CREST--classification resources for environmental sequence tags.
Sequencing of taxonomic or phylogenetic markers is becoming a fast and efficient method for studying environmental microbial communities. This has resulted in a steadily growing collection of marker sequences, most notably of the small-subunit (SSU) ribosomal RNA gene, and an increased understanding of microbial phylogeny, diversity and community composition patterns. However, to utilize these large datasets together with new sequencing technologies, a reliable and flexible system for taxonomic classification is critical. We developed CREST (Classification Resources for Environmental Sequence Tags), a set of resources and tools for generating and utilizing custom taxonomies and reference datasets for classification of environmental sequences. CREST uses an alignment-based classification method with the lowest common ancestor algorithm. It also uses explicit rank similarity criteria to reduce false positives and identify novel taxa. We implemented this method in a web server, a command line tool and the graphical user interfaced program MEGAN. Further, we provide the SSU rRNA reference database and taxonomy SilvaMod, derived from the publicly available SILVA SSURef, for classification of sequences from bacteria, archaea and eukaryotes. Using cross-validation and environmental datasets, we compared the performance of CREST and SilvaMod to the RDP Classifier. We also utilized Greengenes as a reference database, both with CREST and the RDP Classifier. These analyses indicate that CREST performs better than alignment-free methods with higher recall rate (sensitivity) as well as precision, and with the ability to accurately identify most sequences from novel taxa. Classification using SilvaMod performed better than with Greengenes, particularly when applied to environmental sequences. CREST is freely available under a GNU General Public License (v3) from http://apps.cbu.uib.no/crest and http://lcaclassifier.googlecode.com.


Physical activity at midlife in relation to successful survival in women at age 70 years or older.
Physical activity is associated with reduced risks of chronic diseases and premature death. Whether physical activity is also associated with improved overall health among those who survive to older ages is unclear. A total of 13,535 Nurses' Health Study participants who were free of major chronic diseases at baseline in 1986 and had survived to age 70 years or older as of the 1995-2001 period made up the study population. We defined successful survival as no history of 10 major chronic diseases or coronary artery bypass graft surgery and no cognitive impairment, physical impairment, or mental health limitations. After multivariate adjustment for covariates, higher physical activity levels at midlife, as measured by metabolic-equivalent tasks, were significantly associated with better odds of successful survival. Significant increases in successful survival were observed beginning at the third quintile of activity: odds ratios (ORs) (95% confidence intervals [CIs]) in the lowest to highest quintiles were 1 [Reference], 0.98 (0.80-1.20), 1.37 (1.13-1.65), 1.34 (1.11-1.61), and 1.99 (1.66-2.38) (P < .001 for trend). Increasing energy expenditure from walking was associated with a similar elevation in odds of successful survival: the ORs (95% CIs) of successful survival across quintiles of walking were 1 [Reference], 0.99 (0.80-1.21), 1.19 (0.97-1.45), 1.50 (1.24-1.82), and 1.47 (1.22-1.79) (P < .001 for trend). These data provide evidence that higher levels of midlife physical activity are associated with exceptional health status among women who survive to older ages and corroborate the potential role of physical activity in improving overall health.


Management of sciatica due to lumbar disc herniation in the Netherlands: a survey among spine surgeons.
Although clinical guidelines for sciatica have been developed, various aspects of lumbar disc herniation remain unclear, and daily clinical practice may vary. The authors conducted a descriptive survey among spine surgeons in the Netherlands to obtain an overview of routine management of lumbar disc herniation. One hundred thirty-one spine surgeons were sent a questionnaire regarding various aspects of different surgical procedures. Eighty-six (70%) of the 122 who performed lumbar disc surgery provided usable questionnaires. Unilateral transflaval discectomy was the most frequently performed procedure and was expected to be the most effective, whereas percutaneous laser disc decompression was expected to be the least effective. Bilateral discectomy was expected to be associated with the most postoperative low-back pain. Recurrent disc herniation was expected to be lowest after bilateral discectomy and highest after percutaneous laser disc decompression. Complications were expected to be highest after bilateral discectomy and lowest after unilateral transflaval discectomy. Nearly half of the surgeons preferentially treated patients with 8-12 weeks of disabling leg pain. Some consensus was shown on acute surgery in patients with short-lasting drop foot and those with a cauda equina syndrome, and nonsurgical treatment in patients with long-lasting, painless drop foot. Most respondents allowed postoperative mobilization within 24 hours but advised their patients not to resume work until 8-12 weeks postoperatively. Unilateral transflaval discectomy was the most frequently performed procedure. Minimally invasive techniques were expected to be less effective, with higher recurrence rates but less postoperative low-back pain. Variety was shown between surgeons in the management of patients with neurological deficit. Most responding surgeons allowed early mobilization but appeared to give conservative advice in resumption of work.


Raman mapping of pharmaceuticals.
Raman spectroscopy may be implemented through a microscope to provide fine scale axial and lateral chemical maps. The molecular structure of many drugs makes Raman spectroscopy particularly well suited to the investigation of pharmaceutical systems. Chemometric methods currently used to assess bulk Raman spectroscopic data are typically applied to Raman mapping data from pharmaceuticals; few reports exist where the spatial information inherent to a mapped dataset is used for the calculation of chemical maps. Both univariate and multivariate methods have been applied to Raman mapping data to determine the distribution of active pharmaceutical ingredients (APIs) in tablets, solid dispersions for increased solubility and controlled release devices. The ability to axially (depth) profile using Raman mapping has been used in studies of API penetration through membranes, cellular uptake of drug delivery liposomes, and initial API distribution and subsequent elution from coatings of medical devices. New instrumental developments will increase the efficiency of Raman mapping and lead to greater utilisation of Raman mapping for analyses of pharmaceutical systems.


Femtosecond pulse generation from a topological insulator mode-locked fiber laser.
We reported on the generation of femtosecond pulse in a fiber ring laser by using a polyvinyl alcohol (PVA)-based topological insulator (TI), Bi2Se3 saturable absorber (SA). The PVA-TI composite has a low saturable optical intensity of 12 MW/cm2 and a modulation depth of ~3.9%. By incorporating the fabricated PVA-TISA into a fiber laser, mode-locking operation could be achieved at a low pump threshold of 25 mW. After an optimization of the cavity parameters, optical pulse with ~660 fs centered at 1557.5 nm wavelength had been generated. The experimental results demonstrate that the PVA could be an excellent host material for fabricating high-performance TISA, and also indicate that the filmy PVA-TISA is indeed a good candidate for ultrafast saturable absorption device.


Anticancer immunochemotherapy using adjuvants with direct cytotoxic effects.
Conventional chemotherapeutics may induce immunogenic cancer cell death or stimulate immune effectors via so-called off-target effects. The study by Besch et al. in this issue of the JCI now demonstrates that agents designed to stimulate the innate immune system by activating intracellular pattern recognition receptors can kill cancer cells in a direct, cell-autonomous fashion (see the related article beginning on page 2399). The authors show that ligation of viral RNA sensors, such as RIG-I or MDA-5, by viral RNA mimetics triggers mitochondrial apoptosis in human melanoma cells in an IFN-independent fashion. The data suggest that tumor cell killing and immunostimulation may synergize for optimal anticancer immunochemotherapy.


Measuring researcher independence using bibliometric data: A proposal for a new performance indicator.
Bibliometric indicators are increasingly used to evaluate individual scientists-as is exemplified by the popularity of the many other publication and citation-based indicators used in evaluation. These indicators, however, cover at best some of the quality dimensions relevant for assessing a researcher: productivity and impact. At the same time, research quality has more dimensions than productivity and impact alone. As current bibliometric indicators are not covering various important quality dimensions, we here contribute to developing better indicators for those quality dimensions not yet addressed. One of the quality dimensions lacking valid indicators is an individual researcher's independence. We propose indicators to measure different aspects of independence: two assessing whether a researcher has developed an own collaboration network and two others assessing the level of thematic independence. Taken together they form an independence indicator. We illustrate how these indicators distinguish between researchers that are equally productive and have a considerable impact. The independence indicator is a step forward in evaluating individual scholarly quality.


Integrative assessment of chlorine-induced acute lung injury in mice.
The genetic basis for the underlying individual susceptibility to chlorine-induced acute lung injury is unknown. To uncover the genetic basis and pathophysiological processes that could provide additional homeostatic capacities during lung injury, 40 inbred murine strains were exposed to chlorine, and haplotype association mapping was performed. The identified single-nucleotide polymorphism (SNP) associations were evaluated through transcriptomic and metabolomic profiling. Using ≥ 10% allelic frequency and ≥ 10% phenotype explained as threshold criteria, promoter SNPs that could eliminate putative transcriptional factor recognition sites in candidate genes were assessed by determining transcript levels through microarray and reverse real-time PCR during chlorine exposure. The mean survival time varied by approximately 5-fold among strains, and SNP associations were identified for 13 candidate genes on chromosomes 1, 4, 5, 9, and 15. Microarrays revealed several differentially enriched pathways, including protein transport (decreased more in the sensitive C57BLKS/J lung) and protein catabolic process (increased more in the resistant C57BL/10J lung). Lung metabolomic profiling revealed 95 of the 280 metabolites measured were altered by chlorine exposure, and included alanine, which decreased more in the C57BLKS/J than in the C57BL/10J strain, and glutamine, which increased more in the C57BL/10J than in the C57BLKS/J strain. Genetic associations from haplotype mapping were strengthened by an integrated assessment using transcriptomic and metabolomic profiling. The leading candidate genes associated with increased susceptibility to acute lung injury in mice included Klf4, Sema7a, Tns1, Aacs, and a gene that encodes an amino acid carrier, Slc38a4.


Beneficial effects of the extract from Corydalis yanhusuo in rats with heart failure following myocardial infarction.
As indicated in ancient Chinese medical books, Corydalis yanhusuo has therapeutic effects on cardiovascular diseases. The analgesic effect of this plant has been fully elucidated, and l-tetrahydropalmatine has been shown to be the main active principle. The aim of this investigation was to evaluate its protective effects in a rat heart failure model. Rats were subjected to coronary artery ligation, and orally administered with ethanolic extract of Corydalis yanhusuo 50, 100, or 200 mg kg(-1) daily, from the 7th day after surgery. We measured cardiac function, plasma atrial natriuretic peptide (ANP), relative heart and lung weights, infarct size and ventricular dilatation after treatment for 8 weeks. Administration with Corydalis yanhusuo led to a significant reduction in infarct size and improvement in cardiac function as demonstrated by lower left ventricular end diastolic pressure (LVEDP) and elevated +/-dp/dt(max). We also found that Corydalis yanhusuo significantly reduced left ventricular (LV)/body weight ratio, lung/body weight ratio and significantly inhibited neurohormonal activation. Taken together, this study indicated that Corydalis yanhusuo exerted salutary effects on heart failure induced by myocardial infarction in rats.


