Gas dispersion and immobile gas volume in solid and porous particle biofilter materials at low air flow velocities.
Gas-phase dispersion in granular biofilter materials with a wide range of particle sizes was investigated using atmospheric air and nitrogen as tracer gases. Two types of materials were used: (1) light extended clay aggregates (LECA), consisting of highly porous particles, and (2) gravel, consisting of solid particles. LECA is a commercial material that is used for insulation, as a soil conditioner, and as a carrier material in biofilters for air cleaning. These two materials were selected to have approximately the same particle shape. Column gas transport experiments were conducted for both materials using different mean particle diameters, different particle size ranges, and different gas flow velocities. Measured breakthrough curves were modeled using the advection-dispersion equation modified for mass transfer between mobile and immobile gas phases. The results showed that gas dispersivity increased with increasing mean particle diameter for LECA but was independent of mean particle diameter for gravel. Gas dispersivity also increased with increasing particle size range for both media. Dispersivities in LECA were generally higher than for gravel. The mobile gas content in both materials increased with increasing gas flow velocity but it did not show any strong dependency on mean particle diameter or particle size range. The relative fraction of mobile gas compared with total porosity was highest for gravel and lowest for LECA likely because of its high internal porosity.


Ambient Assisted Living as Support for Aging in Place: Quantitative Users' Acceptance Study on Ultrasonic Whistles.
Given the fact of an aging society, new supply measures and living concepts are needed, especially as health impairments along with care dependency increase with age. As many elderly people wish to stay at home for as long as possible, ambient assisted living (AAL) represents a support for aging in place. AAL combines medical and care technology within living environments and is, therefore, a promising approach to cope with demographic change in terms of fast-growing care needs and fewer skilled workers. Ultrasonic whistles represent one innovative technical possibility for such supportive housing solutions. Central fields of application are home automation, emergency service, and positioning. As AAL technologies affect sensitive areas of life, it is of great interest under which conditions they are accepted or rejected, taking individual user requirements into account. Hence, the aim of this study was to investigate users' perception and evaluation of ultrasonic whistles. In this study, we examined the acceptance of ultrasonic whistles in home care by function and room using a Web-based questionnaire. Besides an evaluation of the overall usefulness, we focused on the intention to use ultrasonic whistles; 270 participants assessed home automation, emergency service, and positioning as specific functions of ultrasonic whistles. Furthermore, bathroom, bedroom, and living room were evaluated as specific usage locations (rooms). With regard to the user's perspective, the focus was set on age and attitudes toward aging of care receivers. This study revealed a significant influence of function (F2,269=60.444; P<.001), room (F2,269=41.388; P<.001), and the interaction of function and room (F4,269=8.701; P<.001) on the acceptance of ultrasonic whistles. The use of emergency services within the bathroom represented the most accepted alternative, whereas positioning within the living room received the comparably lowest evaluations. Although user diversity played a minor role for acceptance overall, the assessment of single applications differed among user groups, particularly with regard to age differences (F20,500=1.988; P<.01) in the evaluation of specific installation options such as automated doors. The study revealed profound insights into the user-centered assessment of ultrasonic whistles in home care and discovered function and room as influencing acceptance parameters. Concerning user characteristics, age, and attitude toward aging partly affected these evaluations, forming the basis for and showing the importance of further investigations in this context.


Expression of the deleted in colorectal cancer gene is related to prognosis in DNA diploid and low proliferative colorectal adenocarcinoma.
Whether or not the deleted in colorectal cancer (DCC) gene is implicated in metastases or in predicting prognosis in patients with colorectal cancer has not previously been substantiated. Our aims were to investigate DCC expression in primary colorectal cancers and in metastases to identify any prognostic significance. DCC expression was examined immunohistochemically in 195 primary colorectal adenocarcinomas and in 23 paired primary tumors and lymph node metastases. DNA content and S-phase fraction were measured by flow cytometry. The absence of DCC expression was observed in 55 primary tumors (28%). DCC negativity was significantly related to poor prognosis in patients with DNA diploid tumors (P =.03) and those with a low S-phase fraction (< 5%, P =.02) but not in patients with nondiploid tumors or those with a higher S-phase fraction. Furthermore, DCC expression retained its prognostic significance in the diploid subgroup after adjusting for sex, age, site, stage, growth pattern, and differentiation (P =.01). DCC expression was similar in primary tumors and their metastases. The absence of DCC predicted a poor outcome in the patients with diploid tumors and those tumors with a low S-phase fraction. Immunohistochemistry may be considered as a practical test to assess prognosis in this subgroup of patients.


Fourier transform infrared spectroscopy to quantify collagen and elastin in an in vitro model of extracellular matrix degradation in aorta.
Extracellular matrix (ECM) is a key component and regulator of many biological tissues including aorta. Several aortic pathologies are associated with significant changes in the composition of the matrix, especially in the content, quality and type of aortic structural proteins, collagen and elastin. The purpose of this study was to develop an infrared spectroscopic methodology that is comparable to biochemical assays to quantify collagen and elastin in aorta. Enzymatically degraded porcine aorta samples were used as a model of ECM degradation in abdominal aortic aneurysm (AAA). After enzymatic treatment, Fourier transform infrared (FTIR) spectra of the aortic tissue were acquired by an infrared fiber optic probe (IFOP) and FTIR imaging spectroscopy (FT-IRIS). Collagen and elastin content were quantified biochemically and partial least squares (PLS) models were developed to predict collagen and elastin content in aorta based on FTIR spectra. PLS models developed from FT-IRIS spectra were able to predict elastin and collagen content of the samples with strong correlations (RMSE of validation = 8.4% and 11.1% of the range respectively), and IFOP spectra were successfully used to predict elastin content (RMSE = 11.3% of the range). The PLS regression coefficients from the FT-IRIS models were used to map collagen and elastin in tissue sections of degraded porcine aortic tissue as well as a human AAA biopsy tissue, creating a similar map of each component compared to histology. These results support further application of FTIR spectroscopic techniques for evaluation of AAA tissues.


A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma : a North Central Cancer Treatment Group Study, N057E(1).
There is increasing evidence that paclitaxel and carboplatin are clinically active in the treatment of metastatic melanoma (MM). ABI-007 is an albumin-bound formulation of paclitaxel that has demonstrated single-agent activity against metastatic melanoma. A parallel phase II trial was conducted in patients with unresectable stage IV melanoma who were either chemotherapy naive (CN) or previously treated (PT). The treatment regimen consisted of ABI-007 (100 mg/m(2) ) and carboplatin area under the curve (AUC2) administered on days 1, 8, and 15 every 28 days. The primary aim of this study was objective response rate (RECIST). Seventy-six patients (41 CN and 35 PT) were enrolled between November 2006 and July 2007. Three patients withdrew consent prior to starting treatment. The median number of treatment cycles was 4. There were 10 (25.6%) responses (1 complete response [CR] and 9 partial responses [PRs]) in the CN cohort (90% CI, 16.7%-42.3%) and 3 (8.8%) responses (3 PRs) in the PT cohort (90% CI, 2.5%-21.3%). Median progression-free survival was 4.5 months in the CN cohort and 4.1 months in the PT cohort. Median overall survival (OS) was 11.1 months in the CN group and 10.9 months in the PT group. Severe toxicities in both groups (Common Terminology Criteria for Adverse Effects v.3.0 ≥grade 3) included neutropenia, thrombocytopenia, neurosensory problems, fatigue, nausea, and vomiting. The weekly combination of ABI-007 and carboplatin appears to be moderately well tolerated, with promising clinical activity as therapy in patients who are chemotherapy naive and with modest antitumor activity in those previously treated.


Interest in Using Workplace Energy Expenditure Devices Among Primary Care Patients.
Workplace energy expenditure devices (WEEDs), such as bicycle desks and treadmill desks, can contribute to weight gain prevention and disease risk-reduction. Little is known about the extent to which adults with diverse health risk factors are interested in using WEEDs. Primary care patients aged 18 to 65 years at 2 outpatient clinics in Central Pennsylvania completed a cross-sectional survey in April, 2014 to assess interest in using "a small pedaling device under the desk" and "walking on a treadmill with a desk attached" if these options were provided at no cost. Demographic and health risk factors were also assessed. Multiple logistic regression analyses were used to examine the associations of demographic and health risk factors with interest in using WEEDs. Among 240 patients, 106 (44.2%) reported interest in using WEEDs. Of these 106 patients, interest in using a bicycle desk (91.5%) was higher than interest in using a treadmill desk (65.1%), P < .001. Females were more likely than males to be interested in using a bicycle desk, and patients aged 18 to 44 years were more likely than those aged 45 to 65 years to be interested in using a treadmill desk. Results suggest that diverse patient populations may have interest in using WEEDs. Promoting use of WEEDs in primary care practices could help meet national standards for providing comprehensive, patient-centered care.


Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.
Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone. A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated. For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp) in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs. Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.


