minus parasites grow and divide normally in culture and still express the PFR-1 protein. They lack most of the PFR structure demonstrating that the PFR-2 protein is an essential constituent of the PFR. Detailed ultrastructural analysis of the PFR-2 null mutant reveals the presence of a residual inner substructure of the PFR which contains PFR-1 protein, indicating that PFR-1 can polymerize in the absence of PFR-2. The PFR-2 null mutant displays pronounced changes in flagellar beat waveform and forward swimming velocity, compared to wild type parasites consistent with decreased internal elastic bending resistance in PFR-lacking flagella, and indicating a functional role for the PFR in the motility of Leishmania.


Pax3 functions at a nodal point in melanocyte stem cell differentiation.
Most stem cells are not totipotent. Instead, they are partially committed but remain undifferentiated. Upon appropriate stimulation they are capable of regenerating mature cell types. Little is known about the genetic programmes that maintain the undifferentiated phenotype of lineage-restricted stem cells. Here we describe the molecular details of a nodal point in adult melanocyte stem cell differentiation in which Pax3 simultaneously functions to initiate a melanogenic cascade while acting downstream to prevent terminal differentiation. Pax3 activates expression of Mitf, a transcription factor critical for melanogenesis, while at the same time it competes with Mitf for occupancy of an enhancer required for expression of dopachrome tautomerase, an enzyme that functions in melanin synthesis. Pax3-expressing melanoblasts are thus committed but undifferentiated until Pax3-mediated repression is relieved by activated beta-catenin. Thus, a stem cell transcription factor can both determine cell fate and simultaneously maintain an undifferentiated state, leaving a cell poised to differentiate in response to external stimuli.


G-Anchor: a novel approach for whole-genome comparative mapping utilizing evolutionary conserved DNA sequences.
Cross-species whole-genome sequence alignment is a critical first step for genome comparative analyses, ranging from the detection of sequence variants to studies of chromosome evolution. Animal genomes are large and complex, and whole-genome alignment is a computationally intense process, requiring expensive high-performance computing systems due to the need to explore extensive local alignments. With hundreds of sequenced animal genomes available from multiple projects, there is an increasing demand for genome comparative analyses. Here, we introduce G-Anchor, a new, fast, and efficient pipeline that uses a strictly limited but highly effective set of local sequence alignments to anchor (or map) an animal genome to another species' reference genome. G-Anchor makes novel use of a databank of highly conserved DNA sequence elements. We demonstrate how these elements may be aligned to a pair of genomes, creating anchors. These anchors enable the rapid mapping of scaffolds from a de novo assembled genome to chromosome assemblies of a reference species. Our results demonstrate that G-Anchor can successfully anchor a vertebrate genome onto a phylogenetically related reference species genome using a desktop or laptop computer within a few hours and with comparable accuracy to that achieved by a highly accurate whole-genome alignment tool such as LASTZ. G-Anchor thus makes whole-genome comparisons accessible to researchers with limited computational resources. G-Anchor is a ready-to-use tool for anchoring a pair of vertebrate genomes. It may be used with large genomes that contain a significant fraction of evolutionally conserved DNA sequences and that are not highly repetitive, polypoid, or excessively fragmented. G-Anchor is not a substitute for whole-genome aligning software but can be used for fast and accurate initial genome comparisons. G-Anchor is freely available and a ready-to-use tool for the pairwise comparison of two genomes.


The lipoprotein of the outer membrane of Escherichia coli: a B-lymphocyte mitogen.
The lipoprotein of the outer membrane of Escherichia coli is a B-cell mitogen in mice. Polyclonal activation of B lymphocytes was measured by an increase in thymidine uptake, by the development of plaque-forming cells against densely coupled trinitrophenylated sheep red cells, and by selectively increased rates of synthesis and secretion of leucine-labeled IgM. Murein-free and muropeptides-containing lipoprotein are effective in B-cell activation, while free murein is inactive. Removal of ester-linked fatty acids from the amino-terminal end of the lipoprotein by alkaline hydrolysis abolishes the mitogenicity of the lipoprotein. B lymphocytes from high responder (C3H/Tif and BALB/c nu/nu) or from low responder (C3H/HeJ) mice to the mitogen lipopolysaccharide (LPS) both respond well to the lipoprotein. Anti-immunoglobulin antibodies inhibit the mitogenic stimulation of B cells by lipoprotein. A complex of structures including the Ig-receptor molecules, the LPS receptor, and the lipoprotein receptor appear involved in the regulation of mitogenic stimulation of B cells to proliferation and differentiation to IgM-secreting cells.