Optimization and Evaluation of a Novel Size Based Circulating Tumor Cell Isolation System.
Isolation of circulating tumor cells (CTCs) from peripheral blood has the potential to provide a far easier "liquid biopsy" than tumor tissue biopsies, to monitor tumor cell populations during disease progression and in response to therapies. Many CTC isolation technologies have been developed. We optimized the Parsortix system, an epitope independent, size and compressibility-based platform for CTCs isolation, making it possible to harvest CTCs at the speed and sample volume comparable to standard CellSearch system. We captured more than half of cancer cells from different cancer cell lines spiked in blood samples from healthy donors using this system. Cell loss during immunostaining of cells transferred and fixed on the slides is a major problem for analyzing rare cell samples. We developed a novel cell transfer and fixation method to retain >90% of cells on the slide after the immunofluorescence process without affecting signal strength and specificity. Using this optimized method, we evaluated the Parsortix system for CTC harvest in prostate cancer patients in comparison to immunobead based CTC isolation systems IsoFlux and CellSearch. We harvested a similar number (p = 0.33) of cytokeratin (CK) positive CTCs using Parsortix and IsoFlux from 7.5 mL blood samples of 10 prostate cancer patients (an average of 33.8 and 37.6 respectively). The purity of the CTCs harvested by Parsortix at 3.1% was significantly higher than IsoFlux at 1.0% (p = 0.02). Parsortix harvested significantly more CK positive CTCs than CellSearch (p = 0.04) in seven prostate cancer patient samples, where both systems were utilized (an average of 32.1 and 10.1 respectively). We also captured CTC clusters using Parsortix. Using four-color immunofluorescence we found that 85.8% of PC3 cells expressed EpCAM, 91.7% expressed CK and 2.5% cells lacked both epithelial markers. Interestingly, 95.6% of PC3 cells expressed Vimentin, including those cells that lacked both epithelial marker expression, indicating epithelial-to-mesenchymal transition. CK-positive/Vimentin-positive/CD45-negative, and CK-negative/Vimentin-positive/CD45-negative cells were also observed in four of five prostate cancer patients but rarely in three healthy controls, indicating that Parsortix harvests CTCs with both epithelial and mesenchymal features. We also demonstrated using PC3 and DU145 spiking experiment that Parsortix harvested cells were viable for cell culture.


Origami and 4D printing of elastomer-derived ceramic structures.
Four-dimensional (4D) printing involves conventional 3D printing followed by a shape-morphing step. It enables more complex shapes to be created than is possible with conventional 3D printing. However, 3D-printed ceramic precursors are usually difficult to be deformed, hindering the development of 4D printing for ceramics. To overcome this limitation, we developed elastomeric poly(dimethylsiloxane) matrix nanocomposites (NCs) that can be printed, deformed, and then transformed into silicon oxycarbide matrix NCs, making the growth of complex ceramic origami and 4D-printed ceramic structures possible. In addition, the printed ceramic precursors are soft and can be stretched beyond three times their initial length. Hierarchical elastomer-derived ceramics (EDCs) could be achieved with programmable architectures spanning three orders of magnitude, from 200 μm to 10 cm. A compressive strength of 547 MPa is achieved on the microlattice at 1.6 g cm-3. This work starts a new chapter of printing high-resolution complex and mechanically robust ceramics, and this origami and 4D printing of ceramics is cost-efficient in terms of time due to geometrical flexibility of precursors. With the versatile shape-morphing capability of elastomers, this work on origami and 4D printing of EDCs could lead to structural applications of autonomous morphing structures, aerospace propulsion components, space exploration, electronic devices, and high-temperature microelectromechanical systems.


Analysis of the outcome of ileal pouch-anal anastomosis in patients with Crohn's disease.
Ileal pouch-anal anastomosis has come to represent the procedure of choice for patients requiring surgery for mucosal ulcerative colitis. In contrast, a proven diagnosis of Crohn's disease is generally held to preclude ileal pouch-anal anastomosis. However, patients with ileal pouch-anal anastomosis for apparent mucosal ulcerative colitis who are subsequently found to have Crohn's disease have a variable course. We reviewed our experience in this scenario to determine whether selected patients with Crohn's disease may be candidates for ileal pouch-anal anastomosis. A retrospective review of the prospectively maintained ileal pouch-anal anastomosis database was undertaken to identify patients with a diagnosis of Crohn's disease after ileal pouch-anal anastomosis. Clinical outcome and quality-of-life data were obtained from the database and chart review. End points were the development of recrudescent Crohn's disease, pouch failure, and quality of life and functional outcome at the time of data collection. Differences between groups were calculated using the chi-squared test. Cumulative incidence of recrudescent Crohn's disease and pouch loss were calculated by the Kaplan-Meier method. Factors predictive of development of recrudescent Crohn's disease and pouch loss were examined by univariate analysis. Sixty patients (32 females; median age, 33 (range, 15-74) years) who underwent ileal pouch-anal anastomosis for mucosal ulcerative colitis subsequently had that diagnosis revised to Crohn's disease. Median follow-up of all patients was 46 (range, 4-158) months at time of data collection by which time 21 patients (35 percent) had developed recrudescent Crohn's disease. No pre-ileal pouch-anal anastomosis factors examined were predictors of the development of recrudescent Crohn's disease on univariate analysis. Median follow-up of the latter group was 63 (range, 0-132) months from time of diagnosis, by which time six patients underwent pouch excision and another patient was permanently defunctioned. The overall pouch loss rate for the entire cohort was 12 percent and 33 percent for those with recrudescent Crohn's disease. Median daily bowel movements in those with ileal pouch-anal anastomosis in situ at the time of data collection was 7 (range, 3-20), with 50 percent of patients rarely or never experiencing urgency and 59 percent reporting perfect or near perfect continence. Median quality of life, health, and happiness scores were 9.9 and 10 of 10. The secondary diagnosis of Crohn's disease after ileal pouch-anal anastomosis is associated with protracted freedom from clinically evident Crohn's disease, low pouch loss rate, and good functional outcome. Such results only can be improved by the continued development of medical strategies for the long-term suppression of Crohn's disease. These data support a prospective evaluation of ileal pouch-anal anastomosis in selected patients with Crohn's disease.


Statistical symmetries of the Lundgren-Monin-Novikov hierarchy.
It was shown by Oberlack and Rosteck [Discr. Cont. Dyn. Sys. S, 3, 451 2010] that the infinite set of multipoint correlation (MPC) equations of turbulence admits a considerable extended set of Lie point symmetries compared to the Galilean group, which is implied by the original set of equations of fluid mechanics. Specifically, a new scaling group and an infinite set of translational groups of all multipoint correlation tensors have been discovered. These new statistical groups have important consequences for our understanding of turbulent scaling laws as they are essential ingredients of, e.g., the logarithmic law of the wall and other scaling laws, which in turn are exact solutions of the MPC equations. In this paper we first show that the infinite set of translational groups of all multipoint correlation tensors corresponds to an infinite dimensional set of translations under which the Lundgren-Monin-Novikov (LMN) hierarchy of equations for the probability density functions (PDF) are left invariant. Second, we derive a symmetry for the LMN hierarchy which is analogous to the scaling group of the MPC equations. Most importantly, we show that this symmetry is a measure of the intermittency of the velocity signal and the transformed functions represent PDFs of an intermittent (i.e., turbulent or nonturbulent) flow. Interesting enough, the positivity of the PDF puts a constraint on the group parameters of both shape and intermittency symmetry, leading to two conclusions. First, the latter symmetries may no longer be Lie group as under certain conditions group properties are violated, but still they are symmetries of the LMN equations. Second, as the latter two symmetries in its MPC versions are ingredients of many scaling laws such as the log law, the above constraints implicitly put weak conditions on the scaling parameter such as von Karman constant κ as they are functions of the group parameters. Finally, let us note that these kind of statistical symmetries are of much more general type, i.e., not limited to MPC or PDF equations emerging from Navier-Stokes, but instead they are admitted by other nonlinear partial differential equations like, for example, the Burgers equation when in conservative form and if the nonlinearity is quadratic.


Single-dose perioperative mitomycin-C versus thiotepa for low-grade noninvasive bladder cancer.
Mitomycin-C (MMC) and thiotepa are intravesical agents effective in reducing the recurrence of low-grade noninvasive bladder cancer when instilled perioperatively. No studies have compared these agents as a single-dose perioperative instillation. This study tests whether there is a difference in recurrence-free survival in patients with low-grade noninvasive bladder cancer who received intravesical MMC versus thiotepa. A retrospective review was performed of patients who underwent cystoscopic excision of a bladder mass identified as a small, low-grade, treatment-naïve, noninvasive, wild-type urothelial carcinoma of the bladder and who received either intravesical thiotepa (30 mg/15 cc) or MMC (40 mg/20 cc) between January 1, 2002, and January 1, 2016. Data were collected for demographic characteristics, comorbid conditions, operative information, surveillance, and recurrence. The primary outcome was disease-free survival. Cohorts were compared via the doubly robust estimation approach, which used logistic regression to model the probability of recurrence. Of 154 total patients, 84 received intravesical MMC; 70, thiotepa. No statistical differences were shown between groups for age, sex, race, body mass index, smoking status, or baseline comorbid conditions; mass size, tumor multifocality, or tumor grade; and unadjusted recurrence rates (MMC, 36.0%; thiotepa, 46.0%; p = .33) at similar median follow up (MMC, 20.4; thiotepa, 22.8 months; p = .46). The robust logistic regression analysis yielded no differences in recurrence rates between MMC and thiotepa (OR, 0.65 [95% CI, 0.33-1.31]; p = .23). No episodes of myelosuppression or frozen pelvis were identified. As single-dose perioperative agents, both thiotepa and MMC were associated with similar recurrence-free survival rates.