Neurophysiology of locomotor automatism.
It had long been known that the decapitated cock can cross a yard. During the last century an automatic mechanism controlling stepping movements has also been found in other vertebrates. The system controlling locomotion has many features similar to these systems controlling other natural movements: respiration (28), micturition (98), scratching (154), mastication (33), etc. Today we know that there are spinal automatisms for each limb generating its stepping movements. Activity of these automatisms depends essentially on the afferent inflow from the moving limbs. There also is interaction of the limbs during locomotion that promotes their coordination. The existence of two descending systems with different functions in the control of locomotion (Fig. 1) also can be considered as an established fact. Activity of a number of neurons involved in the control of locomotion has been studied directly during locomotion in decorticate, thalamic, and mesencephalic cats. To explain the experimental data at hand, several hypotheses of organization of the spinal automatism of stepping have been forwarded: a chain-reflex hypothesis, a hypothesis of two reciprocal half-centers, and a ring hypothesis (Fig. 2). Although general features of the system controlling locomotion are more or less clear, many questions are not yet answered. It is unknown what relative contributions to motoneuronal activity are made by proprioceptive reflexes versus influences from the automatism of stepping. Furthermore the structure of the spinal stepping automatism is not known. It is not clear if the spinal stepping automatisms of the forelimbs are as potent as those of the hindlimbs. The descending system responsible for activation of the spinal automatism of stepping has not yet been identified in direct experiments. The inputs and outputs of the subthalamic and midbrain "locomotor" regions have not been found, and we know almost nothing about intrinsic interaction of neurons in these regions. The role of inhibitory thalamic influences is scarcely known. Finally, we have no data concerning the influence of either cortical (42, 186) or visual mechanisms in locomotor control.


The guinea-pig tracheal potential difference as an in vivo model for the study of epithelial sodium channel function in the airways.
The epithelial sodium channel (ENaC) is a key regulator of airway mucosal hydration and mucus clearance. Negative regulation of airway ENaC function is predicted to be of clinical benefit in the cystic fibrosis lung. The aim of this study was to develop a small animal model to enable the direct assessment of airway ENaC function in vivo. Tracheal potential difference (TPD) was utilized as a measure of airway epithelial ion transport in the guinea-pig. ENaC activity in the trachea was established with a dose-response assessment to a panel of well-characterized direct and indirect pharmacological modulators of ENaC function, delivered by intra-tracheal (i.t.) instillation. The TPD in anaesthetized guinea-pigs was attenuated by the direct ENaC blockers: amiloride, benzamil and CF552 with ED(50) values of 16, 14 and 0.2 microg kg(-1) (i.t.), respectively. 5-(N-Ethyl-N-isopropyl) amiloride, a structurally related compound but devoid of activity on ENaC, was without effect on the TPD. Intra-tracheal dosing of the Kunitz-type serine protease inhibitors aprotinin and placental bikunin, which have previously been demonstrated to inhibit proteolytic activation of ENaC, likewise potently attenuated TPD in guinea-pigs, whereas alpha(1)-antitrypsin and soya bean trypsin inhibitor were without effect. The pharmacological sensitivity of the TPD to amiloride analogues and also to serine protease inhibitors are both consistent with that of ENaC activity in the guinea-pig trachea. The guinea-pig TPD therefore represents a suitable in vivo model of human airway epithelial ion transport.


Cycloartenyl trans-ferulate, a component of the bran byproduct of sake-brewing rice, inhibits mammalian DNA polymerase and suppresses inflammation.
During the screening of selective DNA polymerase (pol) inhibitors, we isolated cycloartenyl trans-ferulate (CAF), which is a major component of γ-oryzanol, which is a byproduct formed during the production of Japanese rice wine "sake". CAF selectively inhibited the activity of mammalian A, B, and X pol families, but Y family pols were not affected. CAF did not influence the activities of plant or prokaryotic pols, nor the activity of other DNA metabolic enzymes tested. Individual chemical components of CAF, including cycloartenol (CA) and ferulic acid (FA), did not inhibit pol enzyme activities. CAF suppressed TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation in the mouse ear, but CA and FA did not. The ability to inhibit mammalian pol enzymes in vitro was positively correlated with their propensity to suppress inflammation in vivo. These results suggest that this byproduct formed during the sake-brewing process is useful as an anti-inflammatory agent.


Specifically differentiated T cell subset promotes tumor immunity over fatal immunity.
Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9IL-33 cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9IL-33 cells offers an attractive approach for separating GVL activity from GVHD.


3D bioprinting by reinforced bioink based on photocurable interpenetrating networks for cartilage tissue engineering.
Cartilage has a limited ability to repair itself, highlighting the urgent need for suitable materials for cartilage regeneration. Achieving a balance between cell survival environment and hydrogel crosslinking density is crucial for photosensitive cell-laden cartilage repair materials to achieve both high strength and good cell viability. Here, an interpenetrating hydrogel consisted of methacrylate gelatin (GelMA) and glycidyl methacrylate silk fibroin (SG) was introduced. Compared to GelMA hydrogel, GelMA/SG had desired mechanical properties, with achieving up to 5 times of compression modulus and 6 times of compression failure energy. Meanwhile, the chondrocytes inside GelMA/SG exhibited great viability which was over 90 %. GelMA/SG as a bioink had favorable printability for digital light processing (DLP) bioprinting. The mesh DLP-printed scaffolds with high precision were created and GelMA/SG had a better shape retention ability than GelMA. Moreover, GelMA/SG cell-laden scaffolds had high strength while chondrocytes proliferated significantly in vitro culture. They were implanted under the skin of nude mice to evaluate ectopic chondrogenesis in vivo. The GelMA/SG cell-laden scaffolds indicated little deformation and high expression of collagen type II and glycosaminoglycans, which was advantageous for cartilage regeneration. The scaffold and its fabrication strategy provide potential solutions for clinical cartilage repair problems in the future.


Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms.
A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A > C (IVS9-2A > C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-scale genetic and clinical resources from the ENIGMA, CIMBA and BCAC consortia to assess pathogenicity of c.594-2A > C. The combined odds for causality considering case-control, segregation and breast tumor pathology information was 3.23 × 10-8 Our data indicate that c.594-2A > C is always in cis with c.641A > G. The spliceogenic effect of c.[594-2A > C;641A > G] was characterized using RNA analysis of human samples and splicing minigenes. As expected, c.[594-2A > C; 641A > G] caused exon 10 skipping, albeit not due to c.594-2A > C impairing the acceptor site but rather by c.641A > G modifying exon 10 splicing regulatory element(s). Multiple blood-based RNA assays indicated that the variant allele did not produce detectable levels of full-length transcripts, with a per allele BRCA1 expression profile composed of ≈70-80% truncating transcripts, and ≈20-30% of in-frame Δ9,10 transcripts predicted to encode a BRCA1 protein with tumor suppression function.We confirm that BRCA1c.[594-2A > C;641A > G] should not be considered a high-risk pathogenic variant. Importantly, results from our detailed mRNA analysis suggest that BRCA-associated cancer risk is likely not markedly increased for individuals who carry a truncating variant in BRCA1 exons 9 or 10, or any other BRCA1 allele that permits 20-30% of tumor suppressor function. More generally, our findings highlight the importance of assessing naturally occurring alternative splicing for clinical evaluation of variants in disease-causing genes.


Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK.
Mitogen-activated protein kinase-activated protein kinase-1 (MAPKAP-K1; also known as p90rsk) contains two protein kinase domains in a single polypeptide. The N-terminal kinase domain is necessary for the phosphorylation of peptide substrates, whereas the C-terminal kinase domain is required for full activation of the N-terminal domain. Here we identify six sites in MAPKAP-K1a that become phosphorylated in transfected COS-1 cells. The inactive form of MAPKAP-K1a in unstimulated cells is partially phosphorylated at Ser222 and Ser733. Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of Thr360, Ser364, Thr574, and Ser381 and increases the phosphorylation of Ser222 and Ser733. Our data indicate that mitogen-activated protein kinase activates the C-terminal kinase domain by phosphorylating Thr574 and contributes to the activation of the N-terminal kinase domain by phosphorylating Ser364. The activated C-terminal domain phosphorylates Ser381, which, together with phosphorylation of Ser364, activates the N-terminal kinase domain. The phosphorylation of Ser222 and Ser733, which can be catalyzed by the N-terminal domain, does not activate MAPKAP-K1a per se, but Ser222 phosphorylation appears to be required for activation. Ser222, Ser364, and Ser381 are situated in analogous positions to phosphorylation sites in protein kinase B, protein kinase C, and p70S6K, suggesting a common mechanism of activation for these growth factor-stimulated protein kinases.


[Radiosensitivity of Drosophila lines. VII. The effect of the maternal genotype on the yield of recessive and dominant lethal mutations induced by the gamma irradiation of males].
The effect of material repair on induction of paternal mutations was tested with radiosensitive rad(2)201G1 mutant. Basc males were irradiated at doses from 0 to 60 Gy of gamma-rays and mated to the radiosensitive mutant or control females. Frequencies of sex-linked recessive lethals and dominant lethals (induced in the paternal genome) were determined. With control females, the rate of recessive lethals increased linearly from 0 to 60 Gy. With rad(2)201G1 mutant, an increase in spontaneous and induced rates of paternal dominant lethals was observed; the rate of sex-linked recessive lethals increased non-linearly from 0 to 60 Gy.


Cyclophilin A potentiates TRIM5α inhibition of HIV-1 nuclear import without promoting TRIM5α binding to the viral capsid.
The host immunophilin cyclophilin A (CypA) binds to the capsid protein (CA) of HIV-1 and regulates its infectivity. Depending on the target cell type, CypA can either promote or inhibit HIV-1 infection. The ability of CypA to promote HIV-1 infection has been extensively studied and linked to several steps in early replication including uncoating, reverse transcription and nuclear import. By contrast, the mechanism by which CypA inhibits infection is less well understood. We investigated the mechanism by which CypA potentiates restriction of HIV-1 by the tripartite motif-containing protein 5 (TRIM5α). Depletion of TRIM5α in the African green monkey cell line Vero, resulted in a loss of inhibition of infection by CypA, demonstrating that inhibition by CypA is mediated by TRIM5α. Complementary genetic and biochemical assays failed to demonstrate an ability of CypA to promote binding of TRIM5α to the viral capsid. TRIM5α inhibits HIV-1 reverse transcription in a proteasome-dependent manner; however, we observed that inhibition of proteasome activity did not reduce the ability of CypA to inhibit infection, suggesting that CypA acts at a step after reverse transcription. Accordingly, we observed a CypA-dependent reduction in the accumulation of nuclear HIV-1 DNA, indicating that CypA specifically promotes TRIM5α inhibition of HIV-1 nuclear import. We also observed that the ability of CypA to inhibit HIV-1 infection is abolished by amino acid substitutions within the conserved CPSF6-binding surface in CA. Our results indicate that CypA inhibits HIV-1 infection in Vero cells not by promoting TRIM5α binding to the capsid but by blocking nuclear import of the HIV-1 preintegration complex.