Sex-biased miRNAs in gonad and their potential roles for testis development in yellow catfish.
Recently, YY super-male yellow catfish had been created by hormonal-induced sex reversal and sex-linked markers, which provides a promising research model for fish sex differentiation and gonad development, especially for testis development. MicroRNAs (miRNAs) have been revealed to play crucial roles in the gene regulation and gonad development in vertebrates. In this study, three small RNA libraries constructed from gonad tissues of XX female, XY male and YY super-male yellow catfish were sequenced. The sequencing data generated a total of 384 conserved miRNAs and 113 potential novel miRNAs, among which 23, 30 and 14 miRNAs were specifically detected in XX ovary, XY testis, and YY testis, respectively. We observed relative lower expression of several miR-200 family members, including miR-141 and miR-429 in YY testis compared with XY testis. Histological analysis indicated a higher degree of testis maturity in YY super-males compared with XY males, as shown by larger spermatogenic cyst, more spermatids and fewer spermatocytes in the spermatogenic cyst. Moreover, five miR-200 family members were significantly up-regulated in testis when treated by 17α-ethinylestradiol (EE2), high dose of which will impair testis development and cell proliferation. The down-regulation of miR-141 and 429 coincides with the progression of testis development in both yellow catfish and human. At last, the expression pattern of nine arbitrarily selected miRNAs detected by quantitative RT-PCR was consistent with the Solexa sequencing results. Our study provides a comprehensive miRNA transcriptome analysis for gonad of yellow catfish with different sex genotypes, and identifies a number of sex-biased miRNAs, some of that are potentially involved in testis development and spermatogenesis.


Sex differences in the effect of fish-oil supplementation on the adaptive response to resistance exercise training in older people: a randomized controlled trial.
Resistance exercise increases muscle mass and function in older adults, but responses are attenuated compared with younger people. Data suggest that long-chain n-3 polyunsaturated fatty acids (PUFAs) may enhance adaptations to resistance exercise in older women. To our knowledge, this possibility has not been investigated in men. We sought to determine the effects of long-chain n-3 PUFA supplementation on resistance exercise training-induced increases in muscle mass and function and whether these effects differ between older men and women. Fifty men and women [men: n = 27, mean ± SD age: 70.6 ± 4.5 y, mean ± SD body mass index (BMI; in kg/m2): 25.6 ± 4.2; women: n = 23, mean ± SD age: 70.7 ± 3.3 y, mean ± SD BMI: 25.3 ± 4.7] were randomly assigned to either long-chain n-3 PUFA (n = 23; 3 g fish oil/d) or placebo (n = 27; 3 g safflower oil/d) and participated in lower-limb resistance exercise training twice weekly for 18 wk. Muscle size, strength, and quality (strength per unit muscle area), functional abilities, and circulating metabolic and inflammatory markers were measured before and after the intervention. Maximal isometric torque increased after exercise training to a greater (P < 0.05) extent in the long-chain n-3 PUFA group than in the placebo group in women, with no differences (P > 0.05) between groups in men. In both sexes, the effect of exercise training on maximal isokinetic torque at 30, 90, and 240° s-1, 4-m walk time, chair-rise time, muscle anatomic cross-sectional area, and muscle fat did not differ (P > 0.05) between groups. There was a greater (P < 0.05) increase in muscle quality in women after exercise training in the long-chain n-3 PUFA group than in the placebo group, with no such differences in men (P > 0.05). Long-chain n-3 PUFAs resulted in a greater decrease (P < 0.05) than the placebo in plasma triglyceride concentrations in both sexes, with no differences (P > 0.05) in glucose, insulin, or inflammatory markers. Long-chain n-3 PUFA supplementation augments increases in muscle function and quality in older women but not in older men after resistance exercise training. This trial was registered at clinicaltrials.gov as NCT02843009.