Transcription start site associated RNAs (TSSaRNAs) are ubiquitous in all domains of life.
A plethora of non-coding RNAs has been discovered using high-resolution transcriptomics tools, indicating that transcriptional and post-transcriptional regulation is much more complex than previously appreciated. Small RNAs associated with transcription start sites of annotated coding regions (TSSaRNAs) are pervasive in both eukaryotes and bacteria. Here, we provide evidence for existence of TSSaRNAs in several archaeal transcriptomes including: Halobacterium salinarum, Pyrococcus furiosus, Methanococcus maripaludis, and Sulfolobus solfataricus. We validated TSSaRNAs from the model archaeon Halobacterium salinarum NRC-1 by deep sequencing two independent small-RNA enriched (RNA-seq) and a primary-transcript enriched (dRNA-seq) strand-specific libraries. We identified 652 transcripts, of which 179 were shown to be primary transcripts (∼7% of the annotated genome). Distinct growth-associated expression patterns between TSSaRNAs and their cognate genes were observed, indicating a possible role in environmental responses that may result from RNA polymerase with varying pausing rhythms. This work shows that TSSaRNAs are ubiquitous across all domains of life.


Use of telehealth for facilitating the diagnostic assessment of Autism Spectrum Disorder (ASD): A scoping review.
There is a significant delay between seeking help and a confirmed diagnosis of Autism Spectrum Disorder (ASD). This delay can lead to poor outcomes for both the families and individuals. Telehealth potentially offers a way of improving the diagnostic pathway for ASD. We conducted a scoping review examining which telehealth approaches are used in the diagnosis and assessment of ASD in children and adults, whether they are feasible and acceptable, and how they compare with face-to-face diagnosis and assessment methods. A search for all peer-reviewed articles, combining the terms of autism and telehealth was conducted from 2000 to 2019. A total of 10 studies were identified for inclusion in the review. This review of the literature found there to be two methods of using telehealth: (a) Real-Time method e.g. video conferencing that enables teams in different areas to consult with the families and to assess the child/adult in real time and (b) A Store-and-Forward method as Naturalistic Observation Diagnostic Assessment (NODA) system to upload videos of child's behaviors to a webportal that enables the clinicians to make an assessment remotely. The findings were positive, finding there to be high agreement in terms of the diagnosis between remote methods and face to face methods and with high levels of satisfaction among the families and clinicians. This field is in the very early stages and so only studies with small sample size using surveys and interviews were identified but the findings suggest that there is potential for telehealth methods to improve access to assessment and diagnosis of ASD used in conjunction with existing methods, especially for those with clear autism traits and adults with ASD. Larger randomised controlled trials of this technology are warranted.


Determination of macro-scale soil properties from pore scale structures: image-based modelling of poroelastic structures.
We show how a combination of X-ray computed tomography (X-CT) and image-based modelling can be used to calculate the effect of moisture content and compaction on the macroscopic structural properties of soil. Our method is based on the equations derived in Daly & Roose (2018 Proc. R. Soc. A474, 20170141. (doi:10.1098/rspa.2017.0141)), which we have extended so they can be directly applied to the segmented images obtained from X-CT. We assume that the soils are composed of air-filled pore space, solid mineral grains and a mixed phase composed of both clay particles and water. We considered three different initial soil treatments, composed of two different compaction levels and two different moisture contents. We found that the effective properties of the soils were unaffected by compaction over the range tested in this paper. However, changing the moisture content significantly altered the hydraulic and mechanical properties of the soils. A key strength of this method is that it enables the optimization or even design of soils composed from different constituents, with specific mechanical and hydraulic properties.


Role of Ni in hetero-architectured NiO/Ni composites for enhanced catalytic performance.
A facile, one-step combustion synthesis in solution is reported for preparing hetero-architectured NiO/Ni nanocomposites using different organic fuels. The prepared nanocomposites were physicochemically characterized for crystal structure, functional groups, and morphology. It was found that the content of Ni in the nanocomposite varied due to different combustion fuels. A photocatalytic (PC) investigation of these nanocomposites was performed using rhodamine 6G (RG) under UV light. A citric acid combusted NiO/Ni (N-CA) composite containing 20% Ni phase showed the highest photoactivity in comparison to pure NiO due to its large porous channels and high surface area (∼28 ± 2 m2 g-1). The N-CA catalyst was further evaluated for the degradation of cationic, anionic dyes and chloro/nitro-phenols under both UV and visible light. Photoelectrocatalysis (PEC) of RG with N-CA resulted in complete degradation of the dye. The mechanism governing the catalytic processes was determined from the trapping experiments. The potential reasons for the enhanced photoactivity of the NiO/Ni nanocomposite were that Ni acted as an electron sink, and the applied bias of +1.0 V separated the electron-hole, reducing its rate of recombination.


Mortality among Paris sewage workers.
To describe the mortality of Paris sewage workers. A cohort of all Paris sewage workers since 1970 was established and followed up in mortality until 1999. The causes of death were determined by matching with a national database. The mortality rates were compared to the rates of a local reference population. A large excess in mortality (standardised mortality ratio (SMR) = 1.25; 530 cases, 95% CI 1.15 to 1.36) and in particular mortality from cancer (SMR = 1.37, 235 cases) was detected which was particularly important in the subgroup of subjects who had left employment because they resigned or were laid off (SMR = 1.77; 50 cases). The excess mortality is to a large extent due to alcohol related diseases (SMR = 1.65, 122 cases) especially malignant (SMR = 1.85, 16 cases) and non-malignant (SMR = 1.68, 38 cases) liver diseases, lung cancer (SMR = 1.47, 68 cases), and infectious diseases (SMR = 1.86, 25 cases). The SMRs for some diseases (all cancers, cancers of the oesophagus and lung, all alcohol related diseases) seem to increase with duration of employment as a sewage worker. Other than lung cancer, smoking related diseases were not in excess. The increased mortality by both malignant and non-malignant liver diseases is probably due to excessive alcohol consumption, but could be partially the result of occupational exposure to chemical and infectious agents and interactions of these factors. The excess lung cancer is unlikely to be due to an increased smoking prevalence.


[Exogenous human albumin supplementation in total parenteral nutrition of critically ill newborns].
In view of the controversies found in the literature, the present study was conducted to determine the effect of the use of exogenous human albumin on the nutritional status of newborn infants submitted to total parenteral nutrition. Thirty critically ill newborn infants weighing less than 2,500 g were divided into two groups: 15 infants receiving total parenteral nutrition without human albumin (C control group) and 15 with human albumin (group A). Total protein, albumin, prealbumin, and retinol-binding protein were determined at the beginning (3-4 days of postnatal age) and at the end of the study (10-11 days of postnatal age). On the seventh day of the study, nitrogen balance (retention) was measured. The following clinical parameters were evaluated: weight, age at the beginning of enteral nutrition, time to reach a full enteral volume, length of stay in the intensive care unit, total hospitalization time, and mortality. The results showed a significant difference (p < 0.05) in serum albumin and total protein levels (p < 0.05) between groups at the end of the study. Median albumin levels were 2.95 g/dl in group C (2.71-3.16 g/dl), whereas group A showed median albumin levels of 4.10 g/dl, (3.76-4.66 g/dl). Total protein levels were 4.9 g/dl (4.4-5.2 g/dl) and 5.6 g/dl (5.5-6.3 g/dl), respectively, with no repercussions on any of the remaining parameters evaluated. On the basis of the results obtained in the present study, no benefits were derived from the use of human albumin in total parenteral nutrition in severely ill newborns; therefore its use cannot be recommended, unless the objective is exclusively to elevate albumin levels.


Adiponectin and resistin--new hormones of white adipose tissue.
Adiponectin and resistin are recently described secretory products of adipose tissue. Adiponectin is secreted by fat cells and circulates in the blood. Plasma adiponectin concentration is reduced in obese animals and humans and in patients with type 2 diabetes mellitus. Adiponectin stimulates fatty acids oxidation, decreases plasma triglycerides, and improves glucose metabolism by increasing insulin sensitivity. In addition, adiponectin inhibits the inflammatory process and possibly atherogenesis by suppressing the migration of monocytes/macrophages and their transformation into foam cells. Plasma adiponectin is lower in patients with ischemic heart disease than in body mass index-matched healthy individuals. Hypoadiponectinemia may contribute to insulin resistance and accelerated atherogenesis associated with obesity. Resistin/FIZZ3 is a member of the newly discovered cysteine-reach secretory protein family, referred to as 'resistin-like molecules' (RELM) or 'found in inflammatory zone' (FIZZ), together with FIZZ1/RELMalpha and FIZZ2/RELMbeta. Each of these has unique tissue distribution. Both resistin and FIZZ1/RELMalpha are expressed in adipose tissue. Initial studies in rodents suggested that resistin is upregulated in obesity and may be involved in the development of insulin resistance. Later studies failed to confirm this hypothesis and demonstrated reduced resistin expression in adipose tissue of obese animals. In human adipose tissue resistin is detectable at a very low level, and there is no relationship between resistin expression and obesity. Although the role of resistin in linking human obesity with type 2 diabetes is thus questionable, this protein is detected in peripheral blood monocytes,


Stochastic threshold for ion heating with beating electrostatic waves.
The stochastic threshold for the heating of ions in a magnetized plasma with two electrostatic waves is experimentally characterized. Two obliquely propagating electrostatic modes are launched in a magnetized plasma with frequencies that differ by the ion cyclotron frequency. The values of the wave amplitudes where a rapid increase in the local ion temperature occurs is then parametrically investigated. It is found that the two threshold wave amplitudes are linearly related and that this dependence translates to a lower required energy density for the onset of heating when compared to the case of a single electrostatic wave. Agreement also is demonstrated between the experimentally observed threshold for stochastic heating and an analytical prediction [B. Jorns and E. Y. Choueiri, Phys. Rev. E 87, 013107 (2013)] for this threshold.


Renal Denervation Normalizes Arterial Pressure With No Effect on Glucose Metabolism or Renal Inflammation in Obese Hypertensive Mice.
Hypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) and improves glucose metabolism in drug-resistant hypertensive patients with high body mass index. In addition, RDNx has been shown to reduce renal inflammation in the mouse model of angiotensin II hypertension. The present study tested the hypothesis that RDNx reduces AP and renal inflammation and improves glucose metabolism in obesity-induced hypertension. Eight-week-old C57BL/6J mice were fed either a low-fat diet (10 kcal%) or a high-fat diet (45 kcal%) for 10 weeks. Body weight, food intake, fasting blood glucose, and glucose metabolism (glucose tolerance test) were measured. In a parallel study, radiotelemeters were implanted in mice for AP measurement. High fat-fed C57BL/6J mice exhibited an inflammatory and metabolic syndrome phenotype, including increased fat mass, increased AP, and hyperglycemia compared with low-fat diet mice. RDNx, but not Sham surgery, normalized AP in high-fat diet mice (115.8±1.5 mm Hg in sham versus 96.6±6.7 mm Hg in RDNx). RDNx had no significant effect on AP in low-fat diet mice. Also, RDNx had no significant effect on glucose metabolism or renal inflammation as measured by the number of CD8, CD4, and T helper cells or levels of inflammatory cytokines in the kidneys. These results indicate that although renal nerves play a role in obesity-induced hypertension, they do not contribute to impaired glucose metabolism or renal inflammation in this model.