Spatiotemporal endometrial transcriptome analysis revealed the luminal epithelium as key player during initial maternal recognition of pregnancy in the mare.
During the period of maternal recognition of pregnancy (MRP) in the mare, the embryo needs to signal its presence to the endometrium to prevent regression of the corpus luteum and prepare for establishment of pregnancy. This is achieved by mechanical stimuli and release of various signaling molecules by the equine embryo while migrating through the uterus. We hypothesized that embryo's signals induce changes in the endometrial gene expression in a highly cell type-specific manner. A spatiotemporal transcriptomics approach was applied combining laser capture microdissection and low-input-RNA sequencing of luminal and glandular epithelium (LE, GE), and stroma of biopsy samples collected from days 10-13 of pregnancy and the estrous cycle. Two comparisons were performed, samples derived from pregnancies with conceptuses ≥ 8 mm in diameter (comparison 1) and conceptuses ≤ 8 mm (comparison 2) versus samples from cyclic controls. The majority of gene expression changes was identified in LE and much lower numbers of differentially expressed genes (DEGs) in GE and stroma. While 1253 DEGs were found for LE in comparison 1, only 248 were found in comparison 2. Data mining mainly focused on DEGs in LE and revealed regulation of genes related to prostaglandin transport, metabolism, and signaling, as well as transcription factor families that could be involved in MRP. In comparison to other mammalian species, differences in regulation of genes involved in epithelial barrier formation and conceptus attachment and implantation reflected the unique features of equine reproduction at the time of MRP at the molecular level.


Occupational exposure to particulate air pollution and mortality due to ischaemic heart disease and cerebrovascular disease.
A growing number of epidemiological studies are showing that ambient exposure to particulate matter air pollution is a risk factor for cardiovascular disease; however, whether occupational exposure increases this risk is not clear. The aim of the present study was to examine whether occupational exposure to particulate air pollution increases the risk for ischaemic heart disease and cerebrovascular disease. The study population was a cohort of 176,309 occupationally exposed Swedish male construction workers and 71,778 unexposed male construction workers. The definition of exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), wood dust, fumes (metal fumes, asphalt fumes and diesel exhaust) and gases and irritants (organic solvents and reactive chemicals) was based on a job-exposure matrix with focus on exposure in the mid-1970s. The cohort was followed from 1971 to 2002 with regard to mortality to ischaemic heart disease and cerebrovascular disease. Relative risks (RR) were obtained by the person-years method and from Poisson regression models adjusting for baseline values of blood pressure, body mass index, age and smoking habits. Any occupational particulate air pollution was associated with an increased risk for ischemic heart disease (RR 1.13, 95% CI 1.07 to 1.19), but there was no increased risk for cerebrovascular disease (RR 0.97, 95% CI 0.88 to 1.07). There was an increased risk for ischaemic heart disease and exposure to inorganic dust (RR 1.07, 95% CI 1.03 to 1.12) and exposure to fumes (RR 1.05, 95% CI 1.00 to 1.10), especially diesel exhaust (RR 1.18, 95% CI 1.13 to 1.24). There was no significantly increased risk for cerebrovascular disease and exposure to inorganic dust, fumes or wood dust. Occupational exposure to particulate air pollution, especially diesel exhaust, among construction workers increases the risk for ischaemic heart disease.


Poverty and Academic Achievement Across the Urban to Rural Landscape: Associations with Community Resources and Stressors.
Poor children begin school with fewer academic skills than their nonpoor peers, and these disparities translate into lower achievement, educational attainment, and economic stability in adulthood. Child poverty research traditionally focuses on urban or rural poor, but a shifting spatial orientation of poverty necessitates a richer examination of how urbanicity intersects with economic disadvantage. Combining geospatial administrative data with longitudinal survey data on poor children from kindergarten through second grade (N ≈ 2,950), this project explored how differences in community-level resources and stressors across urbanicity explain variation in achievement. Resources and stressors increased in more urbanized communities and were associated with academic achievement. Both mediated differences in poor children's achievement. Mediation was both direct and indirect, operating through cognitive stimulation and parental warmth.


How do people with cancer wish to be cared for in primary care? Serial discussion groups of patients and carers.
In most economically developed countries, patients, their informal and professional carers and policy makers are calling for more care in the community. To involve patients with cancer, and their carers, in designing a framework for providing effective cancer care in primary care. Two discussion groups comprising 18 people with current cancer and carers met monthly over a year in the south of Scotland. Patients with cancer and their carers identified five key times in the cancer journey as being especially significant from their perspective: around diagnosis, during treatment, after discharge, at recurrence and the final weeks. At each key time, there were five major issues of concern: information, communication, equity, a holistic approach and patient-centred care. Using these, the group members developed a checklist of recommended interventions for each stage in the illness trajectory and suggested how they might be implemented in primary care. Proactive and ongoing contact, if wished by the patient, was considered the central plank of cancer care in the community. Patients with cancer and their carers believe that there is an important and unique role for primary care in offering continuity of care and information that is patient-centred and holistic, throughout the cancer trajectory, from first presentation. This study successfully brought patient, carer and professional perspectives to the development of a care framework for primary care.


Activation of cAMP-dependent protein kinase is necessary for actin rearrangements in human neutrophils during phagocytosis.
We have investigated the role of cAMP and cAMP-dependent protein kinase (cAPK) in neutrophil phagocytosis. Inhibition of cAPK with H-89 reduced complement- and IgG-dependent phagocytosis to 83 and 46%, respectively. Fluorescence intensity measurements of phalloidin-stained actin in neutrophils showed a reduced amount of filamentous actin (F-actin) in pseudopods and around the phagosome in cells treated with H-89 or cAMP-elevating agents (forskolin and rolipram). The amount of phosphotyrosine-containing proteins was also reduced in pseudopods and around the phagosome. Taken together, the data show that cAMP/cAPK regulates F-actin reorganization during receptor-mediated phagocytosis, particularly triggered by IgG-FcR interaction. Our results support the hypothesis that active subcortical reorganization of F-actin is a prerequisite for FcR-mediated phagocytosis, but is less important during CR3-mediated ingestion.


Carbohydrate 19-9 antigen is not a marker of liver disease in patients with cystic fibrosis.
Serum concentration of carbohydrate 19-9 antigen (CA 19-9), a sensitive marker of pancreatic cancer and cholangiocarcinoma, increases in a variety of liver diseases due to higher production and release by bile duct cells. Biliary epithelial cells are primarily affected in liver disease associated with cystic fibrosis (CF), which develops in up to 30% of CF patients. Our aim was to evaluate the usefulness of serum CA 19-9 concentration as a test of liver involvement in CF. Serum concentration of CA 19-9, liver enzymes, bile acids, and total amylase was determined in 107 CF patients (49 with and 58 without liver disease) and 56 healthy subjects. Serum CA 19-9 concentration was significantly higher in CF patients (67 U/ml, 95% CI 53.5-80.5 U/ml) than in controls (11.8 U/ml, 95% CI 2.5-44 U/ml; p < 0.001) and in CF patients with liver disease (92.3 U/ml, 95% CI 75-109.5 U/ml) compared to CF patients without liver disease (46.6 U/ml, 95% CI 27.8-65.4 U/ml; p < 0.001). In CF patients, stepwise logistic regression analysis identified alanine aminotransferase, gamma-glutamyltranspeptidase, amylase, and CA 19-9 as the most useful predictors of liver disease (p < 0.0001). Receiver-operating characteristic (ROC) curve analysis revealed gamma-glutamyltranspeptidase and CA 19-9 as the best tests for identification of liver disease in CF patients; at a CA 19-9 cut-off arbitrarily fixed at 73 U/ml, positive and negative predictive value was 70% and 78%, respectively (sensitivity 57%, specificity 81%). To increase sensitivity to 94%, the cut-off had to be fixed at 31 U/ml, which corresponds to a specificity of only 36.2% (predictive value 33%). Our study indicates that measurement of the serum CA 19-9 concentration alone cannot be proposed as a reliable test of early hepatic involvement in CF.


A qualitative analysis of nursing students' tweets during the COVID-19 pandemic.
The COVID-19 outbreak has profoundly changed daily life and the ways in which students learn and interact. This study explores the nature and content of tweets posted by students enrolled in nursing programs (hereafter nursing students) in the United Kingdom, the United States, and South Korea during the COVID-19 pandemic between March 4 and April 7, 2020. A total of 8856 tweets from the Twitter accounts of 95 self-identified nursing students were included in our qualitative analysis. The findings revealed five categories of tweet content: (i) reactions to COVID-19; (ii) everyday life; (iii) role as a student; (iv) social connections; and (v) sociopolitical issues. Students shared concerns about the impact of COVID-19 on their education, discussed their experiences as nursing students, tweeted details of their daily lives, and sought social connections for support as well as for information sharing. The findings of this study can inform nurse educators to better understand their students' responses to and sentiments about the COVID-19 pandemic. Nurse educators should incorporate this understanding into curricula for pandemic preparedness and response efforts.


Layering of calcifications in synovial effusions.
The layering out of calcific particles within synovial effusions was detected with horizontal beam radiography in the shoulder of one patient and in the knee of another. This finding has been illustrated only once previously. We suspect that it may be a feature of hydroxyapatite deposition disease, but this remains to be proven.