The impact of noise and hearing loss on the processing of simultaneous sentences.
To examine the impact of hearing impairment on a listener's ability to process simultaneous spoken messages. Nine young listeners with bilateral sensorineural hearing loss and nine young listeners with normal hearing participated in this study. Two messages of equal level were presented separately to the two ears. The messages were systematically degraded by adding speech-shaped noise. Listeners performed a single task in which report of one message was required and a dual task in which report of both messages was required. As the level of the added noise was increased, performance on both single and dual tasks declined. In the dual task, performance on the message reported second was poorer and more sensitive to the noise level than performance on the message reported first. When compared to listeners with normal hearing, listeners with hearing loss showed a larger deficit in recall of the second message than the first. This difference disappeared when performance of the hearing loss group was compared to that of the normal-hearing group at a poorer signal to noise ratio. A listener's ability to process a secondary message is more sensitive to noise and hearing impairment than the ability to process a primary message. Tasks involving the processing of simultaneous messages may be useful for assessing hearing handicap and the benefits of rehabilitation in realistic listening scenarios.


Update on endovascular therapies for cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage.
Cerebral vasospasm remains a major source of morbidity and death in patients with aneurysmal subarachnoid hemorrhage (SAH). When vasospasm becomes refractory to maximal medical management consisting of induced hypertension and hypervolemia and administration of calcium channel antagonists, endovascular therapies should be considered. The primary goal of endovascular treatment is to increase cerebral blood flow to prevent cerebral infarction. Two of the more frequently studied endovascular treatments are transluminal balloon angioplasty and intraarterial papaverine infusion. These two have been used either alone or in combination for the treatment of vasospasm. Other pharmacological vasodilating agents currently being investigated are intraarterial nimodipine, nicardipine, verapamil, and milrinone. Newer intraarterial agents, such as fasudil and colforsin daropate, have also been investigated. In this article the authors review the current options in terms of endovascular therapies for treatment of cerebral vasospasm. The mechanism of action, technique of administration, clinical effect and outcomes, and complications of each modality are discussed.


Gene therapy using IL-27 ameliorates Sjögren's syndrome-like autoimmune exocrinopathy.
Sjögren's syndrome (SjS) is a systemic autoimmune disease characterized by decreased salivary and lacrimal gland secretions, resulting in severe dry mouth and dry eyes. Recent studies have suggested that TH17 cells and its signature cytokine IL-17 are involved in the underlying pathogenic mechanisms leading to destructive inflammation and autoimmunity. In the present study, we examined whether IL-27, a natural inhibitor of TH17 activity, could down-regulate or reverse SjS in C57BL/6.NOD-Aec1Aec2 mice, a model of primary-SjS. Recombinant serotype 2 adeno-associated viral (AAV2) vectors expressing either IL-27 (rAAV2-IL27) or LacZ (rAAV2-LacZ) were injected into 6 or 14 week-old C57BL/6.NOD-Aec1Aec2 mice. Changes in IL-27, IL-17, and IL-10 cytokine levels in peripheral blood were determined by ELISAs, while flow cytometry analyses were used to quantify cytokine-positive splenocytes. Histological assessment of salivary glands, anti-nuclear autoantibody (ANA) staining, and stimulated saliva flow rates were used to profile SjS disease severity. Mice systemically treated with intravenous rAAV2-IL27 injections at either 6 or 14 weeks of age exhibited long-term elevated levels of serum IL-27 with concomitantly reduced levels of IL-17 compared with sera from mice injected with rAAV2-LacZ or saline out to 20 weeks post-inoculation. Most importantly, disease profiles revealed that rAAV2-IL27 treatment had little effect on lymphocytic focus (LF) scores, but resulted in structural changes in LF, lower titers of ANAs with changes in staining patterns, and a less severe clinical disease as determined by saliva flow rates. These data support the concept that IL-27, when provided exogenously, can induce a suppressive effect on SjS development and thus may be an effective therapeutic agent for regulating TH17 pro-inflammatory activity in autoimmune diseases where the TH17 system has been shown to play an important role in their pathogenesis.


Mechanisms for mechanical trapping of geologically sequestered carbon dioxide.
Carbon dioxide (CO2) sequestration in subsurface reservoirs is important for limiting atmospheric CO2 concentrations. However, a complete physical picture able to predict the structure developing within the porous medium is lacking. We investigate theoretically reactive transport in the long-time evolution of carbon in the brine-rock environment. As CO2 is injected into a brine-rock environment, a carbonate-rich region is created amid brine. Within the carbonate-rich region minerals dissolve and migrate from regions of high-to-low concentration, along with other dissolved carbonate species. This causes mineral precipitation at the interface between the two regions. We argue that precipitation in a small layer reduces diffusivity, and eventually causes mechanical trapping of the CO2. Consequently, only a small fraction of the CO2 is converted to solid mineral; the remainder either dissolves in water or is trapped in its original form. We also study the case of a pure CO2 bubble surrounded by brine and suggest a mechanism that may lead to a carbonate-encrusted bubble owing to structural diffusion.