Magnetic resonance imaging characteristics of ascending hemorrhagic myelomalacia in a dog.
A 4-year-old neutered female terrier-cross was evaluated for an acute onset of paraplegia. Utilizing magnetic resonance (MR) imaging, the cause of the neurologic deficits was determined to be a lumbar intervertebral disc extrusion. The MR study additionally demonstrated parenchymal hyperintensity on T2-weighted images and similarly located diffuse hypointensity on gradient echo images, cranial and caudal to the compressive extradural lesion. Hemorrhagic myelomalacia was suspected based on these MR characteristics, which was subsequently confirmed surgically and histopathologically.


Association of postoperative organ space infection after intraoperative irrigation in appendicitis.
The benefit of intraoperative irrigation on postoperative abscess rates compared to suction alone is unclear. The American Association for the Surgery of Trauma grading system provides distinct disease severity stratification to determine if prior analyses were biased by anatomic severity. We hypothesized that for increasing appendicitis severity, patients receiving (high, ≥2 L) intraoperative irrigation would have increased postoperative organ space infection (OSI) rate compared to (low, <2 L) irrigation. Single-institution review of adults (>18 years) undergoing appendectomy for appendicitis during 2010-2016. Demographics, operative details, irrigation volumes, duration of stay, and complications (Clavien-Dindo classification) were collected. American Association for the Surgery of Trauma grades were assigned by two independent reviewers based on operative findings. Summary, univariate, and area under the receiver operating curve analyses were performed. Patients (n = 1187) were identified with a mean (SD) age of 41.6 (18.4) years (45% female). Operative approach included laparoscopy (n = 1122 [94.5%]), McBurney incision (n = 10 [0.8%]), midline laparotomy (n = 16 [1.3 %]), and laparoscopy converted to laparotomy (n = 39 [3.4%)]. The mean (SD) volume of intraoperative irrigation was 410 (1200) mL. Complication rate was 26.1%. Median volume of intraoperative irrigation in patients who developed postoperative OSI was 3 [0-4] compared to 0 [0-0] in those without infection (p < 0.0001). Area under the receiver operating curve analysis determined that 2 or more liters of irrigation was associated with postoperative OSI (c statistic: 0.83, 95% confidence interval, 0.76-0.89; p < 0.001). Irrigation is used for increasingly severe appendicitis with wide variation. Irrigation volumes of 2 L or greater are associated with postoperative OSI. Improving standardization of irrigation volume (<2 L) may prevent morbidity associated with this high-volume disease. Therapeutic, level IV.


The "intracellular" poly(3-hydroxybutyrate) (PHB) depolymerase of Rhodospirillum rubrum is a periplasm-located protein with specificity for native PHB and with structural similarity to extracellular PHB depolymerases.
Rhodospirillum rubrum possesses a putative intracellular poly(3-hydroxybutyrate) (PHB) depolymerase system consisting of a soluble PHB depolymerase, a heat-stable activator, and a 3-hydroxybutyrate dimer hydrolase (J. M. Merrick and M. Doudoroff, J. Bacteriol. 88:60-71, 1964). In this study we reinvestigated the soluble R. rubrum PHB depolymerase (PhaZ1). It turned out that PhaZ1 is a novel type of PHB depolymerase with unique properties. Purified PhaZ1 was specific for amorphous short-chain-length polyhydroxyalkanoates (PHA) such as native PHB, artificial PHB, and oligomer esters of (R)-3-hydroxybutyrate with 3 or more 3-hydroxybutyrate units. Atactic PHB, (S)-3-hydroxybutyrate oligomers, medium-chain-length PHA, and lipase substrates (triolein, tributyrin) were not hydrolyzed. The PHB depolymerase structural gene (phaZ1) was cloned. Its deduced amino acid sequence (37,704 Da) had no significant similarity to those of intracellular PHB depolymerases of Wautersia eutropha or of other PHB-accumulating bacteria. PhaZ1 was found to have strong amino acid homology with type-II catalytic domains of extracellular PHB depolymerases, and Ser(42), Asp(138), and His(178) were identified as catalytic-triad amino acids, with Ser(42) as the putative active site. Surprisingly, the first 23 amino acids of the PHB depolymerase previously assumed to be intracellular revealed features of classical signal peptides, and Edman sequencing of purified PhaZ1 confirmed the functionality of the predicted cleavage site. Extracellular PHB depolymerase activity was absent, and analysis of cell fractions unequivocally showed that PhaZ1 is a periplasm-located enzyme. The previously assumed intracellular activator/depolymerase system is unlikely to have a physiological function in PHB mobilization in vivo. A second gene, encoding the putative true intracellular PHB depolymerase (PhaZ2), was identified in the genome sequence of R. rubrum.


Biological effects of high-energy neutrons measured in vivo using a vertebrate model.
Interaction of solar protons and galactic cosmic radiation with the atmosphere and other materials produces high-energy secondary neutrons from below 1 to 1000 MeV and higher. Although secondary neutrons may provide an appreciable component of the radiation dose equivalent received by space and high-altitude air travelers, the biological effects remain poorly defined, particularly in vivo in intact organisms. Here we describe the acute response of Japanese medaka (Oryzias latipes) embryos to a beam of high-energy spallation neutrons that mimics the energy spectrum of secondary neutrons encountered aboard spacecraft and high-altitude aircraft. To determine RBE, embryos were exposed to 0-0.5 Gy of high-energy neutron radiation or 0-15 Gy of reference gamma radiation. The radiation response was measured by imaging apoptotic cells in situ in defined volumes of the embryo, an assay that provides a quantifiable, linear dose response. The slope of the dose response in the developing head, relative to reference gamma radiation, indicates an RBE of 24.9 (95% CI 13.6-40.7). A higher RBE of 48.1 (95% CI 30.0-66.4) was obtained based on overall survival. A separate analysis of apoptosis in muscle showed an overall nonlinear response, with the greatest effects at doses of less than 0.3 Gy. Results of this experiment indicate that medaka are a useful model for investigating biological damage associated with high-energy neutron exposure.


A blunt chest trauma causing left anterior descending artery dissection and acute myocardial infarction treated by deferred angioplasty.
Traumatic coronary artery dissection is an uncommon cause of acute myocardial infarction (AMI). We report a case of blunt chest trauma resulting from a motorcycle collision causing ostial dissection of the left anterior descending (LAD) artery in a 31-year-old previously healthy male. The patient also suffered from compound comminuted fractures of the humerus and ulna and severe liver laceration, which hampered both percutaneous and surgical acute revasularization. After a stormy hospital course, a bare metal stent was implanted to seal the LAD artery dissection. The patient was discharged in a stable condition and was followed-up for rehabilitation. This case report underscores the multidisciplinary approach in facing challenges encountered after rare sequelae of chest trauma.


Trapping cells on a stretchable microwell array for single-cell analysis.
There is a need for a technology that can be incorporated into routine laboratory procedures to obtain a continuous, quantitative, fluorescence-based measurement of the dynamic behaviors of numerous individual living cells in parallel, while allowing other manipulations, such as staining, rinsing, and even retrieval of targeted cells. Here, we report a simple, low-cost microarray platform that can trap cells for dynamic single-cell analysis of mammalian cells. The elasticity of polydimethylsiloxane (PDMS) was utilized to trap tens of thousands of cells on an array. The PDMS microwell array was stretched by a tube through which cells were loaded on the array. Cells were trapped on the array by removal of the tube and relaxation of the PDMS. Once that was accomplished, the cells remained trapped on the array without continuous application of an external force and permitted subsequent manipulations, such as staining, rinsing, imaging, and even isolation of targeted cells. We demonstrate the utility of this platform by multicolor analysis of trapped cells and monitoring in individual cells real-time calcium flux after exposure to the calcium ionophore ionomycin. Additionally, a proof of concept for target cell isolation was demonstrated by using a microneedle to locally deform the PDMS membrane in order to retrieve a particular cell from the array.


Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations.
Thin filament hypertrophic cardiomyopathy (HCM) mutations increase myofilament Ca2+ sensitivity and alter Ca2+ handling and buffering. The myosin inhibitor mavacamten reverses the increased contractility caused by HCM thick filament mutations, and we here test its effect on HCM thin filament mutations where the mode of action is not known. Mavacamten (250 nM) partially reversed the increased Ca2+ sensitivity caused by HCM mutations Cardiac troponin T (cTnT) R92Q, and cardiac troponin I (cTnI) R145G in in vitro ATPase assays. The effect of mavacamten was also analyzed in cardiomyocyte models of cTnT R92Q and cTnI R145G containing cytoplasmic and myofilament specific Ca2+ sensors. While mavacamten rescued the hypercontracted basal sarcomere length, the reduced fractional shortening did not improve with mavacamten. Both mutations caused an increase in peak systolic Ca2+ detected at the myofilament, and this was completely rescued by 250 nM mavacamten. Systolic Ca2+ detected by the cytoplasmic sensor was also reduced by mavacamten treatment, although only R145G increased cytoplasmic Ca2+. There was also a reversal of Ca2+ decay time prolongation caused by both mutations at the myofilament but not in the cytoplasm. We thus show that mavacamten reverses some of the Ca2+-sensitive molecular and cellular changes caused by the HCM mutations, particularly altered Ca2+ flux at the myofilament. The reduction of peak systolic Ca2+ as a consequence of mavacamten treatment represents a novel mechanism by which the compound is able to reduce contractility, working synergistically with its direct effect on the myosin motor.NEW & NOTEWORTHY Mavacamten, a myosin inhibitor, is currently in phase-3 clinical trials as a pharmacotherapy for hypertrophic cardiomyopathy (HCM). Its efficacy in HCM caused by mutations in thin filament proteins is not known. We show in reductionist and cellular models that mavacamten can rescue the effects of thin filament mutations on calcium sensitivity and calcium handling although it only partially rescues the contractile cellular phenotype and, in some cases, exacerbates the effect of the mutation.