Caring in full circle: the legacy of Edith Honeycutt.
Edith Folsom Honeycutt, now retired, is the only staff nurse in the United States to be honored by a funded chair at a major university. In 1990, a chair of oncology nursing was established in her name at Emory University by the Metropolitan Atlanta Community Foundation. A life history method was used to examine the professional life of Edith Honeycutt through interviews and with a focus group of nurses who had worked with her. Three themes emerged: teaching by showing; expecting excellent practice; and investing in each other. A synthesized overall theme of "caring in full circle" was identified as the core descriptor. The findings of this study demonstrate how clinical education and expertise are shared and learned among staff nurses. Findings also suggest how nursing knowledge can be, and is, developed at the bedside. The connection between Emory University and Edith Honeycutt demonstrates an enduring link between a university setting and a practice arena.


Assessment of the quantities of waste electrical and electronic equipment (WEEE) in Scotland.
The EC Directives on Waste Electrical and Electronic Equipment (WEEE) and on the Restriction of the use of certain Hazardous Substances (RoHS) in electrical and electronic equipment forms the basis of legislative control over the ultimate recovery and disposal of electronic and electrical products. Understanding the quantities and composition of WEEE arising will be critical in the development of an appropriate collection and recovery infrastructure to meet the requirements of the directive. However in advance of implementation of the directive only limited information is currently available. This paper reviews recent estimates of WEEE arisings, considers the results of trial collection schemes, and presents the findings of the authors own analysis of WEEE arisings in Scotland. The results cover the period of 1998-2008 and suggest that the amount of waste electrical and electronic equipment will increase until 300,000-350,000 metric tons per annum is reached.


Dietary soybean lecithin promoted growth performance and feeding in juvenile Chinese perch (Siniperca chuatsi) could be by optimizing glucolipid metabolism.
To explore the potential benefits of dietary phospholipids (PLs) in fish glucose metabolism and to promote feed culture of Chinese perch (Siniperca chuatsi), we set up six diets to feed Chinese perch (initial mean body weight 37.01 ± 0.20 g) for 86 days, including: Control diet (CT), 1% (SL1), 2% (SL2), 3% (SL3), 4% (SL4) soybean lecithin (SL) and 2% (KO2) krill oil (KO) supplemental diets (in triplicate, 20 fish each). Our study found that the SL2 significantly improved the weight gain rate and special growth rate, but the KO2 did not. In addition, the SL2 diet significantly improved feed intake, which is consistent with the mRNA levels of appetite-related genes (npy, agrp, leptin A). Additionally, in the CT and SL-added groups, leptin A expression levels were nearly synchronized with serum glucose levels. Besides, the SL2 significantly upregulated expression levels of glut2, gk, cs, fas and downregulated g6pase in the liver, suggesting that it may enhance glucose uptake, aerobic oxidation, and conversion to fatty acids. The SL2 also maintained the hepatic crude lipid content unchanged compared to the CT, possibly by significantly down-regulating the mRNA level of hepatic lipase gene (hl), and by elevating serum low-density lipoprotein (LDL) level and intraperitoneal fat ratio in significance. Moreover, the serum high-density lipoprotein levels were significantly increased by PL supplementation, and the SL2 further significantly increased serum total cholesterol and LDL levels, suggesting that dietary PLs promote lipid absorption and transport. Furthermore, dietary SL at 1% level could enhance non-specific immune capacity, with serum total protein level being markedly higher than that in the CT group. In conclusion, it is speculated that the promotion of glucose utilization and appetite by 2% dietary SL could be linked. We suggest a 1.91% supplementation of SL in the diet for the best growth performance in juvenile Chinese perch.


Hepatitis C Virus Infection and Chemotherapy in Breast Cancer: A Retrospective Chart Analysis.
Breast cancer and hepatitis C virus (HCV) infection are major health problems in the U.S. Despite these highly prevalent diseases, there is limited information on the effect of HCV infection among patients with breast cancer receiving chemotherapy and the potential challenges they face during treatment. Currently, there are no guidelines for chemotherapy administration in HCV-positive patients with breast cancer. We performed a retrospective case-control analysis on six patients with breast cancer with active HCV infection and 12 HCV-negative matched controls who received chemotherapy between January 2000 and April 2015. We investigated dose delays, dose changes, hospitalization, hematologic reasons for dose delays, and variation in blood counts during chemotherapy from the patients' medical records. Fisher's exact test was used for statistical comparison of the outcome variables between the two groups. When compared with the HCV-negative patients, the HCV-positive group was at a significantly higher risk of dose delays (100% vs. 33%, p value .013), dose changes (67% vs. 8%, p value .022), hospitalization during chemotherapy (83% vs. 25%, p value .043), and hematotoxicity related dose delays (83% vs. 8%, p value .003). HCV-positive patients took a longer time to complete treatment than the HCV-negative group. Patients with HCV receiving chemotherapy for breast cancer are more likely to experience complications such as dose delays, dose modifications, and hospitalization. Future studies to confirm our findings and investigate on the effect of concurrent HCV and breast cancer treatment are warranted. This study found that hepatitis C infection is associated with a greater risk of treatment delays and dose modifications in patients with breast cancer receiving cytotoxic chemotherapy. Hepatitis C-positive patients have a higher treatment burden with dose changes, hospitalizations, and longer treatment periods than noninfected patients. Further prospective investigations to confirm these findings are warranted in a larger patient population. Given that hepatitis C infection can be curable with direct-acting antivirals, treatment of hepatitis C may alleviate treatment challenges during chemotherapy and improve survival for patients with breast cancer.


[Hypoxic training of high qualification sportsmen].
Normobaric intermittent hypoxic training (IHT) is an effective method for improving of of the functional respiration system (FRS) state, increase of aerobic productivity, general and special capacity for work in sportsmen of high qualification. The advantage of the use of intermittent hypoxic training during the preparation of high qualification sportsmen is so that hypoxic hypoxia and hypoxia of load influence on the sportsman organism in different time (IHT is doing during the rest, out of the planned sport training without the influence on it). This is a difference with the hypoxic training in mountain conditions where two types of hypoxia influence on the sportsman organism simultaneously and permanently--hypoxia of load and hypoxic hypoxia, and additive destructive action of the both types of hypoxia may be revealed. High efficacy of intermittent hypoxic training in improving of all parts of sportsmen FRS is a result alternating of hypoxic influences and normoxic intervals between them during which the level of plastic processes remains increased, oxygen tension in arterial blood and tissues increases to normoxic values. After IHT course, the state of respiration organs improves, the respiration volume, part of alveolar ventilation in the minute volume of respiration, saturation of arterial blood by oxygen, haemoglobin content in blood--increase as well as increase economy and efficacy of oxygen regimes of organism, general and special (especially important) physical capacity for work increase too.


"Putting a face" on HIV infection/AIDS in older adults: a psychosocial context.
Older HIV-1-seropositive individuals largely have not been investigated with respect to their psychosocial characteristics. In this article, the authors review research reported to date regarding the psychosocial context of this growing subgroup of HIV-1-infected individuals. Specifically, the authors consider the characteristics of mood state, life stressor burden, social support network, and coping strategies that individuals older than 50 years are more likely to adopt in adjusting to HIV-1 infection. The authors also separately consider issues of caregiving burden. Data supporting a theoretically based stressor-support-coping model are presented and related to targeting psychotherapeutic interventions for this age group.


Secondary operations of the anterior abdominal wall following microvascular breast reconstruction with the TRAM and DIEP flaps.
Secondary operations of the anterior abdominal wall following breast reconstruction with abdominal flaps are sometimes performed to improve outcome. The purpose of this study was to review a single surgeon's experience with secondary abdominal wall operations following breast reconstruction with the deep inferior epigastric perforator (DIEP) and free transverse rectus abdominis musculocutaneous (TRAM) flaps. Over a 7-year period, 330 women had microvascular breast reconstruction using abdominal flaps. Indications for secondary abdominal operations that were considered necessary included bulge, abdominal skin necrosis (wound), hematoma, neuroma, and seroma. Indications that were considered elective included lateral dog-ear scars and lipodystrophy. Mean follow-up time was 40 months (range, 3 to 84 months). Secondary abdominal operations were performed in 59 women (17.9 percent). The cumulative number of indications was 64. The indications were considered necessary in 33 women (10 percent) and elective in 31 women (9.4 percent). Lower abdominal bulge was the most common necessary indication and was repaired in 9.3 percent of free TRAM flaps and 4.7 percent of DIEP flaps. Dog-ear scars were the most common elective indication and were revised in 29 women (8.8 percent). Neuromas of the anterior abdominal wall were diagnosed in three women (0.9 percent). Secondary procedures for indications with a low frequency included skin necrosis (n = 3), hematoma (n = 3), seroma (n = 1), and lipodystrophy (n = 2). The incidence of secondary procedures of the abdominal wall following microvascular breast reconstruction using abdominal flaps approximates 20 percent, with an equal distribution between necessary and elective procedures. Women considering breast reconstruction using a free TRAM or DIEP flap should be advised of these statistics.


[Postsynaptic potentials of motor neurons of neck muscles in the cat evoked by stimulation of the horizontal semicircular canals].
PSPs, evoked by stimulation of the ipsi- and contralateral horizontal semicircular canals (HSC) in motoneurons of neck muscles, were studied in acute experiments on cats under chloralose-nembutal anesthesia. Ipsilateral stimulation evoked EPSP with latencies ranging from 1.8 to 10.0 ms in 25 motoneurons and IPSP with latencies 1.9-3.9 ms in 10 motoneurons. Calculation of conduction time from ipsilateral canal via Deiters nucleus to neck motoneurons gives reason to consider EPSP with latencies less than 3.8 ms as disynaptic, and those with greater latencies as polysynaptic. Contralateral stimulation evoked EPSP with latencies 1.8-6.0 ms in 19 motoneurons and IPSP with latencies 3.2 and 3.9 ms in 2 motoneurons. Possible pathways conducting these influences and their functional role are discussed.