Radiographic recommendations for the transitional dentition: comparison of general dentists and pediatric dentists.
A survey which included brief case histories and intraoral photos of four transitional dentitions, including examples of ectopic and delayed eruption, as well as carious lesions, was mailed to a random sample of 2000 general dentists and 1000 pediatric dentists. Radiographic options were listed, from which each dentist was to indicate all films needed for each child's examination. Surveys were returned by 1273 (43%) dentists, including 713 (36%) general dentists and 560 (56%) pediatric dentists. The pediatric dentists took significantly more diagnostic radiographs than did the general dentists for each of the four transitional dentition cases. Pediatric dentists were more likely than the general dentists to take panoramic films and combinations which included panoramic films, bite-wing radiographs and periapical films. The most frequently ordered combinations were bite-wing radiographs plus panoramic films and bite-wing radiographs plus anterior periapical films. General dentists recommended bite-wing radiographs films only more frequently than did pediatric dentists. In view of the results of this study and the USDHHS guidelines for radiographic examinations, (1987) education must be provided for both general dentists and pediatric dentists regarding appropriate radiographic examinations for transitional dentition patients.


The last 59 amino acids of Smoothened cytoplasmic tail directly bind the protein kinase Fused and negatively regulate the Hedgehog pathway.
The Hedgehog (HH) signaling pathway is crucial for the development of many organisms and its inappropriate activation is involved in numerous cancers. HH signal controls the traffic and activity of the seven-pass transmembrane protein Smoothened (SMO), leading to the transcriptional regulation of HH-responsive genes. In Drosophila, the intracellular transduction events following SMO activation depend on cytoplasmic multimeric complexes that include the Fused (FU) protein kinase. Here we show that the regulatory domain of FU physically interacts with the last 52 amino acids of SMO and that the two proteins colocalize in vivo to vesicles. The deletion of this region of SMO leads to a constitutive activation of SMO, promoting the ectopic transcription of HH target genes. This activation is partially dependent of FU activity. Thus, we identify a novel link between SMO and the cytoplasmic complex(es) and reveal a negative role of the SMO C-terminal region that interacts with FU. We propose that FU could act as a switch, activator in presence of HH signal or inhibitor in absence of HH.


Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome.
Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A plant-derived, highly purified CBD formulation with a known and constant composition has been approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. In the European Union, the drug has been authorized by the European Medicines Agency for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome, in conjunction with clobazam, and is under regulatory review for the treatment of seizures in patients with tuberous sclerosis complex. This systematic review aimed to summarize the currently available body of knowledge about the use of this US Food and Drug Administration/European Medicines Agency-approved oral formulation of pharmaceutical-grade CBD in patients with epileptic conditions, especially developmental and epileptic encephalopathies other than Dravet syndrome and Lennox-Gastaut syndrome. The relevant studies were identified through MEDLINE and the US National Institutes of Health Clinical Trials Registry in October 2020. There were no date limitations or language restrictions. The following types of studies were included: clinical trials, cohorts, case-control, cross-sectional, clinical series, and case reports. Participants had to meet the following criteria: any sex, any ethnicity, any age, diagnosis of epilepsy, receiving plant-derived, highly purified (> 98% w/w) CBD in a sesame oil-based oral solution for the treatment of seizures. Data extracted from selected records included efficacy, tolerability, and safety outcomes. Five hundred and seventy records were identified by database and trial register searching. Fifty-seven studies were retrieved for detailed assessment, of which 42 were eventually included for the review. The participants of the studies included patients of both pediatric and adult age. Across the trials, purified CBD was administered at dosages up to 50 mg/kg/day. In a randomized double-blind controlled trial in patients with tuberous sclerosis complex, CBD was associated with a significantly greater percent reduction in seizure frequency than placebo over the treatment period. Open-label studies suggested the effectiveness of CBD in the treatment of children and adults presenting with other epilepsy syndromes than those addressed by regulatory trials, including CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences. The most common adverse events observed during treatment with CBD included somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. The currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies. The existing evidence can provide preliminary support for additional research.