Perioperative renal function in patients undergoing orthotopic liver transplantation. A randomized trial of the effects of verapamil.
Patients who undergo orthotopic liver transplantation often experience a significant drop in GFR postoperatively. Postulated mechanisms include intraoperative hemodynamic changes, suboptimal renal perfusion during the anhepatic stage, and cyclosporine administration. We undertook a prospective double-blind study to investigate these factors, as well as to determine the protective effects of verapamil on perioperative renal function. Twenty-five patients with normal renal function undergoing OLT received either placebo (n = 13) or verapamil (n = 12) intraoperatively and for six weeks post-OLT. No CsA was administered until after reperfusion of the graft liver, and venovenous bypass (VVB) was utilized in all cases. Patients completing six weeks of the study experienced 61% and 48% decreases in GFR within the placebo and verapamil groups respectively. A significant decrease in GFR occurred in the placebo group between one and six weeks post-OLT, and a significant drop in GFR occurred in the verapamil group by one week post-OLT. Differences between the groups were not significant, however. Systemic, renal, and hepatic hemodynamics were similar at all times between groups, and renal hemodynamics and urine output were unchanged during VVB. We conclude that (1) perioperative factors do not contribute to renal dysfunction post-OLT when VVB is used; (2) VVB preserves renal hemodynamics during the anhepatic phase; (3) CsA is the most likely causative agent for post-OLT renal dysfunction; and (4) intraoperative verapamil serves no protective role, as administered in this study.


Functional imaging with 11C-metomidate PET for subtype diagnosis in primary aldosteronism.
Endocrine Society guidelines recommend adrenal venous sampling (AVS) in primary aldosteronism (PA) if adrenalectomy is considered. We tested whether functional imaging of adrenal cortex with 11C-metomidate (11C-MTO) could offer a noninvasive alternative to AVS in the subtype classification of PA. We prospectively recruited 58 patients with confirmed PA who were eligible for adrenal surgery. Subjects underwent AVS and 11C-MTO-PET without dexamethasone pretreatment in random order. The lateralization of 11C-MTO-PET and adrenal CT were compared with AVS in all subjects and in a prespecified adrenalectomy subgroup in which the diagnosis was confirmed with immunohistochemical staining for CYP11B2. In the whole study population, the concordance of AVS and 11C-MTO-PET was 51% and did not differ from that of AVS and adrenal CT (53%). The concordance of AVS and 11C-MTO-PET was 55% in unilateral and 44% in bilateral PA. In receiver operating characteristics analysis, the maximum standardized uptake value ratio of 1.16 in 11C-MTO-PET had an AUC of 0.507 (P = n.s.) to predict allocation to adrenalectomy or medical therapy with sensitivity of 55% and specificity of 44%. In the prespecified adrenalectomy subgroup, AVS and 11C-MTO-PET were concordant in 10 of 19 subjects with CYP11B2-positive adenoma and in 6 of 10 with CYP11B2-positivity without an adenoma. The concordance of 11C-MTO-PET with AVS was clinically suboptimal, and did not outperform adrenal CT. In a subgroup with CYP11B2-positive adenoma, 11C-MTO-PET identified 53% of cases. 11C-MTO-PET appeared to be inferior to AVS for subtype classification of PA.


Highly stable nanostructured membrane electrode assembly based on Pt/Nb2O5 nanobelts with reduced platinum loading for proton exchange membrane fuel cells.
Proton exchange membrane fuel cells are promising candidates for the next-generation power sources; however, poor durability and high cost impede their widespread application. To address this dilemma, a nanostructured membrane electrode assembly (MEA) based on Pt/Nb2O5 nanobelts (NBs) was constructed through hydrothermal synthesis and the physical vapour deposition method. Pt/Nb2O5 NBs were directly aligned with Nafion membrane without ionomer as a binder. The prepared catalyst layer is ultrathin and has ultralow Pt loading. A single cell performance of 5.80 kW gPt-1 (cathode) and 12.03 kW gPt-1 (anode) was achieved by the Pt/Nb2O5 NBs-based MEA (66.0 μgPt cm-2). The accelerated durability test indicates that the Pt/Nb2O5 NBs-based MEA is far more stable than conventional Pt/C-based MEA.


Genetic structure of Lycorma delicatula (Hemiptera: Fulgoridae) populations in Korea: implication for invasion processes in heterogeneous landscapes.
Lycorma delicatula (White) was identified in 2004 as an invasive pest in South Korea, where it causes serious damage to vineyard crops. To investigate the population structure and dispersal pattern of L. delicatula in South Korea, we estimated the population genetic structure and gene flow among nine locations across the country using seven microsatellite markers. Although L. delicatula spread throughout most of its geographical range in South Korea within 5-7 years following invasion, its populations show evidence of genetic structuring across the range with a low but significant global F ST (genetic differentiation across all populations) of 0.0474. Bayesian-based clustering analysis indicates the presence of at least three genetically unique populations in South Korea, including populations in northeastern South Korea, which show a distinct genetic background. However, isolation by distance suggests that populations in South Korea have not yet reached genetic equilibrium. Estimates of the historical rate of gene flow (N e m) indicate that relatively high rates of flow have been maintained among populations within the western region, which may indicate recent range expansion. A population assignment test using the first-generation migrant detection method suggested that long-distance dispersal of L. delicatula may have occurred over large areas of South Korea. More complex dispersal patterns may have occurred during L. delicatula invasion of heterogeneous landscapes in South Korea.


Automated telephone communication systems for preventive healthcare and management of long-term conditions.
Automated telephone communication systems (ATCS) can deliver voice messages and collect health-related information from patients using either their telephone's touch-tone keypad or voice recognition software. ATCS can supplement or replace telephone contact between health professionals and patients. There are four different types of ATCS: unidirectional (one-way, non-interactive voice communication), interactive voice response (IVR) systems, ATCS with additional functions such as access to an expert to request advice (ATCS Plus) and multimodal ATCS, where the calls are delivered as part of a multicomponent intervention. To assess the effects of ATCS for preventing disease and managing long-term conditions on behavioural change, clinical, process, cognitive, patient-centred and adverse outcomes. We searched 10 electronic databases (the Cochrane Central Register of Controlled Trials; MEDLINE; Embase; PsycINFO; CINAHL; Global Health; WHOLIS; LILACS; Web of Science; and ASSIA); three grey literature sources (Dissertation Abstracts, Index to Theses, Australasian Digital Theses); and two trial registries (www.controlled-trials.com; www.clinicaltrials.gov) for papers published between 1980 and June 2015. Randomised, cluster- and quasi-randomised trials, interrupted time series and controlled before-and-after studies comparing ATCS interventions, with any control or another ATCS type were eligible for inclusion. Studies in all settings, for all consumers/carers, in any preventive healthcare or long term condition management role were eligible. We used standard Cochrane methods to select and extract data and to appraise eligible studies. We included 132 trials (N = 4,669,689). Studies spanned across several clinical areas, assessing many comparisons based on evaluation of different ATCS types and variable comparison groups. Forty-one studies evaluated ATCS for delivering preventive healthcare, 84 for managing long-term conditions, and seven studies for appointment reminders. We downgraded our certainty in the evidence primarily because of the risk of bias for many outcomes. We judged the risk of bias arising from allocation processes to be low for just over half the studies and unclear for the remainder. We considered most studies to be at unclear risk of performance or detection bias due to blinding, while only 16% of studies were at low risk. We generally judged the risk of bias due to missing data and selective outcome reporting to be unclear.For preventive healthcare, ATCS (ATCS Plus, IVR, unidirectional) probably increase immunisation uptake in children (risk ratio (RR) 1.25, 95% confidence interval (CI) 1.18 to 1.32; 5 studies, N = 10,454; moderate certainty) and to a lesser extent in adolescents (RR 1.06, 95% CI 1.02 to 1.11; 2 studies, N = 5725; moderate certainty). The effects of ATCS in adults are unclear (RR 2.18, 95% CI 0.53 to 9.02; 2 studies, N = 1743; very low certainty).For screening, multimodal ATCS increase uptake of screening for breast cancer (RR 2.17, 95% CI 1.55 to 3.04; 2 studies, N = 462; high certainty) and colorectal cancer (CRC) (RR 2.19, 95% CI 1.88 to 2.55; 3 studies, N = 1013; high certainty) versus usual care. It may also increase osteoporosis screening. ATCS Plus interventions probably slightly increase cervical cancer screening (moderate certainty), but effects on osteoporosis screening are uncertain. IVR systems probably increase CRC screening at 6 months (RR 1.36, 95% CI 1.25 to 1.48; 2 studies, N = 16,915; moderate certainty) but not at 9 to 12 months, with probably little or no effect of IVR (RR 1.05, 95% CI 0.99, 1.11; 2 studies, 2599 participants; moderate certainty) or unidirectional ATCS on breast cancer screening.Appointment reminders delivered through IVR or unidirectional ATCS may improve attendance rates compared with no calls (low certainty). For long-term management, medication or laboratory test adherence provided the most general evidence across conditions (25 studies, data not combined). Multimodal ATCS versus usual care showed conflicting effects (positive and uncertain) on medication adherence. ATCS Plus probably slightly (versus control; moderate certainty) or probably (versus usual care; moderate certainty) improves medication adherence but may have little effect on adherence to tests (versus control). IVR probably slightly improves medication adherence versus control (moderate certainty). Compared with usual care, IVR probably improves test adherence and slightly increases medication adherence up to six months but has little or no effect at longer time points (moderate certainty). Unidirectional ATCS, compared with control, may have little effect or slightly improve medication adherence (low certainty). The evidence suggested little or no consistent effect of any ATCS type on clinical outcomes (blood pressure control, blood lipids, asthma control, therapeutic coverage) related to adherence, but only a small number of studies contributed clinical outcome data.The above results focus on areas with the most general findings across conditions. In condition-specific areas, the effects of ATCS varied, including by the type of ATCS intervention in use.Multimodal ATCS probably decrease both cancer pain and chronic pain as well as depression (moderate certainty), but other ATCS types were less effective. Depending on the type of intervention, ATCS may have small effects on outcomes for physical activity, weight management, alcohol consumption, and diabetes mellitus. ATCS have little or no effect on outcomes related to heart failure, hypertension, mental health or smoking cessation, and there is insufficient evidence to determine their effects for preventing alcohol/substance misuse or managing illicit drug addiction, asthma, chronic obstructive pulmonary disease, HIV/AIDS, hypercholesterolaemia, obstructive sleep apnoea, spinal cord dysfunction or psychological stress in carers.Only four trials (3%) reported adverse events, and it was unclear whether these were related to the interventions. ATCS interventions can change patients' health behaviours, improve clinical outcomes and increase healthcare uptake with positive effects in several important areas including immunisation, screening, appointment attendance, and adherence to medications or tests. The decision to integrate ATCS interventions in routine healthcare delivery should reflect variations in the certainty of the evidence available and the size of effects across different conditions, together with the varied nature of ATCS interventions assessed. Future research should investigate both the content of ATCS interventions and the mode of delivery; users' experiences, particularly with regard to acceptability; and clarify which ATCS types are most effective and cost-effective.