Startle response related genes.
The startle reaction (also known as the startle response, the startle reflex, or the alarm reaction) is the psychological and physiological response to a sudden unexpected stimulus, such as a flash of light, a loud noise (acoustic startle reflex), or a quick movement near the face. Abnormalities of startle response have been observed in many stress-related mental disorders, such as schizophrenia and post-traumatic stress disorder (PTSD). However, the molecular mechanisms of startle in stress-associated conditions--for example, whether the startle reaction is associated with any gene variance--is still unknown. In this paper, we will carry out a systematic review by retrieving, assessing, and combining, when applicable, individual studies investigating association of the molecular variation of candidate gene with the startle response. The systematic review is based on the search for numerous publications using the keywords "startle gene" on September 15, 2010 using PubMed, which comprises more than 20 million citations for biomedical literature from MEDLINE and life science journals. A total of 486 publications regarding genes associated with startle have been obtained and reviewed here. There are fewer than 20 publications associating genes with the startle response between 1979, when the first valuable paper was published, and 1999. However, publications have dramatically increase from 2001 and reaches over 70 in 2009. We have characterized them into three categories: startle-associated gene studies in humans, in animals, as well as in both human and animals. This review of research strategy may provide the information for identifying a biomarker for startle response, with the objective of translating research into clinical utility: diagnosis and treatment of stress-induced mental disorders.


Accurate Prediction of Aqueous Free Solvation Energies Using 3D Atomic Feature-Based Graph Neural Network with Transfer Learning.
Graph neural network (GNN)-based deep learning (DL) models have been widely implemented to predict the experimental aqueous solvation free energy, while its prediction accuracy has reached a plateau partly due to the scarcity of available experimental data. In order to tackle this challenge, we first build a large and diverse calculated data set Frag20-Aqsol-100K of aqueous solvation free energy with reasonable computational cost and accuracy via electronic structure calculations with continuum solvent models. Then, we develop a novel 3D atomic feature-based GNN model with the principal neighborhood aggregation (PNAConv) and demonstrate that 3D atomic features obtained from molecular mechanics-optimized geometries can significantly improve the learning power of GNN models in predicting calculated solvation free energies. Finally, we employ a transfer learning strategy by pre-training our DL model on Frag20-Aqsol-100K and fine-tuning it on the small experimental data set, and the fine-tuned model A3D-PNAConv-FT achieves the state-of-the-art prediction on the FreeSolv data set with a root-mean-squared error of 0.719 kcal/mol and a mean-absolute error of 0.417 kcal/mol using random data splits. These results indicate that integrating molecular modeling and DL would be a promising strategy to develop robust prediction models in molecular science. The source code and data are accessible at: https://yzhang.hpc.nyu.edu/IMA.


Recent updates in cancer immunotherapy: a comprehensive review and perspective of the 2018 China Cancer Immunotherapy Workshop in Beijing.
The immune system is the hard-wired host defense mechanism against pathogens as well as cancer. Five years ago, we pondered the question if the era of cancer immunotherapy was upon us (Li et al., Exp Hem Oncol 2013). Exciting progresses have been made at all fronts since then, including (1) sweeping approval of six agents by the US Food and Drug Administration (FDA) to block the PD-1/PD-L1 pathway for treatment of 13 cancer types; (2) a paradigm shifting indication of PD-1 and CTLA4 blockers for the management of a broad class of cancers with DNA mismatch repair defect, the first-ever tissue agnostic approval of cancer drugs; (3) real world practice of adoptive T cell therapy with two CD19-directed chimeric antigen receptor T cell products (CAR-T) for relapsed and/or refractory B cell malignancies including acute lymphoid leukemia and diffuse large B cell lymphoma, signaling the birth of a field now known as synthetic immunology; (4) the award of 2018 Nobel Prize in Physiology and Medicine from the Nobel Committee to Tasuku Honjo and James Allison "for their discovery of cancer medicine by inhibition of negative immune regulation" ( www.nobelprize.org/prizes/medicine/2018 ); and (5) the emerging new concept of normalizing rather than amplifying anti-tumor immunity for guiding the next wave of revolution in the field of immuno-oncology (IO) (Sanmamed and Chen, Cell 2018).This article will highlight the significant developments of immune-oncology as of October 2018. The US FDA approved indications of all seven immune checkpoint blockers, and two CD19-directed CAR-T products are tabulated for easy references. We organized our discussion into the following sections: introduction, cell therapy, emerging immunotherapeutic strategies, expediting oncology drug development in an era of breakthrough therapies, new concepts in cancer immunology and immunotherapy, and concluding remarks. Many of these topics were covered by the 2018 China Cancer Immunotherapy Workshop in Beijing, the fourth annual conference co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), China FDA (CFDA; now known as China National Medical Product Administration (NMPA)), and the Tsinghua University. We significantly expanded our discussion of important IO developments beyond what were covered in the conference, and proposed a new Three Rs conceptual framework for cancer immunotherapy, which is to reverse tolerance, rejuvenate the immune system, and restore immune homeostasis. We conclude that the future of immuno-oncology as a distinct discipline of cancer medicine has arrived.


PFAS concentrations in plasma samples from Danish school children and their mothers.
Perfluoroalkyl substances (PFASs) are accumulating in our environment and human exposure to these potentially harmful chemicals are of growing concern. In the present study, 116 children aged 6-11 and 143 mothers in two locations in Denmark donated blood samples as a supplement to their participation in the large European human biomonitoring project, DEMOCOPHES (Demonstration of a study to COordinate and Perform Human Biomonitoring on a European Scale). The blood samples were analyzed by LC-MS/MS for the concentration of six PFASs: PFOA, PFHxS, PFNA, PFDA, br-PFOS and n-PFOS. All measured compounds were above the detection limit in both mothers and children except for PFHxS in one child. There was a significant correlation between the levels in children and their mothers, indicating a family-related exposure pattern. However, we also found that the levels of PFOA, PFNA, PFDA, br-PFOS and total-PFOS were significantly higher in children compared to their mothers. This may be due to higher exposure in children through for example dust and soil, and due to the fact that children are smaller in body size and blood volume and hence have a lower storage capacity. Furthermore, we found an association between plasma levels and the age of the mothers and higher levels of plasma PFASs in mothers with low parity. There were no associations between PFAS concentrations and residential area, dietary habits of the participants or with respect to the birth order of the children. The levels are comparable to concentrations found in other Western countries.


Glycine receptor: light microscopic autoradiographic localization with [3H]strychnine.
Glycine receptors have been localized by autoradiography in the rat central nervous system (CNS) using [3H]strychnine. The gross distribution of receptors is in excellent accord with the distribution determined by filtration binding assays. Specifically, the density of glycine receptors is greatest in the gray matter of the spinal cord and decreases progressively in regions more rostral in the neuraxis. Glycine receptors were found to be associated with both sensory and motor systems in the CNS. Moreover, there is a striking correlation between areas of high strychnine binding site density and areas in which glycine has been found to be electrophysiologically active. Finally, the anatomic localization of strychnine binding sites may help explain many of the signs and symptoms of strychnine ingestion. For example, individuals consuming subconvulsive doses of strychnine frequently experience altered cutaneous and auditory sensation. We have localized strychnine receptors in areas of the acoustic system known to influence discriminative aspects of audition and in areas of the spinal cord and trigeminal nuclei which modulate discriminative aspects of cutaneous sensation. The alteration of visceral functions (e.g., blood pressure and respiratory rate) associated with strychnine ingestion may be accounted for in a similar manner.


Improving medical and psychiatric outcomes among individuals with bipolar disorder: a randomized controlled trial.
Comorbid medical conditions, notably cardiovascular disease, occur disproportionately among persons with bipolar disorder; yet the quality and outcomes of medical care for these individuals are suboptimal. This pilot study examined a bipolar disorder medical care model (BCM) and determined whether, compared with usual care, individuals randomly assigned to receive BCM care had improved medical and psychiatric outcomes. Persons with bipolar disorder and cardiovascular disease-related risk factors were recruited from a large Department of Veterans Affairs mental health facility and randomly assigned to receive BCM or usual care. BCM care consisted of four self-management sessions on bipolar disorder symptom control strategies, education and behavioral change related to cardiovascular disease risk factors, and promotion of provider engagement. Primary outcomes were physical and mental health-related quality of life; secondary outcomes included functioning and bipolar symptoms. Fifty-eight persons participated. Twenty-seven received BCM care, and 31 received usual care. The mean+/-SD age was 55+/-8 years, 9% were female, 90% were white, and 10% were African American. Repeated-measures analysis was used, and significant differences were observed between the two groups in change in scores from baseline to six months for the 12-Item Short-Form Health Survey (SF-12) subscale for physical health (t=2.01, df=173, p=.04), indicating that the usual care group experienced a decline in physical health over the study period. Change in SF-12 scores also indicated that compared with the usual care group, the BCM group showed improvements in mental health-related quality of life over the six-month study period; however, this finding was not significant. Compared with usual care, BCM care may have slowed the decline in physical health-related quality of life. Further studies are needed to determine whether BCM care leads to long-term positive changes in physical and mental health-related quality of life and reduced risk of cardiovascular disease among persons with bipolar disorder.