Thymine glycols and urea residues in M13 DNA constitute replicative blocks in vitro.
Thymine glycols were produced in M13 DNA in a concentration dependent manner by treating the DNA with osmium tetroxide (OsO4). For the formation of urea-containing M13 DNA, OsO4-oxidized DNA was hydrolyzed in alkali (pH 12) to convert the thymine glycols to urea residues. With both thymine glycol- and urea-containing M13 DNA, DNA synthesis catalyzed by Escherichia coli DNA polymerase I Klenow fragment was decreased in proportion to the number of damages present in the template DNA. Sequencing gel analysis of the products synthesized by E. coli DNA polymerase I and T4 DNA polymerase showed that DNA synthesis terminated opposite the putative thymine glycol site and at one nucleotide before the putative urea site. Substitution of manganese for magnesium in the reaction mix resulted in increased processivity of DNA synthesis so that a base was incorporated opposite urea. With thymine glycol-containing DNA, processivity in the presence of manganese was strongly dependent on the presence of a pyrimidine 5' to the thymine glycol in the template.


Brief psychotherapy for depression: a systematic review and meta-analysis.
Because evidence-based psychotherapies of 12 to 20 sessions can be perceived as too lengthy and time intensive for the treatment of depression in primary care, a number of studies have examined abbreviated psychotherapy protocols. The purpose of this study was to conduct a systematic review and meta-analysis to determine the efficacy of brief psychotherapy (i.e., < or =8 sessions) for depression. We used combined literature searches in PubMed, EMBASE, PsycINFO, and an Internet-accessible database of clinical trials of psychotherapy to conduct two systematic searches: one for existing systematic reviews and another for randomized controlled trials (RCTs). Included studies examined evidence-based psychotherapy(s) of eight or fewer sessions, focused on adults with depression, contained an acceptable control condition, were published in English, and used validated measures of depressive symptoms. We retained 2 systematic reviews and 15 RCTs evaluating cognitive behavioral therapy, problem-solving therapy, and mindfulness-based cognitive therapy. The systematic reviews found brief psychotherapies to be more efficacious than control, with effect sizes ranging from -0.33 to -0.25. Our meta-analysis found six to eight sessions of cognitive behavioral therapy to be more efficacious than control (ES -0.42, 95% CI -0.74 to -0.10, 12 = 56%). A sensitivity analysis controlled for statistical heterogeneity but showed smaller treatment effects (ES -0.24, 95% CI -0.42 to -0.06, 12 = 0%). Depression can be efficaciously treated with six to eight sessions of psychotherapy, particularly cognitive behavioral therapy and problem-solving therapy. Access to non-pharmacologic treatments for depression could be improved by training healthcare providers to deliver brief psychotherapies.


Assessing bimanual performance in brain tumor resection with NeuroTouch, a virtual reality simulator.
Validated procedures to objectively measure neurosurgical bimanual psychomotor skills are unavailable. The NeuroTouch simulator provides metrics to determine bimanual performance, but validation is essential before implementation of this platform into neurosurgical training, assessment, and curriculum development. To develop, evaluate, and validate neurosurgical bimanual performance metrics for resection of simulated brain tumors with NeuroTouch. Bimanual resection of 8 simulated brain tumors with differing color, stiffness, and border complexity was evaluated. Metrics assessed included blood loss, tumor percentage resected, total simulated normal brain volume removed, total tip path lengths, maximum and sum of forces used by instruments, efficiency index, ultrasonic aspirator path length index, coordination index, and ultrasonic aspirator bimanual forces ratio. Six neurosurgeons and 12 residents (6 senior and 6 junior) were evaluated. Increasing tumor complexity impaired resident bimanual performance significantly more than neurosurgeons. Operating on black vs glioma-colored tumors resulted in significantly higher blood loss and lower tumor percentage, whereas altering tactile cues from hard to soft decreased resident tumor resection. Regardless of tumor complexity, significant differences were found between neurosurgeons, senior residents, and junior residents in efficiency index and ultrasonic aspirator path length index. Ultrasonic aspirator bimanual force ratio outlined significant differences between senior and junior residents, whereas coordination index demonstrated significant differences between junior residents and neurosurgeons. The NeuroTouch platform incorporating the simulated scenarios and metrics used differentiates novice from expert neurosurgical performance, demonstrating NeuroTouch face, content, and construct validity and the possibility of developing brain tumor resection proficiency performance benchmarks.


Exercise Bouts at Three Different Intensities Fail to Potentiate Concentric Power.
Postactivation potentiation (PAP) has been hypothesized previously to occur during voluntary, concentric actions. We tested the hypothesis that one of at least three different intensities of conditioning exercises would evoke potentiation of power during the concentric, bench press throw (BPT). Twelve men (age = 22.9 ± 2.7 years, bench press 1 repetition maximum (1RM) = 1.20 ± 0.12 kg·kg-1 body weight) completed five isotonic conditioning presses at ~55, 70, and 86% 1RM, in counterbalanced order, and on separate days. Average and peak power of the BPT using a load of 55% 1RM along with surface electromyography (EMG) of the triceps brachii were collected prior to and 4-minutes following each conditioning bout. Both average and peak power and EMG values (mean ± SD), respectively, were evaluated using two-way analyses of variance with repeated measures. Significant main effect decreases (p < 0.05) in average (-18.6 ± 4.9 W) and peak power (-37.4 ± 9.9 W) occurred across the three different intensities evaluated. No main effects or interactions were observed with the EMG data. Contrary to the previously reported hypothesis, we were unable to demonstrate that conditioning exercise, with three different intensities, can evoke potentiation of power using a load equating to that which is optimum for power production.


Cloning and characterization of the L15 ribosomal protein gene homologue from the crayfish Orconectes limosus.
A cDNA homologue of the large unit rat ribosomal protein L15 was cloned from an epidermal cDNA library of the crayfish Orconectes limosus, being the first crustacean ribosomal protein gene cloned to date. It contains 204 amino acids, deduced from the nucleotide sequence, and reveals 70-76% sequence identity with other arthropod and vertebrate ribosomal L15s. A single, abundant 0.7-kb mRNA transcript was constitutively expressed and revealed similar expression levels, among various adult crayfish tissues.


Do men and women differ in their response to interdisciplinary chronic pain management?
Women report more pain than men. It also seems that gender may moderate responses to pharmacological agents used to combat pain, suggesting that men and women differ in treatment efficacy. Recent research suggests that gender differences may also exist in response to interdisciplinary pain management interventions. We, therefore, report data from a treatment-outcome program at a UK Pain Management Unit. The sample consisted of 98 chronic pain patients (33 males; 65 females) who completed a series of measures relating to pain and distress at three different time points: immediately prior, on completion, and 3 months following an interdisciplinary pain management intervention. The pain management intervention consisted of a 3- or 4-week residential program that aimed to enhance daily functioning, and which involved physiotherapists, occupational therapists, a nurse, physicians, and clinical psychologists. Analyses revealed that the pain management intervention produced improvements in a range of domains of outcome for both men and women, and that such effects were sustained at 3 months following treatment. However, although both men and women exhibited significant post-treatment reduction in measures of current pain intensity and with one measure of pain-related distress, at 3 months following treatment men showed similar reductions as at post-treatment, whereas for women there were no significant differences from pre-treatment scores. This suggests that gender may play a role in reports of pain and distress following interdisciplinary chronic pain management. However, the current results are different from those previously reported. We discuss potential reasons for such differences.


Induction of the G2/M transition stabilizes haploid embryonic stem cells.
The recent successful establishment of mouse parthenogenetic haploid embryonic stem cells (phESCs) and androgenetic haploid ESCs (ahESCs) has stimulated genetic research not only in vitro but also in vivo because of the germline competence of these cell lines. However, it is difficult to maintain the haploid status over time without a frequent sorting of the G1 phase haploid ESCs by fluorescence-activated cell sorting (FACS) at short intervals, because haploid cells tend to readily self-diploidize. To overcome this spontaneous diploid conversion, we developed a phESC culture condition using a small molecular inhibitor of Wee1 kinase to regulate the cell cycle by accelerating the G2/M phase transition and preventing re-entry into extra G1/S phase. Here, we demonstrate that, under this condition, phESCs maintained the haploid status for at least 4 weeks without the need for FACS. This method will greatly enhance the availability of these cells for genetic screening.


1α,25-dihydroxyvitamin D3 in combination with transforming growth factor-β increases the frequency of Foxp3⁺ regulatory T cells through preferential expansion and usage of interleukin-2.
A high prevalence of vitamin D insufficiency and deficiency exists worldwide, which is associated with an increased incidence and severity of a range of immune-mediated diseases. This has resulted in considerable interest in the immunodulatory functions of vitamin D. The active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to increase the frequency of Foxp3(+) CD4(+) T regulatory (Treg) cells when present at high concentrations or under strong T-cell stimulation in culture. Supporting evidence exists in vivo for a positive association between serum 25(OH)D and Foxp3(+) Treg cell numbers in humans. The aim of this work was to identify the cytokine milieu required in vitro to promote Foxp3(+) Treg cells in cultures containing 1,25(OH)2D3 at more moderate concentrations (10(-7) M). Stimulation of human CD4(+) T cells with a combination of 1,25(OH)2D3 and transforming growth factor-β (TGF-β) greatly increased the frequency of Foxp3(+) Treg cells, which is proposed to result from the preferential expansion of Foxp3(+) Treg cells, as compared with the Foxp3(-) effector T cells, in culture. The differential effect on proliferation may result from enhanced availability and usage of interleukin-2 by the Foxp3(+) Treg cells compared with Foxp3(-) effector T cells. In summary, modulation of the cytokine environment to one high in TGF-β in the presence of 1,25(OH)2D3(10(-7) M) significantly increased Foxp3(+) Treg cell frequency. These data provide additional evidence for the important immunomodulatory properties of 1,25(OH)2D3 that exist and may help to control inflammatory diseases.


Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection.
To investigate the expression of interleukin (IL)-33 in the cornea and human corneal epithelial cells (HCECs) exposed to Aspergillus fumigatus (A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to A. fumigatus infection. The mRNA and protein expression of IL-33 in HCECs and mice corneas were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. IL-33 expression was also detected in cornea samples from healthy donors and patients with fungal keratitis with immunohistochemistry. The cultured HCECs were treated with inactive A. fumigatus hyphae at various concentrations with or without recombinant human IL-33 protein, soluble recombinant ST2 protein, specific ST2 neutralizing antibody, or the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 for evaluation of the expression and activation of IL-33/ST2/p38 signaling in the regulation of proinflammatory cytokines. The production levels of IL-6 and IL-1β were determined by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). The proliferation of HCECs was determined by a Cell Counting Kit-8 (CCK8) assay and cell count. IL-33 expression levels increased in the corneal tissues of patients with fungal keratitis and in mice corneas of experimental A. fumigatus infection, as well as in HCECs with infection of A. fumigatus. A. fumigatus strongly stimulated HCECs-generated proinflammatory cytokine (IL-6 and IL-1β) production at both the mRNA and protein levels. This production of pro-inflammatory mediators stimulated by A. fumigatus was further stimulated by IL-33 and was prevented by soluble ST2 protein or ST2 neutralizing antibody. Moreover, IL-33 naturally promoted the p38 phosphorylation induced by A. fumigatus, which was suppressed by soluble ST2 protein. The MAPK p38 inhibitor SB203580 also inhibited the A. fumigatus-induced proinflammatory cytokine production. IL-33 administration for 48h and 72h promoted the proliferation of HCECs, which was attenuated by treatment with soluble recombinant human ST2 protein. A. fumigatus elevates IL-33 expression in human and mice corneas and HCECs. Thus, IL-33/ST2/p38 signaling may play an important role in amplifying the immune response of corneal epithelial cells to A. fumigatus infection. Besides, IL-33 promotes the cell proliferation of HCECs via its receptor ST2. These findings suggest a novel autocrine mechanism of amplification of the fungal-induced inflammatory response in the corneal epithelium, highlighting a potential therapeutic target for fungal keratitis.


DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice.
Chronic inflammation increases cancer risk. While it is clear that cell signaling elicited by inflammatory cytokines promotes tumor development, the impact of DNA damage production resulting from inflammation-associated reactive oxygen and nitrogen species (RONS) on tumor development has not been directly tested. RONS induce DNA damage that can be recognized by alkyladenine DNA glycosylase (Aag) to initiate base excision repair. Using a mouse model of episodic inflammatory bowel disease by repeated administration of dextran sulfate sodium in the drinking water, we show that Aag-mediated DNA repair prevents colonic epithelial damage and reduces the severity of dextran sulfate sodium-induced colon tumorigenesis. Importantly, DNA base lesions expected to be induced by RONS and recognized by Aag accumulated to higher levels in Aag-deficient animals following stimulation of colonic inflammation. Finally, as a test of the generality of this effect we show that Aag-deficient animals display more severe gastric lesions that are precursors of gastric cancer after chronic infection with Helicobacter pylori. These data demonstrate that the repair of DNA lesions formed by RONS during chronic inflammation is important for protection against colon carcinogenesis.


Aerobic and strength training exercise programme for cognitive impairment in people with mild to moderate dementia: the DAPA RCT.
Approximately 670,000 people in the UK have dementia. Previous literature suggests that physical exercise could slow dementia symptom progression. To estimate the clinical effectiveness and cost-effectiveness of a bespoke exercise programme, in addition to usual care, on the cognitive impairment (primary outcome), function and health-related quality of life (HRQoL) of people with mild to moderate dementia (MMD) and carer burden and HRQoL. Intervention development, systematic review, multicentred, randomised controlled trial (RCT) with a parallel economic evaluation and qualitative study. 15 English regions. People with MMD living in the community. A 4-month moderate- to high-intensity, structured exercise programme designed specifically for people with MMD, with support to continue unsupervised physical activity thereafter. Exercises were individually prescribed and progressed, and participants were supervised in groups. The comparator was usual practice. The primary outcome was the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). The secondary outcomes were function [as measured using the Bristol Activities of Daily Living Scale (BADLS)], generic HRQoL [as measured using the EuroQol-5 Dimensions, three-level version (EQ-5D-3L)], dementia-related QoL [as measured using the Quality of Life in Alzheimer's Disease (QoL-AD) scale], behavioural symptoms [as measured using the Neuropsychiatric Inventory (NPI)], falls and fractures, physical fitness (as measured using the 6-minute walk test) and muscle strength. Carer outcomes were HRQoL (Quality of Life in Alzheimer's Disease) (as measured using the EQ-5D-3L) and carer burden (as measured using the Zarit Burden Interview). The economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year (QALY) gained from a NHS and Personal Social Services perspective. We measured health and social care use with the Client Services Receipt Inventory. Participants were followed up for 12 months. Between February 2013 and June 2015, 494 participants were randomised with an intentional unequal allocation ratio: 165 to usual care and 329 to the intervention. The mean age of participants was 77 years [standard deviation (SD) 7.9 years], 39% (193/494) were female and the mean baseline ADAS-Cog score was 21.5 (SD 9.0). Participants in the intervention arm achieved high compliance rates, with 65% (214/329) attending between 75% and 100% of sessions. Outcome data were obtained for 85% (418/494) of participants at 12 months, at which point a small, statistically significant negative treatment effect was found in the primary outcome, ADAS-Cog (patient reported), with a mean difference of -1.4 [95% confidence interval (CI) -2.62 to -0.17]. There were no treatment effects for any of the other secondary outcome measures for participants or carers: for the BADLS there was a mean difference of -0.6 (95% CI -2.05 to 0.78), for the EQ-5D-3L a mean difference of -0.002 (95% CI -0.04 to 0.04), for the QoL-AD scale a mean difference of 0.7 (95% CI -0.21 to 1.65) and for the NPI a mean difference of -2.1 (95% CI -4.83 to 0.65). Four serious adverse events were reported. The exercise intervention was dominated in health economic terms. In the absence of definitive guidance and rationale, we used a mixed exercise programme. Neither intervention providers nor participants could be masked to treatment allocation. This is a large well-conducted RCT, with good compliance to exercise and research procedures. A structured exercise programme did not produce any clinically meaningful benefit in function or HRQoL in people with dementia or on carer burden. Future work should concentrate on approaches other than exercise to influence cognitive impairment in dementia. Current Controlled Trials ISRCTN32612072. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full programme and will be published in full in Health Technology Assessment Vol. 22, No. 28. See the NIHR Journals Library website for further project information. Additional funding was provided by the Oxford NIHR Biomedical Research Centre and the Oxford NIHR Collaboration for Leadership in Applied Health Research and Care.


Study protocol for promoting respectful maternity care initiative to assess, measure and design interventions to reduce disrespect and abuse during childbirth in Kenya.
Increases in the proportion of facility-based deliveries have been marginal in many low-income countries in the African region. Preliminary clinical and anthropological evidence suggests that one major factor inhibiting pregnant women from delivering at facility is disrespectful and abusive treatment by health care providers in maternity units. Despite acknowledgement of this behavior by policy makers, program staff, civil society groups and community members, the problem appears to be widespread but prevalence is not well documented. Formative research will be undertaken to test the reliability and validity of a disrespect and abuse (D&A) construct and to then measure the prevalence of disrespect and abuse suffered by clinic clients and the general population. A quasi-experimental design will be followed with surveys at twelve health facilities in four districts and one large maternity hospital in Nairobi and areas before and after the introduction of disrespect and abuse (D&A) interventions. The design is aimed to control for potential time dependent confounding on observed factors. This study seeks to conduct implementation research aimed at designing, testing, and evaluating an approach to significantly reduce disrespectful and abusive (D&A) care of women during labor and delivery in facilities. Specifically the proposed study aims to: (i) determine the manifestations, types and prevalence of D&A in childbirth (ii) develop and validate tools for assessing D&A (iii) identify and explore the potential drivers of D&A (iv) design, implement, monitor and evaluate the impact of one or more interventions to reduce D&A and (v) document and assess the dynamics of implementing interventions to reduce D&A and generate lessons for replication at scale.


Use of microbubble contrast in the diagnosis of a left ventricular papillary fibroelastoma.
A papillary fibroelastoma is a rare, avascular, cardiac tumour that is often found incidentally using transthoracic echocardiography (TTE). Peripheral i.v. injection of a microbubble contrast agent is often used to characterize abnormal masses within the heart allowing further delineation of physical features, the area of attachment, and vascularity of the mass in order to differentiate the growth from a tumour or a thrombus. This case highlights a potential pitfall when assessing a cardiac tumour's vascularity using contrast TTE. A cardiac mass was identified on a TTE of a 53-year-old man and was further investigated with microbubble contrast-enhanced TTE. Contrast TTE imaging suggested a vascularized structure in the left ventricle. However, after histological examination the tumour was found to be entirely avascular. Differentiation of cardiac tumour is usually best performed with contrast echocardiography.Contrast echocardiography may not be best tool to determine if cardiac mass is vascularized.A papillary fibroelastoma can appear vascularized with contrast echocardiography due to it's frond-like structures.Physicians should be aware of this potential confusion when assessing a cardiac tumour in patients.


Infrared spectral changes identified during different stages of herpes viruses infection in vitro.
Microscopic Fourier transform infrared spectroscopy (FTIR) which is based on the characteristic molecular vibrational spectra of cells was previously applied for the identification of various biological samples. In the present study, FTIR spectroscopy was used for the characterization of different stages during the development of herpes viruses infection. Vero cells in culture were infected with high and low doses of different herpes viruses [herpes simplex virus types 1 and 2 (HSV-1, -2) or varicella-zoster virus (VZV)], and cellular changes were observed by optical and electron microscopy and analyzed by FTIR microscopy at different periods of time post-infection. Specific different spectral changes were observed at various stages of the viral infection development. The spectral intensity in the 1220-1260 cm(-1) region (mainly attributed to phosphate levels) was considerably increased in all infected cells compared to normal uninfected cells during the early stages of the viral infection development. However, at the late stages of the viral infection development (when all the cells in the infected culture lost their spindle shape and became circular) the spectral intensities in this region significantly decreased in the infected compared to the control cells. In addition, the peak at 1023 cm(-1), attributed to carbohydrates, almost fully disappeared at early stages of the viral infection development, whereas at late stages of the infection it raised to an equivalent or higher level than that of the uninfected control cells. These results support the potential of developing FTIR microspectroscopy as a simple, reagent free method for the early detection and accurate differentiation of different stages during the development of herpes virus infection.