Complexity of the Basic Reproduction Number (R0).
The basic reproduction number (R0), also called the basic reproduction ratio or rate or the basic reproductive rate, is an epidemiologic metric used to describe the contagiousness or transmissibility of infectious agents. R0 is affected by numerous biological, sociobehavioral, and environmental factors that govern pathogen transmission and, therefore, is usually estimated with various types of complex mathematical models, which make R0 easily misrepresented, misinterpreted, and misapplied. R0 is not a biological constant for a pathogen, a rate over time, or a measure of disease severity, and R0 cannot be modified through vaccination campaigns. R0 is rarely measured directly, and modeled R0 values are dependent on model structures and assumptions. Some R0 values reported in the scientific literature are likely obsolete. R0 must be estimated, reported, and applied with great caution because this basic metric is far from simple.


Structures of Coxsackievirus A10 unveil the molecular mechanisms of receptor binding and viral uncoating.
Coxsackievirus A10 (CVA10), a human type-A Enterovirus (HEV-A), can cause diseases ranging from hand-foot-and-mouth disease to polio-myelitis-like disease. CVA10, together with some other HEV-As, utilizing the molecule KREMEN1 as an entry receptor, constitutes a KREMEN1-dependent subgroup within HEV-As. Currently, there is no vaccine or antiviral therapy available for treating diseases caused by CVA10. The atomic-resolution structure of the CVA10 virion, which is within the KREMEN1-dependent subgroup, shows significant conformational differences in the putative receptor binding sites and serotype-specific epitopes, when compared to the SCARB2-dependent subgroup of HEV-A, such as EV71, highlighting specific differences between the sub-groups. We also report two expanded structures of CVA10, an empty particle and uncoating intermediate at atomic resolution, as well as a medium-resolution genome structure reconstructed using a symmetry-mismatch method. Structural comparisons coupled with previous results, reveal an ordered signal transmission process for enterovirus uncoating, converting exo-genetic receptor-attachment inputs into a generic RNA release mechanism.


Methicillin-resistant Staphylococcus aureus. Past, present, and future.
The MRSA control program at UCDMC is one of many approaches used in hospitals today. With this less restrictive program, we have been able to maintain control of MRSA for approximately 5 years. By establishing a threshold for investigation at four new nosocomial cases per month, the ICD has been able to maintain a manageable endemic level of MRSA. Figure 2 shows the downward trend of new cases of MRSA per fiscal year. During 1991, however, we experienced clustering of cases in two areas of the hospital along with a major outbreak in our burn unit. This is reflected in the significant rise in the number of new cases for that year. Even with these outbreaks, however, we have been able to re-establish control. Figure 3 represents the number of new MRSA cases per month during fiscal year 1991. After the peak in April, we have again seen a downward trend, with an average of four new cases per month during the first quarter of fiscal year 1992. The success of this program is attributed to the cooperation and excellent communication among the hospital departments who are active participants in this control program. It is also owing to the establishment of a very active antibiotic control program that discourages inappropriate use of antimicrobial agents. This team effort is critical to the success of any infection control program. Infection control protocols are constantly changing, even if they are directed toward the same pathogen. Hospital epidemiology provides us with a very systematic approach to controlling the spread of disease. During the process, however, we are constantly collecting new information about the pathogen, allowing us to re-evaluate and, we hope, improve our approach to control. This is one reason for the numerous approaches to control found in the vast array of MRSA literature. MRSA continues to be a challenge of the 1990s. It appears to be an increasing problem in US hospitals, regardless of hospital size. Although its elusive behavior evades the most comprehensive and carefully planned control programs of even the most skilled hospital epidemiologists, hospitals continue to struggle for control of this organism. The alternative to control is probable resistance to vancomycin, which would have devastating public health consequences, particularly as alternative antibiotic therapy is not yet available.


Myocardial Recovery Strategy with Decommissioning for the HeartWare Left Ventricular Assist Device.
To manage myocardial recovery in patients with the HeartWare left ventricular assist device (HVAD), we describe a minimally invasive approach (decommissioning) that involves disconnecting the driveline and occluding the outflow tract through a small left thoracotomy incision, leaving the device in situ, in conjunction with optimal medical therapies and comprehensive assessment of left ventricular recovery. Nine patients (all male, 37 ± 12 years, all nonischemic dilated cardiomyopathy) had an HVAD implanted for 766 ± 343 days. When left ventricular function improved to mild impairment by echocardiography, patients underwent assessment at reduced flow (2578 ± 148 to 1822 ± 67 rpm) with documentation of compensated right heart hemodynamics and ejection fraction 52 ± 8%. Eight of nine patients underwent decommissioning, and 1 patient had a hybrid procedure of percutaneous occlusion of outflow graft and surgical division of driveline. Two patients died postoperatively at 413 days (sepsis) and 810 days (heart failure). In conclusion, in selected patients with nonischemic dilated cardiomyopathy, a prolonged period of HVAD support in conjunction with heart failure medications can lead to recovery of left ventricular function. Surgical decommissioning is then an option to remove these patients from support. These patients are, however, not cured and remain at risk for future deterioration in ventricular function and infections.


The NoHoW protocol: a multicentre 2×2 factorial randomised controlled trial investigating an evidence-based digital toolkit for weight loss maintenance in European adults.
Obesity and associated diseases place a severe burden on healthcare systems. Behavioural interventions for weight loss (WL) are successful in the short term but often result in weight regain over time. Self-regulation of eating and activity behaviours may significantly enhance weight loss maintenance (WLM) and may be effectively augmented by contextual behavioural approaches to emotion regulation. The NoHoW trial tests the efficacy of a theoretically informed, evidence-based digital toolkit using a mobile-enabled website, activity trackers and Wi-Fi scales for WLM aiming to target (1) self-regulation and motivation, and (2) emotion regulation in adults who achieved clinically significant (≥5%) WL in the previous 12 months (initial body mass index (BMI) ≥25 kg/m2). The study is an 18-month, 3-centre, 2×2 factorial single-blind, randomised controlled trial, which recruited 1627 participants achieving ≥5% WL between March 2017 and March 2018. Participants are randomly allocated to one of four arms: (1) self-monitoring only (self-weighing and activity tracker), (2) self-regulation and motivation, (3) emotion regulation or (4) combined self-regulation, motivation and emotion regulation. Participants attend four clinical investigation days at 0, 6, 12 and 18 months and are instructed to use the digital toolkit for 18 weeks during the first 6 months and at their discretion for the remaining 12 months. The primary outcome is change in weight (kg) at 12 months from baseline. Secondary outcomes are body composition (eg, bioimpedance analysis), health biomarkers (glycated haemoglobin, lipids, blood pressure, hair cortisol), dietary intake, physical activity, sleep, motivational, self-regulatory, emotion regulatory moderators/mediators of WLM, engagement, user experience, acceptability and cost-effectiveness of the interventions. Ethical approval was granted by Institutional Ethics Committees at the Universities of Leeds (17-0082; 27 February 2017), Lisbon (17/2016; 20 February 2017) and Capital Region of Denmark (H-16030495, 8 March 2017). Results will be published in scientific journals. ISRCTN88405328.


Compact micro-displacement sensor with high sensitivity based on a long-period fiber grating with an air-cavity.
We proposed and experimentally demonstrated a compact micro-displacement sensor with high sensitivity based on a long-period fiber grating (LPG) with an air-cavity. The sensor head is obtained by composing an air-cavity with the ends of a LPG and a single mode fiber (SMF). The wavelength shift of the LPG has a linear relationship with the length of the air gap which agrees well with the theoretical analysis. The experimental results show that the sensitivity is ~0.22 nm/µm within the micro-displacement range of 0 to 140 µm.


Isolation of human T-cell lymphotropic virus type 2 from Guaymi Indians in Panama.
Human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and with a chronic degenerative myelopathy. However, another major type of HTLV, HTLV-II, has been isolated only sporadically, and little is known of disease associations, transmission routes, and risk factors for HTLV-II infection. Recent studies indicate that a high percentage of certain groups of i.v. drug users and blood donors are infected with HTLV-II. Seroepidemiologic studies have found an elevated rate of seroreactivity to HTLV among Guaymi Indians from Bocas del Toro Province, Panama. To identify the cause of seroreactivity among this unique population we used HTLV-II-specific polymerase chain reaction techniques to detect HTLV genetic sequences from blood leukocytes of three seropositive Guaymi Indians. The HTLV-II primer-amplified polymerase chain reaction products from two of these subjects were partially sequenced and matched published HTLV-II nucleotide sequences in both p24 gag (94% of 107 bases) and pol (98% of 112 bases) regions. A CD4+ T-lymphocyte line established from one of these same subjects produced HTLV-II-specific proteins when tested in antigen-capture and immunoblot assays, as well as mature HTLV particles. The demonstration of HTLV-II infection in this geographically and culturally isolated Central American Indian population without typical risk factors for HTLV infection suggests that HTLV-II infection is endemic in this population and provides an important clue to potential natural reservoir for this virus.


The use of Perkins' traction in the treatment of femoral shaft fractures.
The treatment of fractures of the femoral shaft by traction may delay union and produce stiffness of the knee. The technique of Perkins' method is described and the results reported in 50 cases. All patients had at least 120 degrees of flexion of the knee when traction was discontinued, and 47 patients were considered to have clinical and radiological union of the fracture by 12 weeks. The main complications of the method was loosening of the Denham pin or infection of the pin-track in the proximal tibia. It is suggested that Perkins' traction is an excellent form of treatment for fractures of the femoral shaft, and has several advantages over other forms of traction.


Brain-generated estradiol drives long-term optimization of auditory coding to enhance the discrimination of communication signals.
Auditory processing and hearing-related pathologies are heavily influenced by steroid hormones in a variety of vertebrate species, including humans. The hormone estradiol has been recently shown to directly modulate the gain of central auditory neurons, in real time, by controlling the strength of inhibitory transmission via a nongenomic mechanism. The functional relevance of this modulation, however, remains unknown. Here we show that estradiol generated in the songbird homolog of the mammalian auditory association cortex, rapidly enhances the effectiveness of the neural coding of complex, learned acoustic signals in awake zebra finches. Specifically, estradiol increases mutual information rates, coding efficiency, and the neural discrimination of songs. These effects are mediated by estradiol's modulation of both the rate and temporal coding of auditory signals. Interference with the local action or production of estradiol in the auditory forebrain of freely behaving animals disrupts behavioral responses to songs, but not to other behaviorally relevant communication signals. Our findings directly show that estradiol is a key regulator of auditory function in the adult vertebrate brain.


On-demand tailored vector beams.
We introduce an effective optical system to produce optical beams with arbitrary, inhomogeneous polarization states. Using our system, we are capable of generating vector beams with discretionarily chosen transverse complex fields in a straightforward way. We generate several different instances of well-known vector beams and the less common spirally polarized vector beams, as well as a full Poincaré beam. We visually show the continual transition between azimuthally and radially polarized beams via a collection of spirally polarized beams. We experimentally determine the polarization states of the generated beams and quantitatively assess the performance of our system. We find that the measured polarization distributions accurately coincide with the intended input polarization distributions.


Songbirds avoid the oxidative stress costs of high blood glucose levels: a comparative study.
Chronically high blood glucose levels (hyperglycaemia) can compromise healthy ageing and lifespan at the individual level. Elevated oxidative stress can play a central role in hyperglycaemia-induced pathologies. Nevertheless, the lifespan of birds shows no species-level association with blood glucose. This suggests that the potential pathologies of high blood glucose levels can be avoided by adaptations in oxidative physiology at the macroevolutionary scale. However, this hypothesis remains unexplored. Here, we examined this hypothesis using comparative analyses controlled for phylogeny, allometry and fecundity based on data from 51 songbird species (681 individuals with blood glucose and 1021 individuals with oxidative state data). We measured blood glucose at baseline and after stress stimulus and computed glucose stress reactivity as the magnitude of change between the two time points. We also measured three parameters of non-enzymatic antioxidants (uric acid, total antioxidants and glutathione) and a marker of oxidative lipid damage (malondialdehyde). We found no clear evidence for blood glucose concentration being correlated with either antioxidant or lipid damage levels at the macroevolutionary scale, as opposed to the hypothesis postulating that high blood glucose levels entail oxidative costs. The only exception was the moderate evidence for species with a stronger stress-induced increase in blood glucose concentration evolving moderately lower investment into antioxidant defence (uric acid and glutathione). Neither baseline nor stress-induced glucose levels were associated with oxidative physiology. Our findings support the hypothesis that birds evolved adaptations preventing the (glyc)oxidative costs of high blood glucose observed at the within-species level. Such adaptations may explain the decoupled evolution of glycaemia and lifespan in birds and possibly the paradoxical combination of long lifespan and high blood glucose levels relative to mammals.


Purification, crystallization and preliminary X-ray analysis of the inverse F-BAR domain of the human srGAP2 protein.
Bin-Amphiphysin-Rvs (BAR) domain proteins play essential roles in diverse cellular processes by inducing membrane invaginations or membrane protrusions. Among the BAR superfamily, the `classical' BAR and Fes/CIP4 homology BAR (F-BAR) subfamilies of proteins usually promote membrane invaginations, whereas the inverse BAR (I-BAR) subfamily generally incur membrane protrusions. Despite possessing an N-terminal F-BAR domain, the srGAP2 protein regulates neurite outgrowth and neuronal migration by causing membrane protrusions reminiscent of the activity of I-BAR domain proteins. In this study, the inverse F-BAR (IF-BAR) domain of human srGAP2 was overexpressed, purified and crystallized. The crystals of the srGAP2 IF-BAR domain protein diffracted to 3.50 Å resolution and belonged to space group P2(1). These results will facilitate further structural determination of the srGAP2 IF-BAR domain and the ultimate elucidation of its peculiar behaviour of inducing membrane protrusions rather than membrane invaginations.


Resistance to Second-Line Antituberculosis Drugs and Delay in Drug Susceptibility Testing among Multidrug-Resistant Tuberculosis Patients in Shanghai.
Introduction. Second-line antituberculosis drugs (SLDs) are used for treating multidrug-resistant tuberculosis (MDR-TB). Prolonged delays before confirming MDR-TB with drug susceptibility testing (DST) could result in transmission of drug-resistant strains and inappropriate use of SLDs, thereby increasing the risk of resistance to SLDs. This study investigated the diagnostic delay in DST and prevalence of baseline SLD resistance in Shanghai and described the distribution of SLD resistance with varied delays to DST. Methods. All registered patients from 2011 to 2013 in Shanghai were enrolled. Susceptibility to ofloxacin, amikacin, kanamycin, and capreomycin was tested. Total delay in DST completion was measured from the onset of symptoms to reporting DST results. Results. Resistance to SLDs was tested in 217 of the 276 MDR-TB strains, with 118 (54.4%) being resistant to at least one of the four SLDs. The median total delay in DST was 136 days. Patients with delay longer than median days were roughly twice more likely to have resistance to at least one SLD (OR 2.22, 95% CI 1.19-4.11). Conclusions. During prolonged delay in DST, primary and acquired resistance to SLDs might occur more frequently. Rapid diagnosis of MDR-TB, improved nosocomial infection controls, and regulated treatment are imperative to prevent SLD resistance.


Rectal perforations and fistulae secondary to a glycerin enema: closure by over-the-scope-clip.
Rectal perforations due to glycerin enemas (GE) typically occur when the patient is in a seated or lordotic standing position. Once the perforation occurs and peritonitis results, death is usually inevitable. We describe two cases of rectal perforation and fistula caused by a GE. An 88-year-old woman presented with a large rectal perforation and a fistula just after receiving a GE. Her case was further complicated by an abscess in the right rectal wall. The second patient was a 78-year-old woman who suffered from a rectovesical fistula after a GE. In both cases, we performed direct endoscopic abscess lavage with a saline solution and closed the fistula using an over-the-scope-clip (OTSC) procedure. These procedures resulted in dramatic improvement in both patients. Direct endoscopic lavage and OTSC closure are very useful for pararectal abscess lavage and fistula closure, respectively, in elderly patients who are in poor general condition. Our two cases are the first reports of the successful endoscopic closure of fistulae using double OTSCs after endoscopic lavage of the debris and an abscess of the rectum secondary to a GE.


In vitro transformation of human B-cell follicular lymphoma cells by Epstein-Barr virus.
Human low-grade B-cell lymphoma cells cannot be readily maintained in long-term tissue culture. In an effort to obtain low-grade B-cell lymphoma cell lines for in vitro study, we used Epstein-Barr virus (EBV) as a transforming agent. T-cells were removed prior to EBV transformation by rosetting with sheep erythrocytes, followed by treatment with anti-T11 monoclonal antibody plus complement. The resulting cell population was cocultured with EBV prepared from tissue culture supernatants of marmoset cell line B95-8. Identical immunoglobulin gene rearrangements of tumor cells and EBV-transformed cells were the criteria used to determine that the transformed cells were of tumor origin. DNA was prepared from both biopsy tissue and EBV cell lines and digested with restriction endonucleases, and Southern blots were prepared by standard methods. B-cells isolated from biopsies of four low-grade B-cell lymphomas of follicular, small cleaved cell type and one of follicular, mixed cell type were transformed by EBV into rapidly growing in vitro tissue culture lines. Two of the five transformed cell lines had immunoglobulin heavy chain and light chain gene rearrangements which were present in cells from the original tumor biopsy, indicating that these EBV-transformed cell lines are of tumor origin.


Dissociable representations of environmental size and complexity in the human hippocampus.
The hippocampus is widely assumed to play a central role in representing spatial layouts in the form of "cognitive maps." It remains unclear, however, which properties of the world are explicitly encoded in the hippocampus, and how these properties might contribute to the formation of cognitive maps. Here we investigated how physical size and complexity, two key properties of any environment, affect memory-related neural activity in the human hippocampus. We used functional magnetic resonance imaging and a virtual maze-learning task to examine retrieval-related activity for three previously learned virtual mazes that differed systematically in their physical size and complexity (here defined as the number of distinct paths within the maze). Before scanning, participants learned to navigate each of the three mazes; hippocampal activity was then measured during brief presentations of static images from within each maze. Activity within the posterior hippocampus scaled with maze size but not complexity, whereas activity in the anterior hippocampus scaled with maze complexity but not size. This double dissociation demonstrates that environmental size and complexity are explicitly represented in the human hippocampus, and reveals a functional specialization for these properties along its anterior-posterior axis.


[A Colombian institutional response to Colombian children infected with HIV/AIDS].
Children with HIV/AIDS is a social issue,the approach to which transcends the health sector. The normative, political, institutional and service sector responses have specificities related to children. A proposed approach is based on the following points: health care, nutrition, education, family-socioeconomic status, psychosocial repercussions, protection, housing, stigmatization and discrimination. Based on these guidelines,a survey was conducted of an institutional responseapplying the Bioecological Model of Human Development. Life of children in the institution is described and analyzed. A group of 31 children and 30 adults participated in this ethnographic study. The institutional response concerning health, nutrition, education and basic care, is satisfactory. The main weaknesses identified were nondisclosure of the diagnosis, stigmatization and discrimination, institutionalization validation, psychoemotional repercussions and stigmatization management, and the research budget. The children acknowledge that the institution satisfies their basic-needs and disapprove of some stigmatizing and coercive practices. The reintegration of the children with their families is recommended as a future strategy based on evidence that shows it has better bio-psychosocial results and lower costs.