The Effect of K and Acidity of NiW-Loaded HY Zeolite Catalyst for Selective Ring Opening of 1-Methylnaphthalene.
Bi-functional catalysts were prepared using HY zeolites with various SiO2/Al2O3 ratios for acidic function, NiW for metallic function, and K for acidity control. 1-Methylnaphthalene was selected as a model compound for multi-ring aromatics in heavy oil, and its selective ring opening reaction was investigated using the prepared bi-functional catalysts with different levels of acidity in a fixed bed reactor system. In NiW/HY catalysts without K addition, the acidity decreased with the SiO2/Al2O3 mole ratio of the HY zeolite. Ni1.1W1.1/HY(12) catalyst showed the highest acidity but slightly lower yields for the selective ring opening than Ni1.1W1.1/HY(30) catalyst. The acidity of the catalyst seemed to play an important role as the active site for the selective ring opening of 1-methylnaphthalene but there should be some optimum catalyst acidity for the reaction. Catalyst acidity could be controlled between Ni1.1W1.1/HY(12) and Ni1.1W1.1/HY(30) by adding a moderate amount of K to Ni1.1W1.1/HY(12) catalyst. K0.3Ni1.1W1.1/HY(12) catalyst should have the optimum acidity for the selective ring opening. The addition of a moderate amount of K to the NiW/HY catalyst must improve the catalytic performance due to the optimization of catalyst acidity.


VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology.
Giant cell tumour of bone (GCTB) is a primary bone tumour that contains numerous very large, hyper-nucleated osteoclastic giant cells. Osteoclasts form from CD14+ monocytes and macrophages in the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). GCTB contains numerous growth factors, some of which have been reported to influence osteoclastogenesis and resorption. We investigated whether these growth factors are capable of substituting for M-CSF to support osteoclast formation from cultured human monocytes and whether they influence osteoclast cytomorphology and resorption. Vascular endothelial growth factor-A (VEGF-A), VEGF-D, FLT3 ligand (FL), placental growth factor (PlGF) and hepatocyte growth factor (HGF) supported RANKL-induced osteoclastogenesis in the absence of M-CSF, resulting in the formation of numerous TRAP+ multinucleated cells capable of lacunar resorption. Monocytes cultured in the presence of M-CSF, HGF, VEGF-A and RANKL together resulted in the formation of very large, hyper-nucleated (GCTB-like) osteoclasts that were hyper-resorptive. M-CSF and M-CSF substitute growth factors were identified immunohistochemically in GCTB tissue sections and these factors stimulated the resorption of osteoclasts derived from a subset of GCTBs. Our findings indicate that there are growth factors that are capable of substituting for M-CSF to induce human osteoclast formation and that these factors are present in GCTB where they influence osteoclast cytomorphology and have a role in osteoclast formation and resorption activity.


Changes in the growth, but not the survival, of American kestrels (Falco sparverius) exposed to environmentally relevant polybrominated diphenyl ethers.
Polybrominated diphenyl ether (PBDEs) concentrations are increasing exponentially in biota. We studied the growth of American kestrel (Falco sparverius) nestlings exposed in ovo and during development to environmentally relevant PBDE congeners and concentrations. Eggs within each clutch, divided between groups by laying sequence, were injected into the air cell at 19 days of incubation with safflower oil or penta-BDE congeners BDE-47, -99, -100, and -153 dissolved in safflower oil (18.7 microg total sigmaPBDEs/egg), approximating current levels in Great Lakes herring gulls. The measured proportions of BDE congeners found in the dosing oil were 56.4% of BDE-47; 27.2% of BDE-99; 24.8% of BDE-100; and 0.6% of BDE-153. For 29 days, nestlings were orally gavaged daily with the same sigmaPBDE mixture (15.6 +/- 0.3 ng/g body weight/day). Relative congener abundances in the dosing mixture compared to the carcasses suggest biotransformation of BDE-47; BDE-183 was also detected. PBDE exposure did not affect hatching or fledging success. PBDE-exposed nestlings were larger (weight, bones, feathers) as they gained weight more quickly and ate more food, the latter in association with their SigmaPBDE body burdens. BDE-100 was most influential on nestling growth, being positively associated with size, weight gain, and food consumption. Increasing concentrations of BDE-183 and -153 were related to longer bones, and BDE-99 to longer feathers. The larger size of the PBDE-exposed birds may be detrimental to their bone structure and have excessive energetic costs. The repeated relationships with BDE-100 and growth may be important for wild Falconidae, since this is the predominant penta-BDE congener in these raptors.


Arboviruses and pregnancy: maternal, fetal, and neonatal effects.
Arboviruses are an expanding public health threat, with pregnant women facing unique complications from arbovirus infections. These infections, such as dengue and Crimean-Congo haemorrhagic fever, can be more severe in pregnant women than in the general population. Vertical transmission is reported for many arboviruses and can severely affect pregnancy outcome. Indeed, arboviruses-particularly flaviviruses and alphaviruses-are associated with increased risks of fetal loss and premature birth. Arboviruses can be teratogenic, as is the case for Zika virus and Venezuelan equine encephalitis virus. Finally, intrapartum transmission can result in severe neonatal infections, as is true for chikungunya virus. Although the global burden of arboviruses is well recognised, few studies have provided data on arbovirus infection specifically in the context of maternal and child health. Epidemiological and clinical studies are therefore needed to better assess the burden of arbovirus infections during pregnancy and to improve the prevention and clinical management of these viral infections. In this Review, we analyse the information available and identify gaps in knowledge that require further assessment.


Assessment of ciliates in the sheep rumen by DGGE.
This work was carried out to develop a rapid molecular profiling technique to screen ciliate populations in the rumen of sheep. DGGE was used to study the ciliate diversity in the rumen of sheep. There was considerable variation between sheep which were co-housed, and fed the same diet. However, no difference in the major banding patterns was detected, when samples were collected from a single sheep sampled at different points. Following dietary changes, use of a pair-wise comparison of lanes, demonstrated that although there was still diversity between the ciliate population of sheep, the effects as a result of dietary changes were greater. The technique generated molecular profiles which are sufficiently different to allow comparison between samples, and to permit molecular ecological studies on the rumen ciliate population. The outcome of this study means that ciliate diversity in the rumen may now be studied by those unfamiliar with morphological identification of these organisms.


Heterosexual transmission of human immunodeficiency virus type 1 subtype C: Macrophage tropism, alternative coreceptor use, and the molecular anatomy of CCR5 utilization.
Human immunodeficiency virus type 1 transmission selects for virus variants with genetic characteristics distinct from those of donor quasispecies, but the biological factors favoring their transmission or establishment in new hosts are poorly understood. We compared primary target cell tropisms and entry coreceptor utilizations of donor and recipient subtype C Envs obtained near the time of acute infection from Zambian heterosexual transmission pairs. Both donor and recipient Envs demonstrated only modest macrophage tropism, and there was no overall difference between groups in macrophage or CD4 T-cell infection efficiency. Several individual pairs showed donor/recipient differences in primary cell infection, but these were not consistent between pairs. Envs had surprisingly broad uses of GPR15, CXCR6, and APJ, but little or no use of CCR2b, CCR3, CCR8, GPR1, and CXCR4. Donors overall used GPR15 better than did recipients. However, while several individual pairs showed donor/recipient differences for GPR15 and/or other coreceptors, the direction of the differences was inconsistent, and several pairs had unique alternative coreceptor patterns that were conserved across the transmission barrier. CCR5/CCR2b chimeras revealed that recipients as a group were more sensitive than were donors to replacement of the CCR5 extracellular loops with corresponding regions of CCR2b, but significant differences in this direction were not consistent within pairs. These data show that sexual transmission does not select for enhanced macrophage tropism, nor for preferential use of any alternative coreceptor. Recipient Envs are somewhat more constrained than are donors in flexibility of CCR5 use, but this pattern is not universal for all pairs, indicating that it is not an absolute requirement.


Greater occipital nerve blocks in chronic cluster headache: a prospective open-label study.
Greater occipital nerve blockade (GONB) has been shown to be effective in episodic cluster headache. However, its use in chronic cluster headache (CCH) is less certain. The study aims to prospectively assess the efficacy and consistency of response to GONB in a large series of CCH patients. CCH patients who had a unilateral GONB and were referred to the National Hospital for Neurology and Neurosurgery were studied prospectively. Headache characteristics were collected using headache diaries. Responders were considered to be patients with a complete or partial response lasting at least 7 days. In a subgroup of responders the outcomes of serial GONB performed at 3-monthly intervals were also analysed. Eighty-three CCH patients were studied. After the first GONB, a positive response was observed in 47 (57%) patients: 35 (42%) were rendered pain free, 12 (15%) had a partial benefit and one patient obtained <50% improvement. The duration of a positive response lasted a median of 21 days (range 7-504 days). There was a transient worsening of condition in 6% of patients. The overall rate and average duration of response remained consistent after the second [n = 37; 31 responders (84%); median duration 21 days], third [n = 28; 20 responders (71%); median duration 25 days] and fourth [n = 14; 10 responders (71%); median duration 23 days] injections. GONB seems to be an efficacious treatment with reproducible effects in CCH patients. Performed three monthly, GONB may have a useful role in the management of CCH.


Anti-inflammatory effect of lemon mucilage: in vivo and in vitro studies.
The mucilage extracted from a lemon juice centrifugation pulp was studied for its anti-inflammatory effect in rat. In vivo the lemon mucilage significantly inhibited carrageenan-induced edema in rat paw from 59% to 73.5% showing the highest effect at the third hour. In vitro, at the doses of 10(-8), 10(-6), 10(-4) or 10(-2) mg/mL the lemon mucilage stimulated the superoxide anion production in rat testing neutrophils in whole blood but inhibited it in FMLP stimulated cells at the dose of 10(-2) mg/mL. The neutrophils of rats receiving p.o. the lemon mucilage for 21 days showed a significant decrease of 45.5% in O2- generation after FMLP stimulation, and a not-significant increase after phorbol-12-myristate-13-acetate (PMA) or zymosan stimulation. Since the activity on zymosan- and PMA-induced O2- production was not significant, the inhibition exerted by FMLP in rat neutrophils occurred mainly through the blockade of phospholipase D.