The Importance of Shared Decision-Making for Patients with Glioblastoma.
Navigating care for patients with cancer can be overwhelming considering the multiple specialists they encounter and the numerous decisions they must make. For patients with glioblastoma (GBM), management is further complicated by a poor prognosis, feelings of isolation, urgency to treat, and cognitive decline associated with this rare and progressive disease. For these reasons, it is imperative that shared decision-making (SDM) be integrated into standard practice to ensure that the risks and benefits of all treatments are discussed and weighed with the patient's expectations and goals in mind. In this manuscript, the importance of SDM in GBM and the potential benefits to the practice and patient are discussed from the unique perspective of advocacy leaders. Their insights from interactions with patients and caregivers provide a template for empowering patients, improving patient-physician communication and understanding, and reducing patient and caregiver anxieties. Ultimately, increased SDM may lead to a better quality of life and improved treatment outcomes.


Impact of fecal contamination on surface water quality in the São Francisco River hydrographic basin in Minas Gerais, Brazil.
Proper water quality monitoring is a valuable tool for water resource management, helping to identify polluting sources and risks related to the use of water resources. One of the main types of contamination found in Brazilian water bodies is fecal contamination, which originates mainly from point source pollution through wastewater disposal. Thus, this study analyzed water quality monitoring data from the responsible environmental body (Minas Gerais Institute of Water Management, IGAM), related to the fecal contamination indicator (FCI), for the years 2000-2018. This was done for the Minas Gerais portion of the São Francisco River basin (SFRB-MG), one of the most important basins in the country. The 10 sub-basins in the area were compared using statistical tools. The work found significant differences between the sub-basins in terms of FCI concentration, highlighting the most impacted ones (SF2, SF3, and SF5) as also being the most densely populated. It is necessary to invest in sanitation measures in order to ensure that water resources are preserved, as well as to reduce the public health risks of downstream municipalities that are supplied with previously contaminated water.


Gingival abrasion and recession in manual and oscillating-rotating power brush users.
To assess gingival recession (GR) in manual and power toothbrush users and evaluate the relationship between GR and gingival abrasion scores (GA). This was an observational (cross-sectional), single-centre, examiner-blind study involving a single-brushing exercise, with 181 young adult participants: 90 manual brush users and 91 oscillating-rotating power brush users. Participants were assessed for GR and GA as primary response variables. Secondary response variables were the level of gingival inflammation, plaque score reduction and brushing duration. Pearson correlation was used to describe the relationship between number of recession sites and number of abrasions. Prebrushing (baseline) and post-brushing GA and plaque scores were assessed and differences analysed using paired tests. Two-sample t-test was used to analyse group differences; ancova was used for analyses of post-brushing changes with baseline as covariate. Overall, 97.8% of the study population had at least one site of ≥1 mm of gingival recession. For the manual group, this percentage was 98.9%, and for the power group, this percentage was 96.7% (P = 0.621). Post-brushing, the power group showed a significantly smaller GA increase than the manual group (P = 0.004); however, there was no significant correlation between number of recession sites and number of abrasions for either group (P ≥ 0.327). Little gingival recession was observed in either toothbrush user group; the observed GR levels were comparable. Lower post-brushing gingival abrasion levels were seen in the power group. There was no correlation between gingival abrasion as a result of brushing and the observed gingival recession following use of either toothbrush.


Pyrosequencing reveals the microbial communities in the Red Sea sponge Carteriospongia foliascens and their impressive shifts in abnormal tissues.
Abnormality and disease in sponges have been widely reported, yet how sponge-associated microbes respond correspondingly remains inconclusive. Here, individuals of the sponge Carteriospongia foliascens under abnormal status were collected from the Rabigh Bay along the Red Sea coast. Microbial communities in both healthy and abnormal sponge tissues and adjacent seawater were compared to check the influences of these abnormalities on sponge-associated microbes. In healthy tissues, we revealed low microbial diversity with less than 100 operational taxonomic units (OTUs) per sample. Cyanobacteria, affiliated mainly with the sponge-specific species "Candidatus Synechococcus spongiarum," were the dominant bacteria, followed by Bacteroidetes and Proteobacteria. Intraspecies dynamics of microbial communities in healthy tissues were observed among sponge individuals, and potential anoxygenic phototrophic bacteria were found. In comparison with healthy tissues and the adjacent seawater, abnormal tissues showed dramatic increase in microbial diversity and decrease in the abundance of sponge-specific microbial clusters. The dominated cyanobacterial species Candidatus Synechococcus spongiarum decreased and shifted to unspecific cyanobacterial clades. OTUs that showed high similarity to sequences derived from diseased corals, such as Leptolyngbya sp., were found to be abundant in abnormal tissues. Heterotrophic Planctomycetes were also specifically enriched in abnormal tissues. Overall, we revealed the microbial communities of the cyanobacteria-rich sponge, C. foliascens, and their impressive shifts under abnormality.


A unifying conceptual framework of factors associated to cardiac vagal control.
Cardiac vagal control (CVC) reflects the activity of the vagus nerve regulating cardiac functioning. CVC can be inferred via heart rate variability measurement, and it has been positively associated to a broad range of cognitive, emotional, social, and health outcomes. It could then be considered as an indicator for effective self-regulation, and given this role, one should understand the factors increasing and decreasing CVC. The aim of this paper is to review the broad range of factors influencing CVC, and to provide a unifying conceptual framework to integrate comprehensively those factors. The structure of the unifying conceptual framework is based on the theory of ecological rationality, while its functional aspects are based on the neurovisceral integration model. The structure of this framework distinguishes two broad areas of associations: person and environment, as this reflects adequately the role played by CVC regarding adaptation. The added value of this framework lies at different levels: theoretically, it allows integrating findings from a variety of scientific disciplines and refining the predictions of the neurovisceral integration model; methodologically, it helps identifying factors that increase and decrease CVC; and lastly at the applied level, it can play an important role for society regarding health policies and for the individual to empower one's flourishing.


The use of mental health services by Australian adolescents with mental disorders and suicidality: Findings from a nationwide cross-sectional survey.
Mental disorders and suicidality among adolescents have been identified as a major public health concern worldwide; however, they often do not get the necessary attention from parents, school and health professional, and therefore are left untreated. This study aimed to investigate the factors associated with the use of mental health services among Australian adolescents aged 13-17 with mental disorders and/or suicidality. Adolescents aged 13-17 (n = 2134) from Young Minds Matter (YMM): the Second Australian Child and Adolescent Survey of Mental Health and Wellbeing were included in this study. The YMM is a cross-sectional nationwide survey, in which information was collected from both parents and adolescents (aged 13-17 years). Both bivariate and multivariate analyses were conducted to identify the factors that have an impact on the use of mental health services (outcome variable) in two subsamples: (1) adolescents with mental disorder and (2) adolescents with suicidality. Overall, 740 (34.7%) and 168 (7.9%) adolescents reported a mental disorder and/or suicidality, respectively. The incidence of seeking any service was higher among adolescents with suicidality (approximately 50%) compared to those with a mental disorder (about 30%). Girls, older age-group (15-17), adolescents living with disadvantaged families (lower-income, less educated and unemployed parents), those who had multiple mental disorders and history of substance use were most likely to use mental health services regardless of mental disorder and suicidality. Health services and online services were the most popular type of mental health service among adolescents aged 13-17 across two subgroups, while, school and telephone services were less utilized. Many adolescents with mental disorders and/or suicidality do not use mental health services. The findings indicate differences in factors associated with the use of mental health services among adolescents with mental disorder and suicidality. Further research is needed to address the specific barriers that limit the use of the services.


Cognitive control and cortisol response to stress in generalised anxiety disorder: a study of working memory capacity with negative and neutral distractors.
We investigated the association between cognitive control and individual differences in cortisol response to stress in participants with generalised anxiety disorder (GAD) and in never-disordered controls (CTL). To assess cognitive control, participants completed an affective version of the reading span task, which measures working memory capacity (WMC) in the presence of negative and neutral distractors. Participants then completed a standard psychosocial stressor and provided salivary cortisol samples throughout. The relation between WMC and cortisol response to stress was dependent on diagnostic group and distractor valence. Within the GAD group, greater WMC in the presence of neutral distractors was associated with attenuated cortisol response to stress, and greater WMC in the presence of negative distractors was associated with faster cortisol recovery from stress. In contrast, within the CTL group, WMC was unrelated to cortisol stress reactivity or recovery.


Genome-wide fungal stress responsive miRNA expression in wheat.
MicroRNAs (miRNAs) are small non-coding class of RNAs. They were identified in many plants with their diverse regulatory roles in several cellular and metabolic processes. A number of miRNAs were involved in biotic and abiotic stress responses. Here, fungal stress responsive wheat miRNAs were analyzed by using miRNA-microarray strategy. Two different fungi (Fusarium culmorum and Bipolaris sorokiniana) were inoculated on resistant and sensitive wheat cultivars. A total of 87 differentially regulated miRNAs were detected in the 8 × 15 K array including all of the available plant miRNAs. Using bioinformatics tools, the target transcripts of responsive miRNAs were predicted, and related biological processes and mechanisms were assessed. A number of the miRNAs such as miR2592s, miR869.1, miR169b were highly differentially regulated showing more than 200-fold change upon fungal-inoculation. Some of the miRNAs were identified as fungal-inoculation responsive for the first time. The analyses showed that some of the differentially regulated miRNAs targeted resistance-related genes such as LRR, glucuronosyl transferase, peroxidase and Pto kinase. The comparison of the two miRNA-microarray analyses indicated that fungal-responsive wheat miRNAs were differentially regulated in pathogen- and cultivar-specific manners.